4167_JPCC_MAR_APR_2020

Print ISSN: 2349-6592, E-ISSN: 2455-7099
Editorial Board
Editor In Chief Managing Editor Founder Editor
Dr. Kundan Mittal Dr. Vinayak Patki Dr. Praveen Khilnani
(PGIMS, Rohtak) (Wanless Hospital, Miraj) (Madhukar Rainbow Hospital, New Delhi)
Executive Editor
Dr. Satish Deopujari Dr. Pradeepkumar Sharma
(Nelson Hospital, Nagpur) (Shri Baiaj Action Hospital, New Delhi)
Associate Editors
Dr. Santosh Soans Dr. Arun Baranwal Dr. Atul Jindal
(AJ Institute, Mangalore) (PGI, Chandigarh) (AllMS, Raipur)
Dr. Vishram Buche Dr. Sasidaran K. Dr. Utpal Bhalala
(Nelson Hospital, Nagpur) (Mehta Children Hospital, Chennai) (Baylor College of Medicine, USA)
Dr. Manindar Dhaliwal
(Medanta, Gurgaon)
Senior Editors
Dr. (Prof) Sunit Singhi Dr. Karunakara BP Dr. Basavaraja GV
(Medanta, Gurgaon) (Ramayya Hospital, Banglore) (IGICH, Banglore)
Dr. Uma Ali Dr. Sachin Shah Dr. Arun Bansal
(Wadia Hospital, Mumbai) (Surya Hospital, Pune) (PGl, Chandigarh)
International Advisory Board

Dr. Mark C. Rogers Dr. Suneel Poobonl Dr. Govlnd BennakattI Dr. Traci Wolbrink
(USA) (UK) (NMC Royal Hospital, Abu Dhabi) (Boston Children’s Hospital, USA)
Dr. Jerry Zimmerman Dr. Paolo Blban Dr. Phuc H Phan Dr. Sapna Kudchakar
(USA) (Italy) (Hanoi,Vietnam) (John Hopkins, USA)
Dr. Peter Cox Dr. Swee Phong Tang Dr. Mark Peters Dr. Vijay Srinivasan
(Canada) (Kualalampur, Malaysia) (London, UK) (Philadelphia, USA)
Dr. Niranjan Kissoon
(Vancouver, Canada)
National Advisers
Dr. Bakul Parekh Dr. Dighant Shastri Dr. Narendra Rungta
(Mumbai) (President IAP 2020) (Surat) (President IAP-2019) (JNUIRC, Jaipur)
Dr. Piyush Gupta Dr. Pratlbha Singhi
(Delhi) (President Elect IAP) (Medanta Hospital, Gurgaon)
Executive Members
Dr. Rameshkumar R. Dr. Lokesh Tiwari Dr. Sameer Sadawarte
(JIPMER, Puduccherry) (AIIMS, Patna) (Fortis Hospital, Mumbai)
Dr. Mahammad Ali Dr. Mihir Sarkar Dr. Raghunath CN
(Mission Hospital, Durgapur, WB) (PGIPS, Kolkotta) (Sagar Hospital, Banglore)
Dr. Raghavendra Vanaki
(SNM-HSK Hospital, Bagalkot)
Biostatistics
Dr. Satyen Gyani Dr. Lalltha A V
(Sparsh Hospital, Bhilai) (St. John’s Hospital, Banglore)
Ethical Committee Members
Dr. M. Jayshree Dr. Preetha Joshi
(PGI, Chandigarh) (K. Ambani Hospital, Mumbai)
Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020 i

Indian Academy Of Pediatrics
Intensive Care Chapter
Excecutive Board 2020
Dr. Basavaraja GV
Chairperson
Dr. Dhiren Gupta

Chairperson Elect
Dr. Bakul Parekh

Past Chairperson
Dr. Dayanand Nakate

Vice Chairperson
Dr. Arun Bansal

Secretary
Dr. Manish Sharma

Joint Secretary
Dr. Vinod Ratagiri

Treasurer
Dr. Praveen Khilnani

Vice Chancellor, IAP-ICC College of Pediatric Critical Care
Dr. Kundan Mittal

Editor, Journal of Pediatric Critical care
South Zone North Zone

Dr. K. Rajendran Dr. Punit Pooni
Dr. Raghunath CN Dr. Manindar Dhaliwal
West Zone Central Zone East Zone

Dr. Vinayak Patki Dr. Satyen Gyani Dr. Mihir Sarkar
Dr. Sameer Sadawarte Dr. Kasi Bandaru Dr. Sibabratta Patnaik
Office: Secretary, IAPICC, R No 3112, Level 3-A,

Advanced Pediatric Centre, Post Graduate Institute of Medical
Education & Research, Sector 12, Chandigarh – 160 012.
ii Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020

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Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020 iii

CONTENTS Volume 7, Issue 2, March-April 2020
Editorials
Hypocalcemia and Vitamin D3 deficiency in critically ill children: Does it matter?
Rakshay Shetty 53
The role of Vitamin D in asthma management: Myth or reality?
Vinayak Patki 55
Risk factors for bronchiolitis ‑ Can we really predict?
Bal Mukund, Ahmed Zaid Jamal 57
Microalbuminuria as a sensitive predictor of early glomerular injury in children with
sickle cell anemia
Govind Benakatti 59
Original Articles
Calcium, phosphate, and Vitamin D abnormalities in critically ill children
Shipra Agrwal, Urmila Jhamb, Smita Kaushik 61
Correlation of severity of asthma with serum Vitamin D3 and serum magnesium level
in children aged 5–14 years
Preeti Sharma, Alok Khanna, Kundan Mittal 69
Diagnostic accuracy of microalbuminuria among sickle cell children with nephropathy
Sitanshu Kumar Meher, Nihar Ranjan Mishra, Deepak Kumar Khamari, Bijan Kumar Nayak 73
Risk factors for bronchiolitis
Preeti Kulhalli, Dakshayini J. N., Vinod H. Ratageri, I. Shivanand, Prakash K. Wari 79
Case Reports
Haberland syndrome: Encephalocraniocutaneous syndrome presenting as status epilepticus
V. S. V. Prasad, Anzad Madathil Amanullah 84
Mycoplasma pneumoniae‑induced cerebral venous sinus thrombosis with autoimmune
hemolytic anemia
Sayali Deshpande, Bhakti Sarangi, Venkat Sandeep Reddy, Ajay Walimbe 88
Amitraz, an unusual poison
Yogesh N. Parikh, Mayur C. Gwalani, Aarti Makwana, Divyaraj A. Bavishi 92
Clinical Update
Chloride in intensive care
Kundan Mittal 95
Letter to Editor
Cardiac arrest secondary to Jervell‑Lange‑Neilson syndrome
Priya Sakte, Jennifer Antin, Sachin Jangam, Vinayak Patki 97
Critical Thinking-PICU Quiz

PICU quiz
Pradeep Kumar Sharma, Praveen Khilnani 99
Book Review
Pediatric respiratory diseases: A comprehensive textbook
Kundan Mittal 102
iv Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020

Editorial
Hypocalcemia and Vitamin D3 deficiency in critically ill

children: Does it matter?
Metabolic derangements are very common in critically ill and associated with severity and disease outcome.[10] Sankar
patients, especially children. Identification and appropriate et al. studied the prevalence of Vitamin D deficiency and its
correction are crucial for the disease management association to clinical outcome in 196 children admitted to
and decreasing mortality and morbidity. Data on the a PICU and found high prevalence of Vitamin D deficiency
abnormalities of calcium, phosphorus, and Vitamin D in critically ill children with increased length of ICU stay.[11]
in critically ill children admitted to a pediatric intensive
care unit (PICU) are scarce, especially from developing In this issue, Agarwal et al.[12] reported the findings from a
countries. prospective cross‑sectional study done in the PICU of a
tertiary care hospital. In the study, calcium, phosphorus,
Hypocalcemia has been reported in 12%–90% of critically and Vitamin D levels of children admitted to PICU were
ill adults and children.[1,2] analyzed. Of the 135 children included in the study, 24.4%
had hypocalcemia. The study showed a very high incidence
Hypophosphatemia is known to develop during the ICU of Vitamin D deficiency (85.9%). Their study showed that
stay, and the studies have shown that 60%–75% children total and ionized hypocalcemia were significantly more
developed hypophosphatemia during the PICU stay.[3] among the nonsurvivors (P = 0.012 and 0.047, respectively).
With Vitamin D deficiency being very common in healthy Hypophosphatemia and hyperphosphatemia were also
individuals, studies have reported the incidence of Vitamin significantly more in the nonsurvivor group (P = 0.048
D in critically ill children to be 17%–79%.[4,5]
and 0.018, respectively). They found that mortality was
higher in the children with total hypocalcemia (P = 0.006)
Abnormality of serum Ca can be due to a variety of
causes, e.g., altered Ca binding due to a change in the blood and ionized hypocalcemia (P = 0.03). They concluded
pH, elevation of fatty acids, sepsis, hypoalbuminemia, that calcium, phosphate, and Vitamin D abnormalities are
blood transfusion, renal failure, and hypomagnesemia.[6] common in critically ill children in a developing country
Hypophosphatemia is influenced by long‑term low intake, and that these abnormalities are associated with poor
decreased absorptive state, intracellular redistribution, outcome.
and increased renal tubular losses.[7] The frequency and
These results are consistent with many studies that
predisposing factors in children are not yet fully understood.
emphasize the importance of identifying the metabolic
Singhi et al. studied calcium profile in 100 children admitted derangements. They analyzed the calcium, phosphorus, and
to a PICU and concluded that hypocalcemia is common in Vitamin D levels together to find a correlation. However,
critically ill children admitted to a PICU and is associated the study population was small and they could not find
with higher mortality.[8] They found hypocalcemia in a relation to Vitamin D levels, probably due to the high
35% of the patients at admission and in another 13% incidence of Vitamin D deficiency in the study group. It is
during hospital stay. In their study cohort, mortality was difficult to conclude that the low Vitamin D levels are due
significantly higher in hypocalcemic (28.3%) group. to the critical illness considering that studies have shown
high incidence of Vitamin D deficiency in healthy subjects
Lodha et al. studied a cohort of 162 children and identified from the same geographic area.[13]
that hypophosphatemia was common in critically ill
children and was associated with prolonged length of stay This study emphasizes the importance of identifying
and increased duration of mechanical ventilation.[9] In their metabolic derangements in a critically ill child. It reinforces
study, serum phosphate <2.5 mg/dL was associated with that timely recognition and appropriate management are
increased mortality. crucial for a favorable outcome in a sick child.
McNally et al. conducted a systematic review on Vitamin D Overall, this study is a welcome addition to the available
deficiency in the PICU and found it to be highly prevalent scant data on calcium, phosphate, and Vitamin D levels
© 2020 Journal of Pediatric Critical Care | Published by Wolters Kluwer - Medknow 53
Shetty: Hypocalcemia and Vitamin D3 deficiency in critically ill children
in critically ill children. However, further systematic 9. Lodha R, Shah S, Irshad M, Gupta N, Kabra S. Hypophosphatemia
in critically ill children. Pediatr Crit Care Med 2014;15:60.
multicenter studies are required to confirm these findings.
10. McNally JD, Nama N, O’Hearn K, Sampson M, Amrein K, Iliriani K,
et al. Vitamin D deficiency in critically ill children: A systematic review
Rakshay Shetty and meta‑analysis. Crit Care 2017;21:287.
11. Sankar J, Lotha W, Ismail J, Anubhuti C, Meena RS, Sankar MJ.
Department of Pediatric Critical Care and Emergency Medicine, Vitamin D deficiency and length of pediatric intensive care unit stay:
Rainbow Children’s Hospital, Marathahalli, Bengaluru, Karnataka, A prospective observational study. Ann Intensive Care 2016;6:3.
India 12. Agarwal S, Jhamb U, Kaushik S. Calcium, phosphate, and Vitamin
D abnormalities in critically ill children. J Pediatr Crit Care
Address for correspondence: Dr. Rakshay Shetty, 2020;7:61-8.
Department of Pediatric Critical Care and Emergency Medicine, 13. Puri S, Marwaha RK, Agarwal N, Tandon N, Agarwal R, Grewal K, et al.
Rainbow Children’s Hospital, Marathahalli, Bengaluru, Karnataka, India. Vitamin D status of apparently healthy schoolgirls from two different
E‑mail: [email protected] socioeconomic strata in Delhi: Relation to nutrition and lifestyle. Br J
Nutr 2008;99:876‑82.
REFERENCES
1. Zivin JR, Gooley T, Zager RA, Ryan MJ. Hypocalcemia: A pervasive Received: 26-02-2020 Accepted: 08-03-2020
metabolic abnormality in the critically ill. Am J Kidney Dis Published: 10-04-2020
2001;37:689‑98.
2. Cardenas‑Rivero N, Chernow B, Stoiko MA, Nussbaum SR, Todres ID.
This is an open access journal, and articles are distributed under the terms of the Creative
Hypocalcemia in critically ill children. J Pediatr 1989;114:946‑51. Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to
3. de Menezes FS, Leite HP, Fernandez J, Benzecry SG, de Carvalho WB. remix, tweak, and build upon the work non‑commercially, as long as appropriate credit
Hypophosphatemia in critically ill children. Rev Hosp Clin Fac Med is given and the new creations are licensed under the identical terms.
Sao Paulo 2004;59:306‑11.
4. Marwaha RK, Sripathy G. Vitamin D and bone mineral density
Access this article online
of healthy school children in Northern India. Indian J Med Res
2008;127:239‑44. Quick Response Code:
Website:
5. Lucidarme O, Messai E, Mazzoni T, Arcade M, du Cheyron D.
Incidence and risk factors of Vitamin D deficiency in critically ill www.jpcc.org.in
patients: Results from a prospective observational study. Intensive
Care Med 2010;36:1609‑11.
DOI:
6. Chernow B, Zaloga G, McFadden E, Clapper M, Kotler M,
10.4103/JPCC.JPCC_36_20
Barton M, et al. Hypocalcemia in critically ill patients. Crit Care Med
1982;10:848‑51.
7. Miller DW, Slovis CM. Hypophosphatemia in the emergency
department therapeutics. Am J Emerg Med 2000;18:457‑61.
How to cite this article: Shetty R. Hypocalcemia and Vitamin D3 deficiency
8. Singhi SC, Singh J, Prasad R. Hypocalcaemia in a paediatric intensive
in critically ill children: Does it matter? J Pediatr Crit Care 2020;7:53-4.
care unit. J Trop Pediatr 2003;49:298‑302.
54 Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020

Editorial
The role of Vitamin D in asthma management: Myth or

reality?
Asthma is a chronic respiratory disease characterized by Esfandiar et al. in their study stated that though the presence
increased airway inflammation and hyperresponsiveness of Vitamin D deficiency effectively predicts increased risk
and is a major public health issue. It is one of the most for childhood asthma, the severity or control status of
common diseases affecting millions of population globally. this event may not be predicted by confirming Vitamin
Association between asthma pathogenesis and Vitamin D D deficiency.[8]
has become a matter of great interest for many researchers
worldwide in the past two decades. In this present issue, Sharma et al., in their prospective
observational study of 75 children, demonstrated that
Vitamin D is a fat‑soluble nutrient which is a modulator 66.66% of the patients admitted with asthma had
of calcium absorption and bone health. It also plays an Vitamin D3 insufficiency and 9.33% had deficiency.
important role in immune regulation and respiratory Among Vitamin D3 deficient patients, 71.4% had moderate
infections.[1] Studies have concluded that decreased level persistent asthma. However, the correlation between the
of serum 25 (OH) D is correlated with an increased level of asthma control and Vitamin D3 sufficiency levels
prevalence, hospitalization, and increased emergency visits could not be demonstrated.[9]
along with declined lung function and increased airway
hyperresponsiveness in asthmatic children.[2] There is no evidence to suggest that asthmatic patients
should be screened for Vitamin D deficiency or insufficiency.
Gupta et al. was one of the pioneer researches to point However, the high‑risk group (obese patients and who have
out the role of Vitamin D in the asthma pathogenesis at limited sun exposure) must be screened for this deficiency.
the molecular level. They found that children with both
moderate and severe asthma had significantly diminished Several clinical trials of Vitamin D to prevent asthma
levels of anti‑inflammatory interleukin (IL)‑10 in airway exacerbation and improve asthma control have been
lavage samples when compared with nonasthmatic controls. conducted in children and adults. Jolliffe et al. in their
The addition of Vitamin D3 enhanced IL‑10 secretion meta‑analysis of seven studies with 955 participants
without increasing IL13 or IL17 levels. Thus, this study also found that Vitamin D supplementation reduced the rate
demonstrated the steroid‑sparing properties of Vitamin D of asthma exacerbation requiring treatment with systemic
which may have additional benefits in the management of corticosteroids among all participants (adjusted incidence
severe asthma.[3]
rate ratio 0·74, 95% confidence interval 0·56–0·97;
P = 0·03; 955 participants in seven studies). There were
A cross‑sectional survey on 75 Italian asthmatic children
found that the prevalence of Vitamin D‑deficiency was no significant differences between the use of Vitamin D
53.3%.[4] In another survey from North America, 17% and placebo in the proportion of participants with at least
of asthmatics had Vitamin D deficiency, and a positive one exacerbation or time of first exacerbation.[10]
correlation was observed between Vitamin D levels and
Martineau et al., in their meta‑analysis which included
lung function.[5]
seven trials involving a total of 435 children and two trials
Kaaviyaa et al. demonstrated that Vitamin D deficiency is involving a total of 658 adults, found that people who were
associated with inadequate asthma control in children with given Vitamin D experienced fewer asthma attacks needing
moderate persistent asthma, on inhaled corticosteroids, treatment with oral steroids. The average number of attacks
in their small observational studies of Indian Children.[6] per person per year went down from 0.44 to 0.28 with
Vitamin D (high‑quality evidence). Vitamin D reduced the
However, a study conducted by Thuesen et al. on 4999 risk of attending hospital with an acute asthma attack from
Danish adults reported contrasting results and concluded 6/100 to around 3/100 (high‑quality evidence). Vitamin
that 25 (OH) D levels do not have any effect on the D had little or no effect on lung function or day‑to‑day
development of asthma and allergic symptoms.[7] asthma symptoms (high‑quality evidence).[11]
Patki: Vitamin D in asthma: Myth or reality?
Trials with larger sample sizes are needed to provide the Linneberg A. The association of serum 25‑OH Vitamin D with atopy,
asthma, and lung function in a prospective study of Danish adults.
evidence of causality between Vitamin D and asthma. These
Clin Exp Allergy 2015;45:265‑72.
trials will also be helpful in establishing the appropriate 8. Esfandiar N, Alaei F, Fallah S, Babaie D, Sedghi N. Vitamin D deficiency
route, dose, and safety of Vitamin D supplementation for and its impact on asthma severity in asthmatic children. Ital J Pediatr
the prevention and treatment of asthma. Further researches 2016;42:108.
9. Sharma P, Alok K, Mittal K. Correlation of severity of asthma with
are needed on the molecular level of Vitamin D receptor serum Vitamin D3 and serum magnesium level in children aged
to explain the role of dietary Vitamin D in the prevention 5‑14 years. J Ped Crit Care 2020;7:69-72.
and management of asthma. 10. Jolliffe DA, Greenberg L, HooperRL, Griffiths CJ, Camargo CA Jr,
Kerley CP, et al. Vitamin D supplementation to prevent asthma
exacerbations: A systematic review and meta‑analysis of individual
Vinayak Patki participant data. Lancet Respir Med 2017;5:881‑90.
11. Martineau AR, Cates CJ, Urashima M, Jensen M, Griffiths AP,
Department of Pediatrics, Wanless Hospital, Miraj, Nurmatov U, et al. Vitamin D for the management of asthma. Cochrane
Maharashtra, India Database Syst Rev 2016;9:CD011511. doi:10.1002/14651858.
CD011511.pub2
Address for correspondence: Dr. Vinayak Patki,
Department of Pediatrics, Wanless Hospital, Miraj, Maharashtra, India.
Received: 29-02-2020 Accepted: 07-03-2020
E‑mail: [email protected]
Published: 10-04-2020
REFERENCES
1. Chambers ES, Hawrylowicz CM. The impact of Vitamin D on This is an open access journal, and articles are distributed under the terms of the Creative
Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to
regulatory T cells. Curr Allergy Asthma Rep 2011;11:29‑36. remix, tweak, and build upon the work non‑commercially, as long as appropriate credit
2. Ali NS, Nanji K. A review on the role of Vitamin D in asthma. Cureus is given and the new creations are licensed under the identical terms.
2017;9:e1288.
3. Gupta A, Dimeloe S, Richards DF, Chambers ES, Black C, Urry Z, Access this article online
et al. Defective IL‑10 expression and in vitro steroid‑induced IL‑17A
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in paediatric severe therapy‑resistant asthma. Thorax 2014;69:508‑15. Website:
4. Chinellato I, Piazza M, Sandri M, Peroni D, Piacentini G, Boner AL. www.jpcc.org.in
Vitamin D serum levels and markers of asthma control in Italian
children. J Pediatr 2011;158:437‑41.
5. Devereux G, Wilson A, Avenell A, McNeill G, Fraser WD. DOI:
A case‑control study of Vitamin D status and asthma in adults. Allergy 10.4103/JPCC.JPCC_37_20
2010;65:666‑7.
6. Kaaviyaa AT, Krishna V, Arunprasath TS, Ramanan PV. Vitamin D
deficiency as a factor influencing asthma control in children. Indian
How to cite this article: Patki V. The role of Vitamin D in asthma
Pediatr 2018;55:969‑71.
management: Myth or reality? J Pediatr Crit Care 2020;7:55-6.
7. Thuesen BH, Skaaby T, Husemoen LL, Fenger M, Jørgensen T,

Editorial
Risk factors for bronchiolitis ‑ Can we really predict?

Acute bronchiolitis (AB) is one of the most common study found increased incidence in younger infant which
respiratory infection in infant and toddler <2 years of age has been attributed to reduced immunity to viral infection
with significant morbidity and huge economic burden to in this vulnerable age group. Low socio economic condition
the society. The incidence peaks in winter and may require has been attributed in studies from China, Spain, and other
hospital admission in around 1.8% of such children.[1] countries too and has been hypothesized to result from
Typically, AB is characterized by generalized peripheral enhanced risk of nutritional deficiency, increased risk of
small airway obstruction and manifests with tachypnea, pollution, low immunization status, environmental hazards
increased work of breathing and low hemidiaphragms contributing to this risk factor.[5,6] Cesarean section as
on chest radiographs. Respiratory syncytial virus (RSV) modality of delivery has been found to a have conflicting
is the most common virus in 50%–80% cases; however, results. In the present study, exposure to pets have been
adenovirus, influenza, parainfluenza, metapneumovirus, found a predictor, similar to another study from this
coronavirus, enterovirus, and rhinovirus are other viral subcontinent by Malla et al. has found, however, such
etiological agents.[2] Pathologically, infection by RSV is predisposition is mired with controversy due to inconsistent
characterized by sloughed necrotic respiratory epithelium, results.[7] In another similar study by Das et al., this study
excessive mucus secretions, bronchial mucosal edema, and also found heightened risk of AB in unvaccinated children
peribronchial inflammation. Most of the symptomatic which might have been due to either other co‑risk factors
children are managed with oxygen therapy and generalized or due to lack of cross protection from other infection in
supportive therapy.[3] None of the pharmacological agents such deprived children.[8] Since very few prospective study
including nebulization has been effective in the management exists for predictor of risk factors of AB in small infant and
of AB.[2] Lately, the use of continuous positive pressure children, it is considered prudent to do such multicentric
and heated humidified high‑flow nasal cannula have been clinic‑epidemiological study to understand risk factors
used with good results. The main predictor of severity and for development and severity of AB in children from our
poor outcome appears to be young age, prematurity, low region. Till we have such studies, it is difficult to predict
birth weight, previous history of pulmonary or cardiac both development and severity of AB.
diseases, immunodeficiency, malnutrion, lack of breast
feeding, presence of apnea, and pulmonary consolidation Bal Mukund, Ahmed Zaid Jamal
on admission chest radiograph.[4] There is paucity of clinical
data from India on risk factors for the development of AB. Departments of Pediatrics and Intensive Care, INHS Kalyani,
Visakhapatnam, Andhra Pradesh, India
In this issue, J of Peds Crit care by Kulhalli. et al., a Address for correspondence: Dr. Bal Mukund,
retrospective study from south India has been published Department of Pediatrics and Intensive Care, INHS Kalyani, Visakhapatnam,
to determine risk factors in the development of AB.[5] All Andhra Pradesh, India.
demographic data, immunization status, socioeconomic REFERENCES
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and allergies were studied. A total of 85 cases and 91 1. Brooks AM, McBride JT, McConnochie KM, Aviram M, Long C,
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hospitalized with respiratory syncytial virus infection. Pediatr
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to pets, and birth by cesarean section were found to have 2. Meissner HC. Viral bronchiolitis in children. N Engl J Med
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Mukund and Jamal: Risk factors for bronchiolitis-can we really predict?
3. Florin TA, Plint AC, Zorc JJ. Viral bronchiolitis. Lancet

2017;389:211‑24.
4. Ralston SL, Lieberthal AS, Meissner HC, Alverson BK,
Baley JE, Gadomski AM, et al. Clinical practice guideline: The This is an open access journal, and articles are distributed under the terms of the Creative
diagnosis, management, and prevention of bronchiolitis. Pediatr Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to
2014;134:e1474‑502. remix, tweak, and build upon the work non‑commercially, as long as appropriate credit
5. Kulhalli P, Dakshayini JN, Ratageri VH, Shivanand I, Kari PK. Risk is given and the new creations are licensed under the identical terms.
factors for bronchiolitis. J Ped Crit Care 2020;7:79-83.
6. Leem JH, Kim HC, Lee JY, Sohn JR. Interaction between
bronchiolitis diagnosed before 2 years of age and socio‑economic Quick Response Code:
Website:
status for bronchial hyperreactivity. Environ Health Toxicol
2011;26:e2011012. www.jpcc.org.in
7. Malla T, Poudyal P, Malla KK. Modifiable demographic factors that
differentiate bronchiolitis from pneumonia in Nepalese children less DOI:
than two years-a hospital based study. Kathmandu Univ Med J(KUMJ)
10.4103/JPCC.JPCC_39_20
2014;12:175-80.
8. Das PK, Saha JB, Basu K, Lahiri S, Sarkar GN. Some
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How to cite this article: Mukund B, Jamal AZ. Risk factors for
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2003;47:66‑71.

Editorial
Microalbuminuria as a sensitive predictor of early

glomerular injury in children with sickle cell anemia
Microalbuminuria (MA) defined as minute elevation in filtration rate [eGFR] <60 ml/min/1.73 m2 body surface
the urine albumin (30–300 mg/24 h in an adult or an area [BSA]) categorized into Stage‑III chronic kidney
albumin: creatinine ratio >20–30 mg/g creatinine in a disease (CKD);[7] understandably, this is quite advanced
random sample) in the absence overt proteinuria that is kidney disease rather than preclinical nephropathy. Again,
not detectable by conventional dipstick methods. It is a the estimation of GFR based on single creatinine value is
nonspecific but sensitive indicator of preclinical renal a crude method that often poorly correlates with measured
and cardiovascular morbidity and mortality. Its role as GFR. McKie et al.[8] analyzed longitudinal data of 191
a sensitive marker in diagnosing nephropathy of varied sickle cell children aged 3–20 years with a mean follow‑up
ethology (glomerular damage caused by hyperfiltration, of 2.19 ± 2.05 years. ACEI and hydroxyurea showed to
hyperperfusion, etc.) and as a predictor of progression reverse MA in half (44% hydroxyurea and 56% ACEI)
to overt renal failure is not something new, for example, of the patients. Therefore, longitudinal studies further in
diabetic nephropathy (DN) where it is widely used to earlier age groups with follow‑ups will address the primary
predict and prognosticate. Other areas of its use are concern of how early these children at risk can be identified
hypertensive nephropathy, cardiovascular disease (CVD) and appropriate (preventive) measures could be applied.
risk, etc.
In nutshell, improved standards of care have reflected
Similar renal damage is known to occur in sickle cell in the longer survival of children with SCA. SCN is an
anemia (SCA). Therefore, similar phenomenon of important risk factor for long‑term morbidity and mortality.
microproteinuria is reported to occur long before it Longitudinal studies involving earlier age groups are needed
progresses to overt proteinuria or renal failure.[1‑3] Renal to address the optimum age for early identification and
damage (sickle cell nephropathy [SCN]) results from then early interventions. Interventions such as ACEI and
hydroxyurea have been shown to retard the progression to
recurrent vaso‑occlusive crisis, ischemia–reperfusion
overt renal failure or CKD in these children.
injury, loss of renal mass, glomerular hyperfiltration, and
sclerosis.[4] Evidence of kidney changes has been observed
as early as infancy, and MA has been detected in as early Govind Benakatti
as 3–4 years.[5] Identification of MA and risk factors may Department of Pediatric Intensive Care, NMC Royal Hospital,
allow early interventions such as ACE inhibitors (ACEI) AD, UAE
and hydroxyurea, which have been shown to retard the Address for correspondence: Dr. Govind Benakatti,
progression to overt renal failure. In this issue of Journal NMC Royal Hospital, AD, UAE.
of Pediatric Critical Care, Meher et al. have tried to address E-mail: [email protected]
the role of MA in SCN similar to DN.[6] Given the limited REFERENCES
data, screening the children with SCA at an early age 1. McBurney PG, Hanevold CD, Hernandez CM, Waller JL, McKie KM.
and follow‑ups for the development of MA would have Risk factors for microalbuminuria in children with sickle cell anemia.
been more apt to address the objectives of the study. J Pediatr Hematol Oncol 2002;24:473‑7.
2. King L, MooSang M, Miller M, Reid M. Prevalence and predictors of
Enrolling a known, in fact, those in quite, advanced microalbuminuria in Jamaican children with sickle cell disease. Arch
nephropathy takes away the whole idea of finding out Dis Child 2011;96:1135‑9.
MA as an early indicator. Therefore, one can wonder 3. Abhulimhen‑Iyoha IB, Ibadin MO, Ofovwe EG. Comparative
that the study adds any value in differentiating those usefulness of serum creatinine and microalbuminuria in detecting
early renal changes in children with sickle cell anaemia in Benin city.
with SCN versus not. According to authors’ enrolment Niger J Paediatr 2009;36:1‑2.
strategy, those with the “disease” (estimated glomerular 4. Pham PT, Pham PC, Wilkinson AH, Lew SQ. Renal abnormalities in

Benakatti: Microalbuminuria and sickle cell nephropathy
sickle cell disease. Kidney Int 2000;57:1‑8.

5. Marsenic O, Couloures KG, Wiley JM. Proteinuria in children with
sickle cell disease. Nephrol Dial Transplant 2008;23:715‑20.
6. Meher SK, Mishra NR, Khamari DK, Nayak BK. Diagnostic accuracy
of microalbuminuria among sickle cell children with nephropathy. This is an open access journal, and articles are distributed under the terms of the Creative
J Ped Crit Care 2020;7:73-8. remix, tweak, and build upon the work non‑commercially, as long as appropriate credit
7. National Kidney Foundation. K/DOQI clinical practice guidelines for is given and the new creations are licensed under the identical terms.
chronic kidney disease: evaluation, classification, and stratification. Am
J Kidney Dis 2002;39:S1‑266.
8. McKie KT, Hanevold CD, Hernandez C, Waller JL, Ortiz L, McKie KM. Access this article online
Prevalence, prevention, and treatment of microalbuminuria and Quick Response Code:
proteinuria in children with sickle cell disease. J Pediatr Hematol Oncol Website:
2007;29:140‑4. www.jpcc.org.in
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10.4103/JPCC.JPCC_41_20
How to cite this article: Benakatti G. Microalbuminuria as a sensitive

predictor of early glomerular injury in children with sickle cell anemia.
J Pediatr Crit Care 2020;7:59-60.

Original Article
Calcium, phosphate, and Vitamin D abnormalities in

critically ill children
Shipra Agrwal, Urmila Jhamb, Smita Kaushik1
Department of Pediatrics and 1Biochemistry, Maulana Azad Medical College, New Delhi, India
Abstract Background and Aims: Calcium, phosphate, and Vitamin D abnormalities are common in critically ill
children, which may affect their outcome. However, data regarding the prevalence of these abnormalities
are scarce from developing countries. This study assessed the prevalence of calcium, phosphate, and Vitamin
D abnormalities in critically ill children and their association with the outcome.
Materials and Methods: This was a prospective, cross‑sectional study of children aged 1 month to 12 years
admitted to the pediatric intensive care unit of a tertiary care public hospital. Relevant clinical information
and PRISM III score were recorded, and blood sample for the estimation of serum calcium, phosphate, Vitamin
D, and other relevant parameters were collected at admission. Children were followed up till final outcome.
Results: A total of 135 children were included with a median age of 36 months. Total and ionized hypocalcemia
were present in 9.6% and 22.9%, respectively, and both were associated with higher mortality (P = 0.006
and 0.03, respectively). Children with total hypocalcemia more often had sepsis and required significantly
more fluid boluses and inotropes. Hypophosphatemia and hyperphosphatemia were present in 28.8% and
10.3%, respectively, and were also associated with significantly higher mortality. 85.6% of the children were
Vitamin D deficient, but no significant association with severity and outcome was found.
Conclusion: Calcium, phosphate, and Vitamin D abnormalities were common in critically ill children. Higher
mortality was associated with hypocalcemia and abnormal phosphate levels but not with Vitamin D deficiency.
There was significant association of hypocalcemia with sepsis, fluid bolus, and inotrope requirement.
Keywords: Critically ill children, hypocalcemia, mortality, pediatric intensive care unit stay, Vitamin D level
Address for correspondence: Dr. Urmila Jhamb, Department of Pediatrics, Maulana Azad Medical College, New Delhi ‑ 110 002, India.
INTRODUCTION hypocalcemia, e.g., hypoalbuminemia, renal failure, Vitamin

D deficiency, and hypoparathyroidism.[1] Some studies
Abnormalities of calcium, phosphate, and Vitamin D are have shown association of hypocalcemia with the duration
common in critically ill children admitted to the pediatric of stay, ventilation, severity of illness, and mortality.[2‑5]
intensive care unit (PICU), but data are scarce from Critically ill children also have various risk factors for
developing countries. Critically ill children have various developing hypophosphatemia, e.g. malnutrition, sepsis,
metabolic derangements which predispose them for diuretics, and steroid use, and this has been shown to
be associated with increased duration of stay and sepsis
Received: 22‑01‑2020 Revised: 22‑02‑2020
Accepted: 29-02-2020 Published: 10-04-2020
Access this article online Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to
remix, tweak, and build upon the work non‑commercially, as long as appropriate credit
Website: is given and the new creations are licensed under the identical terms.
www.jpcc.org.in
For reprints contact: [email protected]
DOI: How to cite this article: Agrwal S, Jhamb U, Kaushik S. Calcium, phosphate,
10.4103/JPCC.JPCC_9_20 and Vitamin D abnormalities in critically ill children. J Pediatr Crit Care
2020;7:61-8.

Agrwal, et al.: Calcium, phosphate, and Vitamin D abnormalities in critically ill children
in some studies, while others have failed to find any • Hyper vitaminosis D – 25 hydroxyvitamin
such association.[6‑8] Occurrence of hypercalcemia and D >100 ng/mL.
hyperphosphatemia is less in critically ill children, and the
association of these abnormalities with the outcome has Serum calcium value was corrected for serum albumin.
not been studied in detail. Studies have shown that Vitamin
D deficiency is common among critically ill children, and Data were analyzed using SPSS 16.0 software (Copyright
there are variable results of studies regarding its association 2007, SPSS Inc, Chicago, IL, USA). A P < 0.05 was
with severity of illness, sepsis, duration of ventilation, and considered statistically significant. For comparison of
PICU stay.[9‑15] High incidence of Vitamin D deficiency has categorical variables, Chi‑square/Fisher’s exact test was
been found even in healthy Indian children.[16,17] applied. Mann–Whitney/Student’s t‑test was applied for
comparison of categorical with quantitative variables.
The present study aims to analyze the prevalence Pearson and Spearman correlation coefficients were
of abnormalities in serum calcium, phosphate, and used to determine the correlation of the quantitative
25‑hydroxyvitamin D levels in the children admitted to the variables.
PICU and to study the association of these abnormalities
with the outcome. The study was approved by the institutional ethical
committee. Informed written consent was taken from the
MATERIALS AND METHODS parents.
This prospective, cross‑sectional study was conducted RESULTS

in the seven‑bedded PICU of a tertiary care hospital in
Delhi. Children aged 1 month to 12 years admitted to the A total of 226 children were admitted in the PICU during
PICU were consecutively enrolled. Children with known the study period (March–September 2014), and 135 were
renal or parathyroid dysfunction or those taking Vitamin included in the study. Ninety‑one were excluded for various
D were excluded. Taking prevalence of 40%, precision of reasons, e.g. death or transfer out of PICU before the sample
10%, and 95% confidence interval, using the formula for was drawn, consent not given, previous kidney disease,
sample size calculation for qualitative, cross‑sectional study, age <1 month, and readmission. Ninety‑three (68.1%)
a sample size of minimal 96 was calculated. were males and 42 (31.9%) were females. Median age
of the study population was 36 months. 33.3% of the
Demographic data, history including drug intake, children were <1 year of age, 29.7% were between 1
anthropometry, examination findings, primary diagnosis at and 5 years of age, and 37% were more than 5 years of
admission, PRISM III score, requirement of mechanical age. Sixty‑five (48.1%) children required ventilator support,
ventilation, and its duration, fluid boluses or inotropic and mortality in the study population was 22.2%. Primary
support, outcome, and duration of stay were recorded. system involved was central nervous system in 24%,
Blood sample for the estimation of serum calcium (total respiratory system in 17%, cardiovascular system in 15.5%,
and ionized), phosphate, sodium, potassium, alkaline and gastrointestinal system in 10.5%. Fourteen percent
phosphatase, blood urea, serum creatinine, serum albumin, were postoperative patients, and the remaining 7.4% had
and Vitamin D was collected within 24 h of admission (first other miscellaneous diagnosis.
morning). Methods used for analysis were O‑cresolphthalein
complexone for serum calcium, phosphomolybdate Table 1 shows the prevalence of various ser um
for serum phosphate, and electrochemiluminescence abnormalities in the study population. 17 (12.6%)
immunoassay method for Vitamin D. children had history of prior calcium supplementation.
There was no significant difference in the occurrence
Cutoff values were taken as follows: of hypocalcemia among those who had received prior
• Hypocalcemia – Total serum calcium <8.5 mg/dL and calcium supplementation (P = 0.93). The study showed
ionized calcium level <1 mmol/L[3] a very high incidence of Vitamin D deficiency (85.9%).
• Hypercalcemia – Total serum calcium >11 mg/dL and 74% of children had levels Vitamin D <10 ng/mL. None
ionized serum calcium >1.25 mmol/L[18] of them had hypervitaminosis D.
• Hypophosphatemia – Serum phosphate <3.7 mg/dL[19]
• Hyperphosphatemia – >6.5 mg/dL[19] Association of calcium abnormalities with demography,
• Vitamin D deficiency – serum 25 hydroxyvitamin PICU morbidities, and outcome is shown in Table 2.
D <20 ng/mL[20] Median age of the children with total hypocalcemia
Table 1: Prevalence of metabolic abnormalities in the study population

Parameter Value
Calcium
Total (mg/dL) Corrected for albumin (mg/dL) Ionized (mmol/L)
Mean (SD) 8.9 (1.2) 9.86 (1.3) 1.08 (0.18)
Males, mean (SD) 9.0 (1.28) 9.9 (1.25) 1.08 (0.19)
Females, mean (SD) 8.8 (1.18) 9.8 (1.29) 1.09 (0.16)
Hypocalcemia, n (%), mild, moderate, severe 33 (24.4) 13 (9.6) 31 (22.9) (1.1, 7.4, 4.4)
Hypercalcemia, n (%), mild, moderate, severe 3 (2.2) 9 (6.6) 17 (12.6) (4.4, 5.9, 2. 2)
Phosphate
Serum phosphate (mg/dL), mean (SD) 4.5 (1.5)
Male, mean (SD) 4.7 (1.5)
Female, mean (SD) 4.0 (1.3)
Hypophosphatemia, n (%) 39 (28.8)
Hyperphosphatemia, n (%) 14 (10.3)
Vitamin D
Serum level (ng/mL), mean (SD) 11.4 (13.2)
Male, mean (SD) 9.7 (12.7)
Female, mean (SD) 9.5 (11.2)
Deficiency (<20 ng/mL), n (%) 116 (85.9)
Insufficiency (20‑30 ng/mL), n (%) 10 (7.4)
Sufficiency (>30 ng/mL), n (%) 9 (6.7)
SD: Standard deviation
was significantly lower (P = 0.006). They were more

likely to have sepsis (P < 0.001) and required more fluid
boluses (P = 0.007) and inotropes support (P = 0.012).
Mean calcium was significantly lower among the children
with sepsis (P = 0.004). Mortality was higher in the
children with total hypocalcemia (P = 0.006) and ionized
hypocalcemia (P = 0.03), but no association was found
with hypercalcemia. There was no statistically significant
difference in gender distribution, need for mechanical
ventilation, duration of PICU stay, and duration of
ventilation between the normal and abnormal calcium
levels. Figure 1: Biochemical abnormalities among survivors and nonsurvivors
We did not find any significant association of abnormal DISCUSSION

serum phosphate levels with various morbidities, such as
sepsis, fluid bolus, inotrope, and ventilation requirement. Hypocalcemia has been reported in 18%–65% of the
PRISM III score and mortality were significantly higher critically ill children and adults.[2‑5,21] We found hypocalcemia
among the children with abnormal serum phosphate at admission in 24.4%; however, when corrected for
levels. The study did not find any significant association albumin, it was 9.6%. One gram per deciliter decrease in
of Vitamin D deficiency with requirement and duration of serum albumin decreases the total calcium by 0.8 mg/day,
mechanical ventilation, duration of PICU stay, biochemical and we considered serum albumin levels of <4 mg/dL
abnormalities of calcium or phosphate, sepsis, requirement as hypoalbuminemia. In our study, 122 (90%) children
of fluid bolus or inotropes, and mortality as shown in had serum albumin <4 mg/dL. Occurrence of total
Tables 3 and 4.
hypocalcemia at admission in our study was lower than
Comparison of the biochemical abnormalities between the study by Singhi et al.[3] (35%) and Cardenas‑Rivero
survivors and nonsurvivors is shown in Figure 1. Total et al.[5] (49%). Singhi et al.[3] found that an additional 13%
and ionized hypocalcemia were significantly more among of the patients developed hypocalcemia during PICU stay.
the nonsurvivors (P value 0.012 and 0.047, respectively). Ionized hypocalcemia at admission in our study was higher
Hypophosphatemia and hyperphosphatemia were also than the study by Broner et al.[4] (12.5%) and Cardenas‑Rivero
significantly more in the nonsurvivor group (P = 0.048 and et al.[5] (17.9%), while it was lower than the study by Naik
0.018, respectively). There was no significant difference in and Dandge[21] (47.5%). We did not check calcium levels
the rate of Vitamin D deficiency (not shown in figure). again during the PICU stay. Children with hypocalcemia had
Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020 63
Table 2: Correlation of calcium abnormalities with patient characteristics, severity of illness, sepsis, and biochemical parameters
Parameter Total Ca++ Ionized Ca++
Normocalcemia Hypocalcemia Hypercalcemia Normocalcemia Hypocalcemia Hypercalcemia
(113) (13) (9) (87) (31) (17)
Age (months), 36 (8‑96) 8 (3 21) 18 (6‑56) 36 (8‑96) 30 (5‑96) 24 (5‑69)
median (IQR) P=0.006 P=0.346 P=0.363 P=0.58
Male, n (%) 79 (69.9) 8 (61.5) 5 (55.6) 57 (65.5) 23 (74.2) 12 (70.6)
P=0.536 P=0.458 P=0.375 P=0.69
MV, n (%) 52 (46.0) 10 (76.9) 3 (33.3) 41 (47.1) 17 (54.8) 7 (41.2)
P=0.076 P=0.511 P=0.46 P=0.65
PICU stay (days), 11 (6‑22) 7 (5‑8.5) 11 (4.5‑14.5) 11 (6‑20) 8 (5‑15) 12 (4.5‑20.5)
median (IQR) P=0.528 P=0.845 P=0.412 P=0.46
MV days, median (IQR) 7 (3‑15) 4.5 (2‑10) 4 (3‑13) 5 (2‑11) 8 (3.5‑12.5) 15 (3‑28)
P=0.350 P=0.683 P=0.342 P=0.23
Fluid boluses, n (%) 29 (25.6) 8 (61.5) 1 (11.1) 22 (25.3) 13 (41.9) 3 (17.6)
P=0.007 P=0.45 P=0.08 P=0.76
Inotropes, n (%) 31 (27.4) 8 (61.5) 1 (11.1) 24 (27.6) 13 (41.9) 3 (17.6)
P=0.012 P=0.443 P=0.14 P=0.55
Sepsis, n (%) 24 (21.2) 9 (69.2) 2 (22.2) 22 (25.3) 13 (41.9) 2 (11.7)
P=0.000 P=1.00 P=0.14 P=0.23
Serum ALP IU/L
Median (IQR) 171 (127‑239) 160 (84‑344) 88 (75‑182) 168 (103‑239) 170 (127‑238) 156 (127‑285)
Mean (SD) 193.5 (112) 400 (550) 161.3 (153) 189 (120) 273 (379) 209 (124)
P=0.83 P=0.07 P=0.58 P=0.59
Serum PO4 (mg/dL)
Median (IQR) 4.3 (3.6‑5.3) 3.9 (3.4‑5.3) 4.2 (3.4‑4.9) 4.2 (3.6‑5.1) 4.0 (3.2‑5.7) 4.6 (4.1‑5.2)
Mean (SD) 4.56 (1.5) 4.25 (1.39) 4.2 (1.27) 4.5 (1.5) 4.4 (1.6) 4.8 (1.5)
P=0.531 P=0.607 P=0.55 P=0.15
Hypophosphatemia, n (%) 32 (28.3) 4 (30.7) 3 (33.3) 26 (29.9) 11 (35.5) 2 (11.8)
P=1.00 P=1.00 P=0.49 P=0.14
Hyperphosphatemia, n (%) 13 (11.5) 1 (7.6) 0 (0) 9 (10.3) 4 (12.9) 1 (5.9)
P=1.00 P=0.58 P=0.73 P=0.68
Serum Vitamin D (ng/mL)
Median (IQR) 4.12 (3‑13.9) 3 (3‑5.3) 3 (3‑3.7) 4.03 (3‑11) 3 (3‑9.6) 4.12 (3‑21.2)
Mean (SD) 10.5 (13) 6.06 (6.53) 4.4 (3.6) 10 (13.2) 8.2 (9.9) 4.4 (3.6)
P=0.087 P=0.04 P=0.46 P=0.70
Vitamin D >30 ng/mL, 9 (7.9) 0 (0) 0 (0) 7 (8.0) 1 (3.2) 1 (5.9)
n (%) P=0.596 P=1.00 P=0.68 P=1.00
20‑30 ng/mL 8 (7) 2 (15.3) 0 (0) 5 (5.7) 2 (6.4) 3 (17.6)
P=0.233 P=1.00 P=1.00 P=0.12
<20 ng/mL 86 (76.1) 11 (84.6) 9 (100) 75 (86.2) 28 (90.3) 13 (76.5)
P=1.00 P=0.358 P=0.76 P=0.39
PRISM score, 3 (0‑7) 6 (2.5‑10) 4 (1.5‑6) 3 (0‑7) 7 (3‑8) 0 (0‑3)
median (IQR) P=0.10 P=0.62 P=0.05 P=0.02
Mortality 21 (18.6) 7 (53.8) 16 (19.5) 12 (40)
P=0.006 P=0.03
PICU: Pediatric intensive care unit, ALP: Alkaline phosphatase, PRISM: Pediatric risk of mortality, SD: Standard deviation, IQR: Interquartile range,
MV: Mechanical ventilation
significantly higher incidence of sepsis and those with sepsis stability. Studies have shown significant association of
had lower mean calcium levels. Higher incidence of sepsis hypocalcemia with hypotension and requirement of
among the hypocalcemic patients was found by Chernow cardiovascular support.[3,5,21,24] Vincent et al.[25] showed that
et al.[2] (P = 0.01 for total hypocalcemia) and Cardenas‑Rivero infusion of intravenous calcium in the critically ill patients
et al.[5] (P = 0.03 for ionized hypocalcemia). Hypocalcemia was associated with significant increase in mean arterial
was found in 57% and 83% of the children with sepsis in pressure that lasted for about 1 h. We also found significant
studies by Singhi et al.[3] and Naik and Dandge, respectively.[21] association of hypocalcemia with fluid and inotrope
Calcium level in the setting of sepsis has been found to be requirement. Children with hypocalcemia had significantly
inversely related to the levels of inflammatory mediators, higher mortality compared to those with normal or high
e.g. tumor necrosis factor, interleukin‑6, and procalcitonin.[22] serum calcium. Our observation was consistent with other
Raised calcitonin precursors have also been implicated as a studies.[3‑5,21]
cause of hypocalcemia in septic patients.[23]
Higher proportion of the children with hypocalcemia
Calcium is an important cation for neuromuscular required mechanical ventilation compared to those
transmission, muscle contraction, and membrane with normal serum calcium, but the difference was not
Table 3: Association of Vitamin D levels with outcome and calcium/phosphate levels

Parameter Deficient Insufficient Sufficient P
Vitamin D <20 ng/mL (n=116) Vitamin D 20‑30 ng/mL (n=10) Vitamin D >30 ng/mL (n=9)
Age (months)
Median (IQR) 36 (8‑96) 13 (2‑39) 6 (5‑42) 0.051
Mean (SD) 54 (48.9) 22.7 (26.7) 29.4 (37.4)
PICU stay (days)
Median (IQR) 11 (6‑19) 10.5 (3.7‑16.7) 16 (8.5‑33.5) 0.36
Mean (SD) 15.8 (14.7) 16.3 (20.1) 12.6 (17.9)
Duration of ventilation
Median 5 (3‑11) 8 (2‑16) 9 (3‑20) 0.24
Mean (SD) 8.6 (8.6) 9.3 (6.8) 18.5 (16.8)
PRISM III score
Median (IQR) 3 (0‑7) 3 (0‑3.3) 3 (1‑7.5) 0.9
Mean (SD) 4.9 (5.6) 3.7 (3.5) 4.6 (4.2)
Serum ALP
Median (IQR) 167 (117‑239) 128 (97‑204) 188 (133‑297) 0.35
Mean (SD) 216.4 (221) 153.4 (68) 209.8 (89.7)
Serum calcium, mean (SD) 9.9 (1.3) 9.3 (1.3) 10.2 (0.6) 0.33
Serum ionized calcium, mean (SD) 1.07 (0.19) 1.09 (0.23) 1.11 (0.13) 0.83
Serum phosphate
Median (IQR) 4.2 (3.5‑5.3) 4.3 (3.8‑5.1) 4.4 (4.3‑5.8) 0.49
Mean (SD) 4.5 (1.5) 4.6 (1.3) 4.9 (1.2)
PICU: Pediatric intensive care unit, ALP: Alkaline phosphatase, SD: Standard deviation, IQR: Interquartile range, PRISM: Pediatric risk of mortality
Table 4: Association of Vitamin D deficiency with biochemical abnormalities and outcome

Vitamin D level Deficient (<20 ng/mL), n (%) Nondeficient (>20 ng/mL), n (%) P
(n=116) (n=19)
Age (months), median (IQR) 36 (8‑96) 5.5 (3‑36) 0.045
Male, n (%) 79 (68.1) 13 (68.4) 0.98
Female, n (%) 37 (31.9) 6 (31.6)
MV, n (%) 52 (44.8) 13 (68.4) 0.056
Fluid boluses, n (%) 34 (29.3) 4 (21) 0.54
Inotropes, n (%) 36 (31) 4 (21) 0.43
Sepsis, n (%) 31 (26.7 6 (31.6) 0.66
Mortality, n (%) 26 (22.4) 4 (21) 0.89
Hypocalcemia, n (%) 11 (9.5) 2 (10.5) 1.00
Hypercalcemia, n (%) 9 (7.7) 0 (0) 0.36
Hypocalcemia (ionized), n (%) 28 (24.1) 3 (15.8) 0.76
Hypercalcemia (ionized), n (%) 13 (11.2) 4 (21) 0.29
Hypophosphatemia, n (%) 36 (31) 3 (15.8) 0.26
Hyperphosphatemia, n (%) 12 (10.3) 2 (10.5) 1.00
IQR: Interquartile range, MV: Mechanical ventilation
statistically significant. We did not find any significant during the PICU stay. [6,7,28] We analyzed phosphate
association of total hypocalcemia with the PRISM III score. levels only at the PICU admission. The incidence of
This was in contrast to other studies which showed higher hypophosphatemia in our study was lower than the study
severity of illness among hypocalcemic patients.[5,26,27] The by Santana e Meneses et al.[28] Malnutrition has been
children with ionized hypocalcemia had significantly higher described as an independent risk factor for the occurrence
PRISM scores. Patients with hypocalcemia have been of hypophosphatemia.[6,28] In our study, malnutrition
shown to stay in the PICU for longer period, but we did was present in 43.6% of the hypophosphatemic patients
not find any association of hypocalcemia with the duration which was similar to the findings of de Menezes et al.
of ventilation or ICU stay.[2,3,21] Our study did not show and Santana e Meneses et al.[6,28] Hypophosphatemia was
any significant association of hypercalcemia with severity significantly associated with malnutrition in the study of
of illness, duration of ventilation or PICU stay, need for de Menezes et al.[6] (P = 0.04), but our study did not show
cardiovascular support, or mortality. any significant association (P = 0.73).
Hypophosphatemia is a common metabolic abnormality in We did not find any significant association of
critically ill children and adults. Hypophosphatemia is known hypophosphatemia with requirement and duration of
to develop during the ICU stay, and studies have shown mechanical ventilation and duration of PICU stay. Our
that 60%–75% children developed hypophosphatemia findings were similar to those of de Menezes et al.[6] and

Ruiz Magro et al.[8] while Kilic et al.[7] found significant D deficiency in our study (85.9% deficient and 7.4%
association of hypophosphatemia with the duration of insufficient) was higher than the other Indian study by
mechanical ventilation and ICU stay (P = 0.02 and 0.001, Lodha et al.[35] (71%). Some studies from the same city
respectively). have shown that the incidence of Vitamin D deficiency
in healthy children is 85%–90%.[16,17] It is difficult to state
Studies have reported the incidence of hypophosphatemia whether the high incidence of Vitamin D deficiency in
among patients with sepsis to be up to 80%.[7,29] Our our study population is due to critical illness or only a
study showed that 35% of the children with sepsis had reflection of the population prevalence. In the critically ill
hypophosphatemia and 13.5% had hyperphosphatemia. children, Vitamin D levels may decline further during the
High levels of inflammatory cytokines are associated ICU stay due to insufficient replacement and the absence
with hypophosphatemia. [29] In our study, 23% of of ultraviolet‑B exposure.[14] We, however, did not repeat
normophosphatemic and 33% of hypophosphatemic the vitamin levels during PICU stay.
patients had sepsis (P = 0.24). This observation was in
contrast to Kilic et al.[7] The effects of Vitamin D are mediated through Vitamin
D receptor. Vitamin D acts on both the adaptive and
Bollaert et al.[30] showed a significant increase in the left innate immunity systems. Vitamin D deficiency has been
ventricular stroke volume and arterial pressure immediately implicated in various immune disorders, e.g. inflammatory
after intravenous phosphate infusion, and it was also bowel disease, asthma, and type one diabetes. [36,37]
associated with increase in arterial pH. However, we did Studies have shown significant association of Vitamin D
not find any significant association of hypophosphatemia deficiency with occurrence of sepsis in children as well as
with the requirement of fluid bolus and inotrope among in adults.[12,38] We did not find any significant association
the critically ill children. This observation was similar to of Vitamin D deficiency with the occurrence of sepsis.
de Menezes et al.[6] Similar observation was made by Amrein et al.[13] Vitamin
D deficiency has been found to be associated with a
In our study, the median PRISM III score was significantly higher requirement of cardiorespiratory support.[9,10]
higher among the hypophosphatemic (P = 0.013) and Severe Vitamin D deficiency is associated with decreased
hyperphosphatemic children (P = 0.008) compared to the muscle strength and may lead to prolonged ventilation
normophosphatemic patients. de Menezes et al.[6] did not find requirement and difficulty in weaning.[39] Some studies
any such association. In the study by Kilic et al.,[7] the mean have found association of Vitamin D deficiency with
PRISM score was higher among the hypophosphatemic a longer duration of stay,[9] while others have failed to
patients, but the difference was not significant. We demonstrate such association.[13,15,39‑41] We did not find
could not find any study comparing the incidence of any significant association of Vitamin D deficiency with
hyperphosphatemia with duration of ventilation, occurrence the cardiorespiratory support requirement, duration of
of sepsis, PRISM score, and mortality. PICU stay, and duration of mechanical ventilation, and
this observation was similar to other studies.[10,14,15] Amrein
We found higher mortality among the children with abnormal et al.[14] found that the mortality was lower among the adult
serum phosphate levels. Incidence of hypophosphatemia ICU patients who were on Vitamin D supplementation
and hyperphosphatemia was significantly higher among compared to those on placebo. We did not find any
nonsurvivors. Suzuki et al. [31] showed that patients significant association of Vitamin D deficiency with
with at least one episode of hypophosphatemia had mortality.
higher mortality, but on multivariate regression analysis,
hypophosphatemia was not an independent predictor Strength of our study was that it was a prospective study
of mortality. Severe hypophosphatemia has been found and we analyzed calcium, phosphate, and Vitamin D
to be associated with eightfold increase in risk of together and tried to find a correlation among them.
mortality in septic patients.[32] Haider et al.[33] found that The limitations of our study were small sample size and
hyperphosphatemia was significantly associated with that we did not analyzed parathyroid hormone levels as
mortality. The deleterious effect of low serum phosphate a cause of calcium and phosphate abnormalities. In our
can be explained by its effect on myocardial function, study, most of the patients had Vitamin D deficiency
response to vasopressors, and ATP generation. or insufficiency. Very small number of patients in our
study had normal Vitamin D levels, and this may be the
Incidence of Vitamin D deficiency in critically ill children reason for not finding any significant association with
ranges from 28% to 71%.[9,34,35] Incidence of Vitamin the outcome.

CONCLUSION Effect of high‑dose Vitamin D3 on hospital length of stay in critically

ill patients with Vitamin D deficiency: The VITdAL‑ICU randomized
clinical trial. JAMA 2014;312:1520‑30.
Our study provides data regarding the prevalence of 15. Venkatram S, Chilimuri S, Adrish M, Salako A, Patel M, Diaz‑Fuentes G.
calcium, phosphate, and Vitamin D abnormalities in Vitamin D deficiency is associated with mortality in the medical
critically ill children in a developing country. Calcium intensive care unit. Crit Care 2011;15:R292.
deficiency has a significant association with cardiovascular 16. Puri S, Marwaha RK, Agarwal N, Tandon N, Agarwal R, Grewal K, et al.
Vitamin D status of apparently healthy schoolgirls from two different
morbidity and incidence of sepsis. Abnormality of calcium socioeconomic strata in Delhi: relation to nutrition and lifestyle. Br J
and phosphate is associated with poorer outcome in Nutr 2008;99:876‑82.
critically ill children. We found very high incidence of 17. Marwaha RK, Sripathy G. Vitamin D & bone mineral density
of healthy school children in Northern India. Indian J Med Res
Vitamin D deficiency. In view of very low number of 2008;127:239‑44.
patients having sufficient Vitamin D levels group, the 18. Egi M, Kim I, Nichol A, Stachowski E, French CJ, Hart GK, et al.
association of Vitamin D deficiency with various PICU Ionized calcium concentration and outcome in critical illness. Crit
morbidities could not be analyzed accurately. Care Med 2011;39:314‑21.
19. Greenbaum LA. Electrolyte and acid base disorders. In: Kliegman RM,
Stanton BF, St. Geme JW, Schor NF, Behrman RE, editors. Nelson
Financial support and sponsorship Textbook of Pediatrics. 20th ed. Philadelphia: Saunders Elsevier; 2013.
Nil. p. 212‑42.
20. Balasubramanian S, Dhanalakshmi K, Amperayani S. Vitamin D
Conflicts of interest deficiency in childhood‑A review of current guidelines on diagnosis
and management. Indian Pediatr 2013;50:669‑75.
There are no conflicts of interest. 21. Naik N, Dandge V. Role of calcium in critically ill children‑Incidence
of hypocalcemia in pediatric intensive care unit set up. Indian J Appl
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Original Article
Correlation of severity of asthma with serum Vitamin D3

and serum magnesium level in children aged 5–14 years
Preeti Sharma, Alok Khanna, Kundan Mittal
Department of Pediatrics, Pandit Bhagwat Dayal Sharma Postgraduate Institute of Medical Sciences, Rohtak, Haryana, India
Abstract Background: Asthma is a common chronic respiratory disease affecting 1%–18% of the population in different
countries. Many factors, such as genetic predisposition, early allergen exposure, infections, diet, tobacco
smoke exposure, pollution, and Vitamin D3 status, are all proposed to influence the development and
severity of asthma. Vitamin D3 alters human airway smooth muscle expression of chemokines and inhibits
the expression of a steroid‑resistant gene. Magnesium ion has an inhibitory action on smooth muscle
contraction, histamine release from mast cells, and acetylcholine release from cholinergic nerve terminals,
thus influencing the function of respiratory smooth muscles.
Aim: The aim is of this study is to assess serum Vitamin D3 level and serum magnesium level in children
with asthma aged 5–14 years.
Materials and Methods: This was a cross‑sectional study involving 75 children of 5–14 years of age having
asthma, who were classified into intermittent, mild, moderate, and severe asthma, and serum Vitamin D3
levels and magnesium levels were estimated.
Results: Serum Vitamin D3 levels were significantly lower in children with severe asthma as compared to
those with mild, moderate, or intermittent asthma, but serum magnesium levels were found to have no
correlation with the severity of asthma in our study.
Conclusion: Vitamin D3 insufficiency is widely prevalent in Indian children with asthma and significantly
correlated with the severity of asthma. Serum magnesium levels within the normal range and correlation
of the severity of asthma with serum magnesium levels cannot be established in our study.
Keywords: Asthma, magnesium, Vitamin D3
Address for correspondence: Dr. Preeti Sharma, Department of Pediatrics, Pandit Bhagwat Dayal Sharma Postgraduate Institute of Medical Sciences,
Rohtak ‑ 124 001, Haryana, India.
INTRODUCTION breath, chest tightness, and cough that vary over time and in
intensity, together with variable expiratory airflow limitation
Asthma is a heterogeneous disease which is characterized affecting an estimated 330 million individuals worldwide
by chronic airway inflammation. It is defined by the history with a reported prevalence of 5%–20% in children
of respiratory symptoms such as wheeze, shortness of aged between 6 and 15 years.[1,2] In India, the estimated
burden of asthma is >30 million. In children, incidence
Received: 02‑01‑2020 Revised: 22-01-2020 reported by 6–7 years and 13–14 years are 2.3% and 3.3%,
www.jpcc.org.in
DOI: How to cite this article: Sharma P, Khanna A, Mittal K. Correlation of severity
10.4103/JPCC.JPCC_13_20 of asthma with serum Vitamin D3 and serum magnesium level in children
aged 5–14 years. J Pediatr Crit Care 2020;7:69-72.

Sharma, et al.: Correlation of severity of asthma with serum Vitamin D3
Table 1: Classifying asthma severity in children 5-11 years of age[8]

Persistent
Intermittent Mild Moderate Severe
Symptoms <2 day/week >2 days/week but not daily Daily Throughout day
Night awakening <2×/month 3-4×/month >1×/week but not nightly >7×/week
SABA use <2 days/week >2 days/week but not daily Daily Several times per day
Interference with normal None Minor limitation Some limitation Extremely limited
activity
Lung functions Normal FEV1 between exacerbations FEV >80% predicted FEV1=60%-80% predicted FEV1 <60% predicted
FEV1 >80% predicted FEV1/FVC >80% FEV1/FVC=75%-80% FEV1/FVC reduced <75%
FEV1/FVC >85%
FVC: Forced vital capacity, FEV1: Forced expiratory volume in 1 s, SABA: Short-acting beta agonists
respectively.[3,4] Vitamin D3 has been shown to have a Reference range:[9]

role in both innate and adaptive immunity by promoting • Category – serum Vitamin D3 levels
phagocytosis and modulating the effects of TH1, TH2, • Sufficiency: >20 ng/ml (>50 nmol/L)
and regulatory T‑cells. [5] Further evidence suggests • Insufficiency: 12–20 ng/ml (30–50 nmol/L)
that Vitamin D3 alters human airway smooth muscle • Deficiency: <12 ng/ml (<30 nmol/L).
expression of chemokines and inhibits the expression of
a steroid‑resistant gene.[6] Magnesium is a cation having Magnesium: serum magnesium was measured by using
modulatory effect on the contractile state of smooth spectrophotometry technique.
muscle cells in various tissues. Hypomagnesemia leads to
contraction while hypermagnesemia leads to relaxation.[7] Reference range: 1.7–2.5 mg/dL.[10]
Hence, this study was carried out to detect the prevalence
of hypomagnesemia with Vitamin D insufficiency and Statistical analysis
deficiency among asthmatic children group (5–14 years) At the end of the study, the data were collected and
of India. This study also aims to assess the relationship entered into Microsoft Excel. Continuous variables were
between serum magnesium and Vitamin D levels with the expressed as mean ± standard deviation and categorical
severity of asthma. variables were expressed as number/percentage. Statistical
analysis was performed using SPSS version 20.0 (IBM
MATERIALS AND METHODS SPSS Statistics).
1. Differences between continuous variables were
This study was a cross‑sectional observational study assessed using Student’s t‑test for normally distributed
conducted in the Department of Pediatrics, in PGIMS data
Rohtak, from January 2018 to February 2019, including 2. Differences between categorical variables were
75 children of age group 5–14 years who were diagnosed assessed using the Chi‑square test or Fischer’s exact
case of asthma and classified according to the severity test. A value of P < 0.05 was considered statistically
as per the EPR3 (guidelines for the diagnosis and significant.
management of asthma Table 1.[8] Among these children,
50 (66.55%) were male and 25 (33.34%) were female. RESULTS
Children with chronic renal disease, disease of calcium,
and bone metabolism or those who were on Vitamin Table 2 shows the demographic profile of the children
D3 supplementation, calcium therapy were excluded from according to gender and the severity of asthma. A total
the study. The ethics committee approved the study. After of 26 males and 17 females found to be intermittent,
taking informed consent, a prestructured pro forma was 15 males and 5 females with mild persistent and 9 males
used to record the relevant information from individual and 3 females as moderate persistent. Severe persistence
cases selected for the study. A detailed clinical examination was not seen in any of the patients. Figure 1 and Table 3
was conducted, and under aseptic precautions, blood was show a significant correlation of serum Vitamin D3 level
drawn for relevant investigations, and then, the child was with the severity of asthma. Among deficient patients,
subjected for pulmonary function test (peak expiratory 71.4% had moderate persistent asthma, 28.5% mild
flow rate). persistent asthma and among insufficient patients, 32% had
moderate persistent asthma, 12% mild persistent asthma,
Vitamin D3 level was measured in the serum of patients 56% intermittent asthma, showing that children who are
using chemiluminescent immunoassay on Beckman Vitamin D3 insufficient or deficient have a higher incidence
Coulter, Access 2 instrument technique. of severe asthma.
Moreover, results show stage‑wise decline in serum levels ratio of 2:1. The slightly higher number of males in the
of Vitamin D3 with an increase in the severity of asthma. study was probably a bias due to small sample size. A male
There is no significant difference in serum magnesium preponderance in asthma has been reported by various
levels in asthmatic patients. According to Table 4, authors. Vittal have been reported a higher prevalence in
Thirty‑eight (50.66%) patients had serum magnesium levels boys (3.1%) as compared to girls (4.1%) in a study from
in the range of 1.7–2, 36 (48%) patients had between 2.1 Shimla.[13] A study by Chhabra et al. from Delhi has shown
and 3 and only 1 (1.33%) patient had magnesium level >3. a significantly higher prevalence of current asthma in boys
All had serum magnesium levels within the normal range. as compared to girls (12.8% and 10.7%, respectively).[14]
As shown in Table 5, no significant correlation can be Our result demonstrated that 66.66% of patients admitted
established between hypomagnesemia and asthma severity. with asthma had Vitamin D3 insufficiency and 9.33%
Furthermore, the duration of pediatric intensive care unit had deficiency and among deficient patients, 71.4% had
stay, number of acute exacerbations, asthma control at the moderate persistent asthma as compared to 28.5% had
time of presentation compared in our study to the asthma mild persistent asthma, while no patient with intermittent
severity but did not show any significant correlation. asthma had Vitamin D deficiency. The study showed that
children who are Vitamin D3 insufficient or deficient have
DISCUSSION
a higher incidence of severe asthma but statistically found
to be insignificant correlation between the level of asthma
Bronchial asthma is a chronic condition characterized by
control and Vitamin D3 sufficiency levels.
recurrent bronchospasm resulting from reversible bronchial
hyperresponsiveness in response to stimuli of a level or All the children included had serum magnesium levels
intensity which usually does not cause such narrowing in within the normal range that is 1.7–2.5 mg/dL. No
most individuals.[11] Asthma is the major health problem
controls were included; therefore, comparison in serum
worldwide and increase in the prevalence of asthma has
magnesium levels between asthmatic and nonasthmatic
been reported in recent years, particularly in developing
children cannot be established. Thus, our study showed no
countries like India with the prevalence of about 2%.
significant correlation between serum magnesium level and
Calcitriol (active form of Vitamin D3) is involved in
asthma severity. Youssef aimed at outlining the possible
insulin secretion, inhibition of interleukin production by
role of magnesium in the pathogenesis and treatment
T‑lymphocytes and immunoglobulin by B‑lymphocytes,
of bronchial asthma including 27 asthmatic children
differentiation of monocyte precursor cells, and modulation
and 15 healthy controls, measuring both intracellular
of cell proliferation. Cells of the immune system such as
and extracellular magnesium levels. The results found a
T‑lymphocytes activated B‑lymphocytes, and dendritic cells
significant correlation between the severity of asthma
express Vitamin D3 receptors.[12] The age of children in the
study population ranged from 5 years to 14 years. The mean
age of the study patients was 8.75 ± 2.64 years. The study
included 50 males and 25 females with a male‑to‑female
Table 2: Severity of asthma according to gender

Male (n=50) Female (n=25) Statistical
significance
Intermittent 26 17 P=0.186
(>0.05 NS)
Mild persistent 15 5 P=0.355
(>0.05 NS)
Moderate persistent 9 3 P=0.404
(>0.05 NS)
Severe persistent 0 0 ‑ Figure 1: Comparison of serum Vitamin D3 levels with severity of
NS: Not significance asthma
Table 3: Correlation between the severity of asthma and Vitamin D3 levels

Vitamin D3 status Statistical analysis
Sufficiency (>20 ng/ml) Insufficiency (12-20 ng/ml) Deficiency (<12 ng/ml)
Intermittent 15 28 0 <0.001 significant
Mild persistent 2 16 2 <0.001 significant
Moderate persistent 1 6 5 <0.001 significant
Severe persistent 0 0 0 ‑

Table 4: Distribution of patients according to their serum Conflicts of interest

magnesium level There are no conflicts of interest.
Serum magnesium (range) Number of patients (%)
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15. Youssef MF. Magnesium status and therapeutic effects in asthmatic
magnesium levels cannot be established in study.
children. EC Paediatr 2018;73:194‑203.
16. Kakish KS. Serum magnesium levels in asthmatic children
Financial support and sponsorship during and between exacerbations. Arch Pediatr Adolesc Med
Nil. 2001;155:181‑3.

Original Article
Diagnostic accuracy of microalbuminuria among sickle cell

children with nephropathy
Sitanshu Kumar Meher, Nihar Ranjan Mishra, Deepak Kumar Khamari, Bijan Kumar Nayak
Department of Pediatrics, Veer Surendra Sai Institute of Medical Sciences and Research, Sambalpur, Odisha, India
Abstract Objective: The aim of this study is to detect the diagnostic accuracy of microalbuminuria (MA) among
sickle cell children with nephropathy.
Materials and Methods: Five hundred and seven sickle cell homozygous children between 5 and 14 years
of age group were enrolled after receiving written informed consent from the parents and/or caregiver.
Children with preexisting kidney diseases, albuminuria, and taking any drugs that will affect renal function
were excluded from the study. Sickle cell nephropathy (SCN) was diagnosed by using the National Kidney
Foundation Kidney Disease Outcome Quality Initiative guidelines.
Study Design: The study design involves diagnostic study Phase I.
Statistical Analysis: Descriptive statistics were done using SPSS version 25.0 (IBM, NY, USA), and diagnostic
statistics such as receiver operating characteristic curve (ROC) and others were done by Dxt version 1.0
software (BRTC, Vellore, India).
Results: Of 507 patients, 268 (52.8%) were male and 239 (47.1%) were female. The mean age of the
study population was 9.42 ± 2.56 years. Cutoff value of MA was ≥47 mg/day (sensitivity [Sn]: 73.9%,
specificity [Sp]: 90.5% and area under curve was 0.841 [0.56, 0.91] with P = 0.001). Sn of MA was
76.1% (61.1%, 80.7%), Sp: 90.9% (87.8%, 93.5%), positive predictive value: 62.4% (52.2%, 71.8%), negative
predictive value: 93.8% (91%–96%), likelihood ratio positive (LR+): 7.894 (5.672, 10.986), likelihood ratio
negative (LR‑): 0.312 (0.224, 0.436), odds ratio: 25.266 (14.277, 44.713) with diagnostic accuracy of 83.62%.
Conclusions: MA can be used as a good screening tool for early detection of SCN. However, larger studies
with a good level of evidence are awaited.
Keywords: Children, microalbuminuria, receiver operating characteristic curve, sickle cell nephropathy
Address for correspondence: Dr. Nihar Ranjan Mishra, Department of Pediatrics, Veer Surendra Sai Institute of Medical Sciences and Research, Burla,
Sambalpur, Odisha, India.
INTRODUCTION people of African descent as well as individuals from the

Middle East, India, and Mediterranean regions. Recent
Sickle cell disease (SCD) is one of the most frequent estimates report about 305,800 babies with SCD are
genetic disorders in the world. It predominantly affects born every year in the world, and over two‑thirds are in
sub‑Saharan Africa rising to over 404,200 by 2050.[1,2]
Received: 21‑01‑2020 Revised: 02-03-2020 The most common and severe form of SCD is sickle
www.jpcc.org.in
DOI: How to cite this article: Meher SK, Mishra NR, Khamari DK, Nayak BK.
10.4103/JPCC.JPCC_2_20 Diagnostic accuracy of microalbuminuria among sickle cell children with
nephropathy. J Pediatr Crit Care 2020;7:73-8.
© 2020 Journal of Pediatric Critical Care | Published by Wolters Kluwer ‑ Medknow 73

Meher, et al.: Urine microalbumin as a screening tool for detection of nephropathy among sickled children
cell anemia (SCA), which is caused by the homozygous urine microalbumin to detect nephropathy in sickle cell
inheritance of the sickle gene.[3,4] homozygous children as there is no previous study. Taking
CI to be 95% and absolute precision of 5%, the minimum
The chronic manifestations of recurrent end‑organ sample size was calculated to be 507 after adjusting for
damage, such as sickle cell nephropathy (SCN), have correction factor and attrition. Of 2563 SCA patients
become a significant issue as comprehensive care and admitted to in‑patients department of Pediatrics during the
effective treatments have significantly improved survival.[5,6] study period, 2131 sickled children were included as per
Nephropathy is a serious complication of SCD that begins the predefined inclusion and exclusion criteria. From this
in childhood and may progress to overt renal failure.[6] Renal study pool, 532 cases were selected by systematic random
involvement is one of the major factors of early death in sampling with sampling interval of 4. Of these, 25 cases
sickle cell populations.[6,7] Previous studies reported that did not give consent to participate in the study; hence,
renal complications occur in 5%–18% of sickle cell children 507 cases were enrolled in the study [Figure 1].
and adolescents and >9% of deaths in young adults
were due to complications related to kidney diseases.[7‑9] Urine microalbumin was estimated by human
End‑stage renal disease (ESRD) develops in 4.2%–11.6% micro‑albuminuria (MA) detection kit (Nephlometry) with
of cases with homozygous sickle cell disease (HbSS) and the trade name of mALB (YZB/Guangdong‑0053–2013,
is an independent predictor of premature mortality in Genrui Biotech Inc., China). Parents/caregiver of enrolled
young adults.[6,7] children were provided with a properly labeled universal
bottle for the collection of early morning mid‑stream
Urine microalbumin has been identified as an early marker urine samples and another bigger container for 24 h
of glomerular dysfunction long before glomerular filtration urine collection (from 7:00 a.m. to next day 7:00 a.m.) of
rate (GFR) declines, which is usually asymptomatic and their child. When tests could not be performed within
appears to be associated with more rapid decline in renal the 1st h of urine collection, urine was stored in the
function.[8] Urine microalbumin, which occurs in the refrigerator (at 2°C–8°C) and tested within 2 h of storage
subclinical phase of SCN, appears in the first decade of in the refrigerator. Refrigerated urine was kept at room
life and precedes the appearance of massive and persistent temperature for 15 min before tests were performed.
proteinuria.[8] Till now, no such studies were done on Measured spot urine microalbumin value was then
the diagnostic accuracy of urine microalbumin for early converted to 24 h urine microalbumin value by taking
detection of nephropathy among sickle cell children. into account the 24 h urine output. GFR was estimated
using modified Schwartz’s formula.[10] Serum creatinine
MATERIALS AND METHODS estimation was done using autoanalyzer (Roche Hitachi
Cobas C 311, USA). Body mass index (kg/m 2) was
This is an observational cross‑sectional analytical diagnostic computed using weight (in kilogram) divided by height
study (Diagnostic Study Phase I), conducted in the (in meters squared). Hb level was estimated by using Sahli’s
in‑patient Department of Pediatrics in an 1100‑bedded hemoglobinometer from fingertip blood sample. The
tertiary care teaching hospital of Western Odisha, from resting systolic blood pressure (SBP) measurement was
November 2017 to October 2019. All the high‑performance obtained from the right upper arm with an age‑appropriate
liquid chromatography/hemoglobin (Hb) Electrophoresis blood pressure cuff size for children. Clinical events such as
confirmed cases of sickle cell homozygous children of no of hospitalizations, number of frequent vaso‑occlusive
either gender between the age group of 5 and 14 years crisis (fVOC), number of units of blood transfusion,
were included in the study. Children with preexisting and the duration of hydroxyurea therapy in months
renal diseases such as congenital renal anomalies, were taken from the medical record. Urine albumin level
nephrotic/nephritic syndrome, those with previously between 30 and 300 mg/day was taken as MA.[11] estimated
diagnosed cases with diabetes mellitus or hypertension, GFR value <60 ml/min/1.73 m2 was taken as having
those with albuminuria in urine routine test and cases nephropathy.[12] fVOC was defined as ≥3 episodes of VOC
on regular angiotensin converting enzymes inhibitors in the past 1 year.[13,14] Systolic hypertension was defined as
therapy for >1 month were excluded from the study. SBP >95th percentile for age and sex.[15]
Estimation of sample size was done based on the diagnostic
test‑confidence interval (CI) estimating sensitivity (Sn) of a All the relevant data were recorded in a predesigned case
new test‑absolute precision method (n Master Version 2.0, report format. Data validation was done manually by two
Biostatistics Resource and Training Centre, Vellore). As separate persons not involved in the study. Continuous
per the rule of assumption, we have taken 50% Sn of data were expressed in mean ± standard deviation;

2563 Sickle cell patients admitted

during the study period 432 Excluded
257 cases with urine routine
microscopy showing +/++
proteinuria
87 cases with previously diagnosed
Inclusion
cases of nephrotic syndrome
criteria
52 previously diagnosed cases of
nephritic syndrome
31 cases with previous
Ultrasound revealing renal
Study pool of anomaly.
2131 patients 5 cases previously diagnosed
cases of diabetes mellitus
532 cases are selected by systematic random

sampling with sampling interval of 4
25 cases did not

give consent
507 cases
enrolled in
the study
Urine microalbumin
Positive-133(26.2%) Negative-374(73.8%)
Nephropathy Nephropathy Nephropathy Nephropathy

positive-67(13.2%) negative-66(13%) positive-21(4.1%) negative-353(69.6%)
DIAGNOSTIC ACURACY TESTS OF URINE MICROALBUMIN
Figure 1: Flow chart
categorical data were expressed in proportions. Data Youden index J > 0.5 was considered acceptable for
normalcy testing of continuous data was done using diagnostic accuracy tests.
Shapiro–Wilk test, and no transformation was required.
All the descriptive statistics were done by SPSS Statistics RESULTS
for Windows, version 25 (IBM Corp., Armonk, N. Y.,
USA), and all the diagnostic accuracy tests were done A total of 507 subjects made up the study group. Of
by Dxt Software for Windows, version 1.0 (Biostatistics these, males were 268 (52.8%) and 239 (47.1%) were
Resource and Training Centre, Vellore). For all statistical female, with being a male:female ratio of 1.12:1. Table 1
purposes, P < 0.05 was considered statistically significant. shows the baseline characteristics of the study participants.
Fifty‑seven (11.2%) had prehypertension. 253 (49.9%) estimated to be ≥47 mg/day. With this cutoff value, urine
were with the history of fVOC. One hundred and micral will identify approximately 74% of homozygous
thirty‑three (26.2%) out of 507 were tested positive for sickle cell children those who are with nephropathy.
MA. Out of 133 cases with MA, 76 (57.1%) were male and Likewise, urine micral will identify approximately 90.5%
57 (42.9%) were female, 22 (16.9%) had prehypertension, of homozygous sickle cell children those who do not have
78 (58.6%) had history of fVOC. nephropathy. Furthermore, probability of homozygous
sickle children who have positive urine micral and actually
Eighty‑eight (17.4%) were identified of having nephropathy, having nephropathy is 50.3% and also the probability of
of which 67 (76.1%) were MA positive and 21 (23.9%) homozygous sickle child with negative urine micral test
were MA negative. From those sickle cell children with and actually do not have nephropathy is 94%.
nephropathy (88), 47 (53.4%) were male and 41 (46.6%)
were female, 14 (15.9%) had prehypertension, 81 (92%) Urine micral level ≥47 mg/day, the probability of
were with history of fVOC. nephropathy among sickle cell children increases by
eight folds and <47 mg/day the probability of detecting
The level of MA (mg/day) was analyzed in response to nephropathy in sickle cell children decreases by 1/3rd.
the presence of nephropathy using receiver operating Hence, overall diagnostic accuracy of MA in detecting MA
characteristic curve [Figure 2]. Cutoff value of urine came to be 83.26%.
microalbumin (urine micral) was estimated to be 47 mg/day
with Sn of 73.9% and specificity of 90.5%, LR+ = 7.737, Similar results, in terms of the prevalence of MA, have
LR− = 0.289 and Youden index J = 0.643, with area under been reported in several studies worldwide with frequencies
curve = 84.1% (75.4%, 90.6%). Applying this above cutoff ranging from 18% to 23%.[16‑28] Furthermore, the proportion
value for urine micral in our study participants, various of MA in sickle cell children >10 years of age was 55.6%.
diagnostic parameters of urine micral are summarized Our findings corroborate those of a previous study, which
in Table 2. The overall diagnostic accuracy of urine reported 62% of MA among children >10 years of age in
micral with cutoff value of ≥47 mg/day for detecting the USA.[23] The prevalence of nephropathy in our study
nephropathy was found to be 83.62%. is 17.4%, which in accordance with previous studies.
DISCUSSION
Table 1: Baseline characteristics of the study participants
Variables Mean±SD
The present study was conducted in the Department of
Age (years) 9.42±2.56
Pediatrics, VIMSAR, Burla, situated in the Western part Height (cm) 122.94±13.21
of Odisha where the prevalence of SCD is very high. The Weight (kg) 21.37±5.38
prevalence of MA and nephropathy was found to be 26.2% BMI (kg/m2) 14±1.85
SBP (mmHg) 96±7
and 17.4%, respectively, in our study. Haemoglobin (g/dl) 7.77±1.68
Number of previous hospitalisation 6±5
As per the diagnostic test used in our study, the cutoff Number of previous blood transfusion 4±4
Duration of hydroxy‑urea treatment in months 77.19±32.62
value for urine microalbumin to detect nephropathy was Serum creatinine (mg/dl) 0.63±0.18
Microalbuminuria level (mg/day) 36.37±49.52
eGFR (ml/min/1.73 m2) 86.66±22.26
BMI: Body mass index, SBP: Systolic blood pressure, eGFR: Estimated
glomerular filtration rate, SD: Standard deviation
Table 2: Diagnostic parameters of urine microalbumin in

detecting nephropathy
Diagnostic parameters Value 95% CI
True prevalence 17.4 14.2‑20.9
Sensitivity 71.6 61‑80.7
Specificity 90.9 87.8‑93.5
PPV 62.4 52.2‑71.8
NPV 93.8 91‑96
Positive likelihood ratio 7.894 5.672‑10.986
Negative likelihood ratio 0.312 0.224‑0.436
Odds ratio 25.266 14.277‑44.713
Youden index 62.5 48.7‑74.2
CI: Confidence interval, NPV: Negative predictive value, PPV: Positive
Figure 2: Receiver operating characteristic curve predictive value

McKie et al. found abnormal albuminuria in 19.4% of Financial support and sponsorship
191 children with homozygous sickle cell disease (HbSS) Nil.
and observed a significant association of albuminuria with
age and lower baseline Hb.[19] Alvarez et al. demonstrated Conflicts of interest
abnormal albuminuria in 16.8% of HbSS children.[20] In There are no conflicts of interest.
a smaller pediatric cohort, Becton et al. found abnormal
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using Schwartz formula, instead “measured GFR” would et al. Chronic renal failure in sickle cell disease: Risk factors, clinical
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bias, diagnosis bias, could not be prevented so far as the Nephrol 2009;20:629‑37.
11. Viberti GC, Hill RD, Jarrett RJ, Argyropoulos A, Mahmud U,
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Keen H. Microalbuminuria as a predictor of clinical nephropathy in
one‑morning urine microalbumin level, but repeated insulin‑dependent diabetes mellitus. Lancet 1982;1:1430‑2.
samples of urine would have increased the strength of 12. National Kidney Foundation. K/DOQI clinical practice guidelines for
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have been followed for the progression of nephropathy. 13. Darbari DS, Onyekwere O, Nouraie M, Minniti CP, Luchtman‑Jones L,
Rana S, et al. Markers of severe vaso‑occlusive painful episode
CONCLUSIONS frequency in children and adolescents with sickle cell anemia. J Pediatr
2012;160:286‑90.
Urine micral can be used as a good screening tool for early 14. Nebor D, Bowers A, Hardy‑Dessources MD, Knight‑Madden J,
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management of high blood pressure in children and adolescents.
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who have continuously encouraged us and at last but not
19. McKie KT, Hanevold CD, Hernandez C, Waller JL, Ortiz L, McKie KM.
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2007;29:140‑4. sickle cell disease. J Pediatr 2000;136:749‑53.

20. Alvarez O, Montane B, Lopez G, Wilkinson J, Miller T. Early blood 25. Bayazit AK, Noyan A, Aldudak B, Ozel A, Anarat A, Kilinç Y, et al.
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Micro‑albuminuria in Ugandan children with sickle cell anaemia: et al. Prevalence and clinical correlates of microalbuminuria in children
A cross‑sectional study. Ann Trop Paediatr 2011;31:115‑21. with sickle cell disease. Pediatr Nephrol 2010;25:1505‑11.
23. Marsenic O, Couloures KG, Wiley JM. Proteinuria in children with 28. Ranque B, Menet A, Diop IB, Thiam MM, Diallo D, Diop S, et al. Early
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Prevalence and clinical correlates of glomerulopathy in children with 2014;1:e64‑73.

Original Article
Risk factors for bronchiolitis

Preeti Kulhalli, Dakshayini J. N., Vinod H. Ratageri, I. Shivanand, Prakash K. Wari
Department of Pediatrics, Karnataka Institute of Medical Sciences, Hubli, Karnataka, India
Abstract Background: Bronchiolitis is a common acute respiratory illness with significant morbidity and mortality
in children aged <2 years. Many risk factors have been proposed though none conclusively proven.
Objective: The objective of the study is to determine the risk factors for bronchiolitis in children
aged <24 months.
Methodology: This was a retrospective study conducted at Karnataka Institute of Medical Sciences, Hubli,
from July to September 2018 on children aged <24 months, with clinically diagnosed bronchiolitis considered
as cases and age‑matched children admitted during the same period for nonrespiratory causes as controls.
Results: Totally, 85 children and 91 controls were included in the study with a mean age at presentation
being 5.5 months (interquartile range = 2–8 months) and male‑to‑female ratio of 1.42:1. The most common
symptoms were cough (98.8%), fever (84.7%), cold (64.7%), hurried breathing (58.8%), chest indrawing (42.2%),
and noisy breathing (35.3%). On univariate analysis, low socioeconomic status (SES), overcrowding,
unimmunized status, exposure to pets, and birth by cesarean section (CS) were significant risk factors. On
applying multiple logistic regression (odds ratio, 95% confidence interval), low SES, unimmunized status,
exposure to pets, and birth by CS were found to be significant.
Conclusion: Low SES, partial/unimmunized status, exposure to pets, and birth by CS were deduced to be
important significant risk factors for bronchiolitis.
Keywords: Bronchiolitis, infants, pets, risk factors, socioeconomic
Address for correspondence: Dr. Vinod H. Ratageri, Department of Pediatrics, Karnataka Institute of Medical Sciences, Hubli ‑ 580 021, Karnataka, India.
INTRODUCTION Mortality rate is approximately 2/100,000 infants and is

higher in developing than developed countries.[3]
Bronchiolitis is an acute respiratory illness of importance
that affects infants and young children and is one of the A number of risk factors and clinical findings have been
most common clinical conditions treated by practicing proposed to predict the severity of disease in children with
pediatricians worldwide. Children typically aged <2 years bronchiolitis. Host‑related factors such as prematurity, low
are affected.[1] Occurrence peaks in winter and rainy birth weight (LBW), age <6–12 weeks, chronic pulmonary
seasons. The incidence of bronchiolitis is estimated to disease, hemodynamically significant congenital heart
range from 265/1000 infants to 16.4/100 children.[2] disease, and immunodeficiency have been implicated.[4]
Malnutrition, nonimmunization, and nonbreastfeeding
Received: 02‑02‑2020 Revised: 28-02-2020
were some significant risk factors for severe bronchiolitis.
Accepted: 08-03-2020 Published: 10-04-2020 The other risk factors deduced in other studies include
Access this article online This is an open access journal, and articles are distributed under the terms of the Creative
Website: remix, tweak, and build upon the work non‑commercially, as long as appropriate credit
is given and the new creations are licensed under the identical terms.
www.jpcc.org.in
DOI:
10.4103/JPCC.JPCC_23_20 How to cite this article: Kulhalli P, Dakshayini JN, Ratageri VH, Shivanand I,
Wari PK. Risk factors for bronchiolitis. J Pediatr Crit Care 2020;7:79-83.

Kulhalli, et al.: Bronchiolitis and risk factors
socioeconomic factors such as parental illiteracy, low as (I) weight for height/length <−3Z score and −2 to −3Z,
SES, overcrowding, prelacteal feeds, and early weaning.[5] respectively; (II) presence of visible severe wasting; (III)
Environmental factors such as presence of older sibling nutritional edema; (IV) mid‑upper arm circumference
and passive smoke exposure have been implicated. of <115 mm, family history of asthma, allergies, history of
bottle feeding, overcrowding,[9] and coexistence with pets.
However, there is a paucity of literature on risk factors for
the development of bronchiolitis, in the Indian context, Statistical analysis
and hence, the present study was undertaken. The data were analyzed using R software version 3.1
(R Foundation for Statistical Computing, Vienna, Austria);
Aim a P ≤ 0.05 was accepted statistically significant. Simple
The aim of the study is to determine risk factors for associations were compared with Chi‑square test as
bronchiolitis in children aged <24 months. appropriate. Odds ratios with 95% confidence interval (CI)
were calculated by risk assessment of Chi‑square analysis,
METHODOLOGY
and logistic regression by the entry method was performed
Study design
using variables found to be statistically different between
This was a retrospective study in children admitted to the two groups.
Pediatrics Department, Karnataka Institute of Medical RESULTS
Sciences, Hubli, from July 2018 to September 2018, who
satisfy the inclusion criteria. Totally, 85 children aged <24 months and 91 controls
were included in the study. Figure 1 shows the flowchart
Inclusion criteria of selection of cases.
All children aged <24 months with clinically diagnosed
bronchiolitis were enrolled in the study. [6] Children The mean age at presentation was 5.5 months
admitted during this period for nonrespiratory pathology (median ‑ 5 months; interquartile range ‑ 2–8 months). The
who were <24 months old, with no prior history of male‑to‑female ratio 1.42:1, with a male preponderance of
bronchiolitis, were considered as controls. 58.8% (n = 50) in the study group and 1.02:1 (n = 46) in the
control group. Age at presentation in the order of frequency
Exclusion criteria
was <6 months (n = 57, 67.05%), 7–12 months (n = 25,
1. Confirmed bronchopneumonia
29.41%), and 13–24 months (n = 3, 3.5%), with P value
2. Children with chronic illness (cardiac, pulmonary,
being significant for under 6 months of age. Details are
neurologic, chromosomal, or craniofacial comorbidities)
summarized in Table 1.
3. Previously diagnosed with asthma.
The common clinical symptoms in the order of frequency
The study was approved by the institutional ethical
were as follows: cough (n = 84, 98.8%), fever (n = 72, 84.7%),
committee.
cold (n = 55, 64.7%), hurried breathing (n = 50, 58.8%), chest
Demographic and risk factor data collected
The medical records of children included in this study
Clinical bronchiolitis in
were reviewed, and the information was collected in a children aged <24 months
predesigned Proforma. n = 93
The following demographic data were recorded: age in

months, sex, delivery by normal or cesarean section (CS),
premature birth (gestational age <37 weeks), and 5 children excluded as
pneumonia, 3 children did
LBW (<2500 g); immunization status was categorized into not have completed records
two groups: group 1 “fully/completely immunized” and
group 2 partial/unimmunized. Fully immunized defined
as a receipt of six vaccines by 12 months of age as per
the National Institute of Health and Family Welfare 85 children included
in the study
guidelines.[7] Socioeconomic class defined as per the n = 85
Modified Kuppuswamy scale 2017;[8] malnutrition defined
by the WHO for severe and moderate acute malnutrition Figure 1: Selection of cases for the study

indrawing (n = 36, 42.4%), and noisy breathing (n = 30, pets, birth by CS, and incomplete immunization showed
35.3%). However, stridor was not observed in any case. On significance on univariate analysis. However, on application
examination, rhonchi in n = 54, 63.5%, and crepitations in of multiple logistic regression analysis, four risk factors,
n = 52, 61.2%, were also noted. Bilateral hyperinflation on such as low SES, birth by CS, exposure to pets, and
the chest X‑ray was seen in n = 77, 90.6%. incomplete immunization, showed significance.
Table 2 shows the risk factors for bronchiolitis. Low Low SES was found as significant risk factor for bronchiolitis,
SES, overcrowding, incomplete immunization, exposure similar to the study done by Díez Domingo et al.[13] Higher
to pets, and birth by CS were the significant risk factors. incidence of hospital admission due to respiratory infection
However, preterm birth, LBW, maternal allergy, atopy, in poor was found in study by Jansson et al.[14] The possible
maternal diabetes/hypertension, malnutrition, family explanations could be that children from low SES are more
history of asthma, and bottle feeding showed no significant vulnerable to air pollution, infection, nutritional deficiency,
association as risk factors. and numerous environmental hazards and possibly because
disadvantaged mothers have less access to healthcare
After application of multiple logistic regression services.[15,16] In a large‑scale study done by Alvarez et al.[17]
analysis [Table 3] with the application of odds ratio with in Brazil, low SES was found as a major risk factor along
95% CI, the results showed significance for lower SES, with birth by CS.
birth by lower segment CS, exposure to pets, and partial/
incomplete immunization only. Birth by CS was identified as a second major risk factor.
Similar results were obtained by a study done at Denmark,
DISCUSSION where increased incidence of bronchiolitis and respiratory
syncytial virus (RSV) infection was seen in CS born children
Bronchiolitis is a common respiratory illness in pediatrics aged <2 years.[18] Shang et al.[19] found almost double the
that causes acute inflammation, edema, necrosis of incidence of bronchiolitis in children born by CS. The same
epithelial cells, increased mucus production, and inadequate findings were however refuted by Achten et al.[20] in 2015
oxygenation and could be potentially life‑threatening. and Hendaus et al.,[21] where no enhanced incidence was
found. The possible analogy could be that CS or delivery
This study aimed at assessing the risk factors for acute
without preceding labor may result in impaired immunity
bronchiolitis. There was male preponderance identified
in newborn, leading to increased risk of early viral lower
in the study. As evidenced by literature, there is a
respiratory tract infections.[22]
greater incidence of bronchiolitis in boys.[5] The study
by Bakalovic et al.[10] at Sarajevo University also stated Another significant variable in this study was exposure to
the higher percentage of hospitalized male infants. This pets in the house. However, studies have shown protection
could be attributable to increased sensitivity of males to of exposed infants from bronchiolitis.[23] Others have
aeroallergens.[11] reported that contact with pets either increases the risk
or induces sensitization or protects against them or has
The median age at presentation was 5 months. Similar to no association at all.[24] Exposure to pets was implicated
this, others have found a significant association between as risk factor in the study done by Malla et al.[25] in Nepal.
the age of <6 months and a higher risk of hospitalization Incidence was statistically higher in those exposed to pets
and severe bronchiolitis.[4,12] This is probably secondary to as in the study by Nenna et al.[26] similar to the current study.
reduced immunity in early infancy toward viral infections. Even with this, it is ridden with controversy regarding the
correlation of pet exposure to bronchiolitis and hence
In this study, of 13 risk factors initially considered, five
needs more validation in the future studies.
risk factors namely low SES, overcrowding, exposure to
RSV and influenza virus have been implicated as major
Table 1: Comparison of sex and age of presentations between
cases and controls pathogens in causation of bronchiolitis and targeting them
Cases Controls P has been stressed.[27] However, vaccination for them was
Male:female ratio 50:35 46:45 0.270 (NS) not given in the present study group due to constraints.
Mean age of presentation (months) This, in addition to lack of cross‑protection in these
<6 57 19 0.025 (S)
7‑12 25 23 0.538 (NS)
incompletely immunized patients, probably explains the
13‑24 03 49 0.512 (NS) enhanced incidence and its role as a major risk factor. In a
S: Significant, NS: Not significant study done by Das et al.,[28] similar results of nonvaccinated
Table 2: Risk factors for bronchiolitis (n=85) ‑ univariate analysis

Case Control Total Chi‑square test
Gender
Male 50 (58.8) 46 (50.5) 96 (54.5) χ2=1.214, P=0.271
Female 35 (41.2) 45 (49.5) 80 (45.5)
Total 85 (100) 91 (100) 176 (100)
Fever
Yes 72 (84.7) 21 (23.1) 93 (52.8) χ2=66.986, P<0.005
No 13 (15.3) 70 (76.9) 83 (47.2)
Total 85 (100) 91 (100) 176 (100)
Preterm birth
Yes 8 (9.4) 7 (7.7) 15 (8.5) χ2=0.167, P=0.683
No 77 (90.6) 84 (92.3) 161 (91.5)
Total 85 (100) 91 (100) 176 (100)
LBW
Yes 15 (17.6) 12 (13.2) 27 (15.3) χ2=0.673, P=0.412
No 70 (82.4) 79 (86.8) 149 (84.7)
Total 85 (100) 91 (100) 176 (100)
Low SES
Yes 32 (37.6) 62 (68.1) 94 (53.4) χ2=16.413, P<0.005
No 53 (62.4) 29 (31.9) 82 (46.6)
Total 85 (100) 91 (100) 176 (100)
Maternal allergy/asthma/smoking
Yes 7 (8.2) 4 (4.4) 11 (6.2) χ2=1.105, P=0.292
No 78 (91.7) 87 (95.6) 165 (93.7)
Total 85 (100) 91 (100) 176 (100)
Maternal DM/HTN
Yes 4 (4.7) 2 (2.2) 6 (3.4) χ2=0.839, P=0.359
No 81 (95.2) 89 (97.8) 170 (96.5)
Total 85 (100) 91 (100) 176 (100)
Overcrowding
Yes 12 (14.1) 25 (27.5) 37 (21) χ2=4.721, P=0.03
No 73 (85.9) 66 (72.5) 139 (79)
Total 85 (100) 91 (100) 176 (100)
Partial/incomplete immunization
Yes 18 (21.2) 5 (5.5) 23 (13.1) χ2=9.514, P=0.002
No 67 (78.8) 86 (94.5) 153 (86.9)
Total 85 (100) 91 (100) 176 (100)
Exposure to pets
Yes 19 (22.3) 8 (8.8) 27 (15.3) χ2=6.223, P=0.0126
No 66 (77.6) 83 (91.2) 149 (84.6)
Total 85 (100) 91 (100) 176 (100)
SAM
Yes 9 (10.6) 7 (7.7) 16 (9.1) χ2=0.446, P=0.504
No 76 (89.4) 84 (92.3) 160 (90.9)
Total 85 (100) 91 (100) 176 (100)
Family history of asthma
Yes 3 (3.5) 1 (1.1) 4 (2.2) χ2=1.168, P=0.279
No 82 (96.4) 90 (98.9) 172 (97.7)
Total 85 (100) 91 (100) 176 (100)
LSCS
Yes 21 (24.7) 12 (13.2) 33 (18.8) χ2=3.828, P=0.05
No 64 (75.3) 79 (86.8) 143 (81.3)
Total 85 (100) 91 (100) 176 (100)
Bottle feeding
Yes 5 (5.9) 1 (1.1) 6 (3.4) χ2=3.054, P=0.081 (Exact=0.108)
No 80 (94.1) 90 (98.9) 170 (96.6)
Total 85 (100) 91 (100) 176 (100)
SES: Socioeconomic status, HTN: Hypertension, DM: Diabetes mellitus, LBW: Low birth weight, SAM: Severe acute malnutrition, LSCS: Lower‑segment
cesarean section
children having increased incidence of bronchiolitis in and hence we did not have satisfactory access to variables
55.55% of patients were seen. being collected from control group.
The pros of this study were the inclusion of several We identified several risk factors for acute bronchiolitis
modifiable risk factors and descriptive cases and controls; such as low SES, partial/incomplete immunization,
however, the limitation was, as it was a retrospective study exposure to pets, and unindicated births by CS. This
Table 3: Multiple logistic regression analysis for risk factors Clinical Center of Sarajevo University. Mater Sociomed 2015;27:154‑7.
for bronchiolitis 11. Guilbert TW, Morgan WJ, Zeiger RS, Bacharier LB, Boehmer SJ,
B SE OR (95% CI) P Krawiec M, et al. Atopic characteristics of children with recurrent
wheezing at high risk for the development of childhood asthma.
Low SES −1.323 0.359 0.266 (0.132‑0.538) <0.005
J Allergy Clin Immunol 2004;114:1282‑7.
Overcrowding −0.643 0.463 0.526 (0.212‑1.304) 0.165
12. Papenburg J, Hamelin MÈ, Ouhoummane N, Carbonneau J,
Partial/nonimmunization 2.102 0.595 8.184 (2.548‑26.28) <0.005
Birth by CS 1.005 0.446 2.733 (1.141‑6.544) 0.024 Ouakki M, Raymond F, et al. Comparison of risk factors for human
Exposure to pets 1.002 0.441 2.613 (0.842‑7.321) 0.019 metapneumovirus and respiratory syncytial virus disease severity in
young children. J Infect Dis 2012;206:178‑89.
SE: Standard error, OR: Odds ratio, CI: Confidence interval, CS: Cesarean
section, SES: Socioeconomic status 13. Díez Domingo J, Ridao López M, Ubeda Sansano I, Ballester Sanz A.
Incidence and cost of hospitalizations for bronchiolitis and respiratory
syncytial virus infections in the autonomous community of Valencia
information would help public health authorities draw in Spain (2001 and 2002). An Pediatr (Barc) 2006;65:325‑30.
up effective preventive measures for bronchiolitis. Early 14. Jansson L, Nilsson P, Olsson M. Socioeconomic environmental factors
identification and prevention of the same may help reduce and hospitalization for acute bronchiolitis during infancy. Acta Paediatr
2002;91:335‑8.
the overall incidence. Due to dearth of studies on risk 15. Leem JH, Kim HC, Lee JY, Sohn JR. Interaction between bronchiolitis
factors of bronchiolitis, this study explores novel factors diagnosed before 2 years of age and socio‑economic status for
to be considered for future research. bronchial hyperreactivity. Environ Health Toxicol 2011;26:e2011012.
16. Koehoorn M, Karr CJ, Demers PA, Lencar C, Tamburic L, Brauer M.
Descriptive epidemiology of bronchioloits in a population based
CONCLUSION
cohort. Pediatr 2008;122:1196‑203.
17. Alvarez AE, Marson FA, Bertuzzo CS, Arns CW, Ribeiro JD.
Low SES, incomplete immunization, exposure to pets, and Epidemiological and genetic characteristics associated with the
birth by CS were deduced to be the important significant severity of acute viral bronchiolitis by respiratory syncytial virus.
J Pediatr (Rio J) 2013;89:531‑43.
risk factors for bronchiolitis.
18. Kristensen K, Fisker N, Haerskjold A, Ravn H, Simões EA,
Stensballe L. Caesarean section and hospitalization for respiratory
Financial support and sponsorship syncytial virus infection: A population‑based study. Pediatr Infect Dis
Nil. J 2015;34:145‑8.
19. Shang X, Liabsuetrakul T, Sangsupawanich P, Xia X, He P, Cao H.
Conflicts of interest Elective cesarean delivery as a predisposing factor of respiratory
syncytial virus bronchiolitis in children. J Med Assoc Thai
There are no conflicts of interest. 2014;97:827‑34.
20. Achten NB, Wu P, Bont L, Blanken MO, Gebretsadik T, Chappell JD,
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1. Welliver RC. Review of epidemiology and clinical risk factors for severe 21. Hendaus MA, Alhammadi AH, Khalifa MS, Muneer E. Does cesarean
respiratory syncytial virus (RSV) infection. J Pediatr 2003;143:S112‑7. section pose a risk of respiratory syncytial virus bronchiolitis in infants
2. M u ñ o z ‑ Q u i l e s C, L ó p e z ‑ L a c o r t M , Ú b e d a ‑ S a n s a n o I , and children? Asian Pac J Trop Med 2014;7S1:S134‑6.
Alemán‑Sánchez S, Pérez‑Vilar S, Puig‑Barberà J, et al. Population‑based 22. Moore HC, de Klerk N, Holt P, Richmond PC, Lehmann D.
analysis of bronchiolitis epidemiology in Valencia, Spain. Pediatr Infect Hospitalisation for bronchiolitis in infants is more common after
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Epidemiological features of bronchiolitis in the Pediatric Clinic of 2003;47:66‑71.

Case Report
Haberland syndrome: Encephalocraniocutaneous syndrome

presenting as status epilepticus
V. S. V. Prasad, Anzad Madathil Amanullah
Pediatric Intensive Care Unit, Lotus Hospitals for Women and Children, Hyderabad, Telangana, India
Abstract We report a 5‑year‑old female child who presented with fever and status epilepticus with a history of
global developmental delay, patchy alopecia over the frontal region, and bilateral dermolipoma in the
conjunctiva and sclera. These findings are consistent with a diagnosis of encephalocraniocutaneous
lipomatosis. This is a rare condition reported infrequently across the world. The child also had the
specific neurological manifestations of this condition, specifically epilepsy presenting as status
epilepticus.
Keywords: Encephalocraniocutaneous lipomatosis, haberland syndrome, status epilepticus
Address for correspondence: Dr. V. S. V. Prasad, #6‑2‑29, Lotus Hospitals for Women and Children, Lakdikapul, Hyderabad, Telangana, India.
INTRODUCTION CASE REPORT
Status epilepticus is a common diagnosis encountered A 5‑year‑old Indian female child presented with a history of
in the pediatric intensive care unit (PICU). We report fever for 1 day, followed by multifocal convulsions lasting for
a rare etiology of status epilepticus, i.e., Haberland around 10 min. She was admitted with a working diagnosis
syndrome. Encephalocraniocutaneous lipomatosis is of status epilepticus. She was evaluated at a medical center
a rare neurocutaneous condition defined in 1970 by and commenced on antiepileptic medications and referred
Haberland and Perou.[1] This condition mostly involves to our hospital. On obtaining a detailed history, we found
unilateral ectodermal and mesodermal tissues of the that this was her third episode of seizures. She had her first
skin/scalp, eyes, and brain. Till date, around eighty episode of seizure in the immediate neonatal period lasting
cases have been reported, with some of them being for a few minutes, and she was admitted into the neonatal
in the pediatric age group. A few of these children are intensive care unit for a couple of days. She was noted to
known to have brain atrophy with global developmental have a patch of alopecia in the frontal area of the scalp. She
delay. A third of them are known to develop epilepsy also had a bony swelling in the right temporomandibular
warranting treatment. This condition is also known as area. There were also lesions involving the conjunctiva and
Fishman syndrome. sclera of both eyes. The second episode of seizure occurred
around 3 years of age, presenting as status epilepticus,
which was associated with fever. She was on antiepileptic
Received: 06‑02‑2020 Revised: 25-02-2020 medications since then, which were discontinued by the
www.jpcc.org.in
DOI: How to cite this article: Prasad VS, Amanullah AM. Haberland syndrome:
10.4103/JPCC.JPCC_25_20 Encephalocraniocutaneous syndrome presenting as status epilepticus. J
Pediatr Crit Care 2020;7:84-7.
84 © 2020 Journal of Pediatric Critical Care | Published by Wolters Kluwer - Medknow

Prasad and Amanullah: Haberland syndrome presenting as status epilepticus
parents after 2 months without proper medical advice. She with some weakness in the left lower limb causing her to
was lost for follow‑up for an extended length of time. At limp. She underwent a magnetic resonance imaging scan
the time of this admission, she underwent investigations previously at 1 year of age, which revealed an arachnoid
for a febrile illness, wherein she was diagnosed with acute cyst and bilateral cerebellopontineangle lipomas. There
dengue fever with warning signs. She was treated according was also atrophy of the right cerebral hemisphere noted in
to the standard PICU protocol for her dengue fever and this scan. A repeat computed tomography (CT) scan was
status epilepticus. performed before this admission to review any progression
of the lesions. The CT scan revealed no change in any
Her developmental history had revealed a global of her lesions in the brain. We would like to report the
developmental delay. She started walking at 3 years of age, phenotype of this child and describe each of the specific
features we observed. The first striking feature was the
alopecic patch in the frontal scalp area [Figure 1]. This patch
of skin is called nevus psiloliparus, which is a hairless fatty
tissue nevus. The next striking feature was the lesions in
her eyes. There were epibulbar choristoma and connective
tissue nevus in the eye [Figure 2]. As mentioned, seizures
are common in these children, and our patient had them
as early as the neonatal period. Unfortunately, the parents
chose to discontinue the treatment. During this admission,
she had presented to us with a breakthrough seizure. She
was also noted to have mild developmental delay with a
developmental age of 3½ years with a chronological age
of 5 years. The other external phenotype noted was the
notable bony swelling in the right temporal bone, which
was a calvarial exostosis. On neurological examination, she
Figure 1: Nevus psiloliparis
was found to have mild left‑sided hemiparesis, especially
involving the lower limbs with a subtle circumduction
gait. Her brain imaging showed atrophy of the right
cerebral hemisphere and cerebellopontine tumors (lipoma)
bilaterally [Figures 3 and 4].
DISCUSSION
Encephalocranialcutaneouslipomatosis is a rare condition

which is thought to have somatic mosaicism as the
Figure 2: Epibulbar choristoma pathophysiology. It is rare and has no preference for
Figure 3: Cerebral atrophy

Figure 4: Cerebellopontine tumor (lipoma)
gender or race. The dysgenesis of the neural tube crest Table 1: Diagnostic criteria
is another hypothesis for this condition. The syndrome Eye
Major criteria
has multisystem involvement of the brain, skin, bone, Choristoma with or without associated anomalies
and eyes. Minor criteria
Corneal and other anterior chamber anomalies
There are diagnostic criteria for the diagnosis of Ocular or eyelid coloboma
Skin
encephalocraniocutaneous lipomatosis which was Major criteria
proposed by Hunter and modified by Moog[2] [Table 1]. Proven NP
Possible NP and ≥1 of minor criteria 2‑5
≥2 of minor criteria 2‑5
The major and minor criteria are mentioned in the table. Minor criteria
Possible NP
A definite case is one in which Patchy or streaky nonscarring alopecia
Subcutaneous lipomas in the frontotemporal region
1. Three systems are involved, with major criteria ≥2 or Focal skin aplasia/hypoplasia on the scalp
2. Three systems involved, proven nevus psiloliparus Small nodular skin tags on eyelids or between the outer canthus
(NP) or possible NP and ≥1 of minor skin criteria 2–5 and tragus
CNS
3. Two systems involved with major criteria, one of which Major criteria
proven NP +. ≥1 minor skin criteria 2–5. Intracranial lipoma
Intraspinal lipoma
≥2 minor criteria
Probable case is defined as one with, Minor criteria
1. Two systems involved with major criteria in both Abnormal intracranial vessels
2. Two systems involved with proven or possible NP. Arachnoid cyst or other abnormality of the meninges
Complete or partial atrophy of a hemisphere
Porencephalic cyst
Clinically, the main differential diagnosis include proteus Asymmetrically dilated ventricles or hydrocephalus
syndrome, neurofibromatosis, Sturge–Weber syndrome, Calcification (not basal ganglia)
Other systems
epidermal nevus syndrome, and Goldenhar syndrome.[3] Major criteria
The natural course of the disease can allow some children Jaw tumor
to lead normal lives.[4] Some of them can have the central Multiple bone cysts
Aortic coarctation
nervous system (CNS) morbidity affecting their quality NP: Nevus psiloliparus, CNS: Central nervous system
of life.[5] The child may develop seizures, sometimes
facial paralysis, hemiplegia, spasticity of the opposite for the skin and ocular lesions, but regular follow‑up for
limb, sensorineural hearing loss, and behavioral changes.[6] the child for the above‑mentioned complications are
There is an increased risk of developing CNS tumors imperative.
in these children which includes low‑grade glioma and
astrocytoma.[7,8] Other neoplasms such as extrapharyngeal Declaration of patient consent
angiofibroma of the gingiva and papillary glioneuronal The authors certify that they have obtained all appropriate
tumor[9,10] is also documented. Hence, regular screening patient consent forms. In the form the patient(s) has/have
for these tumors is an essential part of follow‑up care. The given his/her/their consent for his/her/their images and
ocular manifestations can be treated by surgical techniques other clinical information to be reported in the journal.
based on the extent of the choristoma. There is no specific The patients understand that their names and initials will
therapy for the condition except for anticonvulsant therapy not be published and due efforts will be made to conceal
for seizures or status epilepticus and cosmetic treatment their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship 1999;20:173‑6.

5. Chan CC, Chen JS, Chu CY. Haberland syndrome. Dermatol Sin
Nil. 2005;23:41‑5.
6. Hunter AG. Oculocerebrocutaneous and encephalocraniocutaneous
Conflicts of interest lipomatosis syndromes: Blind men and an elephant or separate
There are no conflicts of interest. syndromes? Am J Med Genet A 2006;140:709‑26.
7. Brassesco MS, Valera ET, Becker AP, Castro‑Gamero AM,
de Aboim Machado A, Santos AC, et al. Low‑grade astrocytoma in
REFERENCES
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2010;96:437‑41.
1. Haberland C, Perou M. Encephalocraniocutaneous lipomatosis. A new
8. Valera ET, Brassesco MS, Scrideli CA, de Castro Barros MV, Santos AC,
example of ectomesodermal dysgenesis. Arch Neurol 1970;22:144‑55. Oliveira RS, et al. Are patients with encephalocraniocutaneous
2. Moog U. Encephalocraniocutaneous lipomatosis. J Med Genet lipomatosis at increased risk of developing low‑grade gliomas? Childs
2009;46:721‑9. Nerv Syst 2012;28:19‑22.
3. T hakur S, T hakur V, Sood RG, T hakur CS, Khanna S. 9. Andreadis DA, Rizos CB, Belazi M, Peneva M, Antoniades DZ.
E n c e p h a l o c r a n i o c u t a n e o u s l i p o m a t o s i s w i t h c a l va r i a l Encephalocraniocutaneous lipomatosis accompanied by maxillary
exostosis – Case report and review of literature. Indian J Radiol compound odontoma and juvenile angiofibroma: Report of a case.
Imaging 2013;23:333‑6. Birth Defects Res A Clin Mol Teratol 2004;70:889‑91.
4. Parazzini C, Triulzi F, Russo G, Mastrangelo M, Scotti G. 10. Phi JH, Park SH, Chae JH, Wang KC, Cho BK, Kim SK. Papillary
Encephalocraniocutaneous lipomatosis: Complete neuroradiologic glioneuronal tumor present in a patient with encephalocraniocutaneous
evaluation and follow‑up of two cases. AJNR Am J Neuroradiol lipomatosis: Case report. Neurosurg 2010;67:E1165‑9.

Case Report
Mycoplasma pneumoniae‑induced cerebral venous sinus

thrombosis with autoimmune hemolytic anemia
Sayali Deshpande, Bhakti Sarangi, Venkat Sandeep Reddy, Ajay Walimbe
Department of Pediatrics, Bharati Hospital, Pune, Maharashtra, India
Abstract Mycoplasma pneumoniae (MP) is a common organism causing pneumonia in school‑going children. Although
the disease is usually mild, it can rarely lead to severe extrapulmonary complications which may be
life‑threatening. We hereby report a case of an 8‑year‑old male child who presented with fever, cough,
a maculopapular rash, and difficulty in breathing for 8 days who, after initially receiving treatment as
community‑acquired pneumonia with synpneumonic effusion, went on to develop severe autoimmune
hemolytic anemia and cerebral venous thrombosis with features of vasculitis. With utilization of DNA
polymerase chain reaction along with other laboratory parameters, the diagnosis of MP infection was made.
The child was treated with oral clarithromycin, pulse dose methylprednisolone, low‑molecular‑weight
heparin, and intravenous immunoglobulin while he also required mechanical ventilation, transfusions,
and vasopressor support. He responded to these measures and survived with no neurological sequelae.
Keywords: Autoimmune hemolytic anemia, cerebral venous sinus thrombosis, low‑molecular‑weight heparin,
methyl prednisolone, Mycoplasma pneumoniae
Address for correspondence: Dr. Venkat Sandeep Reddy, Department of Pediatrics, Bharati Hospital, Pune, Maharashtra, India.
INTRODUCTION MP have specialized transmembrane proteins

(e.g., P1 and P30) that help in adherence and gliding motility
Mycoplasma pneumoniae (MP) is a common cause of along the respiratory epithelium. These adherence proteins
community‑acquired pneumonia most frequently affecting of MP have an affinity for respiratory tract epithelium,
school‑going children. Extrapulmonary complications due and after attachment, they produce hydrogen peroxide
to Mycoplasma are rare, most common being hematological and superoxide radicals, causing injury to epithelial cells
manifestations such as hemolytic anemia. Central nervous and cilia. The clinical manifestations of MP infection are
system (CNS) manifestations such as meningoencephalitis, determined by the immune competency and response
thrombosis, optic neuritis, transverse myelitis, and of the host, indicating that some of the pathogenic
stroke have also been occasionally reported apart from features of MP infection, particularly extrapulmonary
dermatological, gastrointestinal, connective tissue, cardiac, manifestations (e.g., hemolysis and encephalitis), are
ocular, and renal complications. immune mediated. The antibodies produced against the
glycolipid antigens of MP cross‑react with human red cells
and brain cells and may act as autoantibodies.
www.jpcc.org.in
DOI: How to cite this article: Deshpande S, Sarangi B, Reddy VS, Walimbe A.
10.4103/JPCC.JPCC_20_20 Mycoplasma pneumoniae-induced cerebral venous sinus thrombosis with
autoimmune hemolytic anemia. J Pediatr Crit Care 2020;7:88-91.

Deshpande, et al.: M. pneumoniae‑induced extrapulmonary complications in a child
CASE REPORT
An 8‑year‑old male child was referred to our hospital

with complaints of fever and cough for 8 days,
maculopapular rash and difficulty in breathing for 2 days,
and having received treatment for community‑acquired
pneumonia (intravenous [IV] ceftriaxone and oral
doxycycline). Chest X‑ray showed left lung consolidation
with synpneumonic effusion [Figure 1]. Diagnostic tap
revealed lymphocytic predominant cell count. On admission
to our hospital, his sensorium was normal (Glasgow Coma
Scale [GCS]: 15/15) with the only significant findings on
examination being tachypnea (respiratory rate: 48/min),
decreased oxygen saturation (90% in room air), mild
intercostal retractions, and decreased air entry over the Figure 1: Chest X‑ray done on admission
left side.
Considering persistent pneumonia, the child was continued

on oxygen therapy with injection piperacillin‑tazobactam
and injection vancomycin as antibiotic cover after
sending cultures. Computed tomography chest showed
consolidatory changes in both lungs predominantly on
the left [Figure 2]. He continued to remain intermittently
febrile with gradual improvement in respiratory findings
and radiological improvement. On day 8 of admission,
he was noticed to have significant pallor followed by a
steady fall in his GCS score from 15/15 to 12/15 and
subsequently to 10/15 over a period of 4 h. Examination
revealed poor sensorium, tachycardia, and severe pallor
with CNS examination showing signs of pyramidal
tract dysfunction. On investigation, his hemoglobin had Figure 2: Consolidatory changes noted on computed tomography
shown a fall from 9.1 g/dl to 2.1 g/dl [Table 1]. He was
electively intubated and put on mechanical ventilation.
Due to drastic fall in hemoglobin. suspecting hemolysis,
direct and indirect coombs test were done which were
both positive (4+) with cold agglutination. The child was
transfused with packed cells of blood group O negative
due to inability to cross‑match compatible blood type,
and IV methylprednisolone pulse therapy was started to
suppress the autoimmune hemolysis. Magnetic resonance
imaging (MRI) brain done showed thrombosis of the left
transverse and sigmoid sinus, part of the left internal jugular
vein, and partial thrombosis of the right transverse sinus Figure 3: First magnetic resonance imaging brain showing thrombosis
with restricted diffusion in both frontal regions suggesting of the left transverse and sigmoid sinus, visualized part of the left
cytotoxic edema/venous infarcts [Figure 3]. internal jugular vein, and partial thrombosis of the right transverse sinus
With evidence of vasculitis on MRI, IV immunoglobulin while blood specimen tested positive for Mycoplasma IgM
(IVIG) (at 2 g/kg) was also added along with antibodies. Following this, oral clarithromycin was added.
low‑molecular‑weight heparin. Considering possible Antiphospholipid antibodies (beta‑2 glycoprotein‑1
causes for hypercoagulability and the child’s clinical IgM) and cardiolipin antibody anticardiolipin (ACL) IgM
presentation, polymerase chain reaction (PCR) of were found to be positive. The child responded to the
tracheal aspirate for MP was done and was positive above measures, and his sensorium improved. He was

extubated after 4 days of ventilation. Repeat MRI brain However, extensive pulmonary disease in the form of
done after 10 days showed findings similar to previous massive lobar pneumonia with pleural effusions as well
MRI with near‑total recanalization of the right transverse as necrotizing pneumonia has been reported.[1‑3] Pleural
sinus [Figures 4 and 5]. Serial investigations showed fluid data available from these reports have shown the
reducing evidence of hemolysis. The child was discharged pleural effusion to be lymphocyte predominant rather than
on oral steroid and clarithromycin after complete clinical polymorphonuclear leukocyte predominant as was the case
resolution of respiratory and neurological signs with a plan with our child. While all of these children have protracted
to repeat thrombotic workup after 3 months. periods of fever and respiratory distress, early‑stage
diagnosis is difficult due to the lack of obvious symptoms.
DISCUSSION
MP can be detected by PCR, including multiplex PCR
MP, acquired through respiratory secretions of an infected panels which can be performed rapidly and have a high
person, usually presents with symptoms including fever, sensitivity and specificity. They can be done on a respiratory
malaise, sore throat, and cough and becomes noticeable specimen (e.g., nasopharyngeal or throat swab). The yield
after the first 1–3 weeks of exposure. Often referred to as from cerebrospinal fluid is low. Culture can take as long as
“walking pneumonia,” most cases of MP are uncomplicated. 3 weeks and does not take on gram stain as it lacks a cell
wall. If PCR is not available, MP IgM and IgG enzyme
Table 1: Laboratory investigations
immunoassay can be done.
Investigations in PICU Result
Hemogram
Hb 2.1
Drugs used in treatment include erythromycin, azithromycin,
TLC (/cumm) 12,000 clarithromycin, tetracyclines, chloramphenicol,
Neutrophils (%) 80 aminoglycosides, and quinolones. The most commonly
Leukocytes (%) 8
Platelet (L/cu mm) 5.33
used is azithromycin given at 10 mg/kg/day on day 1,
Marked autoagglutination Positive 4+ followed by 5 mg/kg/day for 4 days, while clarithromycin
Direct and indirect Coombs test Positive 4+ at 15 mg/kg/day is administered every 12 h for 10 days.[4]
Serum electrolytes Normal
Retic count (%) 0.5 (0.2‑2)
Serum ferritin (ng/ml) 7568 (7‑140) Among the various extrapulmonary manifestations,
DNA PCR for Mycoplasma in tracheal aspirates Positive (high) hemolytic anemia has been frequently associated with
Mycoplasma IgM (blood) Positive (34.08 NTU)
MP pulmonary infection.[5] Steroids have been used in
Urine for hemosiderin Positive
Cold agglutinin titer Positive (1:256) the management of encephalitis and hemolytic anemia.
Beta‑2 glycoprotein 1 Splenectomy may be necessary if there is no response to
IgM (RU/mL) Positive (88.16)
IgG Negative
steroids or if the remission is not maintained when the
ANA Negative dose of prednisolone is reduced. Immunosuppressive
Cardiolipin antibody ACL IgM (U/mL) Positive (65.08) drugs such as azathioprine and cyclophosphamide may be
Lupus anticoagulant Absent
effective. Thrombosis occurs as a part of extrapulmonary
Hb: Hemoglobin, TLC: Total leukocyte count, PCR: Polymerase chain
reaction, ACL: Anticardiolipin, PICU: Pediatric intensive care unit, complications and responds to anticoagulation. MP
ANA: Anti-nuclear antibody
Figure 4: Repeat magnetic resonance imaging showing near total Figure 5: Repeat magnetic resonance imaging brain showing
recanalization of the right transverse sinus. Few collateral vessels are hyperintense signals on T2‑ and fluid‑attenuated inversion recovery
seen along the surface of the sinus images

is known to cause prothrombotic state leading to the other clinical information to be reported in the journal.
positivity of antiphospholipid antibodies. Antibody titers The patients understand that their names and initials will
during the active infection and at a later date (~3 months) not be published and due efforts will be made to conceal
help to differentiate underlying autoimmune conditions their identity, but anonymity cannot be guaranteed.
from MP‑related prothrombotic state.
Financial support and sponsorship
IVIG (at 2 g/kg) has been used successfully in refractory MP Nil.
infection, especially when there is suspicion of an autoimmune
process with reports showing neurological improvement Conflicts of interest
occurring within 48 h of administration of IVIG.[6,7] There are no conflicts of interest.
Plasmapheresis remains another therapeutic intervention.[8]
REFERENCES
In MP infections and other viral infections, lupus 1. Matsumoto M, Nagaoka K, Suzuki M, Konno S, Takahashi K,
anticoagulant, ACL antibodies, and beta‑2 glycoprotein Takashina T, et al. An adult case of severe life‑threatening Mycoplasma
antibody can be present transiently and require to be pneumoniae pneumonia due to a macrolide‑resistant strain, Japan: A case
report. BMC Infect Dis 2019;19:204.
documented after a period of 3 months to confirm the
2. Jo SY, Na KW, Kim SW, Hwang YH. Mycoplasma pneumoniae‑associated
prothrombotic state secondary to the infection.[9] necrotizing pneumonia in children: A case‑report. Kosin Med J
2019;34:57‑64.
CONCLUSION 3. Cha SI, Shin KM, Jeon KN, Yoo SS, Lee J, Lee SY, et al. Clinical
relevance and characteristics of pleural effusion in patients with
Although often benign, MP can present with severe Mycoplasma pneumoniae pneumonia. Scand J Infect Dis 2012;44:793‑7.
4. Costagliola ML. Pediatric Respiratory Diseases. In: Community‑acquired
pulmonary and extrapulmonary complications. Newer pneumonia. Cham: Springer; 2020. p. 299‑307.
diagnostic techniques such as DNA PCR for Mycoplasma for 5. Bell A, Hughes J, Williams C, Knox S. G547(P) Oh my… a very unusual
direct detection of the antigen are proving useful for rapid coincidence! the case of a boy who developed haemolysis following
etiological diagnosis. Treatment of complications such as a trip to the swimming pool. Archives of Disease in Childhood
2019;104:A221.
autoimmune hemolytic anemia includes administration 6. Attilakos A, Palaiologou P, Lagona E, Voutsioti A, Dinopoulos A.
of steroids while the CNS complications warrant the use Mycoplasma pneumoniae encephalopathy: Recovery after intravenous
of IVIG and plasmapheresis. Underlying autoimmune immunoglobulin. Pediatr Neurol 2008;38:357‑9.
conditions should be differentiated from MP‑related 7. Daba M, Kang PB, Sladky J, Bidari SS, Lawrence RM, Ghosh S.
Intravenous immunoglobulin as a therapeutic option for Mycoplasma
prothrombotic state by repeating antibody titers after a pneumoniae encephalitis. J Child Neurol 2019;34:687‑91.
3‑month period. 8. Hanzawa F, Fuchigami T, Ishii W, Nakajima S, Kawamura Y, Endo A,
et al. A 3‑year‑old boy with Guillain‑Barré syndrome and encephalitis
Declaration of patient consent associated with Mycoplasma pneumoniae infection. J Infect Chemother
2014;20:134‑8.
The authors certify that they have obtained all appropriate 9. Wang Chun K, See Wan Y, Poon Chuen W. Transient presence of lupus
patient consent forms. In the form the patient(s) has/have anticoagulant associated with Mycoplasma pneumonia. Asian Cardiovasc
given his/her/their consent for his/her/their images and Thorac Ann 2016;24:286‑7.

Case Report
Amitraz, an unusual poison

Yogesh N. Parikh, Mayur C. Gwalani, Aarti Makwana, Divyaraj A. Bavishi
Department of Pediatrics, Rajkot Civil Hospital, Pandit Deendayal Upadhyay Medical College, Rajkot, Gujarat, India
Accidental poisoning in children is a common pediatric emergency. Here, we report the case of a 7‑year‑old
Abstract girl with Amitraz poisoning. Ingestion and dermal contact with a dissolved solution of Amitraz lead to acute
toxicity, which mimicked organophosphate poisoning. The patient lost consciousness which prompted
their presentation to the pediatric emergency department. Limited literature is available regarding Amitraz
poisoning. This case report attempts to document the findings and raise awareness to hasten identification
and treatment of a rare and newer poison, Amitraz.
Keywords: Amitraz, pesticide, poisoning, toxicology
Address for correspondence: Dr. Mayur C. Gwalani, Block 972, New GHB Colony, Sanala Road, Morbi, Rajkot, Gujarat, India.
INTRODUCTION bradycardia, hypotension/hypertension, hypothermia,

hyperglycemia, polyuria, decreased gastrointestinal
Amitraz is a formamidine pesticide that is often used motility and intestinal distension, miosis, central nervous
by vets and agriculturists as an insecticide. It is also system (CNS) depression with drowsiness, respiratory
used for controlling ectoparasites in cattle and pets. depression, convulsions, and coma.[1]
Amitraz is available in India under the brand name
NITRAZ and A‑MTIRAZZ at 12.5% concentration as Only limited literature is available regarding Amitraz
an over‑the‑counter pesticide at pet, local chemical, and poisoning, especially in the Indian scenario.
even on online stores, which is then diluted in water for
application. CASE REPORT
It acts as a central α2 adrenergic receptor agonist and We report the case of a 7‑year‑old female child who
peripheral α1 and α2 adrenergic receptor agonist. Amitraz presented with symptoms of poisoning, which was
also inhibits prostaglandin E2 synthesis and monoamine retrospectively confirmed as Amitraz.
oxidase enzyme activity (dose dependent).[1]
The patient suddenly woke up at night and started
Poisoning via Amitraz can occur through inhalational screaming but soon lost consciousness, for which she was
(most potential), cutaneous, and ingestional routes.[2] brought to the pediatric emergency department. She was
Signs and symptoms of toxicity include nausea, vomiting, admitted as a case of unknown poisoning; approximately
6 h after, the first symptoms became apparent to the
parents. The patient was completely all right the previous
night and went to sleep until midnight when she woke the
Website:
www.jpcc.org.in
DOI:
10.4103/JPCC.JPCC_3_20 How to cite this article: Parikh YN, Gwalani MC, Makwana A, Bavishi DA.
Amitraz, an unusual poison. J Pediatr Crit Care 2020;7:92-4.

Parikh, et al.: Amitraz, an unusual poison: A case report
parents up with incomprehensible screaming and soon lost oral ingestional (mucosal) poisoning seemed to have been
consciousness. There was no history of trauma. the probable routes of exposure to Amitraz.
On preliminary examination, the temperature was normal, The patient was discharged after 2 days of uneventful
heart rate was 48/min (bradycardia), and respiratory rate observation.
was 16/min. CNS examination showed altered sensorium
DISCUSSION
with a Glasgow Coma Scale of 3 (eye opening – 1, verbal
response – 1, and motor response – 1). The respiratory
In our case, complete recovery was achieved through
system had bilaterally equal air entry and normal breath
supportive treatment without any sequelae after 11 h
sounds with no crepitations or rhonchi. Cardiovascular
of admission. Maintaining adequate hydration, airway,
system examination yielded normal heart sounds without
breathing, and circulation formed the crux of the
murmurs. The patient was also seen to have miosis,
administered supportive treatment.
polyuria, and a low pulse volume. An unknown poison
was highly suspected, but no history of exposure could CNS symptoms and bradycardia were the primary
be elicited. presenting signs in our patient (α2 adrenergic receptor
agonist action). Miosis and bradycardia were indications
The patient was intubated and kept on pressure assist‑control for atropine initiation and its administration led to
mode (FiO2 at 100%, positive end‑expiratory pressure at an improvement in both. Inotropes (adrenaline and
6, and positive inspiratory pressure at 15). The patient noradrenaline) and IV fluids (normal saline) were started
was given a normal saline bolus of 60 ml/kg along with to treat the state of hypovolemic shock in the patient.
inotropes (adrenaline and noradrenaline) and atropine Intubation and mechanical ventilation were undertaken, as
(for miosis and bradycardia) at standard pediatric doses. the Glasgow Coma Scale was 3. (Standard pediatric doses
Immediate improvement in the vitals on the administration were used for all of the above‑mentioned drugs and fluids
of inotropes and atropine was noted. administered.)
A battery of tests was conducted meanwhile to aid the Bradycardia and miosis can be clinically mistaken as signs
identification of the unknown poison and find the antidote. of organophosphate poisoning, [3] a common clinical
Electrocardiogram was normal; hemoglobin – 11.1 g%; scenario, but Amitraz poisoning yields normal serum
white blood cell count – 4700/mm3; differential count cholinesterase levels, making serum cholinesterase an
(%) – 55/43/1/1/0; platelet count – 219,000/mm3; and important differentiating test.[3] Opioid poisoning should
malarial parasite on peripheral smear was absent. Random also be ruled out.[4]
blood glucose was 126 mg/dL; serum urea – 29 mg/dL; serum
creatinine – 0.8 mg/dL; serum sodium – 136 mEq/L; serum There is no exact antidote for Amitraz poisoning, and most
potassium – 3.9 mEq/L; serum creatine kinase‑mb – 22 IU/L; existing literature deems supportive and symptomatic
serum cholinesterase – 7354 IU/L (normal); prothrombin treatment highly effective. Decontamination methods
time – 13.4 s; and activated partial thromboplastin such as gastric lavage and activated charcoal could be
time – 35.8 s. International normalized ratio was 1.07. considered if a history of oral ingestion of Amitraz is
present,[5] but their role remains unclear.[6] Some studies
Urine routine and microscopy were normal. The tests did report the use of Atropine for bradycardia and miosis, but
not help to determine the causative poison, and hence, no controlled studies proposing its efficacy in a sufficient
supportive treatment was continued. sample size are available. Atropine can be considered
in cases with a predominance of bradycardia.[5] In a
The inotropes were tapered and the patient was extubated systematic review, of 310 cases, nearly 20% and 11.9% of
after 11 h of admission with the improvement of the patients required mechanical ventilation and inotropic
consciousness (Glasgow Coma Scale – 15) and stable support, respectively. Amitraz poisoning carried a good
maintenance of SpO2 (99%). The patient was subsequently prognosis with only six reported deaths (case fatality
shifted from intravenous (IV) fluids to oral fluids. Recovery rate, 1.9%).[6]
was complete.
To conclude, Amitraz poisoning should be suspected in
On regaining consciousness, the patient recounted the poisoning cases if there is a history of exposure to cattle
incident of poisoning, and the father, a dog trainer, insecticide associated with CNS depression, bradycardia,
identified the poison as Amitraz. In this case, dermal and miosis, and normal serum cholinesterase levels. As
Parikh, et al.: Amitraz, an unusual poison: A case report
documented in this case report, prompt administration of Conflicts of interest

supportive treatment on recognizing the above‑mentioned There are no conflicts of interest.
signs forms the crux of the treatment of a case of Amitraz
REFERENCES
poisoning.
1. Jorens PG, Zandijk E, Belmans L, Schepens PJ, Bossaert LL. An
Declaration of patient consent unusual poisoning with the unusual pesticide amitraz. Hum Exp
The authors certify that they have obtained all appropriate Toxicol 1997;16:600‑1.
2. Aydin K, Kurtoğlu S, Poyrazoğlu MH, Uzüm K, Ustünbaş HB,
patient consent forms. In the form the patient(s) has/have Hallaç IK. Amitraz poisoning in children: Clinical and laboratory
given his/her/their consent for his/her/their images and findings of eight cases. Hum Exp Toxicol 1997;16:680‑2.
other clinical information to be reported in the journal. 3. Dhooria S, Behera D, Agarwal R. Amitraz: A mimicker of
organophosphate poisoning. BMJ Case Rep 2015;2015:bcr2015210296.
The patients understand that their names and initials will 4. Balali‑Mood M, Balali‑Mood K, Shirazi H. Recent advances in
not be published and due efforts will be made to conceal treatment of acute organophosphorous nerve agents poisoning. Iranian
their identity, but anonymity cannot be guaranteed. J Pharm Res 2006;2:79‑87.
5. Eizadi‑Mood N, Sabzghabaee AM, Gheshlaghi F, Yaraghi A. Amitraz
poisoning treatment: Still supportive? Iran J Pharm Res 2011;10:155‑8.
Financial support and sponsorship 6. Dhooria S, Agarwal R. Amitraz, an underrecognized poison:
Nil. A systematic review. Indian J Med Res 2016;144:348‑58.

Clinical Update
Chloride in intensive care

Kundan Mittal
Department of Pediatrics, Pt. B. D. Sharma PGIMS, Rohtak, Haryana, India
Abstract Chloride has significant role in the body fluid management and action potential. It also helps in the regulation
of acid–base status and facilitates oxygen unloading. Hyper‑ and hypo‑chloremia associated with certain
conditions are associated with poor outcome.
Keywords: Hyperchloremia, hypochloremia, metabolic acidosis
Address for correspondence: Dr. Kundan Mittal, Department of Pediatrics, Pt. B. D. Sharma PGIMS, Rohtak ‑ 124 001, Haryana, India.
INTRODUCTION FUNCTIONS OF CHLORIDE
Chloride is the most common anion present in the • Acid–base homeostasis

extracellular fluid (ECF). It combines with sodium • Regulation of sodium, potassium, and chloride
and potassium inside the human body. Chloride reabsorption
concentration is high in the cerebrospinal fluid, gastric, • Chloride increases blood pressure
and bile secretion in comparison to ECF. Being • It is inversely related to renin secretion and glomerular
negatively charged, it moves with sodium and helps in filtration rate
maintaining resting action potential, osmolality, and water • Facilitates oxygen unloading
balance. It also helps in maintaining acid–base balance • Contributes to gastric acidity
(chloride and bicarbonate have inverse relationship), plasma • Maintains intestinal osmotic gradient and fluid
oncotic pressure, and carbon dioxide transported in red secretion
cells. • Protein digestion, microorganism homeostasis,
nutrients’ absorption
Normal serum chloride level (related to RBC and free in • Increased level decreases gastric‑pyloric motility.
the blood) is 96–107 mEq/L and intracellular chloride level
is 4 mEq/L. It remains stable with age. Chloride balance is HYPERCHLOREMIA
associated with sodium and bicarbonate, and its regulation
depends on intake, excretion, and reabsorption from Serum level >108 mEq/L may be associated with rise in
kidney. Chloride is mainly excreted through gastrointestinal the sodium level or alone and decrease in the bicarbonate
tract (GIT), kidney, and skin.[1‑5] level. High level is seen in 25%–45% of intensive care
unit patients. Increased level may be due to increased
intake of saline, water loss, absorption, acidosis, retention
Received: 15-02-2020 Revised: 22-02-2020 by kidneys, salicylate toxicity, respiratory alkalosis,
Accepted: 29-02-2020 Published: 10-04-2020 hyperparathyroidism, hypernatremia, saline infusion, and
Website: remix, tweak, and build upon the work non‑commercially, as long as appropriate credit
www.jpcc.org.in
DOI:
10.4103/JPCC.JPCC_33_20 How to cite this article: Mittal K. Chloride in intensive care. J Pediatr Crit
Care 2020;7:95-6.

Mittal: Chloride in intensive care
drug‑related retention. Various drugs associated with calcium levels. Level decreases if intake is less; loss from
raised chloride level are aspirin, acetazolamide, kayexalate, skin, GIT, kidney; or changes in the sodium and acid–base
phenylbutazone, and ammonium chloride. Hyperchloremia level. Certain drugs are also associated with low chloride
does not produce signs and symptoms directly, but indirect level (diuretics, mannitol, corticosteroids, bicarbonate, and
features related to metabolic acidosis appear. Other theophylline). Other causes include low level of sodium
features include altered sensorium, fluid retention, dyspnea, and potassium, metabolic alkalosis, cystic fibrosis, gastric
tachypnea, tachycardia, hypertension, and weakness. High surgery, diabetic ketoacidosis, and heart failure. If chloride
chloride level is also associated with increased sodium level loss is more than sodium, hypochloremic alkalosis develops.
and features suggestive of fluid retention. While assessing Signs and symptoms of the electrolytes imbalance and
the chloride level, it is must to measure serum sodium, metabolic alkalosis appear. Other features are irritability,
bicarbonate, and anion gap. agitation, seizure, coma, tetany, and muscle hypertonicity.
Low chloride level in congestive cardiac failure is associated
Hyperchloremic metabolic acidosis is associated with acute with increased mortality.
kidney injury, vasodilatation, altered neurotransmission,
increased inflammatory markers, decreased cardiac Treatment
activity, hemodynamic instability (both hypo and hyper are • Prevention
detrimental), decreased endogenous catecholamine release, • Correct underlying etiology
and decreased cellular function. Rise more than 5 mEq/l • Correction of other electrolyte abnormalities
is associated with increased mortality. • Fluid therapy and intravenous or oral sodium chloride
• Monitor vitals and other electrolytes.
Treatment
• Prevention Financial support and sponsorship
• Treatment of underlying cause Nil.
• Fluid resuscitation
• Correction of other electrolytes Conflicts of interest
• Acid–base status There are no conflicts of interest.
• In severe case, intravenous sodium bicarbonate is
indicated and rarely diuretic therapy REFERENCES
• Monitor intake and output, vital signs including cardiac
1. Agrò FE. Body Fluid Management: From Physiology to Therapy. Italy:
rhythm, and neurological and respiratory status Springer; 2013.
• Further, monitor serum electrolytes including 2. Waikar SS, Murray PT, Singh AK. Core Concepts in Acute Kidney
bicarbonate level. Injury. USA: Springer; 2018.
3. Kellum JA, Elbers PW. Stewart’s Textbook of Acid‑Base. USA: Lulu.
HYPOCHLOREMIA com; 2009.
4. Mount DB, Sayegh MH, Singh AK. Core Concepts in the Disorders
of Fluid, Electrolytes and Acid‑Base Balance. London: Springer; 2013.
It is defined as serum chloride level <96 mEq/L. Besides, 5. Reddi AS. Fluid, Electrolyte and Acid‑Base Disorders. 2nd ed. USA:
chloride also measures serum sodium, potassium, and Springer; 2018.

Letter to Editor
Cardiac arrest secondary to Jervell‑Lange‑Neilson syndrome

A 6‑year‑old female child, with a known history of She was weaned off ventilator by 24 h of hospitalization
congenital severe bilateral sensory neural deafness, was and was discharged in a stable condition on day 4. She
taken for cochlear implant surgery. She presented with continues to be on treatment with oral metoprolol and
sudden cardiac arrest during the induction of general has had no further cardiac events post-discharge from the
anesthesia. She was transferred to the Advanced Pediatric hospital.
Critical Care Centre, Wanless Hospital, Miraj. There was no
prior history suggestive of syncopal attacks. She was not LQTSs are genetic abnor malities of ventricular
on any medications before her hospitalization. There was repolarization, with an estimated incidence of about 1
no delay in the attainment of motor and social milestones. per 10,000 birth. They present as a long QTc interval
Congenital sensorineural deafness is present in two older on ECG (>0.47 s) and are associated with malignant
female siblings but no history of syncopal attacks or sudden ventricular arrhythmias (torsades de pointes and ventricular
death in any family members. fibrillation). They are a cause of syncope and sudden
death.[1] Jervell‑Lange‑Neilson syndrome (JLNS) is an
Postresuscitation, she was hemodynamically stable on autosomal recessive disorder characterized by congenital
ventilator and adrenaline infusion. There were no significant sensorineural deafness and long QT interval on ECG. It
findings on physical examination revealing the cause for is associated with the genes KCNQ1 (JLNS type 1) and
the cardiac arrest. Laboratory findings and investigations KCNE1 (JLNS type 2).
revealed normal blood count and biochemistry. Chest
radiograph showed normal lung fields and cardiac size. Clinical manifestation of LQTS in children is most often a
Electrocardiogram (ECG) revealed long QTc interval syncopal episode brought on by exercise, fright, or sudden
(0.62 s) [Figure 1]. startle. They may present with seizures, presyncope, or
palpitations. Approximately 10% are initially in cardiac
Two‑dimensional echo (postcardiac arrest) showed trivial arrest.[2] In our case, cardiac arrest was the initial presentation.
TR, mild right ventricular dysfunction, left ventricular
ejection fraction 55%, and structurally normal heart. The diagnosis is based on the ECG and clinical criteria.
A heart rate‑corrected QT interval of >0.47 s is highly
Findings of long QT interval combined with congenital indicative, whereas a QT interval of >0.44 s is suggestive.
sensorineural hearing impairment led to the clinical Other features include notched T‑waves in 3 leads,
diagnosis of Jervell and Lange‑Neilson syndrome, one of T‑wave alternans, a low heart rate for age, a history of
the rarer types of long QT syndromes (LQTSs). The child syncope (especially with stress), and a familial history of
was started on oral beta‑blocker metoprolol (2 mg/kg/day). either LQTS or sudden death. Genotyping can identify the
mutation in approximately 80% of patients known to have
LQTS by clinical criteria.[1]
Treatment of LQTS includes the use of beta‑blocking

agents at doses that blunt the heart rate response to
exercise. Some patients may require a pacemaker because
of drug‑induced bradycardia. In patients with continued
syncope, despite treatment, an implantable cardiac
defibrillator is indicated for those who do not respond to
beta‑blockers and those who have had a cardiac arrest.[1]
Declaration of patient consent

The authors certify that they have obtained all appropriate
patient consent forms. In the form the patient(s) has/have
given his/her/their consent for his/her/their images and
Figure 1: Electrocardiograph long lead II showing long QTc interval other clinical information to be reported in the journal.
Letter to Editor
The patients understand that their names and initials will 2. Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K, et al.
The Jervell and Lange‑Nielsen syndrome: Natural history, molecular
not be published and due efforts will be made to conceal
basis, and clinical outcome. Circulation 2006;113:783‑90.
their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship Received: 15-02-2020 Revised: 28-02-2020

Nil. Accepted: 07-03-2020 Published: 10-04-2020
Conflicts of interest This is an open access journal, and articles are distributed under the terms of the Creative
There are no conflicts of interest. remix, tweak, and build upon the work non‑commercially, as long as appropriate credit
Priya Sakte, Jennifer Antin, Sachin Jangam,

Vinayak Patki
Department of Pediatrics, Advanced Pediatric Critical Care Centre, Website:
Wanless Hospital, Miraj, Maharashtra, India www.jpcc.org.in
Address for correspondence: Dr. Priya Sakte,

Department of Pediatrics, Advanced Pediatric Critical Care Centre, DOI:
Wanless Hospital, Miraj, Maharashtra, India. 10.4103/JPCC.JPCC_32_20
REFERENCES
How to cite this article: Sakte P, Antin J, Jangam S, Patki V. Cardiac
arrest secondary to Jervell-Lange-Neilson syndrome. J Pediatr Crit Care
1. van Hare GF. Long Q‑T syndromes. In: Kleigman, Stanton, St Gene, 2020;7:97-8.
Schor, editors. Nelson Textbook of Pediatrics. 1st South‑East Asia ed.,
© 2020 Journal of Pediatric Critical Care | Published by Wolters Kluwer - Medknow
Vol. 2, Ch. 435. Elsevier India; 2015. p. 2258‑9.

Critical Thinking-PICU Quiz
PICU quiz
1. A 5‑year‑old child with muscular dystrophy is scheduled drip and intermittent benzodiazepine for sedation.
to undergo muscle biopsy for diagnosis. Anesthesia is Which one of the following options would be the most
induced using sevoflurane and you start injecting appropriate next step in management of this patient?
succinylcholine in preparation for intubation. The child A. Use rocuronium for paralysis and start diuretics
develops masseter spasm immediately and temperature to help decrease pleural effusion
rises to 41°C. After immediate discontinuation of B. Use cisatracurium for paralysis and insert the
inhaled anesthesia and succinylcholine, which one of Intercostal drainage (ICD) in the fifth intercostal
the following steps is the most appropriate? space (ICS) in the right mid axillary line
A. Start normal saline bolus C. Use cisatracurium for paralysis and insert the ICD
B. Intravenous (IV) injection of dantrolene in the second ICS in the right mid‑clavicular line
C. Arrange bed in the pediatric intensive care D. Use rocuronium for paralysis and insert the ICD
unit (PICU) in the fifth ICS in the right mid‑axillary line
D. Start 100% oxygen with a high flow rate to wash E. Use rocuronium for paralysis and insert the ICD
out residual sevoflurane in the second ICS in the right mid‑clavicular line.
E. Paralyze and intubate the child with another agent. 4. A 2‑month‑old girl developed poor feeding and
2. An 18‑month‑old boy with Type I spinal muscular irritability early this morning. She was brought to
atrophy is in the PICU with respiratory syncytial the emergency department (ED) due to respiratory
virus bronchiolitis which presented as fever and distress. On examination, she looks mottled and has
copious secretions. He has a respiratory rate (RR) weak pulses. Her rhythm strip in lead II showed the
of 56 breaths/min with deep subcostal retractions following rhythm. The emergency physician tried
and is started on noninvasive positive‑pressure cardioversion with 0.5 J/kg, but rhythm on the monitor
ventilation (PPV) with inspiratory pressure of 15 cm did not change.
H2O and expiratory pressure of 5 cm H2O. After a
while, his retractions are much improved, and RR is
30 breaths/min. However, saturations are only 92% on
40% oxygen, and the chest radiograph reveals basilar Which one of the following options is the next most
atelectasis. Which one of the following treatment plans appropriate intervention?
will best recruit her collapsed lung? A. Synchronized cardioversion with 0.25 J/Kg
A. Increase expiratory pressures to 10 cm of H2O B. 25 mg/kg of IV magnesium sulfate
and inspiratory pressures to 20 cm H2O C. Defibrillation with 2 J/kg
B. Just increase expiratory pressure to 10 cm of H2O D. Synchronized cardioversion with 2 J/kg
C. Give glycopyrolate to decrease secretions E. 0.1 mg/kg of IV adenosine.
D. Intubation and mechanical ventilation 5. A 2‑year‑old infant is brought to the ED after his
E. C h e s t p hy s i o t h e r a p y w i t h m e ch a n i c a l mother found him drinking an unknown substance
insufflation‑exsufflation. from a soda bottle in the family’s pool house.
3. A 4‑year‑old boy is being treated for pneumococcal You suspect that the substance was an acidic pool
pneumonia and sepsis. You have noticed decreased cleaner. Physical examination of the child’s lips,
breath sounds on the right side along with increased tongue, and oropharynx reveals no abnormalities.
ventilatory settings. He has become more edematous, Of the following, the MOST appropriate next step
has decreased urine output, and has oozing around in management is:
his central and arterial lines. His blood workup A. Emergent upper gastrointestinal radiographic
shows thrombocytopenia, elevated liver enzymes, series
coagulopathy, and worsening renal function. His B. Initiation of oral antibiotic therapy
chest radiograph shows a new right‑sided pleural C. Parental reassurance and patient discharge
effusion. You decide to place a right‑sided chest tube D. Placement of a nasogastric tube for lavage
to evacuate the effusion. He is receiving a fentanyl E. Referral for emergency esophagoscopy.

Sharma and Khilnani: Critical thinking‑PICU quiz
6. A 10‑year‑old girl was admitted in the PICU with a C. The child is excessively sensitive to PTH since
history of injury over the right ankle 1 week back. normal levels are stimulating excessive calcium
The child had features of sepsis with septic shock and mobilization from bone
was ventilated for a duration of 48 h. The diagnosis D. You need a parathyroid scan to make a conclusion.
of Methicillin‑resistant Staphylococcus aureus (MRSA) 8. Which is/are correct statements regarding the
septicemia was made, and she had responded well inspiratory time (Ti)
to IV vancomycin. The child was extubated onto A. At the end‑Ti, the expiration phase always starts
nasal prong oxygen and showed significant clinical B. If Ti is set by the inspiration‑to‑expiration ratio,
improvement. After 10 h of extubation, you get a call the Ti is independent of ventilator frequency
from the intensive care unit that the child had sudden C. If Ti is directly set, the expiratory time decreases
deterioration in the form of increased respiratory with increasing ventilator frequency
distress, tachycardia, and hypotension. What are the D. Normal Ti is in the range of 3–4 s.
possibilities you consider and intervention?
9. Causes of right ventricular failure include/s:
A. Tension pneumothorax and needs an emergency
A. Acute pulmonary embolus
ICD insertion
B. Protamine
B. Seizure and needs IV midazolam
C. Acute respiratory distress syndrome (ARDS)
C. Bronchospasm and needs IV steroid and
D. Obstructive sleep apnea
nebulisations
D. Cardiac tamponade secondary to pericardial E. All of the above.
effusion leading to obstructive shock and needs 10. Regarding prone position ventilation which is
urgent echocardiography (ECHO) and drainage correct:
E. Septic shock and needs fluid bolus. A. The PROSEVA study group showed no mortality
7. The child presents with elevated serum free calcium, benefit at 28 days in severe ARDS
but parathyroid hormone (PTH) is in the normal range. B. Alveolar recruitment is affected as drainage of
What is the best conclusion? secretions gets impaired
A. PTH is normal; therefore, problem does not lie in C. A more homogeneous ventilation distribution
parathyroid gland is achieved due to favorable changes in
B. PTH should be low if the parathyroid is thoraco‑abdominal compliance
functioning normally; thus, the problem is in the D. Proning increases extravascular lung water
parathyroid gland E. The optimal duration of prone positioning is 24 h.

Sharma and Khilnani: Critical thinking‑PICU quiz
ANSWERS 6. D: Cardiac tamponade secondary to pericardial

effusion leading to obstructive shock and needs urgent
1. D: Start 100% oxygen with a high flow rate to wash ECHO and drainage
out residual sevoflurane Rationale: MRSA septicemia can lead to collection
Rationale: The child has features of malignant in the pericardial space which if left unnoticed and
hyperthermia. Patients with muscular dystrophy are at monitored can lead to increase and cause obstructive
increased risk of malignant hyperthermia when exposed shock. Urgent ECHO and relieving the tamponade
to inhalational anesthetic agents such as halothane, can be lifesaving. Tension pneumothorax is unlikely if
sevoflurane, isoflurane, and/or succinylcholine. the child remained stable for over 10 h postextubation
Features of malignant hyperthermia are muscle and with no PPV. Other options do not fit in.
rigidity, fever, increased carbon dioxide production, 7. C: Child is excessively sensitive to PTH since normal
acidosis, and tachycardia. It is a fatal condition and levels are stimulating excessive calcium mobilization
immediate intervention in order of sequence includes from bone.
discontinuation of offending agents, oxygenation with 8. C: If Ti is directly set, the expiratory time decreases
100% oxygen to wash out the offending inhalational with increasing ventilator frequency.
agent, IV injection of dantrolene, and use of cold 9. E: All of the above.
normal saline if temperature is above 30°C. Avoid 10. C: A more homogenous ventilation distribution is
paralysis and intubation in this patient. achieved due to favorable changes in thoraco‑abdominal
2. E : C h e s t p hy s i o t h e r a p y w i t h m e ch a n i c a l compliance.
insufflation‑exsufflation
Rationale: The child will need frequent breaks from the Financial support and sponsorship
ventilator to remove secretions. He will need assistance Nil.
in the form of chest physiotherapy and cough assist.
Use of these methods improves strength of cough and Conflicts of interest
helps resolve atelectasis. Increasing pressures might There are no conflicts of interest.
help temporarily but will fail in due course.
3. B: Use cisatracurium for paralysis and insert the ICD Pradeep Kumar Sharma, Praveen Khilnani1
in the fifth ICS in the right mid‑axillary line. Department of Pediatric Critical Care and Pulmonology, Sri Balaji
Rationale: The patient has features of multi‑organ Action Medical Institute, 1Department of Pediatric Critical Care
dysfunction. Cisatracurium is eliminated by Hofmann and Pulmonology, Rainbow Children Hospital, New Delhi, India
elimination, which is spontaneous degradation of the
Address for correspondence: Dr. Pradeep Kumar Sharma,
medication at physiological pH and temperature. Usual Sri Balaji Action Medical Institute, New Delhi, India.
site for thoracentesis or chest tube placement is the fourth E‑mail: [email protected]
or fifth ICS in anterior or mid‑clavicular line. Rocuronium
is not the ideal choice for paralysis in children with renal Received: 26-02-2020 Revised: 04-03-2020
failure, as kidneys mostly eliminate it. Diuretics are not
going to be effective to decrease pleural effusion.
4. D: Synchronized cardioversion with 2 J/kg Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to
Rationale: This is a child with unstable ventricular remix, tweak, and build upon the work non‑commercially, as long as appropriate credit
tachycardia. Rhythm strip shows monophasic
ventricular tachycardia. In this scenario, electrical Access this article online
cardioversion is recommended. If lower energy fails to Quick Response Code:
convert or break ventricular tachycardia synchronized Website:
cardioversion with higher energy should be tried. www.jpcc.org.in
5. E: Referral for emergency esophagoscopy.

Rationale: Upper endoscopy under anesthesia should DOI:
be performed within the first 48 h of caustic ingestion 10.4103/JPCC.JPCC_35_20
to determine the extent of the esophageal injury. The
objective of the endoscopy is to establish the presence
or absence of an esophageal lesion and to determine How to cite this article: Sharma PK, Khilnani P. PICU quiz. J Pediatr Crit
Care 2020;7:99-101.
the extent of the injury.

Book Review
Pediatric respiratory diseases: A comprehensive

textbook
Authors: Pablo Bertrand and Ignacio Sanchez
Hardcover: 807 pages
Publisher: Springer; 1st ed. 2020 edition (February 3, 2020)
Language: English
ISBN‑10: 3030269604
ISBN‑13: 978‑3030269609
Price: $144.53
Respiratory diseases are common in pediatric population Address for correspondence: Dr. Kundan Mittal,
Department of Pediatrics, Pt. B. D. Sharma PGIMS, Rohtak, Haryana, India.
compared to adults due to certain anatomical and E‑mail: [email protected]
physiological differences. This book contains 74 chapters in
five sections. This book covers from physiological basis of
respiratory illnesses, assessment of pulmonary functions, Received: 25-02-2020 Revised: 03-03-2020
immunological aspect, procedures in respiratory illness,
symptoms diagnosis, to various diseases’ management,
including oxygen therapy, nursing care, mechanical This is an open access journal, and articles are distributed under the terms of the Creative
ventilation (acute, chronic, long term), and rehabilitation, Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to
which are common in children. Special emphasis has been is given and the new creations are licensed under the identical terms.
given on ECMO therapy and lung transplantation. This
book has been written in simple language and must read
for every pediatrician and intensivist.
Website:
Financial support and sponsorship www.jpcc.org.in
Nil.
DOI:
Conflicts of interest
10.4103/JPCC.JPCC_34_20
There are no conflicts of interest.
Kundan Mittal
How to cite this article: Mittal K. Pediatric respiratory diseases: A
Department of Pediatrics, Pt. B. D. Sharma PGIMS, Rohtak,
comprehensive textbook. J Pediatr Crit Care 2020;7:102.
Haryana, India
Editor Dr. Vinayak Patki. Printed and published by Wolters Kluwer India Private Limited, on behalf of Intensive Care Chapter of Indian Academy of Pediatrics. Printed at
Kundan Press, Jaysingpur, Dist. Kolhapur, 416101, Maharashtra, India and published by Wolters Kluwer India Private Limited from A-202, 2nd Floor, The Qube, C.T.S.
No.1498A/2 Village Marol, Andheri (East), Mumbai - 400 059, India.

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Print ISSN: 2349-6592, E-ISSN: 2455-7099

International Advisory Board

Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020 i

Excecutive Board 2020

Dr. Dhiren Gupta

Dr. Bakul Parekh

Dr. Dayanand Nakate

Dr. Arun Bansal

Dr. Manish Sharma

Dr. Vinod Ratagiri

Dr. Praveen Khilnani

Dr. Kundan Mittal

South Zone North Zone

West Zone Central Zone East Zone

Office: Secretary, IAPICC, R No 3112, Level 3-A,

ii Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020

Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020 iii

Critical Thinking-PICU Quiz

iv Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020

Hypocalcemia and Vitamin D3 deficiency in critically ill

54 Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020

The role of Vitamin D in asthma management: Myth or

56 Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020

Risk factors for bronchiolitis ‑ Can we really predict?

© 2020 Journal of Pediatric Critical Care | Published by Wolters Kluwer - Medknow 57

3. Florin TA, Plint AC, Zorc JJ. Viral bronchiolitis. Lancet

58 Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020

Microalbuminuria as a sensitive predictor of early

© 2020 Journal of Pediatric Critical Care | Published by Wolters Kluwer - Medknow 59

sickle cell disease. Kidney Int 2000;57:1‑8.

How to cite this article: Benakatti G. Microalbuminuria as a sensitive

60 Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020

Calcium, phosphate, and Vitamin D abnormalities in

INTRODUCTION hypocalcemia, e.g., hypoalbuminemia, renal failure, Vitamin

© 2020 Journal of Pediatric Critical Care | Published by Wolters Kluwer - Medknow 61

This prospective, cross‑sectional study was conducted RESULTS

Table 1: Prevalence of metabolic abnormalities in the study population

was significantly lower (P = 0.006). They were more

We did not find any significant association of abnormal DISCUSSION

Table 3: Association of Vitamin D levels with outcome and calcium/phosphate levels

Table 4: Association of Vitamin D deficiency with biochemical abnormalities and outcome

Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020 65

66 Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020

CONCLUSION Effect of high‑dose Vitamin D3 on hospital length of stay in critically

Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020 67

68 Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020

Correlation of severity of asthma with serum Vitamin D3

Keywords: Asthma, magnesium, Vitamin D3

© 2020 Journal of Pediatric Critical Care | Published by Wolters Kluwer - Medknow 69

Table 1: Classifying asthma severity in children 5-11 years of age[8]

respectively.[3,4] Vitamin D3 has been shown to have a Reference range:[9]

Table 2: Severity of asthma according to gender

Table 3: Correlation between the severity of asthma and Vitamin D3 levels

Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020 71

Table 4: Distribution of patients according to their serum Conflicts of interest

72 Journal of Pediatric Critical Care | Volume 7 | Issue 2 | March-April 2020

Diagnostic accuracy of microalbuminuria among sickle cell

INTRODUCTION people of African descent as well as individuals from the