Dengue GCP Guidelines For Pregnancy 2021
Dengue GCP Guidelines For Pregnancy 2021
Dengue GCP Guidelines For Pregnancy 2021
Adapted and modified from Guidelines for Clinical Management of Dengue Infection in
Pregnancy - Ministry of Health – Sri Lanka
DENGUE 2021
GCP GUIDELINES
1st Edi on
Edited By:
Somia Iqtadar, MBBS, FCPS, FRCP (London)
Associate Professor of Medicine
King Edward Medical University, Lahore Pakistan
Chairperson Dengue Expert Advisory Group, Punjab
Muhammad Ali Khan, MBBS, DCH, MRCP (UK)
Professor of Pediatrics, Rahbar Medical & Dental College
Secretary Dengue Expert Advisory Group, Punjab
DEAG Secretariat
Services Institute of Medical Sciences, Jail Road,
Lahore, Tel: +92 (042) 99205404, Website: www.deag.punjab.gov.pk
Email: [email protected]
DENGUE GCP GUIDELINES FOR PREGNANCY 2021
Foreword
Dengue epidemics have become a serious concern with devasta ng health, social and economic
consequences in most tropical and sub-tropical regions globally. Many countries are repor ng
dengue outbreaks among adolescents and adults, and Pakistan is no excep on. In 2011, Lahore the
Capital City of the Punjab Province reported its first major outbreak of dengue which mostly
affected adults. Early diagnosis and clinical management of dengue in adults is more challenging
and requires standardized approaches to prevent disease complica ons and unwarranted
consequences.
World Health Organiza on (WHO) is aiming to reduce preventable dengue deaths to 'zero' in their
Global Strategy for Dengue Preven on and Control, 2021 - 2030. Increasing number of pregnant
women infected with dengue virus can have poor outcome without early iden fica on of clinical
disease and proper medical care. In fact, dengue haemorrhagic fever (DHF), the more severe form
of dengue illness, will become a leading cause of maternal deaths in endemic countries and
regions. The out-pa ent and in-ward departments of the hospitals in Punjab are seeing pregnant
women with dengue. As such, the recent trends on morbidity and mortality of dengue has caught
the a en on of the Health Services of the Punjab Province. This new guidelines on management of
clinical dengue in pregnant women developed by the Dengue Expert Advisory Group (DEAG),
Punjab Province is expected to further improve the exis ng knowledge and bridge any gaps on this
evolving subject. With the latest concepts highlighted this new guideline will help in strengthening
case management and ul mately reduce the number of severe cases and prevent any deaths due
to dengue associated with pregnancy.
We are extremely happy and humbled to provide guidance to the development of this document
based on the Na onal Guidelines on Clinical Management of Dengue Infec on in Pregnancy,
Ministry of Health Sri Lanka, 2019. Wish to congratulate all those who have ac vely contributed to
this important task. Special men on is necessary for Dr. Somia Iqtadar, Chairperson DEAG for her
un ring dedica on in improving case management of dengue. We sincerely hope that these
guidelines will be prac ced by all clinicians and will help in ensuring safety of mothers affected with
dengue and the safe delivery of healthy babies.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
Objec ves
To provide evidence based guidance in the management of pregnant pa ents with dengue
infec on.
SPECIFIC OBJECTIVES
Ÿ To improve recogni on and diagnosis of dengue fever in pregnancy and provide appropriate
advice for the care to these pa ents.
Ÿ To iden fy severe dengue infec on where it becomes mandatory to provide focused close
monitoring and prompt appropriate management.
Ÿ To provide guidance on appropriate and mely fluid management and the use of blood and
blood products.
Acknowledgement
We have all benefited from clinical wisdom and commitment of our associate authors. Many
students and physicians also have contributed useful sugges on to this manuscript. We con nue
to welcome comments and recommenda ons for future edi on in wri ng or via electronic mail.
We are also thankful to Dr. Muhammad Shahzad Hafeez, (Assistant Secretary DEAG) for his support
and Mr. Sheharyar Khalid (Senior Program Manager, PITB) for contribu ng in designing of this
document.
Secretarial Staff
The authors are indebted to the Mr. Muhammad Adil Bin Ali for providing secretarial assistance in
prepara on of this manuscript.
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PREFACE
Disclosure Statement
None of the primary authors holds shares in pharmaceu cal firms or acts as consultants to such firms.
Sources of Funding
The development of the Dengue GCP guidelines for pregnancy 2021 was supported financially in its
en rety by the Government of the Punjab Pakistan and was developed without any involvement of
the pharmaceu cal industry.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
Guidelines Development
Primary Authors
Dr. Somia Iqtadar
Associate Professor, King Edward Medical Univrsity, Lahore
Prof. Mohammad Ali Khan
Professor of Pediatrics Medicine, Rahbar Medical and Dental College
Contribu ng Authors
Prof. Rubina Sohail
Professor of Gyneocology/Obstetrics. Services Ins tute of Medical Sciences (SIMS), Lahore.
Prof. Tayyaba Wasim
Professor of Gyneocology/Obstetrics. Services Ins tute of Medical Sciences (SIMS), Lahore.
Prof. Zohra Khanum
Professor of Gyneocology/Obstetrics. Fa ma Jinnah Medical University, Lahore.
Prof. Farhat Naz
Professor of Gyneocology/Obstetrics. Allama Iqbal Medical College, Lahore.
Prof. Shamila Ijaz Munir
Professor of Gyneocology/Obstetrics. Fa ma Jinnah Medical University, Lahore.
Associate Authors:
Dr. Muhammad Faheem Afzal
Associate Prof. of Pediatrics Medicine, King Edward Medical University, Lahore.
Prof. Jodat Saleem
Prof. of Anesthesia, Post Graduate Medical Ins tute/LGH, Lahore.
Dr. Kiren Khurshid Malik
Associate Professor Gyneocology/Obstetrics. Services Ins tute of Medical Sciences (SIMS), Lahore.
Dr. Natasha Bushra
Assistant Professor of Gyneocology/Obstetrics. Services Ins tute of Medical Sciences (SIMS), Lahore.
Dr. Sofia Iqbal
Associate Professor of Gyneocology/Obstetrics. Fa ma Jinnah Medical University, Lahore.
Dr. Amna Wasif
Assistant Professor of Gyneocology/Obstetrics. Fa ma Jinnah Medical University, Lahore.
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Preface iv
Guidelines Development v
1. Introduc on 1
1.1 Clinical Manifesta on 1
1.2 Gesta on and Dengue 2
2. Natural Course Of Dengue Illness
3
2.1 Clinical Diagnosis of Dengue Illness 4
2.2 Dengue Fever 5
2.2.1 Clinical and Laboratory Findings
2.3 Dengue Haemorrhagic Fever (DHF) 6
2.3.1 Natural Course of DHF 7
2.3.2 Cri cal Phase in DHF 7
2.3.3 Warning Signs of Plasma Leakage in DHF 7
2.3.4 Features of Fluid Leakage 8
2.3.5 Ultrasound Features of Plasma Leakage in DHF 9
2.4 Dengue Shock Syndrome (DSS) 9
2.5 Convalescent Phase 9
3. Physiological Changes in Pregnancy 10
3.1 Cradiovascular Changes 10
3.1.1 Heart Rate 10
3.1.2 Blood Pressure 10
3.1.3 Systemic Vascular Resistance 11
3.1.4 Pulmonary Vascular Resistance 11
3.1.5 Plasma And Blood Volume 12
3.2 Haematological Changes In Pregnancy 12
3.3 Biochemical Changes In Pregnancy 14
3.4 Respiratory Changes In Pregrancy 14
3.5 Renal Changes In Pregnancy 15
4. Dengue heamarrrhagic Fever and Dengue Shock Syndrome (DSS) in pregnancy 16
4.1 Features of Dengue shock syndrome (DSS) with pregnancy 16
4.1.1 Cri cal Phase 16
4.1.2 Warning Signs 16
4.1.3 Diagnos c signs of Dengue Shock Syndrome 17
4.1.4 Differen al Diagnosis 20
4.1.5 Special Cau ons in Dengue Shock Syndrome with pregnancy 21
4.1.6 Complica ons of Fetomaternal Unit 22
4.2 Haemodynamic Changes in Dengue Shock Syndrome 23
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1. Introduc on
Dr. Somia Iqtadar
There has been a lot of concern related to dengue infec on in pregnant women in recent years due
to an increase in number of infec ons world wide .Pregnant women with dengue need early
iden fica on and their clinical management requires a mul -disciplinary approach. Timely and
precise interven ons in dengue infected pregnant women are needed for op mal outcome. Early
detec on and access to proper medical care in this specific group can reduce complica ons and
mortality.
Dengue fever (DF) is generally an acute febrile illness with severe headache, retro orbital pain,
myalgia, arthralgia and rashes. It is characterized by leucopenia and thrombocytopenia. Although
DF is usually benign, it could be incapacita ng with severe headache, retro orbital pain, muscle,
joint and bone pain, par cularly in adults. Occasionally DF pa ents have unusual hemorrhage such
as epistaxis, gastrointes nal bleeding and menorrhagia or occult bleeding.
Dengue hemorrhagic fever (DHF) is associated with repeated dengue infec on (secondary
infec on) with a different virus serotype.Unlike in DF where usually pa ents will have a brief febrile
phase followed by convalescent phase, in DHF, pa ents will have intermediate cri cal phase where
plasma leaks out of vessels into inters al and serosal spaces. This leads to decreased intravascular
volume and has a tendency to develop hypovolemic shock (dengue shock syndrome). Preceding
warning signs such as persistent vomi ng, severe abdominal pain, lethargy or restlessness, or
irritability and oliguria are important for early detec on of impending shock and warrant
interven on to prevent shock. Bleeding is more frequently seen in DHF than DF.
More recently, there have been reports of DF and DHF with unusual or atypical manifesta ons.
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These include isolated organ involvement such as neurological, severe hepa c, renal and other
organs. These could be explained as complica ons of profound and prolonged shock or associated
with underlying co-infec ons or co-morbidi es. Although a rare clinical en ty, such manifesta ons
are now categorized as Expanded Dengue Syndrome (EDS).
Ÿ In pregnancy with Dengue there is more likelihood of early overt or occult bleeding specially in
DHF. Trauma c procedures during delivery, such as instrumenta on or surgery will further
increase the risk of bleeding. Labour during dengue illness can be associated with worse
maternal outcomes as a result of massive bleeding due to surgical interven ons such as
caesarean sec on and opera ve vaginal delivery. Both mother and the newborn with dengue
infec on, if progress to DSS undetected, may be at an increased risk of severe hemorrhage due
to coagulopathy.
Ÿ Delayed or misdiagnosed DHF/DSS in the early stage can lead to complica on and may even
cause death. Common causes of death in pregnant women with dengue can be prolonged shock
with mul -organ failure, massive bleeding, fluid overload or due to a combina on of the above
condi ons.
Ÿ Ver cal transmission among women with dengue during the late pregnancy period is a well
established fact. All babies born to such mothers should be closely observed during perinatal
period.
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During the ini al few days termed as febrile phase both DF and DHF are clinically similar. While DF
pa ents progress to convalescent phase as temperature se les, DHF pa ents develop the Cri cal
Phase due to increase vascular permeability leading to plasma leakage. Hence, the hallmark of DHF
is plasma leakage which differen ates it from DF.
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• Acute onset of high grade fever (las ng 2-10 days) with headache ,retro orbital pain,
myalgia, arthralgia, rash, abdominal pain or bleeding manifesta on. Some pa ents may
have anorexia,diarrhea, flu like illness and conjunc val infec on.
• Rash looks like flushed skin on day 1 to 2, which may mimic as pregnancy rash.
• Physical examina on may reveal no focus of infec on except facial and skin flushing and
posi ve tourniquet test.
• All suspected pa ents should be subjected to Complete blood count(CBC) which in dengue
infec on typically shows leucopenia and thrombocytopenia.
• While NS1 An gen/IgM An body tests will provide an ae ological diagnosis, a nega ve
result should not exclude dengue if high clinical suspicion is there.
Dengue viraemia in a pa ent is short, typically occurring a day or two before the onset of fever and
lasts for up to four to seven days of illness. During this period the dengue virus, its nucleic acid and
circula ng viral an gen can be detected. Viral an gen detec on (NS1) has become the most
common early diagnos c tool to confirm dengue infec on.
2.2.1.b. NS1 An gen and IgM/IgG An bodies – results depend on the tested day of fever; NS1
an gen is usually diagnos c on first 3-4 days. An -dengue IgM an body is usually detectable by
day 5 of the illness or later. In most pa ents IgM may persist up to 60 days. In primary infec on IgG is
usually detectable few days a er IgM an bodies and in secondary infec on IgG will become
posi ve early. Therefore, IgG might be useful to differen ate primary and secondary dengue
infec ons. If IgG is posi ve by day 3 it would indicate a secondary infec on and may have some use
in predic ng DHF.If pa ent is clinically sugges ve of dengue, even if NS1 an gen is nega ve,
consider dengue as a possibility and manage accordingly.
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RT-PCR remains the gold standard for confirma on. The advantage of this test is its high sensi vity
and specificity in acute sample and iden fica on of serotypes. It is, however, an expensive
technology that requires sophis cated instruments and skilled professionals.
Complete Blood Count (CBC) -
Fever/history of fever and other clinical features with leukopenia (WBC <4,000 cells/μl), is strongly
sugges ve of dengue in endemic areas.
However, in pregnancy, leukopenia may not be a feature (o en WBC could be normal or high)
and serial CBC may only show a drop in the total WBC count with a significant reversal of
lymphocyte to neutrophil ra o with atypical cells in the blood picture.
• Progressive decrease in WBC count is an early indica on of dengue.
• Thrombocytopenia (<100x10⁹/L) or decreasing trend
• Hematocrit (HCT) could be normal or high
Presence of fever with at least 2 signs and symptoms men oned above are sufficient to suspect
dengue illness in pregnancy. Presence of leucopenia and thrombocytopenia in suspected cases
make the diagnosis of probable infec on.All probable dengue cases must be admi ed to
hospital and inves gated via confirmatory tests NS1 an gen ,PCR or An bodies depending upon
the day of illness.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
Dengue fever with haemorrhagic manifesta ons must be differen ated from dengue
haemorrhagic fever heralded by plasma leakage.
In DF –no plasma leakage
In DHF –plasma leakage is seen
Se ling of fever is not a sign of recovery, as the pa ent may leak when fever se les.
Plasma leakage in DHF is selec ve, transient and self-limi ng, usually las ng 24-48 hours.
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In cri cal phase of DHF it is not recommended to rely exclusively on USG for diagnosis of leakage.
Other parameters such as se ling of fever, vital signs, platelet count, gradual rise in HCT and
reduced urine output are important to diagnose the onset of leaking . However, demonstra on of
fluid in the peritoneal cavity and pleural space on repeated ultrasound scan confirms that the
pa ent has developed plasma leakage and is in cri cal phase.
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2.3.5 Ultrasound Features of Plasma Leakage in DHF
• Bed side ultrasound scan of the abdomen and the chest in supine posi on, with no
prepara on, can iden fy free fluid in pleural space or abdomen.
• Gall bladder wall oedema with a thin rim of fluid around it, is the earliest sonographic
finding in plasma leakage.
• Thin rim of fluid in hepato renal recess, indicates approximately six hours has elapsed since
beginning of plasma leakage.
• Fluid in the peritoneal cavity, among bowel loops and in the pelvis, indicates more than six
hours have elapsed since beginning of plasma leakage.
• Fluid in the pleural space, is commonly seen on the right side and indicates more than six
hours have elapsed since beginning of plasma leakage.
• Fluid in the perirenal space, is commonly seen on the right side. This indicates more than six
hours have elapsed since beginning of plasma leakage.
• In a pa ent where bilateral pleaural effusions and ascites is seen; implies that the pa ent is
in the later part of the cri cal phase when major por on of leaking (probably >50% of
leaking) is over.
Fluid therapy for such pa ents should be carefully guided (vital sings and HCT) as increased rates of
fluid can lead to fluid overload.
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Pregnancy results in significant anatomical physiological and bio chemical changes in all organ
systems during antepartum,intrapartum and postpartum period. Understanding these changes
and resul ng clinical implica ons is crucial in the management of dengue fever in a pregnant
pa ent.
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• There is a rise in WBC count during normal pregnancy ranging from 9000-15,000 cell/10¹²
• The platelet count tends to fall progressively during normal pregnancy although it usually
remains within normal limits.
• In a propor on of women (5-10%) the platelet count will reach levels of 100 to 150 x10⁹ /L
by term in the absence of any pathological process however <100x10⁹/L are rarely
encountered.
• Even in gesta onal thrombocytopenia, whose incidence is 6-10%, platelet count seldom fall
below 80x10⁹/L.
• In a normal pregnancy there is a marked increase in some coagula on factors like thrombin,
fibrinogen, factor VII,VIII,IX,X,XII resul ng in increased risk for thromboembolic
complica ons.
• In pregnant pa ent with fever and low platelets count it is important to rule out
dengue.
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• In pregnancy these symptoms can be very confusing as pregnant women especially in third
trimester can be uncomfortable due to gravid uterus pressure on pelvic bones, joints and
major vessels specially in supine posi on.
• Pregnant women can be lethargic due to anaemia which has a high prevalence in Pakistan
(36-52%).
4.1.2 c. Altered Conscious Level
• Altered conscious level may be observed in pa ents with Dengue shock syndrome.
• Altered conscious level in pregnancy can be seen with some pregnancy specific condi ons
as severe pre eclampsia, eclampsia, cerebral thrombosis. Raised Blood Pressure,
protenuria and CT scan brain can help in the diagnosis.
4.1.2. d.Vaginal bleeding
• This is one of the warning signs in DHF and adds to morbidity due to addi onal hypovolemia
leading to DSS.
• In pregnant women bleeding can be due to other causes as placenta previa, placental
abrup on, local causes and systemic causes as gesta onal thrombocytopenia &
hepa s E in pregnancy. A er delivery bleeding can be due to post partum hemorrhage
(PPH) as a result of uterine atony, genital tract injury and retained products of
concep on.
• All these require proper obstetrics history and examina on along with laboratory
inves ga ons.Complete Blood Count including Platelet count, Liver Func on Tests,
Hepa s serology and obstetrical scan is mandatory in such cases.
4.1.2. e.Tender Hepatomegaly
• In non pregnant women presence of enlarged tender liver > 2 cm below costal margin is
considered a warning sign.
• However, It is very difficult to palpate liver in pregnant women especially in third trimester
due to gravid uterus and can easily be missed as an early warning sign.
• As a result of plasma leakage and vasoconstric on, cardiovascular system is affected the
most both in pregnant and non pregnant pa ents. However due to physiological changes in
pregnancy most of the signs described below are difficult to iden fy or appear late in
pregnant pa ents with Dengue Shock Syndrome and ul mately lead to delay in diagnosis
and high morbidity.
• Tachycardia, prolonged capillary refill me, narrow pulse pressure, and low volume of
pulses may be present.
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• Moreover gravid uterus and upward pushing of diaphragm already causes dyspnoea in
pregnant woman and this may mask tachypnea in early stages. Compensatory alkalosis in
pregnancy (PH 7.40-7.45) can lead to delay in detec on of acidosis in pregnant woman with
HDF/DSS. These pose a diagnos c challenge in pregnancy for DSS.
4.1.3.c.Renal System
• Reduc on in renal circula on (GFR) due to vasoconstric on in DSS manifests itself in the
form of reduced urine produc on.
• In normal pregnancy GFR rises by 50%. In pregnancy with dengue shock syndrome
appearance of reduced GFR is delayed making detec on of renal compromise difficult.
• In decompensated shock ul mately severe oliguria (less than 15 ml/hr) or anuria ensues.
• Late features are similar in pregnant women. Though oliguria in pregnancy can be seen in
other condi ons specific to pregnancy as renal failure due to abrup on, severe
hypertension and massive hemorrhage.
Plasma leakage is typical in pleural and peritoneal cavi es both in pregnant and non
pregnant pa ents in DHF. It is severe in pregnancy due to pre exis ng reduced onco c
pressure and increased vascular permeability.
In pregnancy gravid uterus makes it difficult to assess leakage in peritoneal cavity so early
diagnosis of third space fluid loss may be missed. Pregnant women are predisposed to
pulmonary odema due to increased respiratory blood flow and reduced onco c pressure
confounded with lesser space in thoracic cavity, leading to severe respiratory distress.
Hence lesser volume of plasma leakage in pleural cavity can cause more respiratory distress
and ARDS in pregnant woman with DSS.
Ÿ In pregnancy Ultrasound chest and abdomen is used for detec on of fluid and instead of
relying on clinical examina on only, physician must resort to USG early in the disease
course.
• Haematocrit (HCT): Rising HCT 20% or more is taken as an important indicator for detec on
and monitoring of DHF.
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In pregnant woman HCT is already low due to plasma volume expansion by 30-50% (75-82
ml/kg body weight - normal range) and physiological anaemia.HCT is taken as 32-34%
normal in pregnancy as compared to 35-36% in other pa ents. Rise of HCT can be a late sign
in pregnancy with DHF and leads to late detec on and difficulty in monitoring of the
disease.
So logically in second and third trimester of pregnancy with DHF, HCT rise less than 20%
may be considered significant and serial monitoring from baseline is more helpful in a
pregnant women with DHF.
• Serum Albumin: One of the plasma leakage indicator In non pregnant women is serum
albumin measurement and cut off value is <3.5 gm%,
In pregnant women during third trimester there is a fall in serum albumin upto 1gm/dl in
and normal range falls upto 2.5gm%. In pregnancy albumin values has to be interpreted
with cau on and fall of 0.5g/dl from baseline can be taken as an indicator.
• Serum Cholesterol: In DHF serum cholesterol cut off value less than 100 mg/dL is taken as
an indicator. In Pregnancy, there is a natural rise in serum cholesterol in second trimester
and rise reaches its peak around 40% in third trimester and levels return to normal four
weeks postpartum. Hence cut off value must be interpreted with cau on in pregnant
woman with DHF. If normal value of pregnant woman is already known then drop of 20mg
/dl can be taken as significant otherwise this is not good indicator of plasma leakage in
pregnancy.
4.1.3.e.Thrombocytopenia
• Rapid decrease in platelet count is taken as a warning sign of Dengue and progression to
DHF requiring strict observa on and treatment.
• In pregnancy there is a mild fall in platelet count physiologically but less than 100,000/mm³
is rarely encountered. Even in gesta onal thrombocytopenia –a condi on specific to
pregnancy seldom count falls below 80,000/mm3. There can be marked lowering of
platelet count in pregnant woman with DHF as compared to non pregnant.
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Table no.2 Differen al Diagnosis in of DHF and DSS with pregnancy
Differen al
Clinical features Differen al diagnosis diagnosis specific Differen a ng points
to pregnancy
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• Haemoglobinopathies: These pa ents are at risk of bleeding and will require blood
transfusion. Cau on should accompany overhydra on and alkaliniza on therapy, which
can cause fluid overload and hypocalcemia.
• Fetal anomalies are not associated with dengue infec on, however some complica ons of
fetomateual unit may be encountered in pragnant pa ents with dengue.
Maternal Fetal
Complica ons Preterm birth (10-55%)
Preterm birth (41%) Ver cal transmission (5.6%-12%)
Hypertension (12%) Fetal demise (14%)
Haemorrhage (10%) Meconium aspira on
Abrup on (2%) Oligohydroamnios
Post Partum Hemorrhage
Key points
• Features of dengue shock syndrome in pregnancy can mimic other causes of shock in
pregnancy as HELLP syndrome & embolism
• Clinical and laboratory parameters need special interpreta on according to
pregnancy changes
• Bleeding at the me of child birth can further aggravate the shock so prompt
management is necessary
• Physicians should have clear concept of physiological changes of pregnancy to
understand the pathophysiology of Dengue Shock Syndrome (DSS).
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Main features
• Systolic BP <80mmHg and/or reduc on in SystolicBP by >20mmHg
• Mean arterial BP <70 mmHg or un recordable BP at le lateral posi on
Associated features
(All these may not be present at a given me)
• Change of mental state e.g.: restless, comba ve or lethargy
• Prolonged CRFT (capillary refill me) with mo led skin, cold-clammy extremi es
• Severe tachycardia with weak or absent peripheral pulses
• Oliguria or anuria
• Tachypnea with metabolic acidosis.
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Key points
• Vital signs and urine output varies in different phases of DSS and in pregnant women
many features are masked by physiological changes.
• In pregnant females with hypertension or on an hypertensive medica on may cause
difficulty in assessment of Blood Pressure.
• Pulse pressure is one of the important parameters and in pregnancy is masked by
lower diastolic BP due to decreased vascular resistance
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o Restlessness
o Tender hepatomegaly (Liver >2 cm enlarged)
o Capillary Refill Time>2sec.
o Decreased urine output.
o Mucosal Bleed : epistaxis, gum bleed pe chae.
o Rise in HCT (20% of baseline)( If baseline is not known consider 36 as baseline).
If any of these signs develop, label the pa ent in cri cal phase and shi to High Dependency Unit
(HDU).
• Monitor
o Vitals( BP /Pulse/Pulse pressure, Capillary Refill) hourly
o Ultrasound abdomen for any fluid leak and obstetric ultrasound to document fetal
well being. Ultrasound can also be used to measure size of IVC and its collapsibility,
sign of hypovolemic shock or fluid overload.
o Catheterize to know precise UOP hourly ( Aim 0.5ml/kg/hour).
• Treatment
o Start fluid therapy according to algorithm (Page 30).
o Bolus of 5-10ml/kg/hour X 2 hours given followed by 3-5ml/kg/hr as a
maintenance.
o This is monitored by UOP and Pulse pressure
o Avoid induc on of labour/ planned surgery in this phase.
o Monitoring of clinical findings (at least twice a day), vital signs (at least every 1-2
hours) HCT (at least every 4-6 hours), and urine output (at least every 8 hours)
should be done and documented on chart.
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• In majority of cases, mothers have uncomplicated antenatal period but there is risk of post
partum hemorrhage with dengue fever over general popula on.
• If the pa ent is in first or second trimester and <37 weeks of gesta on, con nue the
pregnancy with close monitoring in febrile phase.
Important Points:
• Avoid NSAIDs for fever. Paracetamol upto 4 gm /day can be given
• Tocoly cs may be considered to postpone labour during cri cal phase of dengue illness.
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• A high index of suspicion, early admission, close monitoring, mely interven on and
cri cal considera on of physiological changes of pregnancy when interpre ng clinical
situa on, can help us to achieve the successful outcome in pregnancy.
• Pregnant women with dengue fever should be considered for admission early
because of its unpredictable course.
• Maintaining normothermia and adequate hydra on should be the goal.
• Sharp decline in platelet counts should be taken as a marker of severity of the disease.
• Oligohydramnios is an ominous sign when seen concomitantly with dengue infec on
because the high fetal mortality of associated with it. The exact cause of
oligohydramnios is not known but dehydra on associated with dengue fever may be
contributory.
• Hydra on should be maintained by encouraging oral intake of oral rehydra on
solu on (ORS), fruit juice, and other fluids containing electrolytes and glucose for
replacing losses from fever and associated vomi ng.
• The lack of understanding of the exact pathophysiology of dengue has led to a paucity
of sufficient evidence-based management protocols aimed at specific
pathophysiological phenomena of the illness in pregnancy. Many pa ents, due to lack
of awareness, present late to hospital, some mes in shock; their management is
difficult, with a poor outcome.
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• If possible elec ve delivery should be postponed ll pa ent is out of cri cal phase of
disease.
• Transfusion of platelet concentrates should be ini ated during or at delivery but not too far
aheadof delivery, as the platelet count is sustained by platelet transfusion for only a few
hours during the cri cal phase.
• Fresh whole blood/fresh packed red cells transfusion should be administered as soon as
possible if significant bleeding occurs.
• Do not wait for blood loss to exceed 500ml before replacement, as in postpartum
hemorrhage. Do not wait for the hematocrit to decrease to low levels.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
• Strict monitoring for BP, Pulse, pulse pressure and urine output.
• If delivery occur in less than seven days from appearance of symptoms of dengue fever,
then risk of ver cal transmission is high.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
Ÿ Concealed or Occult, which can occur into gsatrointes nal tract, muscles, abdominal cavity,
thoracic cavity and brain.
Ÿ In pregnancy Antepartum hemorrhage and Postpartum hemorrhage can be a cuase of maternal
mortality. Bleeding can be occult or revealed vaginally (especially in placental abrup on).
Ÿ If the pregnant pa ent is suffering from bleeding due to a pregnancy complica on dengue
illness can add to morbidity and vice versa.
Ÿ Delivery whether vaginal or abdominal can result in life threatening hemorrhage and should be
avoided in cri cal phase.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
Ÿ Hypotensive shock and renal or liver failure and/or severe and persistent metabolic acidosis
Ÿ Drop of HCT >10 points following a bolus of Dextran-40 (administered 10 ml/kg/ hr)
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
Ÿ 500ml: 50cm diameter floor spill Excessive vaginal bleeding—soaking a pad in an hour.
Ÿ Immediately a er the baby's delivery (end of the second stage of labour), the cervix and vagina
should be thoroughly inspected for lacera ons and surgical repair should be performed early.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
Ÿ If the pa ent had delivery either Normal Vaginal Delivery or Lower Segment Caesarean
Sec on( LSCS) it is advisable to replace the es mated lost blood volume immediately.
Ÿ It is essen al to monitor haematocrit and haemodynamic parameters frequently in such
pa ents as they are likely to have con nuous bleeding and may need further blood
transfusions.
Ÿ A drop in haematocrit of >10 points a er Dextran- 40 10 ml/kg (or 500 ml) bolus
Ÿ Dengue shock not responding to adequate fluid therapy i.e. 40-60 ml/kg (Refractory shock)
Ÿ Anaemia in pregnancy – Pregnant women with low haemoglobin (Hb ≤8g/dl) e.g. Iron
Deficiency, Thalassemia Minor, with dengue illness, blood transfusion should be considered
early.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
7.7.1.c Method
Ÿ Transfuse 5 ml/kg of fresh-packed red cells or 10 ml/kg of fresh whole blood at an appropriate
rate and observe the clinical response.
Ÿ Repeat blood transfusion if there is further blood loss or HCT fails to rise appropriately a er
blood transfusion.
Ÿ P transfusions.
Ÿ Prothrombin concentrate complex (containing factors II, VII, IX, X) may have a place in bleeding
with liver failure.
Ÿ Key points
Ÿ High index of suspicion of bleeding should be there if vitals deteriorate inspite of
resuscitative measures in DSS
Ÿ Physician must be aware of indications of blood transfusion
Ÿ In pregnant women delivery can worsen the dengue shock due to hemorrhage so
preventive measures must be taken
Ÿ Clear guidelines of platelet and other product transfusion must be followed to avoid fluid
overload
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
There is insufficient evidence to support the use of intravenous immunoglobulin and Steroids.
Likewise, there appears to be no role for the use of Vitamin K and tranexamic acid in dengue fever.
In pregnancy there is definite role of tranexamic acid in postpartum hemorrhage, hence a pregnant
pa ent with dengue illness suffers from PPH, along with other measures tranexamic acid can be
used.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
Ÿ Monitoring pain. Note pa ent's complaint of pain in specific areas, whether pain is increasing,
diffused, or localized.
Ÿ Vascular access. Maintain patency of vascular access for fluid administra on or blood
replacement as indicated.
Ÿ Medica on regimen. There must be a periodic review of the medica on regimen to iden fy
medica ons that might exacerbate bleeding problems.
Ÿ Fluid replacement. Establish 24-hour fluid replacement needs.
Ÿ Managing nose bleeds. Elevate posi on of the pa ent and apply ice bag to the bridge of the
nose and to the forehead.
Ÿ Trendelenburg Posi on. Place the pa ent in Trendelenburg posi on to restore blood volume to
the head.
If WBC count is normal/Lower side suspect DF and repeat CBC a er 24 hours and compare further
fall in platelets/ rise in PCV (>10% rise is considered as significant).
Monitor:
Ÿ 4 hourly Temperature char ng, pulse, BP.
Ÿ Intake Output record…Ensure urine output at least 4 hourly. (minimum 100 cc every 4 hours)
Ÿ Oral Intake encouraged. ORS, juice all are encouraged apart from rou ne food
Ÿ Aim of at least 2.5 liters of fluid intake in 24hrs.
Ÿ If nausea/vomi ng of pregnancy restrict oral intake give IV fluid (NS) 100 ml/ hour
Ÿ Paracetamol 500-1000mg 6 hourly. Warn the pa ent that fever may not se le with this dose but
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
Ÿ Timely fluid management with appearance of any warning symptom prac cally prevents
further complica on.
Ÿ Monitor Vitals (BP /Temp/Pulse pressure, Capillary Refill) hourly
Ÿ Carrfully trate fluid resuscita on (Normal saline) Bolus of 5-10ml/kg/hour x 2 hours given
followed by 3-5ml/kg/hour as a maintenance. This is monitored by urinary output and pulse
pressure.(DEAG, DHF Algorithms Page 30)
Ÿ Avoid induc on of labour/ planned surgery in this phase.
Ÿ Draw blood for CBC, HCT, grouping cross match, LFTs, Electrolytes, Blood sugar levels.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
Ÿ Delivery should take place in a hospital where blood/blood components with a team of skilled
obstetricians and a neonatologist available.
Ÿ There are increased chances of preterm labour and birth so tocoly c agents and measures to
postpone labor to a suitable me may be considered during the cri cal phase of dengue illness.
However there is currently a lack of evidence on this prac ce.
Ÿ Most cases of dengue fever during pregnancy had favorable outcomes for the mother and
neonates; therefore pregnancy can be con nued un l late term or full term with adequate fluid
therapy.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
Ÿ When outdoors, wear long-sleeved shirts and long pants tucked into socks. When indoors, use
air condi oning if available. Stay away from heavily populated residen al areas.
Ÿ Maintain good hygiene at home and environment.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
9. Dengue In Puerperium
Prof. Zohra Khanum, Prof. Muhammad Ali Khan, Dr. Somia Iqtadar
Introduc on:
Dengue has emerged one of the most important mosquito borne viral diseases of the humans.If
not managed mely and properly it can carry significant morbidity and mortality.Concern
regarding women who are pregnant or in postpartum period ge ng infected with Dengue virus
has been heightened in recent years due to an increase in adolescents and adult infec on.Pregnant
women with Dengue need early iden fica on. Clinical management requires a mul -disciplinary
approach and precise me related interven ons for op mal outcome.Early detec on and access to
medical care will reduce complica ons and mortality in puerperium.
Puerperium:
It is the period of adjustment a er pregnancy and delivery when anatomical and physiological
changes of pregnancy are reversed and the body returns to the normal non pregnant state.It is a
period of 6 weeks which commences following comple on of third stage of labour.
9.1 Physiological Changes during Puerperium
Ÿ Normally hemoglobin and hematocrit fluctuate moderately during the first few postpartum
days.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
may be suspected.
Ÿ Pulse: A er the ini al tachycardia associated with labour and delivery, a bradycardia o en
develops in the early puerperium.By the end of the first week the pulse rate will have returned
to normal.
Ÿ Temperature: A woman may show slight increase in temperature during the first 24 hours a er
birth.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
Symptoms:
Ÿ Sudden,high grade fever
Ÿ Severe headache
Ÿ Fa gue
Ÿ Abdominal Pain
Ÿ Toxemia of pregnancy
Ÿ Pre eclamsia
Following physiological changes in pregnancy may make the diagnosis and assessment of plasma
leakage challenging.
Ÿ Eleva on of HCT in dengue is masked by hemodilu on due to increase in plasma volume
rd
especially in 3 trimester and immediate postpartum period.Serial HCT measurements is crucial
for disease monitoring in pregnancy and puerperium.
Ÿ The detec on of third space fluid accumula on is difficult due to the presence of gravid uterus.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
Management:
Ÿ Reduc on of high grade fever by Paracetamol only.Avoid NSAIDS such as aspirin as they can
increase the risk of bleeding
Ÿ Promote oral feeding:So drink,milk,fruit juice,oral rehydra on solu on(ORS).
Ÿ Avoid IV fluid if there is no vomi ng and moderate/severe dehydra on.
Ÿ Empiric an bio c therapy
Ÿ Transfuse blood,preferably fresh packed red cells as indicated.
Ÿ H2-blockers or proton pump inhibitor may be given to alleviate gastro intes nal bleeding.
Ÿ Watch for warning signs. In case of any warning sign ask pa ent to come immediately in
emergency.
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
produced and transferred to the neonate, conferring a passive immunity. The maternal viremia
would therefore be transferred to the unprotected fetus resul ng in neonatal infec on ranging
from asymptoma c infec on to death.
10.9 Management
Difference in the management of dengue infec on in neonates and children is type of fluid. In
neonates, N/2 + 5% Dextrose is recommended. For rest of management, it is referred to algorithm.
(Page 30)
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DENGUE GCP GUIDELINES FOR PREGNANCY 2021
53
APPENDICES
APPENDIX 1a Dengue Fever Proforma after Admission
54
APPENDIX 1b Radiology Request Form
55
APPENDIX 2 Dengue Monitoring Charts
2a. DEAG DF Form -1 (4 days) Monitoring
56
2b. DEAG DF Form – 2 (To be lled 48 hours data)
57
58
APPENDIX 3a OPD Form
DEAG FORM - O
Revised, June 2019
Dengue Expert
Advisory Group
Filling of all fields is compulsory
Associated symptoms
Headache Rash
Retro orbital pain Bleeding manifestations (epistaxis, gum bleed,
Myalgia bloody stools, hematemesis, hemoptysis,
menorrhagia, hematuria)
Arthralgia/ severe backache/ bone pains Severe abdominal pain
Irritability in infants Decreased urinary output despite adequate fluid intake
Request CBC, HCT & Look for presence of any Warning Signs
DoF HCT WBC Platelet Any 2 or more Warning Signs (one or more)
No clinical improvement / worsening clinical parameters
Persistent vomiting
D3 1. WBC < 4000
Severe abdominal pain
Lethargy and or restlessness
+ OR Giddiness
D4 Pale cold clammy extremities
2. Platelet <100000
Bleeding: epistaxis, gum bleed, bloody stools,
or hematemesis, hemoptysis, menorrhagia, hematuria
D5 Pulse Pressure < 25mmHg
HCT < 30% or
3. > 55% Less / no urine output for 4 - 6 hours
__________________
Name, Signature and Date
PTO
59
60
APPENDIX 4a Reporting for Dengue Patients (Suspected & Probable)
61
APPENDIX 5
62
APPENDIX 6
63
APPENDIX 7
64
APPENDIX 8
Home Care Advice Leaflet for Dengue Pa ents
Front View
1. Bleeding
for example:
— Extensive red spots or patches on the skin
— Excessive bleeding from nose or gums
— Black tarry stools
— Heavy menstrua on / vaginal bleeding
2. Frequent vomi ng
3. Severe abdominal pain
4. Drowsiness or irritability
5. Pale, cold and clammy skin
6. Difficulty in breathing
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APPENDIX 9
Patient Information Brochure in Urdu
66
APPENDIX 10 Diagnostic Criteria – Non Epidemic Setting
67
68
APPENDIX 11 Diagnostic Criteria – Epidemic Setting
69
70
APPENDIX 12 Inpatient Form
71
72
APPENDIX 13 Reporting Form for Dengue Patients (Con rmed)
73
74
75
76
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List of Abbrevia ons (GCP Guidelines for Pregnancy)
APH Antepartum Haemorrhage
ALT Alanine Transaminase
AST Aspartate Aminotransferase
BP Blood Pressure
BU Blood Urea
CRT Capillary Refill Time
CTG Cardiotocography
CVC Central Venous Catheter
CBC Complete Blood Count
CRRT Continuous Renal Replacement Therapy
CS Caesarean Section
DBP Diastolic Blood Pressure
DF Dengue Fever
DIC Disseminated Intravascular Coagulation
DHF Dengue Hemorrhagic Fever
DSS Dengue Shock Syndrome
EDS Expanded Dengue Syndrome
FBC Full Blood Count
FFP Fresh Frozen Plasma
FRC Functional Residual Capacity
GCS Glasgow Coma Scale
GFR Glomerular Filtration Rate
CRFT Capillary Refill Time
GXM Group Cross Match
Hb Hemoglobin
HbA1C Hemoglobin A1c
HCT Hematocrit
HCO3 Bicarbonate
HELLP Hemolysis, Elevated Liver Enzymes, Low Platelets
HI Hemagglutination inhibition
HR Heart Rate
ICU Intensive Care Unit
IgG Immunoglobulin G
IgM I mmunoglobulin M
ITP Immune Thrombocytopenic Purpura
LFT Liver function Test
LSCS Lower Segment Caesarean Section
IUD Intrauterine Devices
MAP Mean arterial pressure
MDT Multi Disciplinary Team
NG Tube Naso - Gastric Tube
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List of Abbrevia ons (GCP Guidelines for Pregnancy)
NSAID Nonsteroidal Anti - inflammatory D rugs
NS1 Ag Non- structural Protein – 1A ntigen
ORS Oral Rehydration Solutions
PCR Polymerase chain reaction
PCO₂ Partial Pressure of Carbon Dioxide
PCV Packed- Cell Volume
PO ₂ Partial Pressure of Oxygen
ROTEM Rotational Thromboelastometry
PLT Platelet
PP Pulse pressure
PPH Post - Partum Hemorrhage
PR Pulse rate
RBS Random blood sugar
RR Respiratory rate
RPOC Retained Products of Conception
RT - PCR Reverse transcriptase Polymerase chain reaction
SBP Systolic blood pressure
SE Serum Electrolytes
SGOT Serum Glutamic - Oxaloacetic Transaminase
SGPT Serum Glutamic - Pyruvic Transaminase
SLE Systemic Lupus Erythematosus
TCO 2 Total CO 2
TTP Thrombotic Thrombocytopenic Purpura
UOP Urinary Output
USG Ultrasonography
UTI Urinary Tract Infection
WBC White Blood cell count
WHO World Health Organization
79