Miranda et al.

BMC Pediatrics (2024) 24:153 BMC Pediatrics

https://doi.org/10.1186/s12887-024-04639-9

RESEARCH Open Access

Risk factors of multidrug-resistant organisms

neonatal sepsis in Surabaya tertiary referral
hospital: a single-center study
Stefani Miranda1*, Aminuddin Harahap2, Dominicus Husada4 and Fara Nayo Faramarisa3

Abstract
Background Bacterial organisms causing neonatal sepsis have developed increased resistance to commonly used
antibiotics. Antimicrobial resistance is a major global health problem. The spread of Multidrug-Resistant Organisms
(MDROs) is associated with higher morbidity and mortality rates. This study aimed to determine the risk factors for
developing MDRO neonatal sepsis in the Neonatal Intensive Care Unit (NICU), dr. Ramelan Navy Central Hospital, in
2020–2022.
Methods A cross-sectional study was performed on 113 eligible neonates. Patients whose blood cultures
were positive for bacterial growth and diagnosed with sepsis were selected as the study sample. Univariate and
multivariate analysis with multiple logistic regression were performed to find the associated risk factors for developing
multidrug-resistant organism neonatal sepsis. A p-value of < 0.05 was considered significant.
Results Multidrug-resistant organisms were the predominant aetiology of neonatal sepsis (91/113, 80.5%). The
significant risk factors for developing MDRO neonatal sepsis were lower birth weight (OR: 1.607, 95% CI: 1.003 − 2.576,
p-value: 0.049), history of premature rupture of the membrane (ProM) ≥ 18 (OR: 3.333, 95% CI: 2.047 − 5.428,
p-value < 0.001), meconium-stained amniotic fluid (OR: 2.37, 95% CI: 1.512 − 3.717, p-value < 0.001), longer hospital
stays (OR: 5.067, 95% CI: 2.912 − 8.815, p-value < 0.001), lower Apgar scores (OR: 2.25, 95% CI: 1.442 − 3.512,
p-value < 0.001), and the use of respiratory support devices, such as invasive ventilation (OR: 2.687, 95% CI:
1.514 − 4.771, p-value < 0.001), and non-invasive ventilation (OR: 2, 95% CI: 1.097 − 3.645, p-value: 0.024).
Conclusions Our study determined various risk factors for multidrug-resistance organism neonatal sepsis and
underscored the need to improve infection control practices to reduce the existing burden of drug-resistant sepsis.
Low-birth-weight, a maternal history of premature rupture of the membrane lasting more than 18 hours, meconium-
stained amniotic fluid, longer hospital stays, a low Apgar score, and the use of ventilators were the risk factors for
developing drug-resistant neonatal sepsis.
Keywords MDRO, Neonatal sepsis, Newborn, Risk factors

2
*Correspondence: Department of Child Health, dr. Ramelan Navy Central Hospital, Jalan
Stefani Miranda Gadung No.1, Surabaya, East Java 60244, Indonesia
3
[email protected] Department of Clinical Microbiology, dr. Ramelan Navy Central Hospital,
1
Department of Child Health, Faculty of Medicine, Hang Tuah University/ Jalan Gadung No.1, Surabaya, East Java 60244, Indonesia
4
dr. Ramelan Navy Central Hospital, Jalan Gadung No. 1, Department of Child Health, Faculty of Medicine, Universitas Airlangga/
Surabaya, East Java 60244, Indonesia Dr. Soetomo Academic General Hospital, Jalan Prof. Dr. Moestopo 6-8,
Surabaya, East Java 60286, Indonesia

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Miranda et al. BMC Pediatrics (2024) 24:153 Page 2 of 8

Background the risk factors that lead to drug-resistant neonatal sep-

Neonatal sepsis is a clinical syndrome characterized by ticemia in order to develop management strategies. As
systemic signs and symptoms of infection and is accom- a result, the purpose of this study was to investigate the
panied by bacteremia within the first month of life [1]. risk factors for developing multidrug-resistant organisms
Neonatal sepsis necessitates intense treatment in the septicemia in neonates in our NICU. It is hoped that our
NICU due to respiratory distress and hemodynamic study will provide a comprehensive picture of the risk
instability [2]. Infants in the NICU are at high risk of factors for developing MDROs septicemia in neonates,
multidrug-resistant organisms’ infection due to their allowing its incidence to be reduced by avoiding modifi-
small gestational age, low body weight, poor resistance, able risk factors.
critical condition, high incidence of invasive procedures,
prolonged hospital stays (≥ 5 days), long-term antimi- Methods
crobial therapy, post-surgical operations, and decreased Study overview
compliance with infection control measures [3–6]. Sepsis This is a cross-sectional study that uses secondary data
caused by MDRO was associated with a higher mortality from dr. Ramelan Navy Central Hospital’s NICU and
rate in neonate population [7]. clinical microbiology department in Surabaya, Indone-
Neonatal sepsis is the third-most common cause of sia. This hospital is the highest tertiary naval hospital in
neonatal death, according to the World Health Orga- East Java. The NICU at this hospital has a total capacity
nization (WHO) [1]. A meta-analysis from 14 coun- of 18 beds and an annual capacity of 810 neonates. This
tries carried out by Fleischmann C. et al. (2021) found hospital has 12 paediatricians on staff, including one neo-
an incidence of 2824 neonatal sepsis cases per 100.000 natologist and one paediatric cardiologist. Infants who
live births. The mortality rate was 17.6% [8]. Bacterial presented with clinical signs and symptoms of sepsis had
organisms that cause neonatal sepsis have become more blood cultures taken. According to the Canadian Paediat-
resistant to commonly used antibiotics [9]. Multidrug- ric Society’s guideline [18], clinical manifestations of neo-
resistant organisms spread is associated with increased natal sepsis may be subtle and include an abnormal heart
costs as well as higher morbidity and mortality rates. rate, poor peripheral perfusion, temperature instabilities,
Antimicrobial resistance is a major global health issue. and signs of respiratory distress.
The WHO has defined the fight against MDRO spread as
a “critical” priority [10]. Population and samples
When pathogens enter the body of a newborn, they can Inclusion criteria
cause an infection. It can lead to sepsis if it is not pre- This study included sepsis neonates treated in dr.
vented because babies lack an immune system capable Ramelan Navy Central Hospital’s NICU, whose blood
of fighting infection [11]. Bacteria develop resistance to drawn for culture.
antimicrobial drugs through well-defined mechanisms
such as enzyme inactivation, changed target sites, efflux, Exclusion criteria
and altered membrane permeability. Antimicrobial drug This study excluded neonates whose blood culture results
resistance in hospitals was driven by hospital hygiene were negative and showed fungal growth.
failures, selective pressures produced by antibiotic over-
use, and mobile genetic elements carrying resistance Definitions
genes that are transmitted across particular bacterium Early-onset sepsis: blood culture–proven infection
species [12, 13]. Antimicrobial stewardship programs occurring in the newborn at < 7 days of age [19].
implementation in conjunction with proper empiri-
cal antibiotic regimens will reduce selective pressure on Late-onset sepsis: blood culture–proven infection occur-
resistant strains and their subsequent deleterious effects ring in the newborn after 7 days of age caused by a post-
in neonates [14]. NICUs should strive to develop effective natal acquisition (nosocomial or community sources)
antimicrobial stewardship through coordinated interven- [19].
tions with other teams such as microbiology, paediatric
infectious diseases, and pharmacists [14–16]. MDRO: organisms with acquired non-susceptibility to at
Multiple pathogens were identified by culture. Accord- least one agent in three or more antimicrobial categories
ing to the Global Antibiotic Research & Development [20].
Partnership (GARDP) neonatal study report (2016),
Klebsiella pneumoniae was the most common pathogen Neonate: a newborn or an infant within its first 28 days.
isolated and is usually associated with hospital-acquired
infections, which are increasingly resistant to existing Neonatal sepsis: a clinical syndrome of systemic illness
antibiotic treatments [17]. It is important to understand
Miranda et al. BMC Pediatrics (2024) 24:153 Page 3 of 8

accompanied by bacteremia occurring in the first month multiple logistic regression with the “enter” method to
of life [19]. determine associated risk factors. The study reported the
odds ratio (OR) and 95% confidence intervals (CIs). A
Sample size determination significance level of p < 0.05 was used. All analyses were
The sample size for this study was calculated manually performed using SPSS Version 29 (SPSS Inc., Chicago,
using a single proportion formula. The proportion of IL).
neonatal sepsis was derived from a study conducted in
Eastern Saudi Arabia, which had a proportion of 5.16% Results
[5]. With a margin of error of 5% and a confidence inter- Searching for medical records
val of 95%, this study’s final sample size was 76 neonates. This study explored 266 electronic medical records from
dr. Ramelan Navy Central Hospital’s NICU in Indonesia.
Sampling techniques The study’s final subjects consisted of 113 neonates who
Total sampling was used as the sampling technique, and had sepsis diagnosed by each attending physician and
the samples were taken sequentially. We included all neo- confirmed by a blood culture examination. From the 212
nates admitted to our NICU between January 1, 2020 and total positive blood cultures, 99 neonates were excluded
December 31, 2022 who met the inclusion and exclusion because they had isolates positive for fungi growth. The
criteria, as we could meet the sample size previously esti- process of looking for medical records is depicted in
mated for this study. Fig. 1.

Data collection and management Demographic features

Data was collected from the clinical microbiology Over a span of three years, the NICU at dr. Ramelan
department’s data entry and patients’ electronic medi- Navy Central Hospital requested 266 blood culture
cal records using a pre-designed data extraction form. examinations, accounting for nearly half (113/266, 42.5%)
The tools contained information on the characteristics of of all examination requests. This study revealed that
the patients, such as gender, onset of sepsis, birth weight, multidrug-resistant organisms were prevalent (91/113,
gestational age, Lubchenco curve, mode of delivery, his- 80.5%). Further details about the MDROs can be found
tory of premature rupture of the membrane for more in the Supplementary Material (Table S1). The majority
than 18 hours, type of amniotic fluid, history of antibiotic of the patients at this hospital were male (59/113, 52.2%),
use during delivery, congenital malformations, admission weighed between 1500 and 2499 g (50/113, 44.2%), and
type, length of hospital stay, Apgar score at 5 minutes, were delivered via caesarean Sect. (71/113, 62.8%). Annu-
history of using respiratory support devices, history of ally, 430 male neonates were admitted to the NICU at
being placed on a vascular access, and the outcome. this hospital.
The clinical microbiology department’s data entry was
utilized to obtain a list of culture examination requests Risk factors associated with the occurrence of MDRO
for neonatal patients. From these lists, patients with posi- neonatal sepsis
tive blood cultures for bacterial growth were selected. We performed a univariate analysis of the risk factors
The medical record numbers of these patients were observed in our study, as shown in Table 1. All of the
recorded, and then the diagnosis of sepsis was manually significant variables were subjected to a multiple logis-
searched for in the patients’ medical records. The attend- tic regression test to determine which of the risk fac-
ing paediatrician was responsible for making the sepsis tors increased the odds of multidrug-resistant organism
diagnosis. Neonatal sepsis patients with an International neonatal sepsis (Table 2). The risk of MDRO neonatal
Classification of Diseases (ICD)-10 code of P36.0 to P36.8 sepsis is significantly increased by several factors, includ-
were included in this study. The medical records of cho- ing low-birth-weight, a maternal history of premature
sen patients were reviewed to gather information about rupture of the membrane lasting more than 18 hours,
the patients’ characteristics. meconium-stained amniotic fluid, longer hospital stays,
a low Apgar score, and the use of ventilators. In particu-
Data analysis lar, lower birth weight (OR: 1.607, 95% CI: 1.003 − 2.576,
Descriptive analysis was carried out by determining the p-value: 0.049) and premature rupture of the mem-
frequency distributions of the patient’s characteristics brane lasting more than 18 hours (OR: 3.333, 95% CI:
based on blood culture results (MDRO vs. non-MDRO). 2.047 − 5.428, p-value < 0.001) are associated with a higher
A univariate analysis was used to compare the two groups risk of MDRO neonatal sepsis. Meconium-stained amni-
using the chi-square test, with blood culture results as otic fluid (OR: 2.37, 95% CI: 1.512 − 3.717, p-value < 0.001)
the independent variable. After identifying significant also poses a greater risk compared to clear amniotic
risk factors, a multivariate analysis was performed using fluid. Additionally, longer hospital stays (OR: 5.067,
Miranda et al. BMC Pediatrics (2024) 24:153 Page 4 of 8

Fig. 1 The flow of medical records search

95% CI: 2.912 − 8.815, p-value < 0.001) and lower Apgar was notably high (45/50, 90%). A study from Ethiopia
scores (OR: 2.25, 95% CI: 1.442 − 3.512, p-value < 0.001) indicated that low-birth-weight neonates had a higher
are linked to an increased risk. Furthermore, the use likelihood of developing drug-resistant neonatal sepsis
of more invasive respiratory support devices, such as compared to those with a normal birth weight [24]. This
invasive ventilation (OR: 2.687, 95% CI: 1.514 − 4.771, finding was also supported by other studies [25–27].
p-value < 0.001), further raises the risk of MDRO neona- However, a study conducted by Licona G. et al. (2023)
tal sepsis, compared to non-invasive ventilation (OR: 2, concluded that birth weight was not a risk factor for
95% CI: 1.097 − 3.645, p-value: 0.024). developing drug-resistant neonatal sepsis [28].
A maternal history of premature rupture of the mem-
Discussion brane lasting over 18 hours was identified as a significant
Septicemia is still one of the leading causes of neonatal risk factor for the development of multidrug-resistance
mortality. Understanding the pathogens responsible for organism neonatal sepsis. The majority of the neonates
neonatal septicemia is essential for developing man- had a maternal history of ProM lasting over 18 hours
agement strategies, particularly empirical antibiotic (80/113, 70.8%), and the rate of multidrug resistance
regimens [21]. Early initiation of appropriate antibiotic among this group was considered high (70/80, 87.5%).
therapy is critical for improving the outcome and suc- Early and prolonged rupture of the membranes increases
cess of neonatal sepsis treatment [9]. Broad-spectrum the risk of ascending infection from the birth canal into
antibiotic overuse and misuse have been linked to the the amniotic sac and foetal membrane, potentially caus-
emergence of antibiotic-resistant pathogens [22]. The ing asphyxia, which frequently causes sepsis [29]. In a
clinical setting is becoming increasingly associated with study by Awad HA. et al. (2016), a maternal history of
the development of antimicrobial resistance due to the ProM was significantly associated with the develop-
high level of antibiotic use [23]. Multidrug-resistance ment of MDRO neonatal sepsis (p-value < 0.001) [9].
organism are recognized as hospital-acquired pathogens, Several studies reported that a maternal history of
and they impose a significant financial burden on health- ProM was not a significant risk factor for developing
care systems [5]. MDRO neonatal sepsis [27, 30, 31]. Neonates born with
In our study, low birth weight proved to be a significant meconium-stained amniotic fluid were at risk for devel-
risk factor for the development of multidrug-resistant oping multidrug-resistance organism neonatal sepsis.
organism neonatal sepsis. The majority of the neonates The majority of the neonates in our research were born
had a low birth weight (50/113, 44.2%). Among the low- with meconium-stained amniotic fluid (74/113, 65.5%),
birth-weight neonates, the rate of multidrug resistance and the rate of multidrug-resistance was high among
Miranda et al. BMC Pediatrics (2024) 24:153 Page 5 of 8

Table 1 Characteristics of the study population

Variables Category MDRO Non-MDRO p value
Frequency (%) Frequency (%)
Gender Female 47 (51.6) 7 (31.8) 0.095
Male 44 (48.4) 15 (68.2)
Onset of sepsis EOS 55 (60.4) 9 (40.9) 0.097
LOS 36 (39.6) 13 (59.1)
Birth weight (grams) ≥ 2500 28 (30.8) 7 (31.9) 0.045*
1500–2499 45 (49.5) 5 (22.7)
1000–1499 11 (12.1) 5 (22.7)
< 1000 7 (7.6) 5 (22.7)
Gestational age Term 37 (40.7) 15 (68.2) 0.02*
Preterm 54 (59.3) 7 (31.8)
Lubchenco curve AGA 64 (70.3) 9 (40.9) 0.011*
SGA 20 (22) 7 (31.8)
LGA 7 (7.7) 6 (27.3)
Mode of delivery Normal labour 34 (37.4) 8 (36.4) 0.931
Caesarean section 57 (62.6) 14 (63.6)
ProM more than 18 h No 21 (23.1) 12 (54.5) 0.004*
Yes 70 (76.9) 10 (45.5)
Amniotic fluid Clear 27 (29.7) 12 (54.5) 0.028*
Meconeal 64 (70.3) 10 (45.5)
Antibiotic use during delivery No 32 (35.2) 7 (31.8) 0.767
Yes 59 (64.8) 15 (68.2)
Congenital malformation No 70 (76.9) 12 (54.5) 0.035*
Yes 21 (23.1) 10 (45.5)
Admission type Inborn 62 (68.1) 9 (40.9) 0.018*
Outborn 29 (31.9) 13 (59.1)
Length of hospital stay (days) ≤7 15 (16.5) 16 (72.7) < 0.001*
>7 76 (83.5) 6 (27.3)
Apgar score at 5 min ≥7 28 (30.8) 13 (59.1) 0.013*
<7 63 (69.2) 9 (40.9)
Respiratory support device None 16 (17.6) 9 (40.9) 0.049*
NIV 32 (35.2) 7 (31.8)
IV 43 (47.2) 6 (27.3)
Vascular access Peripheral vascular access 60 (65.9) 15 (68.2) 0.841
Central vascular access 31 (34.1) 7 (31.8)
Outcome Live 42 (46.2) 16 (72.7) 0.025*
Death 49 (53.8) 6 (27.3)
Notes: *representing the significant p-value
EOS Early-onset sepsis, LOS Late-onset sepsis, SGA Small for gestational age, AGA Appropriate for gestational age, LGA Large for gestational age, ProM Premature
rupture of the membrane, NIV Non-invasive ventilation, IV Invasive ventilation

this group (64/74, 86.5%). Consistent with our findings, multidrug-resistance was high in that group (76/82,
a study in Surabaya also identified meconium-stained 92.7%). Prolonged hospital stays (≥ 5 days) were iden-
amniotic fluid as a risk factor for developing neona- tified as one of the potential risk factors for developing
tal sepsis [32]. Conversely, a case-control study of 248 hospital-acquired MDRO neonatal sepsis in a single-cen-
neonates in southwest Ethiopia found that meconium- ter study in Saudi Arabia [6]. Another study reached the
stained amniotic fluid was not a risk factor for developing same conclusion [22, 33–35]. Exposure to healthcare is
neonatal sepsis [12]. Manandhar S. et al. (2021) reported a risk factor for acquiring colonization or infection with
the same finding in Nepal [33]. antibiotic-resistant bacteria due to cross-transmission or
Our study found that longer hospital stays increased selection pressure on the microbiome during antibiotic
the risk of multidrug-resistance organism neonatal sep- treatment. Conversely, an infection with a resistant strain
sis. The majority of the neonates stayed in our hospi- may lengthen the hospital stay because it is more diffi-
tal for longer than 7 days (82/113, 72.6%). The rate of cult to treat [36]. The Tuzla study revealed that neonates
Miranda et al. BMC Pediatrics (2024) 24:153 Page 6 of 8

Table 2 Multivariate analysis for determining odds ratio of potential risk factors for MDRO neonatal sepsis
Variables Category OR 95% CI p value
Birth weight (grams) ≥ 2500 1 Reference
1500–2499 1.607 1.003 − 2.576 0.049*
1000–1499 0.393 0.196 − 0.789 0.009*
< 1000 0.25 0.109 − 0.572 0.001*
Gestational age Term 1 Reference
Preterm 1.459 0.961 − 2.217 0.076
Lubchenco curve AGA 1 Reference
SGA 0.312 0.189 − 0.516 < 0.001*
LGA 0.109 0.05 − 0.239 < 0.001*
ProM more than 18 h No 1 Reference
Yes 3.333 2.047 − 5.428 < 0.001*
Amniotic fluid Clear 1 Reference
Meconeal 2.37 1.512 − 3.717 < 0.001*
Congenital malformation No 1 Reference
Yes 0.3 0.184 − 0.489 < 0.001*
Admission type Inborn 1 Reference
Outborn 0.468 0.301 − 0.727 < 0.001*
Length of hospital stay (days) ≤7 1 Reference
>7 5.067 2.912 − 8.815 < 0.001*
Apgar score at 5 min ≥7 1 Reference
<7 2.25 1.442 − 3.512 < 0.001*
Respiratory support device None 1 Reference
NIV 2 1.097 − 3.645 0.024*
IV 2.687 1.514 − 4.771 < 0.001*
Notes: *representing the significant p-value
EOS Early-onset sepsis, LOS Late-onset sepsis, SGA Small for gestational age, AGA Appropriate for gestational age, LGA Large for gestational age, ProM Premature
rupture of the membrane, NIV Non-invasive ventilation, IV Invasive ventilation

with MDR sepsis required more intense care (20.7 ± 10.8 ventilation. Neonates with non-invasive ventilation were
vs. 12.4 ± 6.93 days) than the non-MDR sepsis group at a 2-fold risk of developing MDRO neonatal sepsis. A
(p-value < 0.001) [30]. Bandyopadhyay T. et al. (2018) study conducted in eastern Saudi Arabia revealed that
proved that duration of hospital stay was not a significant the use of a mechanical ventilator for ≥ 72 h significantly
risk factor for developing MDRO neonatal sepsis, with a increased the risk of MDR neonatal sepsis (p-value 0.049)
median hospital stay of 22 days [37]. [5]. This finding was supported by other studies [26, 40].
Lower Apgar scores were associated with an increased This study’s strength was that we explored numerous
risk of multidrug-resistant organism neonatal sepsis. The variables as risk factors for developing multidrug-resis-
majority of the neonates in the study were born with an tance organism neonatal sepsis, especially the Lubchenco
Apgar score of less than 7 at 5 minutes (72/113, 63.7%), curve as one of the variables, which is still seldom
and multidrug resistance was prevalent in neonates from observed in previous studies. As a result of this study, it
this group (63/72, 87.5%). This finding aligns with a study is envisaged that the incidence of MDRO neonatal sep-
conducted in Ghana (p-value < 0.001) [38]. However, G/ sis might be reduced by avoiding modifiable risk factors.
eyesus T. et al. (2017) reported the opposite, concluding Our hospital has its own obstetric ward, and nearly all
that a low Apgar score was not a risk factor for devel- neonates were born there. This makes the related data
oping neonatal sepsis (p-value 0.023) [39]. Additionally, obtained for this study more precise and representative,
the use of more invasive respiratory support devices was as incomplete data from referral patients due to missed
found to increase the risk of multidrug-resistant organ- communications could be limited. Although this was a
ism neonatal sepsis. A significant proportion of the neo- thorough study, it has some limitations. First, because
nates in the study relied on invasive ventilation as their this was a single-center study, the findings may be less
respiratory support (49/113, 43.4%). Multidrug resis- generalizable to other institutes. Second, misclassifica-
tance was prevalent among neonates using invasive ven- tion or recollection bias could arise because this was a
tilation (43/49, 87.8%). Neonates on invasive ventilation retrospective medical record-based study.
faced a 2.687-fold greater risk of developing MDRO neo-
natal sepsis compared to those receiving non-invasive
Miranda et al. BMC Pediatrics (2024) 24:153 Page 7 of 8

Funding
Conclusions No funding or grant support.
Our study determined the burden, demographics, and
risk factors for multidrug-resistance organism neona- Data availability
The datasets supporting the conclusion of this article are included within the
tal sepsis. The majority of the isolates in this study grew article and its additional files.
for MDRO. Low-birth-weight, a maternal history of
premature rupture of the membrane lasting more than Declarations
18 hours, meconium-stained amniotic fluid, longer hos-
pital stays, a low Apgar score, and the use of ventilators Ethics approval and consent to participate
The study proposal was approved by the research ethics committee of dr.
were found to be significant independent risk factors for Ramelan Navy Central Hospital (11/EC/KEP/2023). There is no additional
developing drug-resistant neonatal sepsis. sample to be taken from the study participants for the sake of this study. The
Continuous surveillance for antibiotic susceptibil- blood sample collected in the study was part of routine patient investigation
and management at the NICU. The blood sample was collected by trained
ity is required to maintain optimal empirical antibiotic nurses. A written informed consent was obtained from mothers/caretakers of
therapy. Antibiotic susceptibility testing should be used neonates after explaining the objective of the study.
to assess whether antibiotics should be kept, changed, or
Consent for publication
terminated. Improvement of infection control practices, Not applicable.
avoidance of irrational use of antibiotics, and revision
of the protocols for treatment are mandatory to pre- Competing interests
The authors declare no competing interests.
vent further resistance. Auditing and continuous quality
improvement programs are essential. A more representa- Received: 20 August 2023 / Accepted: 12 February 2024
tive multi-center study is expected and should be carried
out in the future.
Abbreviations
AGA Appropriate for Gestational Age References
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