The Cohort of Indonesian Preterm Infants for Long-term Outcomes (CIPTO) study: a protocol.

BACKGROUND: Indonesia has high numbers of preterm birth, i.e., around 600,000 preterm births annually. It imposes a significant burden on the Indonesia's healthcare system. Indonesia therefore requires its own evidence-based reference to manage premature neonates and ex-preterm infants who subsequently survived. No long-term study on preterm infants in Indonesia has been conducted, therefore we aim to evaluate growth and development on ex-preterm infants until the pre-pubertal stage. METHODS: We at the Cipto Mangunkusumo General Hospital (CMGH) designed a prospective cohort study of preterm infants, i.e., the Cohort of Indonesian Preterm Infants for Long-term Outcomes (CIPTO) study. At least 500 subjects will be recruited with an estimation of two-year recruitment (i.e., the recruitment phase will be completed before 2024). The CIPTO study will observe long-term outcomes of ex-preterm infants, primarily on growth and developmental milestones until 8 years old. Aims of this study are to determine the ex-preterm outcomes and to generate an evidence-based reference of preterm care for ensuring optimum outcomes. The pre-specified long-term outcomes in this study are survival rates, growth outcomes, neurodevelopmental outcomes, feeding behavior, as well as hearing and vision impairments. Growth and neurodevelopmental outcomes will be assessed at 0, 2, 4, 6, 9, 12, 15, 18 and 24 months of corrected age as well as at 3, 4, 5, 6, 7 and 8 years old. DISCUSSION: The CIPTO study is the first prospective cohort in Indonesia focusing on preterm infants born at the CMGH. With a follow up until 8 years old, this study may provide useful insights to generate an evidence-based, Indonesia's health care reference in managing premature infants and ensuring the optimum outcomes of ex-preterm infants.

Early-onset neonatal sepsis and antibiotic use in Indonesia: a descriptive, cross-sectional study.

BACKGROUND: Early diagnosis and prompt antibiotic treatment are crucial to reducing morbidity and mortality of early-onset sepsis (EOS) in neonates. However, this strategy remains challenging due to non-specific clinical findings and limited facilities. Inappropriate antibiotics use is associated with ineffective therapy and adverse outcomes. This study aims to determine the characteristics of EOS and use of antibiotics in the neonatal-intensive care units (NICUs) in Indonesia, informing efforts to drive improvements in the prevention, diagnosis, and treatment of EOS. METHODS: A descriptive study was conducted based on pre-intervention data of the South East Asia-Using Research for Change in Hospital-acquired Infection in Neonates project. Our study population consisted of neonates admitted within 72 h of life to the three participating NICUs. Neonates who presented with three or more clinical signs or laboratory results consistent with sepsis and who received antibiotics for 5 consecutive days were considered to have EOS. Culture-proven EOS was defined as positive blood or cerebrospinal fluid culture. Type and duration of antibiotics used were also documented. RESULTS: Of 2,509 neonates, 242 cases were suspected of having EOS (9.6%) with culture-proven sepsis in 83 cases (5.0% of neonatal admissions in hospitals with culture facilities). The causative organisms were mostly gram-negative bacteria (85/94; 90.4%). Ampicillin / amoxicillin and amikacin were the most frequently prescribed antibiotics in hospitals with culture facilities, while a third-generation cephalosporin was mostly administered in hospital without culture facilities. The median durations of antibiotic therapy were 19 and 9 days in culture-proven and culture-negative EOS groups, respectively. CONCLUSIONS: The overall incidence of EOS and culture-proven EOS was high in Indonesia, with diverse and prolonged use of antibiotics. Prospective antibiotic surveillance and stewardship interventions are required.

Cystatin C compared to serum creatinine as a marker of acute kidney injury in critically ill neonates.

BACKGROUND: Acute kidney injury (AKI) is one of the most common causes of neonatal morbidity and mortality. Diagnosing AKI in neonates is challenging as it lacks specific signs, symptoms, and biomarkers. However, detecting AKI in critically ill neonates is crucial to determine appropriate management and prevent complications. Cystatin C (CysC) has been recognized as a superior kidney biomarker reflecting kidney function in neonates. The objective of this study is to evaluate the diagnostic value of CysC as an AKI biomarker in critically ill neonates. METHODS: We performed a diagnostic test between cystatin C-based estimated glomerular filtration rate (eGFR-CysC) and serum creatinine-based estimated glomerular filtration rate (eGFR-SCr) as the gold standard to diagnose AKI in 135 critically ill neonates treated in Cipto Mangunkusumo National Hospital from July 2017 to January 2018. RESULTS: Prevalence of AKI was 23.7% predominantly in neonates with a very preterm gestational age, low birthweight, probable sepsis, and those receiving invasive oxygen therapy or nephrotoxic drugs. The proportion of AKI based on neonate RIFLE criteria was 72.7% risk, 18.9% injury, and 9% failure. eGFR-CysC had the following parameters: sensitivity, 84.8%; specificity, 61.8%; PPV, 41.8%; NPV, 89.7%; LR(+), 2.2; LR(-), 0.24; and accuracy, 67.4%. The AUROC for CysC was 84.9%. The optimal cut-off value for CysC was 1.605 mg/l. CONCLUSIONS: CysC may be used as a screening biomarker of AKI in critically ill neonates; yet, it was not superior to serum creatinine. Graphical abstract.

SLCO1B1 c.388A > G variant incidence and the severity of hyperbilirubinemia in Indonesian neonates.

OBJECTIVE: It has been established that genetic factors play a substantial role in the development of neonatal hyperbilirubinemia. The population of Indonesia and other Southeast Asian countries has similar, yet different genetic makeup compared to the rest of Asia. Aside from UGT1A1, variants of SLCO1B1 have also been known to contribute to the severity of neonatal hyperbilirubinemia in Asian populations. Since there has been no report on SLCO1B1 polymorphism in relation with hyperbilirubinemia in Indonesia, this study aims to explore incidence of SLCO1B1*1B polymorphism in Indonesia based on 3 hospitals from different provinces and population, and their association with hyperbilirubinemia severity. METHODS: Our study included 88 neonates with mild and moderate-severe hyperbilirubinemia from 3 NICU in hospitals representing homogenous and heterogenous populations: Biak General Hospital Papua, Cipto Mangunkusumo Hospital (Jakarta), and M Yunus Hospital (Bengkulu). We collected samples between November 2016 and September 2017. DNA was obtained from existing samples of the patients from previous studies and were subjected to Polymerase Chain Reaction - Restriction Fragment Length Polymorphism (PCR-RFLP). We analyzed the *1B variant located in exon 5 of SLCO1B1 with TaqI restriction endonuclease. Clinical, demographic, and laboratory data was also collected from medical records and parents' interviews. RESULTS: The most dominant variant of SLCO1B1*1B in our population is the homozygous G/G (68.18%), followed by heterozygous A/G (26.14%), and wild type A/A (5.68%). The heterozygous A/G had an Odds Ratio (OR) of 0.73 (95% CI 0.10-5.2) and homozygous G/G with OR of 0.51 (95%CI 0.08-3.27), both were not significant. Genotypic distribution across the different centers were also similar and not significant. The significant risk factors for moderate-severe hyperbilirubinemia were the population the neonate originated from (p = < 0.001) and the delivery location (p = 0.001), while SLCO1B1*1B was not associated with the different severity of hyperbilirubinemia. CONCLUSIONS: SLCO1B1*1B is not associated with higher bilirubin levels among neonates with hyperbilirubinemia in Indonesia. Further study is needed to find other potentially important genetic polymorphisms in the development of severe hyperbilirubinemia in Indonesia.

Agreement test of transcutaneous bilirubin and bilistick with serum bilirubin in preterm infants receiving phototherapy.

BACKGROUND: This study compares the minimally invasive Bilistick and a noninvasive method with standard Total Serum Bilirubin (TSB) measurement in preterm newborns receiving phototherapy. We assess the agreement of Transcutaneous Bilirubinometer (TcB) and Bilistick bilirubin measurements with standard TSB measurement in preterm infants receiving phototherapy. METHODS: Bilirubin was measured by using TcB and Bilistick in 94 preterm infants in RSCM Jakarta Neonatal Ward from October 2016 to March 2017, with gestational ages of < 35 weeks, before phototherapy and after 24 and 48 h of phototherapy. RESULTS: There was significant correlation before, at 24 and 48 h of phototherapy between TSB and either TcB (r = 0.874; r = 0.889; r = 0.878 respectively; p < 0.0001), or Bilistick (r = 0.868; r = 0.877; r = 0.918 respectively; p < 0.0001). The mean difference and limits of agreement before, at 24 and 48 h of phototherapy between TcB and TSB were 0.81 ± 1.51 mg/dL (- 2.14 to 3.77 mg/dL); 0.43 ± 1.57 mg/dL (- 2.66 to 3.51 mg/dL); 0.41 ± 1.58 mg/dL (- 2.69 to 3.50 mg/dL), respectively. For Bilistick they were - 1.50 ± 1.47 mg/dL (- 4.38 to 1.38 mg/dL); - 1.43 ± 1.47 mg/dL (- 4.32 to 1.46 mg/dL); - 1,15 ± 1.31 mg/dL (- 3,72 to 1,42 mg/dL), respectively. CONCLUSIONS: Both methods are reliable for measuring TSB before, during, and after phototherapy in preterm infants. TcB tends to overestimate while Bilistick underestimates TSB.

Prevention and control of blood stream infection using the balanced scorecard approach.

AIM: to obtain formulation of an effective and efficient strategy to overcome blood stream infection (BSI). METHODS: operational research design with qualitative and quantitative approach. The study was divided into two stages. Stage I was an operational research with problem solving approach using qualitative and quantitative method. Stage II was performed using quantitative method, a form of an interventional study on strategy implementation, which was previously established in stage I. The effective and efficient strategy for the prevention and control of infection in neonatal unit Cipto Mangunkusumo (CM) Hospital was established using Balanced Scorecard (BSC) approach, which involved several related processes. RESULTS: the BSC strategy was proven to be effective and efficient in substantially reducing BSI from 52.31°/oo to 1.36°/oo in neonates with birth weight (BW) 1000-1499 g (p=0.025), and from 29.96°/oo to 1.66°/oo in BW 1500-1999 g (p=0.05). Gram-negative bacteria still predominated as the main cause of BSI in CMH Neonatal Unit. So far, the sources of the microorganisms were thought to be from the environment of treatment unit (tap water filter and humidifying water in the incubator). Significant reduction was also found in neonatal mortality rate weighing 1000-1499 g at birth, length of stay, hospitalization costs, and improved customer satisfaction. CONCLUSION: effective and efficient infection prevention and control using BSC approach could significantly reduce the rate of BSI. This approach may be applied for adult patients in intensive care unit with a wide range of adjustment.

Novel scoring system for early diagnosis of necrotizing enterocolitis: integrating clinical and laboratory data with urinary caveolin-1 levels.

Introduction: Necrotizing enterocolitis (NEC) poses a significant threat to preterm infants, with nonspecific early manifestations complicating timely diagnosis. Therefore, this study aimed to develop a novel scoring system for early diagnosis of NEC, incorporating clinical and laboratory data with urinary caveolin-1 levels. Material and methods: A single-center prospective cohort study was conducted at a tertiary hospital in East Java, Indonesia. NEC diagnosis was established by Bell's criteria and proven gut dysbiosis. Urinary levels of claudin-2, caveolin-1, and epidermal growth factor (EGF) were assessed as potential indicators of tight junction disruption. The selected urine biomarker cutoff value was determined using symbolic classification analysis and combined with clinical and laboratory parameters from Bell's criteria to create an NEC scoring system, validated with the Aiken index. Sensitivity and specificity analyses were performed. Results: Thirty-four neonates, comprising NEC, preterm non-NEC, and term infants, were included. qPCR analysis highlighted elevated Klebsiella, Lactobacillus, Clostridium, and Bacteroides levels in NEC patients, indicating a gut dysbiosis trend. Among 3 biomarkers, caveolin-1 ≥ 17.81 ng/dl on day 3 demonstrated 72.86% negative predictive value and 87.50% positive predictive value. The combined scoring system which comprised abdominal cellulitis, distension, radiology, advanced resuscitation at birth, prematurity or low birthweight, platelet count, sepsis, orogastric retention, metabolic acidosis and caveolin-1 findings exhibited an AUC of 0.922 (95% CI: 0.81-1.00, p < 0.001), with ≥ 1.81 as the cutoff, offering 93% sensitivity and 94% specificity. Conclusions: Urine caveolin-1 on day 3 signifies enterocyte tight junction damage and the acute phase of NEC in premature infants. The proposed scoring system demonstrates good performance in predicting NEC incidence in preterm infants.

Feeding intolerance scoring system in very preterm and very low birth weight infants using clinical and ultrasound findings.

Very preterm infants are at a high risk of developing feeding intolerance; however, there are no widely accepted definitions of feeding intolerance. This study aimed to develop a scoring system for feeding intolerance in very preterm infants by combining clinical symptoms and ultrasonography (US) findings. This prospective cohort study included very preterm and/or very low birth weight infants. We defined feeding intolerance as the inability to achieve full feeding (150 ml/kg/day) by 14 days of life. The clinical findings included vomiting, abdominal distention, and gastric fluid color. US findings included intestinal peristaltic frequency, gastric residual volume, peak systolic velocity, and the resistive index of the superior mesenteric artery. We conducted multivariate analyses to evaluate the potential predictors and developed a scoring system to predict feeding intolerance. A total of 156 infants fulfilled the eligibility criteria; however, 16 dropped out due to death. The proportion of patients with feeding intolerance was 60 (42.8%). Based on the predictive ability, predictors of feeding intolerance were determined using data from the US at 5-7 days of age. According to multivariate analysis, the final model consisted of 5 predictors: abdominal distention (score 1), hemorrhagic gastric fluid (score 2), intestinal peristaltic movement ≤18x/2 min (score 2), gastric fluid residue >25% (score 2), and resistive index >0.785 (score 2). A score equal to or above 5 indicated an increased risk of feeding intolerance with a positive predictive value of 84.4% (95% confidence interval:73.9-95.0) and a negative predictive value of 76.8% (95% confidence interval:68.4-85.3). The scoring system had good discrimination (area under the receiver operating characteristic curve:0.90) and calibration (p = 0.530) abilities. This study developed an objective, accurate, easy, and safe scoring system for predicting feeding intolerance based on clinical findings, 2D US, and color Doppler US.

Initial Oxygen Concentration for the Resuscitation of Infants Born at Less Than 32 Weeks' Gestation: A Systematic Review and Individual Participant Data Network Meta-Analysis.

Importance: Resuscitation with lower fractional inspired oxygen (FiO2) reduces mortality in term and near-term infants but the impact of this practice on very preterm infants is unclear. Objective: To evaluate the relative effectiveness of initial FiO2 on reducing mortality, severe morbidities, and oxygen saturations (SpO2) in preterm infants born at less than 32 weeks' gestation using network meta-analysis (NMA) of individual participant data (IPD). Data Sources: MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, and WHO ICTRP from 1980 to October 10, 2023. Study Selection: Eligible studies were randomized clinical trials enrolling infants born at less than 32 weeks' gestation comparing at least 2 initial oxygen concentrations for delivery room resuscitation, defined as either low (≤0.3), intermediate (0.5-0.65), or high (≥0.90) FiO2. Data Extraction and Synthesis: Investigators from eligible studies were invited to provide IPD. Data were processed and checked for quality and integrity. One-stage contrast-based bayesian IPD-NMA was performed with noninformative priors and random effects and adjusted for key covariates. Main Outcomes and Measures: The primary outcome was all-cause mortality at hospital discharge. Secondary outcomes were morbidities of prematurity and SpO2 at 5 minutes. Results: IPD were provided for 1055 infants from 12 of the 13 eligible studies (2005-2019). Resuscitation with high (≥0.90) initial FiO2 was associated with significantly reduced mortality compared to low (≤0.3) (odds ratio [OR], 0.45; 95% credible interval [CrI], 0.23-0.86; low certainty) and intermediate (0.5-0.65) FiO2 (OR, 0.34; 95% CrI, 0.11-0.99; very low certainty). High initial FiO2 had a 97% probability of ranking first to reduce mortality. The effects on other morbidities were inconclusive. Conclusions and Relevance: High initial FiO2 (≥0.90) may be associated with reduced mortality in preterm infants born at less than 32 weeks' gestation compared to low initial FiO2 (low certainty). High initial FiO2 is possibly associated with reduced mortality compared to intermediate initial FiO2 (very low certainty) but more evidence is required.

Contemporary fluid management, humidity, and patent ductus arteriosus management strategy for premature infants among 336 hospitals in Asia.

Objectives: The management of patent ductus arteriosus (PDA) is a critical concern in premature infants, and different hospitals may have varying treatment policies, fluid management strategies, and incubator humidity. The Asian Neonatal Network Collaboration (AsianNeo) collected data on prematurity care details from hospitals across Asian countries. The aim of this study was to provide a survey of the current practices in the management of PDA in premature infants in Asian countries. Methods: AsianNeo performed a cross-sectional international questionnaire survey in 2022 to assess the human and physical resources of hospitals and clinical management of very preterm infants. The survey covered various aspects of hospitals resources and clinical management, and data were collected from 337 hospitals across Asia. The data collected were used to compare hospitals resources and clinical management of preterm infants between areas and economic status. Results: The policy of PDA management for preterm infants varied across Asian countries in AsianNeo. Hospitals in Northeast Asia were more likely to perform PDA ligation (p < 0.001) than hospitals in Southeast Asia. Hospitals in Northeast Asia had stricter fluid restrictions in the first 24 h after birth for infants born at <29 weeks gestation (p < 0.001) and on day 14 after birth for infants born at <29 weeks gestation (p < 0.001) compared to hospitals in Southeast Asia. Hospitals in Northeast Asia also had a more humidified environment for infants born between 24 weeks gestation and 25 weeks gestation in the first 72 h after birth (p < 0.001). A logistic regression model predicted that hospitals were more likely to perform PDA ligation for PDA when the hospitals had a stricter fluid planning on day 14 after birth [Odds ratio (OR) of 1.70, p = 0.048], more incubator humidity settings (<80% vs. 80%-89%, OR of 3.35, p = 0.012 and <80% vs. 90%-100%, OR of 5.31, p < 0.001). Conclusions: In advanced economies and Northeast Asia, neonatologists tend to adopt a more conservative approach towards fluid management, maintain higher incubator humidity settings and inclined to perform surgical ligation for PDA.

Prognostic value of biochemical liver parameters in neonatal sepsis-associated cholestasis.

AIMS: The aim of the study was to evaluate the significance of total bilirubin, aspartate transaminase (AST), alanine transaminase and gamma-glutamyltransferase (GGT) for predicting outcome in sepsis-associated cholestasis. METHODS: A retrospective cohort review of the hospital records was performed in 181 neonates admitted to the Neonatal Care Unit. A comparison was performed between subjects with low and high liver values based on cut-off values from ROC analysis. We defined poor prognosis to be when a subject had prolonged cholestasis of more than 3.5 months, developed severe sepsis, septic shock or had a fatal outcome. RESULTS: The majority of the subjects were male (56%), preterm (56%) and had early onset sepsis (73%). The poor prognosis group had lower initial values of GGT compared with the good prognosis group (P = 0.003). Serum GGT (cut-off value of 85.5 U/L) and AST (cut-off value of 51 U/L) showed significant correlation with the outcome following multivariate analysis. The odds ratio (OR) of low GGT and high AST were OR 4.3 (95% CI:1.6 to 11.8) and OR 2.9 (95% CI:1.1 to 8), respectively, for poor prognosis. In subjects with normal AST values, those with low GGT value had relative risk of 2.52 (95% CI:1.4 to 3.5) for poorer prognosis compared with those with normal or high GGT. CONCLUSION: Serum GGT and AST values can be used to predict the prognosis of patients with sepsis-associated cholestasis.

Experiences of Indonesian nurses in improving preterm oral feeding readiness in special care units: A qualitative descriptive study.

Background: Many preterm infants face feeding difficulties during the transition from enteral to oral feeding due to organ immaturity, resulting in aspiration, airway instability, and oral feeding intolerance. These challenges can increase morbidity and mortality among preterm infants. Nurses play a vital role in providing interventions to minimize negative impacts and enhance the safety of preterm oral feeding. Objective: This study aimed to explore the experiences of Indonesian nurses in improving preterm oral feeding readiness. Methods: A qualitative descriptive study was conducted involving ten nurses working in intensive care units as participants through purposive sampling. Data were collected through semi-structured, in-depth interviews conducted from January to March 2023. Thematic analysis was applied for data analysis. Results: Four key themes developed in this study: 1) comprehensive and holistic nursing assessment, 2) challenging and complex nursing issues, 3) the need for nutritional management skills, and 4) the necessity of collaborative support. Conclusion: Nurses play a pivotal role in enhancing oral feeding readiness among premature infants. Their responsibilities include assessing oral feeding readiness, addressing nursing challenges, and implementing multidisciplinary stimulation involving parents. This study provides a foundational framework for developing interventions to improve preterm oral feeding readiness.

Clinical efficacy of IgM-enriched immunoglobulin as adjunctive therapy in neonatal and pediatric sepsis: a systematic review and meta-analysis.

Background: Sepsis is a major cause of mortality and morbidity globally, with around one-quarter of all sepsis-related deaths occurring in children under the age of 5. We conducted a meta-analysis and systematic review of the literature to evaluate the clinical effectiveness of an IgM-enriched immunoglobulin preparation in pediatrics patients and neonates with sepsis. Methods: Systematic searches of PubMed, the Cochrane Library and Embase databases were performed in November 2022, with no date limitations, to identify studies in which IgM-enriched immunoglobulin was used as adjunctive therapy in neonatal and pediatric patients with sepsis. Results: In total, 15 studies fulfilled the eligibility criteria, 13 neonatal studies and 2 pediatric studies. Pooled estimates from all studies indicated that mortality rates were significantly lower in patients who received treatment with the IgM-enriched immunoglobulin compared with controls (OR 0.41; 95% CI 0.32-0.55). Further analyses in neonatal studies, alone, showed a significant benefit with longer treatment durations (>3 days) vs. the recommended treatment duration (3 days) (OR 0.32; 95% CI 0.22-0.47) vs. (OR 0.61; 95% CI 0.41-0.92). Treatment with IgM-enriched immunoglobulin was associated with a lower mortality risk compared with controls in prospective studies vs. retrospective analyses (OR 0.37; 95% CI 0.27-0.51) vs. (OR 0.73; 95% CI 0.41-1.30). Conclusions: This systematic review suggests that adjunctive treatment with IgM-enriched immunoglobulin may reduce the risk of mortality in neonatal and pediatric populations. However, large randomized controlled trials are required to further substantiate and evaluate these findings.

Defining postnatal growth failure among preterm infants in Indonesia.

Background: Postnatal growth failure (PGF) frequently occurred among preterm infants with malnutrition. The decline in a weight-for-age z-score of ≥1.2 has been proposed to define PGF. It was unknown whether this indicator would be useful among Indonesian preterm infants. Methods: Infants of <37 weeks of gestational age born between 2020 and 2021, both stable and unstable, were recruited for a prospective cohort study during hospitalization in the level III neonatal intensive care unit at the Cipto Mangunkusumo General Hospital, Jakarta, Indonesia. The prevalence of PGF as defined by a weight-for-age z-score of <-1.28 (<10th percentile) at discharge, a weight-for-age z-score of <-1.5 (<7th percentile) at discharge, or a decline in a weight-for-age z-score of ≥1.2 from birth till discharge was compared. The association between those PGF indicators with the preterm subcategory and weight gain was assessed. The association between the decline in a weight-for-age z-score of ≥1.2 with the duration to achieve full oral feeding and the time spent for total parenteral nutrition was analyzed. Results: Data were collected from 650 preterm infants who survived and were discharged from the hospital. The weight-for-age z-score of <-1.28 or <-1.5 was found in 307 (47.2%) and 270 (41.5%) subjects with PGF, respectively. However, both indicators did not identify any issue of weight gain among subjects with PGF, questioning their reliability in identifying malnourished preterm infants. By contrast, the decline in a weight-for-age z-score of ≥1.2 was found in 51 (7.8%) subjects with PGF, in which this indicator revealed that subjects with PGF had an issue of weight gain. Next, a history of invasive ventilation was identified as a risk factor for preterm infants to contract PGF. Finally, the decline in a weight-for-age z-score of ≥1.2 confirmed that preterm infants with PGF took a longer time to be fully orally fed and a longer duration for total parenteral nutrition than the ones without PGF. Conclusion: The decline in a weight-for-age z-score of ≥1.2 was useful to identify preterm infants with PGF within our cohort. This could reassure pediatricians in Indonesia to use this new indicator.

Determinants of neonatal deaths in Indonesia: A national survey data analysis of 10,838 newborns.

Background: Neonatal mortality is one of the key impediments in achieving global sustainable development goals, especially in lower middle income countries (LMICs). As an LMIC with the highest reported neonatal mortality rate in Southeast Asia, Indonesia faces inequitable distribution of health facilities across the archipelago. Therefore, in this paper, we aim to evaluate the determinants of neonatal mortality rate in Indonesia to search for better strategies to overcome this problem. Methods: We conducted an analysis of the 2017 Indonesia Demographic Health Survey dataset of 10,838 live-born infants born from singleton pregnancies in 2017. Using a hierarchical approach, multivariate analysis was conducted to identify potential factors (including socioeconomic, household, and proximate determinants) that contributed to neonatal mortality. Results: The lack of participation in postnatal care [odds ratio (OR) = 20.394, p = 0.01)] and delivery complications other than prolonged labour (OR = 2.072, p = 0.02) were the maternal factors that significantly associated with increased risk of neonatal death. Regarding neonatal factors, low-birth-weight infants appeared to be more vulnerable to neonatal death (OR = 12.489, p = 0.01). Conclusion: Low participation in postnatal care, development of labour complications, and low birth weight were associated with higher neonatal mortality. It implies that in a limited resource and geographically challenging country such as Indonesia, improving the quality and optimizing services of public hospitals with equitable distribution of quality health care services in all regions should be prioritized in the efforts of reducing neonatal mortality rate.

Variations in medical practice of retinopathy of prematurity among 8 Asian countries from an international survey.

Advances in perinatal care have led to the increased survival of preterm infants with subsequent neonatal morbidities, such as retinopathy of prematurity (ROP). This study aims to compare the differences of neonatal healthcare systems, resources, and clinical practice concerning ROP in Asia with review of current literature. An on-line survey at the institutional level was sent to the directors of 336 neonatal intensive care units (NICU) in 8 collaborating national neonatal networks through the Asian Neonatal Network Collaboration (AsianNeo). ROP screening was performed in infants born at < 34 weeks in Indonesia and Japan. In South Korea, Malaysia, and Taiwan, most screened for ROP in infants born at < 32 weeks. In all networks, majority of NICUs conducted ROP screening to infants with birth weight < 1500 g. In most NICU's in-hospital ophthalmologists performed indirect ophthalmoscopy and some were supplemented with digital imaging. Both laser photocoagulation and anti-vascular endothelial growth factor injection are performed for treatment and, vitreous surgeries are conducted less frequently in all countries. Despite limited information collected by the survey, this first study to compare ROP practices implemented in eight Asian countries through AsianNeo will enable an understanding of the differences and facilitate quality improvement by sharing better practices.

Metagenomic profiles of the early life microbiome of Indonesian inpatient neonates and their influence on clinical characteristics.

Determining the initial normal neonatal gut microbiome is challenging. The debate regarding the sterile fetal environment is still ongoing. Therefore, studying and comparing normal and dysbiotic microbiomes requires the elucidation of both the fetal and infant microbiomes. Factors influencing the normal microbiome also include regional and genetic factors specific to different countries. Determining the normal microbiome population in our center and their association with the clinical conditions of infants is helpful as a tool for both the prevention and treatment of related diseases during neonatal care. Here, we employed metagenomic sequencing to characterize meconium and the subsequent early-life gut microbiome of preterm neonates in Jakarta, Indonesia. Microbiome diversity and complexity was higher in the meconium and on day 4 than on day 7. At the genus level, the most abundant genus overall was unidentified Enterobacteriaceae, with meconium samples dominated by Ureaplasma, day 4 fecal samples dominated by Staphylococcus, and day 7 samples dominated by Clostridiales, while at the phylum level the most abundant was Proteobacteria and Firmicutes. Perinatal factors of PROM and mother's diet influenced the meconium microbiome, while day 4 and day 7 microbiome was associated with bacteremia and early administration of antibiotics. One of our sample sets was derived from triplets, and they had varying diversity despite being triplets. These data are valuable for understanding the formation of a healthy microbiome specific to neonates and devising a strategy to improve both the gut health and related clinical outcomes of the neonate.

A review of existing neonatal hyperbilirubinemia guidelines in Indonesia.

Background: Neonatal hyperbilirubinemia is one of the most common conditions for neonate inpatients. Indonesia faces a major challenge in which different guidelines regarding the management of this condition were present. This study aimed to compare the existing guidelines regarding prevention, diagnosis, treatment and monitoring in order to create the best recommendation for a new hyperbilirubinemia guideline in Indonesia. Methods: Through an earlier survey regarding adherence to the neonatal hyperbilirubinemia guideline, we identified that three main guidelines are being used in Indonesia. These were developed by the Indonesian Pediatric Society (IPS), the Ministry of Health (MoH), and World Health Organization (WHO). In this study, we compared factors such as prevention, monitoring, methods for identifying, risk factors in the development of neonatal jaundice, risk factors that increase brain damage, and intervention treatment threshold in the existing guidelines to determine the best recommendations for a new guideline. Results: The MoH and WHO guidelines allow screening and treatment of hyperbilirubinemia based on visual examination (VE) only. Compared with the MoH and WHO guidelines, risk assessment is comprehensively discussed in the IPS guideline. The MoH guideline recommends further examination of an icteric baby to ensure that the mother has enough milk without measuring the bilirubin level. The MoH guideline recommends referring the baby when it looks yellow on the soles and palms. The WHO and IPS guidelines recommend combining VE with an objective measurement of transcutaneous or serum bilirubin. The threshold to begin phototherapy in the WHO guideline is lower than the IPS guideline while the exchange transfusion threshold in both guidelines are comparably equal. Conclusions: The MoH guideline is outdated. MoH and IPS guidelines are causing differences in approaches to the management hyperbilirubinemia. A new, uniform guideline is required.

Effect of tactile-kinesthetic stimulation on growth, neurobehavior and development among preterm neonates.

BACKGROUND: Preterm neonates are at risk of delayed growth and development. Hence, early tactile-kinesthetic stimulation (TKS) is required to improve their growth and development. OBJECTIVE: To evaluate the effect of TKS on growth, neurobehavior and development among preterm neonates. METHOD: An interventional study was conducted from August 2015 to July 2017 in the neonatal unit of Dr. Cipto Mangunkusumo Hospital. Preterm neonates were recruited via random sampling and divided into two groups (the intervention group and control group). TKS was performed for 15 min, three times a day, for 10 days. The anthropometric measurements, neurobehavior (Dubowitz score) and development (Capute Scale score) of neonates in both groups were assessed. RESULTS: There were 126 preterm neonates (n = 63 in each group). During the 10-day TKS period, the intervention group had a significant increment in weight and length compared to the control group (p < 0.05) at 11-14 days, at term and 3 months. Moreover, increased tone, reflexes, and improvement in behavior based on the Dubowitz score were observed during monitoring. However, the result did not differ significantly (p > 0.05). There was no significant difference in terms of cognitive and language development in both groups (Developmental Quotient of Clinical Linguistic Adaptive Milestone Scale, Developmental Quotient of Clinical Adaptive Test and Full Scale Developmental Quotient scores, p > 0.05). CONCLUSION: TKS was significantly effective in promoting growth, particularly weight and length, among preterm neonates. However, it did not significantly influence neurobehavior and development at 3 months of chronological age.

Validation of the vasoactive-inotropic score in predicting pediatric septic shock mortality: A retrospective cohort study.

INTRODUCTION: Mortality in pediatric septic shock remains very high. Vasoactive-inotropic score (VIS) is widely used to predict prognosis in patients with heart disease. It is a simple method that was initially used as a predictor of morbidity and mortality in postoperative patients with congenital heart diseases. Previous reports showed that high VIS score was associated with high mortality in pediatric sepsis. However, its discriminative value remains unclear. We aim to explore the discriminative value of VIS in predicting mortality in pediatric septic shock patients. METHODS: We conducted a retrospective cohort study on medical records of septic shock patients who received care in the pediatric intensive care unit (PICU). We screened medical records of pediatric patients which were diagnosed with septic shock and admitted to the PICU and received vasoactive/inotropic score for more than 8 h. Other supporting examination results were recorded, such as organ function evaluation for calculation of Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. The outcome of patients was recorded. The receiver operating curve was constructed to calculate the area under the curve (AUC), sensitivity, and specificity of each cutoff point. RESULTS: We obtained the optimum cutoff point of VIS > 11 with 78.87% sensitivity and 72.22% specificity. AUC positive was 0.779 (P < 0.001); predictive value and negative predictive value were 91.80% and 46.43%, respectively. CONCLUSION: VIS > 11 has a good ability to predict mortality in children with septic shock.