The incidence of and risk factors for hyperglycemia and hypoglycemia in preterm infants receiving early-aggressive parenteral nutrition.

Introduction: Optimizing nutritional support helps prevent extra uterine growth restriction and adverse long-term outcomes in preterm infants. Objectives: This study aimed to analyze the incidence of and risk factors for hyperglycemia and hypoglycemia in preterm infants receiving early-aggressive parenteral nutrition (PN). Methods: This prospective observational study included preterm infants receiving PN at the Neonatal Intensive Care Unit of Dr. Soetomo General Hospital between April 2018 and May 2019. Potential risk factors analyzed included asphyxia, sepsis, respiratory distress syndrome, multiple congenital anomalies, mortality, necrotizing enterocolitis, retinopathy of prematurity, the postoperative period, inotropic administration, glucose infusion rate (GIR) > 10-12 mg/kg/min, GIR 4-<5.5 mg/kg/min, and increase in GIR <1 mg/kg/min. Results: Of the 105 preterm infants included, hyperglycemia and hypoglycemia were found in 14 (13.3%) and 26 (24.8%) infants, respectively, with most incidents occurring in the first week (hyperglycemia: 85.7%; hypoglycemia: 88.5%). Sepsis was an independent risk factor for hyperglycemia (odds ratio [OR]: 8.743, 95% confidence interval [CI]: 2.392-31.959; P = 0.001). Hypoglycemia independent risk factors included the postoperative period (OR: 4.425, 95% CI: 1.218-16.073; P = 0.024) and use of GIR 4-<5.5 mg/kg/min (OR: 2.950, 95% CI: 1.035-8.405; P = 0.043). Conclusion: Hyperglycemia and hypoglycemia can occur in preterm infants receiving early-aggressive PN; most cases occur within the first week of life. Hypoglycemia correlated with low glucose intake, and hyperglycemia correlated with sepsis. Monitoring blood glucose levels in preterm infants receiving PN, especially in the first weeks of life, may decrease morbidity associated with hyperglycemia or hypoglycemia.

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.

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.

Neonatal resuscitation: A cross-sectional study measuring the readiness of healthcare personnel.

Background: Optimal neonatal resuscitation requires knowledge and experience on the part of healthcare personnel. This study aims to assess the readiness of hospital healthcare personnel to perform neonatal resuscitation. Methods: This was an observational study conducted in May 2021 by distributing questionnaires to nurses, midwives, doctors, and residents to determine the level of knowledge and experience of performing neonatal resuscitation. Questionnaires were adapted from prior validated questionnaires by Jukkala AM and Henly SJ. We conducted the research in four types of hospitals A, B, C, and D, which are defined by the Regulation of the Minister of Health of the Republic of Indonesia. Type A hospitals have the most complete medical services, while type D hospitals have the least medical services. The comparative analysis between participants' characteristics and the knowledge or experience score was conducted. Results: A total of 123 and 70 participants were included in the knowledge and experience questionnaire analysis, respectively. There was a significant difference (p = 0.013) in knowledge of healthcare personnel between the type A hospital (median 15.00; Interquartile Range [IQR] 15.00-16.00) and type C hospital (median 14.50; IQR 12.25-15.75). In terms of experience, the healthcare personnel of type A (median 85.00; IQR 70.00-101.00) and type B (median 92.00; IQR 81.00-98.00) hospitals had significantly (p =0,026) higher experience scores than the type D (median 42.00; IQR 29.00-75.00) hospital, but we did not find a significant difference between other type of hospitals. Conclusions: In this study, we found that the healthcare personnel from type A and type B hospitals are more experienced than those from type D hospitals in performing neonatal resuscitation. We suggest that a type D hospital should refer the neonate to a type A or type B hospital if there is sufficient time in cases of risk at need for resuscitation.

The glucose infusion rate of parenteral nutrition in the first week of life in preterm infants: an observational study.

BACKGROUND: Most preterm infants require a continuous glucose infusion in the early postnatal period due to the interruption of the transplacental glucose supply after birth to promote better neurodevelopmental outcomes. AIMS: To investigate the glucose infusion rate (GIR) on parenteral nutrition (PN) in the first week of life administered in preterm infants and its effect on neonatal morbidity and mortality. METHODS: This study included 97 infants aged < 37 gestational weeks and weighed < 2500 g at birth. Infants recruited in this study were classified into 3 groups based on the GIR usage in parenteral nutrition as follows: GIR usage of 5- < 7 g/kg/day (Group I), GIR usage of 7-13 g/kg/day (Group II), and GIR usage of > 13-15 g/kg/day (Group III). Univariate and multivariate logistic regression analyzes were carried out to investigate whether the GIR usage in the three groups was associated with selected neonatal morbidities and mortality. Neonatal morbidities analyzed included respiratory distress syndrome (RDS), necrotizing enterocolitis, sepsis, retinopathy of prematurity, pulmonary hypertension, hypoglycemia, and hyperglycemia. RESULT: Of 97 preterm infants included, 51.5% infants had a gestational age of 34- < 37 weeks, and 54.6% infants had a birth weight of 1500- < 2500 g. The multivariate logistic regression analysis showed that the GIR usage of 5- < 7 g/kg/day was an independent variable that significantly increased the risk of hypoglycemia (Adjusted Odds Ratio [AOR] = 4.000, 95% Confidence Interval [CI] = 1.384-11.565, P = 0.010) and reduced the risk of sepsis (AOR = 0.096, 95% CI = 0.012-0.757, P = 0.026). The GIR usage in all three groups did not increase the risk of mortality. For neonatal morbidity analyzed in this study, RDS (AOR = 5.404, 95%CI = 1.421-20.548, P = 0.013) was an independent risk factor of mortality. CONCLUSION: The GIR usage of < 7 g/kg/day in PN in the first week of life administered to preterm infants was an independent variable in increasing hypoglycemia, but in contrast, reducing the risk of sepsis.

Current-proven neonatal sepsis in Indonesian tertiary neonatal intensive care unit: a hematological and microbiological profile.

BACKGROUND AND OBJECTIVES: Neonatal sepsis is the third leading cause of neonatal death in the world. The patterns of pathogens causing neonatal sepsis varies in many countries. This study was aimed to identify hematological and microbiological profile of culture-proven neonatal sepsis in Indonesian tertiary neonatal intensive care unit (NICU). MATERIALS AND METHODS: Hospital based cross-sectional study was conducted in all inborn neonates that were suspected sepsis neonatal over a period of six months from April to September 2019. Complete blood count, c-reactive protein (CRP) and blood culture were examined before antibiotic administration. Statistical analysis were calculated based on Chi-Square's Test and Mann-Whitney U test and p <0.05 considered significant. RESULTS: One hundred four inborn neonates admitted to NICU and diagnosed with suspected neonatal sepsis were recruited. Culture-proven neonatal sepsis were confirmed in 52 (50%) neonates, 13 (25%) in early-onset neonatal sepsis (EONS) and 39 (75%) in late-onset neonatal sepsis (LONS). The most common abnormal hematological profile were anemia and thrombocytopenia, with amount of 61.5% and 75%, respectively. High CRP only detected in 36.4% and only 18.5% experienced leukopenia. Gram negative bacteria responsible in 75% from total isolated pathogens. Klebsiella pneumoniae accounted for 48.1% followed by coagulase negative staphylococci (CONS) for 17.3% and Enterobacter cloacae for 11.5%. CONCLUSION: Anemia and thrombocytopenia were the top two hematological profile of culture-proven neonatal sepsis. Most causes of culture-proven neonatal sepsis were Gram negative bacteria and the dominant pathogen was K. pneumoniae.

Kramer Score, an Evidence of Its Use in Accordance with Indonesian Hyperbilirubinemia Published Guideline.

Background: In some hospitals in low/middle-income countries, methods to determine the bilirubin level in newborn infants are unavailable and based on a clinical evaluation, namely a clinical score designed by Kramer. In this study, we evaluated if this score can be used to identify those infants that need phototherapy. Method: Infants admitted between November 2018 and June 2019 to three hospitals in Surabaya, Indonesia were included. The jaundice intensity was scored using the Kramer score. Blood was sampled for total serum bilirubin (TSB) measurement. The infants were categorized into Treatment Needed (TN) group when treatment with phototherapy was indicated and the No Treatment Needed (NTN) group when phototherapy was not indicated, based on the Indonesian Guideline for hyperbilirubinemia. Result: A total of 280 infants with a mean birth weight of 2744.6 ± 685.8 g and a gestational age of 37.3 ± 2.3 weeks were included. Twenty-seven of 113 (24%) infants with Kramer score 2 needed phototherapy, compared with 41 of 90 (46%) infants with score 3 and 20 of 28 (71%) of infants with score 4. The percentage of infants that needed phototherapy was higher with decreasing gestational age. Conclusion: The Kramer score is an invalid method to distinguish between those infants needing phototherapy and those infants where this treatment is not indicated.

Associated neonatal and maternal factors of osteopenia of prematurity in low resource setting: A cross-sectional study.

OBJECTIVE: Determining neonatal and maternal factors that are associated with the incidence of OFP. METHODS: This study employed a cross-sectional design, in which the participants were identified for clinical variables (sex, gestational age, birth weight, etc.), neonatal morbidity (sepsis, necrotizing enterocolitis (NEC), etc.), and maternal risk factors (premature rupture of membranes, preeclampsia, etc.). The data were analyzed using Chi-square test, independent t-test, and logistic regression test with p < 0.05. RESULTS: The birth weight ranged from 800 to 1495 g (1219 ± 225 g), of which 5 newborns (17%) were <1000 g. The gestational age ranged from 27 to 32 weeks, with a mean of 29 ± 1.5 weeks. The signs of OFP were observed in 13 (43%) infants, of which 2 (15%) OFP infants had a birth weight <1000 g. There was significant difference in parenteral nutrition duration (p = 0.018), onset of vitamin D supplementation (p = 0.019), and ALP level (p = 0.012) of infants between the OFP group and the non-OFP group. The variables associated with the incidence of OFP were parenteral nutrition duration >15 days (OR = 5.4; 95% CI 1.120-26.044; p = 0.036), ALP level >500 U/L (OR = 2.889; 95% CI 1.703-4.900; p = 0.014), and PROM (OR = 5.4; 95% CI 1.039-28.533; p = 0.045). CONCLUSION: The lack of phosphate intake, prolonged parenteral nutrition, ALP level >500 U/L, onset of vitamin D supplementation, and premature rupture of membranes are associated with the incidence of OFP.

Spontaneous Ileum Perforation in a premature twin with Coronavirus-19 positive mother.

Spontaneous intestinal perforation (SIP) of the newborn is a single intestinal perforation commonly found in the terminal ileum without distinct causes. These cases often associated with prematurity. The new COVID-19 in pregnancy increased the risk of premature rupture of membranes, preterm delivery, intrauterine fetal death (IUFD), and low birth weight (LBW). Here we report a premature twin with SIP that was born from Coronavirus-19 positive mother.

Neutrophil-to-Lymphocyte Ratio as an Alternative Marker of Neonatal Sepsis in Developing Countries.

OBJECTIVES: We sought to analyze the neutrophil-to-lymphocyte ratio (NLR) as an alternative marker of neonatal sepsis. METHODS: In this cross-sectional study, we undertook consecutive sampling in all inborn neonates admitted to the Neonatal Intensive Care Unit with clinical manifestations of neonatal sepsis. Neonates with congenital anomalies and referred neonates were excluded. Complete blood count, C-reactive protein (CRP), and blood culture were carried out as the septic workup examinations based on the local Clinical Practical Guidelines. NLR is obtained by dividing the absolute count of neutrophils from lymphocytes manually. A cut-off value of NLR is obtained using a receiver operating characteristic curve. RESULTS: The median NLR value of the 104 neonates who met the inclusion and exclusion criteria was 3.63 (2.39-6.12). Neonates with NLR of 2.12 have the area under the curve of 0.630 (95% confidence interval (CI): 0.528-0.741) and 0.725 (95% CI: 0.636-0.814) when combined with CRP = 2.70 mg/dL. Neonates with NLR ≥ 2.12 in clinical neotnatal sepsis had almost double the risk of providing positive blood culture results (relative risk = 1.867, 95% CI: 1.077-3.235; p = 0.011). CONCLUSIONS: NLR, calculated from complete blood count, can be used as an alternative marker of easy and relatively inexpensive neonatal sepsis, especially in developing countries, and detection of proven neonatal sepsis to be better when combined with CRP.

Transcutaneous bilirubin level to predict hyperbilirubinemia in preterm neonates.

Background: Hyperbilirubinemia is common in neonates, with higher prevalence among preterm neonates, which can lead to severe hyperbilirubinemia. Assessment of total serum bilirubin (TSB) and use of a transcutaneous bilirubinometer (TcB) are existing methods to identify and predict hyperbilirubinemia. This study aimed to determine TcB cut-off values during the first day for preterm neonates to predict hyperbilirubinemia at 48 and 72 hours. Methods: A total of 90 neonates born ≤35 weeks were included in the study. They were divided into two groups (Group I: 1000-1500 grams; Group II: 1501-2000 grams). The bilirubin level was measured on the sternum using TcB at the ages of 12, 24, and 72 h. TSB measurements were taken on the third day or if TcB level reached ± 1.24 mg/dL phototherapy threshold and if TcB showed abnormal results (Group I: 5.76-8.24 mg/dL; Group II: 8.76-11.24 mg/dL). Hyperbilirubinemia was defined as TSB ≥7 mg/dL for group I and >10 mg/dL for group II. Results: In total, 38 group I neonates and 48 group II neonates were observed. Almost half of neonates in group I (44.7%) were suffering from hyperbilirubinemia at the age of 48 hours, with 45.8% of group II at the age of 72 hours. To predict hyperbilirubinemia at the age of 48 hours, the best 24-hour-age TcB cut-off values were calculated to be 4.5 mg/dL for group I and 5.8 mg/dL for group II. To predict hyperbilirubinemia at the age of 72 hours, we determined 24-hour-age TcB value of 5.15 mg/dL for group II. Conclusion: TcB values in the early days of life can be used as hyperbilirubinemia predictors on the following days for preterm neonates. Close monitoring should be managed for those with TcB values higher than the calculated cut-off values.

Effect of enteral glutamine supplementation for low-birth-weight infants on weight gain patterns and levels of fecal secretory immunoglobulin A.

AIM: Glutamine is needed for optimal cell growth and for the immune system, especially in the enterocytes of gut mucosal immune responses. Low birth weight makes infants susceptible to glutamine depletion because nutrition is limited in the first week of life. To determine the effect of enteral glutamine supplementation on weight gain patterns and fecal secretory immunoglobulin A. MATERIAL AND METHODS: This study is a double-blind, randomized controlled trial. Infants were randomly assigned to the glutamine group and placebo group. The glutamine group was supplemented with glutamine 400 mg/kg/day for 14 days, and placebo group received glucose 400 mg/kg/day for 14 days. The infants were observed for 30 days. Return-to-birth-weight, weight gain velocity, and fecal secretory immunoglobulin A levels were monitored during the study. RESULTS: Thirty-seven low-birth-weight infants were randomly assigned to the glutamine and placebo groups. The glutamine group had a shorter return-to-birth-weight time than the placebo group (8.1±0.9 vs. 11.0±1.6 days) and faster weight gain velocity (20.0±1.8 vs. 15.5±2.2 g/kg/day) (p<0.001). Secretory immunoglobulin A levels after glutamine supplementation were higher than in the placebo group (0.456±0.057 vs. 0.376±0.035 mg/g) (p<0.001). Levels of secretory immunoglobulin A after treatment in each group were increased. However, there was a significant difference before and after supplementation between the glutamine and placebo groups (0.247±0.024 vs. 0.140±0.016 mg/g) (p<0.001). CONCLUSION: Enteral glutamine supplementation in low-birth-weight infants accelerates return to birth weight, increases the weight gain velocity, and the levels of fecal secretory immunoglobulin A.