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.

Association between glial fibrillary acidic protein, glial-derived neurotrophic factor, and fatty acid-binding protein-2 at birth in the incidence of necrotizing enterocolitis in preterm infants.

Background: This study aimed to analyze the relationship between glial fibrillary acidic protein (GFAP), glial-derived neurotrophic factor (GDNF), and fatty acid-binding protein-2 (FABP-2) in preterm infants on the incidence of NEC. Methods: Preterm infants with a birth weight <1,500 g and gestational age <34 weeks were included in this study. Biomarker examination was performed using the umbilical vein blood at birth (first sample). Biomarker examination was repeated if the infant developed symptoms of NEC using peripheral vein blood (second sample). Infants were observed for 14 days. If NEC did not exist, a biomarker examination was performed at 14 days. Results: This study included 30 preterm infants, nine infants experienced NEC. The values of GFAP, GDNF, and FABP-2 (median and range) in the group with NEC were higher than those in the group without NEC in both the first samples {GFAP [1.40 (0.20-6.50) vs. 0.30 (0.10-1.30) P = 0.014], GDNF [2.84 (1.05-14.11) vs. 1.56 (1.07-3.48) P = 0.050], and FABP-2 [621.70 (278.40-2,207.00) vs. 294.20 (211.40-597.50) P = 0.002]} and second samples {GFAP [2.40 (0.30-3.10) vs. 0.30 (0.10-0.60) P = 0.003], GDNF [2.99 (0.56-10.30) vs. 1.46 (0.85-2.24) P = 0.019], and FABP-2 [646.8 (179.20-1,571.00) vs. 314.90 (184.70-521.60) P = 0.040]}. In infants with NEC, the median values of GFAP [2.40 (0.30-3.10) vs. 1.40 (0.20-6.50) P = 0.767], GDNF [2.99 (0.56-10.30) vs. 2.84 (1.05-14.11) P = 0.859], and FABP-2 [646.80 (179.20-1,571.00) vs. 621.70 (278.40-2,207.00) P = 0.953] in the second sample were higher than those in the first sample. Logistic regression demonstrated that GFAP at birth (Odds Ratio [OR] = 15.629, 95% Confidence Interval [CI] = 1.697-143.906, P = 0.015) and FABP-2 levels at birth (OR = 1.008, 95% CI = 1.001-1.015, P = 0.033) were significantly associated with an increased risk of NEC. Conclusion: Increased GFAP, GDNF, and FABP-2 at birth are associated with NEC occurrence within two weeks of birth. These findings suggest that early-onset NEC is associated with intestinal injury that occurs during the perinatal or even prenatal period.

Observational study on necrotizing enterocolitis in neonates born to SARS-CoV-2-positive mothers.

Background: The impact of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic on expectant mother and their babies extends to many aspects of life. Necrotizing enterocolitis (NEC) has been recognized as a life-threatening gastrointestinal inflammatory process in neonates that has high rates of morbidity and mortality. Objective: To investigate factors associated with NEC in hospitalized neonates whose mothers were SARS-CoV-2-positive and their relationship to mortality. Method: This observational study was conducted from May 2020 to March 2021. All neonates who were hospitalized, after confirming that the mother was SARS-CoV-2-positive, were included in this study. The confirmation of positive SARS-CoV-2 was determined according to the reverse transcription-polymerase chain reaction (PCR) assay. The neonatal SARS-CoV-2 test was performed on the first day of birth. NEC was established based on a suggestive clinical presentation and abnormal abdominal radiographs. Results: Of the 125 neonates enrolled in this study, there were 5 neonates who developed NEC and only one survived. Significant associated factors with NEC included lower birth weight (p < 0.001), lower gestational age (p < 0.001), positive SARS-CoV-2 PCR results (OR = 15.333; 95% CI = 2.074-113.381, p = 0.007), asphyxia (OR = 13.143; 95% CI = 1.411-122.443, p = 0.024), and mortality (OR = 156.000; 95% CI = 13.157-1849.623; p < 0.001). Mortality was significantly associated with lower gestational age (p = 0.025), cesarean section delivery (p = 0.025), and asphyxia (p = 0.025). Conclusion: Significant associated factors with NEC in neonates born to SARS-CoV-2-positive mothers included positive SARS-CoV-2 PCR results, asphyxia, lower gestational age, and lower birth weight. In addition to caesarean section delivery, these factors were related to mortality in neonates in such conditions.

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.

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.

The incidence of osteopenia of prematurity in preterm infants without phosphate supplementation: A prospective, observational study.

ABSTRACT: To meet their requirements for bone mineralization, it is recommended that preterm infants receive nutritional support containing calcium and phosphate. There are no clear data on the incidence of osteopenia of prematurity (OFP) in preterm infants without phosphate supplementation.This study aimed to investigate the incidence of OFP in preterm infants without phosphate supplementation and its relationship with the duration of parenteral nutrition (PN).This was a prospective and observational study.This study included 30 infants aged <32 gestational weeks and weighed <1500 g at birth. All infants received PN according to a standard protocol, beginning on day 1 with calcium, without phosphate. Starting from the first day of life, all infants received human milk without fortifiers. Oral vitamin D (400 IU/d) was administered when enteral nutrition reached 100 mL/kg/d.The diagnosis of OFP was based on radiographs that were taken of both wrists. Serum alkaline phosphatase (ALP) was measured 3 times: at the start of PN (ALP 1), at the end of PN (ALP 2), and at discharge or the expected due date (ALP 3). Radiographs were obtained on the same day as ALP 3. The duration of PN was analyzed in the presence of OFP using receiver operating characteristic curve analysis.Among the 30 infants, 13 (43%) were diagnosed with OFP. The duration of PN was significantly longer in the OFP group than in the group without OFP (16 vs 12 days; P < .05). The provision of PN for >15 days significantly increased the risk of OFP (odds ratio, 5.40; 95% confidence interval, 1.12-26.04; P = .035).We found a high incidence of OFP in preterm infants without phosphate supplementation. An association was found between the duration of PN and the incidence of OFP. Further research is needed to prevent the development of osteopenia in preterm infants.

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.

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.