Single Center Outcome of Multiple Births in the Premature and Very Low Birth Weight Cohort in Singapore.

OBJECTIVE: The aim of this study is to compare neonatal mortality and morbidity in multiple and singleton preterm/very low birthweight (PT/VLBW) multiethnic Asian infants. STUDY DESIGN: Cohort study of 676 singleton and 299 multiple PT/VLBW infants born between 2008 and 2012 at KK Women's and Children's Hospital, the largest tertiary perinatal center in Singapore with further stratification by gestational ages 23 to 25 (Group 1), 26 to 28 (Group 2), and ≥29 (Group 3) weeks. Outcome measures included predischarge mortality and major neonatal morbidity. RESULTS: Overall survival to discharge was comparable for singletons 611/676 (90%) and multiples 273/299 (91%). Use of assisted reproductive technologies (47 vs. 4%), antenatal steroids (80 vs. 68%), and delivery by cesarean section (84 vs. 62%) were significantly higher (p < 0.001) in multiples while pregnancy induced hypertension (8.7 vs. 31.6%, p < 0.001) and maternal chorioamnionitis (31 vs. 41%, p < 0.01) were seen less commonly compared with singleton pregnancies. Survival was comparable between singletons and multiples except for a lower survival in multiples in Group 2 (81.7 vs. 92.4%, p = 0.007). Major neonatal morbidities were comparable for multiples and singletons in the overall cohort. Presence of hemodynamically significant patent ductus arteriosus (HsPDA) requiring treatment (88.9 vs. 72.5%), air leaks (33 vs. 14.6%, p = 0.02), NEC (30 vs. 14.6%, p = 0.04), and composite morbidity (86 vs. 66%, p = 0.031) were significantly higher in multiples in Group 1. A significantly higher incidence of HsPDA (68.1 vs. 52.4%, p = 0.008) was also observed in multiples in Group 2. Multiple pregnancy was not an independent predictor of an adverse outcome on regression analysis (OR: 0.685, 95% confidence interval: 0.629-2.02) even in GA ≤25 weeks. CONCLUSION: Neonatal mortality and morbidity were comparable in our cohort of PT/VLBW singletons and multiple births, but preterm multiple births ≤25 weeks had a higher incidence of neonatal morbidity. KEY POINTS: · Use of assisted reproductive technologies was significantly higher in multiples as compared to singletons.. · Major neonatal morbidities and mortality were similar between singletons and multiples in our cohort.. · In gestations less than 25 weeks multiples had higher neonatal morbidities than their singleton counterparts..

Standardised neonatal parenteral nutrition formulations - Australasian neonatal parenteral nutrition consensus update 2017.

BACKGROUND: The first consensus standardised neonatal parenteral nutrition formulations were implemented in many neonatal units in Australia in 2012. The current update involving 49 units from Australia, New Zealand, Singapore, Malaysia and India was conducted between September 2015 and December 2017 with the aim to review and update the 2012 formulations and guidelines. METHODS: A systematic review of available evidence for each parenteral nutrient was undertaken and new standardised formulations and guidelines were developed. RESULTS: Five existing preterm Amino acid-Dextrose formulations have been modified and two new concentrated Amino acid-Dextrose formulations added to optimise amino acid and nutrient intake according to gestation. Organic phosphate has replaced inorganic phosphate allowing for an increase in calcium and phosphate content, and acetate reduced. Lipid emulsions are unchanged, with both SMOFlipid (Fresenius Kabi, Australia) and ClinOleic (Baxter Healthcare, Australia) preparations included. The physicochemical compatibility and stability of all formulations have been tested and confirmed. Guidelines to standardise the parenteral nutrition clinical practice across facilities have also been developed. CONCLUSIONS: The 2017 PN formulations and guidelines developed by the 2017 Neonatal Parenteral Nutrition Consensus Group offer concise and practical instructions to clinicians on how to implement current and up-to-date evidence based PN to the NICU population.

Maternal Night-Fasting Interval during Pregnancy Is Directly Associated with Neonatal Head Circumference and Adiposity in Girls but Not Boys.

Background: Synchrony between daily feeding-fasting signals and circadian rhythms has been shown to improve metabolic health in animals and adult humans, but the potential programming effect on fetal growth is unknown.Objective: We examined the associations of the maternal night-fasting interval during pregnancy with offspring birth size and adiposity.Methods: This was a cross-sectional study of mother-offspring dyads within the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. For 384 mothers aged 30.8 ± 4.8 y (mean ± SD), the night-fasting interval at 26-28 wk of gestation was determined from a 3-d food diary based on the average of the fasting duration at night (1900-0659). Offspring birth weight, length, and head circumference were measured and converted to weight-for-gestational age (GA), length-for-GA, and head circumference-for-GA z scores, respectively, by using local customized percentile charts. The percentage of neonatal total body fat (TBF) was derived by using a validated prediction equation. Multivariable general linear models, stratified by child sex, were performed.Results: The mean ± SD maternal night-fasting interval was 9.9 ± 1.3 h. In infant girls, each 1-h increase in the maternal night-fasting interval was associated with a 0.22-SD (95% CI: 0.05-, 0.40-SD; P = 0.013) increase in birth head circumference-for-GA and a 0.84% (95% CI: 0.19%, 1.49%; P = 0.012) increase in TBF at birth, after adjustment for confounders. In infant boys, no associations were observed between the maternal night-fasting interval and birth size or TBF.Conclusions: An increased maternal night-fasting interval in the late second trimester of pregnancy is associated with increased birth head circumference and TBF in girls but not boys. Our findings are in accordance with previous observations that suggest that there are sex-specific responses in fetal brain growth and adiposity, and raise the possibility of the maternal night-fasting interval as an underlying influence. This trial was registered at clinicaltrials.gov as NCT01174875.

Meconium Peritonitis: Correlation of Antenatal Diagnosis and Postnatal Outcome - An Institutional Experience over 10 Years.

OBJECTIVE: To identify the fetal and neonatal imaging characteristics of meconium peritonitis (MP) and their clinical outcome. We also studied the role of prenatal ultrasound (US) in antenatal diagnosis and its use in predicting the need for surgical intervention postnatally. MATERIAL AND METHODS: We conducted a retrospective analysis of a cohort of 18 infants with MP from April 2004 to March 2014. RESULTS: Prenatal US detected MP-related abnormalities in 15/18 (83.3%) fetuses. The median gestational age at initial diagnosis of MP was 24 weeks (range 19-31). Fetal ascites (93.3%) was the most common prenatal US finding. Of the 18 infants, 12 (66.7%) required surgical intervention. The overall survival rate was 94.4%. All infants with a prenatal US scan showing meconium pseudocyst or bowel dilatation required surgical intervention postnatally. DISCUSSION: A combination of ascites, intraperitoneal calcification, and echogenic bowel on fetal US raises a high suspicion of MP. Surgical intervention is indicated in the presence of meconium pseudocyst on fetal or postnatal US scan. Antenatal US has high specificity (100%) but low sensitivity (22.2%) in detecting meconium pseudocyst. A favorable outcome can be expected with early antenatal diagnosis and timely surgical intervention in a tertiary hospital.

Ethnic differences translate to inadequacy of high-risk screening for gestational diabetes mellitus in an Asian population: a cohort study.

BACKGROUND: Universal and high-risk screening for gestational diabetes mellitus (GDM) has been widely studied and debated. Few studies have assessed GDM screening in Asian populations and even fewer have compared Asian ethnic groups in a single multi-ethnic population. METHODS: 1136 pregnant women (56.7% Chinese, 25.5% Malay and 17.8% Indian) from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study were screened for GDM by 75-g oral glucose tolerance test (OGTT) at 26-28 weeks of gestation. GDM was defined using the World Health Organization (WHO) criteria. High-risk screening is based on the guidelines of the UK National Institute for Health and Clinical Excellence. RESULTS: Universal screening detected significantly more cases than high-risk screening [crude OR 2.2 (95% CI 1.7-2.8)], particularly for Chinese women [crude OR = 3.5 (95% CI 2.5-5.0)]. Pre-pregnancy BMI > 30 kg/m2 (adjusted OR = 3.4, 95% CI 1.5-7.9) and previous GDM history (adjusted OR = 6.6, 95% CI 1.2-37.3) were associated with increased risk of GDM in Malay women while GDM history was the only significant risk factor for GDM in Chinese women (adjusted OR = 4.7, 95% CI 2.0-11.0). CONCLUSION: Risk factors used in high-risk screening do not sufficiently predict GDM risk and failed to detect half the GDM cases in Asian women. Asian women, particularly Chinese, should be screened to avoid under-diagnosis of GDM and thereby optimize maternal and fetal outcomes.

Concurrent validity of the ages and stages questionnaires with Bayley Scales of Infant Development-III at 2 years - Singapore cohort study.

BACKGROUND: With increasing acceptance of universal developmental screening in primary care, it is essential to evaluate the local validity and psychometric properties of commonly used questionnaires like the parent-completed Ages and Stages Questionnaires, 3rd Edition (ASQ-3) in identifying developmental delays. The aim of this study is to assess the convergent validity of the ASQ-3 with the Bayley Scales of Infant Development-3rd edition (Bayley-III) in identifying developmental delay in a low-risk term cohort in Singapore. METHODS: ASQ-3 and Bayley-III data was collected prospectively with generation of ASQ-3 cut-off scores using three different criteria: 1-standard deviation (SD) (Criterion-I) or 2-SD (Criterion-II) below the mean, and using a Receiver Operator Curve (ROC) (Criterion-III). Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. Correlations between the ASQ-3 and Bayley-III domains were evaluated using Pearson coefficients. RESULTS: With all three criteria across different domains ASQ-3 showed high specificity (72-99%) and NPV (69-98%), but lower sensitivity (19-74%) and PPV (11-59%). Criterion-I identified 11-21% of children as "at-risk of developmental delay," and was the most promising criterion measure, with high specificity (82-91%), NPV (69-74%) and overall agreement of 64-71%. Moderate-strong correlations were seen between ASQ-3 Communication and Bayley-III Language scales (r = 0.44-0.59, p < 0.01). The lowest sensitivities were seen in the motor domains. CONCLUSIONS: ASQ-3 is reliable in low-risk settings in identifying typically developing children not at risk of developmental delay, but it has modest sensitivity. Moderate-strong correlations seen in the communication domain are clinically important for early identification of language delay, which is one of the most prevalent areas of early childhood developmental delay.

Colorimetric CO2 Detector to Improve Effective Mask Ventilations in Very Preterm Infants: A Pilot Randomized Controlled Study.

INTRODUCTION: End-tidal CO2 (ETCO2) detector is currently recommended for confirmation of endotracheal tube placement during neonatal resuscitation. Whether it is feasible to use ETCO2 detectors during mask ventilation to reduce risk of bradycardia and desaturations, which are associated with increased risk of death in preterm babies, is unknown. METHODS: This is a pilot randomized controlled trial (NCT04287907) involving newborns 24 + 0/7 to 32 + 0/7 weeks gestation who required mask ventilation at birth. Infants were randomized into groups with or without colorimetric ETCO2 detectors. Combined duration of any bradycardia (<100 bpm) and time below prespecified target oxygen saturation (SpO2) as measured by pulse oximetry were compared. RESULTS: Fifty participants were randomized, 47 with outcomes analysed (2 incomplete data, 1 postnatal diagnosis of trachea-oesophageal fistula). Mean gestational age and birthweight were 28.5 ± 1.9 versus 29.4 ± 1.6 weeks (p = 0.1) and 1,252.7 ± 409.7 g versus 1,334.6 ± 369.1 g (p = 0.5) in the intervention and control arm, respectively. Mean combined duration of bradycardia and desaturation was 276.7 ± 197.7 s (intervention) and 322.7 ± 277.7 s (control) (p = 0.6). Proportion of participants with any bradycardia or desaturation at 5 min were 38.1% (intervention) and 56.5% (control) (p = 0.2). No chest compressions, epinephrine administration, or death occurred in the delivery room. CONCLUSION: This pilot study demonstrates the feasibility of a trial to evaluate colorimetric ETCO2 detectors during mask ventilation of very preterm infants to reduce bradycardia and low SpO2. Further assessment with a larger population will be required to determine if ETCO2 detector usage at resuscitation reduces risk of adverse outcomes, including death and disability, in very preterm infants.

Exploring the validity of the ASQ-SE for socio-emotional competency screening of a low-risk Asian cohort at 2 years of age.

AIMS: To assess the Ages & Stages Questionnaire: Social-Emotional (ASQ-SE)'s concurrent validity in a low-risk Singapore cohort and study its association with maternal mental health status. METHODS: Concurrent validity of the parent-filled ASQ-SE with Child Behavior Checklist (CBCL1.5-5) was evaluated in 341 children at age 24 months. Data on maternal anxiety and depression were collected using the State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory-Second Version (BDI-II). ASQ-SE cut-off scores based on receiver operating characteristic curve were compared to CBCL scores to derive a local ASQ-SE "at risk" cut-off score. Correlations of ASQ-SE with CBCL scores and with maternal STAI and BDI scores were evaluated using Pearson coefficients. RESULTS: Using a cut-off score of 51 at 24 months, ASQ-SE had acceptable concurrent validity, with an AUC of 0.819(0.765-0.872), 70 % sensitivity and 79 % specificity. Mothers of children with "at-risk" ASQ-SE scores had significantly higher STAI and BDI-II scores. ASQ-SE had moderate- high correlations (r = 0.32-0.53) (p < .01) with CBCL scores at 24 and 48 months and with maternal mental health status(r = 0.32). INTERPRETATION: ASQ-SE can be a useful tool for screening child's socio-emotional competence for primary health care use in Singapore Dyadic mental health screening would be helpful in identifying families at risk.

Serial tissue Doppler imaging in the evaluation of bronchopulmonary dysplasia-associated pulmonary hypertension among extremely preterm infants: a prospective observational study.

Objectives: To evaluate serial tissue Doppler cardiac imaging (TDI) in the evolution of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) among extremely preterm infants. Design: Prospective observational study. Setting: Single-center, tertiary-level neonatal intensive care unit. Patients: Infant born <28 weeks gestation. Main outcome measures: Utility of TDI in the early diagnosis and prediction of BPD-PH and optimal timing for screening of BPD-PH. Results: A total of 79 infants were included. Of them, 17 (23%) had BPD-PH. The mean gestational age was 25.9 ± 1.1 weeks, and mean birth weight was 830 ± 174 g. The BPD-PH group had a high incidence of hemodynamically significant patent ductus arteriosus (83% vs. 56%, p < 0.018), longer oxygen days (96.16 ± 68.09 vs. 59.35 ± 52.1, p < 0.008), and prolonged hospital stay (133.8 ± 45.9 vs. 106.5 ± 37.9 days, p < 0.005). The left ventricular eccentricity index (0.99 ± 0.1 vs. 1.1 ± 0.7, p < 0.01) and the ratio of acceleration time to right ventricular ejection time showed a statistically significant trend from 33 weeks (0.24 ± 0.05 vs. 0.28 ± 0.05, p < 0.05). At 33 weeks, the BPD-PH group showed prolonged isovolumetric contraction time (27.84 ± 5.5 vs. 22.77 ± 4, p < 0.001), prolonged isovolumetric relaxation time (40.3 ± 7.1 vs. 34.9 ± 5.3, p < 0.003), and abnormal myocardial performance index (0.39 ± 0.05 vs. 0.32 ± 0.03, p < 0.001). These differences persisted at 36 weeks after conceptional gestational age. Conclusions: TDI parameters are sensitive in the early evolution of BPD-PH. Diagnostic accuracy can be increased by combining the TDI parameters with conventional echocardiographic parameters. BPD-PH can be recognizable as early as 33-34 weeks of gestation.

Watchful waiting versus pharmacological management of small-for-gestational-age infants with hyperinsulinemic hypoglycemia.

Introduction: Given that reports on severe diazoxide (DZX) toxicity are increasing, we aimed to understand if the short-term clinical outcomes of small-for-gestational-age (SGA) infants with hyperinsulinemic hypoglycemia (HH) managed primarily by supportive care, termed watchful waiting (WW), are different from those treated with DZX. Method: A real-life observational cohort study was conducted from 1 September 2014 to 30 September 2020. The WW or DZX management decision was based on clinical and biochemical criteria. We compared central line duration (CLD), postnatal length of stay (LOS), and total intervention days (TIDs) among SGA-HH infants treated with DZX versus those on a WW approach. Fasting studies determined the resolution of HH. Result: Among 71,836 live births, 11,493 were SGA, and 51 SGA infants had HH. There were 26 and 25 SGA-HH infants in the DZX and WW groups, respectively. Clinical and biochemical parameters were similar between groups. The median day of DZX initiation was day 10 of life (range 4-32), at a median dose of 4 mg/kg/day (range 3-10). All infants underwent fasting studies. Median CLD [DZX, 15 days (6-27) vs. WW, 14 days (5-31), P = 0.582] and postnatal LOS [DZX, 23 days (11-49) vs. WW, 22 days (8-61), P = 0.915] were comparable. Median TID was >3-fold longer in the DZX than the WW group [62.5 days (9-198) vs. 16 days (6-27), P < 0.001]. Conclusion: CLD and LOS are comparable between WW and DZX groups. Since fasting studies determine the resolution of HH, physicians should be aware that clinical intervention of DZX-treated SGA-HH patients extends beyond the initial LOS.

Burden of antibiotic resistance in infections among very-low-birthweight infants in Singapore.

Introduction: Recent reports have described the increasing predominance of Gram-negative organisms among invasive bacterial infections affecting preterm infants. This changing pattern of infections is concerning due to the spread of antibiotic resistance among Gram-negatives. Method: We conducted a single-centre, retrospective cohort study involving very-low-birthweight (VLBW) (<1500 grams) infants born <32 weeks gestation, with culture-proven infections (blood, urine, cerebrospinal fluid [CSF]) in the neonatal intensive care unit from 1 January 2005 to 31 October 2017. Results: A total of 278 out of 2431 (11.4%) VLBW infants born <32 weeks gestation developed 334 infections, i.e. 52 (15.6%) early-onset infections (EOIs) and 282 (84.4%) late-onset infections (LOIs). The overall incidence decreased from 247 to 68 infections per 1000 infants over the study period, corresponding to reductions in LOI (211 to 62 infections per 1000 infants). A total of 378 bacteria were isolated, i.e. Gram-negatives accounted for 70.9% (45 of 59 [76.3%] EOI; 223 of 319 [69.9%] LOI). Specific resistant organisms were noted, i.e. Methicillin-resistant Staphylococcus aureus (8 of 21 S. aureus infections [38.1%]); Cephalosporin-resistant Klebsiella (18 of 62 isolates [29.0%]) and multidrug-resistant [MDR] Acinetobacter (10 of 27 isolates [37.0%]). MDR organisms accounted for 85 of 195 (43.6%) Gram-negative infections from the bloodstream and CSF. Based on laboratory susceptibility testing, only 63.5% and 49.3% of infecting bacteria isolated in blood were susceptible to empiric antibiotic regimens used for suspected EOI and LOI, respectively. Conclusion: Gram-negative bacteria are the predominant causative organisms for EOI and LOI and are frequently MDR. Understanding the pattern of antimicrobial resistance is important in providing appropriate empiric coverage for neonatal infections.

Trends in neonatal mortality and morbidity in very-low-birth-weight (VLBW) infants over a decade: Singapore national cohort study.

BACKGROUND: Very preterm infants are at risk for neurodevelopmental impairment because of postnatal morbidities. This study aims to (1) compare the outcomes of very-low-birth-weight (VLBW) infants in Singapore during two time periods over a decade; 2) compare performances among Singaporean neonatal intensive care units (NICUs); and 3) compare a Singapore national cohort with one from the Australian and New Zealand Neonatal Network (ANZNN). METHODS: Singapore national data on VLBW infants born during two periods, 2007-2008 (SG2007, n = 286) and 2015-2017 (SG2017, n = 905) were extracted from patient medical records. The care practices and clinical outcomes among three Singapore NICUs were compared using SG2017 data. Third, using data from the ANZNN2017 annual report, infants with gestational age (GA) ≤29 weeks in SG2017 were compared with their Oceania counterparts. RESULTS: SG2017 had 9.9% higher usage of antenatal steroids (p < 0.001), 8% better survival for infants ≤26 weeks (p = 0.174), and used 12.7% lesser nonsteroidal anti-inflammatory drugs for patent ductus arteriosus closure (p < 0.001) than those of SG2007 cohort. Rate of late-onset sepsis (LOS) was almost halved (7.4% vs. 14.0%, p < 0.001), and exclusive human milk feeding after discharge increased threefold (p < 0.001). SG2017, in contrast, had a higher rate of chronic lung disease (CLD) (20.0% vs. 15.1%, p = 0.098). Within SG2017, the rates of LOS, CLD, and human milk feeding varied significantly between the three NICUs. When compared with ANZNN2017, SG2017 had significantly lower rates of LOS for infants ≤25 weeks (p = 0.001), less necrotizing enterocolitis for infants ≤27 weeks (p = 0.002), and less CLD across all GA groups. CONCLUSION: Postnatal morbidities and survival rates for VLBW infants in Singapore have improved over a decade. Outcomes for VLBW infants varied among three Singapore NICUs, which provide a rationale for collaboration to improve clinical quality. The outcomes of Singaporean VLBW infants were comparable to those of their ANZNN counterparts.

Consensus statement on Singapore Perinatal Mental Health Guidelines on Depression and Anxiety.

Introduction: Perinatal depression and anxiety are public health concerns affecting approximately 1 in 10 women in Singapore, with clear evidence of association with various adverse outcomes in mother and child, including low birthweight, preterm birth and negative impact on infant neurodevelopment, temperament and behaviour. A workgroup was formed to develop recommendations to address the perinatal mental health needs of women with depression and anxiety. The approach was broad-based and aimed to incorporate holistic methods that would be readily applicable to the network of care providers supporting childbearing women. Method: The Grading and Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision framework was employed to draw these guidelines. Workgroup members-comprising experts in the field of perinatal mental health and obstetric medicine-deliberated on the public health needs of the target population, and reviewed literature published from 2001 to 2022 that were relevant to improve the well-being of women with depression and anxiety during the preconception and perinatal periods. Results: A consensus meeting was held involving a wider professional network, including family physicians, paediatricians, psychiatrists, social services and the Health Promotion Board in Singapore. Conclusion: Ten consensus statements were developed, focusing on the overall aim of achieving optimal perinatal mental health for women with depression and anxiety. They relate to awareness and advice on preconception mental health, screening and assessment, optimising care and treatment. Special considerations were recommended for women who suffered severe maternal events, tailoring care for adolescents and women with special needs, and addressing infant mental health needs.

Consensus statement on Singapore integrated 24-hour activity guide for early childhood.

Introduction: Early childhood is a critical period for growth and development. Adopting healthy lifestyle behaviours during this period forms the foundation for future well-being and offers the best protection against non-communicable diseases. Singapore studies have shown that many young children are not achieving the recommendations on physical activity, sedentary behaviour and sleep. A workgroup was set up to develop recommendations for caregivers of infants, toddlers and preschoolers (aged <7 years) on how to integrate beneficial activities within a daily 24-hour period for optimal development and metabolic health. Method: The Grading of Recommendations Assessment, Development and Evaluation (GRADE)- ADOLOPMENT approach was employed for adoption, adaption or de novo development of recommendations. International and national guidelines were used as references, and an update of the literature reviews up to September 2021 was conducted through an electronic search of PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Results: Four consensus statements were developed for each age group: infants, toddlers and preschoolers. The statements focus on achieving good metabolic health through regular physical activity, limiting sedentary behaviour, achieving adequate sleep and positive eating habits. The 13th consensus statement recognises that integration of these activities within a 24-hour period can help obtain the best results. Conclusion: This set of recommendations guides and encourages caregivers of Singapore infants, toddlers and preschoolers to adopt beneficial lifestyle activities within each 24-hour period.

Safety and efficacy of low-dose diazoxide in small-for-gestational-age infants with hyperinsulinaemic hypoglycaemia.

OBJECTIVES: Diazoxide (DZX) is the drug of choice for treating hyperinsulinaemic hypoglycaemia (HH), and it has potentially serious adverse effects. We studied the safety and efficacy of low-dose DZX in small-for-gestational-age (SGA) infants with HH. DESIGN: An observational cohort study from 1 September 2014 to 31 September 2020. SETTING: A tertiary Women's and Children's Hospital in Singapore. PATIENTS: All SGA infants with HH. INTERVENTION: Diazoxide, at 3-5 mg/kg/day. MAIN OUTCOME MEASURES: Short-term outcomes; adverse drug events and fasting studies to determine 'safe to go home' and 'resolution' of HH. RESULTS: Among 71 836 live births, 11 493 (16%) were SGA. Fifty-six (0.5%) SGA infants with HH were identified, of which 27 (47%) with a mean gestational age of 36.4±2 weeks and birth weight of 1942±356 g required DZX treatment. Diazoxide was initiated at 3 mg/kg/day at a median age of 10 days. The mean effective dose was 4.6±2.2 mg/kg/day, with 24/27 (89%) receiving 3-5 mg/kg/day. Generalised hypertrichosis occurred in 2 (7.4%) and fluid retention in 1 (3.7%) infant. A fasting study was performed before home while on DZX in 26/27 (96%) cases. Diazoxide was discontinued at a median age of 63 days (9-198 days), and resolution of HH was confirmed in 26/27 (96%) infants on passing a fasting study. CONCLUSION: Our study demonstrates that low-dose DZX effectively treats SGA infants with HH as measured by fasting studies. Although the safety profile was excellent, minimal adverse events were still observed with DZX, even at low doses.

Neonatal brain and physiological reactivity in preschoolers: An initial investigation in an Asian sample.

Parasympathetic nervous system (PNS) activity is important to physiological regulation. Limbic structures are important in determining what information the PNS receives, potentially influencing concurrent physiological responsivity and, ultimately, shaping PNS development. Yet, whether individual differences in these structures are linked to PNS activity in early childhood remains unclear. Here, in an exploratory capacity, we examined the association between neonatal limbic structures (i.e., the left and right amygdala and hippocampus) and preschoolers' resting-state respiratory sinus arrhythmia (RSA). RSA is a measure of heart-rate variability, a physiological marker that reflects fluctuation in the PNS and is often found predictive of emotion regulation and psychological wellbeing. Data were extracted from the "Growing Up in Singapore towards Healthy Outcomes" (GUSTO) cohort (n = 73, 39 girls). Neonatal limbic volume was collected within two weeks after birth while infants were asleep. Resting-state RSA was collected during a coloring session at 42 months of age. After controlling for potential confounders, a Bonferroni-corrected significant association between neonatal left hippocampal volume and resting-state RSA emerged wherein larger hippocampal volume was associated with higher resting-state RSA. No significant associations were present between resting-state RSA and right or left amygdala, or right hippocampal volume. These findings contribute to an increasing body of evidence aiming at enhancing our understanding of neurobiological underpinnings of parasympathetic activity and modulation. Results are also discussed with reference to ideas concerning biological sensitivity to context, as both left hippocampal volume and resting-state RSA were previously found to moderate associations between adversity and psychological function.

Risk Factors Predicting the Need for Phototherapy in Glucose 6 Phosphate Dehydrogenase-Deficient Infants in a Large Retrospective Cohort Study.

INTRODUCTION: Glucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of severe neonatal hyperbilirubinemia. This study evaluates the risk factors predicting the need for phototherapy in G6PD-deficient neonates after 72 h of age and assesses the safety of early discharge. METHODS: A retrospective cohort study of 681 full-term G6PD-deficient infants with a birth weight ≥2,500 g over 4 years was conducted. We compared the baseline characteristics, bilirubin level on day 4 (after 72 h of life), day of peak bilirubin, G6PD levels, and concomitant ABO incompatibility between the group that required phototherapy (Group A) and those who did not (Group B). RESULTS: 396 infants (58%), predominantly males, required phototherapy in the first week of life. The infants who required phototherapy had a lower median gestational age (38.3 vs. 38.7 weeks, p < 0.01) and had lower G6PD levels (2.3 ± 2.5 vs. 3 ± 3.4 IU, p < 0.05) compared to the controls. The mean day-four total serum bilirubin (TSB) levels were higher (213 ± 32 vs. 151 ± 37 µmol/L, p < 0.01), with bilirubin level peaking earlier (3 vs. 4 days of life, p < 0.01) in group A. Regression analysis identified TSB levels on day 4, Chinese race, lower gestation, and concomitant ABO incompatibility as the significant predictors for the need for phototherapy in the study population. In particular, coexisting ABO blood group incompatibility increased the risk of jaundice requiring phototherapy (OR 4.27, 95% CI: 1.98-121, p < 0.01). Day four TSB values above 180 µmol/L predicted the need for phototherapy with 86% sensitivity and 80% specificity. The findings were similar across both male and female infants with G6PD deficiency. CONCLUSION: G6PD-deficient infants with day four TSB levels of >180 µmol/L (10.5 mg/dL) and associated ABO blood group incompatibility have a higher risk of requiring phototherapy in the first week of life and should be closely monitored.

Consensus statement on Singapore integrated 24-hour activity guide for children and adolescents.

INTRODUCTION: Lifestyle activities, such as regular physical activity, are important for good metabolic health and the prevention of non-communicable diseases. Epidemiological studies highlight an increase in the proportion of overweight children in Singapore. A workgroup was formed to develop recommendations to encourage children and adolescents (aged 7-17 years) to adopt a holistic approach towards integrating beneficial activities within a daily 24-hour period for good metabolic and general health. METHODS: The Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision framework was employed to formulate the public health question, assess the evidence and draw conclusions for the guide. The evidence for international 24-hour movement guidelines, and guidelines for physical activity, sedentary behaviour, and sleep and eating habits were reviewed. An update of the literature review from August 2018 to end of September 2020 was conducted through an electronic search of Medline and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. RESULTS: Ten consensus statements were developed. The statements focused on the overall aim of achieving good metabolic health through integration of these activities and initiatives: light and moderate- to vigorous-intensity physical activity on a regular basis; muscle- and bone-strengthening activities; limiting sedentary behaviour; regular and adequate sleep; good eating habits and choosing nutritionally balanced foods and drinks; practise safety in exercise; and aiming to achieve more or all aforementioned recommendations for the best results. CONCLUSION: This set of recommendations provides guidance to encourage Singapore children and adolescents to adopt health-beneficial activities within a 24-hour period.

Asymptomatic Hyperinsulinemic Hypoglycemia and Grade 4 Intraventricular Hemorrhage in a Late Preterm Infant.

Hyperinsulinemic hypoglycemia (HH) has the potential to cause acute neurologic dysfunction and neurodevelopmental impairment. Parieto-occipital neuronal injuries have been reported in hypoglycemic infants, but intraparenchymal hemorrhage is rare. On day 5 of life, a late preterm infant was transferred to our care with recurrent asymptomatic hypoglycemia. Prior to arrival, plasma glucose levels were at a median of 1.25 mmol/L (22.5 mg/dL) in the first 6 hours of life, and he required a glucose infusion rate (GIR) of 22.6 mg/kg/min. Hyperinsulinism was confirmed in the presence of detectable insulin, low ketones, and fatty acid when hypoglycemic. A left grade 4 intraventricular hemorrhage (IVH) was noted in the cranial ultrasound scan during the workup for sepsis on the day of admission. However, magnetic resonance imaging of the brain on day 7 of life revealed extensive bilateral IVH. On day 9, he was initiated on diazoxide, and HH resolved within 48 to 72 hours, allowing increment of feeds while weaning GIR. Ventricular drain for post-hemorrhagic ventriculomegaly was advised but not performed. At 3 months, post-hemorrhagic ventriculomegaly was stable, and there were early signs of neurodevelopmental delay. After discontinuing diazoxide at 4 months of age, he passed an 8-hour fasting study confirming the resolution of HH. Severe hypoglycemia has been associated with cerebral hyperperfusion in preterm infants and potentially could cause IVH. Close monitoring and prompt intervention in preterm infants to prevent severe hypoglycemia are paramount. In addition to long-term neurodevelopmental follow-up, infants with recurrent hypoglycemia may benefit from neuroimaging and thereby early intervention if required.

A feed-centric hypoglycaemia pathway ensures appropriate care escalation in at-risk infants.

BACKGROUND: There is a lack of clarity of what constitutes the starting point of a clinical pathway for infants at-risk of hypoglycaemia. Glucose-centric pathways (GCP) identify low glucose in the first 2 hours of life that may not represent clinical hypoglycaemia and can lead to inappropriate glucose management with infusions and medications. OBJECTIVE: To study the impact of a feed-centric pathway (FCP) on the number of admissions for hypoglycaemia to level 2 special care nursery (SCN) and the need for parenteral glucose/medications, compared to GCP. METHODS: This project was conducted over 2 years, before and after switching from a GCP to FCP in our institution. FCP involves skin-to-skin care, early breast feeding, checking glucose at 2 hours and use of buccal glucose. The primary outcome was the number of SCN admissions for hypoglycaemia. Secondary outcomes include the number of infants needing intravenous glucose, medications and length of SCN stay. RESULTS: Of 23 786 live births, 4438 newborns were screened. We screened more infants at-risk for hypoglycaemia using the FCP (GCP:1462/11969, 12.2% vs FCP:2976/11817, 25.1%) but significantly reduced SCN admissions (GCP:246/1462, 16.8% vs FCP:102/2976, 3.4%; p<0.0001). Fewer but proportionally more FCP newborns required intravenous glucose (GCP: 136/246, 55% vs FCP: 88/102, 86%; p=0.000). Compared with GCP, FCP reduced the total duration of stay in SCN by 104 days per annum, reducing the cost of care. However, the mean length of SCN stay for FCP was higher (GCP:2.43 days vs FCP:3.49 days; p=0.001). There were no readmissions for neonatal hypoglycaemia to our institution. CONCLUSION: The use of FCP safely reduced SCN admissions, averted avoidable escalation of care and helped identify infants who genuinely required intravenous glucose and SCN care, allowing more efficient utilisation of healthcare resources.