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Background: Length measurement in young children younger than 18 months is important for monitoring growth and development. Accurate length measurement requires proper equipment, standardized methods, and trained personnel. In addition, length measurement requires young children's cooperation, making it particularly challenging during infancy and toddlerhood., Objective: This study aimed to develop a length artificial intelligence (LAI) algorithm to aid users in determining recumbent length conveniently from smartphone images and explore its performance and suitability for personal and clinical use., Methods: This proof-of-concept study in healthy children (aged 0-18 months) was performed at KK Women's and Children's Hospital, Singapore, from November 2021 to March 2022. Smartphone images were taken by parents and investigators. Standardized length-board measurements were taken by trained investigators. Performance was evaluated by comparing the tool's image-based length estimations with length-board measurements (bias [mean error, mean difference between measured and predicted length]; absolute error [magnitude of error]). Prediction performance was evaluated on an individual-image basis and participant-averaged basis. User experience was collected through questionnaires., Results: A total of 215 participants (median age 4.4, IQR 1.9-9.7 months) were included. The tool produced a length prediction for 99.4% (2211/2224) of photos analyzed. The mean absolute error was 2.47 cm for individual image predictions and 1.77 cm for participant-averaged predictions. Investigators and parents reported no difficulties in capturing the required photos for most participants (182/215, 84.7% participants and 144/200, 72% participants, respectively)., Conclusions: The LAI algorithm is an accessible and novel way of estimating children's length from smartphone images without the need for specialized equipment or trained personnel. The LAI algorithm's current performance and ease of use suggest its potential for use by parents or caregivers with an accuracy approaching what is typically achieved in general clinics or community health settings. The results show that the algorithm is acceptable for use in a personal setting, serving as a proof of concept for use in clinical settings., Trial Registration: ClinicalTrials.gov NCT05079776; https://clinicaltrials.gov/ct2/show/NCT05079776., (©Mei Chien Chua, Matthew Hadimaja, Jill Wong, Sankha Subhra Mukherjee, Agathe Foussat, Daniel Chan, Umesh Nandal, Fabian Yap. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org), 22.11.2024.)

Background: The development of the breast for lactation occurs throughout pregnancy. It is unknown whether pregnancy complications resulting in poor fetal growth can affect breastfeeding (BF) success., Objectives: We examined whether fetal growth-related pregnancy complications were associated with earlier BF cessation and changes in the concentrations of human milk biomarkers of low milk production., Methods: We used data from the Growing Up in Singapore Toward healthy Outcomes study (n = 954). Human milk concentrations of protein, lactose, citrate, sodium, potassium, and zinc at 3 wk postpartum were available for 180 mother-infant dyads. We examined the associations of fetal growth measures, including term infants born small-for-gestational-age (SGA) (<10th percentile), pregnancies complicated by fetal growth deceleration (second to third trimester fetal growth dropped between major centiles), elevated umbilical artery resistance (>90th percentile) or hypertensive disorders of pregnancy (HDP) with 1) risk of ceasing BF (Cox regression) and 2) concentrations of human milk components (weighted linear regression)., Results: Adjusting for maternal education, smoking exposure, BF intentions, and prepregnancy BMI (in kg/m 2 ), individuals who delivered SGA infants and those with HDP were more likely to breastfeed for a shorter duration when compared to those with uncomplicated pregnancies {adjusted hazard ratio [95% confidence interval (CI)]: 1.45 (1.11, 1.89) and 1.61 (1.14, 2.29), respectively}; associations were nonsignificant for fetal growth deceleration and umbilical artery resistance. SGA was not associated with concentrations of human milk biomarkers, but compared to participants with uncomplicated pregnancies, milk produced by those with HDP contained lower zinc concentrations [adjusted β coefficient (95% CI): -0.56 mg/L (-1.08, -0.04) mg/L]., Conclusions: Individuals with HDP and those with SGA infants tend to breastfeed for a shorter duration; however, only HDP appear to be associated with biomarkers of compromised milk production. Further research and support are needed to help individuals with HDP and SGA achieve their BF goals. This trial was registered at clinicaltrials.gov as NCT01174875., Competing Interests: Conflict of interest KMG, S-YC, and Y-SC are part of an academic consortium that has received research funding from Nestec Société Anonyme (SA). C-TL and DTG receive salaries from an unrestricted research grant from Medela Aktiengesellschaft (AG) administered by The University of Western Australia. All other authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: The cognitive benefits of breastfeeding are widely recognized; however, its effects on brain development and later academic skills require further examination. This study aimed to examine the longitudinal relations between breastmilk feeding, neurophysiological changes, and early academic skills., Methods: In the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort, breastmilk feeding practices were collected every 3 months from 3 weeks to 18 months postpartum. Resting electroencephalography (EEG) was recorded at 18 months and power spectral density was derived. The outcomes were a set of early academic assessments administered at age 4 (n = 810). Structural equation modelling was used to investigate EEG power as a mediator between breastmilk duration and early academic skills., Results: Breastmilk feeding for ≥12 months was associated with better general knowledge, numeracy, and language at age 4 compared to shorter durations of breastmilk feeding (Cohen's d: 1.53-17.44). Linear regression showed that breastmilk duration was negatively and positively associated with low- (i.e., delta, theta) and high-frequency power (i.e., gamma), respectively (Cohen's f 2 : 0.03-0.09). After adjusting for demographic and child baseline covariates, a decrease in absolute and relative delta, as well as relative theta was associated with better general knowledge and numeracy (Cohen's f 2 : 0.16-0.25). Relative delta power provided an indirect path between breastmilk duration and early academic skills (x 2 : 18.390, p = 0.010; CFI: 0.978; TLI: 0.954; RMSEA: 0.040)., Conclusions: Extended breastmilk feeding is associated with reduced low-frequency power and better early academic skills, suggesting benefits to brain development. Additional research to confirm this finding is warranted., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: To mitigate the growing burden of non-communicable diseases, doctors training to become paediatricians should be equipped with concepts and knowledge regarding Developmental Origins of Health and Disease (DOHaD)., Methods: We assessed the knowledge, attitudes, and practices (KAP) of medical officers, resident physicians, as well as junior and senior residents practising in the paediatric department of a tertiary women's and children's hospital. This was done through a cross-sectional online survey, with questions developed after focused group discussions with domain experts, and responses based on a 5-point Likert scale., Results: A total of 95 physicians met the inclusion criteria, grouped into Medical Officers (MOs) and Registrars (REGs), and we received a 100% response rate. Results showed that few physicians (n = 22, 23.2%) knew the term DOHaD, and majority rated their colleagues to be inadequately informed (n = 84, 88.4%). Among the physicians, one third (n = 32, 33.7%) were not confident in their ability to counsel patients about initiating healthy feeding practices to prevent future metabolic diseases in their children. However, there was a readiness to be better equipped with DOHaD principles and knowledge, and 95.8% (n = 91) strongly acknowledged the physician's responsibility to optimise early life determinants of cardiometabolic health., Conclusion: In conclusion, the findings suggest a poor translation of DOHaD concepts, indicating that bridging the gap between DOHaD research knowledge and clinical application represents an unmet need. These principles should be inculcated early in the professional training of all healthcare providers., (© 2024. The Author(s).)

Introduction: Vaccination is critical in controlling the coronavirus disease 2019 (COVID-19) pandemic. However, vaccine perception and acceptance among pregnant and lactating women is unknown in Singapore. We aimed to determine the acceptance of COVID-19 vaccination among these two groups of women in Singapore and the factors associated with vaccine acceptance., Methods: We conducted an anonymous, online survey on the perceptions of the COVID-19 vaccine and its acceptance by pregnant and lactating women at a tertiary maternal and child hospital in Singapore from 1 March to 31 May 2021. Information on their demographics and knowledge was collected. These factors were assessed for their relationship with vaccine acceptance., Results: A total of 201 pregnant and 207 lactating women participated. Vaccine acceptance rates in pregnant and lactating women were 30.3% and 16.9%, respectively. Pregnant women who were unsure or unwilling to take the vaccine cited concerns about safety of the vaccine during pregnancy (92.9%), while lactating women were concerned about its potential long-term negative effects on the breastfeeding child (75.6%). Factors that were positively associated with vaccine acceptance included a lower monthly household income or education level, appropriate knowledge regarding vaccine mechanism and higher perceived maternal risk of COVID-19. Most pregnant (70.0%) and lactating women (83.7%) were willing to take the vaccine only when more safety data during pregnancy and breastfeeding were available., Conclusion: COVID-19 vaccine acceptance was low among pregnant and lactating women in Singapore. Addressing the safety concerns when more data are available and education on the mechanism of vaccine action will likely improve acceptance among these women., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)

This study examines relationships between breastfeeding practices and postpartum weight retention (PPWR) at 6 and 12 months postpartum among 379 first-time mothers participating in a clinical trial in Singapore. We categorized feeding modes at 6 months into exclusive breastfeeding, mixed feeding, and exclusive formula feeding. Participants were analyzed in two groups based on their PPWR assessment at 6 and 12 months postpartum, with complete datasets available for each assessment. We calculated PPWR by subtracting pre-pregnancy weight from self-reported weight at 6 and 12 months postpartum, defining substantial PPWR as ≥5 kg retention. Modified Poisson regression models adjusted for potential confounders were performed. At 6 and 12 months, 35% ( n = 132/379) and 31% ( n = 109/347) of women experienced substantial PPWR, respectively. Compared to exclusive breastfeeding, mixed feeding (risk ratio 1.85; 95% confidence interval 1.15, 2.99) and exclusive formula feeding (2.11; 1.32, 3.28) were associated with a higher risk of substantial PPWR at 6 months. These associations were slightly attenuated at 12 months and appeared stronger in women with pre-pregnancy overweight or obesity. This study suggests that breastfeeding by 6 months postpartum may help mitigate PPWR, particularly with exclusive breastfeeding. It also draws attention to targeted interventions to promote breastfeeding among women with overweight or obesity.

Objectives: The Developmental Origins of Health and Disease (DOHaD) concept has gained prominence in maternal and child health (MCH), emphasizing how early-life factors impact later-life non-communicable diseases. However, a knowledge-practice gap exists in applying DOHaD principles among healthcare professionals. Healthy Early Life Moments in Singapore (HELMS) introduced webinars to bridge this gap and empower healthcare professionals. We aimed to conduct a preliminary assessment to gain early insights into the outreach and effectiveness of the educational initiative offered with the HELMS webinars., Methods: We employed a pragmatic serial cross-sectional study approach and targeted healthcare professionals involved in MCH care. We also collected and analyzed data on webinar registration and attendance, participants' profession and organizational affiliations, and post-webinar survey responses., Results: The median webinar attendance rate was 59.6 % (25th-75th percentile: 58.4-60.8 %). Nurses represented 68.6 % of attendees (n=2,589 out of 3,774). Post-webinar surveys revealed over 75 % of the participants providing positive responses to 14 out of 15 survey questions concerning content, delivery, applicability to work, and organization., Conclusions: Assessment of the HELMS webinars provided insight into the outreach and early effectiveness in enhancing healthcare professionals' knowledge and confidence in delivering DOHaD education. Bridging the knowledge-practice gap remains a crucial goal., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Background: Gut dysbiosis contributes to the high risk of bloodstream infection (BSI) among premature infants. Most prior studies of the premature infant gut microbiota were conducted in Western countries and prior to development of current tools for strain-resolved analysis., Methods: We performed metagenomic sequencing of weekly fecal samples from 75 premature infants at a single hospital in Singapore. We evaluated associations between clinical factors and gut microbiota composition using PERMANOVA and mixed effects linear regression. We used inStrain to perform strain-level analyses evaluating for gut colonization by BSI-causing strains., Results: Median (interquartile range) gestation was 27 (25, 29) weeks, and 63% of infants were born via Cesarean section. Antibiotic exposures (PERMANOVA; R 2  = 0.017, p = 0.001) and postnatal age (R 2  = 0.015, p = 0.001) accounted for the largest amount of variability in gut microbiota composition. Increasing postnatal age was associated with higher relative abundances of several common pathogens (Enterococcus faecalis: p < 0.0001; Escherichia coli: p < 0.0001; Klebsiella aerogenes: p < 0.0001; Klebsiella pneumoniae: p < 0.0001). Antibiotic exposures were generally associated with lower relative abundances of both frequently beneficial bacteria (e.g., Bifidobacterium species) and common enteric pathogens (e.g., Enterobacter, Klebsiella species). We identified strains identical to the blood culture isolate in fecal samples from 12 of 16 (75%) infants who developed BSI, including all infections caused by typical enteric bacteria., Conclusions: Antibiotic exposures were the dominant modifiable factor affecting gut microbiota composition in a large cohort of premature infants from South-East Asia. Strain-resolved analyses indicate that the gut is an important reservoir for organisms causing BSI among premature infants., (© 2023. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chandran, Jaya-Bodestyne, Rajadurai, Saffari, Chua and Yap.)

Competing Interests: None

Introduction: Changes in social and lifestyle factors have led to increasing rates of metabolic and mental health problems. We hypothesise that a transformation of the current maternal and child health system is required to deliver interventions that effectively promote a good start to life in populations at risk of metabolic and mental health problems. We describe a single-arm implementation study 'Healthy Early Life Moments in Singapore', which aims to examine whether an integrated lifestyle intervention initiated at preconception and continuing throughout pregnancy and postpartum periods can improve the metabolic and mental health of overweight and obese women, and improve early child growth., Methods and Analysis: This single-centre implementation trial is conducted at KK Women's and Children's Hospital, Singapore. The trial aims to recruit 500 women, aged 21-40 years with a body mass index of 25-40 kg/m 2 who plan to get pregnant, with interventions delivered before conception, until 18 months postdelivery. Primary outcomes comprise pregnancy rate, maternal metabolic and mental health status. Secondary outcomes include maternal reproductive health, pregnancy outcomes and offspring growth. The intervention will be delivered using a mobile health application, to provide anticipatory guidance, raise awareness and guide goal-setting on lifestyle behaviours that include diet, physical activity, mental wellness and sleep hygiene from preconception to postpartum. Women who conceive within 1 year of recruitment will be followed through pregnancy and studied with their infants at six-time points during the first 18 months of life. Questionnaires, anthropometric measurements and multiple biosamples will be collected at each visit., Ethics and Dissemination: The study has been approved by the Centralised Institutional Review Board of SingHealth (2021/2247). Written informed consent will be obtained from all participants. The findings will be published in peer-reviewed journals and disseminated to national and international policy makers., Trial Registration Number: NCT05207059., Competing Interests: Competing interests: KG and YF received reimbursement for speaking at conferences sponsored by companies that sell nutritional products. KG is part of an academic consortium that received research funding from Abbott Nutrition, Nestle and Danone. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Perinatal Palliative Care provides comprehensive and holistic care for expectant and new parents, who receive a diagnosis of life-limiting fetal condition and opt to continue pregnancy and care for their newborn infant. Aim: To develop a service providing individually tailored holistic care during pregnancy, birth, postnatal and bereavement period. Methods: Following a baseline survey of neonatologists and discussions with key stakeholders we launched the Perinatal Palliative service at the KK Women's and Children's hospital, Singapore in January 2017. The multidisciplinary team, led by a Palliative care specialist comprised of Obstetricians, Neonatologists, nurses and medical social workers. The Birth defect clinic referred parents with antenatally diagnosed 'Lethal' fetal conditions. The team checked the understanding and the decision making process of parents and initiated and finalized advance care plans. The service also embraced deserving postnatal referrals upon request. Results: A total of 41 cases were seen from January 2017 to December 2019. Of these, 26/41(63%) were referred antenatally and had completed advance care plans. 18/41 (44%) died during or shortly after birth and 10/41(24%) continue to survive and are supported by the community palliative team. During this time a workflow was formulated and modified based on parent and team feedback. Conclusion: Awareness of the service has increased over the years and a clear workflow has been formulated. Advance care plans are prepared and documented before birth so as to enable service teams on board to provide well timed pertinent care. Feedbacks from parents about this service were positive.

In this paper, we provide guidance to clinicians who care for infants born to mothers with suspected/confirmed COVID-19 during this current pandemic. We reviewed available literature and international guidelines based on the following themes: delivery room management; infection control and prevention strategies; neonatal severe acute respiratory syndrome coronavirus 2 testing; breastfeeding and breastmilk feeding; rooming-in of mother-infant; respiratory support precautions; visiting procedures; de-isolation and discharge of infant; outpatient clinic attendance; transport of infant; and training of healthcare staff. This guidance for clinical care was proposed and contextualised for the local setting via consensus by members of this workgroup and was based on evidence available as of 31 July 2020, and may change as new evidence emerges., Competing Interests: None

Maternal and child health (MCH) in Singapore is entering a new phase, with challenges different to those faced 50 years ago. The advancement of medical technologies and access to MCH resources have led to a dramatic fall in maternal and infant mortality rates. However, there has been a steep rise in the rates of obesity and related metabolic diseases. Alongside this is an emerging mental wellness challenge, with one in ten women experience depression across pre-, during and post-pregnancy. Maternal obesity and mental disorders before and during pregnancy not only increase a woman's risk of pregnancy complications, but also result in increased risks in the offspring of childhood obesity, behavioral disorders and later life metabolic disease, catalyzing vicious cycles of disease. Thus, there is a pressing need to transform the current MCH system to address a burgeoning metabolic and mental health challenge for Singapore. Initiating interventions during preconception and continuing into the postpartum has the potential to confer long-term maternal-child benefits, promoting virtuous cycles of health. However, the current MCH system emphasizes antenatal care and lacks focus on the equally, if not more important, preconception, postpartum and inter-pregnancy stages. We describe a new model-of-care framework that integrates a life-course approach to health across preconception, pregnancy and postpartum phases, with the social-ecological model comprising individual, interpersonal, institutional, community and policy as the major targets for health promotion interventions. This "golden thread" approach is being established at the Singapore KK Women's and Children's Hospital (KKH), to address both metabolic and mental health challenges to achieve the goal of a thriving, healthy nation. This new model-of-care is set up in KKH as a pilot program known as Healthy Early Life Moments in Singapore (HELMS). HELMS will reach out to women planning to conceive through coordinated interventions across preconception, pregnancy and postpartum periods. A mobile health platform is being developed to facilitate interventions and engage participants in the program through a digital, personalized and interactive approach. This new model-of-care is designed to secure a population with healthy life cycles, by influencing each life-course, early-in-life, to provide the best start for generations to come., (© 2022. The Author(s).)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: There is limited information on the functional neutralizing capabilities of breastmilk SARS-CoV-2-specific antibodies and the potential adulteration of breastmilk with vaccine mRNA after SARS-CoV-2 mRNA vaccination., Methods: We conducted a prospective cohort study of lactating healthcare workers who received the BNT162b2 vaccine and their infants. The presence of SARS-CoV-2 neutralizing antibodies, antibody isotypes (IgG, IgA, IgM) and intact mRNA in serum and breastmilk was evaluated at multiple time points using a surrogate neutralizing assay, ELISA, and PCR, over a 6 week period of the two-dose vaccination given 21 days apart., Results: Thirty-five lactating mothers, median age 34 years (IQR 32-36), were included. All had detectable neutralizing antibodies in the serum immediately before dose 2, with significant increase in neutralizing antibody levels 7 days after this dose [median 168.4 IU/ml (IQR 100.7-288.5) compared to 2753.0 IU/ml (IQR 1627.0-4712.0), p <0.001]. Through the two vaccine doses, all mothers had detectable IgG1, IgA and IgM isotypes in their serum, with a notable increase in all three antibody isotypes after dose 2, especially IgG1 levels. Neutralizing antibodies were detected in majority of breastmilk samples a week after dose 2 [median 13.4 IU/ml (IQR 7.0-28.7)], with persistence of these antibodies up to 3 weeks after. Post the second vaccine dose, all (35/35, 100%) mothers had detectable breastmilk SARS-CoV-2 spike RBD-specific IgG1 and IgA antibody and 32/35 (88.6%) mothers with IgM. Transient, low intact vaccine mRNA levels was detected in 20/74 (27%) serum samples from 21 mothers, and 5/309 (2%) breastmilk samples from 4 mothers within 1 weeks of vaccine dose. Five infants, median age 8 months (IQR 7-16), were also recruited - none had detectable neutralizing antibodies or vaccine mRNA in their serum., Conclusion: Majority of lactating mothers had detectable SARS-CoV-2 antibody isotypes and neutralizing antibodies in serum and breastmilk, especially after dose 2 of BNT162b2 vaccination. Transient, low levels of vaccine mRNA were detected in the serum of vaccinated mothers with occasional transfer to their breastmilk, but we did not detect evidence of infant sensitization. Importantly, the presence of breastmilk neutralising antibodies likely provides a foundation for passive immunisation of the breastmilk-fed infant., Competing Interests: LW, WC, and CT are co-inventors on a patent for the surrogate virus neutralization assay commercialized by GenScript Biotechnology under the trade name cPass. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yeo, Chia, Tan, Ong, Yeo, Zhang, Poh, Lim, Sim, Sutamam, Chua, Albani, Wang and Chua.)

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., (© 2022 S. Karger AG, Basel.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Although most studies have reported unfavorable short-term effects of breastfeeding on early-childhood sleep-wake behaviors that potentially attenuate over time, findings have remained inconsistent., Objectives: We assessed associations of breastfeeding with longitudinal day-, night-, and total-sleep trajectories and with sleep-wake behaviors in healthy infants and preschoolers., Methods: Caregivers of naturally conceived, term, singleton infants (n = 654) completed the Brief Infant Sleep Questionnaire (3, 6, 9, 12, 18, and 24 mo) and/or Children's Sleep Habits Questionnaire (54 mo), and provided information on their infants' breastfeeding status at 3 mo. Trajectory analyses derived 4 day- (n = 243), 3 night- (n = 248), and/or 4 total- (n = 241) sleep trajectories, each differing in length of sleep duration (short/moderate/long) and variability (variable/consistent). Sleep-wake behaviors from 3 to 24 mo (day/night/total-sleep durations and duration/number of night awakenings) were also assessed for associations with breastfeeding., Results: After adjusting for potential covariates, formula-fed infants, relative to fully breastfed (predominant or exclusive) infants, were significantly less likely to exhibit moderate (OR: 0.28; 95% CI: 0.11, 0.70) and long consistent (OR: 0.18; 95% CI: 0.07, 0.50) night-sleep trajectories and less likely to exhibit moderate (OR: 0.21; 95% CI: 0.07, 0.61) and long consistent (OR: 0.12; 95% CI: 0.04, 0.38) and long variable (OR: 0.16; 95% CI: 0.05, 0.56) total-sleep trajectories, instead of short variable night- and total-sleep trajectories. Partially breastfed infants did not differ from fully breastfed infants for both night- and total-sleep trajectories. No significant differences were found between all groups for day-sleep trajectories. Fully breastfed infants had longer night- (6, 9, 12, and 24 mo) and total- (3 and 12 mo) sleep durations than formula-fed infants, albeit a greater number of night awakenings (from 6 to 12 mo)., Conclusions: Despite more night awakenings, fully breastfed infants have overall longer night- and total-sleep durations (sleep trajectories) than formula-fed infants., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants. Survivors may suffer both short- and long-term morbidities. Current evidence suggests that the incidence of NEC can be reduced by standardizing the care delivery in addressing key risk factors including an altered gut microbiome, use of formula milk, hyperosmolar feeds, and unrestricted use of high-risk medications METHODS: Since 2014, the department has a workgroup who analyzed all cases of NEC within a month of diagnosis to identify preventable risk factors. Existing evidence-based quality improvement strategies were revised and new ones were implemented sequentially over the next 4 years. These strategies include (1) a standardized feeding protocol, (2) early initiation of enteral feeding using human milk, (3) optimization of the osmolality of preterm milk feeds using standardized dilution guidelines for additives, and (4) promotion of healthy microbiome by use of probiotics, early oral care with colostrum and by restricting high-risk medications and prolonged use of empirical antibiotics RESULTS: Baseline characteristics of the patients including sex, gestational age, and birth weight were similar during the study period. After implementing the evidence-based practices successively over 4 years, the incidence of NEC in very- low birth-weight (VLBW) infants dropped from 7% in 2014 to 0% (P < .001) in 2018. The duration of parenteral nutrition, use of central line, and days to full feeds were also reduced significantly (P < .05) CONCLUSION: Adopting evidence-based best practices resulted in a significant decrease in the incidence of NEC and improved the nutrition outcomes in VLBW infants., (© 2020 American Society for Parenteral and Enteral Nutrition.)

Background: Previous studies focusing on the association between gestational diabetes and breastfeeding duration have been inconclusive., Objectives: We aimed to determine whether maternal gestational hyperglycemia is associated with the duration of breastfeeding and the concentrations of markers linked to breastmilk production., Methods: Data from the prospective, multiethnic Growing Up in Singapore Towards Healthy Outcomes study were used to assess the association of fasting plasma glucose (FPG) and 2-h postglucose challenge (2hPG) measured at 26-28 wk of gestation with duration of breastfeeding and concentrations of protein, lactose, citrate, sodium, potassium, and zinc in breastmilk 3 wk postpartum., Results: Of the 1035 participants, 5.2% and 9.5% had elevated FPG and 2hPG, respectively, consistent with a diagnosis of gestational diabetes mellitus based on International Association of Diabetes and Pregnancy Study Groups criteria. FPG ≥5.1 mmol/L was associated with a crude reduction in median breastfeeding duration of 2.3 mo. In a model adjusted for maternal prepregnancy BMI and intention to breastfeed, FPG ≥5.1 mmol/L predicted earlier termination of any breastfeeding (adjusted HR: 1.47; 95% CI: 1.04, 2.08) but not full breastfeeding (adjusted HR: 1.08; 0.76, 1.55). 2hPG ≥8.5 mmol/L was not significantly associated with the durations of any (adjusted HR: 0.86; 95% CI: 0.62, 1.19) or full (adjusted HR: 0.85; 95% CI: 0.62, 1.18) breastfeeding. Maternal FPG was significantly and positively associated with breastmilk sodium (adjusted coefficient: 1.28; 95% CI: 1.08, 1.51) and sodium-to-potassium ratio (adjusted coefficient: 1.29; 95% CI: 1.08, 1.54) but not with other measured breastmilk components., Conclusions: Women with FPG ≥5.1 mmol/L during pregnancy breastfeed for a shorter duration. Future work involving measurement of milk production is needed to determine whether low milk production predicts breastfeeding duration among women with elevated FPG. This trial was registered at www.clinicaltrials.gov as NCT01174875., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objective: To evaluate prevalence and risk factors of moderate-severe Bronchopulmonary dysplasia (BPD)/Death in extremely low gestation age neonates (ELGANs)., Study Design: Study of 266 ELGANs born at gestational age (GA) ≤ 28 weeks (w). Primary Outcome measure-composite outcome of moderate-severe BPD/Death using the National Institute of Child Health and Human Development NICHD's (2001) BPD definition., Result: Cohort's mean GA and birth-weight (BW) were 25.3 ± 1.4w and 724 ± 14 g respectively with an overall mortality of 19% and moderate-severe BPD of 67%. Prevalence of moderate-severe BPD/death decreased significantly with increasing GA (86-93%) at 23-24 w; to <60% at 27-28w (OR 0.63; 95% CI; 0.52-0.77). On univariate analysis, other risk factors included BW(OR 1.005; 95% CI; 1.003-1.007), Sepsis (OR 2.9; 95% CI, 1.3-6.4), PDA needing treatment (OR 2.2; 95% CI, 1.3-3.9); air leaks (OR 2.7; 95% CI; 1.02-7.3) FiO 2 requirement >25%(OR 1.06; 95% CI; 1.01-1.11); and mechanical ventilation(MV) on Day7 (OR5.5; 95% CI; 2.8-10.8). Only need for Day7 MV was independently predictive of composite outcome (OR1.97; 95% CI; 1.3-3.1)., Conclusion: Risk factor identification will enable initiatives to implement lung protective strategies and develop prospective models for BPD prediction and prognostication., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD., Results: As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome., Conclusions: This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development., Trial Registration: The study was registered in the Dutch Trial Register (Number: 2838 ) on 4th April 2011.

Background: The World Health Organization (WHO) recommendations on infant feeding in the context of COVID-19 uphold standing recommendations for breastfeeding, non-separation, and skin-to-skin contact, including the use of donor human milk when mother's own milk is not available. INSUFFICIENT GUIDANCE ON THE USE OF DONOR HUMAN MILK AND THE ROLE OF HUMAN MILK BANKS IN THE PANDEMIC RESPONSE: COVID-19 clinical management guidelines in seven countries in Southeast Asia are not aligned with WHO recommendations despite the lack of evidence of transmission through either breastmilk or breastfeeding. The use of safe donor human milk accessed through human milk banks is also insufficiently recommended, even in countries with an existing human milk bank, leading to a gap in evidence-based management of COVID-19. This highlights long-standing challenges as well as opportunities in the safe, equitable, and resilient implementation of human milk banks in the region., Conclusions: This statement reflects the expert opinion of the Regional Human Milk Bank Network for Southeast Asia and Beyond on the need to revisit national guidelines based on the best evidence for breastfeeding during the COVID-19 pandemic, to incorporate human milk bank services in national obstetric and newborn care guidelines for COVID-19 where possible, and to ensure that operations of human milk banks are adapted to meet the needs of the current pandemic and to sustain donor human milk supply in the long-term. The Network also recommends sustained engagement with the global human milk bank community.

Background: Patent ductus arteriosus (PDA) causing significant left to right shunt can increase key morbidities in preterm infants. Yet, treatment does not improve outcomes and spontaneous closure is the natural course of PDA. The Impact of PDA on 23-26-week gestation infants is uncertain. Selective treatment of such infants would likely balance outcomes. Objective: To test the hypothesis that treatment of PDA in high-risk VLBW infants [birth weight ≤800 g or gestation <27 weeks, hemodynamically significant, ductal diameter (DD, ≥1.6 mm), and mechanical ventilation] and expectant management in low-risk infants will reduce the need for treatment and surgical ligation, without altering short term morbidities. Methods: This prospective observational study was initiated subsequent to the introduction of a new treatment protocol in 2016. The 12-months before and after protocol introduction were, respectively, defined as standard and early selective treatment periods. In the early selective treatment cohort, PDA was treated with indomethacin, maximum of two courses, 1 week apart. Surgical ligation was considered after 30 days of age if indicated (DD ≥2 mm, mechanical ventilation). Primary outcomes were need for treatment and rate of ligation. Protocol compliance and secondary outcomes were documented. Results: 415 infants were studied, 202 and 213 in the standard treatment and early selective treatment cohorts, respectively. Numbers treated (per protocol) in the standard treatment and early selective treatment cohorts were 27.7 and 19.3% (56/202 and 41/213) ( p = 0.049), and the respective ligation rates were 7.54 and 2.96% ( P = 0.045). Secondary outcomes were comparable. Conclusion: The early selective treatment protocol reduced the rates of treatment and surgical ligation of PDA, without altering key morbidities. Further studies under a randomized control trial setting is warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ibrahim, Abdul Haium, Tapawan, Dela Puerta, Allen, Chandran, Chua and Rajadurai.)

(1) Background: Breastfeeding has been shown to support glucose homeostasis in women after a pregnancy complicated by gestational diabetes mellitus (GDM) and is potentially effective at reducing long-term diabetes risk. (2) Methods: Data from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study were analyzed to understand the influence of breastfeeding duration on long-term dysglycemia (prediabetes and diabetes) risk in women who had GDM in the index pregnancy. GDM and dysglycemia four to seven years postpartum were determined by the oral glucose tolerance test (OGTT). A Poisson regression model with a robust error variance was used to estimate incidence rate ratios (IRRs) for dysglycemia four to seven years post-delivery according to groupings of the duration of any breastfeeding (<1, ≥1 to <6, and ≥6 months). (3) Results: Women who had GDM during the index pregnancy and complete breastfeeding information and OGTT four to seven years postpartum were included in this study ( n = 116). Fifty-one women (44%) had postpartum dysglycemia. Unadjusted IRRs showed an inverse association between dysglycemia risk and ≥1 month to <6 months (IRR 0.91; 95% confidence interval [CI] 0.57, 1.43; p = 0.68) and ≥6 months (IRR 0.50; 95% CI 0.27, 0.91; p = 0.02) breastfeeding compared to <1 month of any breastfeeding. After adjusting for key confounders, the IRR for the ≥6 months group remained significant (IRR 0.42; 95% CI 0.22, 0.80; p = 0.008). (4) Conclusions: Our results suggest that any breastfeeding of six months or longer may reduce long-term dysglycemia risk in women with a history of GDM in an Asian setting. Breastfeeding has benefits for mothers beyond weight loss, particularly for those with GDM.

The Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) is a preconception, longitudinal cohort study that aims to study the effects of nutrition, lifestyle, and maternal mood prior to and during pregnancy on the epigenome of the offspring and clinically important outcomes including duration of gestation, fetal growth, metabolic and neural phenotypes in the offspring. Between February 2015 and October 2017, the S-PRESTO study recruited 1039 Chinese, Malay or Indian (or any combinations thereof) women aged 18-45 years and who intended to get pregnant and deliver in Singapore, resulting in 1032 unique participants and 373 children born in the cohort. The participants were followed up for 3 visits during the preconception phase and censored at 12 months of follow up if pregnancy was not achieved (N = 557 censored). Women who successfully conceived (N = 475) were characterised at gestational weeks 6-8, 11-13, 18-21, 24-26, 27-28 and 34-36. Follow up of their index offspring (N = 373 singletons) is on-going at birth, 1, 3 and 6 weeks, 3, 6, 12, 18, 24 and 36 months and beyond. Women are also being followed up post-delivery. Data is collected via interviewer-administered questionnaires, metabolic imaging (magnetic resonance imaging), standardized anthropometric measurements and collection of diverse specimens, i.e. blood, urine, buccal smear, stool, skin tapes, epithelial swabs at numerous timepoints. S-PRESTO has extensive repeated data collected which include genetic and epigenetic sampling from preconception which is unique in mother-offspring epidemiological cohorts. This enables prospective assessment of a wide array of potential determinants of future health outcomes in women from preconception to post-delivery and in their offspring across the earliest development from embryonic stages into early childhood. In addition, the S-PRESTO study draws from the three major Asian ethnic groups that represent 50% of the global population, increasing the relevance of its findings to global efforts to address non-communicable diseases.

The aetiology of febrile exanthems in children is often difficult to distinguish clinically. A diagnosis of Kawasaki disease (KD) should be considered in infants with exanthematous fever. More perplexing is the increasing incidence of an atypical form of KD. Pathogenesis of KD remains unclear even though an aberrant response of the immune system to an unidentified pathogen is often hypothesised. A 30-fold increase in the incidence of KD in Italy during the SARS-CoV-2 pandemic suggests an immune response to a viral trigger. We report an infant clinically diagnosed with high probability as incomplete KD, who presented with reactivation of the BCG injection site even though fever with rash was only less than 3 days duration. Echocardiography confirmed coronary artery abnormalities and prompt treatment with intravenous immunoglobulin facilitated rapid recovery. Physicians should consider a diagnosis of KD if BCG site reactivation is noted in children presenting with febrile exanthema., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To compare the diagnostic ability of macular intraretinal layer thickness with circumpapillary retinal nerve fiber layer (cpRNFL) thickness, either when used individually or in combination with cpRNFL for detecting early, moderate, and advanced glaucoma., Design: Cross-sectional study., Participants: A total of 423 glaucoma participants and 423 age- and gender-matched normal participants., Methods: Participants underwent Cirrus spectral-domain OCT (SD-OCT) imaging (Carl Zeiss Meditec, Dublin, CA) using the optic disc and macular scanning protocols. Iowa Reference Algorithms (version 3.8.0) were used for intraretinal layer segmentation, and mean thickness of intraretinal layers was rescaled with magnification correction using axial length value. Thickness measurements of each layer/sector and their corresponding areas under the receiver operating characteristic curve (AUCs) were obtained. Glaucoma eyes were subdivided based on of their visual field severity (early, n = 234; moderate, n = 107; advanced, n = 82)., Main Outcome Measures: Intraretinal layers., Results: Some 67% of participants were male, their average ± standard deviation age was 65±9 years. Circumpapillary retinal nerve fiber layer, macular ganglion cell layer (mGCL), and macular inner plexiform layer (mIPL) were significantly thinner in the glaucoma groups (P < 0.0005). The 2 best parameters for detecting normal eyes from early glaucoma was cpRNFL (AUC = 0.861) and mGCL (AUC = 0.842), from moderate glaucoma was mGCL combined with inner plexiform layer (IPL) (AUC = 0.915) and cpRNFL (AUC = 0 .914), and from advanced glaucoma was mGCL-IPL (AUC = 0.984) and cpRNFL (AUC = 0.977). There was no statistical significance between AUCs for the macular parameter and cpRNFL thickness measurement at any of the severities (P > 0.05). Combining macular and cpRNFL parameters improved the diagnostic performance for early glaucoma (AUC = 0.908; P = 0.002) and moderate glaucoma (AUC = 0.944; P = 0.031) but not for advanced glaucoma (AUC = 0.991; P > 0.05)., Conclusions: Single-layer mGCL thickness is comparable to the traditional cpRNFL thickness for the diagnosis of early/moderate glaucoma, whereas cpRNFL thickness remains the most efficient for advanced glaucoma. Combining macular measurements (GCL and GCL-IPL) and cpRNFL improved the discrimination of early/moderate glaucoma but not of advanced glaucoma. For the diagnosis of early glaucoma, both macular and optic disc scans should be used., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Individual differences in children's eating behaviours emerge early. We examined the relationship between breastfeeding exposure and subsequent eating behaviours among children from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Children (n = 970) were grouped according to their breastfeeding exposure: high (full breastfeeding ≥ 4 months with continued breastfeeding ≥ 6 months), low (any breastfeeding < 3 months or no breastfeeding) and intermediate (between low and high breastfeeding categories). Aspects of eating behaviour from ages 15 months to 6 years were captured using a combination of maternal reports (Child Eating Behaviour Questionnaire; Infant Feeding Questionnaire; Preschooler Feeding Questionnaire) and laboratory-based measures of meal size, oral processing behaviours (e.g. average eating speed and bite size) and tendency to eat in the absence of hunger. Most children had low (44%) or intermediate (44%) breastfeeding exposure; only 12% had high exposure. After adjusting for confounders, multivariable linear regression analyses indicated the high (but not intermediate) breastfeeding group was associated with significantly lower reported food fussiness at 3 years compared to low breastfeeding group (-0.38 [-0.70, -0.06]), with similar but non-significant trends observed at 6 years (-0.27 [-0.66, 0.11]). At 3 years, mothers in the high breastfeeding group also reported the least difficulty in child feeding compared to low breastfeeding group (-0.22 [-0.43, -0.01]). However, high breastfeeding was not associated with any other maternal-reports of child feeding or eating behaviours, and no significant associations were observed between breastfeeding exposure and any of the laboratory measures of eating behaviour at any of the time points. These results do not strongly support the view that increased breastfeeding exposure alone has lasting and consistent associations with eating behaviours in early childhood., Competing Interests: Declaration of competing interest KMG, LPS, CGF and Y-SC have received reimbursement for speaking at conferences sponsored by companies selling nutritional products. KMG, S-YC and Y-SC are part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. CGF currently serves on the scientific advisory council for Kerry Taste and Nutrition. The other authors have no financial or personal conflict of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To explore the associations between type of milk feeding (the "nutrients") and mode of breast milk feeding (the "nursing") with child cognition., Methods: Healthy children from the GUSTO (Growing Up in Singapore Toward healthy Outcomes) cohort participated in repeated neurodevelopmental assessments between 6 and 54 months. For "nutrients", we compared children exclusively bottle-fed according to type of milk received: formula only (n = 296) vs some/all breast milk (n = 73). For "nursing", we included only children who were fully fed breast milk, comparing those fed directly at the breast (n = 59) vs those fed partially/completely by bottle (n = 63)., Results: Compared to infants fed formula only, those who were bottle-fed breast milk demonstrated significantly better cognitive performance on both the Bayley Scales of Infant and Toddler Development (Third Edition) at 2 years [adjusted mean difference (95% CI) 1.36 (0.32, 2.40)], and on the Kaufman Brief Intelligence Test (Second Edition) at 4.5 years [7.59 (1.20, 13.99)]. Children bottle-fed breast milk also demonstrated better gross motor skills at 2 years than those fed formula [1.60 (0.09, 3.10)]. Among infants fully fed breast milk, those fed directly at the breast scored higher on several memory tasks compared to children bottle-fed breast milk, including the deferred imitation task at 6 months [0.67 (0.02, 1.32)] and relational binding tasks at 6 [0.41 (0.07, 0.74)], 41 [0.67 (0.04, 1.29)] and 54 [0.12 (0.01, 0.22)] months., Conclusions: Our findings suggest that nutrients in breast milk may improve general child cognition, while nursing infants directly at the breast may influence memory.

Octreotide is a somatostatin analogue used for treating congenital chylothorax and congenital hyperinsulinism in infants. By increasing splanchnic arteriolar resistance and decreasing gastrointestinal blood flow, octreotide indirectly reduces lymphatic flow in chylous effusions.Splanchnic ischaemia following octreotide predisposes infants to necrotising enterocolitis (NEC). Although NEC occurrence in infants treated with octreotide for hyperinsulinaemic hypoglycaemia has been reported widely, its incidence in infants with chylothroax is low. We describe a case of congenital chylothorax in a preterm infant who had poor response to thoracentesis. Although octreotide initiation lead to resolution of chylothorax, he developed NEC. Cessation of octreotide and medical management resulted in rapid resolution of NEC. Since octreotide is generally used as the first-line treatment for chylous effusion, the risk of NEC should be considered, especially when the dosage is increased. Infants on octreotide should be closely observed for early signs and symptoms of NEC to avert surgical emergency., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hemolytic hyperbilirubinemia due to blood group incompatibility or glucose-6-phosphate dehydrogenase deficiency (G6PD) is a common cause of significant hyperbilirubinemia. Hemolysis in a hyperbilirubinemic infant increases the risk of bilirubin neurotoxicity. A new portable device (CoSense) can rapidly detect breath end-tidal carbon monoxide corrected to ambient carbon monoxide (ETCOc). ETCOc levels are surrogate markers of hemoglobin breakdown and bilirubin production., Objective: The aim was to evaluate the association between ETCOc values and hemolysis and its relevance in neonates at risk for significant hyperbilirubinemia., Methods: A prospective study was conducted among newborn infants born at more than 35 weeks and with a birth weight greater than 2,000 g with a G6PD deficiency, blood group incompatibility, or clinical jaundice needing phototherapy during the first 7 days of life. The recruited infants had their breath ETCOc measured twice, first on the day of recruitment and then again on the following day., Results: Fifty infants completed this study. Their mean ETCOc was 1.61 (±0.56) ppm. There was a linear correlation (r = 0.89) between increasing ETCOc values and reticulocyte counts (RC). Sixteen newborns with ABO incompatibility had a significantly higher mean ETCOc of 1.98 ppm (±0.71) as compared to 1.43 (±0.38) ppm in the nonhemolytic hyperbilirubinemia (NHH) group (n = 25) (p = 0.002). This was suggestive of hemolysis as shown by the significantly higher RC of 6.90% (±3.38) compared to 4.68 (±1.26) in the NHH group (p <0.005). Neonates with an ETCOc level ≥1.8 ppm had a higher RC, a lower hemoglobin level, higher serum bilirubin levels, and a rapid rise in serum bilirubin and needed a longer duration of phototherapy. ETCOc values ≥1.8 ppm were suggestive of hemolysis (RC ≥6%), with a sensitivity of 90% and a specificity of 83%., Conclusion: Higher ETCOc values ≥1.8 ppm are suggestive of hemolysis and they are associated with significant hyperbilirubinemia., (© 2020 S. Karger AG, Basel.)

The mode of delivery is a known risk factor for immune-related disorders. Normal term vaginal delivery is an inflammatory process and several cytokines are suggested to be involved. The purpose of the study was to evaluate differences in cord blood cytokine expression between modes of delivery in term-born children. Cord blood was collected from 49 elective Caesarean section (C-section) cases and from 49 normal vaginal term deliveries. Plasma was tested for 17 cytokines with Bio-Plex®-200-system. Mann-Whitney test was used for comparing the groups with Bonferroni correction for multiple testing. Four cytokines showed significant differences between the modes of delivery. Interleukin-6, Interleukin-8 showed a significantly higher expression in the vaginal delivery group, while Tumor-Necrosis Factor-a, Granulocyte-Colony Stimulating Factor showed a significantly higher level of expression in the C-section cord blood. Our study shows that there is differential expression of pro-inflammatory cytokines in elective C-section compared with normal term vaginal delivery., (Copyright © 2019 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

The fetus undergoes a crucial period of neurodevelopment in utero. The maternal hair metabolome provides an integrated record of the metabolic state of the mother prior to, and during pregnancy. We investigated whether variation in the maternal hair metabolome was associated with neurodevelopmental differences across infants. Maternal hair samples and infant neurocognitive assessments (using the Bayley III Scales of Infant Development at 24 months) were obtained for 373 infant-mother dyads between 26-28 weeks' gestation from the Growing Up in Singapore Towards Healthy Outcomes cohort. The hair metabolome was analysed using gas chromatography-mass spectrometry. Intensity measurements were obtained for 276 compounds. After controlling for maternal education, ethnicity, and infant sex, associations between metabolites and expressive language skills were detected, but not for receptive language, cognitive or motor skills. The results confirm previous research associating higher levels of phthalates with lower language ability. In addition, scores were positively associated with a cluster of compounds, including adipic acid and medium-chain fatty acids. The data support associations between the maternal hair metabolome and neurodevelopmental processes of the fetus. The association between phthalates and lower language ability highlights a modifiable risk factor that warrants further investigation.

Background: The major causes of maternal and neonatal mortality in the Philippines are hemorrhages and obstructed labor due to placental implantation abnormalities (PIAs), twin pregnancies and fetal malpresentations. All of which are all easily detected by ultrasound. However, women in rural areas and low-income groups do not have access to ultrasound during their prenatal care. We aimed to provide additional evidence on the benefits of handheld ultrasound (HU) for screening pregnancy related abnormalities in order to avert maternal and neonatal deaths., Methods: Using a HU, we trained community healthcare workers (CHWs) to identify 5 obstetrical conditions: fetal viability and number, placental localization, amniotic fluid volume (AFV) and fetal presentation. Women, between 20th and 24th weeks age of gestation from 2 regions of the Philippines, were scanned using the HU and the GE Logic 5 Premium ultrasound machine for validation. Maternal and neonatal deaths averted were estimated as health outcome measures of the study., Results: Four hundred sixty women were scanned of which 146 (31.7%) showed abnormal ultrasound readings consisting of 17 PIAs, 123 fetal malpresentation, 3 twins and 3 AFV abnormalities. The use of HU could have possibly averted 29 (6.3%) maternal deaths and 14.6% neonatal deaths at the time of delivery. Thirty-two out of the 460 women (~7%) delivered at home and 93% in hospitals or birthing facilities/lying-in centers. We observed approximately 95% agreement between the ultrasound readings of the trainees and the trainers, and 99% agreement between the readings made from the HU with the validation machine., Conclusion: CHWs could be trained in the use of HU for scanning 5 obstetrical parameters. Early detection of abnormalities in these 5 obstetrical parameters can lead to early referral to facilities that are better equipped to manage obstetrical emergencies. Prenatal ultrasound can be an excellent point of care test for screening pregnant women at risk for possible complications and even death during labor and delivery., Trial Registration: Thai Clinical Trial Registry identification number TCTR20171128004 , retrospectively registered November 28, 2017.

Background: Evidence linking maternal diet quality during pregnancy with infant birth outcomes is limited in Asia., Objective: We investigated the association of maternal diet quality with the risk of preterm birth, offspring birth size, and adiposity in a multiethnic Asian birth cohort., Design: Dietary intakes of 1051 pregnant women were ascertained at 26-28 wk of gestation with the use of 24-h recalls and 3-d food diaries, from which diet quality (score range: 0-100) was measured by the Healthy Eating Index for pregnant women in Singapore (HEI-SGP). Gestational age was established by first-trimester ultrasound dating scan. Neonatal weight and length were measured at birth. Body composition was assessed by air displacement plethysmography in a subset of infants (n = 313) within 72 h after birth, and abdominal adiposity was assessed by MRI (n = 316) within the first 2 wk of life. Associations were assessed by multivariable linear regression for continuous outcomes and logistic regression for preterm birth., Results: The mean ± SD maternal HEI-SGP score was 52.1 ± 13.6. Maternal diet quality during pregnancy was not associated with preterm birth or birth weight. Greater adherence to the HEI-SGP (per 10-point increment in HEI-SGP score) was associated with longer birth length [β (95% CI): 0.14 (0.03, 0.24 cm)], lower body mass index (in kg/m2) at birth [-0.07 (-0.13, -0.01)], lower sum of triceps and subscapular skinfold thickness [-0.15 (-0.26, -0.05 mm)], lower percentage body fat [-0.52% (-0.84%, -0.20%)], lower fat mass [-17.23 (-29.52, -4.94 g)], lower percentage abdominal superficial subcutaneous adipose tissue [-0.16% (-0.30%, -0.01%)], and lower percentage deep subcutaneous adipose tissue [-0.06% (-0.10%, -0.01%)]., Conclusions: Higher maternal diet quality during pregnancy was associated with longer birth length and lower neonatal adiposity but not with birth weight and preterm birth. These findings warrant further investigation in independent studies. This trial was registered at clinicaltrials.gov as NCT01174875., (© 2018 American Society for Nutrition. All rights reserved.)

We determined the effect of short-chain galacto-oligosaccharides (scGOS), long-chain fructo-oligosaccharides (lcFOS) and Bifidobacterium breve M-16V on the gut microbiota of cesarean-born infants. Infants were randomized to receive a standard formula (control), the same with scGOS/lcFOS and B. breve M-16V (synbiotic), or with scGOS/lcFOS (prebiotic) from birth until week 16, 30 subjects born vaginally were included as a reference group. Synbiotic supplementation resulted in a higher bifidobacteria proportion from day 3/5 (P < 0.0001) until week 8 (P = 0.041), a reduction of Enterobacteriaceae from day 3/5 (P = 0.002) till week 12 (P = 0.016) compared to controls. This was accompanied with a lower fecal pH and higher acetate. In the synbiotic group, B. breve M-16V was detected 6 weeks postintervention in 38.7% of the infants. This synbiotic concept supported the early modulation of Bifidobacterium in C-section born infants that was associated with the emulation of the gut physiological environment observed in vaginally delivered infants.

Background: Studies examining direct vs. expressed breast milk feeding are scarce. We explored the predictors of mode of breastfeeding and its association with breastfeeding duration in a multi-ethnic Asian population., Methods: We included 541 breastfeeding mother-infant pairs from the Growing Up in Singapore Toward healthy Outcomes cohort. Mode of breastfeeding (feeding directly at the breast, expressed breast milk (EBM) feeding only, or mixed feeding (a combination of the former 2 modes)) was ascertained at three months postpartum. Ordinal logistic regression analyses identified predictors of breast milk expression. Cox regression models examined the association between mode of breastfeeding and duration of any and of full breastfeeding., Results: Maternal factors independently associated with a greater likelihood of breast milk expression instead of direct breastfeeding were Chinese (vs. Indian) ethnicity, (adjusted odds ratio, 95% CI; 3.41, 1.97-5.91), tertiary education (vs. secondary education or lower) (2.22, 1.22-4.04), primiparity (1.54, 1.04-2.26) and employment during pregnancy (2.53, 1.60-4.02). Relative to those who fed their infants directly at the breast, mothers who fed their infants EBM only had a higher likelihood of early weaning among all mothers who were breastfeeding (adjusted hazard ratio, 95% CI; 2.20, 1.61-3.02), and among those who were fully breastfeeding (2.39, 1.05-5.41). Mothers who practiced mixed feeding, however, were not at higher risk of earlier termination of any or of full breastfeeding., Conclusions: Mothers who fed their infants EBM exclusively, but not those who practiced mixed feeding, were at a higher risk of terminating breastfeeding earlier than those who fed their infants directly at the breast. More education and support are required for women who feed their infants EBM only., Competing Interests: K.M.G., and Y.-S.C. have received reimbursement for speaking at conferences sponsored by companies selling nutritional products. These authors are part of an academic consortium that has received research funding from Abbot Nutrition, Nestec, and Danone. None of the other authors report any potential conflict of interest.

Background: Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking., Methods: We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first., Results: A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P=0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P=0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P=0.06)., Conclusions: Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk. (Funded by the Australian National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820 .).

Objectives: This study compared the body contact pressure profiles of 2 types of mattresses: latex and polyurethane., Methods: Twenty participants were required to lie down on the different mattresses in 3 different postures for 6 minutes, and their body contact pressure profiles were recorded with a pressure mat sensor., Results: The data indicated that the latex mattress was able to reduce the peak body pressure on the torso and buttocks and achieve a higher proportion of low-pressure regions compared with the polyurethane mattress., Conclusions: Latex mattress reduced peak body pressure and achieved a more even distribution of pressure compared with polyurethane mattress across different sleeping postures.

Background: Medications added to preterm milk feeds have the potential to raise osmolality, causing feed intolerance and necrotizing enterocolitis., Objective: The aim of this study was to evaluate changes in the osmolality of milk feeds and water with 14 medications and the diluent amounts required to keep the osmolality below the safety threshold of ≤450 mOsm/kg. Changes in the osmolality of milk with medications while on continuous infusion over 2 and 4 h were determined., Methods: This study was designed to measure the osmolality of 14 commonly used medications in preterm infants both neat and when supplemented with expressed breast milk (EBM), EBM with fortifier (EBMF), preterm formula (PTF), and water. Dose-effect curves were plotted, and the volume of each diluent was calculated to keep the osmolality ≤450 mOsm/kg. Time-effect curves were plotted at 2 and 4 h for each medication for both EBM and EBMF., Results: Neat osmolality of all except 5 medications were above 2,000 mOsm/kg. The osmolality rose with decreasing proportions of diluents used, depicting an indirect curvilinear relationship between the increasing dilution and osmolality for all except 2 medications. As a diluent, EBM was required in lower dilutions than EBMF. Dilutions needed for additives with PTF were very similar to those of EBM. The change in osmolality over time with additives was statistically significant for EBMF., Conclusions: EBM and PTF were found to be safer diluents than EBMF for enteral additives. The practice of keeping milk feeds with medications for continuous feeding is safe for a period of 4 h in EBM., (© 2016 S. Karger AG, Basel.)

Background: Confinement (restrictions placed on diet and practices during the month right after delivery) represents a key feature of Asian populations. Few studies, however, have focused specifically on ethnic differences in confinement practices. This study assesses the confinement practices of three ethnic groups in a multi-ethnic Asian population., Methods: Participants were part of a prospective birth cohort study that recruited 1,247 pregnant women (57.2% Chinese, 25.5% Malay, and 17.3% Indian) during their first trimester. The 1,220 participants were followed up 3 weeks postpartum at home when questionnaires were administered to ascertain the frequency of adherence to the following confinement practices: showering; confinement-specific meals; going out with or without the baby; choice of caregiver assistance; and the use of massage therapy., Results: Most participants reported that they followed confinement practices during the first 3 weeks postpartum (Chinese: 96.4%, Malay: 92.4%, Indian: 85.6%). Chinese and Indian mothers tended to eat more special confinement diets than Malay mothers (p < 0.001), and Chinese mothers showered less and were more likely to depend on confinement nannies during this period than mothers from the two other ethnic groups (p < 0.001 for all). Malay mothers tended to make greater use of massage therapy (p < 0.001), whilst Indian mothers tended to have their mothers or mothers-in-law as assistant caregivers (p < 0.001)., Conclusion: Most Singapore mothers follow confinement practices, but the three Asian ethnic groups differed in specific confinement practices. Future studies should examine whether ethnic differences persist in later childrearing practices., (© 2016 Wiley Periodicals, Inc.)