Metformin and insulin exacerbate one-carbon metabolism deficits in pregnant growth restricted rats and impacts the placenta, fetal liver and pancreas.

Fetal growth restriction increases the risk of metabolic conditions such as gestational diabetes mellitus (GDM). One-carbon metabolite and nutrient concentrations are dysregulated in GDM and influenced by antihyperglycaemic medications. However, it remains unclear whether disrupted one-carbon metabolism contributes to GDM onset in growth restricted offspring and whether antihyperglycaemic medications exacerbate this dysregulation.

Endocrine disrupting chemicals in maternal and umbilical cord plasma and their associations with birthweight in the GUSTO cohort.

Background: With daily exposure to multiple endocrine disrupting chemicals (EDCs), understanding individualized co-exposure patterns could better identify chemicals that threaten health. This is particularly pertinent for the vulnerable fetus during in-utero development, where exposure can have long lasting health consequences. As there is limited information of EDC exposure in Asian maternal-offspring populations, this study aimed to (1) determine levels of a selected range of EDCs (focusing on Substances of Very High Concern by the European Chemical Agency) in maternal and corresponding cord blood plasma, (2) investigate the sociodemographic factors associated with plasma EDC concentrations, and (3) associate EDC-mixtures with birthweight, in a Singapore cohort.

Long-read transcriptome assembly reveals vast isoform diversity in the placenta associated with metabolic and endocrine function.

The placenta plays a critical role in fetal development and mediates maternal metabolic effects on offspring health outcomes. Despite its importance, the placenta remains understudied in large-scale genomic initiatives, with most analyses focusing on gene-level expression based on annotations from adult tissue references that obscure isoform diversity particularly vital to understanding function in developmental tissues. Here, we employed largest-in-class long-read RNA sequencing (N = 72) to generate a comprehensive placental transcript reference, yielding 37,661 high-confidence isoforms across 12,302 genes.

Maternal Psychological Well-Being and Caries Experience in 3-Year-Old Offspring: Growing Up in Singapore Towards healthy Outcomes (GUSTO) Study.

Introduction: Dental caries is a biofilm-mediated, multifactorial disease of the dental hard tissues. Maternal psychosocial and behavioral factors can affect a child's risk for many chronic childhood conditions including dental caries. We examined the relationship between maternal psychological well-being during and after pregnancy on caries experience in 3-year-old offspring.

Infant body composition in a randomised trial of a maternal nutritional supplement during preconception and pregnancy.

Background: In a multinational randomized controlled trial, we previously showed that maternal supplementation with myo-inositol, probiotics, and micronutrients was associated with reduced incidence of rapid infant weight gain and high body mass index (BMI) at two years among offspring. It was unclear whether these differences in weight gain and body mass were due to reduced adiposity. Therefore, we aimed to determine whether there were any differences in body composition.

Genetics and epigenetics in gestational diabetes contributing to type 2 diabetes.

Gestational diabetes mellitus (GDM) is a common pregnancy complication and a risk factor for the subsequent development of type 2 diabetes (T2D) in mothers and of several metabolic diseases in offspring. However, the molecular underpinnings of these risks are not well understood. Genome-wide association studies (GWAS) and epigenetic studies may provide complementary insights into the causal relationships between GDM exposure and maternal/offspring metabolic outcomes.

The impact of ingestion of Bifidobacterium longum NCC3001 on perinatal anxiety and depressive symptoms: a randomized controlled trial.

Perinatal mood disorders, including depression and anxiety, are common. Pregnant and lactating women often limit their use of medications, thus a safe and natural solution to improve mood would be welcomed. There is increasing evidence that probiotics such as Bifidobacterium longum NCC3001 can influence mental well-being of adults; however, their impact on mental health during pregnancy and after birth remains unknown.

Associations of fetal and postnatal growth trajectories with child cognition: the GUSTO cohort study.

Background: Using longitudinal ultrasounds as an improved fetal growth marker, we aimed to investigate if increased postnatal growth following fetal abdominal circumference (AC) growth deceleration is associated with improved child cognition.

Methods: Among 797 term-born singletons in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort, we derived 2nd-3rd trimester fetal AC growth z-score, fetal AC growth deceleration, standardized height, weight, and body mass index (BMI) growth at early infancy (0-4 months), late infancy (4-15 months), toddlerhood (15-37 months), and early childhood (3-7 years), and investigated their associations with intelligence quotient (IQ) at ages 4.5 years (verbal, non-verbal) and 7 years (non-verbal-block design, matrix reasoning), adjusting for socio-demographic and biological confounders.

Linking obesity-associated genotype to child language development: the role of early-life neurology-related proteomics and brain myelination.

Background: The association between childhood obesity and language development may be confounded by socio-environmental factors and attributed to comorbid pathways.

Methods: In a longitudinal Singaporean mother-offspring cohort, we leveraged trans-ancestry polygenic predictions of body mass index (BMI) to interrogate the causal effects of early-life BMI on child language development and its effects on molecular and neuroimaging measures. Leveraging large genome-wide association studies, we examined whether the link between obesity and language development is causal or due to a shared genetic basis.

Decentralized clinical trials are better for the participants and for the planet: the case study of a double-blind randomized controlled trial in Singapore (PROMOTE study).

Introduction: Novel technologies have enabled the decentralization of many aspects of clinical trials, but little research has been done on the impact of these changes on the participant experience, trial operations, or the environment.

Methods: A fully decentralized clinical trial conducted in Singapore is used as a case study to evaluate the operational outcomes, environmental impact (via life cycle assessment), and participants experience (qualitative interviews) of the decentralized model compared to a traditional study with in-person visits.

Results: The decentralized study achieved high participant retention rates (97%) and high completion rates for clinical data, even for biological samples.

Characterisation of pregnancy-induced alterations in apolipoproteins and their associations with maternal metabolic risk factors and offspring birth outcomes: a preconception and longitudinal cohort study.

Background: Apolipoproteins as an integral part of lipoproteins are crucial for the transport and metabolism of lipids. However, there is a lack of longitudinal studies to quantify the concentrations of maternal apolipoproteins from preconception to postpartum and their associations with maternal metabolic health and offspring birth outcomes.

Methods: Quantification of apolipoproteins was performed on maternal plasma samples (N = 243 trios) collected at preconception, 26-28 weeks' pregnancy, and three months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study.

Associations of cord blood concentrations of perfluoroalkyl substances with autistic traits in Singaporean children: The growing up in Singapore towards healthy outcomes study.

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behaviors. Environmental pollutants may contribute to the etiology of ASD, but studies of perfluoroalkyl substances (PFAS) have shown conflicting results.

Objectives: We assessed associations between cord blood concentrations of PFAS with autistic traits at age seven years in a Singaporean birth cohort.

The prospective associations of fetal growth-related pregnancy complications with subsequent breastfeeding duration and markers of human milk production.

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.

Exploring multi-omics and clinical characteristics linked to accelerated biological aging in Asian women of reproductive age: insights from the S-PRESTO study.

Background: Phenotypic age (PhenoAge), a widely used marker of biological aging, has been shown to be a robust predictor of all-cause mortality and morbidity in different populations. Existing studies on biological aging have primarily focused on individual domains, resulting in a lack of a comprehensive understanding of the multi-systemic dysregulation that occurs in aging.

Methods: PhenoAge was evaluated based on a linear combination of chronological age (CA) and 9 clinical biomarkers in 952 multi-ethnic Asian women of reproductive age.

Shaping Adoption and Sustained Use Across the Maternal Journey: Qualitative Study on Perceived Usability and Credibility in Digital Health Tools.

Background: Maternal and child health outcomes are positively influenced by early intervention, and digital health (DH) tools provide the potential for a low-cost and scalable solution such as informational platforms or digital tracking tools. Despite the wide availability of DH tools out there for women from before to after pregnancy, user engagement remains low.

Objective: This study aims to explore the factors that shape women's DH adoption and sustained use across the maternal journey from preconception to postbirth, to improve user engagement with DH tools.

Utilizing Continuous Glucose Monitoring for Early Detection of Gestational Diabetes Mellitus and Pregnancy Outcomes in an Asian Population.

Objective: We explored the potential value of continuous glucose monitoring (CGM) in early pregnancy in predicting gestational diabetes mellitus (GDM) and pregnancy outcomes.

Research Design And Methods: The study recruited 103 multiethnic Asian pregnant women with overweight or obesity from a hospital-based, prospective cohort. All of them had worn blinded CGM devices in early pregnancy and underwent the universal GDM screening at 24-28 gestation weeks.

Higher Plasma -Inositol in Pregnancy Associated with Reduced Postpartum Blood Loss: Secondary Analyses of the NiPPeR Trial.

We previously reported that a combined -inositol, probiotics, and enriched micronutrient supplement (intervention) taken preconception and in pregnancy reduced postpartum blood loss (PBL) and major postpartum hemorrhage compared with a standard micronutrient supplement (control), as secondary outcomes of the NiPPeR trial. This study aimed to identify the intervention components that may contribute to this effect. Associations of plasma concentrations of -inositol and vitamins B2, B6, B12, and D at preconception (before and after supplementation), early (~7-weeks), and late pregnancy (~28-weeks) with PBL were assessed by multiple linear regression, adjusting for site, ethnicity, preconception BMI, parity, and previous cesarean section.

Gestational diabetes-related gut microbiome dysbiosis is not influenced by different Asian ethnicities and dietary interventions: a pilot study.

Gut microbiome dysbiosis contributes to the pathophysiology of both gestational diabetes mellitus (GDM) and its associated adverse outcomes in the woman and offspring. Even though GDM prevalence, complications, and outcomes vary among different ethnic groups, limited information is available about the influence of ethnicity on gut microbiome dysbiosis in pregnancies complicated by GDM. This pilot prospective cohort study examined the impact of ethnicity on gut dysbiosis in GDM among three Asian ethnic groups (Chinese, Malay, Indian) living in Singapore, and investigated the potential modulatory roles of diet and lifestyle modifications on gut microbiome post-GDM diagnosis.