Preliminary assessment of the Healthy Early Life Moments (HELMS) webinars in empowering Developmental Origins of Health and Disease (DOHaD) concept among healthcare professionals - a pragmatic serial cross-sectional study.

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.

Umbilical Cord Plasma Lysophospholipids and Triacylglycerols Associated with Birthweight Percentiles.

Dysregulated transplacental lipid transfer and fetal-placental lipid metabolism affect birthweight, as does maternal hyperglycemia. As the mechanisms are unclear, we aimed to identify the lipids in umbilical cord plasma that were most associated with birthweight. Seventy-five Chinese women with singleton pregnancies recruited into the GUSTO mother-offspring cohort were selected from across the glycemic range based on a mid-gestation 75 g oral glucose tolerance test, excluding pre-existing diabetes. Cord plasma samples collected at term delivery were analyzed using targeted liquid-chromatography tandem mass-spectrometry to determine the concentrations of 404 lipid species across 17 lipid classes. The birthweights were standardized for sex and gestational age by local references, and regression analyses were adjusted for the maternal age, BMI, parity, mode of delivery, insulin treatment, and fasting/2 h glucose, with a false discovery-corrected p < 0.05 considered significant. Ten lysophosphatidylcholines (LPCs) and two lysophosphatidylethanolamines were positively associated with the birthweight percentiles, while twenty-four triacylglycerols were negatively associated with the birthweight percentiles. The topmost associated lipid was LPC 20:2 [21.28 (95%CI 12.70, 29.87) percentile increase in the standardized birthweight with each SD-unit increase in log10-transformed concentration]. Within these same regression models, maternal glycemia did not significantly associate with the birthweight percentiles. Specific fetal circulating lysophospholipids and triacylglycerols associate with birthweight independently of maternal glycemia, but a causal relationship remains to be established.

Longitudinal Analysis of Patterns and Correlates of Physical Activity and Sedentary Behavior in Women From Preconception to Postpartum: The Singapore Preconception Study of Long-Term Maternal and Child Outcomes Cohort.

OBJECTIVE: Longitudinal changes in physical activity (PA) and sedentary behavior patterns from preconception to postpartum are not fully characterized. We examined changes and baseline sociodemographic/clinical correlates of PA and sedentary behavior in women from preconception to postpartum. METHODS: The Singapore Preconception Study of Long-Term Maternal and Child Outcomes cohort recruited 1032 women planning pregnancy. Participants completed questionnaires at preconception, 34 to 36 weeks gestation, and 12 months postpartum. Repeated-measures linear regression models were used to analyze changes in walking, moderate to vigorous PA (MVPA), screen time, and total sedentary time, and to identify sociodemographic/clinical correlates associated with these changes. RESULTS: Of the 373 women who delivered singleton live births, 281 provided questionnaires for all time points. Walking time increased from preconception to late pregnancy but decreased postpartum (adjusted means [95% CI]: 454 [333-575], 542 [433-651], and 434 [320-547] min/wk, respectively). Vigorous-intensity PA and MVPA decreased from preconception to late pregnancy but increased postpartum (vigorous-intensity PA: 44 [11-76], 1 [-3-5], and 11 [4-19] min/wk, MVPA: 273 [174-372], 165 [95-234], and 226 [126-325] min/wk, respectively). Screen time and total sedentary time remained consistent from preconception to pregnancy but decreased postpartum (screen: 238 [199-277], 244 [211-277], and 162 [136-189] min/d, total: 552 [506-598], 555 [514-596], and 454 [410-498] min/d, respectively). Individual characteristics of ethnicity, body mass index, employment, parity, and self-rated general health significantly influenced women's activity patterns. CONCLUSION: During late pregnancy, walking time increased, while MVPA declined significantly, and partially returned to preconception levels postpartum. Sedentary time remained stable during pregnancy but decreased postpartum. The identified set of sociodemographic/clinical correlates underscores need for targeted strategies.

Association of increased abdominal adiposity at birth with altered ventral caudate microstructure.

BACKGROUND: Neonatal adiposity is associated with a higher risk of obesity and cardiometabolic risk factors in later life. It is however unknown if central food intake regulating networks in the ventral striatum are altered with in-utero abdominal growth, indexed by neonatal adiposity in our current study. We aim to examine the relationship between striatal microstructure and abdominal adipose tissue compartments (AATCs) in Asian neonates from the Growing Up in Singapore Toward healthy Outcomes mother-offspring cohort. STUDY DESIGN: About 109 neonates were included in this study. Magnetic resonance imaging (MRI) was performed for the brain and abdominal regions between 5 to 17 days of life. Diffusion-weighted imaging of the brain was performed for the derivation of caudate and putamen fractional anisotropy (FA). Abdominal imaging was performed to quantify AATCs namely superficial subcutaneous adipose tissue (sSAT), deep subcutaneous adipose tissue (dSAT), and internal adipose tissue (IAT). Absolute and percentage adipose tissue of total abdominal volume (TAV) were calculated. RESULTS: We showed that AATCs at birth were significantly associated with increased FA in bilateral ventral caudate heads which are part of the ventral striatum (sSAT: ßleft = 0.56, p < 0.001; ßright = 0.65, p < 0.001, dSAT: ßleft = 0.43, p < 0.001; ßright = 0.52, p < 0.001, IAT: ßleft = 0.30, p = 0.005; ßright = 0.32, p = 0.002) in neonates with low birth weights adjusted for gestational age. CONCLUSIONS: Our study provides preliminary evidence of a potential relationship between neonatal adiposity and in-utero programming of the ventral striatum, a brain structure that governs feeding behavior.

High placental inositol content associated with suppressed pro-adipogenic effects of maternal glycaemia in offspring: the GUSTO cohort.

BACKGROUND/OBJECTIVES: Maternal glycaemia promotes fetal adiposity. Inositol, an insulin sensitizer, has been trialled for gestational diabetes prevention. The placenta has been implicated in how maternal hyperglycaemia generates fetal pathophysiology, but no studies have examined whether placental inositol biology is altered with maternal hyperglycaemia, nor whether such alterations impact fetal physiology. We aimed to investigate whether the effects of maternal glycaemia on offspring birthweight and adiposity at birth differed across placental inositol levels. METHODS: Using longitudinal data from the Growing Up in Singapore Towards healthy Outcomes cohort, maternal fasting glucose (FPG) and 2-hour plasma glucose (2hPG) were obtained in pregnant women by a 75-g oral glucose tolerance test around 26 weeks' gestation. Relative placental inositol was quantified by liquid chromatography-mass spectrometry. Primary outcomes were birthweight (n = 884) and abdominal adipose tissue (AAT) volumes measured by neonatal MRI scanning in a subset (n = 262) of term singleton pregnancies. Multiple linear regression analyses were performed. RESULTS: Placental inositol was lower in those with higher 2hPG, no exposure to tobacco smoke antenatally, with vaginal delivery and shorter gestation. Positive associations of FPG with birthweight (adjusted ß [95% CI] 164.8 g [109.1, 220.5]) and AAT (17.3 ml [11.9, 22.6] per mmol glucose) were observed, with significant interactions between inositol tertiles and FPG in relation to these outcomes (p < 0.05). Stratification by inositol tertiles showed that each mmol/L increase in FPG was associated with increased birthweight and AAT volume among cases within the lowest (birthweight = 174.2 g [81.2, 267.2], AAT = 21.0 ml [13.1, 28.8]) and middle inositol tertiles (birthweight = 202.0 g [103.8, 300.1], AAT = 19.7 ml [9.7, 29.7]). However, no significant association was found among cases within the highest tertile (birthweight = 81.0 g [-21.2, 183.2], AAT = 0.8 ml [-8.4, 10.0]). CONCLUSIONS: High placental inositol may protect the fetus from the pro-adipogenic effects of maternal glycaemia. Studies are warranted to investigate whether prenatal inositol supplementation can increase placental inositol and reduce fetal adiposity.

Macronutrient composition and food groups associated with gestational weight gain: the GUSTO study.

PURPOSE: To examine the associations of energy, macronutrient and food intakes with GWG on 960 pregnant women from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) mother-offspring cohort. METHODS: Dietary intake was assessed at 26-28 weeks' gestation with a 24-hour recall and 3-day food diary. GWG z-scores were calculated from first (4-13 weeks' gestation) and last (30-40 weeks gestation) measured weights; inadequate and excessive GWG were defined using the Institute of Medicine recommendations based on weights between 15 and 35 weeks' gestation. Associations were examined using substitution models for macronutrient composition, with linear or multinomial logistic regressions. RESULTS: Mean ± SD daily energy intake was 1868 ± 598 kcal, and percentage energy intakes were 51.8 ± 8.9% from carbohydrate, 15.7 ± 3.9% from protein and 32.6 ± 7.7% from fat. Higher energy intake (per 500 kcal increment) was associated with 0.18 SD higher GWG. In isocaloric diets, higher-carbohydrate and lower-fat intakes (at 5% energy substitution) were associated with 0.07 SD higher GWG, and 14% higher likelihood of excessive GWG. Concordantly, the highest tertile of carbohydrate-rich foods intake was associated with 0.20 SD higher GWG, but the highest tertile of fruit and vegetable intake was independently associated with 60% lower likelihood of inadequate GWG. Additionally, the highest tertile of dairy intake was associated with 0.18 SD lower GWG; and the highest tertile of plant-based protein foods intake was associated with 60% and 34% lower likelihood of inadequate and excessive GWG. CONCLUSIONS: Balancing the proportions of carbohydrates and fat, and a higher intake of plant-based protein foods may be beneficial for achieving optimal GWG.

Relation of plasma tryptophan concentrations during pregnancy to maternal sleep and mental well-being: The GUSTO cohort.

BACKGROUND: Evidence suggests a relation between plasma tryptophan concentrations and sleep and mental well-being. As no studies have been performed in pregnant women, we studied the relation of plasma tryptophan concentrations during pregnancy with sleep quality, and mood during and after pregnancy. METHODS: Pregnant women (n = 572) from the Growing Up in Singapore Towards healthy Outcomes study completed the Pittsburgh Sleep Quality Index (PSQI), the Edinburgh Postnatal Depression Scale (EPDS) and the State-Trait Anxiety Inventory (STAI) at 26-28 weeks gestation and three months post-delivery. Plasma tryptophan concentrations were measured at 26-28 weeks gestation. Poisson regressions estimated prevalence ratios (PR) for the association between tryptophan and poor sleep quality (PSQI global score > 5), probable antenatal depression (EPDS ≥ 15) and probable anxiety (STAI-state ≥ 41) were calculated adjusting for covariates. RESULTS: Mean plasma tryptophan concentrations was 48.0µmol/L (SD: 8.09). Higher plasma tryptophan concentrations were associated with a lower prevalence of antenatal poor sleep quality adjusting for covariates [PR: 0.88 (95% CI 0.80, 0.97) per 10µmol/L], especially in those participants who also suffered from anxiety symptoms [PR: 0.80 (95% CI 0.67, 0.95)]. No associations were observed between tryptophan concentrations during pregnancy and postnatal sleep quality or mental well-being. LIMITATION: Subjective measures were used to assess sleep and mental well-being. CONCLUSIONS: We observed that higher plasma tryptophan concentrations were associated with a 12% lower prevalence of poor sleep quality during pregnancy, in particular among those with anxiety symptoms. These findings suggest the importance of having adequate tryptophan concentrations during pregnancy.

High folate and low vitamin B12 status during pregnancy is associated with gestational diabetes mellitus.

BACKGROUND & AIMS: B-vitamins and homocysteine may contribute to the development of gestational diabetes mellitus (GDM), but existing studies are inconsistent. We examined the cross-sectional associations of plasma folate, vitamins B6, B12, and homocysteine concentrations with GDM and glycemia in a sample of multi-ethnic Asian pregnant women. METHODS: Plasma concentrations of folate, vitamins B6, B12, homocysteine and glucose were measured at 26-weeks' gestation in 913 pregnant women. GDM was diagnosed using the 1999 World Health Organization criteria. Associations were examined with linear or logistic regression, adjusted for confounders and stratified by ethnicity. RESULTS: Higher plasma folate was associated with higher 2-h glucose and higher odds of GDM [0.15 (0.02, 0.23) per 1-SD increment in folate, OR 1.29 (1.00, 1.60)], mainly among Indian mothers. Higher plasma vitamin B12 and homocysteine were associated with lower fasting and 2-h glucose, and lower odds of GDM [-0.04 (-0.07, -0.01) per 1-SD increment in B12 and -0.09 (-0.18, -0.003) respectively, OR: 0.81 (0.68, 0.97); -0.05 (-0.08, -0.02) per 1-SD increment in homocysteine and -0.12 (-0.21, -0.02) respectively, OR: 0.76 (0.62, 0.92)]. The highest odds of GDM were observed among women with combined vitamin B12 insufficiency and high folate concentration [OR: 1.97 (1.05, 3.68)]. An association between higher vitamin B6 and higher 2-h glucose shifted towards null adjusting for other B-vitamins. CONCLUSIONS: Higher maternal folate coupled with vitamin B12 insufficiency was associated with higher GDM risk. This finding has potential implications for antenatal supplement recommendations but will require confirmation in future studies.

Maternal choline status during pregnancy, but not that of betaine, is related to antenatal mental well-being: The growing up in Singapore toward healthy outcomes cohort.

BACKGROUND: Choline and betaine status have previously been associated with symptoms of depression. However, the relation of maternal plasma choline and betaine concentrations in pregnancy to peripartum maternal mood is unknown. METHODS: Maternal plasma choline and betaine concentrations (µmol/L) were measured at 26-28 weeks gestation in the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother-offspring cohort. Participants completed the State-Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EDPS) at 26-28 weeks gestation (n = 949) and at 3 months postnatal (n = 689): higher scores are indicative of more symptoms of anxiety and depression. Multivariate linear regression models were used to estimate the association of choline and betaine with ante- and postnatal mental well-being adjusting for covariates. RESULTS: Mean (SD) antenatal plasma choline and betaine concentrations were 9.2 µmol/L (1.6) and 13.1 µmol/L (2.7), respectively. Plasma choline concentrations were positively associated with antenatal depressive (ß = .24 EPDS score [95% CI: 0.05-0.43] per µmol/L] and anxiety symptoms (ß = .46 STAI-state score [95% CI: 0.03-0.88] per µmol/L) adjusting for covariates. Plasma betaine concentrations were not associated with antenatal depression or anxiety symptoms. No associations were observed between pregnancy choline or betaine and postnatal mental well-being. CONCLUSION: This study suggests that higher maternal plasma choline status during pregnancy is associated with more symptoms of antenatal depression and anxiety, whereas plasma betaine concentrations showed no associations. No associations were observed for postnatal mental well-being. Prospective studies are required to replicate these findings and further examine the direction of causality and possible biological mechanisms.

Prospective associations of appetitive traits at 3 and 12 months of age with body mass index and weight gain in the first 2 years of life.

BACKGROUND: Appetitive traits in childhood such as food responsiveness and enjoyment of food have been associated with body mass index (BMI) in later childhood. However, data on appetitive traits during infancy in relation to BMI in later childhood are sparse. We aimed to relate appetitive traits in infancy to subsequent BMI and weight gain up to 24 months of age. METHODS: Data of 210 infants from the Singapore GUSTO mother-offspring cohort was obtained. The Baby Eating Behavior Questionnaire (BEBQ) and the Child Eating Behavior Questionnaire (CEBQ) were administered to mothers when their offspring were aged 3 and 12 months respectively. Height and weight of offspring were measured at ages 3, 6, 9,12,15,18 and 24 months. The association of appetitive traits with both BMI z-score and weight gain were evaluated using multivariate linear regression. RESULTS: Food responsiveness at 3 months was associated with higher BMI from 6 months up to 15 months of age (p < 0.01) and with greater weight gain between 3 and 6 months of age (p = 0.012). Slowness in eating and satiety responsiveness at 3 months was significantly associated with lower BMI at 6 months (p < 0.01) and with less weight gain between 3 to 6 months of age (p = 0.034). None of the appetitive traits at 12 months were significantly associated with BMI or weight gain over any time period. CONCLUSION: Early assessment of appetitive traits at 3 months of age but not at 12 months of age was associated with BMI and weight gain over the first two years of life. TRIAL REGISTRATION: Clinical Trials identifier NCT01174875.

A new population-based reference for gestational age-specific size-at-birth of Singapore infants.

INTRODUCTION: There is currently a lack of representative data for local gestational age-specific size-at- birth percentile charts. Existing charts also suffer from limitations relating to the measurement of gestational age (GA) and an outdated population. We aim to construct reference values and charts for size-at-birth from 35 to 41 weeks, based on the healthy local population. MATERIALS AND METHODS: Prospective observational birth cohort study which recruited pregnant mothers from the 2 major public hospitals with obstetric service in Singapore, at <14 weeks gestation and data was collected for birth weight, length and head circumference of infants born from November 2009 to May 2011. Percentile curves were created separately for male and female infants using the lambda-mu-sigma (LMS) method. The new percentile curves were then compared with other internationally published growth charts. RESULTS: Smoothened curves for birth weight, length and head circumference centiles were created from 863 infants (460 males, 403 females). Male infants consistently exceeded female infants in all 3 variables at each GA. For a male and female Singapore infant at 38 weeks gestation, the 10-50-90th centile values for weight would be 2663-3096-3597 vs. 2571-2966-3417 grams, for length 46.4-48.6-51.1 vs. 45.6-48.0-50.4 cm, and for head circumference 32.0-33.5-35.2 vs. 31.4-32.9-34.6 cm. There was no statistically significant difference between ethnic groups. On comparing our birth weight curves with data from Finland across all gestations, birth weights in our term infants (GA ≥37 weeks) were found to be lower across the 10-50-90th percentiles. CONCLUSION: The new centile charts in this study may be used as reference charts for size-at-birth for a subgroup of near-term and term infants. The use of foreign charts may lead to misclassification of small for gestational age (SGA) or large for gestational age (LGA) infants.

Effect of maternal glycemia on neonatal adiposity in a multiethnic Asian birth cohort.

CONTEXT: Gestational hyperglycemia increases the risk of obesity and diabetes in offspring later in life. OBJECTIVE: We examined the relationship between gestational glycemia and neonatal adiposity in a multiethnic cohort of Singaporean neonates. DESIGN: A prospective mother-offspring cohort study recruited 1247 pregnant mothers (57.2% Chinese, 25.5% Malay, 17.3% Indian) and performed 75-g, 2-hour oral glucose tolerance tests at 26-28 weeks' gestation; glucose levels were available for 1081 participants. Neonatal anthropometry (birth weight, length, triceps, and subscapular skinfolds) was measured, and percentage body fat (%BF) was derived using our published equation. Associations of maternal glucose with excessive neonatal adiposity [large for gestational age; %BF; and sum of skinfolds (∑SFT)>90th centile] were assessed using multiple logistic regression analyses. RESULTS: Adjusting for potential confounders we observed strong positive continuous associations across the range of maternal fasting and 2-hour glucose in relation to excessive neonatal adiposity; each 1 SD increase in fasting glucose was associated with 1.31 [95% confidence interval (CI) 1.10-1.55], 1.72 (95% CI 1.31-2.27) and 1.64 (95% CI 1.32-2.03) increases in odds ratios for large for gestational age and %BF and ∑SFT greater than the 90th centile, respectively. Corresponding odds ratios for 2-hour glucose were 1.11 (95% CI 0.92-1.33), 1.55 (95% CI 1.10-2.20), and 1.40 (95% CI 1.10-1.79), respectively. The influence of high maternal fasting glucose on neonatal ∑SFT was less pronounced in Indians compared with Chinese (interaction P=.005). CONCLUSIONS: A continuous relationship between maternal glycemia and excessive neonatal adiposity extends across the range of maternal glycemia. Compared with Chinese infants, Indian infants may be less susceptible to excessive adiposity from high maternal glucose levels.