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Abstract Background It is not clear if conventional liver fat cutoff of 5.56% weight which has been used for identifying fatty liver in western populations is also applicable for Asians. In Asian women of reproductive age, we evaluate the optimum metabolic syndrome (MetS)-linked liver fat cutoff, the specific metabolomic alterations apparent at this cutoff, as well as prospective associations of preconception liver fat levels with gestational dysglycemia. Methods Liver fat (measured by magnetic resonance spectroscopy), MetS, and nuclear magnetic resonance (NMR)-based plasma metabolomic profiles were assessed in 382 Asian women, who were planning to conceive. Ninety-eight women went on to become pregnant and received an oral glucose tolerance test at week 26 of gestation. Results The optimum liver fat cutoff for diagnosing MetS was 2.07%weight. Preconception liver fat was categorized into Low (liver fat

Abstract Background Nutritional intervention preconception and throughout pregnancy has been proposed as an approach to promoting healthy postnatal weight gain in the offspring but few randomised trials have examined this. Methods Measurements of weight and length were obtained at multiple time points from birth to 2 years among 576 offspring of women randomised to receive preconception and antenatally either a supplement containing myo-inositol, probiotics, and additional micronutrients (intervention) or a standard micronutrient supplement (control). We examined the influence on age- and sex-standardised BMI at 2 years (WHO standards, adjusting for study site, sex, maternal parity, smoking and pre-pregnancy BMI, and gestational age), together with the change in weight, length, BMI from birth, and weight gain trajectories using latent class growth analysis. Results At 2 years, there was a trend towards lower mean BMI among intervention offspring (adjusted mean difference [aMD] − 0.14 SD [95% CI 0.30, 0.02], p = 0.09), and fewer had a BMI > 95th percentile (i.e. > 1.65 SD, 9.2% vs 18.0%, adjusted risk ratio [aRR] 0.51 [95% CI 0.31, 0.82], p = 0.006). Longitudinal data revealed that intervention offspring had a 24% reduced risk of experiencing rapid weight gain > 0.67 SD in the first year of life (21.9% vs 31.1%, aRR 0.76 [95% CI 0.58, 1.00], p = 0.047). The risk was likewise decreased for sustained weight gain > 1.34 SD in the first 2 years of life (7.7% vs 17.1%, aRR 0.55 [95% CI 0.34, 0.88], p = 0.014). From five weight gain trajectories identified, there were more intervention offspring in the “normal” weight gain trajectory characterised by stable weight SDS around 0 SD from birth to 2 years (38.8% vs 30.1%, RR 1.29 [95% CI 1.03, 1.62], p = 0.029). Conclusions Supplementation with myo-inositol, probiotics, and additional micronutrients preconception and in pregnancy reduced the incidence of rapid weight gain and obesity at 2 years among offspring. Previous reports suggest these effects will likely translate to health benefits, but longer-term follow-up is needed to evaluate this. Trial registration ClinicalTrials.gov, NCT02509988 (Universal Trial Number U1111-1171–8056). Registered on 16 July 2015.

Abstract Background Increasing maternal glycaemia across the continuum during pregnancy may predispose offspring to subsequent cardiometabolic risk later in life. However, evidence of long-term impacts of maternal glycemic status on offspring amino acid (AA) profiles is scarce. We aimed to investigate the association between maternal antenatal glycaemia and offspring mid-childhood amino acid (AA) profiles, which are emerging cardiometabolic biomarkers. Methods Data were drawn from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study, a multi-ethnic Asian birth cohort. A subset of 422 mother–child dyads from the GUSTO study, who was followed from early pregnancy to mid-childhood, was included. Mothers underwent an oral glucose tolerance test (OGTT) at 26–28 weeks gestation, with fasting and 2-h plasma glucose concentrations measured and gestational diabetes mellitus (GDM) diagnosed per WHO 1999 guidelines. Offspring fasting plasma samples were collected at mean age 6.1 years, from which AA profiles of nine AAs, alanine, glutamine, glycine, histidine, isoleucine, leucine, valine, phenylalanine, and tyrosine were measured. Total branched-chain amino acids (BCAAs) were calculated as the sum of isoleucine, leucine, and valine concentrations. Multi-variable linear regression was used to estimate the association of maternal glycemic status and offspring mid-childhood AA profiles adjusting for maternal age, ethnicity, maternal education, parity, family history of diabetes, ppBMI, child sex, age and BMI z-scores. Results Approximately 20% of mothers were diagnosed with GDM. Increasing maternal fasting glucose was significantly associated with higher offspring plasma valine and total BCAAs, whereas higher 2-h glucose was significantly associated with higher histidine, isoleucine, valine, and total BCAAs. Offspring born to mothers with GDM had higher valine (standardized mean difference 0.27 SD; 95% CI: 0.01, 0.52), leucine (0.28 SD; 0.02, 0.53), and total BCAAs (0.26 SD; 0.01, 0.52) than their counterparts. Inconsistent associations were found between maternal GDM and other amino acids among offspring during mid-childhood. Conclusions Increasing maternal fasting and post-OGTT glucose concentrations at 26–28 weeks gestation were significantly associated with mid-childhood individual and total BCAAs concentrations. The findings suggest that elevated maternal glycaemia throughout pregnancy, especially GDM, may have persistent programming effects on offspring AA metabolism which were strongly associated with adverse cardiometabolic profiles at mid-childhood.

Abstract Background Adaptations in lipid metabolism are essential to meet the physiological demands of pregnancy and any aberration may result in adverse outcomes for both mother and offspring. However, there is a lack of population-level studies to define the longitudinal changes of maternal circulating lipids from preconception to postpartum in relation to cardiometabolic risk factors. Methods LC-MS/MS-based quantification of 689 lipid species was performed on 1595 plasma samples collected at three time points in a preconception and longitudinal cohort, Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO). We mapped maternal plasma lipidomic profiles at preconception (N = 976), 26–28 weeks’ pregnancy (N = 337) and 3 months postpartum (N = 282) to study longitudinal lipid changes and their associations with cardiometabolic risk factors including pre-pregnancy body mass index, body weight changes and glycaemic traits. Results Around 56% of the lipids increased and 24% decreased in concentration in pregnancy before returning to the preconception concentration at postpartum, whereas around 11% of the lipids went through significant changes in pregnancy and their concentrations did not revert to the preconception concentrations. We observed a significant association of body weight changes with lipid changes across different physiological states, and lower circulating concentrations of phospholipids and sphingomyelins in pregnant mothers with higher pre-pregnancy BMI. Fasting plasma glucose and glycated haemoglobin (HbA1c) concentrations were lower whereas the homeostatic model assessment of insulin resistance (HOMA-IR), 2-h post-load glucose and fasting insulin concentrations were higher in pregnancy as compared to both preconception and postpartum. Association studies of lipidomic profiles with these glycaemic traits revealed their respective lipid signatures at three physiological states. Assessment of glycaemic traits in relation to the circulating lipids at preconception with a large sample size (n = 936) provided an integrated view of the effects of hyperglycaemia on plasma lipidomic profiles. We observed a distinct relationship of lipidomic profiles with different measures, with the highest percentage of significant lipids associated with HOMA-IR (58.9%), followed by fasting insulin concentration (56.9%), 2-h post-load glucose concentration (41.8%), HbA1c (36.7%), impaired glucose tolerance status (31.6%) and fasting glucose concentration (30.8%). Conclusions We describe the longitudinal landscape of maternal circulating lipids from preconception to postpartum, and a comprehensive view of trends and magnitude of pregnancy-induced changes in lipidomic profiles. We identified lipid signatures linked with cardiometabolic risk traits with potential implications both in pregnancy and postpartum life. Our findings provide insights into the metabolic adaptations and potential biomarkers of modifiable risk factors in childbearing women that may help in better assessment of cardiometabolic health, and early intervention at the preconception period. Trial registration ClinicalTrials.gov, NCT03531658.