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Objectives: To examine associations of the timing of complementary feeding (CF) introduction with adiposity throughout childhood., Methods: We studied 1013 children from Project Viva. Our exposure was CF introduction, categorized as <4 months (19%), 4 to <6 months (68%; reference group), and ≥6 months of age (14%). Our outcomes included adiposity measures in midchildhood (mean: 7.9 years; SD 0.8; n = 896) and early adolescence (mean: 13.2 years; SD 0.9; n = 850). We used linear regression models adjusted for potential confounders and ran separate models for infants who were breastfed at least partly for ≥4 months (categorized as breastfed; 69%) and infants who were never breastfed or stopped breastfeeding at <4 months (categorized as formula fed; 31%)., Results: CF initiated at <4 months was associated with higher adiposity in midchildhood in breastfed children; associations persisted into adolescence for waist circumference, truncal fat mass, and the sum of subscapular and triceps skinfolds (eg, waist circumference: confounder-adjusted β 2.97 [95% confidence interval (CI) 0.47 to 5.47] cm). The effect estimates were larger in formula-fed children, with more associations persisting into adolescence (eg, waist circumference: adjusted β 3.42 [95% CI 0.12 to 6.71] cm). CF initiated at ≥6 months was associated with a higher subscapular/triceps skinfold ratio in midchildhood and adolescence (adjusted β 0.13 [95% CI 0.02 to 0.25]) in formula-fed children., Conclusions: We found associations of early CF introduction with higher adiposity measurements in breastfed and formula-fed children and associations of late introduction of CF with higher adiposity in formula-fed children., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Objective: To investigate the association of preconception parental obesity (body mass index [BMI] ≥30 kg/m 2 ) with offspring pubertal development., Study Design: Among 1377 children from a prospective prebirth cohort in Boston, we examined markers of puberty (age at peak height velocity [PHV], age at menarche, self-reported pubertal development score), and adrenarche (pictograph Tanner pubic hair staging). We used multivariable regression models to examine associations of maternal and paternal obesity with offspring pubertal indices, and applied marginal structural models to estimate the controlled direct effect not mediated by offspring prepubertal BMI., Results: The prevalence of paternal obesity alone, maternal obesity alone, and biparental obesity were 10.5%, 10.1%, and 5%, respectively. After adjusting for demographic and socioeconomic factors, parental heights and maternal age at menarche, maternal obesity alone (vs neither parent with obesity) was associated with earlier age at PHV (β -0.30 years; 95% CI -0.57, -0.03) and higher early adolescent pubertal score (0.29 units; 0.10, 0.48) in boys, but not with pubertal or adrenarchal outcomes in girls. Paternal obesity alone was not associated with any outcomes in either boys or girls. Biparental obesity was associated with earlier age at PHV in boys and earlier menarche in girls. Using marginal structural models with stabilized inverse probability weighting, maternal obesity alone had significant controlled direct effects on age at PHV (-0.31 years; -0.62, 0.00) and on pubertal score (0.22 units; 0.00, 0.44) in boys, independent of prepubertal BMI., Conclusion: Maternal, but not paternal, obesity is associated with earlier pubertal development in boys, and such association is independent of prepubertal BMI., (Copyright © 2019 Elsevier Inc. All rights reserved.)

About a quarter of children with new onset of Kawasaki disease (KD) encounter coronary arterial involvement. While KD is known to cause vasculitis of medium-sized vessels, few studies have been done to study the involvement of the microcirculation. We aimed to investigate the association between coronary arterial dilatation and retinal microvasculature in a pilot setting, in order to further study the pathophysiological mechanism of KD from the perspective of small vessels changes. We performed a cross-sectional, observational, hospital-based study on 11 children aged 2 years and above with new-onset KD. Cardiac imaging technicians performed the echocardiographic examinations and recorded right coronary artery (RCA), left coronary artery (LCA) and left anterior descending artery (LAD). Qualified retinal graders reviewed and graded standardised retinal photographs to assess retinal microvascular parameters. Among 11 participants, there were 7 boys and 4 girls. Median and interquartile range of participants' age were 5.92 (3.08) years. After adjusting for age and sex, each unit increase in LAD (mm) was significantly associated with increment of retinal arteriolar tortuosity (4.25 × 10 -5 units, 95% Confidence Interval: 1.19, 7.32). Retinal arteriolar geometric changes were associated with LAD dilatation in 11 children with new onset of KD. Our pilot provided proof-of-concept that retinal imaging might be useful for detecting coronary arterial involvement in young children with KD and it needs further investigation.

Parents' feeding practices have been shown to be associated with children's food intake and weight status, but little is known about feeding practices in Asian countries. This study used behavioral observation to explore the feeding practices of 201 mothers of 4.5 year-old children in Singapore during an ad libitum buffet lunch. Feeding practices were coded from videos, focusing on behaviors used to prompt the child to eat more food (autonomy-supportive and coercive-controlling prompts to eat, suggesting items from buffet), those to reduce intake (restriction, questioning food choice), and those related to eating rate (hurrying or slowing child eating). Child outcome measures included energy consumed, variety of food items selected, and BMI. Maternal restriction and trying to slow child eating rate were associated with higher energy consumed by the child (r = 0.19 and 0.13, respectively; p < 0.05). Maternal autonomy-supportive prompts and restriction were associated with a greater variety of items selected by children (r = 0.19 and 0.15, respectively; p < 0.05). The frequency of maternal feeding practice use differed across ethnic groups, with Malay mothers using the most prompts to eat (p < 0.05), Chinese mothers most likely to question a child's food choice (p < 0.01), and Indian mothers the last likely to tell the child to eat faster (p < 0.001). There were no differences between ethnic groups for other feeding practices. No associations were found between feeding practices and child BMI. It is possible that feeding practices related to restriction and slowing child eating are adopted in response to children who consume larger portions, although longitudinal or intervention studies are needed to confirm the direction of this relationship and create local recommendations., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Childhood blood pressure (BP) is a strong predictor of later risk of cardiovascular disease. However, few studies have assessed dynamic BP trajectories throughout the early-life period. We investigated the relationship between early-life factors and systolic BP (SBP) from infancy to adolescence using linear spline mixed-effects models among 1,370 children from Project Viva, a Boston, Massachusetts-area cohort recruited in 1999-2002. After adjusting for confounders and child height, we observed higher SBP in children exposed to gestational diabetes mellitus (vs. normoglycemia; age 3 years: β = 3.16 mm Hg (95% confidence interval (CI): 0.28, 6.04); age 6 years: β = 1.83 mm Hg (95% CI: 0.06, 3.60)), hypertensive disorders of pregnancy (vs. normal maternal BP; age 6 years: β = 1.39 mm Hg (95% CI: 0.10, 2.67); age 9 years: β = 1.84 mm Hg (95% CI: 0.34, 3.34); age 12 years: β = 1.70 mm Hg (95% CI: 0.48, 2.92)), higher neonatal SBP (per 10-mm Hg increase; age 3 years: β = 1.26 mm Hg (95% CI: 0.42, 2.09); age 6 years: β = 1.00 mm Hg (95% CI: 0.49, 1.51); age 9 years: β = 0.75 mm Hg (95% CI: 0.17, 1.33)), and formula milk in the first 6 months of life (vs. breast milk only; age 12 years: β = 2.10 mm Hg (95% CI: 0.46, 3.74); age 15 years: β = 3.52 mm Hg (95% CI: 1.40, 5.64); age 18 years: β = 4.94 mm Hg (95% CI: 1.88, 7.99)). Our findings provide evidence of programming of offspring SBP trajectories by gestational diabetes, hypertensive disorders of pregnancy, and formula milk intake and of neonatal BP being a potentially useful marker of childhood BP. These factors could be relevant in identifying children who are at risk of developing elevated BP., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Traditional dietary recommendations for achieving optimal gestational weight gain are ineffective for pregnant women due to the lack of real-time communication and tedious consultation processes., Objective: In this pilot study, we aimed to determine the feasibility of a novel food-coaching smartphone app for controlling gestational weight gain and macronutrient intake among overweight and obese pregnant women., Methods: We designed a randomized controlled trial and recruited 30 overweight and obese pregnant women (1:1 ratio) during 18-20 weeks of gestation and followed them up after 4 and 8 weeks, respectively. Both groups received standard pregnancy dietary orientation at recruitment, while the intervention group received 8 weeks of real-time food coaching via a smartphone app. This food-coaching smartphone app (Glycoleap, Holmusk, Singapore) aimed to improve care and outcomes for people with diabetes. Pregnant women using this app were able to upload food images (eg, a picture of a meal, a drink, or a dessert) and received real-time and detailed food-coaching comments and guidance provided by professional dietitians during the day (8 AM to 8 PM). We recorded detailed characteristics during recruitment and examined anthropometry at all visits. We compared the mean differences of the 8-week gestational weight gain and macronutrient intake between the two groups., Results: Upon study completion, three subjects dropped out from the intervention, and one gave birth prematurely in the control group. The acceptance rate of the smartphone app was 90%. More participants achieved optimal gestational weight gain per week in the intervention group (8/12, 67%) than in the control group (5/14, 36%). After the 8-week intervention, women in the intervention group appeared to have lower gestational weight gain (mean difference=-0.08 kg; 95% CI -1.80 to 1.63) and cholesterol intake (mean difference=-31.73 mg; 95% CI -102.91 to 39.45) than those in the control group., Conclusions: Our findings showed that this food-coaching smartphone app is feasible and favorable for weight gain control and cholesterol intake control among overweight and obese pregnant women. Although our results were not significant (perhaps, attributed to the small sample size), it provided proof of concept for the feasibility of applying such technology in future randomized controlled trials with a larger sample size, an earlier intervention onset, and a longer follow-up for overweight and obese pregnant women., (©Ling-Jun Li, Izzuddin M Aris, Wee Meng Han, Kok Hian Tan. Originally published in JMIR Formative Research (http://formative.jmir.org), 24.10.2019.)

Background: In the past decade, continuous glucose monitoring (CGM) has been proven to have similar accuracy to self-monitoring of blood glucose (SMBG) and yet provides better therapy optimization and detects trends in glucose values due to higher frequency of testing. Even though the feasibility and utility of CGM has been proven successfully in Type 1 and 2 diabetes, there is a lack of knowledge of its application and effectiveness in pregnancy, especially in gestational diabetes mellitus (GDM). In this review, we aimed to summarize and evaluate the updated scientific evidence on the application of CGM in pregnancies complicated with GDM. Methods: A search using keywords related to CGM and GDM on PubMed was conducted and articles were filtered based on full text, year of publication (Jan 1998-Dec 2018), human subject studies, and written in English. Reviews and duplicate articles were removed. A final total of 29 articles were included in this review. Results: In terms of maternal and fetal outcomes, inconsistent evidence was reported. Among GDM patients using CGM and SMBG, two randomized controlled trials (RCTs) found no significant differences in macrosomia, birth weight (BW), and gestational age (GA) at delivery between these two groups, while one prospective cohort found a lower incidence of cesarean section and macrosomia in CGM use subjects. Furthermore, CGM use was consistently found to have increased detection in dysglycemia and glycemic variability compared to SMBG. In terms of clinical utility, CGM use led to more treatment adjustments and lower gestational weight gain (GWG). Lastly, CGM use showed higher postprandial glucose levels in GDM-complicated pregnancies than in normal pregnancies. Conclusion: Current updated evidence suggests that CGM is superior to SMBG among GDM pregnancies in terms of detecting hypoglycemic and hyperglycemic episodes, which might result in an improvement of maternal and fetal outcomes. In addition, CGM detects a wider glycemic variability in GDM mothers than non-GDM controls. Further research with larger sample sizes and complete pregnancy coverage is needed to explore the clinical utility such as screening and predictive values of CGM for GDM., (Copyright © 2019 Yu, Aris, Tan and Li.)

Objective: The aim of this study was to investigate the relationship of BMI with subsequent statural growth among children born in the era of the obesity epidemic., Methods: Among 18,271 children from Belarus (n = 16,781, born 1996 to 1997) and the United States (n = 1,490, born 1999 to 2002), multivariable linear and ordinal logistic regression was used to analyze associations of BMI z score from infancy to adolescence with subsequent standardized length and height velocity, standing height and its components (trunk and leg lengths), and pubertal timing., Results: The prevalence of early adolescent obesity was 6.2% in Belarus and 12.8% in the United States. In both Belarusian and US children, higher BMI z scores in infancy and childhood were associated with faster length and height velocity in early life, while higher BMI z scores during middle childhood were associated with slower length and height velocity during adolescence. Associations with greater standing height and trunk length and earlier pubertal development in adolescence were stronger for BMI z scores at middle childhood than BMI z scores at birth or infancy., Conclusions: These findings in both Belarus and the United States support the role of higher BMI in accelerating linear growth in early life (taller stature and longer trunk length) but earlier pubertal development and slower linear growth during adolescence., (© 2019 The Obesity Society.)

Background: Self-reported maternal active smoking has been associated with reduced offspring birth length and shorter stature in early and late childhood., Objective: To use circulating cotinine as an objective biomarker to investigate the association between smoking and environmental tobacco smoke (ETS) exposure in pregnancy and longitudinal measures of offspring length/height from birth to 60 months., Methods: In 969 maternal-offspring dyads from the GUSTO cohort, maternal plasma cotinine at 26-28 weeks' gestation was measured by LC/MS/MS and categorized into four groups: Group 1: cotinine <0.17 ng/mL (the assay's detection limit) and no ETS exposure; Group 2: cotinine <0.17 ng/mL but self-reported ETS; Group 3: cotinine 0.17-13.99 ng/mL (ETS or light smoking); Group 4: cotinine ≥14 ng/mL (active smoking)., Results: Adjusting for infant sex, gestational age at birth, ethnicity, maternal age, education, parity, BMI, and height, Group 4 offspring were shorter at birth [z-score β = -0.42 SD units (SDs) (95% CI = -0.77 to -0.06)] than Group 1 offspring. Group 4 offspring continued to be shorter at older ages, with similar effect sizes at 3 months [-0.57 SDs (-0.95 to -0.20)], 36 months [-0.53 SDs (-0.92 to -0.15)], 48 months [-0.43 SDs (-0.81 to -0.04)], and 60 months [-0.57 SDs (-0.96 to -0.17)]. Associations were particularly marked in boys. No significant differences in stature were observed in Groups 2 or 3 compared with Group 1., Conclusions: This Asian longitudinal study associated high prenatal cotinine with persistently shorter stature in offspring from birth and into early childhood, whilst low prenatal cotinine levels and ETS exposure showed no such association., Implications: Little is known about the long-term effects of prenatal tobacco exposure on offspring stature in Asia where passive smoking is common. This study has used an objective biomarker to reveal that the association of prenatal tobacco exposure with offspring length/height mainly occurs at a high maternal cotinine level of greater than 14 ng/mL in pregnancy, consistent with active smoking, but no significant associations were found with lower cotinine levels, consistent with passive smoking. Encouraging women to quit smoking prior to or during pregnancy may avert the long-term negative impact on their child's height despite appreciable prenatal ETS exposure., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To provide an updated birth weight-for-gestational age (BW-for-GA) reference in the United States by using the most recent, nationally representative birth data with obstetric estimates of gestational age (GA)., Methods: We abstracted 3 285 552 singleton births between 22 and 42 weeks' gestation with nonmissing race and/or ethnicity, infant sex, parity, birth weight, and obstetric estimate of GA from the 2017 US natality files. We used 2 techniques (nonlinear, resistant smoothing [4253H] and lambda-mu-sigma) to derive smoothed BW-for-GA curves and compared resulting BW-for-GA cut-points at the third, 10th, 90th, and 97th percentiles with US references from 1999 to 2009., Results: The smoothed BW-for-GA curves from both techniques overlapped considerably with each other, with strong agreements seen between the 2 techniques (>99% agreement; κ-statistic >0.9) for BW-for-GA cut-points at the third, 10th, 90th, and 97th percentiles across all GAs. Cut-points from 2017 using the lambda-mu-sigma method captured 9.8% to 10.2% of births <10th and >90th percentiles and 2.6% to 3.3% of births below the third and above the 97th percentile across all GAs. However, cut-points from US references in 1999 and 2009 (when GA was based on last menstrual period) captured a much larger range of proportions of 2017 births at these thresholds, especially among preterm and postterm GA categories., Conclusions: We have provided an updated BW-for-GA reference in the United States using the most recent births with obstetric estimates of GA and information to calculate continuous measures of birth size that are sex or parity specific., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Objectives: Screen-viewing in late childhood has been associated with adiposity and blood pressure (BP), but evidence is lacking at younger ages. To investigate the prospective associations of total and device-specific screen-viewing at age 2-3 years with BMI, sum of skinfold thicknesses and BP among Singaporean children at age 3-5 years., Methods: As part of the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort, mothers/caregivers reported the time per day their 2 and 3-year-old children watched/used television, handheld devices and computers. Average screen-viewing time (total, television and handheld-devices) at ages 2 and 3 years was used in the analyses. Height; weight; triceps, biceps and subscapular skinfold thicknesses; and systolic and diastolic BP were measured at ages 3, 4 and 5. Associations of screen-viewing with BMI, sum of skinfold thicknesses and BP in 956 children were investigated using repeated-measures linear regression models. Analyses were further stratified by sex as we found significant interaction., Results: Among boys and girls combined, screen-viewing was positively associated with sum of skinfold thicknesses, but not with BMI or BP. Sex-specific analyses showed significant associations with both BMI and sum of skinfold thicknesses in boys, but not in girls. Screen-viewing was not associated with BP in boys or girls. The increases in mean (95% CI) BMI per hour increase in daily total, television and handheld-devices screen-viewing among boys were 0.12 (0.03, 0.21), 0.18 (0.06, 0.30) and 0.11 (-0.07, 0.29) kg/m 2 , respectively. The corresponding increases in mean sum of skinfold thicknesses were 0.68 (0.29, 1.07), 0.79 (0.26, 1.32) and 1.18 (0.38, 1.99) mm., Conclusions: Greater screen-viewing at age 2-3 years was associated with later adiposity at 3-5 years in boys, but not in girls. In light of the increasing use of screen devices and cardiometabolic risk in young children, these findings may have important public health implications.

Aim: To examine the associations of physical activity and screen time, a proxy for sedentary behaviour, with fasting and post-load glucose levels in Singaporean women enrolled in a multi-ethnic Asian preconception study., Methods: Moderate and vigorous physical activity and screen time (television and other electronic devices) were self-reported by women enrolled in the S-PRESTO cohort. Fasting, 30-min and 120-min glucose levels before and during a 75-g oral glucose tolerance test were measured. Associations of physical activity and screen time with glucose levels were analysed using multivariable linear marginal regression., Results: A total of 946 women aged 31.4±3.7 years were examined, of whom 72% were of Chinese, 15.5% were of Malay, 9.3% were of Indian and 3.2% were of mixed ethnicity. A total of 32% of women reported being active, 36% watched television ≥2 h/day and 26% used electronic devices ≥3 h/day. In adjusted models, vigorous, but not moderate, physical activity was associated with lower overall glucose levels, and was associated more strongly with post-challenge than fasting glucose levels. Compared to women not engaging in vigorous physical activity, those engaging in physical activity ≥75 min/week had lower mean fasting [-0.14 (95% CI -0.28, -0.01) mmol/l], 30-min [0.35 (95% CI -0.68, -0.02) mmol/l] and 120-min [-0.53 (95% CI -0.16, -0.90) mmol/l] glucose levels (overall P value=0.05). We found no associations of screen time with glucose levels., Conclusions: Independently of the time spent in non-vigorous physical activity and using screens, engaging in vigorous physical activity may be a modifiable factor to improve glucose regulation in women of Asian ethnicity who are attempting to conceive., (© 2019 Diabetes UK.)

The effect of saturated fatty acids (SFAs) on incident type 2 diabetes (T2D) is controversial and few have systematically appraised the evidence. We conducted a comprehensive search of prospective studies examining these relationships that were published in PubMed, Web of Science, or EMBASE from 21 February 1989 to 21 February 2019. A total of 19 studies were included for systematic review and 10 for meta-analysis. We estimated the summarized relative risk (RR) and 95% confidence interval (95% CI) using a random (if I 2 > 50%) or a fixed effects model (if I 2 ≤ 50%). Although the included studies reported inconclusive results, the majority supported a protective effect of odd-chain and an adverse impact of even-chain SFAs. Meta-analysis showed that the per standard deviation (SD) increase in odd-chain SFAs was associated with a reduced risk of incident T2D (C15:0: 0.86, 0.76-0.98; C17:0: 0.76, 0.59-0.97), while a per SD increase in one even-chain SFA was associated with an increased risk of incident T2D (C14:0: 1.13, 1.09-1.18). No associations were found between other SFAs and incident T2D. In conclusion, our findings suggest an overall protective effect of odd-chain SFAs and the inconclusive impact of even- and very-long-chain SFAs on incident T2D., Competing Interests: The authors declare no conflict of interest.

Revised subscales of the Children's Eating Behavior Questionnaire (CEBQ) have been proposed to be more appropriate for assessing appetitive traits in Singaporean 3 year-olds, but the CEBQ has not yet been validated in older children in this population. The current study aimed to validate the CEBQ at ages 5 ( n = 653) and 6 ( n = 449) in the ethnically diverse GUSTO cohort. Confirmatory factor analysis (CFA) examined whether the established eight-factor model of the CEBQ was supported in this sample. Overall, the CFA showed a poor model fit at both ages 5 and 6. At both ages 5 and 6, an exploratory factor analysis revealed a six-factor structure: food fussiness, enjoyment of food, slowness in eating, emotional undereating, emotional overeating and desire to drink. Cronbach's alpha estimates ranged from 0.70 to 0.85 for all subscales. Criterion validity was tested by correlating subscales with the weight status of 6 years of age. At age 5 and 6, lower scores of slowness of eating while higher scores of enjoyment of food was associated with child overweight. At age 6, higher scores of desire to drink was also associated child overweight. In conclusion, a revised six factor-structure of the CEBQ at ages 5 and 6 were more appropriate for examining appetitive traits in this sample.

Bidirectional studies between maternal feeding practices with subsequent child weight are limited, with no studies in Asian populations. In longitudinal analyses, we assessed the directionality of the associations between maternal feeding practices and body mass index (BMI) in preschoolers. Participants were 428 mother child dyads from the GUSTO (Growing Up in Singapore Toward healthy Outcomes) cohort. Feeding practices were assessed using the Comprehensive Feeding Practices Questionnaire (CFPQ) at age 5 y. Child BMI was measured at ages 4 and 6 y. BMI and maternal feeding practices subscales were transformed to SD scores and both directions of their associations examined with multivariable linear regression and pathway modeling. Higher BMI at age 4 was associated with lower encouragement of balance and variety (β = -0.33; 95%CI: -0.53, -0.13), lower pressure to eat (β = -0.49; -0.68, -0.29) and higher restriction (β = 1.10; 0.67, 1.52) at age 5, adjusting for confounders and baseline feeding practices at 3 years. In the reverse direction, only pressure and restriction at age 5 were associated with lower and higher child BMI at age 6 years, respectively. After the adjustment for baseline BMI at age 5, the association with pressure was attenuated to non-significance (β = 0.01 (-0.01, 0.03), while the association with restriction remained significant (β = 0.02; 0.002, 0.03). Overall, associations from child BMI to maternal restriction for weight control and pressure feeding practices was stronger than the association from these maternal feeding practices to child BMI (Wald's statistics = 24.3 and 19.5, respectively; p < 0.001). The strength and directionality suggests that the mothers in the Asian population were likely to adopt these feeding practices in response to their child's BMI, rather than the converse. Clinical Trial Registry Number and Website   This study was registered at clinicaltrials.gov as NCT01174875 (www.clinicaltrials.gov, NCT01174875).

Background: Choline status has been positively associated with weight and fat mass in animal and human studies. As evidence examining maternal circulating choline concentrations and offspring body composition in human infants/children is lacking, we investigated this in two cohorts., Methods: Maternal choline concentrations were measured in the UK Southampton Women's Survey (SWS; serum, n = 985, 11 weeks' gestation) and Singapore Growing Up Towards healthy Outcomes (GUSTO); n = 955, 26-28 weeks' gestation) mother-offspring cohorts. Offspring anthropometry was measured at birth and up to age 5 years. Body fat mass was determined using dual-energy x-ray absorptiometry at birth and age 4 years for SWS; and using air-displacement plethysmography at birth and age 5 years for GUSTO. Linear-regression analyses were performed, adjusting for confounders., Results: In SWS, higher maternal choline concentrations were associated with higher neonatal total body fat mass {β = 0.60 standard deviation [SD]/5 µmol/L maternal choline [95% confidence interval (CI) 0.04-1.16]} and higher subscapular skinfold thickness [β = 0.55 mm/5 µmol/L (95% CI, 0.12-1.00)] at birth. In GUSTO, higher maternal choline concentrations were associated with higher neonatal body mass index-for-age z-score [β = 0.31 SD/5 µmol/L (0.10-0.51)] and higher triceps [β = 0.38 mm/5 µmol/L (95% CI, 0.11-0.65)] and subscapular skinfold thicknesses [β = 0.26 mm/5 µmol/L (95% CI, 0.01-0.50)] at birth. No consistent trends were observed between maternal choline and offspring gain in body mass index, skinfold thicknesses, abdominal circumference, weight, length/height and adiposity measures in later infancy and early childhood., Conclusion: Our study provides evidence that maternal circulating choline concentrations during pregnancy are positively associated with offspring BMI, skinfold thicknesses and adiposity at birth, but not with growth and adiposity through infancy and early childhood to the age of 5 years., (© The Author(s) 2019; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objective: The aim of this study was to investigate the independent associations between age-specific annual weight gain from birth to age 4 years and fat deposition in metabolically distinct compartments at age 4.5 years in a South Asian longitudinal birth cohort., Methods: Volumetric abdominal magnetic resonance imaging with comprehensive segmentation of deep and superficial subcutaneous adipose tissue (SAT) and visceral adipose tissues (VAT) was performed in 316 children (150 boys and 166 girls in three ethnic groups; 158 Chinese, 94 Malay, and 64 Indian) aged 4.5 years. Associations between fat volumes and annual relative weight gain conditional on past growth were assessed overall and stratified by sex and ethnicity., Results: Conditional relative weight gain had stronger associations with greater SAT and VAT at age 4.5 years in girls than boys and in Indians compared with Malay and Chinese. Overall, the magnitude of association was the largest during 2 to 3 years for SAT and 1 to 2 years for VAT. Despite similar body weight, Indian children and girls had the highest deep and superficial SAT volumes at age 4.5 years (all interactions P < 0.05). No significant sex or ethnic differences were observed in VAT. With increasing BMI, Indian children had the highest tendency to accumulate VAT, and girls accumulated more fat than boys in all depots (all interactions P < 0.001)., Conclusions: Indian ethnicity and female sex predisposed children to accumulate more fat in the VAT depot with increasing conditional relative weight gain in the second year of life. Thus, 1 to 2 years of age may be a critical window for interventions to reduce visceral fat accumulation., (© 2019 The Obesity Society.)

Dietary patterns during pregnancy have been shown to influence the development of gestational diabetes mellitus (GDM). However, evidence from Asian populations is limited and inconsistent. We conducted a prospective cohort study in China to assess the relationship between dietary patterns and GDM. We administered three-day food diaries (TFD) and food frequency questionnaires (FFQ) at the second trimester. GDM was diagnosed with a 75 g 2-h oral glucose tolerance test at 24⁻28 weeks of gestation. We identified dietary patterns using principal components analysis and used multivariable logistic regression to investigate associations of dietary patterns with GDM. Of the 1014 participants, 23.5% were diagnosed with GDM. Both the TFD and FFQ identified a "traditional pattern", consisting of high vegetable, fruit, and rice intake, which was associated with a lower GDM risk (odds ratio (OR) for quartile 4 versus quartile 1: 0.40, 95% CI: 0.23⁻0.71 for traditional pattern (TFD); OR: 0.44, CI: 0.27⁻0.70 for traditional pattern (FFQ)). The protective associations were more pronounced among women ≥35 years old. A whole grain⁻seafood TFD pattern was associated with higher risk of GDM (OR: 1.73, 95% CI: 1.10⁻2.74). These findings may provide evidence for making dietary guidelines among pregnant women in Chinese populations to prevent GDM.

Background: Birth weight and weight gain in infancy and early childhood are commonly studied as risk factors for later cardiometabolic diseases. In this study, we explore methods for quantifying weight gain during different age periods and for comparing the magnitude of the associations with later blood pressure., Methods: Based on data from a birth cohort study nested within a large cluster-randomized trial with repeated measures of weight from birth to 16 years of age, we compared the results of four analytic approaches to assess sensitive periods of growth in relation to blood pressure at age 16 years., Results: Approaches based on z-scores of weight or weight gain velocity (both standardized for age and sex) or on regression-based conditional weight standardized residuals yielded more coherent results than an approach based on absolute weight gain velocity. Weight gain standardized by sex and age was positively associated with blood pressure at 16 years at all postnatal age periods, but the magnitude of association was larger during adolescence (11.5-16 years) than during earlier intervals (0-3 months, 3-12 months, 1-6.5 years or 6.5-11.5 years)., Conclusions: Standardization of weight and weight gain by age and sex, or regression-based standardized residuals based on conditional weight, reflects relative gain and thus accounts for the rapid weight gains normally observed in early infancy and puberty. Adolescence appears to be a more sensitive period for relative weight gain effects on later blood pressure than earlier periods, even those of similar duration., (© The Author(s) 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Few studies have examined the independent and combined relationships of body mass index (BMI) peak and rebound with adiposity, insulin resistance and metabolic risk later in life. We used data from Project Viva, a well-characterized birth cohort from Boston with repeated measures of BMI, to help fill this gap., Methods: Among 1681 children with BMI data from birth to mid childhood, we fitted individual BMI trajectories using mixed-effects models with natural cubic splines and estimated age, and magnitude of BMI, at peak (in infancy) and rebound (in early childhood). We obtained cardiometabolic measures of the children in early adolescence (median 12.9 years) and analysed their associations with the BMI parameters., Results: After adjusting for potential confounders, age and magnitude at infancy BMI peak were associated with greater adolescent adiposity, and earlier adiposity rebound was strongly associated with greater adiposity, insulin resistance and metabolic risk score independently of BMI peak. Children with a normal timing of BMI peak plus early rebound had an adverse cardiometabolic profile, characterized by higher fat mass index {β 2.2 kg/m2 [95% confidence interval (CI) 1.6, 2.9]}, trunk fat mass index [1.1 kg/m2 (0.8, 1.5)], insulin resistance [0.2 units (0.04, 0.4)] and metabolic risk score [0.4 units (0.2, 0.5)] compared with children with a normal BMI peak and a normal rebound pattern. Children without a BMI peak (no decline in BMI after the rise in infancy) also had adverse adolescent metabolic profiles., Conclusions: Early age at BMI rebound is a strong risk factor for cardiometabolic risk, independent of BMI peak. Children with a normal peak-early rebound pattern, or without any BMI decline following infancy, are at greatest risk of adverse cardiometabolic profile in adolescence. Routine monitoring of BMI may help to identify children who are at greatest risk of developing an adverse cardiometabolic profile in later life and who may be targeted for preventive interventions., (© The Author(s) 2019; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objectives: Leptin is a hormone produced by adipose tissue that promotes satiety, and some evidence suggests that greater early life leptin exposure prevents excessive adiposity gain in later life. However, few studies have analyzed dynamic changes in leptin throughout childhood in relation to later cardio-metabolic health. Our study aims to identify distinct leptin trajectories in childhood, and to examine their associations with cardio-metabolic outcomes in adolescence., Methods: Among children in the Project Viva cohort born 1999-2002 in Massachusetts, we used latent class growth models to identify leptin trajectories independent of maternal BMI, child sex, race/ethnicity, size at birth and current age and size among 1360 children with leptin measured at least once at birth, early childhood (mean 3.3 ± SD 0.3 years), or mid-childhood (7.9 ± 0.8 years). At research visits in early adolescence (13.2 ± 0.9 years), we assessed cardio-metabolic outcomes including adiposity measures, fasting biomarkers, and blood pressure among 855 children. We then applied multiple regression models to examine associations of the leptin trajectories with these cardio-metabolic outcomes in early adolescence, adjusting for child age at outcome, maternal age, education, prenatal smoking and glucose, total gestational weight gain and paternal BMI., Results: The latent class growth model identified 3 distinct leptin trajectories: "low stable" (n = 1031, 75.8%), "high-decreasing" (n = 219, 16.1%) and "intermediate-increasing" (n = 110, 8.1%). In adjusted models, the intermediate-increasing leptin trajectory was associated with higher early adolescence adiposity measures (e.g. BMI z-score: 0.62 units; 95% confidence interval: 0.28, 0.96 and odds of obesity: 2.84: 1.17, 6.94), but lower systolic blood pressure (-0.46 z-score units; -0.74, -0.18), compared to the low-stable group., Conclusions: Our findings on leptin trajectories in childhood suggest important differences and associations with later metabolic outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Studies to examine the associations of gestational weight gain (GWG) with offspring weight status during infancy are needed, especially among Asian populations. We examined 801 mother⁻infant pairs from a prospective cohort study in China to assess the associations of total and trimester-specific GWG with early infant weight status. We used linear mixed effects models and linear regression models to examine the longitudinal and time-point associations of GWG rate (kg/week) with infant growth measures (z-scores of body-mass-index (BMIZ), weight-for-age (WFAZ) and length-for-age (LFAZ)) at birth, 1, 3, and 6 months. Greater total GWG rate was associated with higher BMIZ (β:1.34 SD units (95% CI: 0.84, 1.83) per 1 kg/week increase in GWG) and higher WFAZ (β:1.18 SD units (95% CI: 1.01, 2.28)) across the first 6 months of life. GWG rate in the first two trimesters but not in the third trimester was positively associated with infant BMIZ. The association between GWG rate and infant BMIZ was significant at all timepoints and more pronounced in normal weight women and among male infants. In conclusion, greater GWG rate is positively associated with offspring BMIZ in the first 6 months of life, the association is mostly driven by GWG in the first two trimesters.

Background: Limited evidence suggests an association between prenatal exposure to traffic pollution and greater adiposity in childhood, but the time window during which growth may be most affected is not known. Methods: We studied 1,649 children in Project Viva, a Boston-area pre-birth cohort. We used spatiotemporal models to estimate prenatal residential air pollution exposures and geographic information systems to estimate neighborhood traffic density and roadway proximity. We used weight and stature measurements at clinical and research visits to estimate a BMI trajectory for each child with mixed-effects natural cubic spline models. In primary analyses, we examined associations of residential PM 2.5 and black carbon (BC) exposures during the third trimester and neighborhood traffic density and home roadway proximity at birth address with (1) estimated BMI at 6 month intervals through 10 years of age, (2) magnitude and timing of BMI peak and rebound, and (3) overall BMI trajectory. In secondary analyses, we examined associations of residential PM 2.5 and BC exposures during the first and second trimesters with BMI outcomes. Results: Median (interquartile range; IQR) concentration of residential air pollution during the third trimester was 11.4 (1.7) μg/m 3 for PM 2.5 and 0.7 (0.3) μg/m 3 for BC. Participants had a median (IQR) of 13 (7) clinical or research BMI measures from 0 to 10 years of age. None of the traffic pollution exposures were significantly associated with any of the BMI outcomes in covariate-adjusted models, although effect estimates were in the hypothesized direction for neighborhood traffic density and home roadway proximity. For example, greater neighborhood traffic density [median (IQR) 857 (1,452) vehicles/day x km of road within 100 m of residential address at delivery] was associated with a higher BMI throughout childhood, with the strongest associations in early childhood [e.g., per IQR increment natural log-transformed neighborhood traffic density, BMI at 12 months of age was 0.05 (-0.03, 0.13) kg/m 2 higher and infancy peak BMI was 0.05 (-0.03, 0.14) kg/m 2 higher]. Conclusions: We found no evidence for a persistent effect of prenatal exposure to traffic pollution on BMI trajectory from birth through mid-childhood in a population exposed to modest levels of air pollution.

Background: Rates of cesarean birth have continued to rise in many high-income countries. We examined the temporal trends and predictors of cesarean birth in Singapore., Methods: Linked hospitalization and Birth Registry data were used to examine all live births to Singaporean citizens and permanent residents between January 1, 2005 and December 31, 2014 (n = 342 932 births). We calculated cesarean rates and age-adjusted average annual percent change (AAPC) in those rates and used sequential multivariable regression modeling to assess the contribution of changes in predictors to the change in cesarean rates over time., Results: The overall cesarean rate in Singapore rose from 32.2% in 2005 to 37.4% in 2014. Among singleton, cephalic, term pregnancies, the two major predictions of cesarean were nulliparity and previous cesarean, each accounting for just over one-third of all cesareans. Higher AAPC was observed in nulliparous women of Indian ethnicity (0.74% [95% confidence interval 0.68-0.80]) compared with Chinese (0.62% [0.60-0.65]) or Malay women (0.63% [0.59-0.68]), and in women who delivered in private hospitals (0.62% [0.60-0.64]) compared with those delivered under subsidized care in public hospitals (0.58% [0.52-0.63]). Parity and education had the largest influences on cesarean birth trend (attenuation of AAPC from 0.62% [0.59-0.66] to 0.39% [0.38-0.40] after adjustment)., Conclusion: Cesarean birth has continued to rise at a steady rate in Singapore. Strategies to curb this temporal increase include avoidance of medically unnecessary primary cesarean and attempts at trial of labor and vaginal delivery among women with a history of prior cesarean., (© 2018 Wiley Periodicals, Inc.)

Introduction: While the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria is widely adopted in many countries, clinicians have questioned the applicability of these diagnostic thresholds for different races/ethnicities. We first compared the prevalence of gestational diabetes mellitus (GDM) diagnosed with different criteria including IADPSG, World Health Organization (WHO) 1999 and Sri Lankan national guidelines, and subsequently related individual guidelines-specific GDM prevalence to offspring birthweight in Sri Lanka. Materials and Methods: We retrospectively collected data on singleton pregnancies ( n = 795) from two tertiary hospitals in Sri Lanka. We applied three diagnostic guidelines to define GDM, namely IADPSG criteria, the Sri Lankan national and WHO 1999 guidelines. We calculated the age- and first booking BMI-adjusted prevalence rates of GDM and assessed the association of GDM (using each guideline) with birthweight. Results: The age- and first booking BMI-adjusted GDM prevalence rates were 31.2, 28.0, and 13.1% for IADPSG criteria, Sri Lankan national and WHO 1999 guidelines, respectively. The IADPSG criteria identified 90 distinctive GDM cases at a lower cut-off of fasting glucose (from 5.1 to 5.5 mmol/L) while Sri Lankan national guideline identified 15 distinctive GDM cases at a lower cut-off for 2-h glucose (from 7.8 to 8.4 mmol/L). After adjusting for age, GDM diagnosed by IADPSG criteria was associated with higher birthweight [90.8 g, 95% CI: 10.8, 170.9], while the associations for GDM diagnosed either by Sri Lankan national or WHO 1999 guidelines were not significant. Conclusion: Adopting the IADPSG criteria for diagnosing GDM may be important in Sri Lankan pregnant population.

Study Question: Are higher overall and central adiposity associated with reduced fecundability, measured by time-to-pregnancy (TTP), in Asian women?, Summary Answer: Higher overall adiposity, but not central adiposity, was associated with longer TTP in Asian women., What Is Known Already: High body mass index (BMI) has been associated with a longer TTP, although the associations of body composition and distribution with TTP are less clear. There are no previous studies of TTP in Asian women, who have a relatively higher percentage of body fat and abdominal fat at relatively lower BMI., Study Design, Size, Duration: Prospective preconception cohort using data from 477 Asian (Chinese, Malay and Indian) women who were planning to conceive and enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) study, 2015-2017., Participants/materials, Setting, Methods: Women's mean age was 30.7 years. Overall adiposity was assessed by BMI, sum of 4-site skinfold thicknesses (SFT) and total body fat percentage (TBF%, measured using air displacement plethysmography); central adiposity was assessed by waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and A body Shape Index (ABSI). Pregnancy occurring within one year from recruitment was ascertained by ultrasonography. Those who did not conceive within one year of recruitment, were lost to follow-up, or initiated fertility treatment were censored. TTP was measured in cycles. Discrete-time proportional hazards models were used to estimate the fecundability ratio (FR) and 95% confidence interval (CI) for each anthropometric measure in association with fecundability, adjusting for confounders., Main Results and the Role of Chance: Compared to women with a normal BMI of 18.5-22.9 kg/m2, women with higher BMI of 23-27.4 and ≥27.5 kg/m2 showed lower FR of 0.66 (95% CI 0.45, 0.97) and 0.53 (0.31, 0.89), respectively. Compared to women in the lowest quartile of SFT (25-52.9 mm), those in the highest quartile of ≥90.1 mm showed lower FR of 0.58 (95% CI 0.36, 0.95). Compared to women in the lowest quartile of TBF% (13.6-27.2%), those in the upper two quartiles of 33.0-39.7% and ≥39.8% showed lower FR of 0.56 (95% CI 0.32, 0.98) and 0.43 (0.24, 0.80), respectively. Association of high BMI with reduced fecundability was particularly evident among nulliparous women. Measures of central adiposity (WC, WHR, WHtR, ABSI) were not associated with fecundability., Limitations Reasons for Caution: Small sample size could restrict power of analysis.The analysis was confined to planned pregnancies, which could limit generalizability of findings to non-planned pregnancies, estimated at around 44% in Singapore. Information on the date of last menstrual period for each month was not available, hence the accuracy of self-reported menstrual cycle length could not be validated, potentially introducing error into TTP estimation. Measures of exposures and covariates such as cycle length were not performed repeatedly over time; cycle length might have changed during the period before getting pregnant., Wider Implications of the Findings: Other than using BMI as the surrogate measure of body fat, we provide additional evidence showing that higher amounts of subcutaneous fat that based on the measure of SFT at the sites of biceps, triceps, suprailiac and subscapular, and TBF% are associated with longer TTP. Achieving optimal weight and reducing total percentage body fat may be a potential intervention target to improve female fertility. The null results observed between central adiposity and TTP requires confirmation in further studies., Study Funding/competing Interest(s): This research is supported by Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council, (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore. Y.S.C., K.M.G., F.Y. and Y.S.L. have received reimbursement to speak at conferences sponsored by companies selling nutritional products. Y.S.C., K.M.G. and S.Y.C. are part of an academic consortium that has received research funding from Abbott, Nutrition, Nestle and Danone. Other authors declared no conflicts of interest., Trial Registration Number: N/A.

Objective: To assess associations of pre-, perinatal, and parental factors with age and magnitude at body mass index (BMI) peak and rebound., Study Design: Among 1681 children with BMI data from birth to mid-childhood in Project Viva, we fitted individual BMI trajectories using mixed-effect models with natural cubic spline functions and estimated age and magnitude at peak in infancy and rebound in early childhood. We used stepwise multivariable regression to identify predictors of peak and rebound in the 1354 (63.6%) children with estimable trajectory milestones., Results: The mean (SD) of age at BMI peak was 8.4 (2.7) months and at rebound was 59.8 (19.6) months, and the mean (SD) of magnitude at peak was 18.0 (1.4) kg/m 2 and at rebound was 15.9 (1.2) kg/m 2 . Girls had a later age at peak, earlier age at rebound, and lower magnitudes at peak and rebound than boys. Maternal isolated hyperglycemia (vs normoglycemia: β 0.7 months [95% CI 0.2-1.2]) and pre-eclampsia (vs normal blood pressure: 1.6 months [0.8-2.4]) were associated with a later peak, and impaired glucose tolerance (vs normoglycemia: -0.5 kg/m 2 [-0.9, -0.1]) was associated with a lower magnitude at peak. Greater maternal first-trimester weight gain, smoking during pregnancy, no breastfeeding, parental obesity, and no university education were associated with greater BMI at rebound., Conclusions: We have identified modifiable prenatal and parental predictors of BMI peak in infancy and rebound in childhood. Early-life interventions that address these factors may be effective in changing BMI peak and rebound and potentially preventing later obesity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In Asia, little is known about how maternal feeding practices are associated with dietary intakes and body mass index (BMI) in preschoolers., Objective: To assess the relationships between maternal feeding practices with dietary intakes and BMI in preschoolers in Asia using cross-sectional analysis in the GUSTO (Growing Up in Singapore Towards healthy Outcomes) cohort., Participant Settings: Mothers (n = 511) who completed the Comprehensive Feeding Practices Questionnaire (CFPQ) and a semi-quantitative Food Frequency Questionnaire (FFQ) when children were 5 years old., Statistical Analysis: Associations between 12 maternal feeding practices (mean scores divided into tertiles) and children's dietary intakes of seven food groups and BMI z-scores were examined using the general linear regression model. Weight and height of the child were measured, and dietary intakes derived from the FFQ., Results: Compared to those in the low tertile, mothers in the high tertile of modelling healthy food intakes had children with higher intakes of vegetables[+20.0g/day (95%CI:11.6,29.5)] and wholegrains[+ 20.9g/day (9.67,31.1)] but lower intakes of sweet snacks[-10.1g/day (-16.3,-4.94)] and fast-foods[-5.84g/day (-10.2,-1.48)]. Conversely, children of mothers in the high tertile for allowing child control (lack of parental control) had lower intake of vegetables[-15.2g/day (-26.6,-5.21)] and wholegrains[-13.6g/day (-22.9,-5.27)], but higher intakes of sweet snacks[+13.7g/day (7.7, 19.8)] and fast-foods[+6.63g/day (3.55,9.72)]. In relation to BMI at 5 years, food restrictions for weight was associated with higher BMI z-scores [0.86SD (0.61,1.21)], while use of pressure was associated with lower BMI z-scores[-0.49SD(-0.78,-0.21)]., Conclusions and Implications: Modelling healthy food intakes by mothers was the key feeding practice associated with higher intakes of healthy foods and lower intakes of discretionary foods. The converse was true for allowing child control. Only food restrictions for weight and use of pressure were associated with BMI z-scores., Competing Interests: P.D.G., 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 commercial affiliations such as Abbott Nutrition, Nestec, and Danone. Lisa Fries is an employee of Nestec SA, working at the Nestlé Research Center. None of the other authors report any potential conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Importance: The American Academy of Pediatrics currently recommends weight for length (WFL) for assessment of weight status in children younger than 2 years but body mass index (BMI) for children older than 2 years. However, the clinical implications of using WFL vs BMI in children younger than 2 years as an indicator of future health outcomes remains understudied., Objective: To compare associations of overweight based on WFL vs BMI in children younger than 2 years with cardiometabolic outcomes during early adolescence., Design, Setting, and Participants: This prospective study of birth cohorts in the United States (Project Viva) and Belarus (Promotion of Breastfeeding Intervention Trial [PROBIT]) performed from June 1, 1996, to November 31, 2002, included 13 666 children younger than 2 years., Main Exposures: Overweight defined as Centers for Disease Control and Prevention (CDC) WFL in the 95th percentile or greater, World Health Organization (WHO) WFL in the 97.7th percentile or greater, or WHO BMI in the 97.7th percentile or greater at 6, 12, 18, or 24 months of age., Main Outcomes and Measures: Primary outcomes were fat mass index, insulin resistance, metabolic risk score, and obesity during early adolescence. Secondary outcomes were height and BMI z scores, sum of skinfolds, waist circumference, and systolic blood pressure during early adolescence., Results: The study included 919 children (mean [SD] age, 12.9 [0.9] years; 460 [50.1%] male; and 598 [65.1%] white) from Project Viva and 12 747 children (mean [SD] age, 11.5 [0.5] years; 6204 [48.7%] male; and 12 747 [100%] white) from PROBIT. During 6 to 24 months of age, in Project Viva, 206 children (22.4%) were overweight at any of the 4 times points according to the CDC WFL, 160 (17.4%) according to WHO WFL, and 161 (17.5%) according to WHO BMI cut points. In PROBIT, 3715 children (29.1%) were overweight at any of the 4 time points according to the CDC WFL, 3069 (24.1%) according to WHO WFL, and 3125 (24.5%) according to WHO BMI cut points. After maternal and child characteristics were adjusted for, being ever overweight (vs never overweight) during 6 to 24 months of age was associated with higher likelihood of adverse cardiometabolic risk markers during early adolescence, but associations did not differ substantially across WFL and BMI cut points in either cohort. For example, for fat mass index in Project Viva, β = 0.9 (95% CI, 0.5-1.4) for the CDC WFL, β = 1.1 (95% CI, 0.6-1.6) for WHO WFL, and β = 1.4 (95% CI, 0.9-1.9) for WHO BMI. For PROBIT, β = 0.5 (95% CI, 0.4-0.6) for the CDC WFL, β = 0.6 (95% CI, 0.5-0.7) for WHO WFL, and β = 0.6 (95% CI, 0.5-0.6) for WHO BMI. Neither growth metric in infancy was superior over the others based on F statistics (Project Viva: 17.1-17.8; PROBIT: 87.1-88.7). Findings were similar for insulin resistance, metabolic risk score, obesity, and secondary outcomes., Conclusions and Relevance: Choice of WFL vs BMI to define overweight during the first 2 years of life may not greatly affect the association with cardiometabolic outcomes during early adolescence. The findings appear to have important implications for investigators seeking to use BMI as a growth metric for epidemiologic research and for practitioners monitoring the weight status of children younger than 2 years.

Purpose of Review: Many of the diseases and dysfunctions described in the paradigm of the developmental origins of health and disease have been studied in relation to prenatal nutrition or environmental toxicant exposures. Here, we selectively review the current research on four exposures-two nutritional and two environmental-that have recently emerged as prenatal risk factors for long-term health outcomes., Recent Findings: Recent studies have provided strong evidence that prenatal exposure to (1) excessive intake of sugar-sweetened beverages, (2) unhealthy dietary patterns, (3) perfluoroalkyl substances, and (4) fine particulate matter, may increase risk of adverse health outcomes, such as obesity, cardiometabolic dysfunction, and allergy/asthma., Summary: Emerging prenatal nutritional factors and environmental toxicants influence offspring long-term health. More work is needed to identify the role of paternal exposures and maternal exposures during the preconception period and to further elucidate causality through intervention studies. The ubiquity of these emerging nutritional and environmental exposures makes this area of inquiry of considerable public health importance., Competing Interests: Conflict of Interest Izzuddin M Aris and Abby F. Fleisch declare no conflicts of interest; Emily Oken reports grants from US National Institutes of Health, during the conduct of the study.

Objectives: Lower vitamin D status has been associated with adiposity in children through adults. However, the evidence of the impact of maternal vitamin-D status during pregnancy on offspring's adiposity is mixed. The objective of this study was to examine the associations between maternal vitamin-D [25(OH)D] status at mid-gestation and neonatal abdominal adipose tissue (AAT) compartments, particularly the deep subcutaneous adipose tissue linked with metabolic risk., Methods: Participants (N = 292) were Asian mother-neonate pairs from the mother-offspring cohort, Growing Up in Singapore Towards healthy Outcomes. Neonates born at ≥34 weeks gestation with birth weight ≥2000 g had magnetic resonance imaging (MRI) within 2-weeks post-delivery. Maternal plasma glucose using an oral glucose tolerance test and 25(OH)D concentrations were measured. 25(OH)D status was categorized into inadequate (≤75.0 nmol/L) and sufficient (>75.0 nmol/L) groups. Neonatal AAT was classified into superficial (sSAT), deep subcutaneous (dSAT), and internal (IAT) adipose tissue compartments., Results: Inverse linear correlations were observed between maternal 25(OH)D and both sSAT (r = -0.190, P = 0.001) and dSAT (r = -0.206, P < 0.001). Each 1 nmol/L increase in 25(OH)D was significantly associated with reductions in sSAT (β = -0.14 (95% CI: -0.24, -0.04) ml, P = 0.006) and dSAT (β = -0.04 (-0.06, -0.01) ml, P = 0.006). Compared to neonates of mothers with 25(OH)D sufficiency, neonates with maternal 25(OH)D inadequacy had higher sSAT (7.3 (2.1, 12.4) ml, P = 0.006), and dSAT (2.0 (0.6, 3.4) ml, P = 0.005) volumes, despite similar birth weight. In the subset of mothers without gestational diabetes, neonatal dSAT was also greater (1.7 (0.3, 3.1) ml, P = 0.019) in neonates with maternal 25(OH)-inadequacy. The associations with sSAT and dSAT persisted even after accounting for maternal glycemia (fasting and 2-h plasma glucose)., Conclusions: Neonates of Asian mothers with mid-gestation 25(OH)D inadequacy have a higher abdominal subcutaneous adipose tissue volume, especially dSAT (which is metabolically similar to visceral adipose tissue in adults), even after accounting for maternal glucose levels in pregnancy.

Background: In randomized trials, supplementation of n-3 (ω-3) long-chain polyunsaturated fatty acids (LC-PUFAs) during pregnancy has resulted in increased size at birth, which is attributable to longer gestation., Objective: We examined this finding by using a Mendelian randomization approach utilizing fatty acid desaturase (FADS) gene variants affecting LC-PUFA metabolism., Design: As part of a tri-ethnic mother-offspring cohort in Singapore, 35 genetic variants in FADS1, FADS2, and FADS3 were genotyped in 898 mothers and 1103 offspring. Maternal plasma n-3 and n-6 PUFA concentrations at 26-28 wk of gestation were measured. Gestation duration was derived from an ultrasound dating scan in early pregnancy and from birth date. Birth length and weight were measured. Eight FADS variants were selected through a tagging-SNP approach and examined in association with PUFA concentrations, gestation duration among spontaneous labors, and birth size with the use of ethnicity-adjusted linear regressions and survival models that accounted for the competing risks of induced labor and prelabor cesarean delivery., Results: Maternal FADS1 variant rs174546, tagging for 8 other variants located on FADS1 and FADS2, was strongly related to plasma n-6 but not n-3 LC-PUFA concentrations. Offspring and maternal FADS3 variants were associated with gestation duration among women who had spontaneous labor: each copy of rs174450 minor allele C was associated with a shorter gestation by 2.2 d (95% CI: 0.9, 3.4 d) and 1.9 d (0.7, 3.0 d) for maternal and offspring variants, respectively. In survival models, rs174450 minor allele homozygotes had reduced time to delivery after spontaneous labor compared with major allele homozygotes [HR (95% CI): 1.51 (1.18, 1.95) and 1.51 (1.20, 1.89) for mothers and offspring, respectively]., Conclusions: With the use of a Mendelian randomization approach, we observed associations between FADS variants and gestation duration. This suggests a potential role of LC-PUFAs in gestation duration. This trial was registered at http://www.clinicaltrials.gov as NCT01174875.

Background: Quantitative magnetic resonance (QMR) has been increasingly used to measure human body composition, but its use and validation in children is limited., Objective: We compared body composition measurement by QMR and air displacement plethysmography (ADP) in preschool children from Singapore's multi-ethnic Asian population (n = 152; mean ± SD age: 5.0 ± 0.1 years)., Methods: Agreements between QMR-based and ADP-based fat mass and fat mass index (FMI) were assessed using intraclass correlation coefficient (ICC), reduced major axis regression and Bland-Altman plot analyses. Analyses were stratified for the child's sex., Results: Substantial agreement was observed between QMR-based and ADP-based fat mass (ICC: 0.85) and FMI (ICC: 0.82). Reduced major axis regression analysis suggested that QMR measurements were generally lower than ADP measurements. Bland-Altman analysis similarly revealed that QMR-based fat mass were (mean difference [95% limits of agreement]) -0.5 (-2.1 to +1.1) kg lower than ADP-based fat mass and QMR-based FMI were -0.4 (-1.8 to +0.9) kg/m 2 lower than ADP-based FMI. Stratification by offspring sex revealed better agreement of QMR and ADP measurements in girls than in boys., Conclusions: QMR-based fat mass and FMI showed substantial agreement with, but was generally lower than, ADP-based measures in young Asian children., (© 2017 World Obesity Federation.)

Background: Women with gestational diabetes mellitus (GDM) are at greater risk of metabolic syndrome (MetS). We studied the association between second-trimester retinal microvasculature and 5-year MetS incidence in women with GDM., Methods: A total of 142 mothers with GDM were recruited and followed up 5years after delivery. Retinal photography was performed at 26-28weeks gestation and metabolic outcomes were assessed at the 5-year postpartum follow-up visit. GDM and MetS were defined based on World Health Organization (WHO) guidelines and Adults Treatment Panel (ATP) III guidelines, respectively. Modified-Poisson regression was applied to study the association between second-trimester retinal microvasculature and incident 5-year maternal MetS, after adjusting for major confounders. Area under the curve (AUC) was calculated based on the final model., Results: Our prospective cohort reported a 9.2% incidence rate of 5-year MetS among women with GDM. After adjusting for maternal age, ethnicity, college degree, pre-pregnancy BMI and fasting glucose at 26-28week gestation, each 10μm widening in retinal venular caliber was associated with an increased relative risk of 1.6 (95% confidence interval [CI]: 1.0, 2.8) in incident MetS. In addition to traditional risks of pre-pregnancy BMI and fasting glucose level at 26-28week gestation, retinal venular caliber mildly increased the prediction of 5-year maternal MetS by 1.8%., Conclusions: Second-trimester retinal venular widening was associated with incident 5-year maternal MetS in women with GDM. Our study suggests that mother with GDM at risk of future MetS development may have already presented retinal microvascular abnormalities during pregnancy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Higher leptin and lower adiponectin correlate with adult and childhood adiposity, but it is unclear how exposure to these adipokines during gestation relates to offspring growth. We aimed to investigate the relationships of maternal and cord adipokines with offspring adiposity across childhood to early adolescence, as well as interactions with child age., Methods: In mother-child pairs in the Project Viva cohort, we measured adipokines in mothers at second trimester (n=1106) and in cord blood at birth (n=657). We measured offspring adiposity indices at early childhood (mean 3.3±s.d. 0.3 years), mid-childhood (7.9±0.8 years) and early adolescence (13.2±0.9 years). We analyzed associations of maternal and cord adipokines with offspring longitudinal adiposity using a linear mixed model adjusting for pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and other confounders., Results: Mothers with higher BMI and GWG had higher leptin. Offspring born to mothers with the highest vs lowest quartile of leptin had lower BMI z-score (-0.49 units, 95% confidence interval (CI):-0.72,-0.26), waist circumference (-2.6 cm, 95% CI: -3.7,-1.5) and sum of subscapular and triceps skinfolds (-2.8 mm, 95% CI: -4.1,-1.4) in early life. An interaction term between maternal leptin and child age was positive, suggesting that the associations between maternal leptin and child adiposity were not constant over time. Offspring born to mothers with lowest vs highest quartile of maternal adiponectin had lower early life adiposity (BMI z-score -0.27 units, 95% CI: -0.48,-0.05). Results were similar for cord leptin but not cord adiponectin., Conclusions: Our findings showed higher maternal and cord leptin, and lower maternal adiponectin are associated with lower offspring adiposity from childhood to early adolescence, independent of maternal BMI and GWG. However, the strength of these associations was not constant over time.

The relationship between sleep apnea and bone health remains controversial. This study explored the relationship between sleep apnea and femoral neck BMD in midlife Asian women. Partner-witnessed apnea predicted higher femoral neck BMD, an effect validated by the STOP index. Our findings suggest that sleep apnea may protect bone health., Purpose: The menopause transition is associated with decline in bone mineral density (BMD) and sleep quality. However, any relationship between these two factors remains controversial. This study explored the association between sleep apnea and femoral neck BMD in middle-aged women., Methods: Participants (n = 1201) aged 45-69 years attending well-women visits at the National University Hospital, Singapore were recruited. Self-reported breathing discomfort and snoring, partner-witnessed apnea and snoring were assessed from the Pittsburgh Sleep Quality Index. Femoral neck BMD was assessed with dual-energy X-ray absorptiometry scan and classified into tertiles based on T-scores. Factors reported to affect sleep apnea and bone health in medical literature were potential covariates, p < 0.10. Multivariable ordinal regression analyses assessed associations between sleep measures and BMD. To further validate our findings, we analyzed four sleep apnea characteristics from the STOP questionnaire, a screening tool for sleep apnea. All analyses were performed using SPSS version 20.0., Results: Mean (SD) age of participants was 56.3 (6.2) years. Partner-witnessed apnea predicted higher BMD tertiles (OR per unit increase in severity 1.39, 95% CI [1.02, 1.89]), independent of age, ethnicity, diabetes, BMI, and handgrip strength. This was further corroborated by the STOP index (OR 1.45, 95% CI [1.07, 1.96])., Conclusions: This study adds to the literature on sleep apnea and bone health in a non-Caucasian and younger population. Our findings support OSA-associated intermittent hypoxia protecting bone health.

Aims: The cumulative effect of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) on postpartum cardio-metabolic diseases is equivocal. We aimed to assess the associations of GDM and HDP's individual and synergic contribution to risks of postpartum cardio-metabolic diseases (metabolic syndrome (MetS), abnormal glucose metabolism and hypertension (HTN))., Methods: Of participants from a Singapore birth cohort, 276 mothers attending the 5-year postpartum visit were included in this study. During this visit, we collected mothers' history of GDM and HDP in all live births in a chronicle sequence and assessed the cardio-metabolic risks based on blood pressure, anthropometry and a panel of serum biomarkers. We diagnosed MetS, abnormal glucose metabolism and HTN according to Adult Treatment Panel III 2000 and World Health Organization guidelines., Results: Of 276 mothers, 157 (56.9%) had histories of GDM while 23 (8.3%) had histories of HDP. After full adjustment, we found associations of GDM episodes with postpartum abnormal glucose metabolism (single episode: relative risk (RR) 2.9 (95% CI: 1.7, 4.8); recurrent episodes (≥2): RR = 3.8 (2.1-6.8)). Also, we found association between histories of HDP and HTN (RR = 3.6 (1.5, 8.6)). Having either (RR 2.6 (1.7-3.9)) or both gestational complications (RR 2.7 (1.6-4.9)) was associated with similar risk of postpartum cardio-metabolic disease., Conclusions: Mothers with GDM or HDP had a threefold increased risk of postpartum abnormal glucose metabolism or HTN, respectively. Having both GDM and HDP during past pregnancies was not associated with additional risk of postpartum cardio-metabolic diseases beyond that associated with either complication alone., (© 2018 The authors.)

Background: Studying the determinants and the long-term consequences of fetal adipose accretion requires accurate assessment of neonatal body composition. In large epidemiological studies, in-depth body composition measurement methods are usually not feasible for cost and logistical reasons, and there is a need to identify anthropometric measures that adequately reflect neonatal adiposity., Methods: In a multiethnic Asian mother-offspring cohort in Singapore, anthropometric measures (weight, length, abdominal circumference, skinfold thicknesses) were measured using standardized protocols in newborn infants, and anthropometric indices (weight/length, weight/length 2 (body mass index, BMI), weight/length 3 (ponderal index, PI)) derived. Neonatal total adiposity was measured using air displacement plethysmography (ADP) and abdominal adiposity using magnetic resonance imaging (MRI). Correlations of the anthropometric measures with ADP- and MRI-based adiposity were assessed using Pearson's correlation coefficients (r p ), including in subsamples stratified by sex and ethnicity., Results: Study neonates (n=251) had a mean (s.d.) age of 10.2 (2.5) days. Correlations between ADP-based fat mass (ADP FM ) and anthropometric measures were moderate (r p range: 0.44-0.67), with the strongest being with weight/length, weight, BMI and sum of skinfolds (r p =0.67, 0.66, 0.62, 0.62, respectively, all P<0.01). All anthropometric measures except skinfold thicknesses correlated more strongly with ADP-based fat-free mass than ADP FM , indicating that skinfold measures may have more discriminative power in terms of neonatal total body adiposity. For MRI-based measures, weight and weight/length consistently showed strong positive correlations (r p ⩾0.7) with abdominal adipose tissue compartments. These correlations were consistent in boys and girls, across different ethnic groups, and when conventional determinants of neonatal adiposity were adjusted for potential confounding. Abdominal circumference was not strongly associated with ADP FM or abdominal fat mass., Conclusions: Simple anthropometric measures (weight and weight/length) correlated strongly with neonatal adiposity, with some evidence for greater discriminative power for skinfold measures. These simple measures could be of value in large epidemiological studies.

Background/objective: Many studies have identified early-life risk factors for subsequent childhood overweight/obesity, but few have evaluated how they combine to influence risk of childhood overweight/obesity. We examined associations, individually and in combination, of potentially modifiable risk factors in the first 1000 days after conception with childhood adiposity and risk of overweight/obesity in an Asian cohort., Methods: Six risk factors were examined: maternal pre-pregnancy overweight/obesity (body mass index (BMI) ⩾25 kg m -2 ), paternal overweight/obesity at 24 months post delivery, maternal excessive gestational weight gain, raised maternal fasting glucose during pregnancy (⩾5.1 mmol l -1 ), breastfeeding duration <4 months and early introduction of solid foods (<4 months). Associations between number of risk factors and adiposity measures (BMI, waist-to-height ratio (WHtR), sum of skinfolds (SSFs), fat mass index (FMI) and overweight/obesity) at 48 months were assessed using multivariable regression models., Results: Of 858 children followed up at 48 months, 172 (19%) had none, 274 (32%) had 1, 244 (29%) had 2, 126 (15%) had 3 and 42 (5%) had ⩾4 risk factors. Adjusting for confounders, significant graded positive associations were observed between number of risk factors and adiposity outcomes at 48 months. Compared with children with no risk factors, those with four or more risk factors had s.d. unit increases of 0.78 (95% confidence interval 0.41-1.15) for BMI, 0.79 (0.41-1.16) for WHtR, 0.46 (0.06-0.83) for SSF and 0.67 (0.07-1.27) for FMI. The adjusted relative risk of overweight/obesity in children with four or more risk factors was 11.1(2.5-49.1) compared with children with no risk factors. Children exposed to maternal pre-pregnancy (11.8(9.8-13.8)%) or paternal overweight status (10.6(9.6-11.6)%) had the largest individual predicted probability of child overweight/obesity., Conclusions: Early-life risk factors added cumulatively to increase childhood adiposity and risk of overweight/obesity. Early-life and preconception intervention programmes may be more effective in preventing overweight/obesity if they concurrently address these multiple modifiable risk factors.

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.)

Aims/hypothesis: Changes in retinal microvasculature may reflect insulin resistance. We examined the association of changes in retinal microvasculature during pregnancy and risk of subsequent abnormal glucose metabolism in a cohort of mothers at baseline and 5 years postpartum., Methods: Of the participants from the Singapore birth cohort (Growing Up in Singapore Towards Healthy Outcomes [GUSTO]), 276 mothers attended both baseline (at 26-28 weeks of gestation) and follow-up (5 year postpartum) visits. At baseline we performed retinal photography and assessed retinal microvascular variables using a validated grading system. At follow-up, we assessed glucose tolerance using a 75 g OGTT. We defined abnormal glucose metabolism if participants: (1) had onset of gestational diabetes mellitus (GDM) in subsequent pregnancies within a 5 year follow-up period (n = 103) or (2) had prediabetes (impaired fasting glucose, impaired glucose tolerance or HbA 1c 5.7-6.4% [39-46 mmol/mol]) and diabetes diagnosed at the 5 year follow-up visit (n = 84), according to WHO guidelines., Results: The incidence of GDM in subsequent pregnancy and abnormal glucose metabolism 5 years postpartum was 25.2% and 30.4%, respectively. Each 10 μm widening in retinal venular calibre was associated with a significant risk of postpartum abnormal glucose metabolism (RR 1.2 [95% CI 1.0, 1.5]), independent of maternal age, college education, ethnicity, pre-pregnancy BMI and GDM at baseline. Narrower retinal arteriolar calibre and venular branching angle at baseline was associated with a higher insulin resistance index (1.4 [95% CI 1.1, 1.7] and 1.3 [95% CI 1.1, 1.6], respectively) at follow-up., Conclusions/interpretation: Retinal microvasculature in pregnant women was associated with abnormal glucose metabolism 5 years postpartum. Alteration of microvascular structure during pregnancy may signal subclinical changes that underlie the development of prediabetes and diabetes.

We investigated body mass index (BMI) trajectories in the first 2 years of life in 1170 children from an Asian mother-offspring cohort in Singapore, and examined their predictors and associations with childhood cardio-metabolic risk measures at 5 years. Latent class growth mixture modelling analyses were performed to identify distinct BMI z-score (BMIz) trajectories. Four trajectories were identified: 73.2%(n = 857) of the children showed a normal BMIz trajectory, 13.2%(n = 155) a stable low-BMIz trajectory, 8.6%(n = 100) a stable high-BMIz trajectory and 5.0%(n = 58) a rapid BMIz gain after 3 months trajectory. Predictors of the stable high-BMIz and rapid BMIz gain trajectories were pre-pregnancy BMI, gestational weight gain, Malay and Indian ethnicity, while predictors of stable low-BMIz trajectory were preterm delivery and Indian ethnicity. At 5 years, children with stable high-BMIz or rapid BMIz gain trajectories had increased waist-to-height ratios [B(95%CI) 0.02(0.01,0.03) and 0.03(0.02,0.04)], sum of skinfolds [0.42(0.19,0.65) and 0.70(0.36,1.03)SD units], fat-mass index [0.97(0.32,1.63)SD units] and risk of obesity [relative risk 3.22(1.73,6.05) and 2.56 (1.19,5.53)], but not higher blood pressure. BMIz trajectories were more predictive of adiposity at 5 years than was BMIz at 2 years. Our findings on BMIz trajectories in the first 2 years suggest important ethnic-specific differences and impacts on later metabolic outcomes.

Objective: There have been hypotheses that early life adiposity gain may influence blood pressure (BP) later in life. We examined associations between timing of height, body mass index (BMI) and adiposity gains in early life with BP at 48 months in an Asian pregnancy-birth cohort., Methods: In 719 children, velocities for height, BMI and abdominal circumference (AC) were calculated at five intervals [0-3, 3-12, 12-24, 24-36 and 36-48 months]. Triceps (TS) and subscapular skinfold (SS) velocities were calculated between 0-18, 18-36 and 36-48 months. Systolic (SBP) and diastolic blood pressure (DBP) was measured at 48 months. Growth velocities at later periods were adjusted for growth velocities in preceding intervals, as well as measurements at birth., Results: After adjusting for confounders and child height at BP measurement, each unit z-score gain in BMI, AC, TS and SS velocities at 36-48 months were associated with 2.3 (95% CI:1.6, 3.1), 2.1 (1.3, 2.8), 1.4 (0.6, 2.2) and 1.8 (1, 2.6) mmHg higher SBP respectively, and 0.9 (0.4, 1.4), 0.9 (0.4, 1.3), 0.6 (0.1, 1.1) and 0.8 (0.3, 1.3) mmHg higher DBP respectively. BMI and adiposity velocities (AC, TS or SS) at various intervals in the first 36 months however, were not associated with BP. Faster BMI, AC, TS and SS velocities, but not height, at 36-48 months were associated with 0.22 (0.15, 0.29), 0.17 (0.10, 0.24), 0.11 (0.04, 0.19) and 0.15 (0.08, 0.23) units higher SBP z-score respectively, and OR=1.46 (95% CI: 1.13-1.90), 1.49 (1.17-1.92), 1.45 (1.09-1.92) and 1.43 (1.09, 1.88) times higher risk of prehypertension/hypertension respectively at 48 months., Conclusions: Our results indicated that faster BMI and adiposity (AC, TS or SS) velocities only at the preceding interval before 48 months (36-48 months), but not at earlier intervals in the first 36 months, are predictive of BP and prehypertension/hypertension at 48 months.

Background: Synchrony between daily feeding-fasting signals and circadian rhythms has been shown to improve metabolic health in animals and adult humans, but the potential programming effect on fetal growth is unknown. Objective: We examined the associations of the maternal night-fasting interval during pregnancy with offspring birth size and adiposity. Methods: This was a cross-sectional study of mother-offspring dyads within the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. For 384 mothers aged 30.8 ± 4.8 y (mean ± SD), the night-fasting interval at 26-28 wk of gestation was determined from a 3-d food diary based on the average of the fasting duration at night (1900-0659). Offspring birth weight, length, and head circumference were measured and converted to weight-for-gestational age (GA), length-for-GA, and head circumference-for-GA z scores, respectively, by using local customized percentile charts. The percentage of neonatal total body fat (TBF) was derived by using a validated prediction equation. Multivariable general linear models, stratified by child sex, were performed. Results: The mean ± SD maternal night-fasting interval was 9.9 ± 1.3 h. In infant girls, each 1-h increase in the maternal night-fasting interval was associated with a 0.22-SD (95% CI: 0.05-, 0.40-SD; P = 0.013) increase in birth head circumference-for-GA and a 0.84% (95% CI: 0.19%, 1.49%; P = 0.012) increase in TBF at birth, after adjustment for confounders. In infant boys, no associations were observed between the maternal night-fasting interval and birth size or TBF. Conclusions: An increased maternal night-fasting interval in the late second trimester of pregnancy is associated with increased birth head circumference and TBF in girls but not boys. Our findings are in accordance with previous observations that suggest that there are sex-specific responses in fetal brain growth and adiposity, and raise the possibility of the maternal night-fasting interval as an underlying influence. This trial was registered at clinicaltrials.gov as NCT01174875., Competing Interests: Author disclosures: SLL, PHW, MTC, YBC, IMA, JKYC, KHT, LP-CS, PN, FM-R, NL, VSR, M-TT, and MF-FC, no conflicts of interest. KMG, PDG, Y-SC, YSL, and FY have received reimbursement for speaking at conferences sponsored by companies selling nutritional products. KMG, PDG, and Y-SC are part of an academic consortium that has received research funding from Abbott Nutrition, Nestlé, and Danone., (© 2017 American Society for Nutrition.)

Background: Polyunsaturated fatty acids (PUFA) are essential for offspring development, but it is less clear whether pregnancy PUFA status affects growth and adiposity., Methods: In 985 mother-offspring pairs from the ongoing Singaporean GUSTO cohort, we analyzed the associations between offspring growth and adiposity outcomes until age 5 years and five PUFAs of interest, measured in maternal plasma at 26-28 weeks' gestation: linoleic acid (LA), arachidonic acid, α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid (DHA). We measured fetal growth by ultrasound (n=924), neonatal body composition (air displacement plethysmography (n=252 at birth, and n=317 at age 10 days), and abdominal magnetic resonance imaging (n=317)), postnatal growth (n=979) and skinfold thicknesses (n=981). Results were presented as regression coefficients for a 5% increase in PUFA levels., Results: LA levels were positively associated with birthweight (β (95% CI): 0.04 (0.01, 0.08) kg), body mass index (0.13 (0.02, 0.25) kg/m 2 ), head circumference (0.11 (0.03, 0.19) cm), and neonatal abdominal adipose tissue volume (4.6 (1.3, 7.8) mL for superficial subcutanous tissue, and 1.2 (0.1, 2.4) mL for internal tissue), but not with later outcomes. DHA levels, although not associated with birth outcomes, were related to higher postnatal length/height: 0.63 (0.09, 1.16) cm at 12 months and 1.29 (0.34, 2.24) cm at 5 years., Conclusions: LA was positively associated with neonatal body size, and DHA with child height. Maternal PUFA status during pregnancy may influence fetal and child growth and adiposity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: : Infant body mass index (BMI) peak has received much interest recently as a potential predictor of future obesity and metabolic risk. No studies, however, have examined infant BMI peak in Asian populations, in whom the risk of metabolic disease is higher., Methods: : We utilized data among 1020 infants from a mother-offspring cohort, who were Singapore citizens or permanent residents of Chinese, Malay or Indian ethnicity with homogeneous parental ethnic backgrounds, and did not receive chemotherapy, psychotropic drugs or have diabetes mellitus. Ethnicity was self-reported at recruitment and later confirmed using genotype analysis. Subject-specific BMI curves were fitted to infant BMI data using natural cubic splines with random coefficients to account for repeated measures in each child. We estimated characteristics of the child's BMI peak [age and magnitude at peak, average pre-peak velocity (aPPV)]. Systolic (SBP) and diastolic blood pressure (DBP), BMI, sum of skinfolds (SSF) and fat-mass index (FMI) were measured during a follow-up visit at age 48 months. Weighted multivariable linear regression was used to assess the predictors (maternal BMI, gestational weight gain, ethnicity, infant sex, gestational age, birthweight-for-gestational age and breastfeeding duration) of infant BMI peak and its associations with outcomes at 48 months. Comparisons between ethnicities were tested using Bonferroni post-hoc correction., Results: : Of 1020 infants, 80.5% were followed up at the 48-month visit. Mean (SD) BMI, SSF and FMI at 48 months were 15.6 (1.8) kg/m 2 , 16.5 (5.3) mm and 3.8 (1.3) kg/m 2 , respectively. Mean (SD) age at peak BMI was 6.0 (1.6) months, with a magnitude of 17.2 (1.4) kg/m 2 and pre-peak velocity of 0.7 (0.3) kg/m 2 /month. Compared with Chinese infants, the peak occurred later in Malay {B [95% confidence interval (CI): 0.64 mo (0.36, 0.92)]} and Indian infants [1.11 mo (0.76, 1.46)] and was lower in magnitude in Indian infants [-0.45 kg/m 2 (-0.69, -0.20)]. Adjusting for maternal education, BMI, gestational weight gain, ethnicity, infant sex, gestational age, birthweight-for-gestational-age and breastfeeding duration, higher peak and aPPV were associated with greater BMI, SSF and FMI at 48 months. Age at peak was positively associated with BMI at 48 months [0.15 units (0.09, 0.22)], whereas peak magnitude was associated with SBP [0.17 units (0.05, 0.30)] and DBP at 48 months [0.10 units (0.01, 0.22)]. Older age and higher magnitude at peak were associated with increased risk of overweight at 48 months [Relative Risk (95% CI): 1.35 (1.12-1.62) for age; 1.89 (1.60-2.24) for magnitude]. The associations of BMI peak with BMI and SSF at 48 months were stronger in Malay and Indian children than in Chinese children., Conclusions: : Ethnic-specific differences in BMI peak characteristics, and associations of BMI peak with early childhood cardio-metabolic markers, suggest an important impact of early BMI development on later metabolic outcomes in Asian populations., (© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)