Yung Seng Lee

Effect of Maternal Glycemia on Neonatal Adiposity in a Multiethnic Asian Birth Cohort

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

Maternal Folate Status, but Not That of Vitamins B-12 or B-6, Is Associated with Gestational Age and Preterm Birth Risk in a Multiethnic Asian Population

BACKGROUNDnMaternal folate, vitamin B-12, and vitamin B-6 concentrations during pregnancy have been shown to influence birth outcomes, but the evidence is inconclusive.nnnOBJECTIVEnWe aimed to examine the associations of maternal B-vitamin status with gestational age, birth weight, and length in a birth cohort study in Singapore.nnnMETHODSnMaternal blood samples (n = 999) collected during weeks 26-28 of gestation were assayed for plasma folate, vitamin B-12, and vitamin B-6 concentrations. Birth weight and gestational age data were obtained from hospital records, and other anthropometric variables were measured within 72 h after birth. Relations between B-vitamin status and birth outcomes were assessed by linear or logistic regression with adjustment for potential confounders.nnnRESULTSnMedian (IQR) plasma concentrations were 34.4 (24.5-44.6) nmol/L for folate, 209 (167-258) pmol/L for vitamin B-12, and 61.8 (25.9-113) nmol/L for vitamin B-6. We found that higher plasma folate concentrations were associated with a longer gestational age (0.12 wk per SD increase in folate; 95% CI: 0.02, 0.21) and tended to be associated with lower risk of all preterm birth (delivery at <37 wk of gestation; OR: 0.79; 95% CI: 0.63, 1.00) and spontaneous preterm birth (OR: 0.76; 95% CI: 0.56, 1.04). Overall, concentrations of maternal folate, vitamin B-12, and vitamin B-6 were not independently associated with birth weight or being born small for gestational age (SGA; birth weight <10th percentile for gestational age).nnnCONCLUSIONSnHigher maternal folate concentrations during late pregnancy were associated with longer gestational age and tended to be associated with a lower risk of preterm birth in this multiethnic Asian population. In contrast, the results of our study suggested little or no benefit of higher folate concentrations for reducing the risk of SGA or of higher vitamin B-6 and vitamin B-12 concentrations for reducing the risk of preterm birth or SGA.

The association of maternal vitamin D status with infant birth outcomes, postnatal growth and adiposity in the first 2 years of life in a multi-ethnic Asian population: the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study

Maternal vitamin D status during pregnancy has been associated with infant birth and postnatal growth outcomes, but reported findings have been inconsistent, especially in relation to postnatal growth and adiposity outcomes. In a mother-offspring cohort in Singapore, maternal plasma vitamin D was measured between 26 and 28 weeks of gestation, and anthropometric measurements were obtained from singleton offspring during the first 2 years of life with 3-month follow-up intervals to examine birth, growth and adiposity outcomes. Associations were analysed using multivariable linear regression. Of a total of 910 mothers, 13·2 % were vitamin D deficient (<50 nmol/l) and 26·5 % were insufficient (50-75 nmol/l). After adjustment for potential confounders and multiple testing, no statistically significant associations were observed between maternal vitamin D status and any of the birth outcomes - small for gestational age (OR 1·00; 95 % CI 0·56, 1·79) and pre-term birth (OR 1·16; 95 % CI 0·64, 2·11) - growth outcomes - weight-for-age z-scores, length-for-age z-scores, circumferences of the head, abdomen and mid-arm at birth or postnatally - and adiposity outcomes - BMI, and skinfold thickness (triceps, biceps and subscapular) at birth or postnatally. Maternal vitamin D status in pregnancy did not influence infant birth outcomes, postnatal growth and adiposity outcomes in this cohort, perhaps due to the low prevalence (1·6 % of the cohort) of severe maternal vitamin D deficiency (defined as of <30·0 nmol/l) in our population.

Body fat in Singaporean infants: development of body fat prediction equations in Asian newborns.

Background/objectives:Prediction equations are commonly used to estimate body fat from anthropometric measurements, but are population specific. We aimed to establish and validate a body composition prediction formula for Asian newborns, and compared the performance of this formula with that of a published equation.Subjects/methods:Among 262 neonates (174 from day 0, 88 from days 1–3 post delivery) from a prospective cohort study, body composition was measured using air-displacement plethysmography (PEA POD), with standard anthropometric measurements, including triceps and subscapular skinfolds. Using fat mass measurement by PEA POD as a reference, stepwise linear regression was utilized to develop a prediction equation in a randomly selected subgroup of 62 infants measured on days 1–3, which was then validated in another subgroup of 200 infants measured on days 0–3.Results:Regression analyses revealed subscapular skinfolds, weight, gender and gestational age were significant predictors of neonatal fat mass, explaining 81.1% of the variance, but not triceps skinfold or ethnicity. By Bland–Altman analyses, our prediction equation revealed a non-significant bias with limits of agreement (LOA) similar to those of a published equation for infants measured on days 1–3 (95% LOA: (−0.25, 0.26)u2009kg vs (−0.23, 0.21)u2009kg) and on day 0 (95% LOA: (−0.19, 0.17)u2009kg vs (−0.17, 0.18)u2009kg). The published equation, however, exhibited a systematic bias in our sample.Conclusions:Our equation requires only one skinfold site measurement, which can significantly reduce time and effort. It does not require the input of ethnicity and, thus, aid its application to other Asian neonatal populations.

Effect of maternal body mass index on the retinal microvasculature in pregnancy

OBJECTIVE: To estimate the effects of maternal body mass index (BMI) and pregnancy weight gain on the retinal microvasculature among pregnant women. METHODS: We studied 814 pregnant women aged 18–46 years who were recruited as part of the Growing Up in Singapore Toward Health Outcomes study, an ongoing birth cohort study from two government hospitals in Singapore since 2009. Recalled prepregnancy weight was recorded, and maternal anthropometric measurements of weight and height were performed at 26 weeks of gestation together with retinal photography. RESULTS: In multiple linear regression models, each standard deviation increase of 26-week pregnancy BMI (4.57) was associated with narrower retinal arteriolar caliber (by 1.58 micrometers, P<.001), wider venular caliber (by 1.28 micrometers, P=.02), and increased retinal venular tortuosity (P=.01). Compared with mothers with normal weight, obese mothers (prepregnancy BMI greater than 30.0) had narrower retinal arteriolar caliber (118.81 compared with 123.38 micrometers, P<.001), wider retinal venular caliber (175.81 compared with 173.01 micrometers; P<.01), and increased retinal venular tortuosity (129.92 compared with 121.49×10−6; P<.01). Pregnant women whose BMI-specific weight gain from prepregnancy to 26 weeks of gestation was above Institute of Medicine recommendations had narrower retinal arteriolar caliber (120.68 micrometers) than women with ideal (121.91 micrometers) and less than ideal weight gain (123.17), respectively (Ptrend=.05). CONCLUSION: These data indicate that greater prepregnancy BMI and pregnancy BMI are associated with adverse retinal microvascular measures, suggesting that maternal obesity has an effect on her microcirculation. LEVEL OF EVIDENCE: III

Associations Between Ethnicity, Body Composition, and Bone Mineral Density in a Southeast Asian Population

CONTEXT AND OBJECTIVEnChinese men in Singapore have a higher incidence of hip fractures than Malay and Indian men. We investigated whether there were corresponding ethnic differences in peak bone mineral density (BMD) in young men and whether differences in body composition influenced peak BMD.nnnDESIGN AND SETTINGnThis was a cross-sectional study of healthy volunteers in a tertiary medical center.nnnPARTICIPANTSnA total of 100 Chinese, 82 Malay, and 80 Indian men aged 21 to 40 years, with body mass index between 18 and 30 kg/m(2) underwent dual-energy x-ray absorptiometry to assess BMD, lean mass (LM) and fat mass (FM), and magnetic resonance imaging to quantify abdominal subcutaneous and visceral adipose tissue. Multiple linear regression models, with adjustment for age and height (as a proxy for skeletal size), were used.nnnRESULTSnMalay and Indian men had significantly higher BMD than Chinese men at the lumbar spine (Malay: B, 0.06 ± 0.02, P = .001; Indian: B, 0.03 ± 0.02, P = .049), femoral neck (Malay: B 0.04 ± 0.02, P = .034; Indian: B, 0.04 ± 0.02, P = .041), hip (Malay: B, 0.05 ± 0.02, P = .016; Indian: B, 0.06 ± 0.02, P = .001), and ultradistal radius (Malay: B, 0.03 ± 0.01, P < .001; Indian: B, 0.02 ± 0.01, P = .029), and this difference was retained after adjustment for LM and FM, except in Malay men at the femoral neck and in Indian men at the ultradistal radius. LM was an important independent determinant of BMD at all sites, whereas FM, subcutaneous adipose tissue, and visceral adipose tissue were not significantly associated with BMD at any site.nnnCONCLUSIONSnLower peak BMD in Chinese men may partly explain the higher fracture incidence in this ethnic group. Further studies are needed to elucidate the reasons for these ethnic differences in bone accumulation.

MC3R gene polymorphisms are associated with early childhood adiposity gain and infant appetite in an Asian population.

Polymorphic variants within human melanocortin‐3 receptor gene (MC3R) gene have been associated with obesity. However, its influence on infancy and early childhood adiposity has not been reported before.

Higher Maternal Dietary Protein Intake Is Associated with a Higher Risk of Gestational Diabetes Mellitus in a Multiethnic Asian Cohort

Background: Dietary protein may affect glucose metabolism through several mechanisms, but results from studies on dietary protein intake and risk of gestational diabetes mellitus (GDM) have been inconsistent.Objective: We examined the cross-sectional associations of dietary protein intake from different food sources during pregnancy with the risk of GDM in a multiethnic Asian population.Methods: We included 980 participants with singleton pregnancies from the Growing Up in Singapore Toward healthy Outcomes (GUSTO) cohort. Protein intake was ascertained from 24-h dietary recall and 3-d food diaries at 26-28 wk gestation. GDM was defined as fasting glucose ≥7.0 mmol/L and/or 2-h postload glucose ≥7.8 mmol/L at 26-28 wk gestation. We evaluated the association of dietary protein intake with GDM risk by substituting carbohydrate with protein in an isocaloric model with the use of multivariable logistic regression analysis.Results: The prevalence of GDM was 17.9% among our participants. After adjustment for potential confounders, a higher total dietary protein intake was associated with a higher risk of GDM; the OR comparing the highest with the lowest quartile of intake was 2.15 (95% CI: 1.27, 3.62; P-trend = 0.016). Higher intake levels of both animal protein (OR: 2.87; 95% CI: 1.58, 5.20; P-trend = 0.001) and vegetable protein (OR: 1.78; 95% CI: 0.99, 3.20; P-trend = 0.009) were associated with a higher risk of GDM. Among the animal protein sources, higher intake levels of seafood protein (OR: 2.17; 95% CI: 1.26, 3.72; P-trend = 0.023) and dairy protein (OR: 1.87; 95% CI: 1.11, 3.15; P-trend = 0.017) were significantly associated with a higher GDM risk.Conclusion: Higher intake levels of both animal and vegetable protein were associated with a higher risk of GDM in Asian women. This trial was registered at clinicaltrials.gov as NCT01174875.

Postnatal height and adiposity gain, childhood blood pressure and prehypertension risk in an Asian birth cohort

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.

Dietary Pattern Trajectories from 6 to 12 Months of Age in a Multi-Ethnic Asian Cohort

Little is known about the dietary patterns of Asian infants in the first year of life, nor of their associations with maternal socio-demographic factors. Based on the Growing Up in Singapore towards healthy Outcomes (GUSTO) mother-offspring cohort, cross-sectional dietary patterns were derived by factor analysis using 24-h recalls and food diaries of infants at 6-, 9- and 12-months of age. Dietary pattern trajectories were modeled by mapping similar dietary patterns across each age using multilevel mixed models. Associations with maternal socio-demographic variables, collected through questionnaires during pregnancy, were assessed using general linear models. In n = 486 infants, four dietary pattern trajectories were established from 6- to 12-months. Predominantly breastmilk: mainly breastmilk and less formula milk, Guidelines: rice porridge, vegetables, fruits and low-fat fish and meat, Easy-to-prepare foods: infant cereals, juices, cakes and biscuits and Noodles (in soup) and seafood: noodle and common accompaniments. In adjusted models, higher maternal education attainment was correlated with higher start scores on Predominantly breastmilk, but lowest education attainment increased its adherence over time. Older mothers had higher start scores on Easy-to-prepare foods, but younger mothers had increased adherence over time. Chinese mothers had higher start scores on Predominantly breastmilk but greater adherence to Guidelines over time, while Indian mothers had higher start scores on Easy-to-prepare foods but greater adherence to Predominantly breastmilk with time (p < 0.05 for all). Changes in trajectories over time were small. Hence, dietary patterns established during weaning are strongly influenced by maternal socio-demographic factors and remain stable over the first year of life.