Izzuddin M. Aris

Maternal Protein Intake during Pregnancy Is Not Associated with Offspring Birth Weight in a Multiethnic Asian Population

BACKGROUND Maternal diet during pregnancy can influence fetal growth. However, the relation between maternal macronutrient intake and birth size outcomes is less clear. OBJECTIVE We examined the associations between maternal macronutrient intake during pregnancy and infant birth size. METHODS Pregnant women (n = 835) from the Singapore GUSTO (Growing Up in Singapore Towards healthy Outcomes) mother-offspring cohort were studied. At 26-28 wk of gestation, the macronutrient intake of women was ascertained with the use of 24 h dietary recalls and 3 d food diaries. Weight, length, and ponderal index of their offspring were measured at birth. Associations were assessed by substitution models with the use of multiple linear regressions. RESULTS Mean ± SD maternal energy intake and percentage energy from protein, fat, and carbohydrates per day were 1903 ± 576 kcal, 15.6% ± 3.9%, 32.7% ± 7.5%, and 51.6% ± 8.7% respectively. With the use of adjusted models, no associations were observed for maternal macronutrient intake and birth weight. In male offspring, higher carbohydrate or fat intake with lower protein intake was associated with longer birth length (β = 0.08 cm per percentage increment in carbohydrate; 95% CI: 0.04, 0.13; β = 0.08 cm per percentage increment in fat; 95% CI: 0.02, 0.13) and lower ponderal index (β = -0.12 kg/m(3) per percentage increment in carbohydrate; 95% CI: -0.19, -0.05; β = -0.08 kg/m(3) per percentage increment in fat; 95% CI: -0.16, -0.003), but this was not observed in female offspring (P-interaction < 0.01). CONCLUSIONS Maternal macronutrient intake during pregnancy was not associated with infant birth weight. Lower maternal protein intake was significantly associated with longer birth length and lower ponderal index in male but not female offspring. However, this finding warrants further confirmation in independent studies. This trial was registered at clinicaltrials.gov as NCT01174875.

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

BACKGROUND Maternal folate, vitamin B-12, and vitamin B-6 concentrations during pregnancy have been shown to influence birth outcomes, but the evidence is inconclusive. OBJECTIVE We aimed to examine the associations of maternal B-vitamin status with gestational age, birth weight, and length in a birth cohort study in Singapore. METHODS Maternal 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. RESULTS Median (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). CONCLUSIONS Higher 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.

Associations of gestational glycemia and prepregnancy adiposity with offspring growth and adiposity in an Asian population

BACKGROUND Maternal obesity and hyperglycemia increase risk of obesity and diabetes in offspring later in life. OBJECTIVE We examined the relation between gestational glycemia and prepregnancy body mass index (ppBMI) with offspring growth in an Asian mother-offspring cohort. DESIGN Pregnant mothers undertook a 75-g 2-h oral-glucose-tolerance test at 26-28 wk of gestation. In 937 singleton offspring, ≤9 serial measurements of weight and length were obtained from birth until 36 mo of age. RESULTS Gestational fasting plasma glucose (FPG) was positively associated with birth weight (B: 0.17; 95% CI: 0.10, 0.24; P < 0.001) and birth BMI (B: 0.15; 95% CI: 0.06, 0.40; P = 0.001) but not at ≥3 mo of age. In contrast, maternal ppBMI was positively associated with birth variables and conditional growth in weight and BMI in the first 36 mo of life. However, gestational FPG and prepregnancy obesity status interacted significantly for the association with offspring growth and overweight status in the first 36 mo of life (P-interaction < 0.01). In nonobese mothers, each unit increase in gestational FPG was associated with increased offspring weight (B: 0.08; 95% CI: 0.008, 0.16; P = 0.03) and BMI (B: 0.08; 95% CI: 0.003, 0.15; P = 0.04) as well as increased risk of overweight in the first 36 mo of life (OR: 1.36; 95% CI: 1.10, 1.68). However, in obese mothers, each unit increase in gestational FPG was associated with decreased offspring weight (B: -0.01; 95% CI: -0.02, -0.003) and BMI (B: -0.008; 95% CI: -0.01, -0.002) velocity (P < 0.01 for both) and decreased risk of overweight (OR: 0.59; 95% CI: 0.41, 0.86) in the first 36 mo of life. CONCLUSIONS Prepregnancy adiposity was associated with offspring growth in early childhood. Although pooled analyses showed no demonstrable difference by 3 mo of age, there were contrasting and opposite associations of gestational glycemia with weight and BMI in the first 36 mo of life in offspring of nonobese and obese mothers separately. This study was registered at clinicaltrials.gov as NCT01174875.

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) kg vs (−0.23, 0.21) kg) and on day 0 (95% LOA: (−0.19, 0.17) kg vs (−0.17, 0.18) kg). 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.

Maternal Macronutrient Intake during Pregnancy Is Associated with Neonatal Abdominal Adiposity: The Growing Up in Singapore Towards healthy Outcomes (GUSTO) Study.

BACKGROUND Infant body composition has been associated with later metabolic disease risk, but few studies have examined the association between maternal macronutrient intake and neonatal body composition. Furthermore, most of those studies have used proxy measures of body composition that may not reflect body fat distribution, particularly abdominal internal adiposity. OBJECTIVE We investigated the relation between maternal macronutrient intake and neonatal abdominal adiposity measured by using MRI in a multiethnic Asian mother-offspring cohort. METHODS The macronutrient intake of mothers was ascertained by using a 24-h dietary recall at 26-28 wk gestation. Neonatal abdominal adiposity was assessed by using MRI in week 2 of life. Mother-offspring dyads with complete macronutrient intake and adiposity information (n = 320) were included in the analysis. Associations were assessed by both substitution and addition models with the use of multivariable linear regressions. RESULTS Mothers (mean age: 30 y) consumed (mean ± SD) 15.5% ± 4.3% of their energy from protein, 32.4% ± 7.7% from fat, and 52.1% ± 9.0% from carbohydrate. A higher-protein, lower-carbohydrate or -fat diet during pregnancy was associated with lower abdominal internal adipose tissue (IAT) in the neonates [β (95% CI): -0.18 mL (-0.35, -0.001 mL) per 1% protein-to-carbohydrate substitution and -0.25 mL (-0.46, -0.04 mL) per 1% protein-to-fat substitution]. These associations were stronger in boys than in girls (P-interaction < 0.05). Higher maternal intake of animal protein, but not plant protein, was associated with lower offspring IAT. In contrast, maternal macronutrient intake was not associated consistently with infant anthropometric measurements, including abdominal circumference and subscapular skinfold thickness. CONCLUSIONS Higher maternal protein intake at the expense of carbohydrate or fat intake at 26-28 wk gestation was associated with lower abdominal internal adiposity in neonates. Optimizing maternal dietary balance might be a new approach to improve offspring body composition. This trial was registered at clinicaltrials.gov as NCT01174875.

Infant body mass index peak and early childhood cardio-metabolic risk markers in a multi-ethnic Asian birth cohort

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 childs 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.

Sleep duration and growth outcomes across the first two years of life in the GUSTO study

BACKGROUND AND AIM Short sleep duration is thought to be a factor contributing to increased body mass index (BMI) in both school-age children and adults. Our aim was to determine whether sleep duration associates with growth outcomes during the first two years of life. STUDY DESIGN Participants included 899 children enrolled in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study. Anthropometric data (weight and body length) and parental reports of sleep duration were collected at 3, 6, 9, 12, 18, and 24 months of age. A mixed-model analysis was used to evaluate the longitudinal association of BMI and body length with sleep duration. In subgroup analyses, effects of ethnicity (Chinese, Indian, and Malay) and short sleep at three months of age (≤12 h per day) were examined on subsequent growth measures. RESULTS In the overall cohort, sleep duration was significantly associated with body length (β = 0.028, 95% confidence interval [CI] 0.002-0.053, p = 0.033), but not BMI, after adjustment for potential confounding factors. Only in Malay children, shorter sleep was associated with a higher BMI (β = -0.042, 95% CI -0.071 to -0.012, p = 0.005) and shorter body length (β = 0.079, 95% CI 0.030-0.128, p = 0.002). In addition, shorter sleep was associated with a higher BMI and shorter body length in children who slept ≤12 h per day at three months of age. CONCLUSION The association between sleep duration and growth outcomes begins in infancy. The small but significant relationship between sleep and growth anthropometric measures in early life might be amplified in later childhood.

Abdominal adipose tissue compartments vary with ethnicity in Asian neonates: Growing Up in Singapore Toward Healthy Outcomes birth cohort study

BACKGROUND A susceptibility to metabolic diseases is associated with abdominal adipose tissue distribution and varies between ethnic groups. The distribution of abdominal adipose tissue at birth may give insights into whether ethnicity-associated variations in metabolic risk originate partly in utero. OBJECTIVE We assessed the influence of ethnicity on abdominal adipose tissue compartments in Asian neonates in the Growing Up in Singapore Toward Healthy Outcomes mother-offspring cohort. DESIGN MRI was performed at ≤2 wk after birth in 333 neonates born at ≥34 wk of gestation and with birth weights ≥2000 g. Abdominal superficial subcutaneous tissue (sSAT), deep subcutaneous tissue (dSAT), and internal adipose tissue (IAT) compartment volumes (absolute and as a percentage of the total abdominal volume) were quantified. RESULTS In multivariate analyses that were controlled for sex, age, and parity, the absolute and percentage of dSAT and the percentage of sSAT (but not absolute sSAT) were greater, whereas absolute IAT (but not the percentage of IAT) was lower, in Indian neonates than in Chinese neonates. Compared with Chinese neonates, Malay neonates had greater percentages of sSAT and dSAT but similar percentages of IAT. Marginal structural model analyses largely confirmed the results on the basis of volume percentages with controlled direct effects of ethnicity on abdominal adipose tissue; dSAT was significantly greater (1.45 mL; 95% CI: 0.49, 2.41 mL, P = 0.003) in non-Chinese (Indian or Malay) neonates than in Chinese neonates. However, ethnic differences in sSAT and IAT were NS [3.06 mL (95% CI:-0.27, 6.39 mL; P = 0.0712) for sSAT and -1.30 mL (95% CI: -2.64, 0.04 mL; P = 0.057) for IAT in non-Chinese compared with Chinese neonates, respectively]. CONCLUSIONS Indian and Malay neonates have a greater dSAT volume than do Chinese neonates. This finding supports the notion that in utero influences may contribute to higher cardiometabolic risk observed in Indian and Malay persons in our population. If such differences persist in the longitudinal tracking of adipose tissue growth, these differences may contribute to the ethnic disparities in risks of cardiometabolic diseases. This trial was registered at clinicaltrials.gov as NCT01174875.

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.