Higher early pregnancy plasma myo-inositol associates with increased postprandial glycaemia later in pregnancy: Secondary analyses of the NiPPeR randomized controlled trial.

AIM: Myo-inositol supplementation from ~13 weeks' gestation reportedly improves glycaemia regulation in metabolically at-risk women, with speculation that earlier supplementation might bring further improvement. However, the NiPPeR trial of a myo-inositol-containing supplement starting preconception did not lower gestational glycaemia in generally healthy women. We postulated that the earlier timing of supplementation influences the maternal metabolic adaptation for gestational glycaemia regulation. METHODS: In total, 585 women were recruited from Singapore, UK and New Zealand for the NiPPeR study. We examined associations of plasma myo-inositol concentrations at 7 and 28 weeks' gestation with 28 weeks plasma glucose (PG; fasting, and 1 h and 2 h in 75 g oral glucose tolerance test) and insulin indices using linear regression adjusting for covariates. RESULTS: Higher 7-week myo-inositol, but not 28-week myo-inositol, associated with higher 1 h PG [ßadj (95% confidence intervals) 0.05 (0.01, 0.09) loge mmol/L per loge µmol/L, p = .022] and 2 h PG [0.08 (0.03, 0.12), p = .001]; equivalent to 0.39 mmol/L increase in 2 h PG for an average 7-week myo-inositol increase of 23.4 µmol/L with myo-inositol supplementation. Higher 7-week myo-inositol associated with a lower 28-week Stumvoll index (first phase), an approximation of insulin secretion [-0.08 (-0.15, -0.01), p = .020] but not with 28-week Matsuda insulin sensitivity index. However, the clinical significance of a 7-week myo-inositol-related increase in glycaemia was limited as there was no association with gestational diabetes risk, birthweight and cord C-peptide levels. In-silico modelling found higher 28-week myo-inositol was associated with lower gestational glycaemia in White, but not Asian, women after controlling for 7-week myo-inositol effects. CONCLUSION: To our knowledge, our study provides the first evidence that increasing first trimester plasma myo-inositol may slightly exacerbate later pregnancy post-challenge glycaemia, indicating that the optimal timing for starting prenatal myo-inositol supplementation needs further investigation.

Maternal and Paternal Dietary Quality and Dietary Inflammation Associations with Offspring DNA Methylation and Epigenetic Biomarkers of Aging in the Lifeways Cross-Generation Study.

BACKGROUND: Early-life nutritional exposures may contribute to offspring epigenetic modifications. However, few studies have evaluated parental dietary quality effects on offspring DNA methylation (DNAm). OBJECTIVES: We aim to fill this gap by elucidating the influence of maternal and paternal whole-diet quality and inflammatory potential on offspring DNAm in the Lifeways Cross-generation cohort. METHODS: Families (n = 1124) were recruited around 16 weeks of gestation in the Republic of Ireland between 2001 and 2003. Maternal dietary intake during the first trimester and paternal diet during the 12 previous months were assessed with an FFQ. Parental dietary inflammatory potential and quality were determined using the energy-adjusted Dietary Inflammatory Index (E-DII), the Healthy Eating Index-2015 (HEI-2015), and the maternal DASH score. DNAm in the saliva of 246 children at age nine was measured using the Illumina Infinium HumanMethylationEPIC array. DNAm-derived biomarkers of aging, the Pediatric-Buccal-Epigenetic clock and DNAm estimator of telomere length, were calculated. Parental diet associations with the DNAm concentrations of 850K Cytosine-phosphate-guanine sites (CpG sites) and with DNAm-derived biomarkers of aging were examined using an epigenome-wide association study and linear regressions, respectively. RESULTS: Maternal HEI-2015 scores were inversely associated with DNAm at CpG site (cg21840035) located near the PLEKHM1 gene, whose functions involve regulation of bone development (ß = -0.0036, per 1 point increase in the score; P = 5.6 × 10-8). Higher paternal HEI-2015 score was related to lower methylation at CpG site (cg22431767), located near cell signaling gene LUZP1 (ß = -0.0022, per 1 point increase in the score, P = 4.1 × 10-8). There were no associations with parental E-DII and DASH scores, and no evidence of major effects on biomarkers of aging. CONCLUSIONS: Parental dietary quality in the prenatal period, evaluated by the HEI-2015, may influence offspring DNAm during childhood. Further research to improve our understanding of parental nutritional programming is warranted.

Maternal diet in pregnancy and child's respiratory outcomes: an individual participant data meta-analysis of 18 000 children.

RATIONALE: Severe fetal malnutrition has been related to an increased risk of respiratory diseases later in life, but evidence for the association of a suboptimal diet during pregnancy with respiratory outcomes in childhood is conflicting. We aimed to examine whether a pro-inflammatory or low-quality maternal diet during pregnancy was associated with child's respiratory health. METHODS: We performed an individual participant meta-analysis among 18 326 mother-child pairs from seven European birth cohorts. Maternal pro-inflammatory and low-quality diets were estimated by energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) scores. Preschool wheezing and school-age asthma were measured using questionnaires and lung function by spirometry. RESULTS: After adjustment for lifestyle and sociodemographic factors, we observed that a higher maternal E-DII score (a more pro-inflammatory diet) during pregnancy was associated only with a lower forced vital capacity (FVC) in children (z-score difference -0.05, 95% CI -0.08- -0.02, per interquartile range increase). No linear associations of the maternal E-DII or DASH score with child's wheezing or asthma were observed. In an exploratory examination of the extremes, a very low DASH score (<10th percentile) (a very low dietary quality) was associated with an increased risk of preschool wheezing and a low forced expiratory volume in 1 s/FVC (z-score <-1.64) (OR 1.20, 95% CI 1.06-1.36 and z-score difference 1.40, 95% CI 1.06-1.85, compared to ≥10th percentile), with corresponding population attributable risk fractions of 1.7% and 3.3%, respectively. CONCLUSION: The main results from this individual participant data meta-analysis do not support the hypothesis that maternal pro-inflammatory or low-quality diet in pregnancy are related to respiratory diseases in childhood.

Breastfeeding may benefit cardiometabolic health of children exposed to increased gestational glycemia in utero.

PURPOSE: There is altered breastmilk composition among mothers with gestational diabetes and conflicting evidence on whether breastfeeding is beneficial or detrimental to their offspring's cardiometabolic health. We aimed to investigate associations between breastfeeding and offspring's cardiometabolic health across the range of gestational glycemia. METHODS: We included 827 naturally conceived, term singletons from a prospective mother-child cohort. We measured gestational (26-28 weeks) fasting plasma glucose (FPG) and 2-h plasma glucose (2 hPG) after an oral glucose tolerance test as continuous variables. Participants were classified into 2 breastfeeding categories (high/intermediate vs. low) according to their breastfeeding duration and exclusivity. Main outcome measures included magnetic resonance imaging (MRI)-measured abdominal fat, intramyocellular lipids (IMCL), and liver fat, quantitative magnetic resonance (QMR)-measured body fat mass, blood pressure, blood lipids, and insulin resistance at 6 years old (all continuous variables). We evaluated if gestational glycemia (FPG and 2 hPG) modified the association of breastfeeding with offspring outcomes after adjusting for confounders using a multiple linear regression model that included a 'gestational glycemia × breastfeeding' interaction term. RESULTS: With increasing gestational FPG, high/intermediate (vs. low) breastfeeding was associated with lower levels of IMCL (p-interaction = 0.047), liver fat (p-interaction = 0.033), and triglycerides (p-interaction = 0.007), after adjusting for confounders. Specifically, at 2 standard deviations above the mean gestational FPG level, high/intermediate (vs. low) breastfeeding was linked to lower adjusted mean IMCL [0.39% of water signal (0.29, 0.50) vs. 0.54% of water signal (0.46, 0.62)], liver fat [0.39% by weight (0.20, 0.58) vs. 0.72% by weight (0.59, 0.85)], and triglycerides [0.62 mmol/L (0.51, 0.72) vs. 0.86 mmol/L (0.75, 0.97)]. 2 hPG did not significantly modify the association between breastfeeding and childhood cardiometabolic risk. CONCLUSION: Our findings suggest breastfeeding may confer protection against adverse fat partitioning and higher triglyceride concentration among children exposed to increased glycemia in utero.

Associations of maternal dietary inflammatory potential and quality with offspring birth outcomes: An individual participant data pooled analysis of 7 European cohorts in the ALPHABET consortium.

BACKGROUND: Adverse birth outcomes are major causes of morbidity and mortality during childhood and associate with a higher risk of noncommunicable diseases in adult life. Maternal periconception and antenatal nutrition, mostly focusing on single nutrients or foods, has been shown to influence infant birth outcomes. However, evidence on whole diet that considers complex nutrient and food interaction is rare and conflicting. We aim to elucidate the influence of whole-diet maternal dietary inflammatory potential and quality during periconceptional and antenatal periods on birth outcomes. METHODS AND FINDINGS: We harmonized and pooled individual participant data (IPD) from up to 24,861 mother-child pairs in 7 European mother-offspring cohorts [cohort name, country (recruitment dates): ALSPAC, UK (1 April 1991 to 31 December 1992); EDEN, France (27 January 2003 to 6 March 2006); Generation R, the Netherlands (1 April 2002 to 31 January 2006); Lifeways, Ireland (2 October 2001 to 4 April 2003); REPRO_PL, Poland (18 September 2007 to 16 December 2011); ROLO, Ireland (1 January 2007 to 1 January 2011); SWS, United Kingdom (6 April 1998 to 17 December 2002)]. Maternal diets were assessed preconceptionally (n = 2 cohorts) and antenatally (n = 7 cohorts). Maternal dietary inflammatory potential and quality were ranked using the energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) index, respectively. Primary outcomes were birth weight and gestational age at birth. Adverse birth outcomes, i.e., low birth weight (LBW), macrosomia, small-for-gestational-age (SGA), large-for-gestational-age (LGA), preterm and postterm births were defined according to standard clinical cutoffs. Associations of maternal E-DII and DASH scores with infant birth outcomes were assessed using cohort-specific multivariable regression analyses (adjusted for confounders including maternal education, ethnicity, prepregnancy body mass index (BMI), maternal height, parity, cigarettes smoking, and alcohol consumption), with subsequent random-effects meta-analyses. Overall, the study mothers had a mean ± SD age of 29.5 ± 4.9 y at delivery and a mean BMI of 23.3 ± 4.2 kg/m2. Higher pregnancy DASH score (higher dietary quality) was associated with higher birth weight [ß(95% CI) = 18.5(5.7, 31.3) g per 1-SD higher DASH score; P value = 0.005] and head circumference [0.03(0.01, 0.06) cm; P value = 0.004], longer birth length [0.05(0.01, 0.10) cm; P value = 0.010], and lower risk of delivering LBW [odds ratio (OR) (95% CI) = 0.89(0.82, 0.95); P value = 0.001] and SGA [0.87(0.82, 0.94); P value < 0.001] infants. Higher maternal prepregnancy E-DII score (more pro-inflammatory diet) was associated with lower birth weight [ß(95% CI) = -18.7(-34.8, -2.6) g per 1-SD higher E-DII score; P value = 0.023] and shorter birth length [-0.07(-0.14, -0.01) cm; P value = 0.031], whereas higher pregnancy E-DII score was associated with a shorter birth length [-0.06(-0.10, -0.01) cm; P value = 0.026] and higher risk of SGA [OR(95% CI) = 1.18(1.11, 1.26); P value < 0.001]. In male, but not female, infants higher maternal prepregnancy E-DII was associated with lower birth weight and head circumference, shorter birth length, and higher risk of SGA (P-for-sex-interaction = 0.029, 0.059, 0.104, and 0.075, respectively). No consistent associations were observed for maternal E-DII and DASH scores with gestational age, preterm and postterm birth, or macrosomia and LGA. Limitations of this study were that self-reported dietary data might have increased nondifferential measurement error and that causality cannot be claimed definitely with observational design. CONCLUSIONS: In this cohort study, we observed that maternal diet that is of low quality and high inflammatory potential is associated with lower offspring birth size and higher risk of offspring being born SGA in this multicenter meta-analysis using harmonized IPD. Improving overall maternal dietary pattern based on predefined criteria may optimize fetal growth and avert substantial healthcare burden associated with adverse birth outcomes.

Maternal dietary quality, inflammatory potential and childhood adiposity: an individual participant data pooled analysis of seven European cohorts in the ALPHABET consortium.

BACKGROUND: Mounting evidence suggests that maternal diet influences pregnancy and birth outcomes, but its contribution to the global epidemic of childhood obesity has not as yet been definitively characterized. We investigated whether maternal whole diet quality and inflammatory potential influence childhood adiposity. METHODS: We harmonized and pooled individual participant data from 16,295 mother-child pairs in seven European birth cohorts. Maternal pre-, early-, late-, and whole-pregnancy (any time during pregnancy) dietary quality and inflammatory potential assessed with the Dietary Approaches to Stop Hypertension (DASH) score and the energy-adjusted Dietary Inflammatory Index (E-DII™) score, respectively. Primary outcome was childhood overweight and obesity (OWOB) (age-and-sex-specific BMI z-score > 85th percentile). Secondary outcomes were sum of skinfold thickness (SST), fat mass index (FMI) and fat-free mass index (FFMI). We used multivariable regression analyses (adjusting for maternal lifestyle and sociodemographic factors) to assess the associations of maternal DASH and E-DII scores with offspring adiposity outcomes in cohort-specific analyses, with subsequent random-effect meta-analyses. RESULTS: The study mothers had a mean (SD) age of 30.2 (4.6) years and a mean BMI of 23.4 (4.2) kg/m2. Higher early-pregnancy E-DII scores (more pro-inflammatory diet) tended to be associated with a higher odds of late-childhood [10.6 (1.2) years] OWOB [OR (95% CI) 1.09 (1.00, 1.19) per 1-SD E-DII score increase], whereas an inverse association was observed for late-pregnancy E-DII score and early-childhood [2.8 (0.3) years] OWOB [0.91 (0.83, 1.00)]. Higher maternal whole pregnancy DASH score (higher dietary quality) was associated with a lower odds of late-childhood OWOB [OR (95% CI) 0.92 (0.87, 0.98) per 1-SD DASH score increase]; associations were of similar magnitude for early and late-pregnancy [0.86 (0.72, 1.04) and 0.91 (0.85, 0.98), respectively]. These associations were robust in several sensitivity analyses and further adjustment for birth weight and childhood diet did not meaningfully alter the associations and conclusions. In two cohorts with available data, a higher whole pregnancy E-DII and lower DASH scores were associated with a lower late-childhood FFMI in males and a higher mid-childhood FMI in females (P interactions < 0.10). CONCLUSIONS: A pro-inflammatory, low-quality maternal antenatal diet may adversely influence offspring body composition and OWOB risk, especially during late-childhood. Promoting an overall healthy and anti-inflammatory maternal dietary pattern may contribute to the prevention of childhood obesity, a complex health issue requiring multifaceted strategy.

Trajectories of Systolic Blood Pressure in Children: Risk Factors and Cardiometabolic Correlates.

OBJECTIVE: To identify systolic blood pressure (SBP) percentile trajectories in children and to describe the early-life risk factors and cardiometabolic correlates of those trajectories. STUDY DESIGN: Using age-, sex-, and height-specific SBP percentiles based on the American Academy of Pediatrics reference, we examined SBP trajectories using latent class mixed models from ages 3 to 8 years (n = 844) from the Growing Up in Singapore Towards healthy Outcomes-study, a Singaporean mother-offspring cohort study. We analyzed associations between SBP trajectories and early-life risk factors using multinomial logistic regression and differences across trajectories in cardiometabolic outcomes using multiple linear regression. RESULTS: Children were classified into 1 of 4 SBP percentile trajectories: "low increasing" (15%), "high stable" (47%), "high decreasing" (20%), and "low stable" (18%). Maternal hypertension during early pregnancy was a predictor of the "high stable" and "low increasing" SBP trajectories. Rapid child weight gain in the first 2 years of life was only associated with the "high stable" trajectory. Compared with children in the "low stable" trajectory, children in the "high stable" SBP trajectory had greater body mass index z scores, sum of skinfold thicknesses, waist circumference from ages 3 to 8 years, and abdominal adipose tissue (milliliters) at 4.5 years (adjusted mean difference [95% CI]: superficial and deep subcutaneous abdominal adipose tissue: 115.2 [48.1-182.3] and 85.5 [35.2-135.8]). Their fat mass (kilograms) (1.3 [0.6-2.0]), triglyceride levels (mmol/L) (0.10 [0.02-0.18]), and homeostasis model assessment of insulin resistance (0.28 [0.11 0.46]) at age 6 years were also greater but not their arterial thickness and stiffness. CONCLUSIONS: Reducing maternal blood pressure during pregnancy and infant weight gain in the first 2 years of life might help to prevent the development of high SBP.

Exercise Capacity and Quality of Life in Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease with a high mortality rate that can be divided into different groups according to etiology and prognosis. Few studies have investigated differences in the exercise capacity and quality of life (QOL) among the different groups of PAH patients. Therefore, we aimed to (1) compare the hemodynamic exercise responses between patients with idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with other diseases (APAH), and (2) determine the factors associated with exercise capacity in patients with PAH. METHODS: Six patients diagnosed with IPAH and eight with APAH [congenital heart disease (CHD)-dominant PAH] were included in this study. The main outcome measures included body composition, exercise capacity, hemodynamic measurements, physical activity levels, fatigue severity, and QOL. RESULTS: The CHD-dominant PAH group had a significantly lower predicted peak oxygen consumption (VO2pred %), pressure of end-tidal carbon dioxide at the peak and at anaerobic threshold (PETCO2peak and PETCO2@AT), and significantly elevated ventilatory equivalent (VE/VCO2slope and VE/VCO2@AT) compared with the IPAH group. Multiple regression analysis indicated that PETCO2@AT was significantly associated with either VO2peak (ß = 0.805, adjusted R2 = 0.619, p = 0.001) or 6-minute walk distance (ß = 0.816, adjusted R2 = 0.638, p < 0.001). CONCLUSIONS: Patients with CHD-dominant PAH had poor exercise capacity and exercise responses compared to those with IPAH. Evaluating exercise capacity and the patient response to exercise using cardiopulmonary exercise testing is increasingly important in view of the etiology of PAH.

Implication of gut microbiota in the association between infant antibiotic exposure and childhood obesity and adiposity accumulation.

BACKGROUND: In animal studies early life antibiotic exposure causes metabolic abnormalities including obesity through microbiota disruption, but evidence from human studies is scarce. We examined involvement of gut microbiota in the associations between infant antibiotic exposure and childhood adiposity. METHODS: Infant antibiotic exposure in the first year of life was ascertained using parental reports during interviewer-administered questionnaires. Primary outcomes were childhood obesity [body mass index (BMI) z-score > 95th percentile] and adiposity [abdominal circumference (AC) and skinfold (triceps + subscapular (SST)) measurements] determined from ages 15-60 months. At age 24 months, when the gut microbiota are more stable, stool samples (n = 392) were collected for the gut microbiota profiling using co-abundancy networks. Associations of antibiotic exposure with obesity and adiposity (n = 1016) were assessed using multiple logistic and linear mixed effects regressions. Key bacteria associated with antibiotics exposure were identified by partial redundancy analysis and multivariate association with linear models. RESULTS: Antibiotic exposure was reported in 38% of study infants. In a fully adjusted model, a higher odds of obesity from 15-60 months of age was observed for any antibiotic exposure [OR(95% CI) = 1.45(1.001, 2.14)] and exposure to ≥3 courses of antibiotics [2.78(1.12, 6.87)]. For continuous adiposity indicators, any antibiotic exposure was associated with higher BMI z-score in boys [ß = 0.15(0.01, 0.28)] but not girls [ß = -0.04(-0.19, 0.11)] (P interaction = 0.026). Similarly, exposure to ≥3 courses of antibiotics was associated with higher AC in boys [1.15(0.05, 2.26) cm] but not girls [0.57(-1.32, 2.45) cm] (P interaction not significant). Repeated exposure to antibiotics was associated with a significant reduction (FDR-corrected P values < 0.05) in a microbial co-abundant group (CAG) represented by Eubacterium hallii, whose proportion was negatively correlated with childhood adiposity. Meanwhile, a CAG represented by Tyzzerella 4 was positively correlated with the repeated use of antibiotics and childhood adiposity. CONCLUSIONS: Infant antibiotic exposure was associated with disruption of the gut microbiota and the higher risks of childhood obesity and increased adiposity.

Maternal Dietary Glycemic and Insulinemic Indexes Are Not Associated with Birth Outcomes or Childhood Adiposity at 5 Years of Age in an Irish Cohort Study.

BACKGROUND: High maternal dietary glycemic index (GI) and glycemic load (GL) may be associated with adverse offspring birth and postnatal adiposity outcomes through metabolic programming, but the evidence thus far, mainly from studies conducted in high-risk pregnant populations, has been inconclusive. No study has examined the influence of maternal insulin demand [measured by food insulinemic index (II) and insulinemic load (IL)] on offspring outcomes. OBJECTIVES: We investigated associations between maternal GI, GL, II, and IL and offspring birth outcomes and postnatal adiposity in a general pregnant population. METHODS: The study was based on data from 842 mother-child pairs from the Lifeways prospective cohort study in Ireland. Through the use of standard methodology, maternal GI, GL, II, and IL were derived from dietary information obtained via a validated food-frequency questionnaire in early pregnancy (12-16 wk). Birth outcomes were abstracted from hospital records. At 5-y follow-up, children's body mass index (BMI) and waist circumference were measured. Associations were assessed through the use of multivariable-adjusted regression analysis. RESULTS: Mothers had a mean ± SD age of 30.3 ± 5.7 y and a mean BMI (kg/m2) of 23.9 ± 4.2. The mean ± SD for dietary glycemic and insulinemic indexes were: GI = 58.9 ± 4.4; GL = 152 ± 49; II = 57.4 ± 14.5; IL = 673 ± 267. After adjustment for confounders, no consistent associations were observed between maternal GI, GL, II, and IL and birth outcomes including birth weight, macrosomia, gestational age, and postterm births. Similarly, no association was observed with BMI and waist circumference z scores and childhood obesity (general and central) at 5-y follow-up. There was no evidence of a nonlinear relation between the studied indexes and outcomes. CONCLUSIONS: We observed no clear relation between maternal GI, GL, II, and IL and offspring birth outcomes and childhood obesity in a general pregnant population.

Effects of exercise training on anabolic and catabolic markers in patients with chronic heart failure: a systematic review.

Decreased anabolism because of alterations in the insulin-like growth factor 1 (IGF-1)/growth hormone (GH) axis and increased catabolism induced by proinflammatory cytokines like tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) have been reported to contribute to muscle wasting in chronic heart failure (CHF). However, it is unclear whether exercise training could modulate anabolic and catabolic markers in CHF patients. The purpose of this study was to investigate the effects of exercise intervention on anabolic and catabolic markers for patients with CHF. Literatures were systematically searched in electronic databases and relevant references. Only published randomized controlled trials (RCTs) focusing on exercise training for CHF were eligible for inclusion. Outcome measurements included serum level and muscle biopsy of TNF-α, IL-6, GH, and IGF-I. Of the six included studies, four showed no significant difference between exercise group and control group in the serum levels of TNF-α, IL-6, GH, and IGF-I. However, two studies showed significant reduction in TNF-α and IL-6 and increase in IGF-I by local skeletal muscle biopsy. We conclude that the decreases in catabolic markers and increases in anabolic after exercise training were evident only by local skeletal muscle biopsy. More RCTs on dose-response relation of exercise programs are needed to further optimize anabolic and anti-inflammatory benefits of exercise training in patients with CHF.

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.

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 [ß (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.

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.

Maternal caffeine intake during pregnancy and risk of pregnancy loss: a categorical and dose-response meta-analysis of prospective studies.

OBJECTIVE: To assess the association between maternal caffeine intake and risk of pregnancy loss using a systematic review and meta-analysis. DESIGN: Categorical and dose-response meta-analysis of prospective studies. SETTING: Relevant articles were identified by searching MEDLINE and SCOPUS databases through 30 January 2015. Two authors independently extracted information from eligible studies. Random-effects models were used to derive the summary relative risks (RR) and corresponding 95% CI for specific categories of caffeine consumption and for a continuous association using generalized least-squares trend estimation. SUBJECTS: A total of 130 456 participants and 3429 cases in fourteen included studies. RESULTS: Compared with the reference category with no or very low caffeine intake, the RR (95% CI) of pregnancy loss was 1·02 (0·85, 1·24; I(2)=28·3%) for low intake (50-149 mg/d), 1·16 (0·94, 1·41; I 2=49·6%) for moderate intake (150-349 mg/d), 1·40 (1·16, 1·68; I(2)=18·6%) for high intake (350-699 mg/d) and 1·72 (1·40, 2·13; I(2)=0·0%) for very high intake (≥ 700 mg/d). In the dose-response analysis, each 100 mg/d increment in maternal caffeine intake (~1 cup of coffee) was associated with 7% (95% CI 3%, 12%) higher risk of pregnancy loss. Our results may have been affected by publication bias, but the association remained significant for the subset of larger studies. Furthermore, adjustment for smoking and pregnancy symptoms may have been incomplete, potentially resulting in residual confounding. CONCLUSIONS: Albeit inconclusive, higher maternal caffeine intake was associated with a higher risk of pregnancy loss and adherence to guidelines to avoid high caffeine intake during pregnancy appears prudent.

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.

Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose-response meta-analysis.

BACKGROUND: Considerable controversy exists regarding the relation between maternal caffeine intake during pregnancy and risk of low birth weight (birth weight <2,500 g). We aim to assess this association using a systematic review and dose-response meta-analysis of prospective studies. METHODS: Potential articles were identified by searching MEDLINE and SCOPUS databases through 17 July 2013. Two authors independently extracted information on study design, participant characteristics and estimates of associations. Random-effects models were used to derive the summary relative risks (RRs) and corresponding 95% confidence intervals (CIs). Dose-response relationships were assessed using generalized least-squares trend estimation. RESULTS: In our meta-analysis, we included 13 prospective studies: 9 with low birth weight as a binary outcome variable (90,747 participants and 6,303 cases) and 6 with birth weight as a continuous outcome variable (10,015 participants; 2 studies reported both types of outcomes). Compared with the reference category with no or very low caffeine intake, the RR (95% CI) of low birth weight was 1.13 (1.06 to 1.21; I 2 0.0%) for low intake (50 to 149 mg/day), 1.38 (1.18 to 1.62; I 2 31.9%) for moderate intake (150 to 349 mg/day), and 1.60 (1.24 to 2.08; I 2 65.8%) for high intake (≥350 mg/day). In the dose-response analysis, each 100-mg/day increment in maternal caffeine intake (around one cup of coffee) was associated with 13% (RR 1.13, 1.06 to 1.21) higher risk of low birth weight. The association persisted in strata defined according to various study characteristics. Moderate (-33 g, 95% CI -63 to -4; I 2 0.3%) and high (-69 g, 95% CI -102 to -35; I 2 0.0%) caffeine intakes were also associated with a significantly lower birth weight as compared with the reference category. CONCLUSIONS: Higher maternal caffeine intake during pregnancy was associated with a higher risk of delivering low birth weight infants. These findings support recommendations to restrict caffeine intake during pregnancy to low levels.

Dietary changes during pregnancy and the postpartum period in Singaporean Chinese, Malay and Indian women: the GUSTO birth cohort study.

OBJECTIVE: To examine changes in food consumption during pregnancy and the postpartum period in women of major Asian ethnic groups. DESIGN: Using interviewer-administered questionnaires, we assessed changes in food consumption during pregnancy (26-28 weeks' gestation) and the postpartum period (3 weeks after delivery) as compared with the usual pre-pregnancy diet. SETTING: Singapore. SUBJECTS: Pregnant women (n 1027) of Chinese, Malay and Indian ethnicity (mean age 30·4 (SD 5·2) years) who participated in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. RESULTS: During pregnancy, participants tended to increase their consumption of milk, fruit and vegetables and decrease their consumption of tea, coffee, soft drinks and seafood (all P < 0·001). Most participants reported adherence to traditional restrictions ('confinement') during the early postpartum period (Chinese: 94·8 %, Malay: 91·6 %, Indian: 79·6 %). During the postpartum period, participants tended to increase their consumption of fish and milk-based drinks and decrease their consumption of noodles, seafood, and chocolates and sweets (all P < 0·001). Ethnic differences in food consumption were pronounced during the postpartum period. For example, most Chinese participants (87·2 %) increased their ginger consumption during the postpartum period as compared with smaller percentages of Malays (31·8 %) and Indians (40·8 %; P for ethnic difference <0·001). Similar ethnic differences were observed for cooking wine/alcohol, herbs and spices, and herbal tea consumption. CONCLUSIONS: Marked changes in food consumption that reflect both modern dietary recommendations and the persistence of traditional beliefs were observed in Singaporean women during pregnancy and the postpartum period. Traditional beliefs should be considered in interventions to improve dietary intakes during these periods.

Scoping review: Exploring the relationship between chrononutrition and glycemic responses in the adult population.

Chrononutrition, an emerging body of evidence on the relationship between biological rhythms and metabolism, has been established to be associated with glycemic responses. However, the available evidence is inconsistent, due to protocol variations. Therefore, this review aims to summarize the findings on chrononutrition characteristics and their association with glycemic responses among adults. Systematic searches were conducted across six databases (PubMed, EBSCO Host, ProQuest Central, MEDLINE & Ovid, Scopus and Web of Science) to identify all relevant studies published from January 2012. Two reviewers independently screened the abstracts and full-text articles based on the inclusion and exclusion criteria. Details about population characteristics, study methods and key findings were extracted following the PRISMA-ScR guideline. The quality of selected studies was evaluated using the mixed methods appraisal tool. The searchers identified 49 studies eligible for analysis. The results showed that meal timing, particularly night-time eating and snacking were associated with glycemic responses. Regarding meal regularity, skipping breakfast may affect glycemic responses, but no clear conclusion was drawn about its effect on insulin. The association between meal frequency and glycemic responses was inconclusive. Night fasting duration and restricted eating window are potentially associated with glycemic responses. The current review extensively investigates the association between chrononutrition factors and glycemic responses in adults. However, more prospective cohort and interventional studies are needed to better understand this causal-effect relationship.

Associations of cord plasma per- and polyfluoroakyl substances (PFAS) with neonatal and child body composition and adiposity: The GUSTO study.

BACKGROUND: The influence of prenatal exposure to per- and poly- fluoroalkyl substances (PFAS) on birth size and offspring adiposity is unclear, especially for the newer, shorter-chained replacement PFAS. METHODS: In the GUSTO multi-ethnic Singaporean mother-offspring cohort, 12 PFAS were measured in 783 cord plasma samples using ultra-performance-liquid chromatography-tandem-mass-spectrometer (UPLC-MS/MS). Outcomes included offspring anthropometry, other indicators of body composition/metabolic health, and MRI-derived abdominal adiposity (subset) at birth and 6 years of age. PFAS were modeled individually, in categories of long-chain and short-chain PFAS, and as scores of three principal components (PC) derived using PC analysis (PC1, PC2, and PC3 reflect predominant exposure patterns to "very-long-PFAS", "long-PFAS", and "short-PFAS", respectively). Associations with outcomes were assessed using multivariable linear regressions, adjusted for important covariates such as maternal sociodemographic and lifestyle factors. RESULTS: Overall, cord PFAS levels showed either no or positive associations (mostly for long-chain PFAS) with birth weight, length and head circumference. In general, PFAS were associated with higher neonatal abdominal adiposity, driven by shorter-chain PFAS. Perfluoroheptanoic acid (PFHpA) was associated with higher volumes of superficial subcutaneous adipose tissue (sSAT) (3.75 [1.13, 6.37] mL per SD increase in PFAS) and internal adipose tissue (IAT) (1.39 [0.41, 2.38] mL). Higher levels of perfluorobutanesulfonic acid (PFBS), short-chain PFAS, and PC3 were associated with higher IAT volume (ß range 1.22-1.41 mL/SD, all P < 0.02), especially in girls. Higher PC3 score was additionally associated with higher sSAT (3.12 [0.45, 5.80] mL) volume. At age 6 years, most observed associations did not persist. No consistent associations were observed between PFAS and whole-body adiposity measures. CONCLUSIONS: Fetal exposure to emerging short-chain PFAS was associated with higher abdominal adiposity at birth but not at age 6 years. Further research is needed to replicate the findings and to determine if these effects may reappear beyond early childhood. Population exposure to newer PFAS and consequent health impact must be monitored.