Dataset Information

Maternal BMI Associations with Maternal and Cord Blood Vitamin D Levels in a North American Subset of Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Participants.

ABSTRACT: OBJECTIVE:Obesity in pregnancy may be associated with reduced placental transfer of 25-hydroxyvitamin D (25-OHD). The objective of this study was to examine associations between maternal BMI and maternal and cord blood levels of 25-OHD in full term neonates born to a single racial cohort residing at similar latitude. Secondary objectives were to examine associations between maternal glucose tolerance with maternal levels of 25-OHD and the relationship between cord blood 25-OHD levels and neonatal size. METHODS:This study was conducted among participants of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study meeting the following criteria: residing at latitudes 41-43°, maternal white race, and gestational age 39-41 weeks. Healthy pregnant women underwent measures of height, weight, and a 75-g fasting oral glucose tolerance test (OGTT) at approximately 28 weeks gestation. Maternal and cord blood sera were analyzed for total 25-OHD by HPLC tandem mass spectrometry. Statistical analyses included ANOVA and linear regression models. RESULTS:Maternal and cord blood (N = 360) mean levels (sd) of 25-OHD were 37.2 (11.2) and 23.4 (9.2) ng/ml, respectively, and these levels were significantly different among the 3 field centers (ANOVA p< 0.001). Maternal serum 25-OHD was lower by 0.40 ng/ml for BMI higher by 1 kg/m2 (p<0.001) in an adjusted model. Maternal fasting plasma glucose, insulin sensitivity, and presence of GDM were not associated with maternal serum 25-OHD level when adjusted for maternal BMI. Cord blood 25-OHD was lower by 0.26 ng/ml for maternal BMI higher by 1 kg/m2 (p<0.004). With adjustment for maternal age, field center, birth season and maternal serum 25-OHD, the association of cord blood 25-OHD with maternal BMI was attenuated. Neither birth weight nor neonatal adiposity was significantly associated with cord blood 25-OHD levels. CONCLUSION:These results suggest that maternal levels of 25-OHD are associated with maternal BMI. The results also suggest that interpretation of neonatal 25-OHD levels may need to incorporate specific maternal factors in addition to season of birth and latitude.

SUBMITTER: Josefson JL

PROVIDER: S-EPMC4778858 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Maternal BMI Associations with Maternal and Cord Blood Vitamin D Levels in a North American Subset of Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Participants.

Josefson Jami L JL Reisetter Anna A Scholtens Denise M DM Price Heather E HE Metzger Boyd E BE Langman Craig B CB

PloS one 20160304 3

<h4>Objective</h4>Obesity in pregnancy may be associated with reduced placental transfer of 25-hydroxyvitamin D (25-OHD). The objective of this study was to examine associations between maternal BMI and maternal and cord blood levels of 25-OHD in full term neonates born to a single racial cohort residing at similar latitude. Secondary objectives were to examine associations between maternal glucose tolerance with maternal levels of 25-OHD and the relationship between cord blood 25-OHD levels and ...[more]

PMID: 26942930

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Project description:Low and high birth weight are not only major causes of neonatal morbidity and mortality, but epidemiological data have established an association between birth weight and later life risk of adult metabolic diseases. Fetal growth is determined by complex interactions between fetal genes and the maternal uterine environment. Subtle or overt variation in maternal glucose tolerance, which is, in part, genetically determined, is related to fetal size at birth. Moreover, new emerging data suggest that genetic variation in the fetus can impact maternal metabolism (e.g., blood pressure and glucose tolerance). Given the above, we are addressing the hypothesis that, during pregnancy, gene-environment interactions in the context of the maternal-fetal unit impact fetal size at birth and maternal metabolism. Genes that control fetal growth or maternal metabolism during pregnancy are largely unknown, so the first step to address our hypothesis will be to identify genetic variation that impacts fetal growth and maternal metabolism and to determine the interaction of that variation with the intrauterine and fetal environment. To accomplish this, we are performing genome wide association (GWA) mapping on a subset of ~37,000 DNA samples that were collected from mothers and their offspring as part of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. HAPO is a multicenter, international study in which high quality phenotypic data related to fetal growth and maternal glucose metabolism has been collected from 25,000 pregnant women of varied racial and socio-demographic backgrounds using standardized protocols that were uniform across centers. For these studies, we are genotyping 1,500 infants and their mothers of European descent, 1,250 Afro-Caribbean infants and mothers, 800 Hispanic (Mexican-American) infants and mothers, and 1200 Thai infants and mothers. Genotyping is being performed using the Illumina Human610 Quad (European ancestry participants), Human1M Duo (Afro-Caribbean and Hispanic participants), and Omni1-Quad_v1-0_B (Thai participants). The specific aims for the project are as follows: (1) To apply analytic approaches for conducting GWA mapping studies on quantitative phenotypes related to offspring size at birth (birth weight, ponderal index, head circumference and adiposity) allowing for other known influences such as gestational age, parity, and maternal weight gain. (2) To apply the above approaches to identify genetic variation that impacts maternal glucose tolerance at ~28 weeks of gestation (fasting glucose, glucose during an oral glucose tolerance test, and insulin sensitivity expressed as quantitative traits) allowing for other known influences such as maternal weight gain, parity and age. (3) To examine the interaction between maternal genes, the intrauterine environment, and fetal genes to identify interactions that modulate genetic regulation of size at birth and fetal genetic variation that impacts on maternal glucose tolerance. GWA mapping will provide initial evidence for association of specific SNPs with the quantitative traits outlined above. As low and high birth weight are not only major causes of neonatal morbidity and mortality but have also been associated with increased risk of metabolic diseases in adults, identification of genes that regulate fetal growth and maternal metabolism will provide novel information about the pathways that regulate these processes as well as important insight into susceptibility genes for chronic diseases like type 2 diabetes. The Version 1 (v1) dbGaP release will include data only from the Hispanic study participants. The Version 2 (v2) dbGaP release will include data from the Hispanic and European ancestry study participants. The Version 3 (v3) dbGaP release will include data from the Afro-Caribbean, Hispanic and European ancestry participants. The Version 4 (v4) dbGaP release will include data from all participants (i.e., Afro-Caribbean, Hispanic, European ancestry, and Thai participants). This study is part of the Gene Environment Association Studies initiative (GENEVA, <a href="http://www.genevastudy.org" target="_blank">http://www.genevastudy.org</a>) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to maternal metabolism and birthweight through large-scale genome-wide association studies of infants and their mothers at multiple international sites. Genotyping was performed at the Broad Institute of MIT and Harvard, and at CIDR of Johns Hopkins University, GENEVA genotyping centers. Data cleaning and harmonization was performed at the GEI-funded GENEVA Coordinating Center at the University of Washington.

Project description:Study questionDoes IVF independently increase the risk of gestational diabetes mellitus (GDM) and is this increase in risk modified by maternal body mass index?Summary answerIVF appears to be an independent risk factor for GDM and elevated blood glucose levels in overweight women (BMI > 25 kg/m2).What is known alreadyIVF has been associated with increased risk of GDM, but most previous studies did not adequately assess confounding or effect modification by other risk factors.Study design, size, durationCross-sectional study using data from 1089 women with singleton pregnancies who participated in a Singaporean birth cohort study (GUSTO) and received a 75 g oral glucose tolerance test (OGTT) at 26-28 weeks gestation.Participants/materials, setting, methodsA total of 1089 women (n = 1013 conceived spontaneously, n = 76 conceived through IVF) with singleton pregnancies received a 75 g OGTT at 26-28 weeks gestation. Fasting and 2 h postprandial blood glucose levels were assayed. World Health Organization criteria (1999) standard criteria were used to classify GDM: ≥7.0 mmol/L for fasting and/or ≥7.8 mmol/L for 2-h postprandial plasma glucose levels, which was the clinical guideline in use during the study.Main results and the role of chanceIVF pregnancies had nearly double the odds of GDM (OR = 1.83, 95% CI: 1.03-3.26) and elevated fasting (mean difference = 0.12 mmol/L, 95% CI: 0.00-0.24) and OGTT 2-h blood glucose levels (mean difference = 0.64 mmol/L, 95% CI: 0.27-1.01), after adjusting for commonly recognized risk factors for GDM. After stratification by first-trimester BMI, these increased risks of GDM (OR = 3.54, 95% CI: 1.44-8.72) and elevated fasting (mean difference = 0.39 mmol/L, 95% CI: 0.13-0.65) and 2-h blood (mean difference = 1.24 mmol/L, 95% CI: 0.56-1.91) glucose levels were significant only in the IVF group who is also overweight or obese (BMI > 25 kg/m2).Limitations reasons for cautionOne limitation of our study is the absence of a 1 h post-OGTT plasma glucose sample, as we were using the 1999 WHO diagnostic criteria (the clinical guideline in Singapore) at the time of our study, instead of the revised 2013 WHO diagnostic criteria. Our cohort may not be representative of the general Singapore obstetric population, although participants were recruited from the two largest maternity hospitals in the country and include both private and subsidized patients.Wider implications of the findingsIVF appears to be an independent risk factor for GDM and elevated blood glucose levels in overweight women. Our findings reinforce the need to advise overweight or obese women contemplating IVF to lose weight before the procedure to reduce their risk of GDM and hyperglycemia-related adverse outcomes arising therefrom. In settings where universal GDM screening is not routine, overweight or obese women who conceive by IVF should be screened.Study funding/competing interest(s)This research was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Program and administered by the Singapore Ministry of Health's National Medical Research Council (NMRC), Singapore (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding was provided by the Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR). K.M.G. and Y.S.C. have received lecture fees from Nestle Nutrition Institute and Danone, respectively. K.M.G., Y.S.C. and S.Y.C. are part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. The other authors have nothing to disclose. The other authors have nothing to disclose.Trial registration numberN/A.

Project description:As mothers age, the risk of adverse pregnancy outcomes may increase, but the results so far are controversial and several issues remain unknown, such as the impact of maternal weight on the effects associated with older age. In a prospective cohort of 912 Polish women with singleton pregnancies (recruited in 2015-2016), we assessed the pregnancy outcomes depending on the mother's age (18-24, 25-29, 30-34, 35-39, and ≥40 years). Women aged ≥35 years (vs. <35 years) were assessed in terms of body mass index (BMI). Multidimensional logistic regression was used to calculate the odds ratios (with 95% confidence intervals) of the pregnancy results. The risk profiles (using the Lowess method) were applied to determine the threshold risk. We found that both the youngest and the oldest group members displayed higher adjusted odds ratios of preeclampsia (PE), intrauterine growth restriction (IUGR), and preterm birth <37th week (U-shaped risk). In the remaining cases, the age ≥40 years, compared to the youngest age 18-24 years, was associated with a higher adjusted risk of gestational hypertension (GH) (AOR = 5.76, p = 0.034), gestational diabetes mellitus GDM-1 (AOR = 7.06, p = 0.016), cesarean section (AOR = 6.97, p <0.001), and low birth weight LBW (AOR = 15.73, p = 0.033) as well as macrosomia >4000 g (AOR = 8.95, p = 0.048). We found that older age ≥35 years (vs. <35 years) was associated with higher adjusted odds ratios of all the pregnancy outcomes investigated. In obese women, these adverse older age related results were found to be more intense in GH study, as well as (though weaker) in birth <37th week study, small-for-gestational age birth weight (SGA), LBW, large-for-gestational age birth weight (LGA), and macrosomia. In overweight women, these adverse older age related results were found to be more intense in preterm birth study, as well as (though weaker) in SGA and LBW. In underweight women, adverse pregnancy outcomes related to older age were more intense in a study of cesarean section. At the same time, underweight was associated with reversal of some negative effects of older age (we found lower odds ratios of GDM-1 diabetes). The maternal threshold age above which the risk of GH, PE, GDM, caesarean section, and preterm birth increased was 33-34 years (lower than the threshold of 35 years assumed in the literature), and the threshold risk of IUGR, LBW, SGA, LGA, and macrosomia was 36-37 years. Main conclusions: Older maternal age was associated with a higher chance of all kinds of obstetric complications. Older women should particularly avoid obesity and overweight.

Dataset Information

Maternal BMI Associations with Maternal and Cord Blood Vitamin D Levels in a North American Subset of Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Participants.

Publications

Maternal BMI Associations with Maternal and Cord Blood Vitamin D Levels in a North American Subset of Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Participants.

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