Maternal Glucose Concentrations in Early Pregnancy and Cardiometabolic Risk Factors in Childhood.
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ABSTRACT:
SUBMITTER: Wahab RJ
PROVIDER: S-EPMC7216879 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
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Maternal Glucose Concentrations in Early Pregnancy and Cardiometabolic Risk Factors in Childhood.
Wahab Rama J RJ Voerman Ellis E Jansen Pauline W PW Oei Edwin H G EHG Steegers Eric A P EAP Jaddoe Vincent W V VWV Gaillard Romy R
Obesity (Silver Spring, Md.) 20200501 5
<h4>Objective</h4>This study aimed to examine the associations of maternal early-pregnancy glucose and insulin concentrations with offspring cardiometabolic risk factors and fat distribution.<h4>Methods</h4>In a population-based prospective cohort study among 3,737 mothers and their children, random maternal glucose and insulin concentrations were measured at a median gestational age of 13.2 (95% range 10.5-17.1) weeks. Childhood fat, blood pressure, and blood concentrations of lipids, glucose, ...[more]
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Project description:The objective of this study was to determine the associations between hypertensive disorders of pregnancy and early childhood cardiometabolic risk factors in the offspring. Therefore, 7794 women from the Generation Rotterdam Study were included, an ongoing population-based prospective birth cohort. Women with a hypertensive disorder of pregnancy were classified as such when they were affected by pregnancy induced hypertension, pre-eclampsia or the haemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome during pregnancy. Early childhood cardiometabolic risk factors were defined as the body mass index at the age of 2, 6, 12, 36 months and 6 years. Additionally, it included systolic blood pressure, diastolic blood pressure, total fat mass, cholesterol, triglycerides, insulin and clustering of cardiometabolic risk factors at 6 years of age. Sex-specific differences in the associations between hypertensive disorders and early childhood cardiometabolic risk factors were investigated. Maternal hypertensive disorders of pregnancy were inversely associated with childhood body mass index at 12 months (confounder model: -0.15 SD, 95% CI -0.27; -0.03) and childhood triglyceride at 6 years of age (confounder model: -0.28 SD, 95% CI -0.45; -0.10). For the association with triglycerides, this was only present in girls. Maternal hypertensive disorders of pregnancy were not associated with childhood body mass index at 2, 6 and 36 months. No associations were observed between maternal hypertensive disorders of pregnancy and systolic blood pressure, diastolic blood pressure, body mass index, fat mass index and cholesterol levels at 6 years of age. Our findings do not support an independent and consistent association between maternal hypertensive disorders of pregnancy and early childhood cardiometabolic risk factors in their offspring. However, this does not rule out possible longer term effects of maternal hypertensive disorders of pregnancy on offspring cardiometabolic health.
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Project description:BACKGROUND:Prepregnancy cardiometabolic risk factors are associated with increased risks of adverse pregnancy outcomes. Neighbourhood features may reflect prepregnancy exposures that contribute to poor cardiometabolic health before pregnancy and may contribute to racial disparities in pregnancy outcomes. METHODS:Early pregnancy measurements from 1504 women enrolled in the Prenatal Exposures and Preeclampsia Prevention study were linked to a 2000 Census-based measure of neighbourhood socio-economic status and commercial data (food, alcohol, and retail density) during 1997-2001. Multilevel random-intercept linear regression was used to separately estimate the association between levels of neighbourhood assets (low, mid-low, mid-high, high) and C-reactive protein (CRP), systolic blood pressure (SBP), and body mass index (BMI) in cross-sectional analyses. Low neighbourhood assets have high-poverty/low-retail, whereas high neighbourhood assets have low-poverty/high-retail. Models were adjusted for individual-level factors (age and race), and we assessed effect modification by race. RESULTS:Low compared with high neighbourhood assets were associated with higher BMI (? 1.95 kg/m2 , 95% CI 0.89, 3.00), after adjusting for individual-level covariates. After adjusting for BMI and other covariates, low compared with high assets were associated with higher CRP concentrations (? 0.20 ng/mL, 95% CI 0.01, 0.39). Neighbourhood assets were not associated with SBP. Race did not modify the association between neighbourhood assets and cardiometabolic risk factors. CONCLUSIONS:Early pregnancy adiposity is related to neighbourhood features independent of individual factors. Further, inflammation beyond accounting for adiposity is related to neighbourhood features. Strategies that address neighbourhood assets during preconception and interconception may be promising approaches to improve prepregnancy health.
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Project description:BackgroundThe prevalence of childhood elevated blood pressure (BP) has increased in the United States, particularly among African Americans. The influence of maternal plasma folate levels, alone or in combination with maternal cardiometabolic risk factors (hypertensive disorders, diabetes, and prepregnancy obesity), on child systolic BP (SBP) has not been examined in a prospective birth cohort. We hypothesize that adequate maternal folate levels can reduce the risk of elevated SBP in children born to mothers with cardiometabolic risk factors.MethodsThis study included 1,290 mother-child dyads (875 African Americans (67.8%)) recruited at birth and followed prospectively up to age 9 years from 2003 to 2014 at the Boston Medical Center. Child SBP percentile was calculated according to US reference data and elevated SBP was defined as SBP ≥75th percentile.ResultsMaternal folate levels, overall, were not associated with child SBP. However, we found a significant multiplicative interaction between maternal cardiometabolic risk factors and maternal folate levels (Pinteraction = 0.015) on childhood elevated SBP. Among children born to mothers with any cardiometabolic risk factors, those whose mothers had folate levels above (vs. below) the median had 40% lower odds of elevated childhood SBP (odds ratio = 0.60, 95% confidence interval: 0.40-0.90). The associations did not differ appreciably in analyses restricted to African Americans, and they were not explained by gestational age, size at birth, prenatal folate intake, or breastfeeding.ConclusionsFindings from our urban minority birth cohort suggest that higher levels of maternal folate may help counteract the adverse associations of maternal cardiometabolic risk factors on child SBP.
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Project description:BackgroundWe investigated the individual and additive effects of three modifiable maternal metabolic factors, including pre-pregnancy overweight/obesity, gestational weight gain (GWG), and gestational diabetes mellitus (GDM), on early childhood growth trajectories and obesity risk.MethodsA total of 1425 mother-offspring dyads (953 black and 472 white) from a longitudinal birth cohort were included in this study. Latent class growth modeling was performed to identify the trajectories of body mass index (BMI) from birth to 4 years in children. Poisson regression models were used to examine the associations between the maternal metabolic risk factors and child BMI trajectories and obesity risk at 4 years.ResultsWe identified three discrete BMI trajectory groups, characterized as rising-high-BMI (12.6%), moderate-BMI (61.0%), or low-BMI (26.4%) growth. Both maternal pre-pregnancy obesity (adjusted relative risk [adjRR] = 1.96; 95% confidence interval [CI]: 1.36-2.83) and excessive GWG (adjRR = 1.71, 95% CI: 1.13-2.58) were significantly associated with the rising-high-BMI trajectory, as manifested by rapid weight gain during infancy and a stable but high BMI until 4 years. All three maternal metabolic indices were significantly associated with childhood obesity at age 4 years (adjRR for pre-pregnancy obesity = 2.24, 95% CI: 1.62-3.10; adjRR for excessive GWG = 1.46, 95% CI: 1.01-2.09; and adjRR for GDM = 2.14, 95% = 1.47-3.12). In addition, risk of rising-high BMI trajectory or obesity at age 4 years was stronger among mothers with more than one metabolic risk factor. We did not observe any difference in these associations by race.ConclusionMaternal pre-pregnancy obesity, excessive GWG, and GDM individually and jointly predict rapid growth and obesity at age 4 years in offspring, regardless of race. Interventions targeting maternal obesity and metabolism may prevent or slow the rate of development of childhood obesity.
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Project description:Early life stunting may have long-term effects on body composition, resulting in obesity-related comorbidities. We tested the hypothesis that individuals stunted in early childhood may be at higher cardiometabolic risk later in adulthood. 1753 men and 1781 women participating in the 1982 Pelotas (Brazil) birth cohort study had measurements of anthropometry, body composition, lipids, glucose, blood pressure, and other cardiometabolic traits at age 30 years. Early stunting was defined as height-for-age Z-score at age 2 years below -2 against the World Health Organization growth standards. Linear regression models were performed controlling for sex, maternal race/ethnicity, family income at birth, and birthweight. Analyses were stratified by sex when p-interaction<0.05. Stunted individuals were shorter (β = -0.71 s.d.; 95% CI: -0.78 to -0.64), had lower BMI (β = -0.14 s.d.; 95%CI: -0.25 to -0.03), fat mass (β = -0.28 s.d.; 95%CI: -0.38 to -0.17), SAFT (β = -0.16 s.d.; 95%CI: -0.26 to -0.06), systolic (β = -0.12 s.d.; 95%CI: -0.21 to -0.02) and diastolic blood pressure (β = -0.11 s.d.; 95%CI: -0.22 to -0.01), and higher VFT/SAFT ratio (β = 0.15 s.d.; 95%CI: 0.06 to 0.24), in comparison with non-stunted individuals. In addition, early stunting was associated with lower fat free mass in both men (β = -0.39 s.d.; 95%CI: -0.47 to -0.31) and women (β = -0.37 s.d.; 95%CI: -0.46 to -0.29) after adjustment for potential confounders. Our results suggest that early stunting has implications on attained height, body composition and blood pressure. The apparent tendency of stunted individuals to accumulate less fat-free mass and subcutaneous fat might predispose them towards increased metabolic risks in later life.
| S-EPMC5894958 | biostudies-literature
Project description:BACKGROUND:Intrauterine exposure to a disturbed maternal glucose metabolism is associated with adverse offspring outcomes. DNA methylation is a potential mechanism underlying these associations. We examined whether maternal early-pregnancy glucose and insulin concentrations are associated with newborn DNA methylation. In a population-based prospective cohort study among 935 pregnant women, maternal plasma concentrations of non-fasting glucose and insulin were measured at a median of 13.1?weeks of gestation (95% range 9.4-17.4). DNA methylation was measured using the Infinium HumanMethylation450 BeadChip (Ilumina). We analyzed associations of maternal early-pregnancy glucose and insulin concentrations with single-CpG DNA methylation using robust linear regression models. Differentially methylated regions were analyzed using the dmrff package in R. We stratified the analyses on normal weight versus overweight or obese women. We also performed a look-up of CpGs and differently methylated regions from previous studies to be associated with maternal gestational diabetes, hyperglycemia or hyperinsulinemia, or with type 2 diabetes in adults. RESULTS:Maternal early-pregnancy glucose and insulin concentrations were not associated with DNA methylation at single CpGs nor with differentially methylated regions in the total group. In analyses stratified on maternal BMI, maternal early-pregnancy glucose concentrations were associated with DNA methylation at one CpG (cg03617420, XKR6) among normal weight women and at another (cg12081946, IL17D) among overweight or obese women. No stratum-specific associations were found for maternal early-pregnancy insulin concentrations. The two CpGs were not associated with birth weight or childhood glycemic measures (p values > 0.1). Maternal early-pregnancy insulin concentrations were associated with one CpG known to be related to adult type 2 diabetes. Enrichment among nominally significant findings in our maternal early-pregnancy glucose concentrations was found for CpGs identified in a previous study on adult type 2 diabetes. CONCLUSIONS:Maternal early-pregnancy glucose concentrations, but not insulin concentrations, were associated with DNA methylation at one CpG each in the subgroups of normal weight and of overweight or obese women. No associations were present in the full group. The role of these CpGs in mechanisms underlying offspring health outcomes needs further study. Future studies should replicate our results in larger samples with early-pregnancy information on maternal fasting glucose metabolism.
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Project description:It is well established that genetics, environment, and interplay between them play a crucial role in adult disease. We aimed to evaluate the role of genetics, early life nutrition, and the interaction between them, on optimal adult health. As part of a large international consortium (n ~ 154,000), we identified 60 SNPs associated with both birthweight and adult disease. Utilising the Raine Study, we developed a birthweight polygenic score (BW-PGS) based on the 60 SNPs and examined relationships between BW-PGS and adulthood cardiovascular risk factors, specifically evaluating interactions with early life nutrition. Healthy nutrition was beneficial for all individuals; longer duration of any breastfeeding was particularly associated with lower BMI and lower Systolic Blood Pressure in those with higher BW-PGS. Optimal breastfeeding offers the greatest benefit to reduce adult obesity and hypertension in those genetically predisposed to high birthweight. This provides an example of how precision medicine in early life can improve adult health.
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Project description:BackgroundMaternal abnormal glucose tolerance during pregnancy may adversely affect offspring cognition and behaviour, but few prospective studies investigated this association at multiple points throughout childhood.ObjectivesWe hypothesised that maternal abnormal glucose tolerance is associated with child cognitive and behavioural outcomes in early and mid-childhood.MethodsWe examined the associations of maternal abnormal glucose tolerance at 26-28 weeks of pregnancy with offspring cognitive and behavioural scores in 1421 children in the Project Viva pre-birth cohort. In early (mean 3.3 years) and mid-childhood (mean 7.9 years), we measured child cognition using validated instruments, the Kaufman Brief Intelligence Test, Wide Range Assessment of Memory and Learning, and the Wide Range Assessment of Visual Motor Abilities (WRAVMA); we assessed parent- and teacher-rated behavioural outcomes with the Strengths and Difficulties Questionnaire and the Behavioural Rating Inventory of Executive Function. We used linear regression models adjusted for potential confounders (maternal race/ethnicity, pre-pregnancy BMI, intelligence, age, parity, smoking status, education, and household income at enrolment, in addition to child's sex and age at assessment).ResultsOf 1421 mothers, 69 (4.9%) had gestational diabetes mellitus, 43 (3.0%) impaired glucose tolerance, 122 (8.6%) isolated hyperglycaemia, and 1187 (83.5%) normal glucose tolerance. Offspring born to women with gestational diabetes mellitus had lower total WRAVMA scores (-3.09 points; 95% CI -6.12, -0.05) in early childhood compared with offspring of women with normal glucose tolerance. None of the abnormal glucose tolerance categories during pregnancy were associated with any of the cognitive outcomes (verbal, non-verbal, and visual motor scores) or behavioural measures in mid-childhood.ConclusionsChildren born to mothers who had gestational diabetes mellitus had slightly lower scores on one cognitive test in early childhood. We found no evidence to support that maternal abnormal glucose tolerance was associated with cognitive or behavioural development in mid-childhood.
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