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Association of maternal diabetes mellitus in pregnancy with offspring adiposity into early adulthood: sibling study in a prospective cohort of 280,866 men from 248,293 families.

ABSTRACT: Maternal diabetes mellitus in pregnancy results in greater offspring adiposity at birth. It is unclear whether it is associated with greater adiposity into adulthood, and if so, whether this is via intrauterine mechanisms or shared familial characteristics.A record-linkage prospective cohort study of 280,866 singleton-born Swedish men from 248,293 families was used to explore the intrauterine effect of maternal diabetes mellitus on offspring body mass index (BMI) in early adulthood. Maternal diabetes mellitus during pregnancy was associated with greater mean BMI at age 18 in their sons. The difference in BMI was similar within brothers and between nonsiblings. BMI of men whose mothers had diabetes mellitus during their pregnancy was on average 0.94 kg/m² greater (95% confidence interval [CI], 0.35 to 1.52) than in their brothers born before their mother was diagnosed with diabetes, after adjustment for birth year, maternal age, parity and education, birth weight, gestational age, and age at assessment of BMI. Early-pregnancy BMI was positively associated with son's BMI between nonsiblings, but there was no association within brothers. Adjustment of the maternal diabetes-offspring BMI association for maternal BMI did not alter the association either within brothers or between nonsiblings. Results were also robust to sensitivity analyses restricting the within-sibling analyses to siblings born within 3 years of each other.Maternal diabetes mellitus has long-term consequences for greater BMI in offspring; this association is likely to be via intrauterine mechanisms, and is independent of maternal BMI in early pregnancy.

SUBMITTER: Lawlor DA

PROVIDER: S-EPMC4440894 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Association of maternal diabetes mellitus in pregnancy with offspring adiposity into early adulthood: sibling study in a prospective cohort of 280,866 men from 248,293 families.

Lawlor Debbie A DA Lichtenstein Paul P Långström Niklas N

Circulation 20110110 3

<h4>Background</h4>Maternal diabetes mellitus in pregnancy results in greater offspring adiposity at birth. It is unclear whether it is associated with greater adiposity into adulthood, and if so, whether this is via intrauterine mechanisms or shared familial characteristics.<h4>Methods and results</h4>A record-linkage prospective cohort study of 280,866 singleton-born Swedish men from 248,293 families was used to explore the intrauterine effect of maternal diabetes mellitus on offspring body ma ...[more]

PMID: 21220735

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Project description:OBJECTIVE:To study the impact of maternal smoking during pregnancy on fractures in offspring during different developmental stages of life. DESIGN:National register based birth cohort study with a sibling comparison design. SETTING:Sweden. PARTICIPANTS:1?680?307 people born in Sweden between 1983 and 2000 to women who smoked (n=377?367, 22.5%) and did not smoke (n=1?302?940) in early pregnancy. Follow-up was until 31 December 2014. MAIN OUTCOME MEASURE:Fractures by attained age up to 32 years. RESULTS:During a median follow-up of 21.1 years, 377?970 fractures were observed (the overall incidence rate for fracture standardised by calendar year of birth was 11.8 per 1000 person years). The association between maternal smoking during pregnancy and risk of fracture in offspring differed by attained age. Maternal smoking was associated with a higher rate of fractures in offspring before 1 year of age in the entire cohort (birth year standardised fracture rates in those exposed and unexposed to maternal smoking were 1.59 and 1.28 per 1000 person years, respectively). After adjustment for potential confounders the hazard ratio for maternal smoking compared with no smoking was 1.27 (95% confidence interval 1.12 to 1.45). This association followed a dose dependent pattern (compared with no smoking, hazard ratios for 1-9 cigarettes/day and ?10 cigarettes/day were 1.20 (95% confidence interval 1.03 to 1.39) and 1.41 (1.18 to 1.69), respectively) and persisted in within-sibship comparisons although with wider confidence intervals (compared with no smoking, 1.58 (1.01 to 2.46)). Maternal smoking during pregnancy was also associated with an increased fracture incidence in offspring from age 5 to 32 years in whole cohort analyses, but these associations did not follow a dose dependent gradient. In within-sibship analyses, which controls for confounding by measured and unmeasured shared familial factors, corresponding point estimates were all close to null. Maternal smoking was not associated with risk of fracture in offspring between the ages of 1 and 5 years in any of the models. CONCLUSION:Prenatal exposure to maternal smoking is associated with an increased rate of fracture during the first year of life but does not seem to have a long lasting biological influence on fractures later in childhood and up to early adulthood.

Project description:BackgroundChildhood overweight/obesity is a global public health concern. It is important to identify its early-life risk factors. Maternal poor sleep is common in late pregnancy, and previous studies indicated that poor sleep may influence the offspring's adiposity status. However, very few studies in humans investigated the effect of the different sleep parameters (sleep quantity, quality, and timing) on the offspring's adiposity indicators, and long-term studies are even more scarce. In addition, the underlying mechanism remains unclear. The present study therefore aimed to examine the association between the three maternal sleep dimensions in the late pregnancy and the offspring adiposity indicators and to explore the potential mediating effect of the cord blood DNA methylation in the above association.MethodsIncluded participants in the current study were 2211 healthy pregnant women with singleton gestation from the Shanghai Birth Cohort (SBC) and Shanghai Sleep Birth Cohort (SSBC). Maternal nighttime sleep duration, quality, and midpoint (an indicator of circadian rhythm) were assessed by the same instrument in both cohorts during late pregnancy, and the offspring's body mass index (BMI) and subcutaneous fat (SF) were measured at 2 years old. Additionally, in 231 SSBC samples, the genome-wide DNA methylation levels were measured using the Illumina Infinium Methylation EPIC BeadChip. The multivariate linear regression was used to determine the associations between the maternal sleep parameters and the offspring adiposity indicators. The epigenome-wide association study was conducted to identify the maternal sleep-related CpG sites. The mediation analysis was performed to evaluate the potential intermediate role of DNA methylation in the association between maternal sleep and offspring adiposity indicators.ResultsThe mean maternal nighttime sleep duration and the sleep midpoint for combined cohorts were 9.24 ± 1.13 h and 3.02 ± 0.82, respectively, and 24.5% of pregnant women experienced poor sleep quality in late pregnancy. After adjusting for the covariates, the maternal later sleep midpoint was associated with the increased SF in offspring (Coef. = 0.62, 95% CI 0.37-0.87, p < 0.001) at 2 years old. However, no significant associations of the nighttime sleep duration or sleep quality with the offspring adiposity indicators were found. In the SSBC sample, 45 differential methylated probes (DMPs) were associated with the maternal sleep midpoint, and then, we observed 10 and 3 DMPs that were also associated with the offspring's SF and BMI at 2 years, of which cg04351668 (MARCH9) and cg12232388 significantly mediated the relationship of sleep midpoint and SF and cg12232388 and cg12225226 mediated the sleep midpoint-BMI association, respectively.ConclusionsMaternal later sleep timing in late pregnancy was associated with higher childhood adiposity in the offspring. Cord blood DNA methylation may play a mediation role in that relationship.

Dataset Information

Association of maternal diabetes mellitus in pregnancy with offspring adiposity into early adulthood: sibling study in a prospective cohort of 280,866 men from 248,293 families.

Publications

Association of maternal diabetes mellitus in pregnancy with offspring adiposity into early adulthood: sibling study in a prospective cohort of 280,866 men from 248,293 families.

Similar Datasets

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