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Roles of Birth Mode and Infant Gut Microbiota in Intergenerational Transmission of Overweight and Obesity From Mother to Offspring.

ABSTRACT: Importance:Maternal overweight, which often results in cesarean delivery, is a strong risk factor for child overweight. Little is known about the joint contribution of birth mode and microbiota in the infant gut to the association between maternal prepregnancy overweight and child overweight. Objective:To investigate the association of birth mode with microbiota in the infant gut, and whether this mediates the association between maternal and child overweight. Design, Setting, and Participants:An observational study was conducted of 935 full-term infants born between January 1, 2009, and December 31, 2012, in the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Maternal prepregnancy body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared using height and weight data taken from medical records or maternal report. Infant gut microbiota were profiled with 16S ribosomal RNA sequencing in fecal samples collected at a mean (SD) age of 3.7 (1.0) months. At ages 1 and 3 years, BMI z scores adjusted for age and sex were generated according to World Health Organization criteria. Statistical analysis was conducted from January 29 to June 15, 2017. Exposures:Mothers of normal weight (BMI, 18.5-24.9) and overweight or obese (BMI, ≥25.0) mothers. Main Outcome and Measures:Risk of overweight and obesity (>97th percentile BMI z scores) among children at ages 1 and 3 years. Results:Of the 935 mother-infant pairs in the study (mean [SD] age, 32.5 [4.5] years) 382 (40.9%) were overweight, 69 of 926 infants (7.5%) were overweight at age 1 year, and 90 of 866 infants (10.4%) were overweight at age 3 years. Compared with being born vaginally to a mother of normal weight, infants born vaginally to overweight or obese mothers were 3 times more likely to become overweight at age 1 year (adjusted odds ratio [OR], 3.33; 95% CI, 1.49-7.41), while cesarean-delivered infants of overweight mothers had a 5-fold risk of overweight at age 1 year (adjusted OR, 5.02; 95% CI, 2.04-12.38). Similar risks were also observed at age 3 years. Multiple mediator path modeling revealed that birth mode and infant gut microbiota (Firmicutes species richness, especially of the Lachnospiraceae family) sequentially mediated the association between maternal prepregnancy overweight and childhood overweight at ages 1 and 3 years. Bacterial genera belonging to the Lachnospiraceae family were more abundant in infants of overweight mothers; however, the participating genera of Lachnospiraceae differed between infants delivered vaginally and those delivered via cesarean birth. Conclusions and Relevance:This study found evidence of a novel sequential mediator pathway involving birth mode and Firmicutes species richness (especially higher abundance of Lachnospiraceae) for the intergenerational transmission of overweight.

SUBMITTER: Tun HM

PROVIDER: S-EPMC5875322 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundOverweight/obesity in women of childbearing age is a serious public-health problem. In China, the incidence of maternal overweight/obesity has been increasing. However, there is not a meta-analysis to determine if pre-pregnancy body mass index (BMI) is related to infant birth weight (BW) and offspring overweight/obesity.MethodsThree electronic bibliographic databases (MEDLINE, EMBASE and CINAHL) were searched systematically from January 1970 to November 2012. The dichotomous data on pre-pregnancy overweight/obesity and BW or offspring overweight/obesity were extracted. Summary statistics (odds ratios, ORs) were used by Review Manager, version 5.1.7.ResultsAfter screening 665 citations from three electronic databases, we included 45 studies (most of high or medium quality). Compared with normal-weight mothers, pre-pregnancy underweight increased the risk of small for gestational age (SGA) (odds ratios [OR], 1.81; 95% confidence interval [CI], 1.76-1.87); low BW (OR, 1.47; 95% CI, 1.27-1.71). Pre-pregnancy overweight/obesity increased the risk of being large for gestational age (LGA) (OR, 1.53; 95% CI, 1.44-1.63; and OR, 2.08; 95% CI; 1.95-2.23), high BW (OR, 1.53; 95% CI, 1.44-1.63; and OR, 2.00; 95% CI; 1.84-2.18), macrosomia (OR, 1.67; 95% CI, 1.42-1.97; and OR, 3.23; 95% CI, 2.39-4.37), and subsequent offspring overweight/obesity (OR, 1.95; 95% CI, 1.77-2.13; and OR, 3.06; 95% CI, 2.68-3.49), respectively. Sensitivity analyses revealed that sample size, study method, quality grade of study, source of pre-pregnancy BMI or BW had a strong impact on the association between pre-pregnancy obesity and LGA. No significant evidence of publication bias was observed.ConclusionsPre-pregnancy underweight increases the risk of SGA and LBW; pre-pregnancy overweight/obesity increases the risk of LGA, HBW, macrosomia, and subsequent offspring overweight/obesity. A potential effect modification by maternal age, ethnicity, gestational weight gain, as well as the role of gestational diseases should be addressed in future studies.

Project description:This study assesses socioeconomic inequality in the intergenerational transmission of overweight and obesity from mothers to offsprings in South Africa, including the factors contributing to inequality. Data were drawn from the 2017 National Income Dynamic Study, which collected anthropometric and socioeconomic information. Non-pregnant mothers aged 15-49 years and their offsprings 0-14 years were included in the analysis. The dependent variables used in the study were the intergenerational transmission of overweight and obesity. Socioeconomic inequality was assessed using the concentration index. A positive index means that intergenerational overweight and obesity is more likely among the wealthier populations, while a negative index signifies the opposite. The concentration index was decomposed to understand the factors that explain inequalities in the transmission of overweight and obesity from mothers to offsprings. Concentration indices for the intergenerational transmission of overweight and obesity were positive for boys (0.17) and girls (0.23). Thus the intergenerational transmission of overweight and obesity occurs more among wealthier mothers. Although factors explaining socioeconomic inequality in the intergenerational transmission of overweight and obesity differed by offspring sex, mother's marital status (+38%) and socioeconomic status (around +8%) were central determinants of socioeconomic inequalities in intergenerational overweight, while mother's smoking (around +25%), education (about +13%) and employment status (around +12%) contributed to intergenerational obesity inequality. Policies to reduce overweight and obesity burdens and the intergenerational transmission of overweight and obesity in South Africa should target women who bear a significant burden of overweight and obesity and could transmit them to their offsprings. The policies should also recognise the key factors explaining these socioeconomic inequalities. This approach will reduce the future burden of diseases associated with overweight and obesity in South Africa and improve the country's overall health outcomes.

Project description:Background/objectivesThe intergenerational association of obesity may be driven by mother-to-newborn transmission of microbiota at birth. Yet cesarean delivery circumvents newborn acquisition of vaginal microbiota, and has been associated with greater childhood adiposity. Here we examined the independent and joint associations of maternal pre-pregnancy body mass index (BMI; kg m-2) and delivery mode with childhood overweight or obesity.Subjects/methodsWe prospectively followed 1441 racially and ethnically diverse mother-child dyads in the Boston Birth Cohort until age 5 years (range: 2.0-8.0 years). We used logistic regression to examine the independent and joint associations of delivery mode (cesarean and vaginal delivery) and pre-pregnancy BMI with childhood overweight or obesity (age-sex-specific BMI ⩾85th percentile).ResultsOf 1441 mothers, 961 delivered vaginally and 480 by cesarean. Compared with vaginally delivered children, cesarean delivered children had 1.4 (95% confidence interval (CI) 1.1-1.8) times greater odds of becoming overweight or obese in childhood, after adjustment for maternal age at delivery, race/ethnicity, education, air pollution exposure, pre-pregnancy BMI, pregnancy weight gain and birth weight. Compared with children born vaginally to normal weight mothers, after multivariable adjustment, odds of childhood overweight or obesity were highest in children born by cesarean delivery to obese mothers (odds ratio (OR): 2.8; 95% CI: 1.9-4.1), followed by children born by cesarean delivery to overweight mothers (OR: 2.2; 95% CI: 1.5-3.2), then children born vaginally to obese mothers (OR: 1.8; 95% CI: 1.3-2.6) and finally children born vaginally to overweight mothers (OR: 1.7; 95% CI: 1.2-2.3).ConclusionsIn our racially and ethnically diverse cohort, cesarean delivery and pre-pregnancy overweight and obesity were associated with childhood overweight or obesity. Needed now are prospective studies that integrate measures of the maternal and infant microbiome, and other potentially explanatory covariates, to elucidate the mechanisms driving this association and to explore whether exposure to vaginal microbiota in cesarean delivered newborns may be an innovative strategy to combat the intergenerational cycle of obesity.

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Roles of Birth Mode and Infant Gut Microbiota in Intergenerational Transmission of Overweight and Obesity From Mother to Offspring.

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