Do birth mode and microbiota in the infant gut mediate the association between maternal prepregnancy overweight and childhood overweight?
In this cohort study of 935 mother-infant pairs, both vaginally and cesarean-delivered infants born to overweight and obese mothers were at greater risk of being overweight at ages 1 and 3 years compared with infants born vaginally to a mother of normal weight. Birth mode and microbiota in the infant gut (especially Lachnospiraceae) act sequentially to mediate the association between maternal prepregnancy overweight and child overweight.
Together, birth mode and Lachnospiraceae family microbiota in the infant gut sequentially mediate the intergenerational association of overweight, underscoring their potential contributions in developing child overweight and obesity.
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.
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.
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.
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.
Tun HM, Bridgman SL, Chari R, Field CJ, Guttman DS, Becker AB, Mandhane PJ, Turvey SE, Subbarao P, Sears MR, Scott JA, Kozyrskyj AL, . Roles of Birth Mode and Infant Gut Microbiota in Intergenerational Transmission of Overweight and Obesity From Mother to Offspring. JAMA Pediatr. Published online February 19, 2018. doi:10.1001/jamapediatrics.2017.5535
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