Birth Mode, Infant Microbiota Affect Intergenerational Obesity

Diana Mahoney

February 22, 2018

Babies born to overweight or obese mothers, either vaginally or via cesarean section, are more likely to become overweight or obese than those born vaginally to normal-weight mothers, a new study has shown.

In addition to mode of birth, the presence of microbiota in the infant gut appears to mediate the link between maternal and child overweight status, particularly in cesarean-delivered babies, Hein M. Tun, DVM, PhD, from the Department of Pediatrics, University of Alberta, Edmonton, Canada and colleagues report in their article, published online February 19 in JAMA Pediatrics.

The current study adds important information supporting the interdependency of maternal weight status and mode of delivery in forming the "microbial communities of early life," which are linked to offspring weight status, say Giulia Paolella, MD, from the Pediatric Intermediate Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, and Pietro Vajro, MD, from the Department of Medicine, Surgery and Dentistry at the University of Salerno, Italy, in an accompanying editorial.

Tun and colleagues used sequential mediation analysis (a feature used in other fields but that had not been previously applied to microbiome studies) for their large prospective cohort, which allowed them to successfully examine two original, relevant issues, the editorialists note.

First, they identified indirect or mediating effects of infant fecal abundance of Lachnospiraceae bacteria (phylum: Firmicutes) in children with overweight or obesity (OWOB) with a mean age of 3.7 months, born to mothers with OWOB after either vaginal or cesarean delivery. Second, the authors established that maternal body mass index (BMI) and cesarean delivery together affect the composition of the initial microbial communities in offspring with OWOB.

This additional insight into the mechanisms behind the mother-to-child transmission of overweight and obesity may ultimately "pave the way to novel strategies for obesity prevention that include the interruption of intergenerational transmission of OWOB from mother to offspring," they add, although they do note some limitations of the study.

Babies of Heavy Mums: Higher Risk for Cesarean Delivery and OWOB

In light of epidemiological evidence suggesting that prenatal maternal obesity predisposes newborns to develop OWOB, especially among cesarean vs vaginally delivered babies, and a growing body of research pointing to mother-to-newborn transfer of obesogenic microbes as a biological pathway for the transmission of overweight and obesity, Tun and coinvestigators in the Canadian Healthy Infant Longitudinal Development (CHILD) Study designed the current observational analysis to investigate the association of birth mode with microbiota in the infant gut, and the possibility that this association mediates the link between maternal and child overweight.

The 935 infants included in the study, all full-term, were born between January 1, 2009, and December 31, 2012. Maternal prepregnancy BMI was calculated from self-reported weight and height measures that were validated by prenatal records. Of the mothers included in the study, 553 were classified as normal weight (BMI, 18.5-24.9 kg/m2) and 382 were OWOB (BMI, ≥25.0 kg/m2).

Offspring with BMI z scores greater than the 97th percentile (generated from weight and height measured at ages 1 and 3 years) were considered overweight or obese. Infant gut microbiota were measured via analysis of fecal samples collected at a mean age of 3.7 months.

Sixty-nine (7.5%) of 926 infants became overweight/obese at 1 year, and 90 (10.4%) of 866 infants were classified as such at 3 years, the authors report, noting that childhood weight status was associated with maternal weight status.

OWOB mothers had a 1.50 increased likelihood of cesarean delivery. They were also more likely to undergo scheduled cesarean delivery or to have an emergency cesarean delivery than to deliver vaginally without intrapartum antibiotic prophylaxis (which may interfere with bacterial colonization of the infant's gut), the authors write.

Compared with being born vaginally to a mother of normal weight, infants born via cesarean delivery to OWOB mothers were 5 times more likely to be overweight/obese at 1 year (adjusted odds ratio [OR], 5.02), and those born vaginally to overweight/obese mothers had a 3-fold increased risk of being overweight/obese at 1 year (adjusted OR, 3.33), the authors report. At 3 years, the respective adjusted ORs were similar, at 5.55 and 3.07, the authors write.

Relationship Between Infant Gut Microbiota and Overweight/Obesity

The analyses looking at the association of maternal overweight status and infant gut microbiota and the joint associations of maternal overweight status and birth mode with infant gut microbiota also identified statistically significant relationships.

In particular, a fecal abundance of the family Lachnospiraceae bacteria was observed in overweight children born to OWOB mothers who delivered vaginally or via cesarean, the authors report.

In an analysis of joint associations, the adjusted odds ratio of abundant fecal Lachnospiraceae in babies of OWOB mothers who delivered via emergency cesarean was 2.02, whereas no such relationship was observed after vaginal birth among OWOB mothers.

"We found that enrichment of infant gut microbiota with the family Lachnospiraceae at ages 3 to 4 months mediated the association between maternal OWOB and child OWOB through a birth mode pathway," they add. "A mediation association for richness of total microbial species was also observed for child OWOB."

The latter association was also dependent on birth mode, they write, noting the increased abundance of several microbial species in infants born vaginally to overweight women.

The findings warrant additional investigation, the authors stress. In particular, further study into the roles that breast-feeding and antibiotic exposure — covariates that were adjusted for in the current analyses — play in the sequential mediator pathway should be examined, as should the influence of maternal microbiota (gut, vaginal, and skin) and of gut microbiota in older children in the intergenerational transmission of overweight and obesity.

Collection of More Stool Samples Would Have Strengthened Results

In their editorial, Paolella and Vajro note that one major limitation "was the lack of maternal samples for [intestinal microbiota (IM)] analysis. Maternal vaginal and skin microbiota are also involved in the development of infant IM but were not studied." And infant stool samples "were collected only once at a mean age of 3.7 months. Other stool samples collected at older ages (eg, age 12 months) might have allowed confirmation of the results, especially given the information that infant IM changes during the first year of life and that different factors affecting infant IM (eg, breastfeeding and early exposure to antibiotics) appear pivotal."

Future studies are needed to confirm the finding that increased abundance of Lachnospiraceae play a key role in mother-to-child transmission of overweight and obesity, the editorialists continue.

This research was funded by a grant from the Canadian Institutes of Health Research Canadian Microbiome Initiative. The authors of the study and the accompanying editorial have disclosed no relevant financial relationships.

JAMA Pediatr. Published online February 19, 2018. Article abstract, Editorial extract

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