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Observational Study
. 2018 Apr 1;172(4):368-377.
doi: 10.1001/jamapediatrics.2017.5535.

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

Hein M Tun  1 , Sarah L Bridgman  1 , Radha Chari  2 , Catherine J Field  3 , David S Guttman  4 , Allan B Becker  5 , Piush J Mandhane  1 , Stuart E Turvey  6 , Padmaja Subbarao  7 , Malcolm R Sears  8 , James A Scott  9 , Anita L Kozyrskyj  1 ; Canadian Healthy Infant Longitudinal Development (CHILD) Study Investigators
Affiliations
Observational Study

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

Hein M Tun et al. JAMA Pediatr. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.
Figure 1.. Forest Plots Portraying Odds Ratios and 95% CIs of Factors Associated With Childhood Overweight or Obesity (OWOB)
A, Odds ratios at age 1 year for childhood OWOB in association with maternal weight status, birth mode, and infant gut microbiota. B, Odds ratios at age 3 years for childhood OWOB in association with maternal weight status, birth mode, and infant gut microbiota. C, Joint associations at age 1 year of maternal weight status and birth mode. D, Joint associations at age 3 years of maternal weight status and birth mode. Adjusted (1): Adjusted for location, birth mode, infant sex, socioeconomic status (SES), maternal race/ethnicity, maternal prenatal asthma, maternal prenatal smoking, breastfeeding status, oral antibiotic use (0-12 months), and pet exposure. Adjusted (2): Adjusted for location, infant sex, SES, maternal weight status, maternal race/ethnicity, maternal prenatal asthma, maternal prenatal smoking, breastfeeding status, oral antibiotic use (0-12 months), and pet exposure. Adjusted (3): Adjusted for location, birth mode, infant sex, maternal weight status, maternal race/ethnicity, maternal prenatal asthma, maternal prenatal smoking, breastfeeding status, oral antibiotic use (0-12 months), pet exposure, and age at fecal sampling. Adjusted (4): Adjusted for location, infant sex, SES, maternal race/ethnicity, maternal prenatal asthma, maternal prenatal smoking, breastfeeding status, oral antibiotic use (0-12 months), and pet exposure. Error barrs indicate 95% CIs. CD indicates cesarean delivery; IAP−, no intrapartum antibiotic prophylaxis; IAP+, intrapartum antibiotic prophylaxis; NW, normal-weight; and Ref, reference. The dotted lines indicate an odds ratio of 1.
Figure 2.
Figure 2.. Differences in Relative Abundance of Bacterial Taxa in Microbiota of the Infant Gut Jointly Stratified by Delivery Mode and Maternal Prepregnancy Weight Status
Linear discriminant analysis (LDA) scores provided for differential taxon abundance between normal-weight mothers (BMI, 18.5-24.9 [dark blue]) and overweight mothers (BMI, ≥25 [light blue]). A, Vaginally delivered infants. B, Infants born via scheduled cesarean delivery. C, Infants born via emergency cesarean delivery. BMI indicates body mass index (calculated as weight in kilograms divided by height in meters squared); F, family; G, genus; and O, order.
Figure 3.
Figure 3.. Sequential Mediation Models of Associations Between Maternal Weight Status, Modes of Delivery, and Microbiota of the Infant Gut
A, Firmicutes species richness and childhood overweight or obesity (OWOB). B, Lachnospiraceae abundance and childhood OWOB. CD indicates cesarean delivery; IAP, intrapartum antibiotic prophylaxis; VgIAP–, vaginal delivery without IAP; and VgIAP+, vaginal delivery with IAP. aP < .001. bP < .01. cP < .10. dP < .05.
Figure 4.
Figure 4.. Microbiota Interaction Networks for Groups of Overweight or Obese (OWOB) Phenotype Association Between Mothers and Offspring at Age 1 Year
A, Normal-weight (NW) infants of normal-weight mothers. B, OWOB infants of normal-weight mothers. C, Normal-weight infants of OWOB mothers. D, OWOB infants of OWOB mothers. C indicates class; F, family; and O, order. Connector line thickness represents the value of the Spearman correlation coefficient (ρ), and brackets around the family name represent the proposed taxonomy by the Greengenes database.
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