JAMA Pediatrics Journal Club Slides: Cesarean Delivery, Formula Feeding, and Intestinal Microbiome of Infants Madan JC, Hoen AG, Lundgren SN, et al. Association of cesarean delivery and formula supplementation with the intestinal microbiome of 6-week-old infants. JAMA Pediatr. Published online January 11, 2016. doi:10.1001/jamapediatrics.2015.3732.

Introduction Following birth and the initiation of feeding, the human gastrointestinal tract is colonized by a large diversity of bacterial life. The infant gut-associated microbiome is important for nutrient metabolism and early immune system training. Little is known about the factors that shape the normal development of the infant gut microbiome. Associations between delivery mode (cesarean vs vaginal) and feeding method (breast milk vs formula) have been established, but the importance of delivery mode beyond the first hours after birth and the relative importance of these 2 factors have not been examined. Study Objective To examine the associations of delivery mode and feeding methods with the composition of the intestinal microbiota at approximately 6 weeks of life in 102 infants from the New Hampshire Birth Cohort Study.

Methods Study Design Prospective observational pregnancy cohort study. Setting New Hampshire, United States. Participants 102 Mother-infant dyads. Infants receiving antibiotics were excluded owing to likely effects on their microbiome profiles.

Methods Exposures Delivery mode abstracted from delivery medical records, and feeding method during first 6 weeks ascertained through questionnaires. Outcomes Stool microbiome composition characterized using next-generation sequencing of the 16S rRNA gene. Between-group UniFrac distances compared with permutational multivariate analysis of variance. Limitations Single population sampled at a single time point. While infants were able to be categorized as being fed with breast milk exclusively, formula exclusively, or both, statistical power limitations precluded analysis according to the degree of formula supplementation among combination-fed infants. The study did not distinguish by indication for cesarean birth.

Characteristics of 102 Participants Results Characteristics of 102 Participants

Results Relative Abundance of the 10 Most Abundant Bacterial Genera Identified for All Infants Overall and for Individual Delivery Mode and Feeding Groups

Results Association Between Composition of the Infant Gut Microbiome and Delivery Mode P < .001; Q < .001. Association with cesarean delivery Association with vaginal delivery

Results Association Between Composition of the Infant Gut Microbiome and Feeding Method Exclusive breastfeeding vs exclusive formula feeding Exclusively breastfed vs combination fed: P = .02; Q = .04. Combination fed vs exclusively formula fed: P = .52; Q = .52. Exclusively breastfed vs exclusively formula fed: P = .04; Q = .04. Association with exclusive formula feeding Association with exclusive breastfeeding

Mean Between-Group Comparisons of UniFrac Distances Results Mean Between-Group Comparisons of UniFrac Distances

Comment The gut microbiome of 6-week-old infants is dominated by Bacteroides, Bifidobacteria, and Streptococcus. There are independent associations between stool microbial community composition, mode of delivery, and feeding method. Delivery mode was more strongly associated with infant microbiome composition than was diet at age 6 weeks. The distinction between the microbial communities according to feeding method was largest between infants fed exclusively breast milk and those fed either combination diets or exclusively formula. Infants fed both breast milk and formula had intestinal microbial communities that were similar to infants who were exclusively formula fed and relatively distinct from infants who were exclusively breastfed.

Comment These findings support the tenets of the World Health Organization’s Baby Friendly Hospital Initiative, which promotes exclusive breast milk feeding beginning at birth in hospitals and birthing centers and the avoidance of formula supplementation unless deemed medically necessary. The findings offer evidence for pediatricians as they provide guidance to breastfeeding mothers who may be considering incorporating formula into their infant’s diet, and they may have implications for decisions around the use of donor human milk in cases when supplementation is needed. Detailed longitudinal studies are needed to determine the duration of the effects of these factors on microbiome composition and the associated implications for long-term health. The effects on microbial community structure may be one mechanism for the positive association between breastfeeding and childhood and lifelong health.

Conflict of Interest Disclosures Contact Information If you have questions, please contact the corresponding author: Anne G. Hoen, PhD, Department of Epidemiology, Geisel School of Medicine at Dartmouth, 1 Medical Center Dr, Lebanon, NH 03756 (anne.g.hoen@dartmouth.edu). Funding/Support This work was supported in part by grants from the National Institutes of Health (grants NIEHS P01ES022832, NIEHS P20ES018175, NIGMS P20GM104416, NLM K01LM011985, NLM R01LM009012, and NLM R01LM010098) and the US Environmental Protection Agency (grants RD83459901 and RD83544201). Conflict of Interest Disclosures None reported.