JAMA Pediatrics Journal Club Slides Cesarean Delivery Formula

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. Copyright restrictions may apply

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. Copyright restrictions may apply

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. Copyright restrictions may apply

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 16 S r. RNA gene. – Between-group Uni. Frac 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. Copyright restrictions may apply

Results Characteristics of 102 Participants Copyright restrictions may apply

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

Results Association Between Composition of the Infant Gut Microbiome and Delivery Mode P <. 001; Q <. 001. Association with cesarean delivery Copyright restrictions may apply 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. Copyright restrictions may apply Association with exclusive formula feeding Association with exclusive breastfeeding

Results Mean Between-Group Comparisons of Uni. Frac Distances Copyright restrictions may apply

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. Copyright restrictions may apply

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. Copyright restrictions may apply

Contact Information • If you have questions, please contact the corresponding author: – Anne G. Hoen, Ph. D, 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 P 01 ES 022832, NIEHS P 20 ES 018175, NIGMS P 20 GM 104416, NLM K 01 LM 011985, NLM R 01 LM 009012, and NLM R 01 LM 010098) and the US Environmental Protection Agency (grants RD 83459901 and RD 83544201). Conflict of Interest Disclosures • None reported. Copyright restrictions may apply