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Association of Exposure to Formula in the Hospital and Subsequent Infant Feeding Practices With Gut Microbiota and Risk of Overweight in the First Year of Life.
JAMA Pediatr. 2018 07 02; 172(7):e181161.JP

Abstract

Importance

The effect of neonatal and infant feeding practices on childhood obesity is unclear. The gut microbiome is strongly influenced by feeding practices and has been linked to obesity.

Objective

To characterize the association between breastfeeding, microbiota, and risk of overweight during infancy, accounting for the type and timing of supplementary feeding.

Design, Setting, and Participants

In this study of a subset of 1087 infants from the prospective CHILD pregnancy cohort, mothers were recruited between January 1, 2009, and December 31, 2012. Statistical analysis was performed from February 1 to December 20, 2017.

Main Outcomes and Measures

Feeding was reported by mothers and documented from hospital records. Fecal microbiota at 3 to 4 months (from 996 infants) and/or 12 months (from 821 infants) were characterized by 16S ribosomal RNA sequencing. Infants with a weight for length exceeding the 85th percentile were considered to be at risk for overweight.

Results

There were 1087 infants in the study (507 girls and 580 boys); at 3 months, 579 of 1077 (53.8%) were exclusively breastfed according to maternal report. Infants who were exclusively formula fed at 3 months had an increased risk of overweight in covariate-adjusted models (53 of 159 [33.3%] vs 74 of 386 [19.2%]; adjusted odds ratio, 2.04; 95% CI, 1.25-3.32). This association was attenuated (adjusted odds ratio, 1.33; 95% CI, 0.79-2.24) after further adjustment for microbiota features characteristic of formula feeding at 3 to 4 months, including higher overall richness and enrichment of Lachnospiraceae. A total of 179 of 579 infants who were exclusively breastfed (30.9%) received formula as neonates; this brief supplementation was associated with lower relative abundance of Bifidobacteriaceae and higher relative abundance of Enterobacteriaceae at 3 to 4 months but did not influence the risk of overweight. At 12 months, microbiota profiles differed significantly according to feeding practices at 6 months; among partially breastfed infants, formula supplementation was associated with a profile similar to that of nonbreastfed infants (higher diversity and enrichment of Bacteroidaceae), whereas the introduction of complementary foods without formula was associated with a profile more similar to that of exclusively breastfed infants (lower diversity and enrichment of Bifidobacteriaceae and Veillonellaceae). Microbiota profiles at 3 months were more strongly associated with risk of overweight than were microbiota profiles at 12 months.

Conclusions and Relevance

Breastfeeding may be protective against overweight, and gut microbiota may contribute to this effect. Formula feeding appears to stimulate changes in microbiota that are associated with overweight, whereas other complementary foods do not. Subtle microbiota differences emerge after brief exposure to formula in the hospital. These results identify important areas for future research and distinguish early infancy as a critical period when transient gut dysbiosis may lead to increased risk of overweight.

Authors+Show Affiliations

Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. Developmental Origins of Chronic Diseases in Children Network (DEVOTION), Department of Pediatrics and Child Health, Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada. National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.Developmental Origins of Chronic Diseases in Children Network (DEVOTION), Department of Pediatrics and Child Health, Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada.Developmental Origins of Chronic Diseases in Children Network (DEVOTION), Department of Pediatrics and Child Health, Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada.Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.Department of Agriculture, Food and Nutritional Sciences, University of Alberta, Edmonton, Alberta, Canada.Department of Medicine, McMaster University, Hamilton, Ontario, Canada.Department of Medicine, McMaster University, Hamilton, Ontario, Canada.Developmental Origins of Chronic Diseases in Children Network (DEVOTION), Department of Pediatrics and Child Health, Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada.Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada. Child and Family Research Institute, BC Children's Hospital, Vancouver, British Columbia, Canada.Department of Pediatrics and Physiology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.Department of Pediatrics and Physiology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29868719

Citation

Forbes, Jessica D., et al. "Association of Exposure to Formula in the Hospital and Subsequent Infant Feeding Practices With Gut Microbiota and Risk of Overweight in the First Year of Life." JAMA Pediatrics, vol. 172, no. 7, 2018, pp. e181161.
Forbes JD, Azad MB, Vehling L, et al. Association of Exposure to Formula in the Hospital and Subsequent Infant Feeding Practices With Gut Microbiota and Risk of Overweight in the First Year of Life. JAMA Pediatr. 2018;172(7):e181161.
Forbes, J. D., Azad, M. B., Vehling, L., Tun, H. M., Konya, T. B., Guttman, D. S., Field, C. J., Lefebvre, D., Sears, M. R., Becker, A. B., Mandhane, P. J., Turvey, S. E., Moraes, T. J., Subbarao, P., Scott, J. A., & Kozyrskyj, A. L. (2018). Association of Exposure to Formula in the Hospital and Subsequent Infant Feeding Practices With Gut Microbiota and Risk of Overweight in the First Year of Life. JAMA Pediatrics, 172(7), e181161. https://doi.org/10.1001/jamapediatrics.2018.1161
Forbes JD, et al. Association of Exposure to Formula in the Hospital and Subsequent Infant Feeding Practices With Gut Microbiota and Risk of Overweight in the First Year of Life. JAMA Pediatr. 2018 07 2;172(7):e181161. PubMed PMID: 29868719.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Exposure to Formula in the Hospital and Subsequent Infant Feeding Practices With Gut Microbiota and Risk of Overweight in the First Year of Life. AU - Forbes,Jessica D, AU - Azad,Meghan B, AU - Vehling,Lorena, AU - Tun,Hein M, AU - Konya,Theodore B, AU - Guttman,David S, AU - Field,Catherine J, AU - Lefebvre,Diana, AU - Sears,Malcolm R, AU - Becker,Allan B, AU - Mandhane,Piushkumar J, AU - Turvey,Stuart E, AU - Moraes,Theo J, AU - Subbarao,Padmaja, AU - Scott,James A, AU - Kozyrskyj,Anita L, AU - ,, Y1 - 2018/07/02/ PY - 2018/6/6/pubmed PY - 2019/9/27/medline PY - 2018/6/6/entrez SP - e181161 EP - e181161 JF - JAMA pediatrics JO - JAMA Pediatr VL - 172 IS - 7 N2 - Importance: The effect of neonatal and infant feeding practices on childhood obesity is unclear. The gut microbiome is strongly influenced by feeding practices and has been linked to obesity. Objective: To characterize the association between breastfeeding, microbiota, and risk of overweight during infancy, accounting for the type and timing of supplementary feeding. Design, Setting, and Participants: In this study of a subset of 1087 infants from the prospective CHILD pregnancy cohort, mothers were recruited between January 1, 2009, and December 31, 2012. Statistical analysis was performed from February 1 to December 20, 2017. Main Outcomes and Measures: Feeding was reported by mothers and documented from hospital records. Fecal microbiota at 3 to 4 months (from 996 infants) and/or 12 months (from 821 infants) were characterized by 16S ribosomal RNA sequencing. Infants with a weight for length exceeding the 85th percentile were considered to be at risk for overweight. Results: There were 1087 infants in the study (507 girls and 580 boys); at 3 months, 579 of 1077 (53.8%) were exclusively breastfed according to maternal report. Infants who were exclusively formula fed at 3 months had an increased risk of overweight in covariate-adjusted models (53 of 159 [33.3%] vs 74 of 386 [19.2%]; adjusted odds ratio, 2.04; 95% CI, 1.25-3.32). This association was attenuated (adjusted odds ratio, 1.33; 95% CI, 0.79-2.24) after further adjustment for microbiota features characteristic of formula feeding at 3 to 4 months, including higher overall richness and enrichment of Lachnospiraceae. A total of 179 of 579 infants who were exclusively breastfed (30.9%) received formula as neonates; this brief supplementation was associated with lower relative abundance of Bifidobacteriaceae and higher relative abundance of Enterobacteriaceae at 3 to 4 months but did not influence the risk of overweight. At 12 months, microbiota profiles differed significantly according to feeding practices at 6 months; among partially breastfed infants, formula supplementation was associated with a profile similar to that of nonbreastfed infants (higher diversity and enrichment of Bacteroidaceae), whereas the introduction of complementary foods without formula was associated with a profile more similar to that of exclusively breastfed infants (lower diversity and enrichment of Bifidobacteriaceae and Veillonellaceae). Microbiota profiles at 3 months were more strongly associated with risk of overweight than were microbiota profiles at 12 months. Conclusions and Relevance: Breastfeeding may be protective against overweight, and gut microbiota may contribute to this effect. Formula feeding appears to stimulate changes in microbiota that are associated with overweight, whereas other complementary foods do not. Subtle microbiota differences emerge after brief exposure to formula in the hospital. These results identify important areas for future research and distinguish early infancy as a critical period when transient gut dysbiosis may lead to increased risk of overweight. SN - 2168-6211 UR - https://www.unboundmedicine.com/medline/citation/29868719/Association_of_Exposure_to_Formula_in_the_Hospital_and_Subsequent_Infant_Feeding_Practices_With_Gut_Microbiota_and_Risk_of_Overweight_in_the_First_Year_of_Life_ L2 - https://jamanetwork.com/journals/jamapediatrics/fullarticle/10.1001/jamapediatrics.2018.1161 DB - PRIME DP - Unbound Medicine ER -