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Abstract
Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development. Here, we investigate the long-term impact of antibiotic treatment in the neonatal period and early childhood on child growth in an unselected birth cohort of 12,422 children born at full term. We find significant attenuation of weight and height gain during the first 6 years of life after neonatal antibiotic exposure in boys, but not in girls, after adjusting for potential confounders. In contrast, antibiotic use after the neonatal period but during the first 6 years of life is associated with significantly higher body mass index throughout the study period in both boys and girls. Neonatal antibiotic exposure is associated with significant differences in the gut microbiome, particularly in decreased abundance and diversity of fecal Bifidobacteria until 2 years of age. Finally, we demonstrate that fecal microbiota transplant from antibiotic-exposed children to germ-free male, but not female, mice results in significant growth impairment. Thus, we conclude that neonatal antibiotic exposure is associated with a long-term gut microbiome perturbation and may result in reduced growth in boys during the first six years of life while antibiotic use later in childhood is associated with increased body mass index.
In this study, Omry Koren, Samuli Rautava and colleagues report a sex-specific association between neonatal antibiotic exposure and weight and height gain during the first six years of life and showing that boys but not girls exposed to neonatal antibiotics exhibit impaired weight and height development.
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1 Bar Ilan University, Azrieli Faculty of Medicine, Safed, Israel (GRID:grid.22098.31) (ISNI:0000 0004 1937 0503)
2 University of Turku and Turku University Hospital, Department of Pediatrics, Turku, Finland (GRID:grid.1374.1) (ISNI:0000 0001 2097 1371)
3 Bar-Ilan University, Department of Mathematics, Ramat-Gan, Israel (GRID:grid.22098.31) (ISNI:0000 0004 1937 0503)
4 Federal Research Institute of Nutrition and Food, Institute of Child Nutrition, Max Rubner-Institut, Karlsruhe, Germany (GRID:grid.72925.3b) (ISNI:0000 0001 1017 8329)
5 Ludwig-Maximilians-Universität München, Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), Faculty of Medicine, Munich, Germany (GRID:grid.5252.0) (ISNI:0000 0004 1936 973X)
6 Bar Ilan University, Azrieli Faculty of Medicine, Safed, Israel (GRID:grid.22098.31) (ISNI:0000 0004 1937 0503); Zefat Academic College, Safed, Israel (GRID:grid.460169.c) (ISNI:0000 0004 0418 023X)
7 University of Trento, Department CIBIO, Trento, Italy (GRID:grid.11696.39) (ISNI:0000 0004 1937 0351)
8 Migal – Galilee Research Institute, Qiryat Shemona, Israel (GRID:grid.425662.1) (ISNI:0000 0004 0404 5732)
9 Bar Ilan University, Azrieli Faculty of Medicine, Safed, Israel (GRID:grid.22098.31) (ISNI:0000 0004 1937 0503); Ziv Medical center, Safed, Israel (GRID:grid.415739.d) (ISNI:0000 0004 0631 7092)
10 University of Turku, Functional Foods Forum, Turku, Finland (GRID:grid.1374.1) (ISNI:0000 0001 2097 1371)
11 University of Turku, Department of Biostatistics, Faculty of Medicine, Turku, Finland (GRID:grid.1374.1) (ISNI:0000 0001 2097 1371); University of Turku and Turku University Hospital, Department of Public Health, Turku, Finland (GRID:grid.1374.1) (ISNI:0000 0001 2097 1371)
12 University of Turku, Department of Biostatistics, Faculty of Medicine, Turku, Finland (GRID:grid.1374.1) (ISNI:0000 0001 2097 1371)
13 University of Turku and Turku University Hospital, Department of Public Health, Turku, Finland (GRID:grid.1374.1) (ISNI:0000 0001 2097 1371)
14 Migal – Galilee Research Institute, Qiryat Shemona, Israel (GRID:grid.425662.1) (ISNI:0000 0004 0404 5732); Tel-Hai Academic College, Qiryat Shemona, Israel (GRID:grid.443193.8) (ISNI:0000 0001 2107 842X)
15 Ludwig-Maximilians-Universität München, Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), Faculty of Medicine, Munich, Germany (GRID:grid.5252.0) (ISNI:0000 0004 1936 973X); University Children’s Hospital, Heinrich Heine University Düsseldorf, Department of General Pediatrics, Neonatology and Pediatric Cardiology, Düsseldorf, Germany (GRID:grid.5252.0)
16 University of Turku and Turku University Hospital, Department of Pediatrics, Turku, Finland (GRID:grid.1374.1) (ISNI:0000 0001 2097 1371); University of Helsinki & Helsinki University Hospital, New Children’s Hospital, Pediatric Research Center, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071)