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The relationship of prenatal and infant antibiotic exposure with childhood overweight and obesity: a systematic review

Published online by Cambridge University Press:  18 November 2019

Ruth Baron Open the ORCID record for Ruth Baron [Opens in a new window] ,
Meron Taye ,
Isolde Besseling-van der Vaart ,
Joanne Ujčič-Voortman ,
Hania Szajewska ,
Jacob C. Seidell  and
Arnoud Verhoeff
Ruth Baron
Affiliation:
Public Health Service Amsterdam, Sarphati Amsterdam, Amsterdam, the Netherlands
Meron Taye
Affiliation:
Public Health Service Amsterdam, Sarphati Amsterdam, Amsterdam, the Netherlands
Isolde Besseling-van der Vaart
Affiliation:
Winclove Probiotics B.V., Amsterdam, the Netherlands
Joanne Ujčič-Voortman
Affiliation:
Public Health Service Amsterdam, Sarphati Amsterdam, Amsterdam, the Netherlands
Hania Szajewska
Affiliation:
Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland
Jacob C. Seidell
Affiliation:
Department of Health Sciences, Amsterdam Public Health Research Institute, Vrije Universiteit, Amsterdam, the Netherlands
Arnoud Verhoeff*
Affiliation:
Public Health Service Amsterdam, Sarphati Amsterdam, Amsterdam, the Netherlands
*
Address for correspondence: Email: averhoeff@ggd.amsterdam.nl
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Abstract

This study aimed to assess the evidence regarding the relationship between early-life antibiotic exposure and childhood overweight/obesity by reviewing observational studies on prenatal antibiotic exposure and systematic reviews on infant antibiotic exposure. A search in Pubmed, Embase and Google Scholar covering the period 1st January till 1st December 2018 led to the identification of five studies on prenatal antibiotic exposure and four systematic reviews on infant antibiotic exposure. Positive trends between prenatal antibiotic exposure and overweight/obesity were reported in all studies; two studies reported a significant overall relationship and the other three reported significant relationships under certain conditions. Effect sizes ranged from odds ratio (OR): 1.04 (0.62–1.74) to relative risk (RR): 1.77 (1.25–2.51). Regarding infant antibiotics, one review concluded there was substantial evidence that infant antibiotic exposure increased the risk of childhood overweight/obesity [pooled effect sizes: RR: 1.21 (1.09–1.33) for overweight and RR: 1.18 (1.12–1.25) for obesity]. Two reviews concluded there was some evidence for a relationship [pooled effect sizes: OR: 1.05 (1.00–1.11) and OR: 1.11 (1.02–1.20)]. The fourth review concluded the studies were too heterogeneous for meta-analyses and the evidence regarding the relationship between infant antibiotic exposure and childhood overweight/obesity was inconclusive. More well-designed studies are needed that include data on intra-partum antibiotics and address important potential confounders (including maternal and childhood infections). This review points to some evidence of a relationship between early-life antibiotic exposure and childhood overweight/obesity; this is especially evident in certain children (i.e. exposed to multiple and broad-spectrum antibiotics, earlier postnatal exposure and male gender) and merits further research.

Keywords

Early lifeantibioticsmicrobiomeoverweight and obesitychronic diseases

Information

Type
Review
Information
Journal of Developmental Origins of Health and Disease , Volume 11 , Issue 4 , August 2020 , pp. 335 - 349
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019

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Footnotes

*

Members of the Sarphati Amsterdam/Warsaw group on ANtibiotic long-Term Impact (SAWANTI): (in alphabetical order) Ruth Baron, Isolde Besseling-van der Vaart, Dorota Gieruszczak-Białek, Andrea Horvath, Jan Łukasik, Maciej Kołodziej, Bernadeta Patro-Gołąb, Małgorzata Pieścik-Lech, Jacob C Seidell, Agata Skórka, Hania Szajewska, Meron Taye, Joanne Ujčič-Voortman, and Arnoud Verhoeff

References

Hanson, MA, Gluckman, PD. Developmental origins of health and disease--global public health implications. Best Pract Res Clin Obstet Gynaecol. 2015; 29, 24–31.CrossRefGoogle Scholar
World Health Organization. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Updated 2018.Google Scholar
Ogden, CL, Carroll, MD, Kit, BK, Flegal, KM. Prevalence of childhood and adult obesity in the united states, 2011–2012. JAMA. 2014; 311, 806–814.CrossRefGoogle ScholarPubMed
Centraal Bureau voor de Statistiek (Statistics Netherlands). https://Opendata.cbs.nl/statline/#/CBS/nl/dataset/81565NED/table?ts=1518773067183. Updated 2017.Google Scholar
Llewellyn, A, Simmonds, M, Owen, CG, Woolacott, N. Childhood obesity as a predictor of morbidity in adulthood: a systematic review and meta-analysis. Obes Rev. 2016; 17, 56–67.CrossRefGoogle ScholarPubMed
Kumar, S, Kelly, AS. Review of childhood obesity: from epidemiology, etiology, and comorbidities to clinical assessment and treatment. Mayo Clin Proc. 2017; 92, 251–265.CrossRefGoogle ScholarPubMed
Woo Baidal, JA, Locks, LM, Cheng, ER, Blake-Lamb, TL, Perkins, ME, Taveras, EM. Risk factors for childhood obesity in the first 1,000 days: a systematic review. Am J Prev Med. 2016; 50, 761–779.CrossRefGoogle ScholarPubMed
Cox, LM, Blaser, MJ.Antibiotics in early life and obesity. Nat Rev Endocrinol. 2015; 11, 182–190.CrossRefGoogle ScholarPubMed
Nogacka, AM, Salazar, N, Arboleya, S, et al. Early microbiota, antibiotics and health. Cell Mol Life Sci. 2018; 75, 83–91.CrossRefGoogle ScholarPubMed
Jukes, TH, Williams, WL. Nutritional effects of antibiotics. Pharmacol Rev. 1953; 5, 381–420.Google ScholarPubMed
Cho, I, Yamanishi, S, Cox, L, et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature. 2012; 488, 621–626.CrossRefGoogle ScholarPubMed
Cox, LM, Yamanishi, S, Sohn, J, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014; 158, 705–721.CrossRefGoogle ScholarPubMed
Azad, MB, Moossavi, S, Owora, A, Sepehri, S. Early-life antibiotic exposure, gut microbiota development, and predisposition to obesity. Nestle Nutr Inst Workshop Ser. 2017; 88, 67–79.CrossRefGoogle ScholarPubMed
Korpela, K, de Vos, WM. Antibiotic use in childhood alters the gut microbiota and predisposes to overweight. Microb Cell. 2016; 3, 296–298.CrossRefGoogle ScholarPubMed
Martinez de Tejada, B. Antibiotic use and misuse during pregnancy and delivery: benefits and risks. Int J Environ Res Public Health. 2014; 11, 7993–8009.CrossRefGoogle ScholarPubMed
Stokholm, J, Schjorring, S, Pedersen, L, et al. Prevalence and predictors of antibiotic administration during pregnancy and birth. PLoS ONE. 2013; 8, e82932.CrossRefGoogle ScholarPubMed
de Jonge, L, Bos, HJ, van Langen, IM, de Jong-van den Berg, LT, Bakker, MK.Antibiotics prescribed before, during and after pregnancy in the Netherlands: a drug utilization study. Pharmacoepidemiol Drug Saf. 2014; 23, 60–68.CrossRefGoogle ScholarPubMed
Dekker, ARJ, Verheij, TJM, van der Velden, AW. Antibiotic management of children with infectious diseases in Dutch primary care. Fam Pract. 2017; 34, 169–174.Google ScholarPubMed
Wells, GA, Shea, B, O’Connell, D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Retrieved from http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.Google Scholar
Wang, B, Liu, J, Zhang, Y, et al. Prenatal exposure to antibiotics and risk of childhood obesity in a multicenter cohort study. Am J Epidemiol. 2018; 187, 2159–2167.CrossRefGoogle Scholar
Cassidy-Bushrow, AE, Sitarik, A, Levin, AM, et al. Maternal group B streptococcus and the infant gut microbiota. J Dev Orig Health Dis. 2016; 7, 45–53.CrossRefGoogle ScholarPubMed
Poulsen, MN, Pollak, J, Bailey-Davis, L, Hirsch, AG, Glass, TA, Schwartz, BS. Associations of prenatal and childhood antibiotic use with child body mass index at age 3 years. Obesity (Silver Spring). 2017; 25, 438–444.CrossRefGoogle ScholarPubMed
Mueller, NT, Whyatt, R, Hoepner, L, et al. Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity. Int J Obes (Lond). 2015; 39, 665–670.CrossRefGoogle ScholarPubMed
Mor, A, Antonsen, S, Kahlert, J, et al. Prenatal exposure to systemic antibacterials and overweight and obesity in Danish schoolchildren: a prevalence study. Int J Obes (Lond). 2015; 39, 1450–1455.CrossRefGoogle ScholarPubMed
Kuhle, S, Tong, OS, Woolcott, CG. Association between caesarean section and childhood obesity: a systematic review and meta-analysis. Obes Rev. 2015; 16, 295–303.CrossRefGoogle ScholarPubMed
Gillman, MW. Interrupting intergenerational cycles of maternal obesity. Nestle Nutr Inst Workshop Ser. 2016; 85, 59–69.CrossRefGoogle ScholarPubMed
Li, DK, Chen, H, Ferber, J, Odouli, R.Infection and antibiotic use in infancy and risk of childhood obesity: a longitudinal birth cohort study. Lancet Diabetes Endocrinol. 2017; 5, 18–25.CrossRefGoogle ScholarPubMed
Blomstrom, A, Karlsson, H, Gardner, R, Jorgensen, L, Magnusson, C, Dalman, C. Associations between maternal infection during pregnancy, childhood infections, and the risk of subsequent psychotic disorder–a Swedish cohort study of nearly 2 million individuals. Schizophr Bull. 2016; 42, 125–133.Google ScholarPubMed
Aromataris, E, Fernandez, R, Godfrey, CM, Holly, C, Khalil, H, Tungpunkom, P. Summarizing systematic reviews: methodological development, conduct and reporting of an umbrella review approach. Int J Evid Based Healthc. 2015; 13, 132–140.CrossRefGoogle ScholarPubMed
Whiting, P, Savovic, J, Higgins, JP, et al. ROBIS: a new tool to assess risk of bias in systematic reviews was developed. J Clin Epidemiol. 2016; 69, 225–234.CrossRefGoogle ScholarPubMed
Vidal, AC, Murphy, SK, Murtha, AP, et al. Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring. Int J Obes. 2013; 37, 907–913.CrossRefGoogle ScholarPubMed
Whitaker, RC. Predicting preschooler obesity at birth: the role of maternal obesity in early pregnancy. Pediatrics. 2004; 114, e29–e36.CrossRefGoogle ScholarPubMed
Shao, X, Ding, X, Wang, B, et al. Antibiotic exposure in early life increases risk of childhood obesity: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2017; 8, 170.CrossRefGoogle ScholarPubMed
Rasmussen, SH, Shrestha, S, Bjerregaard, LG, et al. Antibiotic exposure in early life and childhood overweight and obesity: a systematic review and meta-analysis. Diabetes Obes Metab. 2018; 20, 1508–1514.CrossRefGoogle ScholarPubMed
Partap, U, Allcock, SH, Parker, E, Gurdasani, D, Young, EH, Sandhu, MS. Association between early life antibiotic use and childhood overweight and obesity: a narrative review. Glob Health Epidemiol Genom. 2018; 3, e18.CrossRefGoogle ScholarPubMed
Slattery, J, MacFabe, DF, Frye, RE. The significance of the enteric microbiome on the development of childhood disease: a review of prebiotic and probiotic therapies in disorders of childhood. Clin Med Insights Pediatr. 2016; 10, 91–107.CrossRefGoogle ScholarPubMed
Korpela, K, Zijlmans, MA, Kuitunen, M, et al. Childhood BMI in relation to microbiota in infancy and lifetime antibiotic use. Microbiome. 2017; 5. doi: 5(1):26 10.1186/s40168-017-0245-yCrossRefGoogle Scholar
Stanislawski, MA, Dabelea, D, Wagner, BD, et al. Gut microbiota in the first 2 years of life and the association with body mass index at age 12 in a Norwegian birth cohort. MBio. 2018; 9, 10.1128/mBio.01751-18.Google Scholar
Stokholm, J, Schjorring, S, Eskildsen, CE, et al. Antibiotic use during pregnancy alters the commensal vaginal microbiota. Clin Microbiol Infect. 2014; 20, 629–635.CrossRefGoogle ScholarPubMed
Kalliomaki, M, Collado, MC, Salminen, S, Isolauri, E. Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr. 2008; 87, 534–538.CrossRefGoogle ScholarPubMed
Munyaka, PM, Khafipour, E, Ghia, JE. External influence of early childhood establishment of gut microbiota and subsequent health implications. Front Pediatr. 2014; 2, 109.CrossRefGoogle ScholarPubMed
Fouhy, F, Ross, RP, Fitzgerald, GF, Stanton, C, Cotter, PD. Composition of the early intestinal microbiota: knowledge, knowledge gaps and the use of high-throughput sequencing to address these gaps. Gut Microbes. 2012; 3, 203–220.CrossRefGoogle ScholarPubMed
Mitre, E, Susi, A, Kropp, LE, Schwartz, DJ, Gorman, GH, Nylund, CM. Association between use of acid-suppressive medications and antibiotics during infancy and allergic diseases in early childhood. JAMA Pediatr. 2018; 172, e180315.CrossRefGoogle ScholarPubMed
Stark, CM, Susi, A, Emerick, J, Nylund, CM. Antibiotic and acid-suppression medications during early childhood are associated with obesity. Gut. 2019; 68, 62–69.CrossRefGoogle ScholarPubMed
Shreiner, AB, Kao, JY, Young, VB. The gut microbiome in health and in disease. Curr Opin Gastroenterol. 2015; 31, 69–75.CrossRefGoogle Scholar
Federico, A, Dallio, M, DI Sarno, R, Giorgio, V, Miele, L. Gut microbiota, obesity and metabolic disorders. Minerva Gastroenterol Dietol. 2017; 63, 337–344.Google ScholarPubMed
Mackeen, AD, Packard, RE, Ota, E, Berghella, V, Baxter, JK. Timing of intravenous prophylactic antibiotics for preventing postpartum infectious morbidity in women undergoing cesarean delivery. Cochrane Database Syst Rev. 2014, CD009516. doi: 10.1002/14651858.CD009516.pub2CrossRefGoogle Scholar
Kozyrskyj, AL, Kalu, R, Koleva, PT, Bridgman, SL. Fetal programming of overweight through the microbiome: boys are disproportionately affected. J Dev Orig Health Dis. 2016; 7, 25–34.CrossRefGoogle ScholarPubMed
Miller, JE, Wu, C, Pedersen, LH, de Klerk, N, Olsen, J, Burgner, DP. Maternal antibiotic exposure during pregnancy and hospitalization with infection in offspring: a population-based cohort study. Int J Epidemiol. 2018; 47, 561–571.CrossRefGoogle ScholarPubMed
Block, JP, Bailey, LC, Gillman, MW, et al. Early antibiotic exposure and weight outcomes in young children. Pediatrics. 2018; 142, 10.1542/peds.2018-0290. Epub 2018 Oct 31.Google Scholar
Zhu, T, Zhang, L, Qu, Y, Mu, D. Meta-analysis of antenatal infection and risk of asthma and eczema. Medicine (Baltimore). 2016; 95, e4671.CrossRefGoogle ScholarPubMed
Nicolini, G, Sperotto, F, Esposito, S. Combating the rise of antibiotic resistance in children. Minerva Pediatr. 2014; 66, 31–39.Google ScholarPubMed
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