Neonatal Ampicillin/Gentamicin Exposure and the Risk of Childhood Obesity in South Bronx Pediatric Population

Abstract

Objective This study aimed to assess the association between neonatal antibiotic exposure and the risk of childhood obesity.

Study Design This retrospective cohort study enrolled neonates born between 2011 and 2015 and followed up until 5 years. The incidence of obesity at 5 years old, and other characteristics were compared between the antibiotic-exposed and unexposed groups. Chi-square test was conducted on categorical variables and Student's t-test for normally distributed continuous variable. Significant variables (p < 0.05) in bivariate analysis were modelled in a stepwise multivariate logistic regression analysis to ascertain independent predictors of obesity at 5 years.

Results Of the 1,447 subjects, 749 (51.8%) received ampicillin and gentamicin, and 333 (23%) were obese. Neonates exposed to antibiotics were more likely to be obese compared with those unexposed (26 vs. 20%, p = 0.01). In the adjusted model, this association persisted (adjusted odds ratio: 1.37, p = 0.02).

Conclusion Neonatal antibiotic exposure is associated with early childhood obesity and may play a significant role in the weight trajectories of these children. Hence, antibiotic stewardship in this period cannot be overemphasized.

Key Points

• Findings from our study showed that neonatal antibiotic exposure is associated with early childhood obesity.

• The prevalence of childhood obesity at 5 years is high (23%).

• Further exploration of the role of antibiotics on the gut microbiome and its effect on weight trajectories is needed.

Keywords

antibiotics - neonates - obesity - childhood - gut microbiome

Ethics Approval and Patient Consent

This retrospective cohort study was approved by the BronxCare Health System Institutional Review Board (approval number: 01142111).

Authors' Contributions

A.A. conceptualization, data management, and statistical analysis, manuscript writing, and editing. A.P.T. conceptualization, data extraction, manuscript writing, and editing. M.A.A.G. conceptualization, data extraction, and manuscript editing. N.M. conceptualization, data extraction, and manuscript editing. T.O. data extraction and manuscript editing, S.D. data extraction and manuscript editing. M.A. manuscript writing and editing. O.P. manuscript writing and editing. A.P. conceptualization, supervision of project, manuscript editing.

Publikationsverlauf

Eingereicht: 13. März 2023

Angenommen: 10. August 2023

Artikel online veröffentlicht:
15. September 2023

• References

• 1 Kumar S, Kelly AS. Review of childhood obesity: from epidemiology, etiology, and comorbidities to clinical assessment and treatment. Mayo Clin Proc 2017; 92 (02) 251-265
• 2 Scott FI, Mamtani R. Antibiotics and obesity—a burgeoning or thinning argument?. JAMA Pediatr 2017; 171 (02) 118-120
• 3 Manuel M, Regalado E, Mochizuki M. Pediatric dyslipidemia in a minority mostly-immigrant inner city population. J Sci Innov Med 2019; 2 (02) 1-2
• 4 Childhood Obesity Facts / Overweight & Obesity / CDC. Accessed May 20, 2023. https://www.cdc.gov/obesity/data/childhood.html
• 5 Al-Hamad D, Raman V. Metabolic syndrome in children and adolescents. Transl Pediatr 2017; 6 (04) 397-407
• 6 Magge SN, Goodman E, Armstrong SC. COMMITTEE ON NUTRITION, SECTION ON ENDOCRINOLOGY, SECTION ON OBESITY. The metabolic syndrome in children and adolescents: shifting the focus to cardiometabolic risk factor clustering. Pediatrics 2017; 140 (02) e20171603
• 7 Scott FI, Horton DB, Mamtani R. et al. Administration of antibiotics to children before age 2 years increases risk for childhood obesity. Gastroenterology 2016; 151 (01) 120-129.e5
• 8 Duranti S, Ferrario C, van Sinderen D, Ventura M, Turroni F. Obesity and microbiota: an example of an intricate relationship. Genes Nutr 2017; 12: 18
• 9 Dreyer JL, Liebl AL. Early colonization of the gut microbiome and its relationship with obesity. Hum Microbiome J 2018; 10: 1-5
• 10 Chong CYL, Bloomfield FH, O'Sullivan JM. Factors affecting gastrointestinal microbiome development in neonates. Nutrients 2018; 10 (03) 274
• 11 Hoskin-Parr L, Teyhan A, Blocker A, Henderson AJW. Antibiotic exposure in the first two years of life and development of asthma and other allergic diseases by 7.5 yr: a dose-dependent relationship. Pediatr Allergy Immunol 2013; 24 (08) 762-771
• 12 Lamont RF, Møller Luef B, Stener Jørgensen J. Childhood inflammatory and metabolic disease following exposure to antibiotics in pregnancy, antenatally, intrapartum and neonatally. F1000 Res 2020; 9: F1000 Faculty Rev-144
• 13 Goldman JL, Jackson MA. Tip of the iceberg: understanding the unintended consequences of antibiotics. Pediatrics 2015; 136 (02) e492-e493
• 14 Block JP, Bailey LC, Gillman MW. et al; PCORnet Antibiotics and Childhood Growth Study Group. Early antibiotic exposure and weight outcomes in young children. Pediatrics 2018; 142 (06) e20180290
• 15 Rinninella E, Raoul P, Cintoni M. et al. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms 2019; 7 (01) 14
• 16 Trasande L, Blustein J, Liu M, Corwin E, Cox LM, Blaser MJ. Infant antibiotic exposures and early-life body mass. Int J Obes 2013; 37 (01) 16-23
• 17 Dawson-Hahn EE, Rhee KE. The association between antibiotics in the first year of life and child growth trajectory. BMC Pediatr 2019; 19 (01) 23
• 18 Koebnick C, Tartof SY, Sidell MA. et al. Effect of in-utero antibiotic exposure on childhood outcomes: methods and baseline data of the Fetal Antibiotic EXposure (FAX) cohort study. JMIR Res Protoc 2019; 8 (07) e12065
• 19 Rogawski ET, Platts-Mills JA, Seidman JC. et al; MAL-ED Network Investigators. Early antibiotic exposure in low-resource settings is associated with increased weight in the first two years of life. J Pediatr Gastroenterol Nutr 2017; 65 (03) 350-356
• 20 Mueller NT. The gut microbiome and childhood obesity: connecting the dots. Child Obes 2015; 11 (03) 227-230
• 21 Rogawski ET, Westreich DJ, Adair LS. et al. Early life antibiotic exposure is not associated with growth in young children of Vellore, India. J Pediatr 2015; 167 (05) 1096-102.e3
• 22 Gerber JS, Bryan M, Ross RK. et al. Antibiotic exposure during the first 6 months of life and weight gain during childhood. JAMA 2016; 315 (12) 1258-1265
• 23 Sidener HM, Park B, Gao L. Effect of antibiotic administration during infancy on growth curves through young adulthood in rhesus macaques (Macaca mulatta). Comp Med 2017; 67 (03) 270-276
• 24 Braun T, Filleböck V, Metze B, Bührer C, Plagemann A, Henrich W. Long term alterations of growth after antenatal steroids in preterm twin pregnancies. J Perinat Med 2020; 49 (02) 127-137
• 25 Daniels SR. Is post-term birth associated with increased risk of obesity?. J Pediatr 2012; 160 (05) A5
• 26 Wang Y, Chen HJ. Use of percentiles and Z-scores in anthropometry. In: Handbook of Anthropometry: Physical Measures of Human Form in Health and Disease. Springer; New York: 2012: 29-48
• 27 Freedman DS, Butte NF, Taveras EM. et al. BMI z-Scores are a poor indicator of adiposity among 2- to 19-year-olds with very high BMIs, NHANES 1999-2000 to 2013-2014. Obesity (Silver Spring) 2017; 25 (04) 739-746
• 28 Wei R, Ogden CL, Parsons VL, Freedman DS, Hales CM. A method for calculating BMI z-scores and percentiles above the 95^th percentile of the CDC growth charts. Ann Hum Biol 2020; 47 (06) 514-521
• 29 Pyle AK, Cantey JB, Brown LS. et al. Antibiotic exposure and growth patterns in preterm, very low birth weight infants. Matern Health Neonatol Perinatol 2021; 7 (01) 7
• 30 Kamphorst K, Oosterloo BC, Vlieger AM. et al. Antibiotic treatment in the first week of life impacts the growth trajectory in the first year of life in term infants. J Pediatr Gastroenterol Nutr 2019; 69 (01) 131-136
• 31 Li DK, Chen H, Ferber J, Odouli R. Maternal infection and antibiotic use in pregnancy and the risk of childhood obesity in offspring: a birth cohort study. Int J Obes 2020; 44 (04) 771-780
• 32 Cox LM, Blaser MJ. Pathways in microbe-induced obesity. Cell Metab 2013; 17 (06) 883-894
• 33 Page KA, Luo S, Wang X. et al. Children exposed to maternal obesity or gestational diabetes mellitus during early fetal development have hypothalamic alterations that predict future weight gain. Diabetes Care 2019; 42 (08) 1473-1480
• 34 Mueller NT, Bakacs E, Combellick J, Grigoryan Z, Dominguez-Bello MG. The infant microbiome development: mom matters. Trends Mol Med 2015; 21 (02) 109-117
• 35 Azad MB, Bridgman SL, Becker AB, Kozyrskyj AL. Infant antibiotic exposure and the development of childhood overweight and central adiposity. Int J Obes 2014; 38 (10) 1290-1298