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Infant antibiotic exposures and early-life body mass.

ABSTRACT: OBJECTIVES:To examine the associations of antibiotic exposures during the first 2 years of life and the development of body mass over the first 7 years of life. DESIGN:Longitudinal birth cohort study. SUBJECTS:A total of 11?532 children born at ?2500?g in the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based study of children born in Avon, UK in 1991-1992. MEASUREMENTS:Exposures to antibiotics during three different early-life time windows (<6 months, 6-14 months, 15-23 months), and indices of body mass at five time points (6 weeks, 10 months, 20 months, 38 months and 7 years). RESULTS:Antibiotic exposure during the earliest time window (<6 months) was consistently associated with increased body mass (+0.105 and +0.083 s.d. unit, increase in weight-for-length Z-scores at 10 and 20 months, P<0.001 and P=0.001, respectively; body mass index (BMI) Z-score at 38 months +0.067 s.d. units, P=0.009; overweight OR 1.22 at 38 months, P=0.029) in multivariable, mixed-effect models controlling for known social and behavioral obesity risk factors. Exposure from 6 to 14 months showed no association with body mass, while exposure from 15 to 23 months was significantly associated with increased BMI Z-score at 7 years (+0.049 s.d. units, P=0.050). Exposures to non-antibiotic medications were not associated with body mass. CONCLUSIONS:Exposure to antibiotics during the first 6 months of life is associated with consistent increases in body mass from 10 to 38 months. Exposures later in infancy (6-14 months, 15-23 months) are not consistently associated with increased body mass. Although effects of early exposures are modest at the individual level, they could have substantial consequences for population health. Given the prevalence of antibiotic exposures in infants, and in light of the growing concerns about childhood obesity, further studies are needed to isolate effects and define life-course implications for body mass and cardiovascular risks.

SUBMITTER: Trasande L

PROVIDER: S-EPMC3798029 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Infant antibiotic exposures and early-life body mass.

Trasande L L Blustein J J Liu M M Corwin E E Cox L M LM Blaser M J MJ

International journal of obesity (2005) 20120821 1

<h4>Objectives</h4>To examine the associations of antibiotic exposures during the first 2 years of life and the development of body mass over the first 7 years of life.<h4>Design</h4>Longitudinal birth cohort study.<h4>Subjects</h4>A total of 11 532 children born at 2500 g in the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based study of children born in Avon, UK in 1991-1992.<h4>Measurements</h4>Exposures to antibiotics during three different early-life time windows ...[more]

PMID: 22907693

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Project description:BackgroundThe human gut microbiome harbors a collection of bacterial antimicrobial resistance genes (ARGs) known as the resistome. The factors associated with establishment of the resistome in early life are not well understood. We investigated the early-life exposures and taxonomic signatures associated with resistome development over the first year of life in a large, prospective cohort in the United States. Shotgun metagenomic sequencing was used to profile both microbial composition and ARGs in stool samples collected at 6 weeks and 1 year of age from infants enrolled in the New Hampshire Birth Cohort Study. Negative binomial regression and statistical modeling were used to examine infant factors such as sex, delivery mode, feeding method, gestational age, antibiotic exposure, and infant gut microbiome composition in relation to the diversity and relative abundance of ARGs.ResultsMetagenomic sequencing was performed on paired samples from 195 full term (at least 37 weeks' gestation) and 15 late preterm (33-36 weeks' gestation) infants. 6-week samples compared to 1-year samples had 4.37 times (95% CI: 3.54-5.39) the rate of harboring ARGs. The majority of ARGs that were at a greater relative abundance at 6 weeks (chi-squared p < 0.01) worked through the mechanism of antibiotic efflux. The overall relative abundance of the resistome was strongly correlated with Proteobacteria (Spearman correlation = 78.9%) and specifically Escherichia coli (62.2%) relative abundance in the gut microbiome. Among infant characteristics, delivery mode was most strongly associated with the diversity and relative abundance of ARGs. Infants born via cesarean delivery had a trend towards a higher risk of harboring unique ARGs [relative risk = 1.12 (95% CI: 0.97-1.29)] as well as having an increased risk for overall ARG relative abundance [relative risk = 1.43 (95% CI: 1.12-1.84)] at 1 year compared to infants born vaginally.ConclusionsOur findings suggest that the developing infant gut resistome may be alterable by early-life exposures. Establishing the extent to which infant characteristics and early-life exposures impact the resistome can ultimately lead to interventions that decrease the transmission of ARGs and thus the risk of antibiotic resistant infections.

Project description:ImportancePast studies have showed associations between antibiotic exposure and child weight outcomes. Few, however, have documented alterations to body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) trajectory milestone patterns during childhood after early-life antibiotic exposure.ObjectiveTo examine the association of antibiotic use during the first 48 months of life with BMI trajectory milestones during childhood in a large cohort of children.Design, setting, and participantsThis retrospective cohort study used electronic health record data from 26 institutions participating in the National Patient-Centered Clinical Research Network from January 1, 2009, to December 31, 2016. Participant inclusion required at least 1 valid set of same-day height and weight measurements at each of the following age periods: 0 to 5, 6 to 11, 12 to 23, 24 to 59, and 60 to 131 months (183 444 children). Data were analyzed from June 1, 2019, to June 30, 2020.ExposuresAntibiotic use at 0 to 5, 6 to 11, 12 to 23, 24 to 35, and 36 to 47 months of age.Main outcomes and measuresAge and magnitude of BMI peak and BMI rebound.ResultsOf 183 444 children in the study (mean age, 3.3 years [range, 0-10.9 years]; 95 228 [51.9%] were boys; 80 043 [43.6%] were White individuals), 78.1% received any antibiotic, 51.0% had at least 1 episode of broad-spectrum antibiotic exposure, and 65.0% had at least 1 episode of narrow-spectrum antibiotic exposure at any time before 48 months of age. Exposure to any antibiotics at 0 to 5 months of age (vs no exposure) was associated with later age (β coefficient, 0.05 months [95% CI, 0.02-0.08 months]) and higher BMI (β coefficient, 0.09 [95% CI, 0.07-0.11]) at peak. Exposure to any antibiotics at 0 to 47 months of age (vs no exposure) was associated with an earlier age (-0.60 months [95% CI, -0.81 to -0.39 months]) and higher BMI at rebound (β coefficient, 0.02 [95% CI, 0.01-0.03]). These associations were strongest for children with at least 4 episodes of antibiotic exposure. Effect estimates for associations with age at BMI rebound were larger for those exposed to antibiotics at 24 to 35 months of age (β coefficient, -0.63 [95% CI, -0.83 to -0.43] months) or 36 to 47 (β coefficient, -0.52 [95% CI, -0.72 to -0.31] months) than for those exposed at 0 to 5 months of age (β coefficient, 0.26 [95% CI, 0.01-0.51] months) or 6 to 11 (β coefficient, 0.00 [95% CI, -0.20 to 0.20] months).Conclusions and relevanceIn this cohort study, antibiotic exposure was associated with statistically significant, but small, differences in BMI trajectory milestones in infancy and early childhood. The small risk of an altered BMI trajectory milestone pattern associated with early-life antibiotic exposure is unlikely to be a key factor during prescription decisions for children.

Project description:BackgroundFew studies have examined the independent and combined relationships of body mass index (BMI) peak and rebound with adiposity, insulin resistance and metabolic risk later in life. We used data from Project Viva, a well-characterized birth cohort from Boston with repeated measures of BMI, to help fill this gap.MethodsAmong 1681 children with BMI data from birth to mid childhood, we fitted individual BMI trajectories using mixed-effects models with natural cubic splines and estimated age, and magnitude of BMI, at peak (in infancy) and rebound (in early childhood). We obtained cardiometabolic measures of the children in early adolescence (median 12.9 years) and analysed their associations with the BMI parameters.ResultsAfter adjusting for potential confounders, age and magnitude at infancy BMI peak were associated with greater adolescent adiposity, and earlier adiposity rebound was strongly associated with greater adiposity, insulin resistance and metabolic risk score independently of BMI peak. Children with a normal timing of BMI peak plus early rebound had an adverse cardiometabolic profile, characterized by higher fat mass index {β 2.2 kg/m2 [95% confidence interval (CI) 1.6, 2.9]}, trunk fat mass index [1.1 kg/m2 (0.8, 1.5)], insulin resistance [0.2 units (0.04, 0.4)] and metabolic risk score [0.4 units (0.2, 0.5)] compared with children with a normal BMI peak and a normal rebound pattern. Children without a BMI peak (no decline in BMI after the rise in infancy) also had adverse adolescent metabolic profiles.ConclusionsEarly age at BMI rebound is a strong risk factor for cardiometabolic risk, independent of BMI peak. Children with a normal peak-early rebound pattern, or without any BMI decline following infancy, are at greatest risk of adverse cardiometabolic profile in adolescence. Routine monitoring of BMI may help to identify children who are at greatest risk of developing an adverse cardiometabolic profile in later life and who may be targeted for preventive interventions.

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Infant antibiotic exposures and early-life body mass.

Publications

Infant antibiotic exposures and early-life body mass.

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