Association of Repeated Antibiotic Exposure Up to Age 4 Years With Body Mass at Age 4.5 Years.
ABSTRACT: Importance:Antibiotic exposures in early life may affect weight by altering gut microbiota, potentially increasing the likelihood of childhood obesity. Objective:To examine whether repeated antibiotic exposure by age 48 months is associated with higher body mass index (BMI) at age 54 months. Design, Setting, and Participants:This research was undertaken within a prospective cohort study in New Zealand (Growing Up in New Zealand) that recruited 6853 children antenatally during 2009 to 2010. At the 54-month follow-up, 5734 of 6156 children (93%) had their weight and height measured. Community pharmacy antibiotic dispensing data were obtained from the New Zealand Pharmaceutical Collection database for children whose parents consented to external data linkage. The analytic sample comprised singletons with 54-month weight and height measurements, community antibiotic dispensing and birth weight data, gestational age greater than 27 weeks, and no congenital anomalies. Data analysis took place from 2017 to 2018. Exposures:Antibiotic exposure (yes or no), the number of dispensings, age at first exposure, and timing (age) of exposures between birth and age 48 months. Main Outcomes and Measures:World Health Organization BMI-for-age z scores; and International Obesity Task Force overweight and obesity cutoff points that pass through adult BMI values of 25 and 30. Results:Of the 5128 singletons (2622 [51%] male; mean [SD] birth weight of 3527  g), 4886 (95%) had an antibiotic prescription by age 48 months and 437 (9%) had obesity at age 54 months. Adjusted mean (SE) BMI-for-age z scores increased significantly with the number of antibiotic dispensings for 4 to 6, 7 to 9, and more than 9 dispensings (unexposed, 0.87 [0.09]; 1-3 exposures, 0.92 [0.06] [P?=?.57]; 4-6 exposures, 1.06 [0.06] [P?=?.02]; 7-9 exposures, 1.06 [0.06] [P?=?.02]; >9 exposures, 1.08 [0.05] [P?=?.01]). Additionally, receiving more than 9 dispensings was associated with greater likelihood of obesity compared with no exposure (adjusted odds ratio, 2.41; 95% CI, 1.07-5.41). Children whose exposure began in the first year of life had a higher adjusted mean (SD) BMI-for-age z score than those not exposed (1.06 [0.05] vs 0.89 [0.09]; P?=?.03), whereas those whose exposure commenced after the first year of life did not (1.02 [0.06] vs 0.89 [0.09]; P?=?.10). Conclusions and Relevance:In this study, repeated antibiotic exposure in early childhood was associated with higher mean BMI-for-age z score and an increased likelihood of obesity. Future research could examine whether interventions such as antibiotic stewardship programs, which are designed to reduce overprescribing of antibiotics, also reduce early childhood obesity.
Project description:Background:It has been hypothesized that antibiotic usage in early life could contribute to development of overweight in childhood. Studies have seen association between antibiotic usage and overweight in childhood. We aimed to investigate the relationship between antibiotic exposure in infancy and development of body mass index (BMI) and body composition. Methods:A prospective mother-child cohort study of 738 pregnant women and their 700 children, Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010). Information on antibiotic exposure was collected by interviews. Height/length and weight measures were collected at age 1, 2, 3, 4, 5 and 6 years and body composition was determined by a dual-energy X-ray absorptiometry (DXA) scan at age 3.5 and 6 years. Findings:306 (46%) of the 661 children were exposed to antibiotics before 1 year of age. There were no differences in BMI z-score development at age 1-6 years between children exposed to antibiotics compared to unexposed: z-score difference, -0.06 (95%CI: -0.17;0.06), p?=?0.33, and no sex-differences (p-interaction?=?0.48). Children exposed vs. not exposed to antibiotics had comparable fat percentage at 6 years of age: log(mean difference), 0.60% (95%CI: -0.212 to 1.41), p?=?0.15. Interpretation:Children exposed to antibiotics had similar BMI, BMI z-score and body composition between 1 and 6 years of life compared to unexposed children. Our study does not support the hypothesis that antibiotic exposure in infancy leads to development of obesity in the first 6 years of life. Funding:The Lundbeck Foundation, The Ministry of Health, Danish Council for Strategic Research and The Capital Region Research Foundation.
Project description: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.
Project description:Evidence suggests that childhood near-roadway air pollution (NRAP) exposures contribute to increased body mass index (BMI); however, effects of NRAP exposure during the vulnerable periods including in utero and first year of life have yet to be established. In this study, we examined whether exposure to elevated concentrations of NRAP during in utero and/or first year of life increase childhood BMI growth.Participants in the Children's Health Study enrolled from 2002 to 2003 with annual visits over a four-year period and who changed residences before study entry were included (n?=?2318). Annual height and weight were measured and lifetime residential NRAP exposures including in utero and first year of life periods were estimated by nitrogen oxides (NOx) using the California line-source dispersion model. Linear mixed effects models assessed in utero or first year near-road freeway and non-freeway NOx exposures and BMI growth after adjusting for age, sex, race/ethnicity, parental education, Spanish questionnaire, and later childhood near-road NOx exposure.A two-standard deviation difference in first year of life near-road freeway NOx exposure was associated with a 0.1 kg/m2 (95% confidence interval (CI): 0.03, 0.2) faster increase in BMI growth per year and a 0.5 kg/m2 (95% CI: 0.02, 0.9) higher attained BMI at age 10 years.Higher exposure to early life NRAP increased the rate of change of childhood BMI and resulted in a higher attained BMI at age 10 years that were independent of later childhood exposures. These findings suggest that elevated early life NRAP exposures contribute to increased obesity risk in children.
Project description:Childhood obesity is increasing and is associated with adult obesity. Antibiotics have been used to promote weight gain in livestock for several decades. Antibiotics are commonly prescribed for children, but it is not clear how exposure to antibiotics early in life affects risk for obesity. We performed a population-based cohort study to assess the association between antibiotic exposure before age 2 years and obesity at age 4 years.We performed a retrospective cohort study of 21,714 children in The Health Improvement Network-a population-representative dataset of >10 million individuals derived from electronic medical records from 1995 through 2013 in the United Kingdom. Eligible subjects were registered within 3 months of birth with complete follow-up and height and weight were recorded within 12 months of their 4th birthday. Antibiotic exposure was assessed before age 2 years, and classified based on anti-anaerobic activity. The primary outcome was obesity at age 4 years. We performed logistic regression analyses, adjusting for maternal and sibling obesity, maternal diabetes, mode of delivery, socioeconomic status, year and country of birth, and urban dwelling.In the cohort, 1306 of the children (6.4%) were obese at 4 years of age. Antibiotic exposure was associated with an increased risk of obesity at 4 years (odds ratio [OR] = 1.21; 95% confidence interval [CI]: 1.07-1.38). ORs increased with repeated exposures: for 1-2 prescriptions, OR = 1.07 (95% CI, 0.91-1.23); for 3-5 prescriptions, OR = 1.41 (95% CI, 1.20-1.65); and for 6 or more prescriptions, OR = 1.47 (95% CI, 1.19-1.82). Antifungal agents were not associated with obesity (OR = 0.81; 95% CI, 0.59-1.11).Administration of 3 or more courses of antibiotics before children reach an age of 2 years is associated with an increased risk of early childhood obesity.
Project description:OBJECTIVES:The potential growth-promoting effects of antibiotics are not well understood among undernourished children in environments with high pathogen exposure. We aimed to assess whether early antibiotic exposure duration and class were associated with growth to 2 years of age across 8 low-resource sites in the MAL-ED birth cohort study. METHODS:We followed 1954 children twice per week from birth to 2 years to record maternally reported antibiotic exposures and measure anthropometry monthly. We estimated the associations between antibiotic exposure before 6 months of age and weight-for-age and length-for-age (LAZ) z scores to 2 years. We assessed the impact of class-specific exposures and duration, and compared these results to effects of antibiotic exposures after 6 months of age. RESULTS:Antibiotic use before 6 months of age was associated with increased weight from 6 months to 2 years, whereas associations with length were less consistent across sites and antibiotic classes. Compared to unexposed children, 2 or more courses of metronidazole, macrolides, and cephalosporins were associated with adjusted increases in weight-for-age of 0.24 (95% confidence interval (CI): 0.04, 0.43), 0.23 (95% CI: 0.05, 0.42), and 0.19 (95% CI: 0.04, 0.35) from 6 months to 2 years, respectively. CONCLUSIONS:Antibiotic use in low-resource settings was most associated with the ponderal growth of children who had multiple exposures to antibiotics with broad spectrum and anaerobic activity in early infancy. Opportunities for rational and targeted antibiotic therapy in low resource settings may also promote short-term weight gain in children, although longer-term physical growth and metabolic impacts are unknown.
Project description:Background:Midlife women have a higher risk of cardiometabolic disease than younger women, but the lifelong biological/lifestyle factors responsible for this increase are unclear. Objectives:We investigated whether pregnancy history is a risk factor for midlife overweight/obesity and evaluated potential hormonal mechanisms. Methods:The Baltimore Midlife Women's Health Study, a prospective cohort, recruited 772 women aged 45-54 y. Women reported pregnancy characteristics via questionnaires, trained staff measured weight/height to calculate midlife BMI, and serum hormones were assessed by ELISA. Logistic regression models assessed associations of pregnancy history with risk of midlife overweight/obesity and BMI gain since age 18. We additionally explored whether associations differed by menopausal status, and whether midlife hormones mediated relationships of pregnancy history and midlife BMI. Results:These premenopausal or perimenopausal women were 66% Caucasian/White and 30% African American/Black, with a median of 2 live births (range: 0-11) and median age at first birth of 27 y (range: 12-46 y). Women with 0 and ?2 live births had lower odds of overweight/obesity than those with 1 birth (OR = 0.47; 95% CI: 0.23, 0.96; P = 0.04, and OR = 0.58; 95% CI: 0.35, 0.95; P = 0.03, respectively). Women with ?2 live births also had lower odds of BMI gain than those with 1 birth (OR = 0.66; 95% CI: 0.41, 1.06; P = 0.08). Furthermore, women who were older at their first birth had lower odds of overweight/obesity (OR = 0.96; 95% CI: 0.92, 1.00; P = 0.03) and BMI gain (OR = 0.97; 95% CI: 0.93, 1.00; P = 0.06). Number of pregnancies and age at last pregnancy were not associated with midlife overweight/obesity or BMI gain. Associations did not differ by menopausal status and were not explained by midlife hormones. Conclusions:Earlier childbirth and having 1 child increased women's risk of midlife overweight/obesity and BMI gain since age 18. Additional studies should focus on women's childbearing years as a critical determinant of midlife metabolic health.
Project description:Importance:Describing potential mortality risk reduction associated with weight loss between early adulthood and midlife is important for informing primary and secondary prevention efforts for obesity. Objective:To examine the risk of all-cause mortality among adults who lost weight between early adulthood and midlife compared with adults who were persistently obese over the same period. Design, Setting, and Participants:Combined repeated cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey III (1988-1994) and continuous waves collected in 2-year cycles between 1999 and 2014. The data analysis was conducted from February 10, 2019, to April 20, 2020. Individuals aged 40 to 74 years at the time of survey (baseline) were included in the analyses (n?=?24 205). Exposures:Weight history was assessed by self-reported weight at age 25 years, at 10 years before baseline (midlife: mean age, 44 years; interquartile range, 37-55), and measured weight at baseline. Body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) at each time was categorized as normal (18.5-24.9), overweight (25.0-29.9), and obese (?30.0). Weight change patterns were assessed from age 25 years (early adulthood) to 10 years before baseline (midlife). Main Outcomes and Measures:Incident all-cause mortality using linked data from the National Death Index. Results:Of the 24?205 participants, 11?617 were women (49.0%) and 11?567 were non-Hispanic White (76.9%). The mean (SD) BMI was 29.0 (6.1) at baseline. During a mean (SD) follow-up of 10.7 (7.2) years, 5846 deaths occurred. Weight loss from obese to overweight was associated with a 54% (hazard ratio, 0.46; 95% CI, 0.27-0.77) reduction in mortality risk compared with individuals with stable obesity between early adulthood and midlife. An estimated 3.2% (95% CI, 1.6%-4.9%) of early deaths could have been avoided if those who maintained an obese BMI instead lost weight to an overweight BMI by midlife. Overall, an estimated 12.4% (95% CI, 8.1%-16.5%) of early deaths may be attributable to having weight in excess of the normal BMI range at any point between early and mid-adulthood. Conclusions and Relevance:In this study, weight loss from obesity to overweight between early adulthood through midlife appeared to be associated with a mortality risk reduction compared with persistent obesity. These findings support the importance of population-based approaches to preventing weight gain across the life course and a need for greater emphasis on treating obesity early in life.
Project description:PURPOSE:Previous epidemiologic studies have shown that smoking, obesity, and physical inactivity are associated with poor survival following a diagnosis of ovarian cancer. Yet, the combined relationship of these unfavorable lifestyle factors on ovarian cancer survival has not been sufficiently investigated. METHODS:Using data pooled from 13 studies, we examined the associations between combined exposures to smoking, overweight/obesity weight, and physical inactivity and overall survival (OS) as well as progression-free survival (PFS) among women diagnosed with invasive epithelial ovarian carcinoma (n?=?7,022). Using age- and stage-adjusted Cox proportional hazards regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) associated with joint exposure to these factors. RESULTS:Combined exposure to current smoking, overweight/obesity, and physical inactivity prior to diagnosis was associated with a significantly increased risk of mortality compared to women who never smoked, had normal body mass index (BMI), and were physically active (HR?=?1.37; 95% CI 1.10-1.70). The association for a joint exposure to these factors exceeded that of each exposure individually. In fact, exposure to both current smoking and overweight/obesity, and current smoking and physical inactivity was also associated with increased risk of death (HR?=?1.28; 95% CI 1.08-1.52, and HR?=?1.26; 95% CI 1.04-1.54, respectively). The associations were of a similar magnitude when former smoking was assessed in combination with the other exposures and when excessive weight was limited to obesity only. No significant associations were observed between joint exposure to any of these factors and PFS. CONCLUSIONS:Joint exposure to smoking, excessive weight, and physical inactivity may negatively impact survival of ovarian cancer patients. These results suggest the importance of examining the combined effect of lifestyle factors on ovarian cancer patients' survival.
Project description:OBJECTIVE:The benefits of antibiotic treatment during pregnancy are immediate, but there may be long-term risks to the developing child. Prior studies show an association between early life antibiotics and obesity, but few have examined this risk during pregnancy. SUBJECTS:To evaluate the association of maternal antibiotic exposure during pregnancy on childhood BMI-z at 5 years, we conducted a retrospective cohort analysis. Using electronic health record data from seven health systems in PCORnet, a national distributed clinical research network, we included children with same-day height and weight measures who could be linked to mothers with vital measurements during pregnancy. The primary independent variable was maternal outpatient antibiotic prescriptions during pregnancy (any versus none). We examined dose response (number of antibiotic episodes), spectrum and class of antibiotics, and antibiotic episodes by trimester. The primary outcome was child age- and sex-specific BMI-z at age 5 years. RESULTS:The final sample was 53,320 mother-child pairs. During pregnancy, 29.9% of mothers received antibiotics. In adjusted models, maternal outpatient antibiotic prescriptions during pregnancy were not associated with child BMI-z at age 5 years (??=?0.00, 95% CI -0.03, 0.02). When evaluating timing during pregnancy, dose-response, spectrum and class of antibiotics, there were no associations of maternal antibiotics with child BMI-z at age 5 years. CONCLUSION:In this large observational cohort, provision of antibiotics during pregnancy was not associated with childhood BMI-z at 5 years.
Project description:BACKGROUND:Chemical and nonchemical environmental exposures are increasingly suspected to influence the development of obesity, especially during early life, but studies mostly consider single exposure groups. OBJECTIVES:Our study aimed to systematically assess the association between a wide array of early-life environmental exposures and childhood obesity, using an exposome-wide approach. METHODS:The HELIX (Human Early Life Exposome) study measured child body mass index (BMI), waist circumference, skinfold thickness, and body fat mass in 1,301 children from six European birth cohorts age 6-11 y. We estimated 77 prenatal exposures and 96 childhood exposures (cross-sectionally), including indoor and outdoor air pollutants, built environment, green spaces, tobacco smoking, and biomarkers of chemical pollutants (persistent organic pollutants, metals, phthalates, phenols, and pesticides). We used an exposure-wide association study (ExWAS) to screen all exposure-outcome associations independently and used the deletion-substitution-addition (DSA) variable selection algorithm to build a final multiexposure model. RESULTS:The prevalence of overweight and obesity combined was 28.8%. Maternal smoking was the only prenatal exposure variable associated with higher child BMI (z-score increase of 0.28, 95% confidence interval: 0.09, 0.48, for active vs. no smoking). For childhood exposures, the multiexposure model identified particulate and nitrogen dioxide air pollution inside the home, urine cotinine levels indicative of secondhand smoke exposure, and residence in more densely populated areas and in areas with fewer facilities to be associated with increased child BMI. Child blood levels of copper and cesium were associated with higher BMI, and levels of organochlorine pollutants, cobalt, and molybdenum were associated with lower BMI. Similar results were found for the other adiposity outcomes. DISCUSSION:This first comprehensive and systematic analysis of many suspected environmental obesogens strengthens evidence for an association of smoking, air pollution exposure, and characteristics of the built environment with childhood obesity risk. Cross-sectional biomarker results may suffer from reverse causality bias, whereby obesity status influenced the biomarker concentration. https://doi.org/10.1289/EHP5975.