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 11532 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.

MECHANISMS IN ENDOCRINOLOGY: Gut microbiota in patients with type 2 diabetes mellitus

“…It has been speculated that the introduction of antibiotics in the early twentieth century may have contributed to the obesity epidemic and epidemiological studies have supported this notion as they have demonstrated that exposure to antibiotics in early childhood increases the risk of overweight in later childhood (52,53,54,55). Compared with children of normal-weight mothers not receiving antibiotics, the risk of overweight at age 7 years was increased by 1.5-fold among children receiving antibiotics during the first 6 months of life and born to normal-weight mothers (52).…”

“…For comparison, the risk of overweight was increased by twofold among children not receiving antibiotics but born to overweight mothers (52). A later study reported a 1.2-fold increased risk of obesity at 38 months of age among children receiving antibiotics before 6 months of age (55). Correspondingly, a recently published study of w64 000 children has reported a 1.1-fold increased risk of obesity at age 2-5 years among children receiving antibiotics four or more times during their first 2 years of life, but, interestingly, no association was observed between narrow-spectrum antibiotics and obesity (53).…”

Changes in weight and body fat after use of tetracycline and Lactobacillus gasseri in rats

“…Cho used a different methodology and showed that giving animals antibiotics increased their body fat, despite not finding differences in weight (Cho et al, 2012). There is ample evidence showing that the use of antibiotics may be causing weight gain in humans, especially when administered to children (Perrini, 1951;Macdougall, 1957;Garly et al, 2006;Southern et al, 2012;Trasande et al, 2013). This adverse effect should not limit the use of antibiotics.…”

“…Although relatively stable, the gut microbiota is affected by age, gender, geography, diet, and environmental factors, such as exposure to antibiotics, especially in children and newborns (Backhed et al, 2005;Agans et al, 2011;Vael et al, 2011;Grzeskowiak et al, 2012;Markle et al, 2013;Trasande et al, 2013). There are numerous studies related to gut microbiota changes (dysbiosis) caused by antibiotics and probiotics, including weight modifications in humans and animals (Ley et al, 2006;Turnbaugh et al, 2008;Xu et al, 2012;Bibiloni, Pons, Tur, 2013).…”

“…Studies show that increases in body weight caused by microbial antibiotics is becoming more frequent, particularly when the antibiotic has a broad spectrum of activity. Alternatively, the use of probiotics has been associated with weight loss and could presumably protect against the effect caused by antibiotics in the microbiota (Haight, Pierce, 1955;Saiman et al, 2010;Thuny et al, 2010;Saiman et al, 2012;Trasande et al, 2013).…”