Impact of maternal pre-pregnancy overweight on infant overweight at 1 year of age: associations and sex-specific differences.

BACKGROUND: Maternal overweight or obesity (OWOB) is linked to gestational diabetes, fetal macrosomia and higher rates of caesarean delivery. OBJECTIVES: The study aims to assess whether maternal pre-pregnancy OWOB is associated with infant overweight in a sex-dependent manner, independent of microbiota-altering variables. METHODS: Weight and length measurements of 955 mother-infant pairs were obtained from the Canadian Healthy Infant Longitudinal Development cohort. Maternal pre-pregnancy weight was defined as follows: normal, overweight (25 ≤ body mass index < 30) and obese (body mass index ≥ 30). Age and sex-adjusted weight-for-length z-scores >97th percentile were classified as infant overweight at age 1 year. Associations between pre-pregnancy and infant overweight were determined by linear and logistic regression, adjusting for covariates. RESULTS: Maternal pre-pregnancy OWOB were associated with infant weight-for-length and overweight risk at 1 year. Except for pre-pregnancy obesity, these associations were not attenuated appreciably after adjustment for birth mode, exclusivity of breastfeeding, exposure to antibiotics and infant sex. Yet only boys born to mothers with obesity were three times more likely to become overweight at age 1 independent of microbiota-altering variables. Pre-pregnancy obesity was associated with weight-for-length in male and female infants. CONCLUSIONS: Maternal pre-pregnancy OWOB increases the risk of infant overweight, and this association is more evident in male infants.

Infant gut immunity: a preliminary study of IgA associations with breastfeeding.

Secretory immunoglobulin A (IgA) plays a critical role in gut mucosal immune defense. Initially provided by breastmilk, IgA production by the infant gut is gradually stimulated by developing gut microbiota. This study reports associations between infant fecal IgA concentrations 4 months after birth, breastfeeding status and other pre/postnatal exposures in 47 infants in the Canadian Healthy Infant Longitudinal Development cohort. Breastfed infants and first-born infants had higher median fecal IgA concentrations (23.11 v. 9.34 µg/g protein, P<0.01 and 22.19 v. 8.23 µg/g protein, P=0.04). IgA levels increased successively with exclusivity of breastfeeding (ß-coefficient, 0.37, P<0.05). This statistical association was independent of maternal parity and household pets. In the absence of breastfeeding, female sex and pet exposure elevated fecal IgA to levels found in breastfed infants. In addition to breastfeeding, infant fecal IgA associations with pre/postnatal exposures may affect gut immunity and risk of allergic disease.

Fetal programming of overweight through the microbiome: boys are disproportionately affected.

Maternal and childhood obesity in pregnancy are worrisome public health issues facing our world today. New gene sequencing methods have advanced our knowledge of the disruptive effect of birth interventions and postnatal exposures on the maturation of gut microbiota and immunity during infancy. Yet, little is known about the impact of maternal pregnancy overweight on gut microbes and related processes, and how this may affect overweight risk in offspring. To address this gap in knowledge, we surveyed human studies for evidence in children, infants and pregnant women to piece together the limited literature and generate hypotheses for future investigation. From this literature, we learned that higher Lactobacillus yet lower Bacteroides spp. colonization of gut microbiota within 3 months of birth predicted risk for infant and child overweight. The abundance of bifidobacteria and staphylococci also appeared to play a role in the association with overweight, as did infant fecal immunoglobulin A levels, glycoproteins of the gut immune system that are acquired from breast milk and produced by the infant. We proposed that pregnancy overweight influences the compositional structure of gut microbiota in infants through vertical transfer of microbiota and/or their metabolites during pregnancy, delivery and breastfeeding. Finally, we brought forward emerging evidence on sex dimorphism, as well as ethnic and geographic variation, in reported associations between maternal overweight-induced gut microbiota dysbiosis and overweight risk.

Infant antibiotic exposure and the development of childhood overweight and central adiposity.

BACKGROUND: Obesity has been associated with disruption of the gut microbiota, which is established during infancy and vulnerable to disruption by antibiotics. OBJECTIVES: To investigate the association between early-life antibiotic exposure and subsequent development of overweight and central adiposity. METHODS: Provincial health-care records were linked to clinical and survey data from a Canadian longitudinal birth cohort study. Antibiotic exposure during the first year of life was documented from prescription records. Overweight and central adiposity were determined from anthropometric measurements at ages 9 (n=616) and 12 (n=431). Associations were determined by multiple logistic regression. RESULTS: Infants receiving antibiotics in the first year of life were more likely to be overweight later in childhood compared with those who were unexposed (32.4 versus 18.2% at age 12, P=0.002). Following adjustment for birth weight, breastfeeding, maternal overweight and other potential confounders, this association persisted in boys (aOR 5.35, 95% confidence interval (CI) 1.94-14.72) but not in girls (aOR 1.13, CI 0.46-2.81). Similar gender-specific associations were found for overweight at age 9 (aOR 2.19, CI 1.06-4.54 for boys; aOR 1.20, CI 0.53-2.70 for girls) and for high central adiposity at age 12 (aOR 2.85, CI 1.24-6.51 for boys; aOR 1.59, CI 0.68-3.68 for girls). CONCLUSIONS: Among boys, antibiotic exposure during the first year of life was associated with an increased risk of overweight and central adiposity in preadolescence, indicating that antibiotic stewardship is particularly important during infancy. Given the current epidemic of childhood obesity and the high prevalence of infant antibiotic exposure, further studies are necessary to determine the mechanisms underlying this association, to identify the long-term health consequences, and to develop strategies for mitigating these effects when antibiotic exposure cannot be avoided.