Early skin inflammatory biomarker is predictive of development and persistence of atopic dermatitis in infants.

BACKGROUND: The Short-Term Topical Application for Prevention of Atopic Dermatitis (STOP AD) study, a randomized, open-label trial evaluating the effect of short-term (from the first 4 postnatal days to age 8 weeks) skin barrier protection using Aveeno Dermexa Fast & Long-Lasting Balm (Johnson & Johnson, New Brunswick, NJ) in infants with a parent with allergic disease, demonstrated decreased cumulative incidence and decreased prevalence of atopic dermatitis (AD) at age 12 months. OBJECTIVE: In the STOP AD study, we aimed to identify skin biomarkers that are associated with risk of development of AD. METHODS: Skin swabs were collected from the cheek and antecubital fossa (AF) at baseline, age 8 weeks, and age 12 months from subsets of study participants from the intervention arm (n = 43 of 119) and control arm (n = 43 of 138) and were analyzed for specific cytokines (CCL27, CXCL2, human ß-defensin-1 [hBD-1], IL-18, IL-8, IL-1α, IL-1 receptor antagonist [IL-1RA], IL-1ß, S100A8/9, and IL-36γ) by ELISA. RESULTS: Higher titers of S100A8/9 at the AF at age 8 weeks in infants with the filaggrin wild-type genotype (FLGwt), but not in those with filaggrin loss-of-function mutation (FLGmut), predicted (1) development of AD in the first year of life (P = .033), (2) presence of AD at ages 6 or 12 months (P = .009 and .035, respectively), (3) persistence of AD between ages 6 and 12 months (P < .001), and (4) development of AD with the emollient intervention. CONCLUSION: Increased titers of S100A8/9 from skin swabs of the AF in high-risk infants at age 8 weeks with FLGwt were predictive of AD development in the first year of life and other AD features. These findings suggest that there are different molecular pathways leading to AD in individuals with FLGmut and in individuals with FLGwt. Early identification of infants who are likely to develop AD will allow more targeted interventions.

Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood: An individual participant data meta-analysis.

BACKGROUND: Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. METHODS AND FINDINGS: We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. CONCLUSIONS: In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.

Cord blood leptin and gains in body weight and fat mass during infancy.

OBJECTIVES: Low early-life leptin concentrations may promote faster weight gain in infancy. We aimed to examine the associations between cord blood leptin concentrations and changes in weight and body composition during infancy. DESIGN AND METHODS: Serum leptin was measured at 15 weeks gestation, in umbilical cord blood collected at delivery and at 2 years in 334 children from the Cork Baseline Birth Cohort Study. Body composition was measured at 2 days and 2 months using air displacement plethysmography. Conditional change in weight standard deviation scores over a number of age intervals in the first 2 years and conditional change in fat mass index (FMI) and fat-free mass index (FFMI) (kg/(length)m(2)) between birth and 2 months were calculated and associations with cord blood leptin were examined using linear regression. RESULTS: At birth, cord blood leptin was positively correlated with FMI (r = 0.48, P < 0.001) and showed a weaker correlation with FFMI (r = 0.12, P = 0.05). After adjustment for confounders, higher cord blood leptin (per ng/mL) was associated with slower conditional weight gain between birth and 2 months (ß (95% CI): -0.024 (-0.035, -0.013), P < 0.001) but not over subsequent age intervals. Cord blood leptin was also inversely associated with conditional change in FMI (-0.021 (-0.034, -0.007, P = 0.003) but not FFMI between birth and 2 months. CONCLUSIONS: These are the first data to show that associations between higher cord blood leptin and slower weight gain during infancy are driven by lower increases in adiposity, at least in early infancy.

Neonatal adiposity increases the risk of atopic dermatitis during the first year of life.

BACKGROUND: Early nutrition and adiposity have been linked to atopic dermatitis (AD) development. OBJECTIVE: We sought to describe risk factors for AD in the first year of life in infants participating in the Cork BASELINE birth cohort study (n = 1537). METHODS: Prospective data on early-life events, infant feeding, and nutritional and environmental exposures were collected at 15 weeks' gestation, birth, and 2, 6, and 12 months of age. Body composition was assessed by using air displacement plethysmography at day 2 and 2 months. The primary outcome, persistent AD, was determined if the U.K. Working Party Diagnostic Criteria were satisfied at both 6 and 12 months. RESULTS: At 6 and 12 months, the point prevalence of AD was 14.2% (99% CI, 10.5% to 17.8%) and 13.7% (99% CI, 10.3% to 17.6%), respectively; 7.5% (99% CI, 5.0% to 9.9%) of infants had AD at both 6 and 12 months of age. At hospital discharge, 35% of infants were exclusively breast-fed, decreasing to 14% by 2 months. Complementary feeding was commenced at a median of 19 weeks (interquartile range, 17-22 weeks; 19% at <17 weeks and 6% at ≥26 weeks). Median fat mass at day 2 was 0.35 kg (interquartile range, 0.25-0.48 kg). A parental history of atopic disease was self-reported by 43% of mothers and 34% of fathers. Risk factors for AD at 6 and 12 months were maternal atopy (adjusted odds ratio, 2.99; 99% CI, 1.35-6.59; P = .0004) and fat mass of the 80th percentile or greater at day 2 (adjusted odds ratio, 2.31; 99% CI, 1.02-2.25; P = .009). CONCLUSION: This is the first report of neonatal adiposity as a predictor of AD at 6 and 12 months of age in a well-characterized atopic disease-specific birth cohort.