Perfluorinated alkylate substances (PFASs) are highly persistent and may cause immunotoxic effects. PFAS-associated attenuated antibody responses to childhood vaccines may be affected by PFAS exposures during infancy, where breastfeeding adds to PFAS exposures. Of 490 members of a Faroese birth cohort, 275 and 349 participated in clinical examinations and provided blood samples at ages 18 months and 5 years. PFAS concentrations were measured at birth and at the clinical examinations. Using information on duration of breastfeeding, serum-PFAS concentration profiles during infancy were estimated. As outcomes, serum concentrations of antibodies against tetanus and diphtheria vaccines were determined at age 5. Data from a previous cohort born eight years earlier were available for pooled analyses. Pre-natal exposure showed inverse associations with the antibody concentrations five years later, with decreases by up to about 20% for each two-fold higher exposure, while associations for serum concentrations at ages 18 months and 5 years were weaker. Modeling of serum-PFAS concentration showed levels for age 18 months that were similar to those measured. Concentrations estimated for ages 3 and 6 months showed the strongest inverse associations with antibody concentrations at age 5 years, particularly for tetanus. Joint analyses showed statistically significant decreases in tetanus antibody concentrations by 19–29% at age 5 for each doubling of the PFAS exposure in early infancy. These findings support the notion that the developing adaptive immune system is particularly vulnerable to immunotoxicity during infancy. This vulnerability appears to be the greatest during the first 6 months after birth, where PFAS exposures are affected by breast-feeding.

OBJECTIVE: To investigate the long-term association of exposure to perfluoroalkylated substances, including perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), during childhood (9 years) and adolescence (15 years) on indicators of adiposity and glucose metabolism in adolescence (15 years) and young adulthood (21 years). Secondarily, we aim to clarify the degree of tracking of exposure from childhood into young adulthood. RESEARCH DESIGN AND METHODS: Data derived from a large multicenter prospective cohort study, in which the same participants have been observed from childhood (N = 590), during adolescence (N = 444), and into young adulthood (N = 369). Stored plasma samples were analyzed for PFOS and PFOA. Indicators of adiposity comprising body height, body weight, sum of four skinfolds, and waist circumference, as well as indicators of glucose metabolism, comprising fasting blood glucose, triglyceride, and insulin levels, β-cell function, and insulin resistance, have been collected at all study waves. Multiple linear regression was applied in order to model earlier exposure on later outcome while controlling for baseline outcome levels, sex, age, and socioeconomic factors. RESULTS: Childhood exposure to PFOS was associated with indicators of adiposity at 15 years of age that are displayed in elevated BMI, skinfold thickness, and waist circumference, as well as increased skinfold thickness and waist circumference at 21 years of age. PFOA exposure in childhood was associated with decreased β-cell function at 15 years of age. We did not observe associations between exposure during adolescence and indicators of adiposity and glucose metabolism in young adulthood. CONCLUSIONS: This study found evidence for childhood exposure to PFOS and PFOA predicting adiposity at 15 and 21 years of age and impaired β-cell function at 15 years of age, respectively.

Objective: Our objective was to explore whether childhood exposure to perfluorinated and polyfluorinated compounds (PFCs), widely used stain- and grease-repellent chemicals, is associated with adiposity and markers of glycemic control. Materials and Methods: Body mass index, skinfold thickness, waist circumference, leptin, adiponectin, insulin, glucose, and triglyceride concentrations were assessed in 8- to 10-year-old children in 1997 in a subset of the European Youth Heart Study, Danish component. Plasma PFC concentrations were available from 499 children. Linear regression models were performed to determine the association between PFC exposure and indicators of adiposity and markers of glycemic control. Results: There was no association between PFC exposures and adiposity or markers of glycemic control in normal-weight children. Among overweight children, an increase of 10 ng perfluorooctane sulfonic acid/mL plasma was associated with 16.2% (95% confidence interval [CI], 5.2%–28.3%) higher insulin concentration, 12.0% (95% CI, 2.4%–22.4%) higher β-cell activity, 17.6% (95% CI, 5.8%–30.8%) higher insulin resistance, and 8.6% (95% CI, 1.2%–16.5%) higher triglyceride concentrations, and an increase of 10 ng perfluorooctanoic acid/mL plasma was associated with 71.6% (95% CI, 2.4%–187.5%) higher insulin concentration, 67.5% (95% CI, 5.5%–166.0%) higher β-cell function, 73.9% (95% CI, 0.2%–202.0%) higher insulin resistance, and 76.2% (95% CI, 22.8%–153.0%) higher triglyceride concentrations. Discussion: Increased PFC exposure in overweight 8- to 10-year-old children was associated with higher insulin and triglyceride concentrations. Chance findings may explain some of our results, and due to the cross-sectional design, reverse causation cannot be excluded. The findings therefore need to be confirmed in longitudinal studies.

Bacillus Calmette–Guérin (BCG) vaccine against tuberculosis (TB) is recommended at birth in TB‐endemic areas. Currently, BCG vaccination programmes use “BCG vaccination coverage by 12 months of age” as the performance indicator. Previous studies suggest that BCG‐vaccinated children, who develop a scar, have better overall survival compared with BCG‐vaccinated children, who do not develop a scar. We summarized the available studies of BCG scarring and child survival. A structured literature search for studies with original data and analysis of BCG scarring and mortality were performed. Combined analyses on the effect of BCG scarring on overall mortality. We identified six studies covering seven cohorts, all from Guinea‐Bissau, West Africa, with evaluation of BCG scarring amongst BCG‐vaccinated children and follow‐up for mortality. Determinants of BCG scarring were BCG strain, intradermal injection route, size of injection wheal, and co‐administered vaccines and micronutrients. In a combined analysis, having a BCG scar vs. no BCG scar was associated with a mortality rate ratio (MRR) of 0.61 (95% CI: 0.51–0.74). The proportion with a BCG scar varied from 52 to 93%; the estimated effect of a BCG scar was not associated with the scar prevalence. The effect was strongest in the first (MRR = 0.48 (0.37–0.62)) and second (MRR = 0.63 (0.44–0.92)) year of life, and in children BCG‐vaccinated in the neonatal period (MRR = 0.45 (0.36–0.55)). The effect was not explained by protection against TB. Confounding and genetic factors are unlikely to explain the strong association between BCG scarring and subsequent survival. Including “BCG scar prevalence” as a BCG vaccination programme performance indicator should be considered. The effect of revaccinating scar‐negative children should be studied.