BACKGROUND: Obesity and diabetes are highly prevalent among pregnant women in the United States. No study has examined the independent and combined effects of maternal prepregnancy obesity and maternal diabetes on the risk of autism spectrum disorder (ASD) in parallel with other developmental disorders (DDs).

Food allergy (FA) affects 2–10% of U.S. children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk, and egg) in 2,759 U.S. participants (1,315 children; 1,444 parents) from the Chicago Food Allergy Study; and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (p=5.5×10−8) and rs9275596 (p=6.8×10−10), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (p<5×10−8); and differential DNA methylation of the HLA-DQB1 and HLA-DRB1 genes partially mediate the identified SNP-PA associations. This study suggests that the HLA-DR and -DQ gene region likely poses significant genetic risk for PA.

Importance Although previous reports have linked preterm birth with insulin resistance in children and adults, it is not known whether altered insulin homeostasis is detectable at birth and tracks from birth onwards. Objective To investigate whether preterm birth is associated with elevated plasma insulin levels at birth and whether this association persists into early childhood. Design, Setting, and Participation A prospective birth cohort of 1358 children recruited at birth from 1998 to 2010 and followed prospectively from 2005 to 2012 at the Boston Medical Center, Boston, MA. Main Outcome Measures Random plasma insulin levels were measured at two time points: at birth (cord blood) and in early childhood (venous blood) (median age (25th–75th percentile): 1.4 (0.8–3.3) years) among four gestational age groups: term (≥37 weeks), and further grouped into full term (≥39 weeks) and early term (37–38 weeks); preterm (<37 weeks), and further grouped into late preterm (34–36 weeks) and early preterm (<34 weeks). Results The geometric mean (95% confidence interval(CI)) of insulin levels for full term, early term, late preterm and early preterm births was 9.2(8.4–10.0), 10.3(9.3–11.5), 13.2(11.8–14.8) and 18.9(16.6–21.4) µU/ml, respectively at birth, and 11.2(10.3–12.0), 12.4(11.3–13.6), 13.3(11.9–14.8) and 14.6(12.6–16.9) µU/ml, respectively in early childhood. At birth, insulin levels were 1.13(95% CI: 0.97–1.28), 1.45(95%CI: 1.25–1.65) and 2.05(95%CI: 1.69–2.42) folds higher for early term, late preterm and early preterm, respectively, than those born full term. In early childhood, plasma random insulin levels in those born early term, late preterm and early preterm were 1.12(95%CI: 0.99–1.25), 1.19(95%CI: 1.02–1.35), and 1.31(95%CI: 1.10–1.52) folds higher, respectively, than those born full term. The association was attenuated after adjustment for postnatal weight gain and was not significant after adjustment for insulin levels at birth. Children ranked in the top insulin tertile at birth were more likely to remain in the top tertile in early childhood relative to children ranked in the lowest tertile (41.2% vs. 28.6%). Conclusion and Relevance There was an inverse association between gestational age and elevated plasma insulin levels at birth and in early childhood. The implications for future development of insulin resistance and type 2 diabetes warrant further investigation.