Background: To examine the prospective association between multivitamin supplementation during pregnancy and biomarker measures of maternal plasma folate and vitamin B 12 levels at birth and child's Autism Spectrum Disorder (ASD) risk. Methods: This report included 1257 mother-child pairs, who were recruited at birth and prospectively followed through childhood at the Boston Medical Center. ASD was defined from diagnostic codes in electronic medical records. Maternal multivitamin supplementation was assessed via questionnaire interview; maternal plasma folate and B 12 were measured from samples taken 2-3 days after birth. Results: Moderate (3-5 times/week) self-reported supplementation during pregnancy was associated with decreased risk of ASD, consistent with previous findings. Using this as the reference group, low (≤2 times/week) and high (>5 times/week) supplementation was associated with increased risk of ASD. Very high levels of maternal plasma folate at birth (≥60.3 nmol/L) had 2.5 times increased risk of ASD [95% confidence interval (CI) 1.3, 4.6] compared to folate levels in the middle 80th percentile, after adjusting for covariates including MTHFR genotype. Similarly, very high B 12 (≥536.8 pmol/L) showed 2.5 times increased risk (95% CI 1.4, 4.5). Conclusion: There was a 'U shaped' relationship between maternal multivitamin supplementation frequency and ASD risk. Extremely high maternal plasma folate and B 12 levels at birth were associated with ASD risk. This hypothesis-generating study does not question the importance of consuming adequate folic acid and vitamin B 12 during pregnancy; rather, raises new questions about the impact of extremely elevated levels of plasma folate and B 12 exposure in-utero on early brain development.

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.

Prior studies have raised concern about maternal acetaminophen use during pregnancy and increased risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in their children; however, most studies have relied on maternal self-report.OBJECTIVE To examine the prospective associations between cord plasma acetaminophen metabolites and physician-diagnosed ADHD, ASD, both ADHD and ASD, and developmental disabilities (DDs) in childhood. DESIGN, SETTING, AND PARTICIPANTSThis prospective cohort study analyzed 996 mother-infant dyads, a subset of the Boston Birth Cohort, who were enrolled at birth and followed up prospectively at the Boston Medical Center from October 1, 1998, to June 30, 2018.EXPOSURES Three cord acetaminophen metabolites (unchanged acetaminophen, acetaminophen glucuronide, and 3-[N-acetyl-L-cystein-S-yl]-acetaminophen) were measured in archived cord plasma samples collected at birth. MAIN OUTCOMES AND MEASURESPhysician-diagnosed ADHD, ASD, and other DDs as documented in the child's medical records. RESULTSOf 996 participants (mean [SD] age, 9.8 [3.9] years; 548 [55.0%] male), the final sample included 257 children (25.8%) with ADHD only, 66 (6.6%) with ASD only, 42 (4.2%) with both ADHD and ASD, 304 (30.5%) with other DDs, and 327 (32.8%) who were neurotypical. Unchanged acetaminophen levels were detectable in all cord plasma samples. Compared with being in the first tertile, being in the second and third tertiles of cord acetaminophen burden was associated with higher odds of ADHD diagnosis (odds ratio [OR] for second tertile, 2.26; 95% CI, 1.40-3.69; OR for third tertile, 2.86; 95% CI, 1.77-4.67) and ASD diagnosis (OR for second tertile, 2.14; 95% CI, 0.93-5.13; OR for third tertile, 3.62; 95% CI, 1.62-8.60). Sensitivity analyses and subgroup analyses found consistent associations between acetaminophen buden and ADHD and acetaminophen burden and ASD across strata of potential confounders, including maternal indication, substance use, preterm birth, and child age and sex, for which point estimates for the ORs vary from 2.3 to 3.5 for ADHD and 1.6 to 4.1 for ASD. CONCLUSIONS AND RELEVANCECord biomarkers of fetal exposure to acetaminophen were associated with significantly increased risk of childhood ADHD and ASD in a dose-response fashion. Our findings support previous studies regarding the association between prenatal and perinatal acetaminophen exposure and childhood neurodevelopmental risk and warrant additional investigations.