Neonatal Thyroid Hormone Levels in Association with Autism Spectrum Disorder
Thyroid hormones (TH) are critical in early neurodevelopment, but whether neonatal TH levels influence risk of autism spectrum disorder (ASD) is not well-researched.
The goal of this study was to examine whether neonatal levels of thyroxine (T4) and thyroid-stimulating hormone (TSH) are related to risk of ASD, using existing data from California state-wide programs.
Program data from California neonatal screening in 1996 and 2002 were linked with live birth certificates and Department of Developmental Services records in order to examine TH levels in association with ASD (defined as ever receiving services for ASD by 2014). T4 and TSH levels were measured in newborn bloodspots as part of routine screening. Mean levels of T4 (measured in 1996) and raw and log-transformed TSH (measured in 2002) were compared between ASD cases and the general population of births from the same years. Binomial regression, using categories of T4 and TSH percentiles separately by year, was used to obtain crude and adjusted risk ratios (RR), adjusting for maternal age, race, education, parity, and child gestational age and gender as well as hours until specimen draw. In addition, a number of stratified analyses were conducted to examine potential effect modification.
447,059 singleton births from 1996 and 446,424 from 2002 were used in these analyses, including 4,818 ASD cases. ASD cases had significantly lower mean levels of T4 than those of comparison births. Individuals in the lowest 5th percentile of T4 levels (<9.3ug/dl) had modestly increased risk of ASD, an association that was no longer significant in primary adjusted analyses (RR 1.13, 95% 0.93-1.37). This association appeared stronger in certain subgroup analyses, including those with advanced maternal age (≥35 years; RR 1.43, 95% CI 0.96, 2.12), those with Cesarean deliveries (RR= 1.35, 95% CI 0.94, 1.94), and in particular, those with blood drawn ≥24 hours after birth (RR=1.46, 95% CI 1.11, 1.91), after which TH levels become more stable. No significant associations were found with TSH levels and ASD in primary crude or adjusted analyses, though a significant reduction in risk was seen for those in the highest percentile (≥95thpercentile, corresponding to ≥1.05 log-transformed concentration) of TSH for those with Cesarean deliveries (RR=0.56, 95% CI 0.32, 0.96). No other subgroups demonstrated significant associations with TSH levels and ASD.
Results from this large, population-based study did not suggest strong associations between neonatal TH and ASD, but individuals with the lowest T4 levels may have modest increases in risk of ASD.