Neonatal Thyroid Stimulating Hormone and Subsequent Diagnosis of Autism Spectrum Disorders and Intellectual Disability

Abstract

Hypothyroid conditions in early life, if left untreated, are associated with adverse neurodevelopmental outcomes, including intellectual disability (ID). However, evidence addressing the role of neonatal thyroid hormone insufficiencies in the altered neurobiology underlying autism spectrum disorders (ASD), particularly among its subphenotypes, is limited. We conducted a population‐based, case–control study among a sample of children born during 2000–2003 in Southern California. We examined neonatal thyroid‐stimulating hormone (TSH) measured during routine newborn screening among children later diagnosed with ASD (n = 518) or ID (n = 145) and general population (GP) controls (n = 399). TSH was further analyzed in relation to ASD subgroups of intellectual ability and onset type (early‐onset ASD vs. ASD with regression) ascertained by expert review of developmental services records. Odds ratios (ORs) of the differences in TSH between groups were obtained from multivariate logistic regression. We examined neonatal TSH as continuous (ln‐transformed) and as quartiles. We found no association between continuous neonatal TSH levels and ASD (adj‐OR: 1.00, 95% CI: 0.79–1.26) nor ID (adj‐OR = 1.01, 95% CI: 0.73–1.40). Among ASD subphenotypes, we observed a suggestive inverse trend between ASD with regression and TSH, though the association only reached statistical significance in the highest TSH quartile (adj‐OR: 0.50, 95% CI: 0.26–0.98). While there was little evidence that neonatal TSH is related to overall ASD risk, more work is needed to understand the influence of thyroid hormones on ASD subphenotypes. Autism Res 2020, 13: 444–455. © 2019 International Society for Autism Research,Wiley Periodicals, Inc. Lay Summary Low levels of thyroid hormone at birth can negatively impact brain development. We studied whether newborn levels of thyroid stimulating hormone (TSH) were associated with autism spectrum disorder (ASD) and its subtypes in a sample of children born in California. Newborn TSH was not related to the overall risk of ASD or intellectual disability. However, the relationships of thyroid hormone levels at birth and specific subtypes of ASD, particularly ASD with developmental regression, may need more research.

iTRAQ-Based Proteomics Analysis of Rat Cerebral Cortex Exposed to Valproic Acid before Delivery

“…Thyroid hormones (TH), including triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH), have been shown to play an important role in the etiology of ASD. 75 Several studies have shown that compared with healthy controls, neonates with low T4 had a moderately increased risk of ASD by 13%. TSH promotes the production of T4, and low T4 levels will feedback-regulate the increase of TSH.…”

“…Moreover, our results demonstrated that the thyroid hormone synthesis pathway was significantly enriched. Thyroid hormones (TH), including triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH), have been shown to play an important role in the etiology of ASD . Several studies have shown that compared with healthy controls, neonates with low T4 had a moderately increased risk of ASD by 13%.…”

Systematic Review and Bioinformatic Analysis of microRNA Expression in Autism Spectrum Disorder Identifies Pathways Associated With Cancer, Metabolism, Cell Signaling, and Cell Adhesion

“…Maternal thyroid disorders during pregnancy were found to be associated with an increased risk of ASD in offspring ( 123 ), and brain genes were altered ( 124 ). However, few studies have examined whether postnatal thyroid hormone levels influence the risk of ASD and the underlying mechanisms remain unclear ( 125 ). The thyroid hormone and its receptor-related genes (including THRA, TPO, TRIP12 , and NR4A2 ) have been linked with ASD, and miRNAs are necessary for thyroid hormone production ( 126 ).…”

The immune system and autism spectrum disorder: association and therapeutic challenges

“…Besides, no connection has been found between the overall ASD prevalence and the increased blood levels of TSH as a sign of hypothyroidism in the early life period. However, it has been suggested that the high TSH level may have an association with the regressive sub-phenotype of ASD (Ames et al, 2020).…”