Maternal thyroid hormones play crucial roles in fetal neurodevelopment, with hypothyroidism and hyperthyroidism consistently being reported as potential risk factors for autism spectrum disorder (ASD) in offspring. Nevertheless, the mechanism underlying this association remains vague. In this retrospective cohort study of 51,296 singleton births in a single hospital, we examined the impact of different maternal thyroid conditions on the risk of ASD in the offspring. Chronic and gestational hyper-and hypothyroidism were determined based on ICD-9 criteria and maternal thyroid hormone levels, respectively. ASD diagnosis was determined based on DSM-5 criteria. Kaplan-Meier plots and Cox regression models were used to assess ASD risk in the offspring of women with and without thyroid conditions. A total of 4,306 (8.4%) of the mothers showed abnormal thyroid function. ASD cumulative incidence was similar in the offspring of women with normal and abnormal thyroid function (log-rank p=0.28). However, further classification of the study groups revealed an increased ASD risk in the offspring of women with both chronic and gestational thyroid dysfunction (aHR= 2.68, 95%CI=1.52-4.72). In addition, trimester-specific analysis revealed a dose effect in that the longer the period of thyroid imbalance, the higher the ASD risk, namely, for one, two or three trimesters of hypo- or hyperthyroidism, aHR= 1.69 (95%CI=1.19-2.83), aHR=2.39 (95%CI=1.24-5.78), aHR=3.25 (95%CI=1.07-7.21), respectively. Thus, the findings suggest that uncontrolled gestational thyroid dysfunction is associated with an elevated risk of ASD in offspring, underscoring the importance of routine thyroid function screening and treatment throughout pregnancy in mitigating ASD risk in offspring.

The authors have declared no competing interest.

This study did not receive any funding

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The ethics committee of Soroka University Medical Center gave ethical approval for this work

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors