Maternal levothyroxine exposure not associated with neurodevelopmental disorders in offspring

Levothyroxine exposure during pregnancy is not associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) in the offspring, a territory-wide retrospective cohort study in Hong Kong has shown.

“Thyroid diseases are the second most common endocrine disorder in pregnancy. Although previous studies have suggested an association of maternal hypothyroidism with an increased risk of neurodevelopmental disorders in the offspring, little is known about the influence of maternal levothyroxine treatment during pregnancy,” wrote the researchers.

Using the Hong Kong Clinical Data Analysis and Reporting System (CDARS), the study included 422,156 mother-child pairs in Hong Kong between January 2001 and December 2015, and the children were followed up till December 2020. The exposure group was defined as mothers with at least two dispensing records of thyroid hormone treatment before giving birth (n=2,125; mean age at delivery, 33.95 years), while the euthyroid control group was mothers without a history of thyroid-related diagnoses or prescriptions (n=398,909; mean age at delivery, 31.50 years). [BMC Med 2022;20:390]

After adjusting for covariates, including age at delivery, parity, calendar year at delivery, birth hospital and underlying medical conditions in mothers (ie, pre-existing diabetes, gestational diabetes, epilepsy, hypertension and psychiatric conditions), results showed that gestational levothyroxine treatment was not associated with an increased risk of ADHD (4.00 percent vs 3.80 percent; weighted odds ratio [wOR], 1.10; 95 percent confidence interval [CI], 0.88–1.37; p=0.41) or ASD (3.06 percent vs 2.71 percent; wOR, 1.00; 95 percent CI, 0.78 –1.29; p=1.00) in the offspring vs euthyroid placebo.

However, maternal levothyroxine use during pregnancy was associated with an increased risk of preterm birth (12.05 percent vs 8.39 percent; wOR, 1.22; 95 percent CI, 1.07–1.39; p=0.0032), and a higher risk of very or extremely preterm birth (very preterm: wOR, 1.43; 95 percent CI, 1.14–1.82) (extremely preterm: wOR, 1.94; 95 percent CI, 1.27–2.96), vs euthyroid placebo.

Similarly, an increased risk of preterm birth was found in mothers who used levothyroxine during pregnancy vs mothers who had used levothyroxine before but stopped during pregnancy (wOR: 2.16; 95 percent CI, 1.09–4.25; p=0.003).

“There could be a potential effect of gestational exposure [to levothyroxine] on the increased risk of preterm birth in the offspring,” commented the researchers. “Such risk might be confounded by the underlying maternal thyroid disease itself. However, we cannot exclude the possibility that the severity of maternal hypothyroidism may also play a role in the association.”

“Importantly, the severity of hypothyroidism may also potentially influence the association, and other major adverse outcomes may occur due to unstable maternal thyroid status if the treatment is abruptly stopped,” pointed out the researchers. “Clinicians and pregnant women need to have individual discussions about their gestational [levothyroxine] treatment ... and assess the risks and benefits in the context of both mothers and children.”