Thoughts about the ‘Antenatal Thyroid Screening and Childhood Cognitive Function’ Study

Dear Sir, The results of the long awaited Antenatal Thyroid Screening and Childhood Cognitive Function study have finally been published in the New England Journal of Medicine after a preliminary presentation of findings at the International Thyroid Congress in Paris in 2010 [1]. The aim of the study was to evaluate the impact of levothyroxine (LT4) treatment on the intelligence quotient (IQ) of 3-year-old children born from mothers with mild thyroid impairment. This prospective, randomized, multicenter study involved almost 22,000 patients who were recruited within the first 16 weeks of gestation. Patients were divided into a ‘screening’ group and a ‘control’ group. In the screening group, patients were tested for TSH and free T4 (FT4) at the time of recruitment, and women with a TSH >97.5 percentile and/or FT4 <2.5 percentile were treated with levothyroxine at an initial dosage of 150 μg/day. Patients in the control group had their blood drawn at the time of recruitment, but their thyroid function test results were not known until after delivery. Thyroid dysfunction was found in 4.6% of the screening group and in 5% of the control group. There were no differences in patient characteristics between the two groups (age, smoking, weight, education, preterm birth). LT4 treatment was initiated at 13 weeks' gestation in the screening group (median). The standardized IQ of children in the control group was 100 points (404 children, 73.3% of the children of the women who tested positive), whereas the IQ of children in the screening group (390 children, 78.2% of the children of the women who tested positive) was 99.2 points (p = 0.40). The proportion of patients with an IQ <85 points was 12.1% in the screening group versus 14.1% in the control group (p = 0.39). A post-hoc analysis revealed no difference when controls were compared with different patient subgroups, namely women with elevated TSH only, low FT4 only, or women who started treatment either before or after 14 weeks' gestation. In conclusion, the Antenatal Thyroid Screening and Childhood Cognitive Function study demonstrated that in pregnant women with mild thyroid impairment, treatment with LT4 initiated at a median of 13 weeks' gestation did not improve the IQ of their offspring when tested at age 3 years. This study involved 10 centers in the United Kingdom and 1 center in Italy (Turin), and has the merit of being one of the very few prospective studies of intervention for thyroid disease during pregnancy. There is an extensive and ongoing debate regarding the pros and cons of universal screening for thyroid dysfunction during pregnancy. At the center of the debate has been the limited data on the utility, or lack thereof, for treating subclinical hypothyrodism during pregnancy (as there is unanimous consensus about treating overt hypothyroidism) [2]. As the study results did not demonstrate a benefit for LT4 treatment during pregnancy, it provides data against the benefit of universal screening. As with all studies, this one has its debatable points, which are discussed below.