Abstract
Objective: To determine if first trimester maternal thyroid dysfunction is a critical determinant of child scholastic performance and overall educational attainment. Design: Prospective cohort study. Setting: Avon Longitudinal Study of Parents and Children cohort in the UK. Participants: 4615 mother-child pairs with an available first trimester sample (median 10 weeks gestation, interquartile range 8-12). Exposures: Free thyroxine, thyroid stimulating hormone, and thyroid peroxidase antibodies assessed as continuous measures and the seven clinical categories of maternal thyroid function. Main outcome measures: Five age-specific national curriculum assessments in 3580 children at entry stage assessment at 54 months, increasing up to 4461 children at their final school assessment at age 15. Results: No strong evidence of clinically meaningful associations of first trimester free thyroxine and thyroid stimulating hormone levels with entry stage assessment score or Standard Assessment Test scores at any of the key stages was found. Associations of maternal free thyroxine or thyroid stimulating hormone with the total number of General Certificates of Secondary Education (GCSEs) passed (range 0-16) were all close to the null: free thyroxine, rate ratio per pmol/L 1.00 (95% confidence interval 1.00 to 1.01); and thyroid stimulating hormone, rate ratio 0.98 (0.94 to 1.02). No important relationship was observed when more detailed capped scores of GCSEs allowing for both the number and grade of pass or when language, mathematics, and science performance were examined individually or when all educational assessments undertaken by an individual from school entry to leaving were considered. 200 (4.3%) mothers were newly identified as having hypothyroidism or subclinical hypothyroidism and 97 (2.1%) subclinical hyperthyroidism or hyperthyroidism. Children of mothers with thyroid dysfunction attained an equivalent number of GCSEs and equivalent grades as children of mothers with euthyroidism. Conclusions: Maternal thyroid dysfunction in early pregnancy does not have a clinically important association with impaired child performance at school or educational achievement.
Highlights
Overt and subclinical thyroid diseases affect up to 10% of pregnancies depending on the laboratory reference range used.[1]
Case-control and cohort studies have suggested that maternal thyroid dysfunction, and low levels of maternal thyroid hormone in particular, in the first trimester are associated with lower intellectual function and impaired cognitive processes in exposed children Two randomised controlled trials of levothyroxine therapy in newly diagnosed mothers with hypothyroidism have not observed any decrement in cognitive function at age 3 or 5 compared compared with untreated mothers Current clinical guidelines recommend treatment for mothers with thyroid dysfunction as long term intellectual effects are unknown
Our study shows that maternal thyroid stimulating hormone levels and free thyroxine concentrations in the first trimester are not associated with performance in national curricular assessments from age 54 months to age 15 years Women with thyroid dysfunction in pregnancy can be reassured that their thyroid disease will not impact their child’s school performance or educational attainment were all close to the null: free thyroxine, rate ratio per pmol/L 1.00 (95% confidence interval 1.00 to 1.01); and thyroid stimulating hormone, rate ratio 0.98 (0.94 to 1.02)
Summary
Overt and subclinical thyroid diseases affect up to 10% of pregnancies depending on the laboratory reference range used.[1] Thyroid hormone is essential for normal brain development, with both congenital thyroid deficiency and excessive exposure during fetal life associated with long term cognitive impairment.[2 3] As the developing fetus is dependent on maternal thyroid hormones until the late first trimester,[4] profound untreated maternal hypothyroidism in early pregnancy has been associated with an overall seven point reduction in child intelligence quotient.[5] Maternal subclinical hypothyroidism and isolated hypothyroxinaemia have been associated with impairments in child intelligence quotient,[2 5,6,7] arithmetic skills,[8] scholastic performance,[9] and motor skills,[5 7] as well as poorer reaction time,[10] delays in attention,[5] and increased attention deficit hyperactivity disorder symptoms.[11] Maternal subclinical thyroid dysfunction has been associated with an increased risk of miscarriage, gestational hypertension, preeclampsia, gestational diabetes, and preterm birth,[12 13] and that treatment in some but not all studies improved outcomes,[14,15,16] has prompted calls for universal thyroid function screening to facilitate early identification and treatment of both overt and subclinical disease.[17 18] This is despite appropriately powered trials demonstrating that intervention with maternal levothyroxine treatment is not effective at notably improving perinatal or childhood cognitive outcomes for women with subclinical thyroid dysfunction.[19,20,21]
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