Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up study

TLDR: Evaluation of the impact of maternal hypothyroxinaemia during early gestation and any subsequent changes in fT4 during gestation on infant development and TSH within the reference range are evaluated.

Abstract: Summary OBJECTIVE To evaluate the impact of maternal hypothyroxinaemia during early gestation (fT4 below the lowest tenth percentile and TSH within the reference range: 0·15‐2·0 mIU/l) on infant development, together with any subsequent changes in fT4 during gestation. DESIGN A prospective 3-year follow-up study of pregnant women and their children up to the age of 2 years. MEASUREMENTS Child development was assessed by means of the Bayley Scales of Infant Development in children of women with hypothyroxinaemia (fT4 below the tenth percentile at 12 weeks’ gestation) at 12 weeks’ gestation (cases), and in children of women with fT4 between the 50th and 90th percentiles at 12 weeks’ gestation, matched for parity and gravidity (controls). Maternal thyroid function (fT4 and TSH) was assessed at 12, 24 and 32 weeks’ gestation. The mental and motor function of 63 cases and 62 controls was compared at the age of 1 year, and of 57 cases and 58 controls at the age of 2 years. RESULTS Children of women with hypothyroxinaemia at 12 weeks’ gestation had delayed mental and motor function compared to controls: 10 index points on the mental scale (95% CI: 4·5‐15 points, P = 0·003) and eight on the motor scale at the age of 1 year (95% CI: 2·3‐12·8 points, P = 0·02), as well as eight index points on the mental (95% CI: 4‐12 points, P = 0·02), and 10 on the motor scale (95%CI: 6‐16 points, P = 0·005) at the age of 2 years. Children of hypothyroxinaemic women in whom the fT4 concentration was increased at 24 and 32 weeks’ gestation had similar scores to controls, while in the controls, the developmental scores were not influenced by further declines in maternal fT4 at 24 and 32 weeks’ gestation. CONCLUSIONS Maternal hypothyroxinaemia during early gestation is an independent determinant of a delay in infant neurodevelopment. However, when fT4 concentrations increase during pregnancy in women who are hypothyroxinaemic during early gestation, infant development appears not to be adversely affected. In the past decade, interest has been rekindled in the relationship between maternal plasma thyroid hormone concentration during pregnancy and subsequent infant neurodevelopment (Pop et al ., 1995, 1999a; Haddow et al ., 1999; Lazarus, 1999; Smit et al ., 2000). It is well known that both maternal thyroid dysfunction during pregnancy (especially hypothyroidism) and severe iodine deficiency adversely affect the outcome of neurodevelopment in children (Delange, 1994; Glinoer, 1997; Mestman, 1999). Even in areas in which there is sufficient iodine intake in the general population, pregnant women often have fT4 plasma levels in the lower ranges, without elevated TSH. This is defined as hypothyroxinaemia, and is generally regarded as a normal condition. However, there is growing concern that hypothyroxinaemia during early gestation could be harmful to the offspring (Pop et al ., 1999b; Utiger, 1999; Morreale de Escobar et al ., 2000). In fact, little is known about maternal fT4 levels during normal pregnancy, or their relationship to the development of the child. This paper describes the results of a longitudinal prospective study that investigates whether maternal thyroid hormone levels, assessed in women without (sub)clinical thyroid function at three different trimesters during pregnancy, are adversely related to child development at 1 and 2 years of age.