Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy

Clin Endocrinol (Oxf). 1999 Feb;50(2):149-55. doi: 10.1046/j.1365-2265.1999.00639.x.


Background: Maternal thyroid function during early pregnancy is an important determinant of early fetal brain development because the fetal thyroid is unable to produce any T4 before 12-14 weeks' gestation. Overt maternal hypothyroidism as seen in severe iodine-deficient areas is associated with severely impaired neurological development of the offspring. At present, it is not known whether low free T4 (fT4) levels during pregnancy in healthy women from iodine sufficient areas may affect fetal neurodevelopment.

Methods: Neurodevelopment was assessed at 10 months of age in a cohort of 220 healthy children, born after uncomplicated pregnancies and deliveries, using the Bayley Scales of Infant Development. Maternal TSH, fT4 and TPO antibody status were assessed at 12 and 32 weeks' gestation. Maternal gestational fT4 concentration was defined as an independent parameter for child development.

Results: Children of women with fT4 levels below the 5th (< 9.8 pmol/l, n = 11) and 10th (< 10.4 pmol/l, n = 22) percentiles at 12 weeks' gestation had significantly lower scores on the Bayley Psychomotor Developmental Index (PDI) scale at 10 months of age, compared to children of mothers with higher fT4 values (t test, mean difference: 14.1, 95% confidence interval (CI): 5.9-22 and 7.4, 95% CI: 1.1-13.9, respectively). At 32 weeks' gestation, no significant differences were found. In the group of women with the lowest 10th percentile fT4 concentrations at 12 weeks' gestation, a positive correlation was found between the mothers' fT4 concentration and children's PDI scores (linear regression, R: 0.46, P = 0.03). After correction for confounding variables, a fT4 concentration below the 10th percentile at 12 weeks' gestation was a significant risk factor for impaired psychomotor development (RR): 5.8, 95% CI: 1.3-12.6).

Conclusions: Low maternal plasma fT4 concentrations during early pregnancy may be an important risk factor for impaired infant development.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / blood
  • Female
  • Humans
  • Infant
  • Iodide Peroxidase / immunology
  • Pregnancy / blood*
  • Pregnancy / immunology
  • Pregnancy Trimester, First / blood
  • Pregnancy Trimester, Third / blood
  • Prenatal Exposure Delayed Effects
  • Psychomotor Performance*
  • Regression Analysis
  • Risk Factors
  • Thyrotropin / blood
  • Thyroxine / blood*


  • Antibodies
  • Thyrotropin
  • Iodide Peroxidase
  • Thyroxine