An estimated 2.5 percent of pregnant women in the United States have hypothyroidism. Even subclinical hypothyroidism has been associated with adverse pregnancy outcomes. The fetus depends on maternal thyroid hormone until fetal thyroid function begins at about 10 to 12 weeks’ gestation, but some reliance on maternal thyroxine (T4) continues throughout pregnancy. Low maternal T4 levels at 12 weeks’ gestation have been linked to impaired psychomotor development in infants. In several studies, maternal hypothyroidism has been associated with lower IQ scores in children. Because T4 metabolism fluctuates during pregnancy, adequate control of thyroid function may be underestimated. As a result, pregnant women may be inadequately treated, with adverse effects on the fetus. Blazer and colleagues studied thyroid function in the neonatal stage of children born in an Israeli university medical center to determine the adequacy of treatment of pregnant women with hypothyroidism.
The authors studied 259 infants born during a six-year period to mothers who were being treated for hypothyroidism. The mothers of 208 infants had been treated before conception for primary hypothyroidism. The remaining 51 were diagnosed with gestational hypothyroidism and began treatment during pregnancy. Those in the control group were 139 infants born to mothers who had at least two documented normal thyroid tests during pregnancy. The two groups of mothers were matched for age, parity, smoking, and hypertension. Blood samples were collected between 25 and 48 hours or 49 and 120 hours after birth for determination of thyroid-stimulating hormone (TSH) and free T4 levels.
The study and control infants were similar in gestational age and Apgar scores at delivery; however, birth weight and head circumferences were significantly smaller in the study group. TSH and T4 levels were significantly higher in the study group than in control patients (see accompanying table). Between 49 and 120 hours after birth, 44.7 percent of study infants had free T4 levels higher than the 95th percentile of control patients, and 16.8 percent of study infants had significantly higher TSH levels. The levels of neonatal TSH after 48 hours of birth correlated with maternal pregnancy TSH levels. Three infants in the study group had thyroid dysgenesis, a rate significantly higher than expected, and one infant had a loss of TSH receptor function.
The authors conclude that the pituitary-thyroid axis of newborns is significantly affected by maternal hypothyroidism. The finding of significant abnormalities in neonatal infants despite apparently satisfactory thyroid management for the mothers raises concerns that current standards of care may be inadequate for pregnant women with thyroid conditions. The authors call for more stringent monitoring and adjustment of therapy for such mothers and long-term neurodevelopmental follow-up of their infants.
|Thyroid-stimulating hormone (IU per mL)||Free thyroxine (T4) (pmol per L)|
|Age at testing||Study group||Control group||Study group||Control group|
|25 to 48 hours||10.1 0.8 (n = 61)||9.1 0.8* (n = 39)||33.3 (2.59 ng per dL)||30.9 (2.4 ng per dL)|
|1.3 (0.1 ng per dL) (n = 61)||1.0* (0.08 ng per dL) (n = 39)|
|49 hours||5.4 0.4 (n = 161)||4.3 0.2 (n = 100)||31.6 (2.46 ng per dL)||25.7 (2.0 ng per dL)|
|0.7† (0.05 ng per dL) (n = 161)||0.3 (0.02 ng per dL) (n = 100)|
|Whole group||6.8 0.3‡ (n = 222)||5.6 0.3 (n = 139)||32.6 (2.53 ng per dL)||27.0 (2.10 ng per dL)|
|0.6§ (0.05 ng per dL) (n = 222)||0.4 (0.03 ng per dL) (n = 139)|