In total, 147 (4.7%) women had TPOAb levels higher than 100
IU/mL and were defined as TPOAb-positive. Of the remainder, 40 had TPOAb levels between 60–100
IU/mL. Plasma TSH was higher in TPOAb-positive than TPOAb-negative women (3.81±4.13 vs. 1.53±1.04, mean difference=2.28±0.12, p
<0.001). fT4 did not differ between the TPOAb-negative and positive women (15.40±3.72 vs. 15.06±4.80, mean difference=0.34±0.33, p
Next, we examined whether maternal TPOAbs were associated with neonatal thyroid status. The fT4 and TSH levels in child cord blood did not differ between TPOAb-positive and TPOAb-negative women (mean difference for fT4=0.55±0.22, p=0.55, and mean difference for TSH=0.26±0.92, p=0.78).
Maternal and child characteristics are shown in . Pregnant women who were TPOAb negative or TPOAb positive had relatively similar education levels (33.3% vs. 35.4% for higher levels of education). About 14% of the TPOAb-negative women continued smoking during pregnancy. This percentage was 10.2% in TPOAb-positive women.
Participants' Characteristics (n=3,139)
We found that elevated titers of TPOAbs during the first half of pregnancy did not predict language development in children at 2.5 years (OR=0.99 for delayed vocabulary development, 95% CI: 0.39–2.50, p=0.98 and OR=1.49 for delayed phrase development, 95% CI: 0.71–3.12, p=0.28). Children of TPOAb-positive mothers did not have a higher risk than children of TPOAb-negative mothers to develop nonverbal cognitive delay (OR=1.09, 95% CI: 0.67–1.77, p=0.74).
summarizes the association between maternal TPOAbs and internalizing problem scores in children at 3 years. Elevated titers of TPOAbs in pregnant women were not associated with internalizing problems in the offspring (whether problems were rated by mother or father). In line with this finding, there was no association between maternal TPOAbs and affective or anxiety problems.
Maternal Thyroid Peroxidase Antibodies During Pregnancy and Child's Internalizing Problem, the Generation R Study
The relation between elevated titers of TPOAbs in mothers during early pregnancy and externalizing problem scores in the children are presented in . Children of TPOAb-positive women had about 60% higher risk of developing externalizing problems than children of TPOAb-negative women (OR=1.60 for problems rated by mothers, 95% CI: 1.08–2.38, p=0.02). A very similar association was found with father-rating problems (OR=1.61, 95% CI: 1.04–2.49, p=0.03). Using a GEE approach to pool mother and father-rating problem behavior, we found that children of TPOAb-positive mothers were at an increased risk for externalizing problems at 3 years (OR=1.64 for mother- and father-rating problems, 95% CI: 1.17–2.29, p=0.004). This association remained significant after correction for multiple comparisons (α level 0.0125). Next, in the subsequent analyses of the DSM-oriented scales, we found that children of TPOAb-positive mothers were at an increased risk to obtain high scores on the attention deficit/hyperactivity problems as rated by fathers (OR=1.89, 95% CI: 1.16–3.07, p=0.01). The findings were similar for attention deficit/hyperactivity problems rated by mothers, but did not reach significance (OR=1.60, 95% CI: 0.90–2.87, p=0.11). To show the effect of elevated titers of TPOAbs on child problem behavior independent of the rater, we performed further analyses, using the GEE approach to pool mother and father rating of behavior. We observed an association between elevated titers of TPOAbs and the risk of attention deficit/hyperactivity problems (OR=1.77, 95% CI: 1.15–2.72, p=0.01). The association between maternal TPOAbs and the risk of attention deficit/hyperactivity in children remained significant after adjustment for multiple comparisons. No association was found between elevated titers of TPOAbs and the oppositional deviant problems scores.
Maternal Thyroid Peroxidase Antibodies During Pregnancy and Child's Externalizing Problem, the Generation R Study
The results were essentially unchanged if we added maternal depressive symptoms to the analyses (data not shown).
Next, we explored whether altered thyroid status of the mother explained the relation between TPOAbs and externalizing behavior in the offspring. First, we found that TPOAb status was associated with TSH levels in pregnant women (mean plasma TSH in TPOAb-positive women=3.83±4.13 vs. mean plasma TSH in TPOAb-negative women=1.53±1.04, p<
0.001). Second, as previously reported (14
), maternal TSH was associated with children's externalizing problems rated by mothers and by fathers (B=
0.18 per SD of TSH, 95% CI: 0.02–0.34, p
=0.03). Third, after adding maternal TSH to the model, the effect of maternal TPOAbs on externalizing problems of the children was attenuated by 8% only and remained significant (OR=
1.56, 95% CI: 1.14, 2.14, p
In similar analyses, the alternative cut-off for TPOAb levels and CBCL/1½–5 scores was used, but the results remained essentially unchanged.