Background: Early pregnancy fetal growth is a relevant determinant of pregnancy outcome and child health during later life. During the first trimester, fetal growth depends on the transfer of maternal thyroid hormone, and optimal thyroid hormone availability is ensured via stimulation of the maternal thyroid by human chorionic gonadotropin (hCG). The potent stimulatory effects of hCG on gestational thyroid function and its clinical relevance with early fetal growth remain unknown and need to be examined.
Methods: This study comprised 46,186 mothers for whom early pregnancy thyrotropin (TSH), free thyroxine (fT4), triiodothyronine, thyroperoxidase antibodies, hCG, as well as ultrasound crown-rump length (CRL) measurements were available. Data were also available on potential confounders, including maternal age, parity, anthropometrics, and fetal sex.
Results: There was a negative association of TSH with CRL and a positive association of fT4 with CRL, with effect estimates of roughly 0.1 standard deviation (SD) across the full ranges. However, when taking into account thyroid stimulation by hCG, an impaired thyroidal response to hCG stimulation was associated with up to a 0.2 SD lower CRL (high hCG with high TSH) and up to a 0.6 SD lower CRL (high hCG with low fT4). Even within the normal range of TSH and fT4, an impaired thyroidal response to hCG stimulation was associated with a lower CRL.
Conclusions: Low maternal thyroid function during the first trimester is associated with a modestly lower CRL. However, an impaired thyroidal response to hCG stimulation is associated with a considerably lower CRL for which effect estimates are in the range of or even supersede those of well-known risk factors. These data can help to improve the identification of pregnancies at high risk of fetal growth restriction and adverse pregnancy or child outcomes.
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