Endocrine Abstracts

Objectives: Polycystic ovary syndrome (PCOS) and thyroid disorders have separately been linked to adverse pregnancy and neonatal outcomes. Even small variations in thyroid function within the normal range may influence fetal growth. Previous data have shown that metformin-treatment of pregnant women with PCOS reduced late miscarriages and preterm births, and resulted in less decrease of fT4 compared to placebo. Moreover, metformin exposure in utero altered the offspring anthropometrics leading to larger head size. Our aim was to investigate whether newborn anthropometrics are associated with maternal thyroid function in PCOS-pregnancies, and explore the potential modifying effect of metformin.

Methods: Post-hoc analyses of two randomized, double-blinded, placebo-controlled trials, in which pregnant women with PCOS were randomized to metformin or placebo, from first trimester to delivery. Maternal serum levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) were longitudinally measured at gestational weeks (gw) 5-12, 19, 32 and 36 in 309 singleton pregnancies. The mean z-scores of birthweight, birth length, and head circumference were estimated in offspring. The associations between maternal thyroid parameters and offspring anthropometrics were studied using regression analyses.

Results: There were no associations between maternal TSH and fT4 during pregnancy and head circumference z-score of the newborns. However, in early pregnancy (gw 5-12), one pmol/l increase in maternal natural logarithm (ln)-transformed fT4 levels was associated with a reduction in birthweight z-score of 1.34 units (b=-1.34, P = 0.010) and a reduction in birth length z-score of 1.32 units (b=-1.32, P = 0.035). In the third trimester (gw 32), one pmol/l increase in maternal ln-transformed fT4 levels was associated with a reduction in birthweight z-score of 1.39 units (b=-1.39, P = 0.018). The aforementioned associations were observed independently of treatment group. For the placebo group only, significant negative linear associations were observed between TSH at gw (5-12) and gw36 and birth length z-score, where one mIU/l increase in square root transformed TSH was associated with a 0.53- and 0.79-units decrease in birth length z-score respectively (b=-0.53, P = 0.048 and b=-0.79, P = 0.030 respectively).

Conclusions. In early pregnancy, maternal fT4 was inversely associated with birthweight and length. In late pregnancy, maternal fT4 was inversely associated with birthweight. Inverse associations were observed between maternal TSH in early and late pregnancy and birthweight in the placebo group. Subclinical changes in maternal thyroid function parameters may influence anthropometrics in babies born to women with PCOS.