Anastasia Trouva, Michael Alvarsson, Jan Calissendorff, Bjørn Olav Åsvold, Dorina Ujvari, Angelica Lindén Hirschberg, Eszter Vanky
Journal: Frontiers in endocrinology 2024;15():1388473
PMID: 38868742
Both thyroid dysfunction and polycystic ovary syndrome (PCOS) have been linked to adverse pregnancy and neonatal outcomes. Metformin treatment affects the changes in thyroid hormones which naturally occur during pregnancy (decrease in thyroid stimulating hormone (TSH), increase in free thyroxine (fT4)). The aim of this post-hoc analysis of 2 randomised controlled trials of metformin in pregnant women with PCOS was to evaluate the effect of thyroid hormone levels on anthropometric parameters of the newborn in this population and potential effects of metformin. Treatment with metformin was associated with a smaller increase in fT4 but did not affect TSH. A higher baseline fT4 level was associated with a lower birth weight and lengths, whilst a higher increase in fT4 was associated with higher birth weight and length. This was independent of treatment group, i.e. metformin or placebo. There was no statistically significant association between baseline TSH or decrease in TSH and birth weight or length. There was no association between thyroid hormones and head circumference. Neither baseline fT4 or increase in fT4 were associated with either large or small for gestational age infants (LGA/SGA), except for the metformin group where a reduced risk of SGA was seen with a higher increase in fT4. TSH, on the other hand, was associated with SGA/LGA. A higher baseline TSH was associated with a lower risk of LGA, whilst a larger increase in TSH was associated with a higher risk of LGA. A higher TSH at baseline decreased the risk of SGA in women treated with metformin only. The authors conclude that subclinical variations in thyroid hormones during pregnancy may affect birth anthropometrics of the offspring of women with PCOS.
OBJECTIVES
Polycystic ovary syndrome (PCOS) and thyroid disorders have both been linked to adverse pregnancy and neonatal outcomes. Even small variations in thyroid function within the normal range may influence fetal growth. Our aim was to investigate whether maternal thyroid function is associated with newborn anthropometrics in PCOS and explore the potential modifying effect of metformin.
METHODS
analyses of two RCTs 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 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 the offspring. Associations of maternal thyroid parameters with offspring anthropometrics and the outcomes large for gestational age (LGA) and small for gestational age (SGA) were studied using linear and logistic regression models, with adjustment for body mass index (BMI) when relevant.
RESULTS
Maternal fT4 at baseline was negatively associated with birth length (b= -0.09, p=0.048). Furthermore, ΔfT4 during pregnancy correlated positively to z-score of both birth weight and length (b=0.10, p=0.017 and b=0.10, p=0.047 respectively), independently of treatment group. TSH at baseline and gw19 was inversely associated with LGA (OR 0.47, p=0.012 and OR 0.58, p=0.042), while ΔTSH was positively associated with LGA (OR 1.99, p=0.023). There were inverse associations between TSH at baseline and SGA (OR 0.32, p=0.005) and between ΔfT4 and SGA (OR 0.59, p=0.005) in the metformin group only. There were no associations between maternal thyroid function and head circumference of the newborns.
CONCLUSION
In women with PCOS, a higher maternal fT4 in early pregnancy and a greater decrease in fT4 during pregnancy was associated with a lower offspring birthweight and shorter birth length. Higher TSH by mid-gestation and smaller increase in TSH during pregnancy was associated with less risk of LGA. Subclinical variations in maternal thyroid function might play a role for birth anthropometrics of PCOS offspring.
Copyright © 2024 Trouva, Alvarsson, Calissendorff, Åsvold, Ujvari, Hirschberg and Vanky.
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