Association of Gestational Free and Total Triiodothyronine With Gestational Hypertension, Preeclampsia, Preterm Birth, and Birth Weight: An Individual Participant Data Meta-analysis

Abstract

Context Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to TSH and FT4, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes. Methods We collected individual participant data from prospective cohort studies on gestational free and/or total T3 (FT3 or TT3), adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age (SGA) and large for gestational age (LGA)) and potential confounders. We used mixed-effects regression models adjusting for potential confounders. Results Final study population comprised of 33,118 mother–child pairs of which 27,331 had data on FT3 and 16,164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = 0.0069) and a J-shaped association with the risk of gestational hypertension (P = 0.029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 [95% CI]: 1.20 [1.08 to 1.33]; P = 0.0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR [95% CI]: 0.72 [0.55 to 0.94]; P = 0.018). TT3 but not FT3 was positively associated with birth weight (Mean difference per 1-SD increase in TT3 [95% CI]: 12.8 [6.5 to 19.1] grams, P < 0.0001) but there was no association with SGA or LGA. Conclusion This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes which form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes.