Objective: Preterm birth is the most important risk factor for child morbidity and mortality worldwide. We aimed to study if maternal thyroid dysfunction and thyroid autoimmunity are risk factors for preterm birth.

Data Sources and Methods: After a systematic search we included prospective cohort studies that consecutively and unselectively included pregnant women, provided that TSH, FT4 or thyroid peroxidase antibodies (TPOAb) measurements and data on gestational age at birth were available. We performed one-step and two-step meta-analysis of individual-participant thyroid function data using mixed-effects models adjusting for potential confounders in association with late (<37 weeks), moderate (<34 weeks) and very (<32 weeks) preterm birth and mean gestational age at birth.

Results: Data sets from nineteen prospective cohorts (N=46,421) were analyzed. In continuous analyses, lower maternal FT4 and T3 concentrations were associated with a higher risk of very preterm birth (FT4: OR 0.88 per SD [0.79-0.95]; T3: OR 0.76 per SD [0.59-0.98]). Maternal isolated hypothyroxinemia was associated with a 1.5, 1.9 and 2.6-fold higher risk of late, moderate and very preterm birth, respectively (late preterm: OR 1.46 [1.12-1.90]; moderate preterm: OR 1.88 [1.21-2.92]; very preterm: OR 2.57 [1.55-4.27]). TPOAb positivity was associated with a 1.3, 2.1 and 2.5-fold higher risk of late, moderate and very preterm birth, respectively (late preterm: OR 1.33 [1.15-1.56]; moderate preterm: OR 2.11 [1.65-2.69]; very preterm: OR 2.45 [1.81-3.32]).

Conclusions: We identified that isolated hypothyroxinemia, lower T3 concentration and TPOAb positivity are associated with a higher risk of early preterm birth. These data indicate that low thyroid hormone availability as well as TPOAb positivity during pregnancy are risk factors for preterm birth and can help to improve the identification of high-risk groups.