Maternal Thyroid Disease and Preterm Birth: Systematic Review and Meta-Analysis

Abstract

Context: Thyroid disease in pregnancy is increasing with rising average maternal ages in developed countries. The evidence for an association between preterm birth and thyroid disease has been confounded by small studies with varying outcomes and methodology. Objective: The aim of this meta-analysis is to review the literature regarding thyroid disease including subclinical and overt hypothyroidism, hyperthyroidism, and isolated hypothyroxinemia and the specific outcome of preterm birth. Data Sources: A search of PubMed and Embase databases was performed in May 2015. A fixed-effects model was used to calculate the overall combined odds ratio (OR) with its corresponding 95% confidence interval (95% CI) to evaluate the relationship between thyroid disease and preterm delivery. Study Selection: Studies were considered eligible if they met the following criteria: prospective cohort study or a case control study; the exposure of interest was maternal thyroid disease, including subclinical hypothyroidism, overt hypothyroidism, hyperthyroidism, or isolated hypothyroxinemia; the outcome of interest was preterm delivery; and data regarding numbers of preterm births in each cohort were reported. Data Extraction: Data were recorded in a database evidence table including any incidence data for maternal thyroid disease and preterm birth compared to a reference group. Data Synthesis: Fourteen cohort studies and one case control study involving 2 532 704 participants were included. The combined OR of preterm delivery for pregnant women with overt hypothyroidism compared with the reference group was 1.19 (95% CI, 1.12–1.26; P < .00001). There was also a significant risk of preterm birth in women with hyperthyroidism (OR, 1.24 [95%, CI 1.17–1.31]; P < .00001). Subclinical hypothyroidism and isolated hypothyroxinemia showed no significant increase in OR. Sensitivity analysis made no change to these results. Conclusion: Both overt hypothyroidism and hyperthyroidism are associated with a small but statistically significant increase in OR for preterm birth not seen in subclinical hypothyroidism or isolated hypothyroxinemia.