A Systematic Review and Meta-Analysis Examining the Risk of Adverse Pregnancy and Neonatal Outcomes in Women with Isolated Hypothyroxinemia in Pregnancy

Background: The relationship between isolated hypothyroxinemia (IH) in pregnancy and adverse pregnancy outcomes is controversial, with no consensus on the need for treatment. Summary: We conducted a systematic review and meta-analysis examining adverse pregnancy and neonatal outcomes in women with IH in pregnancy. We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials for publications from inception to December 2022. Randomized clinical trials and cohort studies were included. Random-effects meta-analyses were used to estimate pooled relative risks (RRs) for each outcome. We included 21 articles, of which 19 investigated the relationship between IH and maternal and neonatal outcomes and 4 investigated the efficacy of levothyroxine (LT4) treatment. Compared with euthyroid pregnancies, IH pregnancies were associated with an increased risk of preterm birth (RR 1.35 [confidence interval, CI, 1.16-1.56]; I2 = 9%), premature rupture of membranes (RR 1.41 [CI 1.08-1.84]; I2 = 0%), gestational diabetes (RR 1.34 [CI 1.07-1.67]; I2 = 76%), macrosomia (RR 1.62 [CI 1.31-2.02]; I2 = 42%), and fetal distress (RR 1.72 [CI 1.15-2.56]; I2 = 0%). However, no statistically significant differences were noted in adverse outcomes according to LT4 treatment status. Conclusions: There is evidence suggesting that IH in pregnancy may be associated with an increased risk of adverse pregnancy and neonatal outcomes. However, it is unclear whether LT4 may mitigate the risk of these adverse outcomes.