Isolated maternal hypothyroxinemia and adverse pregnancy outcomes: A systematic review

Maternal thyroid hormones are vital for a normal pregnancy and the development of fetus and childhood; inadequate availability of thyroid hormones during pregnancy is associated with adverse pregnancy outcomes. Isolated maternal hypothyroxinemia (IMH) is defined as a low maternal T4 in the absence of TSH elevation. This systematic review aimed to investigate the association between IMH and adverse pregnancy outcomes. PubMed, Scopus and Web of science were searched for retrieving observational studies published up to September 2020, investigating the association of IMH with adverse pregnancy outcomes. From a total of 308 articles, 17 met our eligibility criteria and were used for the purpose of the present study. Definition of IMH varied in different studies. While some studies reported no adverse pregnancy outcomes for IMH, other studies found a positive association between first trimester IMH and feto-maternal outcomes including gestational hypertension, gestational diabetes, preterm delivery, fetal distress, small for gestational age, musculoskeletal malformations, spontaneous abortion, placental abruption and macrosomia. IMH, identified in the second trimester was associated with an increase in the risk of gestational diabetes, and hypertensive disorders of pregnancy in one study. There is no consensus on the adverse effects of IMH on pregnancy outcomes. Further comprehensive cohort studies using one standard definition for IMH, with large sample size and control of important confounders such as iodine status and maternal Thyroid peroxidase antibody (TPOAb) are needed for precise assessment of this association.