Abstract
OBJECTIVE: To examine the association between isolated maternal hypothyroxinaemia (IMH) and adverse obstetric outcomes and offspring outcomes and also investigate the effects of levothyroxine therapy on IMH for the above outcomes. METHODS: We systematically searched PubMed, EMBASE, and Cochrane Library, and the reference lists of key reviews were hand searched on June 9, 2021. Two authors independently screened titles/abstracts. Full articles were further assessed if the information suggested that the study met the inclusion/exclusion criteria, and two researchers performed data extraction and risk-of-bias assessment using standardized tables. Summary relative risks or the mean difference between maternal effects and offspring outcomes were calculated by a random-effects model. RESULTS: We identified 38 eligible articles (35 cohort studies and two randomized controlled trials [RCT]). Meta-analysis showed that maternal IMH was associated with increased gestational diabetes mellitus, preterm premature rupture of membranes, preterm birth, fetal distress, and macrosomia outcomes in IMH compared to euthyroid women, and the relative risks were 1.42 (1.03-1.96), 1.50 (1.05-2.14), 1.33 (1.15-1.55), 1.75 (1.16-2.65) and 1.62 (1.35-1.94), respectively. IMH was not associated with placenta previa, gestational hypertension, pre-eclampsia, intrauterine growth restriction, and offspring outcomes like birth weight, low birth weight infants, fetal macrosomia, neonatal intensive care, neonatal death, or fetal head circumference. In addition, we did not find an association between IMH and adverse offspring cognitive defects. Due to insufficient data for meta-analysis, it failed to pool the evidence of levothyroxine's therapeutic effect on IMH and their offspring. CONCLUSIONS AND RELEVANCE: IMH in pregnancy may relate to a few maternal and offspring outcomes. Moreover, there is currently no sufficient evidence that levothyroxine treatment during pregnancy reduces adverse maternal outcomes and disability in offspring. Further investigation to explore the beneficial effects of levothyroxine therapy is warranted.