Maternal Thyrotropin Receptor Antibody Concentration and the Risk of Fetal and Neonatal Thyrotoxicosis: A Systematic Review

Background: In pregnant women with Graves' disease, maternal thyrotropin receptor antibodies (TRAb) can cross the placenta and induce fetal or neonatal thyrotoxicosis. Symptoms of fetal thyrotoxicosis are tachycardia, intrauterine growth restriction, and intra-uterine death. Recommendations on an upper limit of TRAb concentrations below which intensive fetal monitoring can be safely omitted vary between different guidelines. The objective of this study was to define an evidence-based cutoff level for maternal TRAb necessitating additional fetal monitoring during pregnancy. Methods: A literature search was performed to identify studies on pregnant women with Graves' disease and fetal and/or neonatal thyrotoxicosis. Only studies that reported TRAb were included. Results: From a total of 229 identified titles, 20 articles could be included in the analysis. A total of 53 cases of fetal and/or neonatal thyrotoxicosis were described. The lowest level of maternal TRAb leading to neonatal thyrotoxicosis was 4.4U/L, which corresponds to 3.7 times the upper limit of normal. The level of evidence for this threshold is moderate to low. Conclusion: In women with Graves' disease, intensive fetal monitoring is recommended when maternal TRAb concentrations are >3.7 times the upper limit of normal. This cutoff level should be interpreted with caution, since evidence is limited