Evaluating the Risks of Systemic Maternal Ivermectin Exposure During Pregnancy in Human and Vertebrate Animals: A Scoping Review

Background: Ivermectin is widely used for the treatment of neglected tropical diseases associated with adverse maternal and fetal outcomes when the infection complicates the pregnancy. However, the United States FDA classification and current distribution protocols limit ivermectin treatment in pregnant women because antepartum safety has not been well-established. Objective: We conducted a scoping review to address the question of what is known from both human and vertebrate animal studies about the safety of systemic ivermectin exposure during pregnancy. Methods: We searched PubMed for adverse outcomes related to systemic ivermectin exposure in human and vertebrate animal pregnancies, including English-language primary articles from 1900 - 2019. Results: We identified 23 primary articles for evaluation, including 10 human studies and 13 vertebrate animal studies of interest. One prospective randomized, controlled trial investigating the safety of systemic ivermectin exposure during pregnancy and four retrospective human studies did not identify a significant association with adverse birth outcome metrics. Out of the three human case reports, two reported uncomplicated prenatal courses and one reported stillbirth and maternal death. A retrospective cross-sectional study concluded a positive association between onchocerciasis and spontaneous abortion, mitigated by ivermectin mass drug administration. While adverse pregnancy outcomes were observed at high doses in mice, rats, and rabbits, there was overall a lack of evidence to support concerns that therapeutic doses of ivermectin (0.2 mg/kg) cause adverse pregnancy outcomes. Conclusion: Further research is warranted to address safety concerns regarding the use of ivermectin in pregnant women in treating and preventing neglected helminth infections that threaten maternal-child health.