Reproduction Abstracts

Identifying effective, safe, and affordable treatment of HG is critical to improving maternal and child health. We recently demonstrated that genetic predisposition to HG is mediated by low pre-pregnancy levels of GDF15, resulting in hypersensitivity to its rise during pregnancy. Because metformin increases GDF15, we hypothesized that its use before pregnancy will desensitize patients to GDF15 and lower HG risk. By structured questionnaire, visitors to HER Foundation Social Media sites from January-July 2022 reported daily use of 33 common substances in the month before each pregnancy and level of NVP. Crude and multivariate associations between use of substances were estimated by logistic regression. Associations between use of each substance and severe NVP/HG in the subsequent pregnancy was estimated by logistic regression. Multivariate models included tobacco use and maternal age; number and type of additional drugs used, and race/ethnicity had little influence and were not retained. Estimates for first and second pregnancies were combined by random effects meta-analysis. Participants from 46 countries reported on 3,740 pregnancies. Using metformin before pregnancy was significantly associated with lower risk of severe NVP/HG [adjusted OR=0.42 (95%CI=0.20-0.88)], as was using cyclobenzaprine (aOR=0.30;95%CI=0.10-0.89) and tobacco (aOR=0.40;95%CI=0.28-0.56). Pre-pregnancy metformin treatment may ameliorate NVP symptoms. Generic metformin, which is routinely used prior to and during pregnancy for other conditions, may be a safe and affordable treatment to prevent HG. Clinical trials are warranted to investigate its use prior to pregnancy to lower HG risk and mitigate the associated adverse maternal and offspring outcomes.

Keywords: Hyperemesis Gravidarum; metformin; tobacco