KPWHRI awarded funding to study antinausea drugs in pregnancy

Findings will help pregnant people make informed treatment decisions with greater confidence

Nausea and vomiting are common in pregnancy, affecting 70% of pregnant people. Besides having a significant impact on daily life and well-being, these symptoms can also take a toll on mental health — and severe nausea and vomiting can endanger both the pregnant person and their fetus. Up to 20% of pregnant people take a prescription antinausea medication. While several medications are available, there is limited data on which works best, and questions have been raised about the safety of some medications for the fetus.

Sascha Dublin, MD, PhD, and colleagues are aiming to fill this important research gap through a new patient-centered comparative clinical effectiveness research (CER) project. They will examine the effectiveness and safety of 4 commonly used prescription medications: ondansetron (brand name Zofran), promethazine, metoclopramide, and doxylamine-pyridoxine (brand names Diclegis and Bonjesta). The researchers will compare the medications with each other and with taking no prescription medications. Conducted in real-world care settings, the project will generate evidence on outcomes that matter to patients, helping them and their care teams make better-informed health care decisions.

“Because the medications are already widely available, study results could rapidly affect clinical practice,” said Dublin, a physician with Kaiser Permanente Washington and a senior investigator with Kaiser Permanente Washington Health Research Institute (KPWHRI). “There is a huge need for better evidence to help pregnant people weigh the benefits and risks of different antinausea medications. These findings will also be valuable to inform clinical guidelines.”

The project will include an advisory committee of patient partners, health care providers, and community organizations that serve pregnant people. Community members with lived experience helped shape the proposal and will serve as co-investigators guiding the study. One patient co-investigator, Alli Berard of Minneapolis, said, “This study will provide the kind of data women desperately need: clear, evidence-based answers about what treatments work and what is safe. Having access to this information will help women feel empowered and supported in choosing the care they need without guilt or fear.”

The project will include a prospective cohort study enrolling pregnant people and following them over time to assess medication effectiveness. It will also use electronic health data going back to 2010 to better understand medication safety.

• The prospective study will recruit 1,200 people with moderate or severe nausea early in pregnancy. Researchers will follow participants until 6 months postpartum, using questionnaires to collect information on medication and supplement use, severity of nausea and vomiting, depression, sleep, and other outcomes. Participants will be recruited from 4 health care systems: Kaiser Permanente Washington, Kaiser Permanente Southern California, Kaiser Permanente Georgia, and HealthPartners, based in Minnesota.
   
• To study safety outcomes, researchers will analyze electronic health data from 1.3 million pregnancies. The large sample size will enable researchers to compare the medications on rare safety outcomes, such as major congenital and cardiac malformations, as well as on preterm birth, child neurodevelopment, and other outcomes. These data will come from the same 4 health care systems plus a large health insurance plan.

​​​​The study is being funded through a $12.5 million award from the Patient-Centered Outcomes Research Institute (PCORI). The award has been approved pending completion of PCORI’s business and programmatic review and issuance of a formal award contract.

PCORI is a nonprofit organization with a mission to fund patient-centered CER designed to provide patients and those who care for them with evidence to make better-informed health care decisions.

By Sophie Ramsey