NEVER WASTE A GOOD CRISIS: Real-world evidence on the safety of medication use and vaccination during pregnancy

Abstract

The COVID-19 pandemic, declared in March 2020, significantly disrupted healthcare systems globally, with pregnant women facing heightened risks of severe illness. However, these women were largely excluded from clinical trials assessing COVID-19 treatments and vaccines, which exacerbated gaps in knowledge about medication safety during pregnancy. Despite growing awareness of the importance of including pregnant women in medical research, less than 5% of medications provide safety data for pregnancy, and less than 1% of clinical trials include pregnant participants. This dissertation focuses on the safety of COVID-19-related medications and vaccines during pregnancy, with an emphasis on real-world evidence (RWE) as a critical resource for filling these research gaps. One of the key findings is the low usage of COVID-19 treatments among pregnant women, even in severe cases. Many hospitalized pregnant women did not receive the appropriate medical treatment, which likely contributed to an increased risk of adverse outcomes such as preterm birth and cesarean sections. These findings underscore the need for clear treatment guidelines and better access to medication during pandemics. The research also highlights the significant challenges around maternal vaccination. Despite the proven benefits of vaccines in protecting both mothers and newborns, vaccine hesitancy remains widespread among pregnant women, often driven by safety concerns. While limited randomized clinical trials (RCTs) exist, real-world data increasingly suggests that maternal vaccines are both safe and effective, though concerns about fetal safety persist and require further investigation. This dissertation emphasizes the importance of international collaborations and RWE in advancing maternal health research. Initiatives such as the Innovative Medicines Initiative (IMI)-funded ConcePTION and the International Network of Obstetrics Survey Systems (INOSS) have facilitated large-scale data collection, providing valuable insights into medication use and pregnancy outcomes. These networks were instrumental in providing evidence during the pandemic and must be sustained to ensure continuous progress in understanding medication safety for pregnant women. In conclusion, the COVID-19 pandemic revealed significant gaps in research regarding medication safety during pregnancy, but also presented an opportunity to advance global collaboration and RWE. Moving forward, it is crucial to maintain and expand these research infrastructures, focusing on investigating the safety of commonly used medications during pregnancy. This requires ongoing international collaboration, harmonized data collection, and continued investment in real-world data, ultimately supporting better-informed decision-making for healthcare providers and pregnant women.