Maternal mortality rates continue to increase in the U.S., outpacing rates of other developed countries. In 2021, 1,025 women in the U.S. died due to pregnancy or childbirth-related causes, compared to 861 women in 2020 and 754 in 2019, according to the U.S. Centers for Disease Control and Prevention. The most common causes contributing to pregnancy-related deaths in the U.S. include infection, sepsis, cardiovascular conditions, hypertensive disorders, and hemorrhage. In July, NIAID hosted a workshop of technology developers, immunologists, maternal health researchers and clinicians to explore the importance and challenges of measuring, predicting and improving reproductive health in the context of maternal and fetal immune systems.
Specifically, the workshop focused on leveraging immune metrics to improve diagnosis and care of pregnant individuals. Attendees discussed the role of immune metrics and function during healthy pregnancy compared to adverse pregnancy outcomes, identified technology gaps, and provided insight into strategies for reducing maternal morbidity and mortality. Specific topics of interest included: enhancing existing laboratory and animal models of pregnancy, identifying optimal timing and dosage of vaccination during pregnancy, obtaining minimally invasive samples to explore biomarkers, and defining clinical consensus on preterm birth and labor.
Discussions at the workshop identified multiple areas in which the field of maternal-fetal immunity can continue to advance. One specific identified area of concern was the use of many different animal models across the field that make it difficult to interpret results across studies. Furthermore, findings from animal models are often not translatable to human-relevant outcomes. Harmonization of animal models, as well as availability of improved models of human disease, will better support translational research, the attendees concluded. Additionally, workshop attendees identified a need for more thorough exploration of infection and vaccination during pregnancy to improve vaccination implementation. Existing protocols for vaccination during pregnancy are not backed by substantial evidence, and it is crucial to understand both the necessary dosage of vaccines and the most effective timing of vaccine administration for optimal immune responses for both the mother and fetus. Another point of significant discussion focused on the need to define the biological and molecular processes that lead to preterm birth and preterm labor. It is believed consensus on a biomolecular definition will improve identification and prevention of adverse outcomes.
Attendees acknowledged that identification of biomarkers during pregnancy to detect infection or other complications quickly and accurately is critical to reverse the upward trends in U.S. maternal mortality. Biomarkers that were originally used for screening fetal chromosomal abnormalities have now been found to be helpful for early detection of certain cancers in pregnant individuals is a poignant example. In conjunction with the need for more extensive biomarker research, there is also a need for improving the range of information gleaned from less invasive patient samples, such as peripheral blood and urine.
The workshop also highlighted the necessity of a multidisciplinary collaborative approach to markedly advance the field. Overall, further integration of technology and multiple perspectives across research disciplines to break down research silos was a primary theme across the workshop. Indeed, the incorporation of social sciences exploring inequity and social determinants of health is vital to this field. Access and ability to obtain prenatal care remains a barrier for many to minimize adverse pregnancy outcomes. Research is needed to understand existing inequities and public health action is needed to address these disparities.
In conjunction with the workshop, NIAID and the NIH Office of Research on Women’s Health issued a funding opportunity to support research on immune mechanisms at the maternal-fetal interface. Competitive applications are expected to focus on one or more of the following goals: 1) improving the understanding of the roles and interactions of immune cells at the maternal-fetal interface that support pregnancy and enable optimal placental development and function; or 2) elucidating the mechanisms by which infection and/or vaccination during gestation modulate immune responses in the pregnant individual and alter systemic or tissue-specific immunity in the offspring. This funding opportunity will support projects aimed at addressing many of the ongoing concerns in the field of maternal-fetal immunity identified in the workshop.