Pregnancy and SARS-CoV-2: an opportunity to systematically study the complexity of maternal health
Authors: Elizabeth Barr, Damiya Whitaker, Pamela Stratton
Journal: The Lancet Digital Health (2022)

Despite a worldwide, strategic, rapid, multi-pronged approach to developing viral-specific testing, therapeutics, and vaccines as the SARS-CoV-2 pandemic unfolded and its pathobiology became understood, the scientifically complex population of pregnant people were routinely excluded from these clinical trials.1Beigi RH Krubiner C Jamieson DJ et al.The need for inclusion of pregnant women in COVID-19 vaccine trials.Vaccine. 2021; 39: 868-870Crossref PubMed Scopus (33) Google Scholar Nearly 2 years later, an information gap on pregnancy-specific therapeutics or vaccines for SARS-CoV-2 persists. Using electronic health records, Samantha Piekos and colleagues2Piekos S Roper R Hwang YM et al.Maternity and SARS-CoV-2: predicting gestational age at delivery by gestational age at infection.Lancet Digit Health. 2021; (published online Jan 13.)https://doi.org/10.1016/S2589-7500(21)00250-8Google Scholar contribute to the evolving knowledge on birth outcomes modified by the pregnancy trimester in which the infection occurred. Comparing pregnant people who had undergone testing and adjusting for common covariates impacting birth outcomes, those with mild or moderate SARS-CoV-2 infections in the first and second trimester had an increased risk of preterm birth and stillbirth. In their study,2Piekos S Roper R Hwang YM et al.Maternity and SARS-CoV-2: predicting gestational age at delivery by gestational age at infection.Lancet Digit Health. 2021; (published online Jan 13.)https://doi.org/10.1016/S2589-7500(21)00250-8Google Scholar details about treatments and management during pregnancy are largely unknown. No one was vaccinated. One could speculate that symptomatic people infected in the first or second trimester of pregnancy received anticoagulation to mitigate the thrombotic risk. As of December, 2021, therapies administered during pregnancy for SARS-COV-2 infection, like most other therapies, are extrapolated from studies of non-pregnant people due largely to barriers excluding women and pregnant people from clinical research.1Beigi RH Krubiner C Jamieson DJ et al.The need for inclusion of pregnant women in COVID-19 vaccine trials.Vaccine. 2021; 39: 868-870Crossref PubMed Scopus (33) Google Scholar, 3Stratton P Gorodetsky E Clayton J Pregnant in the United States in the COVID-19 pandemic: a collision of crises we cannot ignore.J Natl Med Assoc. 2021; 113: 499-503Crossref PubMed Scopus (3) Google Scholar If treatment lessened their risk of thrombotic or microvascular placental disease, their risk of preterm birth or stillbirth might be decreased compared with asymptomatic pregnant people without such treatment. Worldwide, symptomatic pregnant people experienced a higher risk for intensive care, mechanical ventilation, and death accompanied by the suggestion of increased rates of preterm birth.1Beigi RH Krubiner C Jamieson DJ et al.The need for inclusion of pregnant women in COVID-19 vaccine trials.Vaccine. 2021; 39: 868-870Crossref PubMed Scopus (33) Google Scholar, 3Stratton P Gorodetsky E Clayton J Pregnant in the United States in the COVID-19 pandemic: a collision of crises we cannot ignore.J Natl Med Assoc. 2021; 113: 499-503Crossref PubMed Scopus (3) Google Scholar Other respiratory infectious diseases also disproportionately affect pregnant people and neonates albeit at higher rates and virus-specific vaccination improves their outcomes.1Beigi RH Krubiner C Jamieson DJ et al.The need for inclusion of pregnant women in COVID-19 vaccine trials.Vaccine. 2021; 39: 868-870Crossref PubMed Scopus (33) Google Scholar The effect of specific SARS-CoV-2 treatments or vaccination on pregnancy outcome remain unknown. Furthermore, women constitute a higher proportion of those with post-acute sequelae of SARS-CoV-2, yet descriptions of their maternal or pregnancy outcomes are similarly unknown. For pregnant people in the USA, the SARS-CoV-2 pandemic has been a collision of crises.3Stratton P Gorodetsky E Clayton J Pregnant in the United States in the COVID-19 pandemic: a collision of crises we cannot ignore.J Natl Med Assoc. 2021; 113: 499-503Crossref PubMed Scopus (3) Google Scholar To date, studies show differences in risk and outcomes across multiple axes, including sex, gender, race, and age and a disproportionate physical, psychological, and an economic toll on Black, Indigenous, People of colour communities, people living at, near, and below the poverty line, and women.4Webb Hooper M Nápoles AM Pérez-Stable EJ COVID-19 and racial/ethnic disparities.JAMA. 2020; 323: 2466-2467Crossref PubMed Scopus (1052) Google Scholar, 5Rushovich T Boulicault M Chen JT et al.Sex disparities in COVID-19 mortality vary across US racial groups.J Gen Intern Med. 2021; 36: 1696-1701Crossref PubMed Scopus (27) Google Scholar Notably, after adjusting for these sociodemographic factors, the authors report an increased risk of preterm birth and stillbirth in those with less severe SARS-CoV-2 infections acquired early in pregnancy.2Piekos S Roper R Hwang YM et al.Maternity and SARS-CoV-2: predicting gestational age at delivery by gestational age at infection.Lancet Digit Health. 2021; (published online Jan 13.)https://doi.org/10.1016/S2589-7500(21)00250-8Google Scholar Thus, at the heart of the scientific response to SARS-CoV-2, is the question—how can research answer crucial questions fast enough to alleviate suffering, save lives, and ensure that findings are relevant and of benefit for all, including pregnant people? The pandemic revealed an unprecedented opportunity to ensure, even during a crisis, that research is both scientifically rigorous and equitable—concepts that are mutually reinforcing. The complexity of pregnancy with its distinct susceptibilities and physiologies offers a vitally important opportunity to generate much needed evidence through responsible inclusion of pregnant people in research. Contemporary research on the developmental origins of disease has shown that social and structural determinants of health inequities embed themselves epigenetically.3Stratton P Gorodetsky E Clayton J Pregnant in the United States in the COVID-19 pandemic: a collision of crises we cannot ignore.J Natl Med Assoc. 2021; 113: 499-503Crossref PubMed Scopus (3) Google Scholar, 6Hanson M Modi N Focusing on mothers and children for recovery after Covid: where health meets economics and social justice.https://wsimag.com/science-and-technology/66122-focusing-on-mothers-and-children-for-recovery-after-covidDate: 2021Date accessed: October 28, 2021Google Scholar In recognition of the opportunity to incorporate an equity lens and support meaningful integration of sex and gender considerations into SARS-CoV-2 research, the National Institute for Health (NIH) Office of Research on Women's Health (ORWH) developed a set of guiding principles: first, multidimensional approaches to the health of women including pregnancy; second, inclusion across the life course; third, consideration of sex as a biological variable; fourth, assessment of COVID-19's impact on careers; and fifth, purposeful study of understudied, under-represented, and under-reported populations of women.7National Institutes of Health—Office of Research on Women's HealthGuiding principles: sex and gender influences in COVID-19 and the health of women.https://orwh.od.nih.gov/sites/orwh/files/docs/ORWHGuidingPrinciple.pdfDate accessed: October 28, 2021Google Scholar The current NIH Strategic Plan for Women's Health Research and the NIH-Wide Strategic Plan for COVID-19 Research identify pregnancy, maternal health, and prevention of severe morbidity as key areas of focus.8National Institutes of HealthNIH-wide strategic plan for COVID-19 research.https://covid19.nih.gov/sites/default/files/2021-05/NIH-Wide-COVID-19-StratPlan_2021_508_1.pdfDate: 2021Date accessed: October 29, 2021Google Scholar, 9National Institutes of Health—Office of Research on Women's HealthAdvancing science for the health of women. the trans-NIH strategic plan for women's health research.https://orwh.od.nih.gov/sites/orwh/files/docs/ORWH_Strategic_Plan_2019_508C_0.pdfDate: 2019–2023Date accessed: October 29, 2021Google Scholar The Task Force on Research Specific to Pregnant Women and Lactating Women promulgated implementation plans that could guide inclusion of this vulnerable population in research.10Task Force on Research Specific to Pregnant Women and Lactating WomenReport implementation plan.https://www.nichd.nih.gov/sites/default/files/inline-files/PRGLAC_Implement_Plan_083120.pdfDate: 2020Date accessed: October 28, 2021Google Scholar Maternal health disparities in the USA can no longer be ignored, nor can we ignore disparities associated with SARS-CoV-2. It has dramatically illuminated both persistent health inequities and the failure of research, clinical care, and medical education to address the social and structural factors that generate and perpetuate these inequities among those at greatest risk of adverse pregnancy outcome. For populations of women already burdened by historical marginalisation and health impacts of social inequality, the consequences of SARS-CoV-2 are staggering. Internationally, the Venice Forum of researchers and economists argued that sustainable recovery from COVID-19 will require investment in maternal, neonatal, and child health.6Hanson M Modi N Focusing on mothers and children for recovery after Covid: where health meets economics and social justice.https://wsimag.com/science-and-technology/66122-focusing-on-mothers-and-children-for-recovery-after-covidDate: 2021Date accessed: October 28, 2021Google Scholar Intentional consideration of the NIH ORWH guiding principles offers a way to both inspire a more inclusive body of research and encourage a crucial dialogue on the importance of maternal health care and infectious disease prevention in improving the health of women.7National Institutes of Health—Office of Research on Women's HealthGuiding principles: sex and gender influences in COVID-19 and the health of women.https://orwh.od.nih.gov/sites/orwh/files/docs/ORWHGuidingPrinciple.pdfDate accessed: October 28, 2021Google Scholar Piekos and colleagues' recommendation to closely monitor preganant people who have had a SARS-CoV-2 infection during the first or second trimester of pregnancy is an essential beginning. EB and DW declare no competing interests. PS declares royalties and fees paid by UpToDate for a chapter on Diagnosis and Management of Acute Pelvic Pain; McGraw Hill for a chapter in Current Diagnosis and Treatment—Obstetrics and Gynecology; Current Obstetrics and Gynecology Reports for work as a Section Editor on Endometriosis; AbbVie for being a member of the advisory panel on treatment of chronic pelvic pain with botulinum toxin; World Endometriosis Research Foundation for being a member of a panel developing pain specific physical examination criteria; and American Society for Reproductive Medicine for an award for the best clinical abstract in Endometriosis. The acknowledgments are available in the appendix. Download .pdf (.15 MB) Help with pdf files Supplementary appendix The effect of maternal SARS-CoV-2 infection timing on birth outcomes: a retrospective multicentre cohort studyThese results suggest that pregnant people would benefit from increased monitoring and enhanced prenatal care after first or second trimester SARS-CoV-2 infection, regardless of acute COVID-19 severity. Full-Text PDF Open Access