Protect Pregnant and Lactating Women with COVID-19 Through Research, Not from Research

Abstract

Breastfeeding MedicineVol. 15, No. 6 President's CornerFree AccessProtect Pregnant and Lactating Women with COVID-19 Through Research, Not from ResearchAlison StuebeAlison Stuebe—Alison Stuebe, MD, MSc, President, Academy of Breastfeeding Medicine Search for more papers by this authorPublished Online:9 Jun 2020https://doi.org/10.1089/bfm.2020.29155.amsAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail As the COVID-19 pandemic continues, more and more women are giving birth while battling SARS-CoV-2. New evidence suggests that remdesivir may be a promising therapy for severe disease, and the United States Food and Drug Administration has authorized the drug for emergency use.1 However, we have no data on whether the drug is present in human milk, leaving clinicians with minimal information to counsel lactating mothers with severe disease.Before the FDA's emergency use authorization, remdesivir was available for compassionate use for pregnant women and for children <18 years. However, women receiving compassionate use treatment were forbidden to breastfeed, posing a dilemma for women giving birth with critical COVID-19 disease. Should she access potentially life-saving therapy, or provide human milk for her infant, which confers innate and specific immune protection, and may contain Immunoglobulin A (IgA) antibodies that will protect her infant from contracting COVID-19?Breastfeeding mothers were also excluded from clinical trials of remdesivir; thus nursing mothers with severe COVID-19 had to choose between continuing to breastfeed during a global pandemic and potential access to effective therapy. And because lactating women were excluded, there are no data on presence of the drug in milk, or on outcomes among infants breastfed while mothers were on therapy. The only data are a single case report of a newborn with Ebola treated with remdesivir.2What we do know is that remdesivir is administered intravenously. It is a relatively small molecule, so it may transfer into milk, but to affect the infant's health, it would have to be absorbed from the gastrointestinal tract in its active form. According to breastfeeding pharmacologist Tom Hale, the molecule would be unstable in the stomach and would be easily broken down before oral absorption, thus it is only administered intravenously. It is, therefore, very unlikely that the active drug would reach the infant's circulation.Although clinical trials and compassionate use protocols forbid breastfeeding, the FDA's Emergency Use Authorization Fact Sheet3 leaves some room for shared decision making. In the risk summary, it states:Because of the potential for viral transmission to SARS-CoV-2-negative infants and adverse reactions from the drug in breastfeeding infants, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for remdesivir and any potential adverse effects on the breastfed child from remdesivir or from the underlying maternal condition.Although the acknowledgment of the developmental and health benefits of breastfeeding is welcome, it is troubling that this document alludes to the potential for viral transmission of SARS-CoV-2 through milk, given that both the World Health Organization4 and the Centers for Disease Control and Prevention5 recommend that infants of COVID-19-positive mothers be fed mother's milk. If anything, the risks of iatrogenic cessation of breastfeeding are magnified in the setting of the COVID-19 pandemic. Artificial feeding is associated with a 3.6-fold higher rate of infant hospitalization for severe pneumonia, compared with being exclusively breastfed for ≥4 months.6 A mother with COVID-19 who discontinues breastfeeding to avoid the theoretical risk of exposing her infant to remdesivir may thus triple the risk of hospitalization if her child contracts the virus.The current dilemma regarding remdesivir therapy in breastfeeding mothers is not an isolated circumstance—it is the consequence of longstanding policies to exclude pregnant and lactating women from clinical trials. In 1977, driven, in part, by tragic outcomes of thalidomide, diethylstilbestrol, and the Dalkon Shield, the FDA excluded women of childbearing potential from phase 1 and early phase 2 clinical trials.7 As a result, important differences in safety and efficacy of medications between women and men were not evaluated. In 1994, the Institute of Medicine explored the ethical and legal issues of including women in clinical studies, noting that because pregnant and lactating women are often excluded from research studies, clinicians and patients are forced to make treatment decisions in the absence of evidence.8Nevertheless, for decades, research among pregnant and breastfeeding women has languished. This approach has left clinicians with a paucity of information to make decisions about therapy for pregnant and breastfeeding mothers. Too often, clinicians opt not to treat maternal diseases such as depression and anxiety during pregnancy, or advise women to wean when they start treatment, without considering the risks of iatrogenic weaning for the health and well-being of mother and child.Pregnant and lactating women deserve evidence-based treatment for medical conditions. To address this gap, the Coalition on Maternal Therapeutics (CAMT),9 of which the Academy of Breastfeeding Medicine is a member, successfully advocated for the 21st Century Cures Act to establish the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC). In September 2018, PRGLAC issued 15 recommendations to the Secretary of Health and Human Services.10 The report urges a proactive approach to protocol development and study design to include pregnant women and lactating women in clinical research.Although many medications are present in human milk, levels are typically quite low, and the breastfeeding child consumes a fraction of a therapeutic dose. Moreover, for a drug that is present in milk to affect the child, it must survive passage through the digestive system and be orally absorbed in its active form. These nuances are often lost on clinicians, who advise women to suspend or stop breastfeeding "just to be safe." As with so many flaws in our health system, the dangers of this mindset have been magnified by the COVID-19 pandemic. For the mother with COVID-19, suspending breastfeeding to initiate treatment may be the least safe thing she can do for her infant.In light of COVID-19, the CAMT is now advocating with industry and trade groups to ensure inclusion of pregnant and lactating women in clinical trials. As the CAMT argued in a letter to the National Institutes of Health and the Food and Drug Administration,11 "there needs to be a cultural shift to protect women through research rather than protecting them from research." The last 2 months have transformed every facet of our lives. Going forward, let us all work together to make sure that medical research fully includes pregnant and lactating women.References1. Hinton DM, Food and Drug Administration. Remdesivir for the treatment of hospitalized 2019 coronavirus disease (COVID-19) patients. Available at https://www.fda.gov/media/137564/download (accessed May 3, 2020). Google Scholar2. Anderson PO. Breastfeeding and respiratory antivirals: Coronavirus and influenza. Breastfeed Med 2020;15:128. Link, Google Scholar3. Food and Drug Administration. Fact sheet for health care providers emergency use authorization (EUA) of remdesivir (GS-5734TM). Available at https://www.fda.gov/media/137566/download (accessed May 2, 2020). Google Scholar4. World Health Organization. Clinical Management of Severe Acute Respiratory Infection (SARI) When COVID-19 Disease Is Suspected. Geneva: World Health Organization, 2020. Google Scholar5. Centers for Disease Control and Prevention. Interim Considerations for Infection Prevention and Control of Coronavirus Disease 2019 (COVID-19) in Inpatient Obstetric Healthcare Settings. Available at https://www.cdc.gov/coronavirus/2019-ncov/hcp/inpatient-obstetric-healthcare-guidance.html (accessed May 2, 2020). Google Scholar6. Bachrach VR, Schwarz E, Bachrach LR. Breastfeeding and the risk of hospitalization for respiratory disease in infancy: A meta-analysis. Arch Pediatr Adolesc Med 2003;157:237–243. Crossref, Medline, Google Scholar7. Gee RE, Wood SF, Schubert KG. Women's health, pregnancy, and the U.S. Food and Drug Administration. Obstet Gynecol 2014;123:161–165. Crossref, Medline, Google Scholar8. Risks to Reproduction and Offspring. In: Mastroianni ACFaden RFederman D, eds. Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies: Volume I. Washington, DC: National Academies Press (US), 1994. Google Scholar9. Coalition to advance maternal therapeutics. Available at https://www.smfm.org/advocacy/camt (accessed May 3, 2020). Google Scholar10. Task force on Research Specific to Pregnant Women and Lactating Women. Report to Secretary, Health and Human Services, Congress. Washington, DC, 2018. Google Scholar11. Coalition on Maternal Therapeutics. COVID-19 and pregnant women and lactating women. Available at https://s3.amazonaws.com/cdn.smfm.org/media/2268/Final_CAMT_COVID_Letter_March_2020.pdf (accessed May 3, 2020). 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