; Professor and Vice-Chair of Obstetrics and Gynecology; Gillette Professorship of Obstetrics and Gynecology; and Chief of Maternal-Fetal Medicine at 

Catherine Y. Spong, MD

I applaud providers for encouraging COVID-19 vaccination for pregnant and lactating women. Recent data published from the V-safe pregnancy registry, v-safe after vaccination health checker surveillance system, and the vaccine Adverse Event Reporting System provides reassurance of the use of the mRNA vaccine in pregnancy.

This report of 35,691 pregnant women who received the COVID vaccine did not identify safety signals. Given that neither pregnant nor lactating women were included in the preauthorization clinical trials, post-authorization monitoring was performed to evaluate the safety of the vaccine. As we have previously highlighted, pregnant and lactating women need to be included in the evaluation of new therapeutic products.

 Importantly, given the risks of COVID, professional societies and organizations encouraged vaccination for these women even without such data. 

Moving forward it is essential for us, as practitioners, to advocate for our patients and continue to push for their inclusion in the development and evaluation of products important for their care.

® highlights another area of vital importance for our patients. With the emphasis on severe maternal morbidity and public reporting of adverse maternal outcomes, attention is driven to optimize maternal health. By optimizing health prior to and in pregnancy, both maternal and fetal outcomes may be improved. One example is maternal anemia, which is estimated to affect 42% of pregnant women globally.

 Maternal anemia is associated with a number of adverse maternal outcomes including preterm birth, fetal growth restriction, and transfusion. Transfusion is a leading cause of severe maternal morbidity. Therefore, prevention of anemia is an important goal both for the practitioner and the pregnant woman.

Maternal anemia is in part a physiologic response to the doubling of blood volume and increased requirements of the development of the fetus and placenta. It is usually due iron deficiency. Iron demands increase substantially in pregnancy, when there is an estimated total iron requirement of 1040 mg, with the greatest need in the third trimester. These needs are met through both dietary iron intake and mobilization of maternal iron stores (which often are insufficient).

Although oral iron supplementation is routinely recommended in pregnancy, it is often poorly tolerated. Furthermore, iron absorption is poor, thus increasing intake does not necessarily parallel iron uptake. Intravenous iron supplementation is increasingly available, and formulations have mitigated adverse outcomes and complications. Shrayva Govindappagari, MD, and colleagues provide insight on the role of IV iron in the setting of iron deficiency anemia in pregnancy in this issue. As they describe, the evidence base is growing and now include clinical trials, systematic reviews, and meta-analyses. In the first and second trimesters, reliance on oral supplementation and dietary counseling is best, with progression to IV iron if these fail, given the importance of adjudication of anemia prior to delivery.

As practitioners, advocating for our patients and managing common conditions to facilitate optimal pregnancy outcomes through preventative measures such as vaccination and addressing anemia have the potential for major impact. 

Shimabukuro TT, Kim SY, Myers TR, et al. Preliminary findings of mRNA Covid-19 vaccine safety in pregnant persons. 

 2021; 384 (24):2273-2282.doi: 10.1056/NEJMoa2104983. Epub 2021 Apr 21.

Spong CY. Addressing inequities in women's health research. 

Adhikari EH, Spong CY. COVID-19 vaccination in pregnant and lactating women. 

. 2021;325(11):1039–1040. doi:10.1001/jama.2021.1658

Goonewardene M, Shehata M, Hamad A. Anaemia in pregnancy. 

2012; 26(1):3-24. doi: 10.1016/j.bpobgyn.2011.10.010

Articles

As practitioners, advocating for our patients and managing common conditions to facilitate optimal pregnancy outcomes through preventative measures such as vaccination and addressing anemia have the potential for major impact.

Steps to optimize maternal health

Attention and accountability are the 2 “A’s” that drive change. It’s true in medicine, business, even family. If it is not monitored, it is not regarded as important nor will change be affected. As ob/gyns, we see this in our practice. Those where cesarean delivery, open, and laparoscopic hysterectomy rates (among others) are publically known, ideally alongside others in similar practice, typically adjust if they become an outlier. 

Proving the point, several studies have shown that institutional interest in a metric directly affects change. Oshiro and colleagues demonstrated that implementing a policy and institutional awareness to reduce elective early-term deliveries affected an 83% decline in 1 year, from 37.8% to 4.8%.

 Wilson-Leedy and colleagues demonstrated a reduction in overall cesarean delivery rate and cesarean after induction of labor after implementing a labor management guideline at their institution.

The key features are that leadership agrees the metric is important, it is tracked, and reported out regularly. Metrics that help guide decisions and ensure accountability are also useful. Without knowledge, we cannot affect change. In his 2015 book “

,” Yuval Noah Harari wrote that knowledge is power.

 The real test of knowledge, he said, is not whether it is true, but whether it empowers us.

I can’t help but ask how we can use these concepts to enhance inclusion. I believe we can all find in our inbox invitations to meetings with expert panels— often with photos of the experts. Interestingly, and often, many experts seem to share similar characteristics. Although it is essential that those participating are considered experts— how do we ensure that we are truly expanding these rosters to represent the best cross-section? 

When we developed a roster such as for a meeting, review group, or advisory panel at the National Institutes of Health, it was essential that the panel was diverse. Each roster was submitted with a table that listed the name, gender, race, ethnicity, and geographic location. These were attempts to ensure diversity. In my mind, this exercise is both positive and negative. 

On one hand, experts must be at the table, and people are not included simply on the basis of a characteristic. However, this method only ensures diversity and gives the appearance of being inclusive. Without directed thought to truly achieve real diversity, this method is not sufficient. It is critical to measure something meaningful, not just something easily measured. 

A difficulty in identifying diversity lies in the knowledge of who is creating the roster, who they know, and who is considered an expert in the topic. To enhance diversity, amplifying experts across gender, race, ethnicity, geography, and any other grouping is essential. A few groups have started this process. 

For example, there are lists of women in maternal and fetal health, microbiology, infectious diseases, cardiology, pelvic floor disorders, women’s health policy, and more, just as examples, that should be curated and then used to ensure representation. One such group is the Womxn’s Health Collaborative. At 

WomxnsHealthCollaborative.org/list-of-women-in-womens-health-research

, you will find a working list of women in women’s health research. If you are so inclined, you should add your own name there and your areas of expertise. If you know of others who should be added, please also let them know.

Throughout human existence, the challenge has been putting new knowledge to work meaningfully as it is acquired in scientific research. We must continually assess where we are and where we want to be so that the knowledge we build upon becomes a true representation of the human race. Evolving science requires critical thinking for an effective model that will benefit human health. As physicians and scientists who dedicate our lives to women’s health, we should want that to be our legacy. 

Oshiro BT, Kowalewski L, Sappenfield W, et al. A multistate quality improvement program to decrease elective deliveries before 39 weeks of gestation. 

. 2013;121(5):1025-1031. doi: 10.1097/AOG.0b013e31828ca096. Erratum in: Obstet Gynecol. 2013 Jul;122(1):160.

Wilson-Leedy JG, DiSilvestro AJ, Repke JT, Pauli JM. Reduction in the cesarean delivery rate after obstetric care consensus guideline implementation. 

. 2016;128(1):145-152. doi: 10.1097/AOG.0000000000001488

Attention and accountability are the 2 “A’s” that drive change. It’s true in medicine, business, even family. If it is not monitored, it is not regarded as important nor will change be affected. 

Moving Beyond Checking the Box

New variants of coronavirus disease 2019 (COVID-19) and slow vaccination rates are prolonging the quarantine, and there is no certain end in sight. Without a clear path to a semblance of normalcy for our careers, families, and communities, it should be no surprise that our well-being is in jeopardy.

From private practice to academic medicine, strategies to proactively address physician wellness are urgently needed. Results from a survey of 1122 academic faculty across the nation reported that individuals feeling very or extremely stressed more than doubled from 2019 (32%) to 2020 (70%), and almost 3 times as many had increased anger (12% vs 35%).

During the same time frame, more than 12,000 physicians surveyed reported their rate of being “somewhat” or “very” happy declined from 82% to 58%,with a similar decline reported for ob/gyn physicians (81% to 57%).

 Female faculty members reported a dramatic increase in feeling stressed, from 34% to 75%, and they experienced stress at higher rates than men, 75% to 59%.

Since May 2020, 40% of women reported symptoms of anxiety or depression (

), which is almost 4 times higher than the 11% reported in 2019.

Figure. Anxiety and Depression in Women and Men: 2020-2021

Given the predominance of female ob/gyns—83% of residents are women—these statistics really hit home. The shift to remote learning and limited child care options have affected these colleagues, as women disproportionally shouldered the burden.

 For women, the dual role of being the family’s primary caregiver and practicing medicine has made the balancing act untenable for many, affecting both their mental health and career.

Many accept—often request—night and/or weekend shifts to maximize time at home to assist with child care and remote learning. In return, they have no down time, time to accomplish academic goals, or opportunity to recharge. Remote working has resulted in busier schedules and often longer hours for many, with fewer breaks as virtual meetings are stacked one on top of another. As eloquently stated in a recent Womxn’s Health Collaborative online post, the effort “comes at the expense of our own health and well-being.”

Solutions are not obvious, especially for ob/gyns. Early responses have been to encourage us to take care of ourselves, but when can we do this? Others have recommended taking time off; this burdens our colleagues and often results in insurmountable amounts of catch-up when we return.

 Physician burnout as a critical topic predates the pandemic. 

The National Academy of Medicine launched a resource repository on clinical burnout and well-being in 2018.

 There is a wealth of information on causes, effects, and solutions for clinical burnout available. Solutions include organizational and individual strategies, such as fostering communication, cultivating teamwork, and practicing mindfulness; however, data demonstrating their effectiveness are limited. Ultimately, system changes to address the inequity are needed to adjust metrics and support women in all roles: career, family, and community.

Physician burnout and the need for wellness will not be resolved once the pandemic is behind us. The American College of Obstetricians and Gynecologists has 5 warning signs of burnout: dread, increased complaining, irritability, lapses in confidentiality, and loosening boundaries.

For ourselves and our colleagues, let’s keep these in mind and work with each other to identify and address burnout proactively. A first step, although clearly not a solution, is having someone to talk to, someone to share the realities of life with. This can help us to address our burnout and provide an outlet. 

Although we cannot eliminate the current emphasis on virtual working, remote learning, and limited child care, we can enhance our support for each other. 

1. On the verge of burnout: COVID-19’s impact on faculty well-being and career plans. Chronicle of Higher Education

https://connect.chronicle.com/rs/931-EKA-218/images/Covid%26FacultyCareerPaths_Fidelity_ResearchBrief_v3%20%281%29.pdf

2. Martin KL. Medscape physician lifestyle & happiness report 2021. January 15, 2021. Accessed March 22, 2021. 

http://www.medscape.com/slideshow/2021-lifestyle-happiness-6013446

3. Martin KL. Medscape obstetrician & gynecologist lifestyle, happiness & burnout report 2021. February 19, 2021. Accessed March 22, 2021. 

http://www.medscape.com/slideshow/2021-lifestyle-obgyn-6013515

4. Anxiety and depression: Household Pulse Survey. Centers for Disease Control and Prevention. Updated March 10, 2021. Accessed March 22, 2021. 

http://www.cdc.gov/nchs/covid19/pulse/mental-health.htm

5.Sevilla A, Smith S.Baby steps: the gender division of childcare during the COVID-19 pandemic. 

. 2020;36(suppl 1):S169-S186. doi:10.1093/oxrep/graa027

6. Johnson C, Thornton H. Bracing for impact. Womxns Health Collaborative. Accessed March 22, 2021. 

https://womxnshealth.medium.com/bracing-for-impact-894b9f13db84

7. Sharing knowledge to combat clinician burnout. Clinician Well-Being Knowledge Hub. Accessed March 22, 2021. 

8. At risk for burnout? Check these 5 warning signs. The American College of Obstetricians and Gynecologists. January 28, 2019. Accessed March 22, 2021. 

http://www.acog.org/news/news-articles/2019/01/at-risk-for-burnout-check-these-5-warning-signs

Rarely a day goes by without a post, article, or email about physician burnout. 

Smoldering

As is clear from publications (and even my daughter's eighth grade science project, “COVID-19 Vaccine: Effectiveness Limited by Inclusion?”), neither group was included in therapeutic product or vaccine development for COVID-19.

As one who is passionate on the topic, I am disheartened by the lack of progress. Of many recommendations by experts, I see some opportunities that are surmountable and some that are critical, but difficult, to address.

First, an inclusion mandate should be required for pregnant and lactating people in research. At present, pregnant people are excluded from research by default. Those governing, funding, and/or mandating trials should require an explanation of why pregnant and lactating people are excluded. In 1993, with the passage of the National Institutes of Health (NIH) Revitalization Act, NIH-funded investigators were required to include women in human subject research

The 2000 U.S. Government Accountability Office Report on Women’s Health found significant progress in representation of women in clinical trials because of the requirement of assessment of their inclusion as part of the scientific merit of the research grant

. In the past several decades this has expanded and now all NIH grant applications include a section on inclusion on the basis of sex/gender, race, ethnicity, and age in clinical research

. Further expansion to include pregnant and lactating people is an attainable short-term goal that will focus the inclusion by default.

Second, recommendations for pregnant and lactating people should be more clear and not phrased in language that has a negative connotation. The phrasing of recommendations, especially for pregnant and lactating people, is critical; and when written in a confusing or negative framing, raise alarm. 

For example, although not included in the clinical trials, both the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention were permissive for pregnant and lactating people to receive the vaccine. Our professional organizations, the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM), worked with the experts to devise guidance in the absence of data. However, in an attempt to be unfailingly cautious, the verbiage for pregnant women is negative – “should not be withheld,” rather than positive – “should be offered,” as is the case for nonpregnant and lactating people 

Table 1. Professional Guidance for COVID-19 Vaccine for Pregnant and Lactating Women

Similarly, the NIH’s Coronavirus Disease 2019 (COVID-19) Treatment Guidelines include a section on pregnancy, which I take as a positive step to be included in the considerations; however, the language is negative, “The COVID-19 Treatment Guidelines Panel…recommends that potentially effective treatment for COVID-19 should not be withheld from pregnant women because of theoretical concerns related to the safety of therapeutic agents in pregnancy.

Furthermore, at times guidance was unclear and misguided, as noted by the World Health Organization’s statement on January 26, 2021, that pregnant women should not receive the Moderna vaccine, then rescinding that statement days later—but the damage was done. With these missteps, additional education and clarification are needed, and opportunities for vaccination are lost.

As is often said, the elephant in the room for inclusion is that of liability, intertwined with litigation. Until progress is made to mitigate liability, implement targeted incentive programs, and/or strengthen the authority of the FDA to require clinically relevant data on pregnant and lactating people, real progress on inclusion of pregnant people in development of therapeutic products or vaccines is not possible. 

Understandably, pharmaceutical companies are not interested in testing novel therapeutics in pregnant and lactating people given the potential of teratogenicity – further complicated by the complex physiology and metabolism. This seemingly insurmountable task has been discussed ad infinitum by experts. 

With no entity charged or overseeing the task, there is no clear path forward. A champion is urgently needed to motivate, legislate, and/or creatively innovate a path forward.

Clearly the COVID-19 pandemic has further highlighted the disparity for pregnant and lactating people. Without data, education and communication are key for the discussion of COVID-19 vaccination and therapies in our patients. One thing is certain—death crosses the placenta, and we all have seen or heard of fatal cases of COVID-19 in pregnancy. 

Preventing severe and critical COVID-19 illness in our pregnant and lactating patients is of highest priority. Creating the evidence base through research for our pregnant and lactating patients is essential, with a default of inclusion not exclusion. 

1. National Institutes of Health (NIH). Title 42—The Public Health and Welfare. § 289a–2. Accessed February 19, 2021. https://www.govinfo.gov/content/pkg/USCODE-2011-title42/pdf/USCODE-2011-title42-chap6A-subchapIII-partH-sec289a-2.pdf

2. U.S. Government Accountability Office. Women’s Health: NIH Has Increased Its Efforts to Include Women in Research. HEHS-00-96: Published: May 2, 2000. Publicly Released: May 2, 2000. Accessed February 19, 2021. https://www.gao.gov/products/HEHS-00-96

3. National Institutes of Health. Guidelines for the Review of Inclusion on the Basis of Sex/Gender, Race, Ethnicity, and Age in Clinical Research. Updated March 18, 2019. Accessed February 19, 2021.https://grants.nih.gov/grants/peer/guidelines_general/Review_Human_Subjects_Inclusion.pdf

4. National Institutes of Health (NIH). COVID-19 Treatment Guidelines. Special considerations in pregnancy. Updated August 27, 2020. Accessed February 19, 2021. https://www.covid19treatmentguidelines.nih.gov/special-populations/pregnancy/

A major missed opportunity. Decades of effort including the development of guidance and implementation by individuals, groups, professional organizations, even the United States Congress, to address and facilitate inclusion of pregnant and lactating people in research and trials held no sway in the studies addressing the coronavirus disease 2019 (COVID-2019) pandemic.

Catherine Y. Spong, MD

Articles

Steps to optimize maternal health

Moving Beyond Checking the Box

Smoldering

A Missed Opportunity