How Research as a Medical Student Shaped My Career Trajectory

My interests at the intersection of reproductive health and healthcare disparities led me to a multidisciplinary research team at Hopkins studying sickle cell disease (SCD) and reproductive health. In this reflection, I will summarize my journey to leading research projects during my medical school career.

In my first study, I wanted to know what patient-facing information existed about in vitro fertilization with preimplantation genetic testing (IVF+PGT) and SCD. I conducted an environmental scan and measured understandability of existing education materials using three validated scales. I found that no materials existed that addressed SCD, and that the average reading level for existing materials was 14.5th grade – inaccessible to most patients.¹

In an effort to fill this gap, I aimed to develop a study. My goal was to design a tool that explained IVF +PGT and other reproductive options for people with SCD or sickle cell trait that met national health literacy standards. I engaged multidisciplinary stakeholders, including reproductive endocrinologists, hematologists, public health researchers, genetic counselors, community health workers, patient advocates, and people with SCD. With input from this working group, we developed a pamphlet detailing IVF + PGT and additional reproductive options that was written at the 5th grade level and met national literacy standards for plain language. I then interviewed young adult patients with SCD to gain their perspectives on the pamphlet. Patients reported feeling hopeful, and all participants considered the pamphlet useful, clear, and appropriate for distribution.² The final education tool is now available on the Sickle Cell Reproductive Health Education Directive (SC RED) website.³

Next Steps

As this work concluded, I realized I wanted more time in medical school to answer under-explored questions about SCD and pregnancy. I thus applied for and received an ASH Medical Student Physician-Scientist Career Development Award, which protected a full-time year of research between my MS3 and MS4 years.

In 2008, Villers and colleagues published a study of national SCD pregnancy morbidity and mortality using the National Inpatient Sample, a U.S.-based national administrative dataset, which includes a sample of 20% of all admissions to acute care hospitals.⁴ As it had been over 10 years since such study outcomes had been reported, we desired to update the figures. The first aim of my project was to use the CDC’s Severe Maternal Morbidity and Mortality Index to compare outcomes between SCD pregnancies and unaffected pregnancies and to consider the effects of racism and prenatal anemia on these outcomes. We found that the maternal mortality rate for people with SCD was 26 times greater than in control deliveries of pregnant people with non-Black race and more than 10 times greater than deliveries among Black pregnant people. Deliveries among people with SCD had significantly higher odds of severe maternal morbidity, and racial disparities explained on average 28.9% of the increased risk in SCD deliveries, suggesting that people with SCD would benefit from addressing racial disparities in pregnancy outcomes and that SCD-specific interventions are needed.⁵ In a second study using the same dataset, we compared pregnancy outcomes among those with prenatal anemia to those with SCD. We found that risks associated with prenatal anemia and SCD were similar for many adverse pregnancy outcomes, especially those associated with ischemia and abnormal placentation, suggesting that prenatal anemia may be a mediator of pregnancy risk in SCD.⁶

While our epidemiological data was important in highlighting disparities and associations, we aimed to gain prospective clinical data in an effort to shape clinical care standards. In the second aim of my ASH Award, I proposed to study blood pressure thresholds in pregnant people with SCD. Baseline blood pressure in adults with SCD is lower than the general population.⁷ The natural history of blood pressure in SCD pregnancy and the appropriate threshold to define hypertensive disorders in this population is unknown. With collaborators in Toronto, we created a multicenter retrospective database of SCD pregnancies that included 292 singleton pregnancies over 30 years. In oral and poster presentations at the ASH annual meeting in 2022, we showed that existing blood pressure thresholds to define hypertensive disorders of pregnancy in the general population are not sensitive for assessing end organ damage associated with preeclampsia in the pregnant SCD population.^8,9

Lessons Learned

I’ll offer the three most important lessons I derived from these experiences:

1. Research can guide your career trajectory. For most of medical school, I planned on becoming an obstetrician. Through my research, I found my own sweet spot, taking an internal medicine approach to approach women’s health in collaboration with brilliant obstetricians.
2. Find a project you care about. In medical school and residency, we squeeze in research in stolen moments around hefty clinical demands. Perhaps your willpower is stronger than mine, but I find it difficult to motivate my tired brain to work on research in “off” moments unless it’s for a project I find compelling.
3. You can get a grant! Protected research time is pivotal and precious, and grants exist at every stage of training to help protect that time (thanks ASH!).

Ms. Early has indicated no relevant conflicts of interest. Dr. Pecker is funded through NIH/NHLBI K23HL146841 and NIH/NHLBI U01 HL156620-01, the American Society of Hematology, Doris Duke Charitable Foundation Grant #2020147, and the Mellon Foundation and Alexion and is a consultant for Global Blood Therapeutics and Novo Nordisk.

Macy Early, [email protected]
Lydia Pecker, [email protected]

References:

1. Early ML, Kumar P, Marcell AV, et al. Literacy assessment of preimplantation genetic patient education materials exceed national reading levels. Journal of Assisted Reproduction and Genetics. 2020:37:1913–1922.
2. Early ML, Strodel RJ, Lake IV, et al. Acceptable, hopeful, and useful: development and mixed-method evaluation of an educational tool about reproductive options for people with sickle cell disease or trait. Journal of Assisted Reproduction and Genetics. 2020.
3. https://sicklecellred.org/resources/
4. Villers MS, Jamison MG, De Castro LM, et al. Morbidity associated with sickle cell disease in pregnancy. American Journal of Obstetrics and Gynecology. 2008:199:125.e1-5.
5. Early ML, Eke AC, Gemmill A, et al. Severe maternal morbidity and mortality in sickle cell disease in the national inpatient sample (2012-2018). JAMA Network Open. 2023:6(2):e2254545.
6. Early ML, Eke AC, Gemmill A, et al. Comparisons of severe maternal morbidity and other adverse pregnancy outcomes in pregnant people with sickle cell disease versus anemia: shared ischemic and placental complications. JAMA Network. 2023:6(2):e2254552.
7. Pegelow CH, Colangelo L, Steinberg M, et al. Natural history of blood pressure in sickle cell disease: Risks for stroke and death associated with relative hypertension in sickle cell anemia. American Journal of Medicine. 1997:102(2):171–177. https://doi.org/10.1016/S0002-9343(96)00407-X.
8. Early ML, Malinowski AK, Solow M, et al. Trajectory of blood pressure in pregnant people with sickle cell disease: A multinational study. Poster presentation at 2022 American Society of Hematology Annual Meeting, Dec 2022.
9. Early ML, Malinowski AK, Solow M, et al. Sickle cell disease-specific blood pressure thresholds for hypertensive disorders of pregnancy: A multinational study. Oral presentation at: 2022 American Society of Hematology Annual Meeting, Dec 2022.