The Year's Best in Sickle Cell Disease: A Global Perspective on Pregnancy in 2019

Research in pregnant females has been a daunting task due to the limitation in studies that can be completed in a population designated as “vulnerable” by governing research bodies. The irony of pregnant women being classified as “vulnerable,” thus obstructing rigorous research, is that such a culture results in more “experimentation” in how we approach pregnancy. This is particularly accurate for women with sickle cell disease (SCD), where our understanding of management and outcomes is exceptionally poor and fragmented. Pregnancy in SCD is a critical concern and requires immense attention to detail in the management of both mother and child. In this article, we will spotlight meaningful efforts undertaken this year to patch the gaps in our quilt of knowledge relating to both maternal and fetal management and outcomes of pregnancy in SCD.

In a series of several unique papers, a common theme of disparities on outcomes among pregnant women with SCD emerged across several continents. In the United States, Dr. Evelyn Bae and colleagues compared post-partum outcomes in patients with and without SCD.¹  This massive undertaking was a retrospective analysis of discharge data from almost seven million inpatient deliveries in California, Florida, New York, Maryland, and Kentucky during a seven-year span. Outcomes of interest were 30- and 90-day readmission rates, in hospital mortality, length of stay, and total hospital charges. And while the results of this study may be predictable, the degree of disparity is staggering. Pregnant women with SCD were found to be more than two times as likely to die in the hospital, 27 percent more likely to be readmitted 30 days post-partum, and 92 percent more likely to be readmitted 90 days post-partum. They also found longer lengths of stay, increase in hospital charges, and increased likelihood of post-partum complications compared to the non-SCD group. Beyond this, women with SCD were also found to have increased rates of sickle cell-associated complications, including deep venous thrombosis, urinary tract infections, sepsis/shock, supraventricular arrhythmias, cardiac arrest, myocardial infarction, stroke, pulmonary embolism, pneumonia, and acute renal failure. While there are limitations in using claims data to generate information, this study must be lauded for its expansive nature, and its ability to shed light on a mountain of disparities in outcomes of pregnant women with SCD. Dr. Bae’s study reminds us that the implementation of targeted strategies to narrow the outcomes gap between these groups of patients is critically overdue.

In Saudi Arabia, Drs. Yasmeen Haseeb and Nourah Al Qahtani completed the first study in pregnant women with SCD in the country.²  This retrospective cohort study done in the Eastern Province of Saudi Arabia identified 302 SCD patients and compared them to 600 pregnant women matched for age and parity over 10 years in a tertiary care teaching hospital. Their results highlight a higher complication rate among pregnant women with SCD. Hypertensive disorders and intrauterine growth restriction were the more common findings, with thromboembolism and stroke following. Both the use of Neonatal Intensive Care Unit services and still births were also increased compared to the control population. 

Similar poor outcomes were described by Dr. Siris Patel and colleagues in India, who undertook an eight-year retrospective study of pregnancy outcomes among women with SCD.³  This study found that about half of the total pregnancies were uneventful in that they did not have any painful events or history of blood transfusions or other medical or obstetric complications. Of the rest, one third of pregnancies had a history of painful events, just over one third of pregnancies required blood transfusion with an average hospitalization of 0.5 times per pregnancy besides during delivery.

In perhaps the most sickle cell burdened area, Lagos, Nigeria, Dr. Ochuwa Babah, completed a prospective case-control study that compared women with SCD to women without SCD at two tertiary care centers in Nigeria.⁴  Vaso-occlusive crisis, pregnancy induced hypertension, urinary tract infection, and intrauterine growth restriction were more common. The incidence of low birth weight was 38 percent in HbSS and 4 percent in the non-SCD group, which once again, highlights the need for specialized care in this group of individuals. These studies underscored the fact that poor health outcomes among pregnant women with SCD appears to be a global problem.

To tackle this mammoth problem, a brave team of investigators led by Dr. Michael DeBaun of Vanderbilt University along with colleagues in Ghana took on the challenge of addressing the substantial disparity in pregnancy outcomes with a prospective cohort study after implementation of a multidisciplinary care program.⁵  The first achievement is one of implementation of uniformity in care for pregnant women with SCD at the Korle-Bu Teaching Hospital, the largest tertiary care center in Ghana. The cases included pregnant women with SCD (HbSS or HbSC) and a comparison group of pregnant women without SCD or sickle cell trait attending the same antenatal clinic, matched for age and parity. All participants were followed during pregnancy and for up to six weeks post-partum. The implementation strategy was multipronged and included generation of buy-in of new treatment protocols from the Ghanaian team, creation of a multidisciplinary sickle cell-obstetric team, adaption of an environment that expected, supported and rewarded innovation, and the development of a communication system to discuss patients. The new approach to obstetric care allowed the team to identify high-risk SCD patients and generate a blueprint for closer follow-up, initiation of incentive spirometry (innovatively using latex balloons), clear identification and delineation of vaso-occlusive pain episodes and acute chest syndrome, routine evaluation for malaria, and widespread testing for SCD in all newborns in the cohort. During a 20-month period, 152 pregnant women with SCD (HbSS, 55; HbSC, 97) and 122 pregnant women without SCD were enrolled. The standardized multidisciplinary care approach reduced maternal and perinatal mortality rates among pregnant women with SCD by about 90 percent. There were only two deaths in the SCD group (acute chest syndrome and pulmonary embolism) and this was comparable to the outcomes among pregnant women without SCD (one death: anesthesia related complications).

This impressive study demonstrated that implementation of low-technology strategies in a low-resource environment result in the dramatic reduction of high prenatal and perinatal maternal mortality rates in SCD that were essentially decreased to levels comparable to women without SCD. The cohort study identified several key themes: women with SCD had increased rates of preeclampsia, hospitalization for malaria, preterm births and low birthweight infants; preeclampsia and low body mass index (BMI) is associated with preterm birth and low birthweight in women with SCD; and compared to HbSC, pregnant women with HbSS had higher rates of perinatal morbidities. Furthermore, the study showed that pre-eclampsia, low BMI, and HbSS phenotypes were associated with premature delivery (< 37 weeks) in women with SCD.

In summary, while the therapeutic landscape of SCD is rapidly moving towards a zenith, there remain many gaps in our ability to provide comprehensive care to individuals with SCD. In 2019, the data that have been presented to us by colleagues worldwide are consistent and sobering; it is imperative that we acknowledge the disparity in outcomes in pregnant women with SCD and work as a community to drive forward with higher quality and rigor in our care of these patients. If there is one crucial theme to consider, it is that revolution does not entail extravagant and convoluted methodologies but rather clear and consistent change, as a team of dedicated individuals brought to Ghana. In a country without updated and comprehensive guidelines on pregnancy in SCD, perhaps this snapshot will serve as a reminder that change is needed right here at home.