TO THE EDITOR:
Pregnant women with sickle cell disease (SCD) are at an increased risk for both pregnancy and SCD related morbidity and mortality in low, middle, and high-income countries.1 The maternal death rate in pregnant women with SCD in sub-Saharan Africa is 7% to 12%.2-4
At the Korle-Bu Teaching Hospital (KBTH), a national referral center in Accra, Ghana, the maternal and perinatal mortality rates were 10 791 per 100 000 live births (case fatality rate: 9.5%) and 60.8 per 1000 total births, respectively, between January 2014 and April 2015.5 In May 2015, the multidisciplinary sickle cell disease (SCD) obstetrics team started the following interventions: a joint obstetrics and hematology outpatient visit, weekly case conference to discuss challenging cases with SCD, and simple protocols for inpatient management of acute chest syndrome (ACS) and acute pain episodes. Periodic training of nursing and medical staff on the management of pregnant women with SCD both on outpatient and in-patient basis was also provided. These interventions resulted in a dramatic reduction in maternal and perinatal mortality in this cohort by 89.1% and 62.2%, respectively, after just 13 months of intervention. The maternal and perinatal mortality rates after intervention were reduced to 1176 (1/85) per 100 000 live births (case fatality rate: 1.1%) and perinatal mortality rate of 23.0 per 1000 total births, respectively.5
Using our preestablished protocols for care of pregnant women with SCD,5,6 the multidisciplinary SCD obstetrics team at KBTH tested the hypothesis that the low maternal and perinatal mortality incidence rates at KBTH will be sustained over 3 years. We conducted a retrospective cohort postintervention quality assessment study of standard care (1 June 2016 to 31 December 2019 [43 months]: sustainability period) and compared the results to our previously documented postintervention period (1 May 2015 to 31 May 2016; 13 months) as a historical control.5 Institutional approval was obtained from the KBTH Institutional Review Board. The study was performed in accordance with the Declaration of Helsinki. Maternal and perinatal mortality were the principal variables assessed. Members of the team adjudicated all acute maternal events requiring hospitalization and all maternal deaths. As per our previously published case series, all deaths before arrival at the hospital, and those without documented evidence of hemoglobin phenotype were excluded.7 We also excluded all cases that were nonattendants at the multidisciplinary SCD obstetrics outpatient clinic. The maternal mortality records, patients’ admission and discharge files, labor ward records, and autopsy reports of all SCD-related maternal deaths within the study period were retrieved and reviewed by the team. We defined maternal death as direct and indirect obstetric causes according to the World Health Organization International Classification of Diseases (ICD-10).8 Data were summarized as simple descriptive statistics. The Mann-Whitney U-test and Fisher exact test evaluated differences between pregnant women with Hemoglobin SS (HbSS) vs Hemoglobin SC (HbSC). P < .05 was considered statistically significant. SPSS version 24 (IBM Corporation) was used for analyses.
A total of 342 (HbSS: 139; HbSC: 203) pregnancies by women with SCD were evaluated during the sustainability period of 43 months. There was no difference in the demographic characteristics of the study participants in both the postintervention and sustainability groups (Table 1). During the postintervention and sustainability intervals, the maternal mortality rates were 1176 (1/85) per 100 000 live births (case fatality: 1.1% [95% confidence interval (CI), 0.0%-6.4%]) and 2800 (9/320) per 100 000 live births (case fatality: 2.8% [95% CI, 1.3%-5.3%]), respectively (P = .69). During the postintervention and sustainability periods, the perinatal mortality rates were comparable at 27.4 (2/90) per 1000 total births (case fatality: 2.2% [95% CI, 0.2%-7.8%]) and 23.0 (9/342) per 1000 total births (case fatality: 2.7% [95% CI, 1.2%-4.9%]), respectively (P = 1.0).
The single death during the postintervention period was a participant with clinical evidence of ACS, later confirmed by autopsy as a massive bilateral pulmonary embolism 4 days postpartum (Table 2). In comparison, the causes of death during the sustainability period included 6 cases of ACS, 1 case of autopsy-confirmed massive bilateral pulmonary embolism from a left popliteal vein thrombus, 1 case of congestive cardiac failure, and 1 case of obstetric hemorrhage (Table 2).
In a case series of deaths in pregnant women with SCD at KBTH from January of 2010 through December 2016, ACS was the cause of nearly 87% (33 of 38) of SCD-related maternal deaths.9 Approximately 80% of ACS cases occur during the third trimester and early postpartum period <2 weeks.9 Similarly, an ACS diagnosis was the most common cause of death in the current study; 2 pregnant women with HbSC phenotype had a clinical diagnosis of rapidly progressive ACS10 with multiorgan failure, requiring ventilatory support.10 Both women developed thrombocytopenia (<80 000/μL), multiorgan failure (hepatic dysfunction, coagulopathy), altered mental status, and stroke.
We provide further evidence that, as standard care, establishing a multidisciplinary SCD and obstetric team in a low-resource setting can reduce the maternal and perinatal mortality rates. Our next challenge is to determine whether our low-budget multidisciplinary strategy is expandable to other settings in Ghana and parts of Africa in hospitals without SCD expertise.
Acknowledgments: The authors thank the leadership, Department of Obstetrics and Gynecology, KBTH, for administrative support and the members of the team for helpful comments and review of the manuscript. The authors also acknowledge the donation of pulse oximetry machines by the team from Vanderbilt University Medical Center.
This study was supported by funds from University of Ghana Research Fund, Phillips Family Donation, Aaron Ardoin Foundation for Sickle Cell Anemia, and J.C. Peterson endowed chair funds from Vanderbilt University School of Medicine.
Authorship: Contribution: S.A.O., M.R.D., A.K., and E.O. designed the study; A.S-D., R.A.B., E.V.A., T.K.B., and S.A.O. collected the data; S.A.O., E.O., Y.D.-A., T.K.B., C.H.-B., A.S.-D., R.A.B., E.V.A., M.R.D. and A.K. adjudicated on the case files; A.S.-D., E.V.A., R.A.B, J.A.-N, M.R.D., and M.R. performed the analyses; and M.R.D., A.S.-D., R.A.B., E.V.A., and S.A.O. interpreted the results. All authors participated in writing the article and reviewed and approved the manuscript before submission. S.A.O. confirms that he had full access to all the data in this study and had final responsibility for the decision to submit for publication.
Conflict-of-interest disclosure: M.R.D. and his institution are the sponsors of 2 externally funded research investigator–initiated projects. Global Blood Therapeutics will provide funding for the cost of these clinical studies but will not be a cosponsor of either study. M.R.D. is not receiving any compensation for the conduct of these 2 investigator-initiated observational studies. M.R.D. is a member of the Global Blood Therapeutics advisory board for a proposed randomized controlled trial for which he receives compensation; is on the steering committee for a Novartis-sponsored phase 2 trial to prevent priapism in men; was a medical advisor for developing the CTX001 Early Economic Model; provided medical input on the economic model as part of an expert reference group for Vertex/CRISPR CTX001 Early Economic Model in 2020; and consulted the Forma Pharmaceutical company about sickle cell disease in 2021. All remaining authors declare no competing financial interests.
Correspondence: Samuel A. Oppong, University of Ghana Medical School, P.O. Box GP 4236, Accra, Ghana. e-mail: firstname.lastname@example.org.
A.S.-D. and E.V.A. contributed equally to this study.
Requests for data sharing may be submitted to Samuel A. Oppong (email@example.com).