Maternal–fetal prognosis of major sickle cell disease in pregnant women at a university hospital in a low–middle-income country

Is integrating sickle cell disease and HIV screening logical?

Sickle cell disorder (SCD) is a genetic disorder of haemoglobin with a wide spectrum of severity and manifestations. It is a significant global public health problem and is mainly widespread among many tribal populations. Sickle cell disease (SCD) in pregnancy poses a unique challenge due to the physiological changes in pregnancy, the multitude of various organs involved, and its complications. The databases of PubMed, MedLine ResearchGate, EMbase, Scopus and Google Scholar were searched for literature about SCDs published up to 2021. Search terms and phrases used were 'sickle cell disease', 'sickle cell disease and pregnancy', 'anaesthesia and analgesia in sickle cell disease' and 'transfusion in sickle cell disease'. Original articles, guidelines, review articles, case reports, letters to editor and abstracts were reviewed with particular focus on pathophysiology and anaesthetic implications of sickle cell anaemia with pregnancy. While ample literature is available on SCDs, there is a paucity of literature on SCDs with pregnancy. In this review, we have attempted to present the relevant literature in a comprehensible manner.

Sickle cell disease (SCD) in pregnancy is uncommon in Malaysia. We present a case of sickle cell disease in pregnancy with maternal and fetal complications. The patient presented with acute pain crisis and hemolysis in the third trimester. Despite thromboprophylaxis, she developed deep vein thrombosis. The pregnancy was further complicated by severe pre-eclampsia and intrauterine growth restriction which require preterm caesarean section. The baby was admitted to Neonatal Intensive Care Unit due to prematurity and low birth weight. Multidisciplinary approach in managing pregnant patient with SCD is essential in achieving good obstetrics outcome.

HIV and sickle cell disease (SCD) are significant causes of morbidity and mortality in sub-Saharan Africa. Given their separate roles in immune dysregulation, our objective was to characterise the impact that SCD has on the presentation and progression of paediatric HIV. The study was a retrospective cohort study (study period 2004-2018). Cases of HIV+and SCD-afflicted patients (HIV+/SCD+) were obtained via electronic chart review from a paediatric HIV clinic in Kampala, Uganda and matched 1:3 with HIV+controls without SCD (HIV+/SCD-). Thirty-five HIV+/SCD+subjects and 95 HIV+/SCD- controls were analysed (39% female (51/130), age 3.6years (SD3.9)). At baseline, WHO clinical stage (64% total cohort Stage III/IV) and nutritional status (9.4% severe acute malnutrition) were similar for both groups, whereas HIV+/SCD+had higher though non-significant baseline CD4 count (1036 (SD713) vs 849 (SD638) cells/microlitre, P=0.20, two-tailed t-test). There were 19 deaths, 6 (17%) HIV+/SCD+and 13 (14%) HIV+/SCD-, with unadjusted/adjusted models showing no significant difference. Nutritional progression and clinical stage progression showed no significant differences between groups. Kaplan-Meier analysis showed a slower rate of treatment failures in the HIV+/SCD+cohort (P=0.11, log-rank survival test). Trajectory analysis showed that in the time period analysed, the HIV+/SCD+cohort showed a more rapid rise and higher total CD4 count (P=0.012, regression analysis). The study suggests that SCD does not adversely affect the progression of HIV in patients on ART. Further, HIV+/SCD+achieved higher CD4 counts and fewer HIV treatment failures, suggesting physiological effects due to SCD might mitigate HIV progression.

Proliferative sickle cell retinopathy (PSCR) is the most frequent vision-threatening complication of sickle cell disease (SCD). We investigated the relationship between the severity of sickle cell retinopathy in heterozygous (SC) or homozygous (SS) adult SCD patients and the clinical and laboratory data obtained during visits to a national SCD referral center. This retrospective longitudinal analysis included 942 SCD patients (313 patients with SC and 629 with SS disease) with ophthalmologic evaluations who were followed over a 19-year period by a multidisciplinary team in a referral center. PSCR was graded using the Goldberg classification. We identified patient and SCD characteristics associated with sickle cell retinopathy severity using multinomial logistic-regression models. Multivariate analysis associated severe PSCR forms (stages III-V) with older age (p=0.032), pulmonary involvement (documented pulmonary hypertension with pulmonary arterial pressure≥40 mm Hg, restrictive syndrome>20%, or previous history of pulmonary embolism diagnosed by vascular imaging) (p=0.029), deafness or tinnitus (p=0.026), and no history of osteomyelitis (p=0.013) for SC patients; and with older age (p<0.001), male sex (p=0.003), and acute pyelonephritis (p=0.04) for SS patients. The model of severe PSCR versus no PSCR showed good calibration and discrimination for SC and SS patients. Awareness of the clinical and laboratory factors significantly associated with severe PSCR in patients with SC or SS SCD may contribute to improved preventive strategies.

Use of Conventional Transfusion Thresholds Contributes to Ongoing Iron Overload Issues in Patients with Homozygous (SS) Sickle Cell Disease

La drépanocytose homozygote, fait partie des hémoglobinopathies les plus fréquentes au Maroc. La drépanocytose est caractérisée par une grande variabilité d’expressions clinique et biologique qui dépendent des facteurs génétiques modulateurs et environnementaux. Elle se manifeste par une anémie régénérative de gravité très variable selon les individus. L’évolution spontanée en l’absence de traitement est le décès précoce. La drépanocytose est caractérisée par une grande variabilité d’expression clinique et biologique qui dépend des facteurs génétiques et environnementaux. Un tableau clinique sévère marqué par une fréquence de transfusion élevée et précoce, des complications infectieuses graves et une mortalité précoce. Un état inflammatoire constant caractérisé par des protéines inflammatoires élevées et état nutritionnel compromis. L’objectif est de déterminer le profil des paramètres hématologiques du drépanocytaire homozygote (SS) marocain au cours des stades stationnaires. Nous avons fait une étude descriptive transversale de 87 patients drépanocytaires (SS). Nous avons réalisé une étude biologique comportant: l’hémogramme avec étude morphologique des globules rouges en coloration MGG et numération automatique des réticulocytes. Les électrophorèses de l’hémoglobine à pH alcalin (8.8) sur gel d’agarose avec intégration densitométrique. L’âge moyen est de 13.22 ans ± 16.36 avec un sex- ratio (H/F) de 1.175 et des extrêmes allant de 0.6 à 36 ans. La répercussion de l’anémie sur le plan biologique, est intense chez 88.5% des patients, 67.8% ont une anémie normocytaire contre 29.9% présentant une microcytose, et 2.3% qui présentaient une macrocytose. Le degré d’anisocytose est lié au degré d’anémie, très évocatrice chez les drépanocytaires homozygotes S/S (95,4%). Une réticulocytose était observée chez nos patients (81,6%) et 52.9% présentaient une thrombocytose. Une leucocytose était observée chez 64.4% des patients et 80.5% ont présenté une neutropénie. Les paramètres de l’hémogramme serviront de base de comparaison lors des crises et permettront d’évaluer l’efficacité de la prise en charge par le clinicien. Les valeurs élevées des globules blancs, plaquettes et CCHM semblent déterminants dans l’expression sévère de la drépanocytose au Maroc. Le profil hématologique du drépanocytaire marocain montre des données semblables à celles rapportées en littérature chez ceux de l’Afrique centrale, avec une leucocytose. Les résultats de notre étude suggèrent que, la drépanocytose est un problème de santé le plus fréquent chez les marocains et que nos résultats sont comparables à ceux décrits dans le syndrome drépanocytaire majeur.

Sickle cell disease (SCD) is the most common inherited hemoglobinopathy and is associated with increased risk of complications and early mortality. Nowadays, with improved health care facilities, antibiotic prophylaxis, vaccination, and availability of drugs like hydroxyurea, the life expectancy of SCD patients has improved. More women are reaching reproductive age group and are expressing their desire to reproduce. Though SCD adversely affects pregnancy, leading to increased incidence of maternal and perinatal complications like pre-eclampsia, preterm labor, IUGR, abortions etc., adequate care throughout pregnancy ensures a better outcome. Also, recent advancements in the fields of prenatal diagnosis and preimplantation genetic diagnosis, help couples suffering from SCD to have a healthy baby. This paper focuses on the effects of SCD on pregnancy outcomes and effective management of complications during pregnancy, also comparing maternal and perinatal outcomes in studies conducted in different countries. The second part of the paper summarizes pregnancy management in SCD for better maternal and fetal outcomes.

Presentation Date: 6/8/2024 Presentation Start Time: 6:00 PM Background Despite advancements in medical care, maternal and perinatal mortality rates among pregnant individuals with sickle cell disease (SCD) remain disproportionately high [1]. While existing evidence suggests a potential benefit of prophylactic transfusions with reference to maternal and perinatal outcomes, the limited number of studies and methodological constraints necessitate further investigation [2,3]. Considering these findings, we have attempted to retrospectively analyze the incidence of maternal and perinatal complications among transfused pregnant patients of different sickle genotypes. Methods We conducted a retrospective analysis of medical records from New York City Health and Hospitals/Kings County, which is an urban inner-city hospital providing care to an underserved population. We identified pregnant patients diagnosed with sickle cell disease for nine years between January 1, 2015, and January 1, 2024. Access to patient medical records was facilitated through the hospital’s EPIC and Quadramed software. We performed statistical analysis on maternal sickle cell/obstetric and perinatal complications among patients and stratified them by genotype, mean hemoglobin level, race, and age. Results Patients with homozygous sickle cell disease (HbSS) comprised 69% of the study population, with 66% of the patients being above 35 years of age. The mean hemoglobin for patients with HbSS disease was approximately 7.0 g/dl at baseline, which was maintained relatively constant throughout their pregnancy for the vast majority. In contrast, patients with heterozygous sickle genotypes like HbSC and HbS Beta+ thalassemia had mean baseline hemoglobin levels of approximately 9.5 g/dl and approximately 7.0 g/dl, respectively, with mean pregnancy levels averaging at approximately 8.0 g/dl for both groups. Obstetric complications were more prevalent among HbSS patients compared to other genotypes. In the HbSS subgroup, pre-eclampsia was most prevalent (100%), followed by postpartum hemorrhage (56%) and cesarean section (69%). Among HbSC patients, none experienced pre-eclampsia, 44% had postpartum hemorrhage, and 22% underwent cesarean section. Among HbS Beta+ thalassemia patients, none experienced pre-eclampsia or postpartum hemorrhage, and 9% underwent cesarean section. Pre-eclampsia rates were significantly higher in the HbSS genotype (100%) and did not occur in other genotypes at their hemoglobin level. Miscarriages occurred in 80% of HbSS patients as compared to 20% of HbSC patients, while none were noted among HbS Beta+ thalassemia patients. Fetal complications also varied among genotypes. Intrauterine growth retardation (IUGR) was predominantly noted in HbSS patients (67%), while only 33% of HbSC patients encountered the same, and none were noted in HbS Beta+ thalassemia patients. Fetal distress was noted in only 33% of HbSS patients, while it accounted for 67% among HbSC patients, and none were noted in HbS Beta+ thalassemia patients. Intrauterine fetal demise was noted in only 33% of HbSS patients, while it accounted for 67% among HbSC patients, and none were noted in HbS Beta+ thalassemia patients. Vaso-occlusive episodes occurred in 29% of all patients, with varying incidence among different genotypes. Among HbSS patients, 84% experienced Vaso-occlusive episodes, compared to 8% among HbSC patients and 8% among HbS Beta+ thalassemia patients. Transfusion rates during pregnancy were highest among HbSS patients (80%) compared to 16% among HbSC patients and 4% among HbS Beta+ thalassemia patients. Conclusion Our retrospective analysis underscores the complex association between pregnancy-related complications of sickle cell disease and transfusion therapy. While our findings generally highlight a correlation between mean hemoglobin levels and adverse outcomes, further research is imperative to elucidate the optimal management strategies for pregnant individuals with SCD. Prospective studies integrating comprehensive clinical and laboratory assessments are essential to delineate the role of prophylactic transfusions in mitigating maternal, fetal, and sickle cell-related complications. Such endeavors are pivotal in advancing evidence-based practices and ultimately improving outcomes for this vulnerable patient population.

Background:Sickle cell disease in pregnancy is associated with high maternal and fetal mortality. However, studies reporting pregnancy, fetal, and neonatal outcomes in women with sickle cell disease are extremely limited.Objectives:The objectives of the study are to determine whether women with sickle cell disease have a greater risk of adverse pregnancy, fetal, and neonatal outcomes than women without sickle cell disease and identify the predictors of adverse pregnancy, fetal, and neonatal outcomes in women with sickle cell disease.Design:A retrospective pair-matched case-control study was conducted to compare 171 pregnant women with sickle cell disease to 171 pregnant women without sickle cell disease in Muscat, Sultanate of Oman.Methods:All pregnant Omani women with sickle cell disease who delivered between January 2015 and August 2021 at Sultan Qaboos University Hospital and Royal Hospital, who were either primipara or multipara and who had a gestational age of 24–42 weeks, were included as patients, whereas women who had no sickle cell disease or any comorbidity during pregnancy, who delivered within the same timeframe and at the same hospitals, were recruited as controls. The data were retrieved from electronic medical records and delivery registry books between January 2015 and August 2021.Results:Women with sickle cell disease who had severe anemia had increased odds of (χ2 = 58.56, p < 0.001) having adverse pregnancy outcomes. Women with sickle cell disease had 21.97% higher odds of delivering a baby with intrauterine growth retardation (χ2 = 17.80, unadjusted odds ratio = 2.91–166.13, p < 0.001). Newborns born to women with sickle cell disease had 3.93% greater odds of being admitted to the neonatal intensive care unit (χ2 = 16.80, unadjusted odds ratio = 1.97–7.84, p < 0.001). In addition, the children born to women with sickle cell disease had 10.90% higher odds of being born with low birth weight (χ2 = 56.92, unadjusted odds ratio = 5.36–22.16, p < 0.001). Hemoglobin level (odds ratio = 0.17, p < 0.001, 95% confidence interval = 0.10–3.0), past medical history (odds ratio = 7.95, p < 0.001, 95% confidence interval = 2.39–26.43), past surgical history (odds ratio = 17.69, p < 0.001, 95% confidence interval = 3.41–91.76), and preterm delivery (odds ratio = 9.48, p = 0.005, 95% confidence interval = 1.95–46.23) were identified as predictors of adverse pregnancy, fetal, and neonatal outcomes in women with sickle cell disease.Conclusion:As pregnant women with sickle cell disease are at increased risk for pregnancy, fetal, and neonatal adverse outcomes; improved antenatal surveillance and management may improve the outcomes.

The Role of Splenectomy in Patients with Sickle Cell Disease

Adverse maternal and perinatal outcomes in pregnant women with sickle cell disease: systematic review and meta-analysis

Background: Sickle cell disease (SCD) is associated with an increased risk of medical complications during pregnancy and they constitute a very high-risk group with associated increased maternal and perinatal morbidity and mortality especially in a low resource setting. Objective: To determine the pregnancy outcomes among women with sickle cell disease delivered at Alex Ekwueme Federal University Teaching Hospital, Abakaliki. Materials and methods: This was a 7-year retrospective case-control study undertaken from January 2012 to December 2018 that compared pregnancy outcomes among women with and without haemoglobinopathy in pregnancy managed at Alex Ekwueme Federal University Teaching Hospital, Abakaliki (AEFUTHA). The statistical analysis was done using SPSS version 22. Results: The incidence of SCD in pregnancy was 6.9 per 1000 deliveries. The age distribution of the women ranged from 18 to 45 years of age with a mean of 26.4 ± 2.4 years. The incidence of stillbirth was higher in women with HbSS when compared with HbSC but this difference did not reach statistical significance (P = 0.05). Live birth rate was higher in women with HbAA genotype when compared with those with SCD. Caesarean section rate was higher among women with SCD when compared with control (SS versus AA, P = 0.004; SC versus AA, P < 0.0001). Babies of mothers with HbSS and HbSC have significantly lower mean birth weight when compared with those of mothers with HbAA (SS versus AA, P = 0.0007; SC versus AA, P < 0.0001). Similarly maternal genotype has a significant effect on other adverse fetal outcomes such as Apgar scores < 7 at 5 minutes and preterm delivery. Women with SCD had higher incidence of pregnancy-induced hypertension and preeclampsia when compared with control. Maternal genotypes have no significant effect on other maternal complications. There was no maternal death in this study. Conclusion: This study showed that the maternal mortality in SS and SC patients in pregnancy was not different from those of HbAA women in our hospital, although other maternal and fetal outcomes were still poor among women with SCD when compared with women without SCD.

1. Kathryn Westphal, MD* 2. Respicius Bakalemwa, MD† 3. Elizabeth Groothuis, MD, MPH* 1. *Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 2. †Department of Pediatrics, Bugando Medical Centre, Mwanza, Tanzania A 12-year-old boy with sickle cell disease (SCD) is admitted to a hospital in Mwanza, Tanzania, with acute onset of periorbital and scalp swelling. Associated symptoms include fever, headache, difficulty breathing, and back pain. Because resources in sub-Saharan Africa are limited, access to comprehensive care for patients with SCD is variable. The general principles of management focus on early diagnosis, parental education, prevention of infection with vaccinations and prophylactic medications, prompt treatment of infection and pain, the use of hydroxyurea for stroke prevention, and blood transfusions for life-threatening anemia. This patient has a known diagnosis of SCD but has infrequent pain episodes and no previous transfusions. He is not receiving hydroxyurea or prophylaxis against bacterial infections or malaria. He has no history of stroke and no known head trauma. On presentation he is afebrile and his heart rate is 120 beats/min, respiratory rate is 40 breaths/min, and blood pressure is 105/75 mm Hg. His oxygen saturation is 92% in room air. Physical examination is significant for pallor, periorbital edema, scalp edema, dyspnea without adventitious lung sounds, and splenomegaly with diffuse abdominal tenderness. His scalp edema is fluctuant and extends posteriorly from the periorbital region, encompassing the entire scalp. Swelling is most prominent in the frontal and parietal areas. The overlying skin is nonerythematous and nontender but is warm to the touch. His neurologic examination has no focal findings, although generally he appears tired. Initial laboratory results demonstrate a white blood cell count of 84,000/μL (84×109/L) with a lymphocytic predominance (57%), a hemoglobin level of …

Retrospective Survey of Sickle Cell Disease in Pregnancy in a Niger-Delta Nigerian Tertiary Health Center