Sickle cell disease (SCD) is an increasing global health problem and one of the most common genetic disorders worldwide, with varying clinical severity, potentially serious complications with high lifetime morbidity and premature mortality.1,2 SCD is defined as an autosomal recessive hemoglobinopathy that includes sickle cell HbSS disease and various compound heterozygous genotypes (e.g., sickle cell HbSC disease or sickle cell beta-thalassemia disease [HbSßthal]).1,2

Although HbS polymerization, vaso-occlusion, and hemolytic anemia are central to the pathophysiology of SCD, they precipitate a cascade of pathologic events, which in turn lead to a wide range of complications. These processes include vascular–endothelial dysfunction, functional nitric oxide deficiency, inflammation, oxidative stress and reperfusion injury, hypercoagulability, increased neutrophil adhesiveness and platelet activation.1 Chronic complications fall into two main groups: those related to large vessel vasculopathy (cerebrovascular disease, pulmonary hypertension, priapism and retinopathy) and those caused by progressive ischemic organ damage (hyposplenism, renal failure, stroke, bone disease and liver damage).1

A better quality of care for individuals with SCD over the last two decades has improved the survival and quality of life and thus, there are increasing numbers of women reaching the reproductive age. It is estimated that 300,000 children are born with the condition each year.1 In Brazil, SCD has an incidence of 1/1000 births, there are 3500 deliveries with SCD each year and the number of pregnancies among women with SCD is yet unknown.3

Several reviews and meta-analyses of available evidence have found an increased risk of maternal deaths and obstetric and fetal complications, compared to controls.4–11 Knowledge of these risks has contributed to the implementation of a multidisciplinary management program, including the early detection and treatment of complications during pregnancy and postpartum, appropriate pain management protocols and transfusion programs adapted to each pregnant patient. Emphasis must be placed on educating patients and providers on pregnancy-related complications and management, as well as the benefit of early prenatal protocol-driven care provided by a multidisciplinary team.2,12

The aim of this study was to describe maternal and perinatal complications in pregnant women with SCD followed at Santa Casa de Sao Paulo (SCSP) over a 10-year period (from January 1, 2010, to December 31, 2019), as well as the impact of red blood cell (RBC) transfusion on maternal and fetal complications during pregnancy.

There were thirty-nine pregnant women with SCD followed at SCSP from January 1, 2010 to December 31, 2019. Four patients were excluded because of a lack of information. Fifty-five records of pregnancies were analyzed among 35 women with SCD. Tables 1 and 2 demonstrate the characteristics of the patients according to the SCD genotype, number of pregnancies and number of pregnancies and SCD genotype, respectively. Of the 55 pregnancies evaluated, 29 (53.0%) were submitted to the pre-natal at SCSP, 14 underwent an external pre-natal and 12 had not initiated the pre-natal. We observed 26 (47.0%) fetal deaths out of 55 pregnancies, of which 24 were intrauterine fetal, being 14 early abortions, 10 late abortions and 2 stillborn. The mean gestational age of fetal death was 14.35 weeks (4.0–29.8) and the mother`s age, 23.8 years (17–41). Twelve out of the 26 abortions had not initiated the pre-natal.

Among the 29 newborns, 19 (65.5%) were full-term newborns and 10, pre-terms; 24 (82.7%) caesareans and 5 (17.2%) natural births were also observed. The mean gestational age and mother’s age at birth were 36.6 weeks (30–40) and 26.7 years (17–39), respectively. As for the birthing, there were 21 (72.5%) birthings at SCSP and 8 external birthings. The two patients with stillborns underwent the pre-natal and birthing at SCSP. The main maternal obstetric complications were pre-eclampsia (3; 5.4%) and gestational diabetes (6; 10.9%). No maternal death was observed. Non-obstetric complications are shown in Table 3.

Because of early diagnosis and improved pediatric care, more individuals with SCD are reaching reproductive age, thereby directing attention to improving reproductive health care and outcomes for pregnant women.1,2,13,14 Despite improvements in health care over the last 4 decades, maternal and fetal morbidity and mortality remain high, with limited therapeutic interventions to improve pregnancy-related outcomes in women with SCD, particularly in those with the HbSS genotype.2,14

The current study, like many observational ones already published,15,16,21 confirmed this high complication rate in terms of maternal and fetal complications. We observed no maternal deaths, but rather, a higher rate of previous history of miscarriage, gestational diabetes, caesarean section, miscarriage and prematurity, compared to other published studies (Table 5).15,16,21

The higher rate of caesarean section for the resolution of childbirth is a phenomenon that has been occurring all over the world. According to the Brazilian Ministry of Health, the percentage of caesarean deliveries in Brazil varies between 30% and 50%, with higher rates of assisted deliveries in public health services, well above the rate of caesarean section with clinical indication recommended by the World Health Organization, which is up to 15%.22,23 In the case of patients with SCD, in addition to the obstetric decision, based on the scientific knowledge of the specialty, there are certainly several orders of factors involved, including the understanding, or lack thereof, in relation to the underlying disease itself, as well as its complications (anemia, VOC and acute chest syndrome), the lack or failure of information about the types of delivery and its risks to the pregnant woman in prenatal care, the obstetric care offered, that is, the obstetrician in prenatal care is often not the same professional who assists the patient at the time of delivery, facilitating the decision for caesarean section, especially in the presence of clinical-obstetric complications, factors related to the evolution of labor and, undoubtedly, to the abuses of medical intervention.22,23

Spontaneous abortion is the most common obstetric complication; it is estimated that up to 20% of pregnancies progress to abortion before 20 weeks and of these, 80% of spontaneous abortions occur by the 12th week of pregnancy. In Brazil, despite the lack of indicators that allow for the measurement of the total number of occurrences of abortions in the general population, it is estimated that in every ten pregnancies, two do not come to term.22,23 It is known that the abortion rate in patients with SCD is higher than the rate of the female population in general; the current study observed a higher number of abortions in relation to other studies (Table 5). Possible explanations for the data found are: 74.2% of the patients studied were of the SS genotype, 5 (14.2%) patients had a obstetric history of 3 or more pregnancies, 3 patients had had 3 or more abortions without laboratory evidence of thrombophilia, difficulty in accessing the health service and/or lack of sufficient economic resources to seek medical care at the appropriate time.

Although studies have showed that prophylactic RBC transfusions may reduce perinatal mortality, neonatal deaths and adverse pregnancy outcomes in pregnant women with SCD, corroborating the likely beneficial role of transfusion during pregnancy,2,13,15–20 the use of chronic transfusion therapy prophylactically throughout pregnancy remains controversial because data are lacking, and clinical studies are limited by methodological problems.2,14

The current study is retrospective and did not aim to evaluate the benefit of transfusion among prophylactically transfused pregnant women versus non-transfused pregnant women, however, we observed that 40 (72.7%) out of 55 pregnancies received transfusion for different reasons, most of them associated with SCD complications. Analyzing the relationship between maternal obstetric and non-obstetric complications and transfusion, as one would expect, the number of complications observed were higher for transfused pregnancies (Table 4). On the other hand, when we analyzed the number of transfusions during pregnancy and the occurrence of abortion and stillbirth, we observed that pregnant women who received 6 or more transfusions had a significantly lower number of abortions, i.e., no cases of early abortion and only 1 case of late abortion versus 14 and 9 cases in pregnancies with 0–5 transfusions, respectively. The number of stillbirths between the two groups was not different. These data suggest that the higher the number of transfusions equal to or greater than 6, regardless of the indication (complication related to SCD and/or pregnancy), the lower the risk of intrauterine fetal death. This observation leads us once more to question the likely beneficial role of transfusions during pregnancy in patients with SCD observed in many other studies, a period prone to an increase in the percentage of maternal and fetal complications.

Despite advances in the management of SCD, pregnant women with SCD (particularly those with HbSS) are at a high risk for maternal and fetal complications, even though they are followed in reference centers. We observed a lower risk for intrauterine fetal death for those women who received 6 or more transfusions throughout pregnancy, regardless of the indication. This observation leads us once more to raise the need for prospective, multicenter, randomized trials to determine whether the potential benefits balance the risks of prophylactic transfusions.

All authors contributed equally to the writing of the manuscript and approved the final version.

Not applicable.

The authors declare no conflicts of interest.