How Can We Better Predict High-Risk Pregnancies for Women with SCD?

Though sickle cell disease (SCD) is associated with significant lifetime morbidity and premature mortality, better quality of care has led to improved survival, with more women reaching reproductive age. Pregnant women with SCD, though, do experience an increased risk of maternal and fetal adverse outcomes.

Given the lack of comprehensive data on pregnancy outcomes in these women, quantifying that risk and identifying groups of women at the highest risk for poor outcomes has been challenging.

A new, first-of-its-kind meta-analysis reports that, when compared to healthy pregnant women, pregnant women with a severe form of SCD are six times more likely to die during or following pregnancy and have an increased risk for stillbirth, high blood pressure, and preterm delivery.

The study, conducted by Eugene Oteng-Ntim, MD, and researchers from King’s College London and the London School of Hygiene & Tropical Medicine, examined 21 published observational studies comparing outcomes in women with and without SCD.

“While we know that women with sickle cell disease will have high-risk pregnancies, we have lacked the evidence that would allow us to confidently tell these patients how likely they are to experience one complication over another,” said Dr. Oteng-Ntim, MD. “This reality makes it difficult for us as care providers to properly counsel our sickle cell patients considering pregnancy.”

Taken together, the studies included 26,349 pregnant women with SCD and 26,151,746 pregnant healthy women. Investigators classified the SCD population based on genotype, including:

  • 1,276 women with the classic form (HbSS genotype)
  • 279 with a milder form (HbSC genotype)
  • 24,794 whose disease genotype was unreported

Based on their analysis, in women with HbSS disease compared to healthy women, there was an increased risk of:

  • Maternal mortality (RR=5.98; 95% CI 1.94-18.44)
  • Pre-eclampsia (RR=2.43; 95% CI 1.75-3.39)
  • Eclampsia (RR=4.89; 95% CI 1.97-12.16)
  • Stillbirth (RR=3.94; 95% CI 2.60-5.96)
  • Neonatal death (RR=2.68; 95% CI 1.49-4.82)
  • Preterm delivery (RR=2.21; 95% CI 1.47-3.31)
  • Infants born small for gestational age (RR=3.72; 95% CI 2.32-5.98)

Thirteen of the studies Dr. Oteng-Ntim and investigators analyzed originated from high-income countries ($30,000 income per capita or greater), while the remaining were from low- to middle-income countries. There was a substantial difference in the magnitude of risk of maternal death and stillbirth for SCD patients from high-income countries, compared to those from low-income countries (OR=0.15; 95% CI 0.02-0.86 and OR=0.28; 95% CI 0.14-0.55, respectively). These results, the authors wrote, “suggest that the risk of death is dependent on the availability of adequate health-care resources and expertise.”

“In high-income countries, women with sickle cell disease are usually managed by a multidisciplinary team of obstetricians, hematologists, specialist midwives, and anesthetists, but the greatest burden of morbidity and mortality undoubtedly lies within low- and middle-income countries where access to specialist antenatal care may be limited,” the authors wrote.

Although women with milder or unreported forms of SCD were less likely than those with HbSS to experience complications, these women still remained at higher risk for most complications compared to healthy mothers. “Our report suggests that, even in developed countries with advanced care, there continues to be a much higher maternal mortality rate in women with sickle cell disease compared to the general population, strongly suggesting that more work must be done to improve outcomes for these patients and their families,” said Dr. Oteng-Ntim. “By improving care providers’ ability to more accurately predict adverse outcomes, this analysis is a first step toward improving universal care for all who suffer from this disease.”


Oteng-Ntim E, Meeks D, Seed PT, et al. Adverse maternal and perinatal outcomes in pregnant women with sickle cell disease: systematic review and meta-analysis. Blood. 2015 March 23. [Epub ahead of print]

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