London School of Hygiene & Tropical Medicine

Pregnant women with a severe form of sickle cell disease are six times more likely than healthy pregnant women to die during or following pregnancy and have an increased risk for stillbirth, high blood pressure, and preterm delivery, according to new research published in Blood.

]The study, conducted  by Guy's and St Thomas' NHS Foundation Trust, King's College London and the London School of Hygiene & Tropical Medicine, is the first to estimate several health risks facing pregnant women with sickle cell disease and identify those who are at highest risk of complications.

People with sickle cell disease produce abnormal haemoglobin, a protein that helps carry oxygen throughout the body. This defect causes the red blood cells to become rigid and sickle-shaped, blocking the flow of blood and oxygen to the body and causing intense pain and other complications such as infections.

Previous research has identified an association between sickle cell disease and high-risk pregnancy; however, specialists have not yet been able to estimate a woman's individual risk for specific complications, nor have they been able to identify groups of women at highest risk.

Study co-author Professor Pat Doyle at the London School of Hygiene & Tropical Medicine, said: "This study shows that pregnancy is more dangerous for women with sickle cell disease than women without, particularly for women living in low and middle income countries where access to specialist antenatal care is limited. There is an urgent need to evaluate interventions aimed at preventing pregnancy complications, and to strengthen health systems to include specialist care teams for pregnant women with this condition."

The researchers examined 21 published observational studies comparing outcomes in women with and without sickle cell disease. The studies included 26,349 pregnant women with sickle cell disease and 26,151,746 pregnant women who shared attributes with the women with sickle cell disease, such as ethnicity or location, but were otherwise healthy. Investigators classified the sickle cell disease population based on genotype, or form of disease. The studies originated from both high-income countries and low- to middle-income countries.

Based on their analysis, researchers concluded that pregnant women with classic sickle cell disease living in a low-income country were at the highest risk for complications. When researchers compared these women to healthy pregnant women, they observed that women with the most severe form of sickle cell disease in both high- and low-income countries were six times more likely to die during or shortly after pregnancy.

Researchers also noted that women with severe sickle cell disease had an increased risk of high blood pressure during pregnancy (known as pre-eclampsia), stillbirth, preterm delivery, and delivering smaller-than-average infants.

While the analysis states that pregnant women with a milder or an unreported form of sickle cell disease were less likely than those with severe disease to experience complications, researchers note that these women remain at higher risk of most complications than healthy mothers.

Researchers also concluded that women with sickle cell disease living in developed countries were less likely to experience death and stillbirth than those in lower-income areas. In addition, pre-eclampsia, preterm delivery, and delivery of smaller-than-average infants were not significantly different between high- and low-income countries, suggesting that risk of these conditions depends on access to care.

The study was led by Dr Eugene Oteng-Ntim, Consultant Obstetrician at Guy's and St Thomas' NHS Foundation Trust, and a research degree student at the London School of Hygiene & Tropical Medicine.

Dr Oteng-Ntim added: "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."

Publication

• Eugene Oteng-Ntim, Daveena Meeks, Paul T Seed, Louise Webster, Jo Howard, Pat Doyle, Lucy C Chappell. Adverse maternal and perinatal outcomes in pregnant women with sickle cell disease: systematic review and meta-analysis.Blood. DOI: 10.1182/blood-2014-11-607317