Sickle Cell Disease: Can genetic variability influence pregnancy outcomes?

Pregnancy in Sickle Cell Disease (SCD), a severe hereditary genetic condition, highly prevalent in Sub-Saharan African countries, is associated with increased risk of complications and severe outcomes in pregnancy, like intrauterine growth restriction, low birth weight, premature birth, miscarriage, stillbirth, pre-eclampsia, and maternal mortality. Several factors have been identified as associated with the heterogeneity of SCD phenotypes, namely the hemoglobin subunit beta (HBB) haplotype and -3.7 kb α-thalassemia deletion.

This study aimed to identify pregnancy complications and severe outcomes, and their association with genetic variability in women with SCD.

In a cohort of 162 pregnant women followed at Maternidade Lucrécia Paim, Luanda, Angola, we collected clinical, hematological, biochemical, and genetic data (Sickle Cell Disease genotype, HBB haplotype, and -3.7 kb α-thalassemia).

The Central African Republic (CAR) haplotype was the most prevalent, being 87% of women homozygous. For the -3.7 kb α-gene deletion 11.7% of women were homozygous, and 36.4% were heterozygous. In this cohort, CAR/CAR women had over 9 times higher odds of having a premature birth, and homozygous women for the -3.7 kb α-thalassemia had over four times higher odds of having a livebirth than the other genotypes. Over 50% of babies were born with low birth weight, and 52,7% were considered premature. Severe maternal complications were registered in 68% of current pregnancies.

These findings highlight the high burden of adverse outcomes in SCD pregnancy and the need for individualized and closer healthcare, especially in low and middle-income countries.