Association Between Haemoglobin Variant Phenotypes and Red Blood Cell Parameters Among Pregnant Women: A...

Haemoglobin (Hb) variants arising from mutations in globin chains can alter red blood cell (RBC) parameters. This may complicate the interpretation of pregnancy-related haematological changes, particularly in sub-Saharan Africa, where both anaemia in pregnancy and Hb variants are highly prevalent. The association between these variants and red cell parameters among Ghanaian pregnant women remains insufficiently characterised. This cross-sectional study investigated the association between Hb variant phenotypes and red cell parameters, and assessed whether such variants were independently associated with anaemia among 400 pregnant women at the Ga West Municipal Hospital, Greater Accra Region, Ghana. Full blood counts and Hb phenotyping by cellulose acetate electrophoresis at pH 8.4 were performed. Multivariable linear and Firth's penalised-likelihood logistic regression models, adjusted for maternal age, body mass index, gestational trimester, parity and haematinic supplementation, were used to estimate associations. Phenotype distribution was HbA 73.2%, HbAS/HbAC 25.3% and HbS/HbC/HbSC 1.5%; anaemia prevalence was 87.5%. Compared with HbA, HbAS/HbAC carriers had lower haematocrit (adjusted β = -1.14%, p = 0.036), mean cell volume (adjusted β = -4.05 fL, p < 0.001), mean cell Hb (adjusted β = -0.89 pg, p = 0.005) and red cell distribution width-standard deviation (RDW-SD) (adjusted β = -2.79 fL, p < 0.001); HbS/HbC/HbSC reductions were larger for haematocrit (adjusted β = -6.29%, p = 0.005) and mean cell volume (adjusted β = -6.87 fL, p = 0.001). Hb phenotype was not independently associated with anaemia, but the adjusted odds of anaemia in the second trimester were significantly higher than in the first (adjusted odds ratio = 3.45, p = 0.001). Hb variant phenotypes were associated with a microcytic, hypochromic red cell profile, whereas gestational trimester, rather than phenotype, was the dominant correlate of anaemia. Given the single-centre, cross-sectional design and the small number of pregnant women with homozygous or compound heterozygous phenotypes, these findings are hypothesis-generating. They support phenotype- and trimester-aware interpretation of red cell parameters in antenatal care; however, whether such interpretation improves maternal outcomes requires evaluation in larger, multicentre studies.