The enormous burden of malaria has resulted in strong evolutionary selection for genes that confer resistance to Plasmodium infection. The best studied examples are red blood cell (RBC) polymorphisms, which have demonstrated varying degrees of protection against malaria in children, in numerous studies. However, the effect of these RBC polymorphisms on Plasmodium species infection in pregnant women, who are most susceptible to malaria after young children, has not been well studied. Malaria in pregnancy is a global health problem with severe consequences for both the mother and the infant.
Here we investigate the associations between RBC polymorphisms, malaria in pregnancy, and adverse maternal and birth outcomes. This study utilized 700 samples and corresponding epidemiological data from pregnant women living in a malaria endemic region of Papua New Guinea, where the prevalence RBC polymorphisms and poor maternal and birth outcomes are high. Pregnant women were genotyped for Complement Receptor 1 (CR1) deficiency, Southeast Asian ovalocytosis (SAO) and α+-thalassemia polymorphisms, which were present at high frequencies (>90%, 5.6% and 17% respectively). Preliminary epidemiological analysis revealed low frequencies of malaria and the adverse birth outcomes low-birthweight and pre-term delivery, and no substantial associations with RBC polymorphisms. However, maternal anaemia was highly prevalent in the cohort, and haemoglobin levels were influenced by RBC polymorphisms. In particular, women with the homozygous α+-thalassemia genotype significantly lower haemoglobin levels at enrolment and delivery, than those seen for wildtypes. While the prevalence of severe anaemia was significantly reduced in women with low CR1 expression genotypes, compared to the high CR1 expression genotype, indicating a potential protective effect. These preliminary findings highlight the need for further investigation into the mechanistic role of these RBC polymorphisms in anaemia, a key pregnancy risk factor in malaria endemic regions.