Risk factors for anaemia during pregnancy and postpartum in Papua New Guinea: a cohort study

Abstract

Anaemia in pregnancy is a substantial public health problem, particularly in resource-limited settings where every second pregnant woman is estimated to be anaemic. This thesis aimed to address gaps in our knowledge of maternal anaemia in order to inform effective prevention strategies in resource-limited settings. Specifically, this thesis sought to determine: the drivers of haemoglobin level changes in pregnancy and the first 12 months postpartum; the interactions between key anaemia risk factors; and the impact of maternal anaemia on infant haemoglobin and iron stores. This was done using a cohort of 699 women and their infants living in the East New Britain province of Papua New Guinea.

Firstly, I determined the relationship between red blood cell genetic polymorphisms, anaemia and the malaria-causing Plasmodium species (spp.) infection in pregnant women; and the subsequent effects on birthweight. Women with the homozygous alpha+-thalassemia genotype had significantly lower haemoglobin levels and babies with significantly lower birthweight compared to wildtype individuals, with the association between alpha+-thalassemia and birthweight mediated largely through mechanisms independent of maternal haemoglobin levels. There were no significant associations between genetic polymorphisms and maternal Plasmodium spp. infection. These findings contribute to our current understanding of how genetic polymorphisms influence pregnancy outcomes.

Secondly, I determined the contribution of iron deficiency to maternal anaemia and assessed temporal changes in haemoglobin and ferritin levels from enrolment through to 12 months postpartum. Haemoglobin levels remained consistently low, with at least 69 percent anaemic throughout the study period (haemoglobin <110g/l in pregnancy; haemoglobin <120g/l postpartum). Ferritin levels were more dynamic with iron deficiency (ferritin <15 micrograms/l) highly prevalent in pregnancy (>80%), but less so in the postpartum period (~30%). Iron deficiency was identified as a key intervenable anaemia risk factor, associated with a significant 5-fold increased odds of anaemia over the entire study period, compared to iron replete. Plasmodium spp. infection was also an important intervenable risk factor for maternal anaemia throughout the study period.

Thirdly, I investigated the relationship between host iron status and Plasmodium spp. infection during pregnancy and postpartum periods, in order to inform the safety of iron supplementation as an anaemia prevention strategy. Host iron status (replete/deficient) was not significantly associated with the prevalence of peripheral Plasmodium spp. infection at any evaluation time, suggesting iron supplement use is safe in this setting. Inflammation was shown to confound the relationship between host iron status and infection, biasing results towards a protective effect for iron deficiency; highlighting the need for future studies assessing this relationship to adjust for inflammation.

Finally, I assessed the impact of maternal anaemia on infant haemoglobin and ferritin stores from birth through to 12 months old. Severe iron deficiency anaemia in pregnancy was associated with significantly lower infant haemoglobin and ferritin levels during the study period; demonstrating that maternal haemoglobin and ferritin levels in pregnancy impact newborn and infant stores. This suggests that infant anaemia could be prevented by targeting maternal anaemia during pregnancy.

Overall, this thesis outlines the high burden of anaemia during pregnancy, as well as the first 12 months postpartum for women in the East New Britain province of Papua New Guinea, and provides a comprehensive assessment of maternal anaemia aetiology. The data suggests that effective provision of iron supplementation both during and between pregnancies, in conjunction with malaria prevention strategies, would significantly reduce maternal anaemia prevalence and improve infant haemoglobin and iron stores.