Abstract
This study in Burkina Faso investigated whether offspring of young mothers who had received weekly periconceptional iron supplementation in a randomised controlled trial were at increased risk of malaria. A child safety survey was undertaken in the peak month of malaria transmission towards the end of the trial to assess child iron biomarkers, nutritional status, anaemia and malaria outcomes. Antenatal iron biomarkers, preterm birth, fetal growth restriction and placental pathology for malaria and chorioamnionitis were assessed. Data were available for 180 babies surviving to the time of the survey when their median age was 9 months. Prevalence of maternal iron deficiency in the last trimester based on low body iron stores was 16%. Prevalence of active placental malaria infection was 24.8%, past infection 59% and chorioamnionitis 55.6%. Babies of iron supplemented women had lower median gestational age. Four out of five children ≥ 6 months were iron deficient, and 98% were anaemic. At 4 months malaria prevalence was 45%. Child iron biomarkers, anaemia and malaria outcomes did not differ by trial arm. Factors associated with childhood parasitaemia were third trimester C‐reactive protein level (OR 2.1; 95% CI 1.1–3.9), active placental malaria (OR 5.8; 1.0–32.5, P = 0.042) and child body iron stores (OR 1.13; 1.04–1.23, P = 0.002). Chorioamnionitis was associated with reduced risk of child parasitaemia (OR 0.4; 0.1–1.0, P = 0.038). Periconceptional iron supplementation of young women did not alter body iron stores of their children. Higher child body iron stores and placental malaria increased risk of childhood parasitaemia.
Highlights
A twofold increased risk in young children of malaria parasitaemia and clinical malaria was seen in mothers experiencing P. falciparum infections during pregnancy (Park et al, 2020), with several studies identifying an association of increased child malaria with placental malaria in their mothers (Agbota, Accrombessi, et al, 2019; Asante et al, 2013; Awine et al, 2016; Bardají et al, 2011; Le Port et al, 2011; Schwarz et al, 2008; Sylvester et al, 2018; Sylvester et al, 2016)
Given the protective effect of iron deficiency during pregnancy for malaria (Diallo et al, 2020; Kabyemela, Fried, Kurtis, Mutabingwa, & Duffy, 2008; Moya-Alvarez et al, 2015; Senga, Harper, Koshy, Kazembe, & Brabin, 2011), it follows that young children born to iron replete mothers, enhanced by routine periconceptional or antenatal iron supplementation, could be at higher risk of malaria, the issue is complex as immunological mechanisms (Brickley et al, 2015; Broen, Brustoski, Engelmann, & Luty, 2007; Dechavanne et al, 2017; Feeney, 2020; Hviid, 2009; Hviid & Staalsoe, 2004; Park et al, 2019; Sylvester et al, 2018) and maternal factors such as breast feeding and use of antimalarial drugs are relevant (Hawking, 1954; Kakuru, Staedke, Dorsey, Rogerson, & Chandramohan, 2019; Natama, Rovira-Vallbona, Sorgho, et al, 2018)
Periconceptional iron supplementation made no difference to placental malaria parasite prevalence, or in children, to malaria-related outcomes or iron biomarker values
Summary
Better iron status has been associated with increased Plasmodium falciparum infection risk early in pregnancy Given the protective effect of iron deficiency during pregnancy for malaria (Diallo et al, 2020; Kabyemela, Fried, Kurtis, Mutabingwa, & Duffy, 2008; Moya-Alvarez et al, 2015; Senga, Harper, Koshy, Kazembe, & Brabin, 2011), it follows that young children born to iron replete mothers, enhanced by routine periconceptional or antenatal iron supplementation, could be at higher risk of malaria, the issue is complex as immunological mechanisms (Brickley et al, 2015; Broen, Brustoski, Engelmann, & Luty, 2007; Dechavanne et al, 2017; Feeney, 2020; Hviid, 2009; Hviid & Staalsoe, 2004; Park et al, 2019; Sylvester et al, 2018) and maternal factors such as breast feeding and use of antimalarial drugs are relevant (Hawking, 1954; Kakuru, Staedke, Dorsey, Rogerson, & Chandramohan, 2019; Natama, Rovira-Vallbona, Sorgho, et al, 2018). A child safety survey became necessary after publication in 2012 (post trial commencement) of two cohort studies that reported iron repletion predicted increased malaria risk in pre-school children in Malawi (Jonker et al, 2012) and Tanzania (Gwamaka et al, 2012). The objectives of this cross-sectional child safety study were firstly, in children under 2 years of age, to determine prespecified malaria-related outcomes and anaemia and iron biomarkers by trial arm, and secondly, to characterise maternal and child iron status and related factors associated with child malaria
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