Iron deficiency during pregnancy is associated with a reduced risk of adverse birth outcomes in a malaria-endemic area in a longitudinal cohort study

Abstract

BackgroundLow birth weight (LBW) and preterm birth (PTB) are major contributors to infant mortality and chronic childhood morbidity. Understanding factors that contribute to or protect against these adverse birth outcomes is an important global health priority. Anaemia and iron deficiency are common in malaria-endemic regions, but there are concerns regarding the value of iron supplementation among pregnant women in malaria-endemic areas due to reports that iron supplementation may increase the risk of malaria. There is a lack of evidence on the impact of iron deficiency on pregnancy outcomes in malaria-endemic regions.MethodsWe determined iron deficiency in a cohort of 279 pregnant women in a malaria-endemic area of Papua New Guinea. Associations with birth weight, LBW and PTB were estimated using linear and logistic regression. A causal model using sequential mediation analyses was constructed to assess the association between iron deficiency and LBW, either independently or mediated through malaria and/or anaemia.ResultsIron deficiency in pregnant women was common (71% at enrolment) and associated with higher mean birth weights (230 g; 95% confidence interval, CI 118, 514; p < 0.001), and reduced odds of LBW (adjusted odds ratio, aOR = 0.32; 95% CI 0.16, 0.64; p = 0.001) and PTB (aOR = 0.57; 95% CI 0.30, 1.09; p = 0.089). Magnitudes of effect were greatest in primigravidae (birth weight 351 g; 95% CI 188, 514; p < 0.001; LBW aOR 0.26; 95% CI 0.10, 0.66; p = 0.005; PTB aOR = 0.39, 95% CI 0.16, 0.97; p = 0.042). Sequential mediation analyses indicated that the protective association of iron deficiency on LBW was mainly mediated through mechanisms independent of malaria or anaemia.ConclusionsIron deficiency was associated with substantially reduced odds of LBW predominantly through malaria-independent protective mechanisms, which has substantial implications for understanding risks for poor pregnancy outcomes and evaluating the benefit of iron supplementation in pregnancy. This study is the first longitudinal study to demonstrate a temporal relationship between antenatal iron deficiency and improved birth outcomes. These findings suggest that iron supplementation needs to be integrated with other strategies to prevent or treat infections and undernutrition in pregnancy to achieve substantial improvements in birth outcomes.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1146-z) contains supplementary material, which is available to authorized users.

Association Between Anaemia And Low Birth Weight Among HIV -Infected Pregnant Women Aged 15 – 49 Years In Zimbabwe : A Cross-Sectional Study

“…On the other hand, some studies have found that pregnant women with high plasma volumes have given birth to infants with a higher birth weight than average [4]. In contrast, Fowkes and colleagues reported an inverse association between birth weight and haemoglobin levels during late stages of pregnancy whereby birthweight of infants was significantly larger among anaemic women in comparison with non-anaemic women [19].Contrary to these findings, Kader & Perera and…”

Understanding the interactions between iron supplementation, infectious disease and adverse birth outcomes is essential to guide public health recommendations

“…Additionally, published reports indicate variable effects of iron supplementation in pregnancy on newborn outcomes [5]. In our recent article published in BMC Medicine [6], we investigated iron deficiency and pregnancy outcomes in a cohort of Papua New Guinean women and found that iron deficiency in pregnancy was associated with a reduced risk of adverse birth outcomes (low birthweight and premature delivery); this association was not simply explained by a potential protective effect of iron deficiency against malaria. We hypothesised that an interaction between iron deficiency and other infectious diseases may explain the observed effect or that other nutritional factors may be contributing to these associations.…”

“…While all women in the study were prescribed daily iron and folate supplementation throughout pregnancy from enrolment, we do not have data on supplement accessibility or compliance (although one would assume that, in the absence of knowing their iron status, iron supplementation uptake would be similar in both iron-replete and iron-deficient women). However, we did investigate, through causal mediation analysis, whether the protective effect of iron deficiency was mediated through anaemia (both at enrolment and at prospective time points throughout pregnancy), which could serve as a proxy for levels of iron absorption [6]. Assuming that iron supplementation does improve haemoglobin concentration differentially in iron-deficient and iron-replete women, thus improving birthweight, we would expect to find a significant proportion of the protective effect to be mediated through that pathway.…”

“…Furthermore, there are other benefits of iron supplementation for the mother and infant that need to be considered in policy decisions. Instead, we concluded that it is essential to provide both iron supplementation for anaemia and effective malaria prophylaxis during pregnancy according to current WHO policy [6], integrated with interventions that address other nutritional deficiencies or infections that may potentially achieve greater health benefits.…”

Antenatal iron supplementation and birth weight in conditions of high exposure to infectious diseases

“…A recent cohort study in Papua New Guinean pregnant women reported an association between iron deficiency (ferritin concentration < 15 μg/L) and higher birth weight (by 230 g), particularly among primigravidae [1]. Despite this finding, the authors conclude that it is essential to provide both iron supplementation and effective malaria chemoprophylaxis during pregnancy.…”