The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen—a prospective cohort study
Unger, Holger W., Longo, Valentina Laurita, Bleicher, Andie, Ome-Kaius, Maria, Karl, Stephan, Simpson, Julie A., Karahalios, Amalia, Aitken, Elizabeth H., and Rogerson, Stephen J. (2021) The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen—a prospective cohort study. BMC Medicine, 19. 236.
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Abstract
Background: Iron deficiency (ID) has been associated with adverse pregnancy outcomes, maternal anaemia, and altered susceptibility to infection. In Papua New Guinea (PNG), monthly treatment with sulphadoxinepyrimethamine plus azithromycin (SPAZ) prevented low birthweight (LBW; <2500 g) through a combination of antimalarial and non-malarial effects when compared to a single treatment with SP plus chloroquine (SPCQ) at first antenatal visit. We assessed the relationship between ID and adverse birth outcomes in women receiving SPAZ or SPCQ, and the mediating effects of malaria infection and haemoglobin levels during pregnancy.
Methods: Plasma ferritin levels measured at antenatal enrolment in a cohort of 1892 women were adjusted for concomitant inflammation using C-reactive protein and α-1-acid glycoprotein. Associations of ID (defined as ferritin <15 μg/L) or ferritin levels with birth outcomes (birthweight, LBW, preterm birth, small-for-gestational-age birthweight [SGA]) were determined using linear or logistic regression analysis, as appropriate. Mediation analysis assessed the degree of mediation of ID-birth outcome relationships by malaria infection or haemoglobin levels.
Results: At first antenatal visit (median gestational age, 22 weeks), 1256 women (66.4%) had ID. Overall, ID or ferritin levels at first antenatal visit were not associated with birth outcomes. There was effect modification by treatment arm. Amongst SPCQ recipients, ID was associated with a 81-g higher mean birthweight (95% confidence interval [CI] 10, 152; P = 0.025), and a twofold increase in ferritin levels was associated with increased odds of SGA (adjusted odds ratio [aOR] 1.25; 95% CI 1.06, 1.46; P = 0.007). By contrast, amongst SPAZ recipients, a twofold increase in ferritin was associated with reduced odds of LBW (aOR 0.80; 95% CI 0.67, 0.94; P = 0.009). Mediation analyses suggested that malaria infection or haemoglobin levels during pregnancy do not substantially mediate the association of ID with birth outcomes amongst SPCQ recipients.
Conclusions: Improved antenatal iron stores do not confer a benefit for the prevention of adverse birth outcomes in the context of malaria chemoprevention strategies that lack the non-malarial properties of monthly SPAZ. Research to determine the mechanisms by which ID protects from suboptimal foetal growth is needed to guide the design of new malaria prevention strategies and to inform iron supplementation policy in malaria-endemic settings.
| Item ID: | 70822 |
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| Item Type: | Article (Research - C1) |
| ISSN: | 1741-7015 |
| Copyright Information: | © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
| Date Deposited: | 17 Nov 2021 03:09 |
| FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3213 Paediatrics > 321302 Infant and child health @ 100% |
| SEO Codes: | 20 HEALTH > 2005 Specific population health (excl. Indigenous health) > 200506 Neonatal and child health @ 100% |
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