The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen—a prospective cohort study
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 sulphadoxine-pyrimethamine plus azithromycin (SPAZ) prevented low birthweight (LBW; <2500 g) t...
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doaj-79ce785b759b43ee9d1a0486d7a4cea52021-10-10T11:19:55ZengBMCBMC Medicine1741-70152021-10-0119111310.1186/s12916-021-02114-1The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen—a prospective cohort studyHolger W. Unger0Valentina Laurita Longo1Andie Bleicher2Maria Ome-Kaius3Stephan Karl4Julie A. Simpson5Amalia Karahalios6Elizabeth H. Aitken7Stephen J. Rogerson8Department of Obstetrics and Gynaecology, Royal Darwin HospitalCatholic University of Sacred HeartDepartment of Medicine (RMH), Peter Doherty Institute for Infection and Immunity, The University of MelbournePapua New Guinea Institute of Medical ResearchAustralian Institute of Tropical Health & Medicine, James Cook UniversityCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of MelbourneCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of MelbourneDepartment of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of MelbourneDepartment of Medicine (RMH), Peter Doherty Institute for Infection and Immunity, The University of MelbourneAbstract 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 sulphadoxine-pyrimethamine plus azithromycin (SPAZ) prevented low birthweight (LBW; <2500 g) through a combination of anti-malarial 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. Trial registration ClinicalTrials.gov NCT01136850 .https://doi.org/10.1186/s12916-021-02114-1Adverse birth outcomesIron storesIron deficiencyIron supplementationInfectionIntermittent preventive treatment |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Holger W. Unger Valentina Laurita Longo Andie Bleicher Maria Ome-Kaius Stephan Karl Julie A. Simpson Amalia Karahalios Elizabeth H. Aitken Stephen J. Rogerson |
spellingShingle |
Holger W. Unger Valentina Laurita Longo Andie Bleicher Maria Ome-Kaius Stephan Karl Julie A. Simpson Amalia Karahalios Elizabeth H. Aitken Stephen J. Rogerson The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen—a prospective cohort study BMC Medicine Adverse birth outcomes Iron stores Iron deficiency Iron supplementation Infection Intermittent preventive treatment |
author_facet |
Holger W. Unger Valentina Laurita Longo Andie Bleicher Maria Ome-Kaius Stephan Karl Julie A. Simpson Amalia Karahalios Elizabeth H. Aitken Stephen J. Rogerson |
author_sort |
Holger W. Unger |
title |
The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen—a prospective cohort study |
title_short |
The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen—a prospective cohort study |
title_full |
The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen—a prospective cohort study |
title_fullStr |
The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen—a prospective cohort study |
title_full_unstemmed |
The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen—a prospective cohort study |
title_sort |
relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen—a prospective cohort study |
publisher |
BMC |
series |
BMC Medicine |
issn |
1741-7015 |
publishDate |
2021-10-01 |
description |
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 sulphadoxine-pyrimethamine plus azithromycin (SPAZ) prevented low birthweight (LBW; <2500 g) through a combination of anti-malarial 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. Trial registration ClinicalTrials.gov NCT01136850 . |
topic |
Adverse birth outcomes Iron stores Iron deficiency Iron supplementation Infection Intermittent preventive treatment |
url |
https://doi.org/10.1186/s12916-021-02114-1 |
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