The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen—a prospective cohort study

Unger, Holger, Laurita Longo, Valentina, 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, Vol 19, Issue 1, p. 236.

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	Research Article, Adverse birth outcomes, Iron stores, Iron deficiency, Iron supplementation, Infection, Intermittent preventive treatment, Plasmodium falciparum
Subjects:	QV Pharmacology > Hematologic Agents > QV 183 Iron. Iron compounds WA Public Health > Health Problems of Special Population Groups > WA 310 Maternal welfare WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria WS Pediatrics > By Age Groups > WS 420 Newborn infants. Neonatology
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1186/s12916-021-02114-1
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	05 Oct 2021 16:17
Last Modified:	05 Oct 2021 16:17
URI:	https://archive.lstmed.ac.uk/id/eprint/19095

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