Sulphadoxine-pyrimethamine plus azithromycin may improve birth outcomes through impacts on inflammation and placental angiogenesis independent of malarial infection

Unger, Holger W., Hansa, Annjaleen, Buffet, Christelle, Hasang, Wina, Teo, Andrew, Randall, Louise, Ome-Kaius, Maria, Karl, Stephan, Anuan, Ayen A., Beeson, James G., Mueller, Ivo, Stock, Sarah J., and Rogerson, Stephen J. (2019) Sulphadoxine-pyrimethamine plus azithromycin may improve birth outcomes through impacts on inflammation and placental angiogenesis independent of malarial infection. Scientific Reports, 9. 2260.

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Intermittent preventive treatment with sulphadoxine-pyrimethamine (SP) and SP plus azithromycin (SPAZ) reduces low birthweight (<2,500 g) in women without malarial and reproductive tract infections. This study investigates the impact of SPAZ on associations between plasma biomarkers of inflammation and angiogenesis and adverse pregnancy outcomes in 2,012 Papua New Guinean women. Concentrations of C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), soluble endoglin (sEng), soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured at enrolment and delivery in a trial comparing SPAZ to SP plus chloroquine (SPCQ). At antenatal enrolment higher CRP (adjusted odds ratio 1.52; 95% confidence interval [CI] 1.03-2.25), sEng (4.35; 1.77, 10.7) and sFlt1 (2.21; 1.09, 4.48) were associated with preterm birth, and higher sEng with low birthweight (1.39; 1.11,3.37), in SPCQ recipients only. Increased enrolment sFlt1: PlGF ratios associated with LBW in all women (1.46; 1.11, 1.90). At delivery, higher AGP levels were strongly associated with low birthweight, preterm birth and small-for-gestational age babies in the SPCQ arm only. Restricting analyses to women without malaria infection did not materially alter these relationships. Women receiving SPAZ had lower delivery AGP and CRP levels (p < 0.001). SPAZ may protect against adverse pregnancy outcomes by reducing inflammation and preventing its deleterious consequences, including dysregulation of placental angiogenesis, in women with and without malarial infection.

Item ID: 57747
Item Type: Article (Research - C1)
ISSN: 2045-2322
Copyright Information: © The Author(s) 2019. 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license 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 license, visit
Funders: Malaria in Pregnancy Consortium (MPC), Bill and Melinda Gates Foundation (BMGF), Pregvax Consortium (PC), European Union's Seventh Framework Programme (EUSFP), Spanish Government (SG), National Health and Medical Research Council (NHMRC), Wellcome Trust (WT), Tommy's Charity (TC)
Projects and Grants: Thrasher Early Career Award (12934), MPC/BMGF 46099, PC/EUSFP (FP7-2007-HEALTH, PREGVAX 201588), SG EUROSALUD 2008 Programme, Pfizer Inc Investigator-Initiated Research grant (WS394663), NHMRC program grant 1092789, NHMRC fellowship 1077636, NHMRC fellowship 1043345, NHMRC fellowship GNT1141441, WT Clinical Career Development Fellowship (209560/Z/17/Z)
Date Deposited: 13 Mar 2019 07:52
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3214 Pharmacology and pharmaceutical sciences > 321402 Clinical pharmacology and therapeutics @ 50%
31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310702 Infectious agents @ 50%
SEO Codes: 92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920404 Disease Distribution and Transmission (incl. Surveillance and Response) @ 20%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 80%
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