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Sci Rep. 2019 Feb 19;9(1):2260. doi: 10.1038/s41598-019-38821-2.

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

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Department of Medicine at the Doherty Institute, University of Melbourne, Parkville, Victoria, Australia.
Department of Medicine at the Doherty Institute, University of Melbourne, Parkville, Victoria, Australia.
Central Clinical School and Department of Microbiology, Monash University, Victoria, Australia.
Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea.
Walter and Eliza Hall Institute, Parkville, Victoria, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.
Burnet Institute, Melbourne, Victoria, Australia.
Institut Pasteur, Paris, France.
Tommy's Centre for Maternal and Fetal Health, MRC Centre for Reproductive Health, Queen's Medical Research Institute, Edinburgh, UK.


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), α-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.

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