Sulphadoxine-pyrimethamine plus azithromycin for the prevention of low birthweight in Papua New Guinea: a randomised controlled trial

Unger, Holger W., Ome-Kaius, Maria, Wangnapi, Regina A., Umbers, Alexandra J., Hanieh, Sarah, Suen, Connie S.N. Li Wai, Robinson, Leanne J., Rosanas-Urgell, Anna, Wapling, Johanna, Lufele, Elvin, Kongs, Charles, Samol, Paula, Sui, Desmond, Singirok, Dupain, Bardaji, Azucena, Schofield, Louis, Menendez, Clara, Betuela, Inoni, Siba, Peter, Mueller, Ivo, and Rogerson, Stephen J. (2015) Sulphadoxine-pyrimethamine plus azithromycin for the prevention of low birthweight in Papua New Guinea: a randomised controlled trial. BMC Medicine, 13. 9. pp. 1-16.

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Background: Intermittent preventive treatment in pregnancy has not been evaluated outside of Africa. Low birthweight (LBW, < 2,500 g) is common in Papua New Guinea (PNG) and contributing factors include malaria and reproductive tract infections.

Methods: From November 2009 to February 2013, we conducted a parallel group, randomised controlled trial in pregnant women (<= 26 gestational weeks) in PNG. Sulphadoxine-pyrimethamine (1,500/75 mg) plus azithromycin (1 g twice daily for 2 days) (SPAZ) monthly from second trimester (intervention) was compared against sulphadoxine-pyrimethamine and chloroquine (450 to 600 mg, daily for three days) (SPCQ) given once, followed by SPCQ placebo (control). Women were assigned to treatment (1: 1) using a randomisation sequence with block sizes of 32. Participants were blinded to assignments. The primary outcome was LBW. Analysis was by intention to treat.

Results: Of 2,793 women randomised, 2,021 (72.4%) were included in the primary outcome analysis (SPCQ: 1,008; SPAZ: 1,013). The prevalence of LBW was 15.1% (305/2,021). SPAZ reduced LBW (risk ratio [RR]: 0.74, 95% CI: 0.60-0.91, P = 0.005; absolute risk reduction (ARR): 4.5%, 95% CI: 1.4-7.6; number needed to treat: 22), and preterm delivery (0.62, 95% CI: 0.43-0.89, P = 0.010), and increased mean birthweight (41.9 g, 95% CI: 0.2-83.6, P = 0.049). SPAZ reduced maternal parasitaemia (RR: 0.57, 95% CI: 0.35-0.95, P = 0.029) and active placental malaria (0.68, 95% CI: 0.47-0.98, P = 0.037), and reduced carriage of gonorrhoea (0.66, 95% CI: 0.44-0.99, P = 0.041) at second visit. There were no treatment-related serious adverse events (SAEs), and the number of SAEs (intervention 13.1% [181/1,378], control 12.7% [174/1,374], P = 0.712) and AEs (intervention 10.5% [144/1,378], control 10.8% [149/1,374], P = 0.737) was similar. A major limitation of the study was the high loss to follow-up for birthweight.

Conclusions: SPAZ was efficacious and safe in reducing LBW, possibly acting through multiple mechanisms including the effect on malaria and on sexually transmitted infections. The efficacy of SPAZ in the presence of resistant parasites and the contribution of AZ to bacterial antibiotic resistance require further study. The ability of SPAZ to improve pregnancy outcomes warrants further evaluation.

Item ID: 37952
Item Type: Article (Research - C1)
ISSN: 1741-7015
Keywords: intermittent preventive treatment, malaria, pregnancy, preterm delivery, sexually transmitted infections
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Ⓒ Unger et al.; licensee BioMed Central. 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Funders: Malaria in Pregnancy Consortium, Pregvax Consortium, European Union’s Seventh Framework Programme FP7-2007-HEALTH, Spanish Government (EUROSALUD 2008 Programme), Pfizer Inc, National Health and Medical Research Council (NHMRC)
Projects and Grants: Bill & Melinda Gates Foundation (46099), PREGVAX 201588, Pfizer WS394663, NHMRC 1016443, NHMRC 1043345
Date Deposited: 17 Mar 2015 15:53
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111716 Preventive Medicine @ 32%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 34%
11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 34%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50%
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