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

BMC Medicine

Stephen J Rogerson⁶  Ivo Mueller⁷  Peter Siba³  Inoni Betuela³  Clara Menendez²  Louis Schofield¹  Azucena Bardaji²  Dupain Singirok³  Desmond Sui³  Paula Samol³  Charles Kongs³  Elvin Lufele³  Johanna Wapling³  Anna Rosanas-Urgell⁴  Leanne J Robinson⁵  Connie SN Li Wai Suen⁵  Sarah Hanieh⁶  Alexandra J Umbers³  Regina A Wangnapi³  Maria Ome-Kaius³  Holger W Unger³ 

[1] Australian Institute of Tropical Health and Medicine, Faculty of Medicine, Health, and Molecular Sciences, James Cook University, Townsville 4811, Queensland, Australia;Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona, Rossello, 132, 7th floor, Barcelona, 08036, Spain;Papua New Guinea Institute of Medical Research, Goroka 441, Eastern Highlands Province, Papua New Guinea;Institute of Tropical Medicine, Nationalestraat 155, Antwerpen, 2000, Belgium;Walter and Eliza Hall Institute (WEHI), Parkville 3052, Victoria, Australia;Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Post Office Royal Melbourne Hospital, Parkville 3050, Victoria, Australia;Department of Medical Biology, The University of Melbourne, Parkville 3010, Victoria, Australia

关键词: Sexually transmitted infections;    Preterm delivery;    Pregnancy;    Malaria;    Intermittent preventive treatment;   

Others  :  1109815
DOI  :  10.1186/s12916-014-0258-3

 received in 2014-10-31, accepted in 2014-12-16,  发布年份 2015

【 摘 要 】

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.

Trial registration

ClinicalTrials.gov NCT01136850 webcite (06 April 2010).

【 授权许可】

   
2015 Unger et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

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Figure 3.

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