Volume 83, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Preterm delivery, which is associated with infections during pregnancy, is common in sub-Saharan Africa. We enrolled 1,320 pregnant women into a randomized, controlled trial in Malawi to study whether preterm delivery and low birth weight (LBW) incidence can be reduced by intermittent preventive treatment of maternal malaria and reproductive tract infections. The participants received either sulfadoxine-pyrimethamine (SP) twice (controls), monthly SP, or monthly SP and two doses of azithromycin (AZI-SP). The incidence of preterm delivery was 17.9% in controls, 15.4% in the monthly SP group ( 0.32), and 11.8% in AZI-SP group (risk ratio = 0.66, 0.01). Compared with controls, those in AZI-SP group had a risk ratio of 0.61 ( 0.02) for LBW. Incidence of serious adverse events was low in all groups. In conclusion, the incidence of preterm delivery and LBW can in some conditions be reduced by treating pregnant women with monthly SP and two azithromycin doses.


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  1. Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH, Rubens C, Menonf R, Van Look PF, , 2010. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ 88: 3138 [Crossref] [Google Scholar]
  2. Schultz LJ, Steketee RW, Macheso A, Kazembe P, Chitsulo L, Wirima JJ, , 1994. The efficacy of antimalarial regimens containing sulfadoxine-pyrimethamine and/or chloroquine in preventing peripheral and placental Plasmodium falciparum infection among pregnant women in Malawi. Am J Trop Med Hyg 51: 515522. [Google Scholar]
  3. Kulmala T, Vaahtera M, Ndekha M, Koivisto AM, Cullinan T, Salin ML, Ashorn P, , 2000. The importance of preterm births for peri- and neonatal mortality in rural Malawi. Paediatr Perinat Epidemiol 14: 219226.[Crossref] [Google Scholar]
  4. Osman NB, Challis K, Cotiro M, Nordahl G, Bergström S, , 2001. Perinatal outcome in an obstetric cohort of Mozambican women. J Trop Pediatr 47: 3038.[Crossref] [Google Scholar]
  5. van den Broek N, Ntonya C, Kayira E, White S, Neilson JP, , 2005. Preterm birth in rural Malawi: high incidence in ultrasound-dated population. Hum Reprod 20: 32353237.[Crossref] [Google Scholar]
  6. Goldenberg RL, Culhane JF, Iams JD, Romero R, , 2008. Epidemiology and causes of preterm birth. Lancet 371: 7584.[Crossref] [Google Scholar]
  7. Saigal S, Doyle LW, , 2008. An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet 371: 261269.[Crossref] [Google Scholar]
  8. Moster D, Lie RT, Markestad T, , 2008. Long-term medical and social consequences of preterm birth. N Engl J Med 359: 262273.[Crossref] [Google Scholar]
  9. Baraldi E, Filippone M, , 2007. Chronic lung disease after premature birth. N Engl J Med 357: 19461955.[Crossref] [Google Scholar]
  10. Espo M, Kulmala T, Maleta K, Cullinan T, Salin ML, Ashorn P, , 2002. Determinants of linear growth and predictors of severe stunting during infancy in rural Malawi. Acta Paediatr 91: 13641370.[Crossref] [Google Scholar]
  11. Victora CG, Adair L, Fall C, Hallal PC, Martorell R, Richter L, Sachdev HS, , 2008. Maternal and child undernutrition: consequences for adult health and human capital. Lancet 371: 340357.[Crossref] [Google Scholar]
  12. Meuris S, Piko BB, Eerens P, Vanbellinghen AM, Dramaix M, Hennart P, , 1993. Gestational malaria: assessment of its consequences on fetal growth. Am J Trop Med Hyg 48: 603609. [Google Scholar]
  13. Gray RH, Wabwire-Mangen F, Kigozi G, Sewankambo NK, Serwadda D, Moulton LH, Quinn TC, O'Brien KL, Meehan M, Abramowsky C, Robb M, Wawer MJ, , 2001. Randomized trial of presumptive sexually transmitted disease therapy during pregnancy in Rakai, Uganda. Am J Obstet Gynecol 185: 12091217.[Crossref] [Google Scholar]
  14. Sullivan AD, Nyirenda T, Cullinan T, Taylor T, Harlow SD, James SA, Meshnick SR, , 1999. Malaria infection during pregnancy: intrauterine growth retardation and preterm delivery in Malawi. J Infect Dis 179: 15801583.[Crossref] [Google Scholar]
  15. World Health Organization, 2009. World Malaria Report 2009. Geneva: World Health Organization. Available at: http://whqlibdoc.who.int/publications/2009/9789241563901_eng.pdf. Accessed June 21, 2010. [Google Scholar]
  16. Verhoeff FH, Brabin BJ, Chimsuku L, Kazembe P, Russell WB, Broadhead RL, , 1998. An evaluation of the effects of intermittent sulfadoxine-pyrimethamine treatment in pregnancy on parasite clearance and risk of low birthweight in rural Malawi. Ann Trop Med Parasitol 92: 141150.[Crossref] [Google Scholar]
  17. Rogerson SJ, Chaluluka E, Kanjala M, Mkundika P, Mhango C, Molyneux ME, , 2000. Intermittent sulfadoxine-pyrimethamine in pregnancy: effectiveness against malaria morbidity in Blantyre, Malawi, in 1997–99. Trans R Soc Trop Med Hyg 94: 549553.[Crossref] [Google Scholar]
  18. White NJ, , 2005. Intermittent presumptive treatment for malaria. PLoS Med 2: e3.[Crossref] [Google Scholar]
  19. Menéndez C, D'Alessandro U, ter Kuile FO, , 2007. Reducing the burden of malaria in pregnancy by preventive strategies. Lancet Infect Dis 7: 126135.[Crossref] [Google Scholar]
  20. Ter Kuile FO, Steketee RW, , 2007. Intermittent preventive therapy with sulfadoxine-pyrimethamine during pregnancy: seeking information on optimal dosing frequency. J Infect Dis 196: 15741576.[Crossref] [Google Scholar]
  21. van den Broek NR, White SA, Goodall M, Ntonya C, Kayira E, Kafulafula G, Neilson JP, , 2009. The APPLe study: a randomized, community-based, placebo-controlled trial of azithromycin for the prevention of preterm birth, with meta-analysis. PLoS Med 6: e1000191.[Crossref] [Google Scholar]
  22. Anderson SL, Berman J, Kuschner R, Wesche D, Magill A, Wellde B, Schneider I, Dunne M, Schuster BG, , 1995. Prophylaxis of Plasmodium falciparum malaria with azithromycin administered to volunteers. Ann Intern Med 123: 771773.[Crossref] [Google Scholar]
  23. Taylor WR, Richie TL, Fryauff DJ, Picarima H, Ohrt C, Tang D, Braitman D, Murphy GS, Widjaja H, Tjitra E, Ganjar A, Jones TR, Basri H, Berman J, , 1999. Malaria prophylaxis using azithromycin: a double-blind, placebo-controlled trial in Irian Jaya, Indonesia. Clin Infect Dis 28: 7481.[Crossref] [Google Scholar]
  24. Ohrt C, Willingmyre GD, Lee P, Knirsch C, Milhous W, , 2002. Assessment of azithromycin in combination with other antimalarial drugs against Plasmodium falciparum in vitro . Antimicrob Agents Chemother 46: 25182524.[Crossref] [Google Scholar]
  25. Vallely A, Vallely L, Changalucha J, Greenwood B, Chandramohan D, , 2007. Intermittent preventive treatment for malaria in pregnancy in Africa: what's new, what's needed? Malar J 6: 16.[Crossref] [Google Scholar]
  26. Pfizer Inc. Zithromax® Product Information. Available at: http://www.pfizer.com/files/products/uspi_zithromax600mg.pdf. Accessed May 31, 2009. [Google Scholar]
  27. Sarkar M, Woodland C, Koren G, Einarson AR, , 2006. Pregnancy outcome following gestational exposure to azithromycin. BMC Pregnancy Childbirth 6: 18.[Crossref] [Google Scholar]
  28. Kulmala T, Vaahtera M, Ndekha M, Koivisto AM, Cullinan T, Salin ML, Ashorn P, , 2001. Gestational health and predictors of newborn weight amongst pregnant women in rural Malawi. Afr J Reprod Health 5: 99108.[Crossref] [Google Scholar]
  29. Center for Social Research, Save the Children Federation USA, Malawi Ministry of Health and Population, MEASURE Evaluation, 2004. Avoiding Unwanted Pregnancy and Sexually Transmitted Infections: A Rural Malawi District Study. Chapel Hill, NC: MEASURE Evaluation. Available at: www.cpc.unc.edu/measure/publications/pdf/tr-04-27.pdf. Accessed October 8, 2009. [Google Scholar]
  30. Binder DA, , 1983. On the variances of asymptotically normal estimators from complex surveys. Int Stat Rev 51: 279292.[Crossref] [Google Scholar]
  31. Swadpanich U, Lumbiganon P, Prasertcharoensook W, Laopaiboon M, , 2008. Antenatal lower genital tract infection screening and treatment programs for preventing preterm delivery. Cochrane Database Syst Rev CD006178. [Google Scholar]
  32. Goldenberg RL, Mwatha A, Read JS, Adeniyi-Jones S, Sinkala M, Msmanga G, Martinson F, Hoffman I, Fawzi W, Valentine M, Emel L, Brown E, Mudenda V, Taha TE, , 2006. The HPTN 024 Study: the efficacy of antibiotics to prevent chorioamnionitis and preterm birth. Am J Obstet Gynecol 194: 650661.[Crossref] [Google Scholar]
  33. Gichangi PB, Ndinya-Achola JO, Ombete J, Nagelkerke NJ, Temmerman M, , 1997. Antimicrobial prophylaxis in pregnancy: a randomized, placebo-controlled trial with cefetamet-pivoxil in pregnant women with a poor obstetric history. Am J Obstet Gynecol 177: 680684.[Crossref] [Google Scholar]
  34. Parise ME, Ayisi JG, Nahlen BL, Schultz LJ, Roberts JM, Misore A, Muga R, Oloo AJ, Steketee RW, , 1998. Efficacy of sulfadoxine-pyrimethamine for prevention of placental malaria in an area of Kenya with a high prevalence of malaria and human immunodeficiency virus infection. Am J Trop Med Hyg 59: 813822. [Google Scholar]
  35. Filler SJ, Kazembe P, Thigpen M, Macheso A, Parise ME, Newman RD, Steketee RW, Hamel M, , 2006. Randomized trial of 2-dose versus monthly sulfadoxine-pyrimethamine intermittent preventive treatment for malaria in HIV-positive and HIV-negative pregnant women in Malawi. J Infect Dis 194: 286293.[Crossref] [Google Scholar]
  36. Hamer DH, Mwanakasale V, Macleod WB, Chalwe V, Mukwamataba D, Champo D, Mwananyanda L, Chilengi R, Mubikayi L, Mulele CK, Mulenga M, Thea DM, Gill CJ, , 2007. Two-dose versus monthly intermittent preventive treatment of malaria with sulfadoxine-pyrimethamine in HIV-seropositive pregnant Zambian women. J Infect Dis 196: 15851594.[Crossref] [Google Scholar]
  37. Nkhoma S, Molyneux M, Ward S, , 2007. Molecular surveillance for drug-resistant Plasmodium falciparum malaria in Malawi. Acta Trop 102: 138142.[Crossref] [Google Scholar]
  38. Brunham RC, Kuo C, Stevens CE, Holmes KK, , 1982. Treatment of concomitant Neisseria gonorrhoeae and Chlamydia trachomatis infections in women: comparison of trimethoprim-sulfamethoxazole with ampicillin-probenecid. Rev Infect Dis 4: 491499.[Crossref] [Google Scholar]
  39. Mumtaz G, Ridgway GL, Felmingham D, , 1988. In vitro activity of sulphamethoxazole/trimethoprim and sulfadoxine/pyrimethamine against Chlamydia trachomatis SA2f in McCoy cell culture. Eur J Clin Microbiol Infect Dis 7: 415417.[Crossref] [Google Scholar]
  40. Dewey KG, Adu-Afarwuah S, , 2008. Systematic review of the efficacy and effectiveness of complementary feeding interventions in developing countries. Matern Child Nutr 4 (Suppl 1): 2485.[Crossref] [Google Scholar]
  41. Peters PJ, Thigpen MC, Parise ME, Newman RD, , 2007. Safety and toxicity of sulfadoxine/pyrimethamine: implications for malaria prevention in pregnancy using intermittent preventive treatment. Drug Saf 30: 481501.[Crossref] [Google Scholar]
  42. Kalilani L, Mofolo I, Chaponda M, Rogerson SJ, Alker AP, Kwiek JJ, Meshnick SR, , 2007. A randomized controlled pilot trial of azithromycin or artesunate added to sulfadoxine-pyrimethamine as treatment for malaria in pregnant women. PLoS ONE 2: e1166.[Crossref] [Google Scholar]
  43. Kenyon S, Pike K, Jones D, Brocklehurst P, Marlow N, Salt A, Taylor DJ, , 2008. Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial. Lancet 372: 13191327.[Crossref] [Google Scholar]
  44. Moher D, Schulz F, Altman DG, , 2001. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. Lancet 357: 11911194.[Crossref] [Google Scholar]

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  • Received : 10 May 2010
  • Accepted : 25 Aug 2010
  • Published online : 06 Dec 2010

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