Intermittent Preventive Therapy for Malaria During Pregnancy Using 2 vs 3 or More Doses of Sulfadoxine-Pyrimethamine and Risk of Low Birth Weight in Africa: Systematic Review and Meta-analysis
Open accessAbstract
IMPORTANCE: Intermittent preventive therapy with sulfadoxine-pyrimethamine to control malaria during pregnancy is used in 37 countries in sub-Saharan Africa, and 31 of those countries use the standard 2-dose regimen. However, 2 doses may not provide protection during the last 4 to 10 weeks of pregnancy, a pivotal period for fetal weight gain. OBJECTIVE: To perform a systematic review and meta-analysis of trials to determine whether regimens containing 3 or more doses of sulfadoxine-pyrimethamine for intermittent preventive therapy during pregnancy are associated with a higher birth weight or lower risk of low birth weight (LBW) (<2500 g) than standard 2-dose regimens. DATA SOURCES AND STUDY SELECTION: ISI Web of Knowledge, EMBASE, SCOPUS, PubMed, LILACS, the Malaria in Pregnancy Library, Cochrane CENTRAL, and trial registries from their inception to December 2012, without language restriction. Eligible studies included randomized and quasi-randomized trials of intermittent preventive therapy during pregnancy with sulfadoxine-pyrimethamine monotherapy. DATA EXTRACTION: Data were independently abstracted by 2 investigators. Relative risk (RR), mean differences, and 95% CIs were calculated with random-effects models. RESULTS: Of 241 screened studies, 7 trials of 6281 pregnancies were included. The median birth weight in the 2-dose group was 2870 g (range, 2722-3239 g) and on average 56 g higher (95% CI, 29-83 g; I2 = 0%) in the ≥3-dose group. Three or more doses were associated with fewer LBW births (RR, 0.80; 95% CI, 0.69-0.94; I 2 = 0%), with a median LBW risk per 1000 women in the 2-dose group (assumed control group risk) of 167 per 1000 vs 134 per 1000 in the ≥3-dose group (absolute risk reduction, 33 per 1000 [95% CI, 10-52]; number needed to treat = 31). The association was consistent across a wide range of sulfadoxine-pyrimethamine resistance (0% to 96% dihydropteroate-synthase K540E mutations). There was no evidence of small-study bias. The ≥3-dose group had less placental malaria (RR, 0.51; 95% CI, 0.38-0.68; I 2 = 0%, in 6 trials, 63 vs 32 per 1000; absolute risk reduction, 31 per 1000 [95% CI, 20-39]). In primigravid plus secundigravid women, the risk of moderate to severe maternal anemia was lower in the ≥3-dose group (RR, 0.60; 95% CI, 0.36-0.99; I2 = 20%; in 6 trials, 36 vs 22 per 1000; absolute risk reduction, 14 per 1000 [95% CI, 0.4-23]). There were no differences in rates of serious adverse events. CONCLUSIONS AND RELEVANCE: Among pregnant women in sub-Saharan Africa, intermittent preventive therapy with 3 or more doses of sulfadoxine-pyrimethamine was associated with a higher birth weight and lower risk of LBW than the standard 2-dose regimens. These data provide support for the new WHO recommendations to provide at least 3 doses of intermittent preventive therapy during pregnancy at each scheduled antenatal care visit in the second and third trimester.
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P. falciparum infection during pregnancy is a major factor underlying low birth weight.
“P. falciparum infection (either microscopically or sub-microscopically) during pregnancy is one of the major factors underlying low birth weight”
From High uptake of Intermittent Preventive Treatment of malaria in pregnancy is associated with improved birth weight among pregnant women in Ghana (2019) · cites this paper as [16]
The passage labeled Abstract > Conclusions and Relevance (page unavailable) says that P. falciparum infection during pregnancy is associated with low birth weight in areas of stable malaria transmission in sub-Saharan Africa. It does not establish infection as a major underlying cause or address the citing sentence’s distinction between microscopic and submicroscopic infection. (LLM, conf=0.83)
Experimental — accuracy not yet measuredOther studies revealed a three-course or monthly IPTp-SP administration to be more effective in reducing low birth weight than the original two-course policy.
“other studies revealed a three-course or monthly IPTp-SP administration to be more effective in reducing low birth weight than the original two-course policy16,17.”
From High uptake of Intermittent Preventive Treatment of malaria in pregnancy is associated with improved birth weight among pregnant women in Ghana (2019) · cites this paper as [16]
Several studies have shown a beneficial effect of IPTp-SP on birth weight with some indication of a dose-dependent relationship.
“several studies have shown the beneficial effect of IPTp-SP on the birth weight with some indication of a dose-dependent relationship with birth weight13,16,22”
From High uptake of Intermittent Preventive Treatment of malaria in pregnancy is associated with improved birth weight among pregnant women in Ghana (2019) · cites this paper as [16]
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- Authors
- Kayentao, K., Garner, P., Maria van Eijk, A., Naidoo, I., Roper, C., Mulokozi, A., MacArthur, J. R., Luntamo, M., Ashorn, P., Doumbo, O. K., & ter Kuile, F. O.
- Affiliations
- Liverpool School of Tropical Medicine (GB)
- Ifakara Health Institute (TZ)
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2013-02-13
- Volume
- 309
- Issue
- 6
- Pages
- 594
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC4669677
- OpenAlex
- W2108741937
- Cited by
- 298
- References
- 44
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 17 · 2023: 23 · 2022: 26 · 2021: 29 · 2020: 23 · 2019: 18 · 2018: 18 · 2017: 21 · 2016: 20 · 2015: 35 · 2014: 27 · 2013: 12 · 2012: 1
- FWCI
- 31.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Institutes of Health (CC999999)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Global Maternal and Child Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- malaria in pregnancy, sulfadoxine-pyrimethamine, low birth weight, birth weight, dosing regimen, fetal growth, malaria prophylaxis, sub-Saharan Africa, neonatal outcomes
- MeSH terms
- Africa, Antimalarials, Drug Administration Schedule, Drug Combinations, Female, Humans, Infant, Low Birth Weight, Infant, Newborn, Malaria, Pregnancy, Pregnancy Complications, Infectious, Pyrimethamine, Risk, Sulfadoxine
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