Adverse Pregnancy Outcomes in an Area Where Multidrug‐Resistant Plasmodium vivax and Plasmodium falciparum Infections Are Endemic
Open accessAbstract
BACKGROUND: Plasmodium falciparum infection exerts a considerable burden on pregnant women, but less is known about the adverse consequences of Plasmodium vivax infection. METHODS: In Papua, Indonesia, where multiple drug resistance to both species has emerged, we conducted a cross-sectional hospital-based study to quantify the risks and consequences of maternal malaria. RESULTS: From April 2004 through December 2006, 3046 pregnant women were enrolled in the study. The prevalence of parasitemia at delivery was 16.8% (432 of 2570 women had infections), with 152 (35.2%) of these 432 infections being associated with fever. The majority of infections were attributable to P. falciparum (250 [57.9%]); 146 (33.8%) of the infections were attributable to P. vivax, and 36 (8.3%) were coinfections with both species. At delivery, P. falciparum infection was associated with severe anemia (hemoglobin concentration, <7 g/dL; odds ratio [OR], 2.8; 95% confidence interval [95% CI], 2.0-4.0) and a 192 g (95% CI, 119-265) reduction in mean birth weight (P<.001). P. vivax infection was associated with an increased risk of moderate anemia (hemoglobin concentration, 7-11 g/dL; OR, 1.8; 95% CI, 1.2-2.9; P=.01) and a 108 g (95% CI, 17.5-199) reduction in mean birth weight (P<.019). Parasitemia was associated with preterm delivery (OR, 1.5; 95% CI, 1.1-2.0; P=.02) and stillbirth (OR, 2.3; 95% CI, 1.3-4.1; P=.007) but was not associated with these outcomes after controlling for the presence of fever and severe anemia, suggesting that malaria increases the risk of preterm delivery and stillbirth through fever and contribution to severe anemia rather than through parasitemia per se. CONCLUSIONS: These observations highlight the need for novel, safe, and effective treatment and prevention strategies against both multidrug-resistant P. falciparum and multidrug-resistant P. vivax infections in pregnant women in areas of mixed endemicity.
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Younger women, particularly adolescents, are at higher risk of malaria infection than older women, independent of parity.
“It is well established that younger women (primigravidae and multigravidae), particularly adolescents, are at higher risk of malaria infection than older women,18–20 and this is independent of parity.20–22”
From Malaria in pregnancy. (2013) · cites this paper as [18]
The Results section, “Risk Factors for Maternal Malaria” (page unavailable), identifies primigravidity—not younger age—as independently associated with parasitemia. The Discussion likewise says first-time mothers were more susceptible than multigravid women. The paper does not establish higher risk among adolescents or an age-related risk independent of parity. (LLM, conf=0.78)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredIn unstable transmission settings, malaria can cause maternal anaemia, more in primigravidae than multigravidae and for falciparum infections more than for vivax infections.
“Where malaria transmission is unstable, malaria can cause maternal anaemia,18,35,39–40 more in primigravidae than in multigravidae and for falciparum infections more than for vivax infections.18,35”
From Malaria in pregnancy. (2013) · cites this paper as [18]
The Results (Maternal Anemia; page unavailable) support a stronger association with anemia for falciparum than vivax infection. But they report severe anemia was more prevalent in multigravid than primigravid women (10.5% versus 7.6%), the opposite of the claimed parity comparison; the Discussion also says multigravid women were more anemic. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredSevere cases of malaria in pregnancy may progress to life-threatening complications such as severe malaria in both the mother and the fetus.
“Severe cases may progress to life-threatening complications such as severe malaria both the mother and the fetus [40, 43, 84].”
From Current update on malaria in pregnancy: a systematic review (2025) · cites this paper as [84]
The Results (Maternal Malaria) report women meeting criteria for severe malaria and two deaths involving P. falciparum infection with multiorgan failure. The Results (Pregnancy Outcomes) and Discussion report stillbirth and other adverse fetal outcomes, but do not describe severe malaria in the fetus or establish that severe cases progressed to it. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn unstable transmission settings, preterm deliveries, still births and neonatal deaths have been associated with malaria.
“In unstable transmission settings, preterm deliveries, still births and neonatal deaths have been associated with malaria.18”
From Malaria in pregnancy. (2013) · cites this paper as [18]
The Results (Pregnancy Outcomes; page not provided) associate maternal malaria with preterm delivery and P. falciparum parasitemia with stillbirth and early neonatal death, although the latter associations were no longer statistically significant after adjustment for fever and severe anemia. The Methods (Study site; page not provided) describe transmission in the Papua study area but do not establish that it was an unstable-transmission setting, so that qualifier is not verified by this source. (LLM, conf=0.78)
Experimental — accuracy not yet measuredFever, anaemia, and high levels of TNF alpha or interleukin 10 have been identified as important risk factors for malaria-related preterm delivery.
“It is unclear what the mechanism at the basis of malaria-related preterm delivery is, though fever, anaemia, and high levels of TNF alpha or interleukin 10 have been identified as important risk factors.18,83–84”
From Malaria in pregnancy. (2013) · cites this paper as [18]
The Discussion identifies concomitant fever and severe anemia as major determinants of prematurity associated with maternal malaria, and the Results report their associations with preterm delivery. The paper does not identify elevated TNF alpha or interleukin 10 as risk factors; searches for those cytokines returned no supporting passage. Page numbers were not available in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Other Plasmodium species, such as P. knowlesi, P. ovale, and P. malariae, are less common causes of malaria in pregnancy.
“Other species, such as P.knowlesi, P.ovale, and P.malariae are less common.”
From Current update on malaria in pregnancy: a systematic review (2025) · cites this paper as [28]
The Results (Maternal Malaria; page not supplied) report that P. malariae and P. ovale accounted for far fewer infections in the pregnant women studied than P. falciparum or P. vivax. The paper does not address P. knowlesi, and its findings from one hospital in Papua do not establish how common these species are in pregnancy generally. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNon-malarial fevers independently increase the risk of miscarriage.
“Indeed, non malarial fevers also independently increase the risk of miscarriage.18,42”
From Malaria in pregnancy. (2013) · cites this paper as [18]
The Discussion (page unavailable) says fever from any cause has been independently associated with premature labor. The Results (page unavailable) also identify fever as a factor in preterm delivery and stillbirth, but the paper does not establish that non-malarial fever independently increases miscarriage risk. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn unstable transmission settings, malaria as a cause of miscarriage seems more common, as the majority of infections evolve towards a clinical attack with fever, which may by itself determine miscarriage.
“Where malaria transmission is unstable, malaria as a cause of miscarriage seems more common, as the majority of infections evolve towards a clinical attack with fever, which may by itself determine miscarriage.”
From Malaria in pregnancy. (2013) · cites this paper as [18]
The Introduction (page unavailable) says infections are more frequently symptomatic in lower-transmission regions, and the Discussion links malaria-associated fever to prematurity and stillbirth. It does not establish that fever causes miscarriage or that a majority of infections develop a febrile attack; in the Results, 35.2% of women with parasitemia at delivery had fever at or shortly before delivery. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThere is an association between parasitemia and preterm delivery and stillbirth, suggesting that the increased risk of malaria is primarily due to fever and severe anemia rather than parasitemia itself.
“Another study also found an association between parasitemia and preterm delivery and stillbirth, suggesting that the increased risk of malaria is primarily due to fever and severe anemia rather than parasitemia itself [40, 43, 84].”
From Current update on malaria in pregnancy: a systematic review (2025) · cites this paper as [84]
Primigravidae are at higher risk of malaria than multigravidae, though less in low transmission settings, while in epidemic areas the risk is not affected by parity.
“Parity also affects the risk of malaria as primigravidae are at higher risk than multigravidae,18–20, 23–24 though less in low transmission settings,15 while in epidemic areas, the risk is not affected by parity.25”
From Malaria in pregnancy. (2013) · cites this paper as [18]
P. vivax infection during pregnancy is associated with stillbirth, preterm delivery, low birthweight, and anaemia.
“Plasmodium vivax is also associated with stillbirth [1], preterm delivery [14], low birthweight [15, 16], and anaemia [16–18]”
From Global estimates of pregnancies at risk of Plasmodium falciparum and Plasmodium vivax infection in 2020 and changes in risk patterns since 2000 (2022) · cites this paper as [16]
Plasmodium vivax infection during pregnancy was associated with adverse outcomes in studies from Thailand and Indonesia.
“Plasmodium vivax infection during pregnancy was associated with adverse outcomes in studies from Thailand and Indonesia (8,9); however, studies in Latin America reported varying results.”
From Clinical outcomes of submicroscopic infections and correlates of protection of VAR2CSA antibodies in a longitudinal study of pregnant women in Colombia (2018) · cites this paper as [9]
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Diagnosis and Treatment of Plasmodium vivax Malaria
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Self-citationUltrasound Evidence of Early Fetal Growth Restriction after Maternal Malaria Infection
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Self-citationClinical impact of vivax malaria: A collection review
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Self-citation<i>Plasmodium knowlesi</i>Malaria During Pregnancy
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Self-citationEffect of malaria on placental volume measured using three-dimensional ultrasound: a pilot study
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Self-citation
- Authors
- Poespoprodjo, J. R., Fobia, W., Kenangalem, E., Lampah, D. A., Warikar, N., Seal, A., McGready, R., Sugiarto, P., Tjitra, E., Anstey, N. M., & Price, R. N.
- Affiliations
- Menzies School of Health Research (AU)
- University College London (GB)
- Churchill Hospital (GB)
- Kementerian Kesehatan Republik Indonesia (ID)
- Charles Darwin University (AU)
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-05
- Volume
- 46
- Issue
- 9
- Pages
- 1374-1381
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC2875100
- OpenAlex
- W2154959709
- Cited by
- 148
- References
- 32
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 12 · 2018: 11 · 2017: 5 · 2016: 11 · 2015: 12 · 2014: 12 · 2013: 10 · 2012: 18
- FWCI
- 8.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (074637, 071614)
- Menzies School of Health Research
- International Center for Responsible Gaming
- Mahidol University
- Medical Research Council
- National Health and Medical Research Council (283321)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- maternal malaria, Plasmodium vivax, Plasmodium falciparum, multidrug resistance, adverse pregnancy outcomes, severe anemia, birth weight, preterm birth, stillbirth, fever, co-infection, Papua, malaria in pregnancy, hemoglobin levels, malaria prevention
- MeSH terms
- Adult, Animals, Antimalarials, Cross-Sectional Studies, Female, Humans, Indonesia, Piperazines, Plasmodium falciparum, Plasmodium vivax, Pregnancy, Pregnancy Outcome, Surveys and Questionnaires, Quinolines, Pregnancy Complications, Parasitic, Malaria, Falciparum, Malaria, Vivax, Drug Resistance, Multiple, Parasitemia, Endemic Diseases, Artemisinins
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