Review
Epidemiology and burden of malaria in pregnancy

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Summary

We reviewed evidence of the clinical implications and burden of malaria in pregnancy. Most studies come from sub-Saharan Africa, where approximately 25 million pregnant women are at risk of Plasmodium falciparum infection every year, and one in four women have evidence of placental infection at the time of delivery. P falciparum infections during pregnancy in Africa rarely result in fever and therefore remain undetected and untreated. Meta-analyses of intervention trials suggest that successful prevention of these infections reduces the risk of severe maternal anaemia by 38%, low birthweight by 43%, and perinatal mortality by 27% among paucigravidae. Low birthweight associated with malaria in pregnancy is estimated to result in 100 000 infant deaths in Africa each year. Although paucigravidae are most affected by malaria, the consequences for infants born to multigravid women in Africa may be greater than previously appreciated. This is because HIV increases the risk of malaria and its adverse effects, particularly in multigravidae, and recent observational studies show that placental infection almost doubles the risk of malaria infection and morbidity in infants born to multigravidae. Outside Africa, malaria infection rates in pregnant women are much lower but are more likely to cause severe disease, preterm births, and fetal loss. Plasmodium vivax is common in Asia and the Americas and, unlike P falciparum, does not cytoadhere in the placenta, yet, is associated with maternal anaemia and low birthweight. The effect of infection in the first trimester, and the longer term effects of malaria beyond infancy, are largely unknown and may be substantial. Better estimates are also needed of the effects of malaria in pregnancy outside Africa, and on maternal morbidity and mortality in Africa. Global risk maps will allow better estimation of potential impact of successful control of malaria in pregnancy.

Introduction

“So long as Woman has walked the earth, malaria may have stalked her”;1 however, the problem of malaria in pregnancy was not described until the early 20th century.2, 3 This was followed by almost four decades of descriptive studies in sub-Saharan Africa that focused on the frequency of Plasmodium falciparum placental infection and its adverse effects.4, 5, 6, 7, 8, 9 In the past two decades, many comprehensive reviews have highlighted various aspects of malaria in pregnancy and its effect on maternal, newborn, and infant health. In this review, we compile these estimates across the spectrum of disease manifestations, including what is known in low and unstable transmission areas within and outside of sub-Saharan Africa and of species other than P falciparum. We used data from review articles, and included new data that were recently published if it provided important new information or insights.

Our aim is to identify gaps in knowledge of the epidemiology and burden of malaria in pregnancy globally, and to chart a course for gathering requisite knowledge to fill those gaps both through special studies and routine data-gathering exercises such as monitoring, surveillance, and evaluation.

Section snippets

Stable transmission in Africa

A myriad of studies have reported on the prevalence of peripheral and placental parasitaemia in areas of stable endemic malaria transmission in Africa. Data from Africa before 1980 have been summarised in a review by Brabin and colleagues.10 In another review of 20 studies from eight countries in Africa done between 1985 and 2000, the median prevalence of maternal malaria infection (defined as peripheral or placental infection) in all gravidae was 27·8%.11 A similar estimate of 26% was obtained

Effects on maternal health

The clinical features of malaria infection during pregnancy vary by the degree of immunity that women have acquired by the time they become pregnant, and thus by the epidemiological setting (figure 1).

Stable transmission in Africa

Malaria in pregnancy has an unequivocally devastating effect on the newborn infant (table 4). Low birthweight (defined as birthweight <2500 g) is associated with a marked increase in infant mortality.11, 30, 50, 52, 53 In areas of high malaria transmission in Africa, the risk of low birthweight approximately doubles if women have placental malaria,12 with the greatest effect in primigravidae.54 The odds ratio of low birthweight associated with malaria is two to seven times higher in primigravid

Effect on infant outcomes

The prevalence of fetal anaemia at birth is high in malaria-endemic areas, and the risk is associated with the presence of high-density parasitaemia in the mother at delivery.61 Few studies report the effect of malaria in the pregnant mother on anaemia or malaria in the infant (Table 5, Table 6). Some studies have now shown that the risk of all-cause anaemia is estimated to be three times higher among infants born to mothers with placental parasitaemia, even after adjusting for environmental

Long-term consequences for the child

There is a dearth of literature on the long-term consequences of malaria in pregnancy for the child. A large number of mainly nutritional studies indicate that exposure to an abnormal intrauterine environment affects mental, metabolic, and anthropometric development, resulting in increased risk of disease later in life. In high-income countries, low birthweight has been associated with higher arterial pressure, chronic kidney disease, ischaemic cardiomyopathy, stroke, diabetes, respiratory

Interaction with HIV

The burden of malaria in pregnancy is exacerbated by co-infection with HIV. Sub-Saharan Africa bears the brunt of this comorbidity, where approximately 25 million pregnant women are at risk of P falciparum infection every year,11, 100 and 77% (13·5 million) of the world's HIV-infected women reside.101 A review of 11 studies from Africa highlights the deleterious effect of HIV on malaria, reporting higher risks of placental malaria (summary relative risk 1·66, 95% CI 1·48–1·87), high-density

Effect of other Plasmodium species

Although all four Plasmodium species can infect pregnant women, only susceptibility to P vivax and P falciparum has been studied.102, 103 Most of the data on P vivax infections are from regions outside Africa. Women are at increased risk of P vivax infection during pregnancy, although the increased risk is less pronounced than with P falciparum; data from Brazil show that the ratio of P falciparum to P vivax was 1:5·6 in a group of non-pregnant infected women, whereas it was only half that

Estimating burden

Any attempt to quantify the global burden of malaria in pregnancy is made more difficult by a lack of an accurate and good quality estimation of both the numerator (ie, women affected by adverse outcomes of malaria in pregnancy) and the denominator (ie, the population at risk). The numbers of women at risk of malaria in pregnancy are underestimated because of the practice of using routine national reporting systems, especially outside Africa, and because the number of unidentified pregnancies

Gaps in public-health knowledge

On the basis of the above review, it is clear that the clinical consequences of malaria in pregnancy to mother and child and the magnitude of the problem are enormous. However, we have very little information from Asia and Latin America, and even for Africa we are currently unable to make an evidence-based statement on whether the overall burden of malaria in pregnancy has increased, decreased, or remained at a steady state in the past few decades. At present, there are substantial knowledge

Conclusion

Although much is known about the epidemiology and burden of malaria in pregnancy, there remain substantial gaps in our understanding that impede our ability to control this important public-health problem. The effect of infection in the first trimester, and the longer term effects of malaria in pregnancy beyond infancy are largely unknown and may be substantial. Better estimates are also needed of the effects of malaria in pregnancy outside Africa, and on maternal morbidity and mortality

Search strategy and selection criteria

Papers for this Review were identified by searches of PubMed with the search terms “malaria” AND [“pregnancy” OR “pregnant”] AND [“burden” OR “prevalence”] to January, 2006. Additional references were obtained from references of the articles in the search, and from malaria in pregnancy databases of published and unpublished literature at CDC and Liverpool School of Tropical Medicine. Special consideration was given to articles identified as reviews in PubMed. Only papers published in

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