Version July 2025
INTRODUCTION —
Malaria infection in pregnancy is a major cause of maternal death, maternal anemia, and adverse pregnancy outcomes (miscarriage, preterm birth, fetal growth restriction, low birth weight, stillbirth, congenital infection, neonatal mortality) in geographic areas where malaria infection occurs in pregnant people [1]. Pregnancy increases the chances of developing malaria infection and severe disease when infected. Pregnant people are particularly vulnerable to Plasmodium falciparum infection because red cells infected with the parasite can sequester in the placenta, and thereby cause adverse pregnancy outcomes. Currently available anti-malarial drug treatments may not completely eradicate peripheral or placental parasitemia [2].
Issues related to the epidemiology, clinical manifestations, diagnosis, and outcome of malaria in pregnancy will be reviewed here. Issues related to prevention and treatment of malaria in pregnancy are discussed separately. (See "Malaria in pregnancy: Prevention and treatment" and "Treatment of severe malaria", section on 'Pregnant patients'.)
General issues related to malaria are also discussed separately:
●(See "Malaria: Epidemiology, prevention, and elimination".)
●(See "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children".)
●(See "Laboratory tools for diagnosis of malaria".)
●(See "Prevention of malaria infection in travelers".)
●(See "Treatment of uncomplicated falciparum malaria in nonpregnant adults and children".)
●(See "Non-falciparum malaria: P. vivax, P. ovale, and P. malariae".)
●(See "Non-falciparum malaria: Plasmodium knowlesi".)
EPIDEMIOLOGY —
Malaria occurs in most tropical countries [3]. Epidemiology within a region may vary considerably depending on location (eg, rural versus city), season (rainy versus dry), human migration patterns, and use of malaria prevention strategies. The risk of locally acquired malaria is extremely low in the United States, but rare cases were identified in 2023 [4]. (See "Malaria: Epidemiology, prevention, and elimination".)
In general, for individuals living in a given geographic area, a higher prevalence of malaria has been observed among pregnant compared with nonpregnant people, younger compared with older pregnant people, first or second pregnancies compared with third or higher gravidity, human immunodeficiency virus (HIV)-infected people compared with those without HIV infection, and in the first and second trimesters of pregnancy compared with the third trimester [5-8].
The increased prevalence of malaria in pregnant people has been attributed to multiple factors, including increased susceptibility to mosquito bites [9,10], immunologic and hormonal changes related to pregnancy, and the ability of infected erythrocytes to adhere to and sequester in the intervillous spaces of the placenta, where maternal blood directly interfaces with the placental trophoblast [11,12] (see 'Pathogenesis' below). The increased risk for acquiring malaria and developing more severe disease persists for at least 60 to 70 days postpartum [13,14].
In sub-Saharan Africa (a high transmission region), the median prevalence of maternal malaria (defined as peripheral or placental infection identified by microscopy) is 28 percent [5]. The prevalence can be even higher when more sensitive diagnostic methods (such as placental histology or polymerase chain reaction) are used [5,15]. In low transmission regions such as Asia and Latin America, the reported median prevalence of maternal malaria was 6.2 percent in 2007 [5]; however, malaria transmission is declining in these regions, so current prevalence may be lower [16,17].
MICROBIOLOGY —
Species of malaria in humans include P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. The effect of malaria on pregnancy varies by species and correlates with the ability of infected erythrocytes to adhere to and sequester in the placenta. (See 'Pathogenesis' below.)
●P. falciparum invades red cells of all ages; it is associated with especially high levels of parasitemia, placental sequestration, and severe adverse maternal-fetal sequelae.
●P. vivax infects only reticulocytes; it is infrequently associated with placental sequestration and less commonly associated with severe adverse maternal and fetal outcomes [18-21].
●P. knowlesi is relatively rare in pregnancy, but severe disease in pregnant people has been described in Southeast Asia [22]. No placental changes have been observed in association with P. knowlesi infection [11].
●P. ovale and P. malariae are not typically associated with severe illness in pregnancy. No placental changes have been observed in association with P. ovale or P. malariae infection [11].
Coinfection with multiple species is relatively uncommon and varies in prevalence with transmission intensity; it is most frequently observed with P. falciparum and P. vivax [23]. Sequential infection with the same or different species occurs more commonly than coinfection.
Issues related to non-falciparum malaria species are discussed further separately. (See "Non-falciparum malaria: P. vivax, P. ovale, and P. malariae".)
PATHOLOGY
Placental infection — Parasites may be absent in the peripheral blood but present in the placenta. In one study of 415 patients in Tanzania with histologic evidence of active placental malaria infection, parasitemia was absent in 46 percent of cases [24].
In endemic settings, placental histology is largely a research tool, as it is only performed after delivery and cannot guide pregnancy management. Histopathologic findings of the malaria-infected placenta include [12]:
●Infected erythrocytes and increased numbers of maternal phagocytic cells, especially monocytes, in the intervillous space.
●Hemozoin (malaria pigment) deposition in phagocytic leucocytes and within fibrin deposits in the intervillous space.
●Trophozoite and schizont stages of the parasite.
●Syncytial degradation and increased syncytial knotting; in rare cases, localized destruction of the villi [25].
Pathogenesis — The key finding of P. falciparum malaria in pregnant people is parasites within erythrocytes sequestered in the intervillous space (picture 1) [26]. These infected erythrocytes are immunologically distinct from infected erythrocytes found in nonpregnant individuals: they express a specific class of variant surface antigen (pregnancy-associated malaria variant surface antigen [VSA-PAM]) that mediates adhesion of infected erythrocytes to chondroitin sulfate A (CSA) on the syncytiotrophoblast lining the intervillous space [27,28]. The binding of VAR2CSA to its ligand has been mapped, but additional VSA-PAMs may also exist [29-31].
Adherence of erythrocytes expressing VSA-PAMs to the surface of syncytiotrophoblast appears to stimulate an inflammatory response. This results in monocyte migration and release of humoral factors, such as tumor necrosis factor-alpha (TNF-alpha), into the intervillous circulation [32]. The concentration of TNF-alpha in the intervillous circulation correlates with the density of P. falciparum-infected erythrocytes. Children who carry the TNF 2 polymorphism in the promoter region of the TNF-alpha gene have heightened TNF-alpha production in response to infection, which is associated with increased risk of preterm delivery, severe infection and cerebral malaria [32]. Recruitment of fetal placental macrophages (Hofbauer cells) in response to placental malaria also occurs [33-35].
Other potential consequences of erythrocyte adherence include placental thickening and altered placental functions, including reduced nutrient transport and production of key hormones (eg, insulin-like growth factor 1) [36,37]. Together, these placental changes may reduce uteroplacental blood flow [38] and, early in pregnancy, may impede villous growth and development [39]. The resulting reduction in the fetal supply of oxygen, nutrients, and growth factors can lead to fetal growth restriction and fetal demise [40-42]. A study utilizing an in vitro model of P. falciparum interaction with first-trimester human placental explants showed upregulation of genes that mitigate oxidative stress damage (eg, heme oxygenase 1) and changes in angiogenesis genes (eg, placental growth factor [PlGF] and its receptor FMS-related receptor tyrosine kinase 1 [FLT1]) [35]. Alterations in FLT1/PlGF ratios have been associated with placental dysfunction in preeclampsia and fetal growth restriction [43,44].
Antibodies formed in response to VSA-PAM (particularly anti-VAR2CSA) prevent adhesion of the infected erythrocyte to the placenta [45,46]. These antibodies are pregnancy specific (ie, men from malaria-endemic areas do not develop VSA-PAM antibodies, nor do people that have not been pregnant) and correlate directly with parity in holoendemic (high transmission) areas. In holoendemic areas, primigravid people have no or low VSA-PAM immunoglobulin G (IgG) levels despite lifelong P. falciparum exposure, and are more prone to complications of pregnancy-associated malaria (eg, low birth weight, preterm delivery, maternal anemia) compared with multigravid people, who have moderate-to-high VSA-PAM IgG levels. Differentiating protective antibody responses from those associated with exposure is challenging, but one study identified multiple features of a potentially protective immune response [47,48].
By comparison, in mesoendemic (low transmission) areas and areas where malaria is promptly treated, multigravid people do not have moderate-to-high VSA-PAM IgG levels and remain at increased risk of complications of malaria in each pregnancy. As an example, when rates of malaria transmission, placental malaria, and peripheral parasitemia fell in Mozambique between 2003 and 2012, a parallel reduction occurred in levels of antimalarial IgG antibodies against both pregnancy-specific parasite lines (placental, or CSA-binding) and more general parasite lines [49]. As a result of this reduced immunity, pregnant people infected with malaria had a higher frequency of adverse pregnancy outcomes (lower maternal hemoglobin and newborn birth weight) than those with malaria in pregnancy prior to this period.
In contrast to the above discussion of P. falciparum, for people with P. vivax, a direct link between adverse outcome and placental changes and placental sequestration of infected erythrocytes has not been clearly demonstrated.
CLINICAL FINDINGS
General principles — The clinical presentation of malaria in pregnant people depends primarily on the endemicity of the region. Infection with more than one malaria species does not substantially alter clinical presentation. (See 'Epidemiology' above.)
●For individuals in holoendemic areas (high transmission rates), most malaria infections in pregnancy are asymptomatic, but the pregnant person is at risk for developing anemia [50,51]. Maternal anemia and placental parasitemia may lead to adverse pregnancy outcomes, particularly low birth weight (which may represent intrauterine growth restriction or preterm birth or both). (See 'Pregnancy outcome' below.)
Primigravid people in holoendemic areas (who have no or low pregnancy-associated malaria variant surface antigen [VSA-PAM] IgG levels) are more prone to complications of pregnancy-associated malaria than multigravid people (who have moderate-to-high VSA-PAM IgG levels), as discussed above. (See 'Pathogenesis' above.)
●For individuals in mesoendemic areas (relatively low transmission rates) or for those returning to holoendemic areas after a prolonged absence, malaria infection is more likely to result in symptomatic illness and serious complications (eg, maternal anemia) than in individuals in holoendemic areas [5,52]. Gravidity tends not to be an important factor because of low immunity. (See 'Pregnancy outcome' below.)
●For individuals in areas of unstable malaria transmission (where there is little acquired immunity), both symptomatic illness and serious complications (eg, severe maternal anemia, severe neurological and respiratory manifestations of malaria, miscarriage, stillbirth, low birth weight) are common when infection occurs. Gravidity tends not to be an important factor because of low immunity. (See 'Pregnancy outcome' below.)
The clinical manifestations of malaria are nonspecific and variable. Virtually all nonimmune individuals experience fever. Other frequent symptoms include chills, sweats, headache, myalgias, fatigue, nausea, abdominal pain, vomiting, diarrhea, jaundice, and cough. Hypoglycemia is a common complication of severe malaria, although the usual signs (sweating, tachycardia, neurologic impairment) are difficult to distinguish from systemic symptoms due to severe malaria. Compared with nonpregnant individuals, pregnant people experience more severe disease, including more hypoglycemia and more respiratory complications (pulmonary edema, acute respiratory distress syndrome) [53,54]. Mortality from severe malaria in pregnancy was 12.2 percent, and was highest in those who had coma, hypotension, or respiratory failure. Among survivors of severe malaria, fetal loss and preterm birth were common [55]. (See "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children".)
There is a semiquantitative relationship between the degree of parasitemia and severity of disease. In general, parasitemia is more prevalent in pregnant compared with nonpregnant people [56-58], with increased risk as early as the first trimester [59]. As an example, in a longitudinal study including more than 270 Beninese individuals followed from the preconception period through delivery, the incidence of microscopic and submicroscopic P. falciparum infections was highest in the first trimester [60].
Anemia is a common complication of malaria in pregnancy; approximately 60 percent of pregnant people presenting with malaria infection are anemic [52,61], and anemia may be one of the few signs of the disease in those with some degree of pre-existing immunity. The anemia is generally normocytic and normochromic, with a striking absence of reticulocytes. Co-existent thalassemia trait and/or iron deficiency may result in microcytosis and hypochromia. Infected red cells may be seen on the peripheral blood smear. One or more other etiologies may co-exist with malaria, including inherited hemoglobinopathies, nutritional deficiencies, and intestinal parasites (especially hookworm infections) in malaria-endemic settings. In one review, 5 to 10 percent of pregnant African people developed severe anemia (hemoglobin <7 to 8 g/dL), and one-quarter of these cases were attributed to malaria [5].
People with HIV infection — Pregnant people with HIV infection are at increased risk for malaria acquisition, placental malaria, high parasite density, severe clinical disease, and maternal and neonatal mortality (relative to pregnant people without HIV infection) [62]. Among people with HIV infection, clinical outcomes for primigravid and multigravid people are comparable [63].
Malaria infection in patients with HIV infection has been associated with CD4 cell decline relative to patients with HIV infection without malaria [62,64]. Malaria infection is associated with a transient increase in HIV viral load, which returns to baseline after antimalarial treatment. Issues related to management of pregnant patients with malaria and HIV infection are discussed separately. (See "Malaria in pregnancy: Prevention and treatment", section on 'Patients with HIV infection'.)
DIAGNOSIS —
Malaria should be suspected in the setting of fever (temperature ≥37.5°C) and relevant epidemiologic exposure (residence in or travel to an area where malaria is endemic).
The approach to diagnosis of malaria in pregnant people is the same as the approach in nonpregnant patients. (See "Laboratory tools for diagnosis of malaria".)
Low-density malaria infections that are detectable by polymerase chain reaction (PCR) but below the detection threshold of microscopy or rapid diagnostic tests (RDTs) can contribute to transmission. Submicroscopic infections can be common. Over half of PCR-detected infections are submicroscopic, and the proportion is highest in the Americas and greater for P. vivax than P. falciparum [65].
However, the clinical value of PCR to detect low-density malaria infection in pregnant people with negative microscopy or RDTs is uncertain, and there is insufficient evidence to warrant routine use of PCR for this purpose. PCR positive, microscopy negative infection detected in pregnant people was associated with poor infant outcomes in Benin [66]; however, this finding was not associated with poor outcomes in other regions such as Malawi [67], Ghana [68], or India [69].
Chorionic villus sampling is not used for prenatal diagnosis of placental malaria and theoretically could contribute to vertical transmission.
PREGNANCY OUTCOME
Overview — Adverse maternal and perinatal outcomes associated with P. falciparum or P. vivax malaria in pregnancy include [17,52,56,70-79]:
●Miscarriage
●Preterm birth (<37 weeks of gestation)
●Low birth weight (LBW; <2500 g at birth)
●Fetal growth restriction
●Stillbirth (intrauterine fetal demise)
●Neonatal mortality
●Congenital malaria infection
●Maternal anemia
●Maternal mortality
●Hypertensive disease of pregnancy
These complications are not mutually independent (eg, preterm birth often results in LBW) and do not occur with similar frequency in all infected people. Nonimmune pregnant people and those in regions of unstable transmission (who generally lack protective antibodies) are at increased risk of these outcomes when they develop malaria [5].
Individuals in areas with high stable transmission rates (who are likely to have developed protective antibodies) are less likely to experience adverse pregnancy outcomes when they develop malaria, although they remain at risk for anemia even if otherwise asymptomatic [80]. Within high transmission areas, young pregnant people and those of low parity are the subgroups most likely to experience an adverse pregnancy outcome because they are most likely to have absent or low protective antibody levels due to lower cumulative exposure to malaria over their lifetime and lower exposure to pregnancy-associated malaria variant surface antigens (VSA-PAMs) due to no or few previous pregnancies [5,11,29,52,80-86].
Fetal effects
Reduction in birth weight — In pregnancies complicated by malaria, both fetal growth restriction (estimated fetal weight <10th percentile for gestational age) and preterm birth (birth <37 weeks of gestation) contribute to LBW (<2500 g at birth) [38,87-91]. An increasing number of P. falciparum infections during a pregnancy increases the risk of LBW [92].
In some settings, malaria may be responsible for up to 70 percent of fetal growth restriction and up to 20 percent of neonates with LBW [5]. Reduction in fetal weight and preterm birth occur primarily in infants of primigravidas, who are more likely to have severe placental sequestration, heavier parasite loads, anemia, and low levels of antibodies formed in response to VSA-PAM compared with multigravidas [29,51,56,57,93]. (See 'Pathogenesis' above.)
Maternal undernutrition, which is common in regions where malaria is prevalent, also plays a role. The effects of malnutrition and malaria infection on LBW appear to be independent, not synergistic [94].
Neurodevelopment — There is emerging evidence that maternal malaria infection may affect neurodevelopment [95-97]. In one study including 493 pregnant people in Benin with malaria infection whose children were followed to six years of age, children whose mothers had placental malaria and/or high-density peripheral blood infection were particularly likely to have impaired processing, cognitive, and learning capabilities [95].
Vertical transmission — All species of malaria parasite can be transmitted in utero; congenital disease is most often associated with P. falciparum and P. vivax. Placental infection is a prerequisite for, but does not predict, congenital disease. Placental infection is more common than cord blood parasitemia, which is more common than detection of parasites in the infant's peripheral blood [98]. Detection of parasite DNA by polymerase chain reaction (PCR) may identify more cases of potential congenital malaria, although this highly sensitive method may detect residual DNA rather than maternal-fetal transmission of infectious parasites.
Among immune pregnant people, the likelihood of transplacental malaria transmission appears to be small (up to 1.5 percent of cases) [99,100]. Semi-immune and nonimmune pregnant people have a much higher likelihood of transplacental malaria transmission (7 to 10 percent) [70,101,102].
Pregnant people with overt symptoms of malaria during pregnancy have a 1 to 4 percent risk of vertical transmission [103]. The low incidence of congenital infection despite the high incidence of placental infection is likely secondary to passive immunization via transplacental acquisition of maternal antibody [104].
Clinical manifestations of congenital malaria in newborns and prognosis are discussed separately. (See "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children", section on 'Children versus adults'.)
Subsequent risk for malaria infection — Malaria infection during pregnancy may increase the subsequent risk of malaria infection in young children. In a meta-analysis of 11 studies, the pooled adjusted odds ratio for clinically defined malaria in young children was 2.82 (95% CI 1.82-4.38) [105]. The risk of malaria may be higher in male than female offspring [106]. The potential immunologic or epidemiologic factors underlying this association are subjects of ongoing study.
Maternal effects — Malaria is a leading cause of maternal mortality in regions of unstable endemicity where there are periodic epidemics among nonimmune patients [107]. Younger maternal age has been associated with higher rates of anemia and worse maternal and fetal outcomes, in part because younger people are more likely to be primigravid and nonimmune or only partially immune [6,52,108]. Maternal death may be related to cerebral malaria, acidosis, organ failure (pulmonary, renal, hepatic), and/or severe anemia.
The following studies are examples of the impact of malaria on maternal mortality in two countries:
●A study performed in The Gambia estimated that, during the malaria season, maternal mortality increased by 168 percent and the proportion of deaths due to anemia increased threefold [109]. It was estimated that malaria accounted for up to 93 maternal deaths per 100,000 live births.
●A review of pregnancy-related maternal deaths in an urban Mozambique setting identified 239 maternal deaths (320 maternal deaths/100,000 live births) [73]. In this series, 15.5 percent of the deaths were directly attributable to malaria, and 19.7 percent of the people who died were parasitemic with P. falciparum. Over one-third of the malaria-related deaths occurred in primigravid adolescents, primarily associated with severe anemia. Autopsies on 161 people showed that 44 (27.3 percent) had histologic evidence of splenic malarial infection.
●A subsequent prospective autopsy study including all consecutive pregnancy-related deaths in a tertiary level referral hospital in Mozambique noted massive accumulation of P. falciparum-infected erythrocytes in the small capillaries of the central nervous system, in most visceral capillaries (heart, lung, kidney, uterus), as well as the intervillous space [110].
PREVENTION AND TREATMENT —
Prevention and treatment of malaria in pregnancy and management of pregnancy are discussed in detail separately. (See "Malaria in pregnancy: Prevention and treatment".)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Malaria".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Malaria (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Epidemiology
•Among individuals living in a geographic region, a higher prevalence of malaria has been observed among pregnant people than in nonpregnant people, younger pregnant people than older pregnant people, people in their first or second pregnancies than in more multigravid people, people with HIV infection than those without HIV infection, and people in the first and second trimesters than people in the third trimester.
•The increased prevalence of malaria in pregnant people has been attributed to multiple factors, including increased susceptibility to mosquito bites, immunologic and hormonal changes related to pregnancy, and the ability of infected erythrocytes to adhere to and sequester in the intervillous space. (See 'Epidemiology' above.)
●Pathophysiology
•In Plasmodium falciparum malaria, the infected erythrocytes (picture 1) are immunologically distinct from infected erythrocytes found in nonpregnant individuals: they express a specific class of variant surface antigen (pregnancy-associated malaria variant surface antigen [VSA-PAM]) that mediates adhesion of infected erythrocytes to chondroitin sulfate A (CSA) on the syncytiotrophoblast lining the intervillous space. VAR2CSA, which is the product of the parasite gene VAR2CSA, appears to be the major VSA-PAM involved. Once parasites adhere to the surface of trophoblastic villi, they induce an inflammatory response that may result in poor birth outcomes. Another consequence is placental thickening from the inflammation, which may reduce placental transport of oxygen and nutrients, leading to fetal growth restriction and, possibly, fetal demise. (See 'Pathogenesis' above.)
•Antibodies formed in response to VSA-PAM (particularly anti-VAR2CSA) prevent cytoadhesion of the infected erythrocyte to the placenta; thus, primigravid people in holoendemic areas (who have no or low VSA-PAM IgG levels despite lifelong P. falciparum exposure) are more prone to complications of pregnancy-associated malaria than multigravid people in holoendemic areas, who have moderate-to-high VSA-PAM IgG levels. By comparison, in mesoendemic (low transmission) areas and areas where malaria is promptly treated, multigravid people do not have moderate-to-high VSA-PAM IgG levels and remain at increased risk of complications of malaria in each pregnancy. (See 'Pathogenesis' above.)
●Clinical findings
•The clinical presentation varies according to the endemicity of the region. For individuals in holoendemic (high transmission) areas, most malaria infections in pregnancy are asymptomatic, but the mother is at risk for developing anemia. For individuals in mesoendemic (relatively low transmission) areas or for those returning to holoendemic areas after a prolonged absence, malaria infection is more likely to result in symptomatic, and potentially life-threatening, illness and serious complications (eg, severe maternal anemia, adverse pregnancy outcome) than it is in people in holoendemic areas. For individuals in areas of unstable malaria transmission (where there is little acquired immunity), both symptomatic illness and serious complications (eg, severe maternal anemia, miscarriage, stillbirth, low birth weight) are common when infection occurs. (See 'Clinical findings' above.)
•Virtually all nonimmune individuals experience fever. Other frequent symptoms include chills, sweats, headache, myalgias, fatigue, nausea, abdominal pain, vomiting, diarrhea, jaundice, and cough, as well as symptoms of hypoglycemia. (See 'Clinical findings' above.)
●Diagnosis – Malaria should be suspected in the setting of fever (temperature ≥37.5°C) and relevant epidemiologic exposure (residence in or travel to an area where malaria is endemic). The approach to diagnosis of malaria in pregnant people is the same as the approach in nonpregnant patients. Peripheral blood smears are typically used for diagnosis but may be negative in people with placental malaria who are otherwise asymptomatic. (See 'Diagnosis' above and "Laboratory tools for diagnosis of malaria".)
●Pregnancy outcome – Adverse pregnancy outcomes associated with malaria include miscarriage, fetal growth restriction/small for gestational age infant, preterm birth, low birth weight, stillbirth and neonatal death, congenital malaria infection, and maternal mortality. (See 'Pregnancy outcome' above.)
