8 Malaria in Pregnancy Pregnant women are 3 times more likely to suffer Regorafenib buy from severe disease as a result of malarial infection compared with their nonpregnant counterparts, and have a mortality rate from severe disease that approaches 50%.6,9 In areas endemic for malaria, it is estimated that at least 25% of pregnant women are infected with malaria, with the highest risk for infection and morbidity in primigravidas, adolescents, and those coinfected with HIV.10 The second trimester appears to bring the highest rate of infection, supporting the need for antepartum care as part of malarial prevention and treatment efforts. It is hypothesized that the majority of sequelae in pregnancy results from 2 main factors: the immunocompromised state of pregnancy and placental sequestration of infected erythrocytes.

As discussed previously, adults who live in malaria-endemic regions generally have some acquired immunity to malaria infection as a result of immunoglobulin production during prior infections in childhood. This immunity diminishes significantly in pregnancy, particularly in primigravidas. A recent study of 300 women delivering in rural Ghana showed higher rates of anemia, clinical malaria, and placental burden of infection among primigravidas compared with multigravidas. The study also noted that babies born to mothers with placental malaria infection were more than twice as likely to be underweight at birth.11 Splenic sequestration of malariainfected erythrocytes leads to folic acid deficiency and microcytic anemia in adults.

In pregnant women, additional sequestration of malariainfected erythrocytes occurs in the placenta. Pregnant women therefore suffer disproportionately from severe anemia as a result of infection. In Africa, it has been estimated that malaria is responsible for 25% of severe anemia during pregnancy (defined as hemoglobin less than 7 gm/dL).10 Women with severe anemia are at higher risk for morbidities such as congestive heart failure, fetal demise, and mortality associated with hemorrhage at the time of delivery (Figure 3). Figure 3 Severe anemia in the third trimester of pregnancy (hemocrit, 13%). Photo courtesy of J. Schantz-Dunn (Belladere, Haiti, 2008). Interestingly, the greatest degree of placental infestation is seen in women who have the highest level of immunity, leading to milder maternal symptoms and a disproportionate increase in fetal complications.

6 It could be hypothesized, therefore, that although primigravidas may develop the clinical symptoms of malaria, women with higher immunity may not demonstrate symptoms, will not receive treatment, and will build a higher placental parasite burden. Fetal complications Cilengitide result from this placental inflammation, as well as maternal anemia, and manifest as stillbirth, intrauterine growth restriction, and low-birth-weight neonates. Low-birth-weight neonates, in turn, are at higher risk for neonatal and newborn death.