Malaria is a disease caused by Plasmodium parasites and transmitted to humans through the bite of infected female Anopheles mosquitoes. While the infection poses a threat to all individuals, it is particularly dangerous for pregnant people living in areas where malaria is common. Pregnancy causes significant changes to the body’s immune system, increasing susceptibility to infection and severe illness. This vulnerability means both the mother and the developing fetus face heightened health risks. Protecting this population requires understanding how the parasite interacts with the pregnant body and implementing targeted medical interventions.
Physiological Impact of Malaria During Pregnancy
The heightened danger of malaria during pregnancy stems from placental sequestration. This occurs when infected red blood cells accumulate and adhere to the lining of the placenta, the organ responsible for nutrient and gas exchange. The primary species involved, Plasmodium falciparum, expresses a specific protein called VAR2CSA on the surface of the infected red blood cells.
The VAR2CSA protein binds specifically to the chondroitin sulfate A (CSA) receptor found in the intervillous spaces of the placenta. This binding locks the parasites into the placental blood space, allowing them to replicate and reach high concentrations. This accumulation triggers a localized inflammatory response within the placental tissue, often without high numbers showing up in the mother’s peripheral bloodstream.
The resulting inflammation and physical blockage compromise the structure and function of the placenta. This pathology impairs blood flow and severely restricts the transfer of oxygen and essential nutrients to the developing fetus. Additionally, the maternal immune system shifts toward tolerance during pregnancy to prevent fetal rejection, which also makes the mother less effective at clearing the parasite.
The unique placental environment provides a protective niche for the parasite, allowing the infection to persist and cause chronic damage. This process is particularly pronounced in first and second pregnancies, where the mother has not yet developed immunity to the placenta-specific VAR2CSA protein. This sequestration mechanism explains why women with pre-existing immunity to general malaria remain susceptible to placental malaria complications.
Health Risks to Mother and Baby
Placental sequestration leads directly to severe health consequences for both the pregnant individual and the baby. For the mother, a frequent complication is severe anemia. The destruction of red blood cells combined with the inflammatory response can drop hemoglobin levels low enough to cause fatigue, heart complications, and increase the risk of maternal death.
Another metabolic risk is hypoglycemia, or dangerously low blood sugar. Pregnant women with severe malaria are prone to this complication, requiring careful monitoring during treatment. Severe infections also increase the likelihood of systemic complications such as cerebral malaria, organ failure, and maternal mortality.
For the fetus, impaired placental function causes a cascade of adverse outcomes. Restricted nutrient and oxygen flow results in Intrauterine Growth Restriction (IUGR), meaning the baby does not grow as expected. This restriction frequently leads to the delivery of a Low Birth Weight (LBW) infant, defined as weighing less than 2,500 grams at birth, which is a major risk factor for infant mortality.
The infection also increases the risk of premature birth (before 37 weeks of gestation), exposing the newborn to challenges like respiratory distress and developmental issues. In severe cases, placental dysfunction and high fever can lead to miscarriage, stillbirth, or neonatal death. The parasite can sometimes cross the placental barrier, leading to congenital malaria in the newborn.
Strategies for Prevention
Preventing malaria infection is paramount for protecting pregnant people and their babies, especially where the disease is widespread. The World Health Organization (WHO) recommends a comprehensive package of interventions, starting with vector control methods. Sleeping under an Insecticide-Treated Net (ITN) every night significantly reduces the likelihood of being bitten by an infected mosquito.
The primary pharmacological strategy is Intermittent Preventive Treatment in Pregnancy (IPTp). This involves administering a full curative dose of an antimalarial drug at scheduled intervals during antenatal care visits. The drug recommended for this purpose in moderate to high-transmission areas is Sulfadoxine-Pyrimethamine (SP). IPTp-SP is given regardless of current infection status to clear asymptomatic infections and prevent new ones.
Dosing with SP should begin as early as possible in the second trimester of pregnancy. The treatment is repeated at each scheduled antenatal care visit, with doses spaced at least one month apart, until delivery. The goal is for the pregnant individual to receive a minimum of three doses of IPTp-SP during the pregnancy.
IPTp-SP is only recommended starting in the second trimester due to developmental concerns regarding drug exposure in the first trimester. Its use must be managed carefully in individuals taking high-dose folic acid supplements, as high folate levels can counteract the antimalarial effect of SP. Individuals are advised to take the standard low dose of 0.4 mg of folic acid daily alongside IPTp-SP.
Guidelines for Safe Treatment
Treating an active malaria infection during pregnancy requires balancing the drug’s effectiveness against potential harm to the developing fetus. Prompt diagnosis and treatment under medical supervision are required to minimize the risk of severe maternal or fetal complications. The choice of antimalarial drug depends on the trimester and the severity of the infection.
For uncomplicated P. falciparum malaria infections in the second and third trimesters, Artemisinin-based Combination Therapies (ACTs) are the preferred first-line treatment. Combinations like artemether-lumefantrine are safe and highly effective during the later stages of pregnancy. ACTs are recommended because they rapidly reduce the parasite load and limit placental damage.
Treatment protocols for the first trimester have historically been cautious due to limited safety data during organ development. Quinine combined with clindamycin was previously the recommended option for uncomplicated P. falciparum malaria during the first trimester. However, recent WHO guidelines now recommend artemether-lumefantrine as the preferred treatment for uncomplicated malaria in the first trimester, based on accumulated safety data.
In cases of severe malaria at any stage of pregnancy, the priority is saving the mother’s life, and injectable artesunate is the treatment of choice. Throughout treatment, the person’s blood sugar levels must be closely monitored, as pregnant individuals are susceptible to developing severe hypoglycemia. All malaria treatment decisions must be made by a healthcare provider due to the complexity of pharmacokinetics in pregnancy.