Pregnant women are at increased risk for severe illness from influenza virus infection. Cardiopulmonary adaptive changes occurring during pregnancy, such as increased heart rate and stroke volume and reduced pulmonary residual capacity, may increase the risk of hypoxemia and contribute to the increased severity. During the pandemic of 1918, maternal mortality was 27% (50% when influenza was complicated by pneumonia), and during the pandemic of 1957, 50% of deaths among reproductive-age women occurred among those who were pregnant.² During the 2009 H1N1 influenza A pandemic, pregnant women were generally at increased risk for severe disease, including disease leading to hospitalization, admission to an intensive care unit, or death, as compared with nonpregnant women and the general population.³ In the United States, 5% of all deaths from pandemic influenza were among pregnant women, although pregnant women represent only about 1% of the U.S. population.⁴ Higher rates of hospital admission and medical encounters for pregnant women with confirmed or suspected influenza, as compared with the general population, and a greater severity of disease during late pregnancy were also found in interpandemic periods.^5-7 During the 2009 H1N1 pandemic, as well as during interpandemic periods, women in the third trimester of pregnancy were at increased risk for severe disease (e.g., disease requiring admission to an intensive care unit or resulting in death), as compared with women in an earlier stage of pregnancy.^4,6,8

Infection with HEV is also more severe in pregnant women, with high mortality during the third trimester. In areas in which HEV infection is highly endemic (India, Southeast Asia, the Middle East, and Africa), it can be a major cause of maternal death and fetal loss. The pathophysiological basis of this increased mortality is not well understood.

In a review of all consecutive cases of acute liver failure from 1989 to 1996 in a region of India in which HEV infection is endemic, 49 of 83 women of childbearing age with acute liver failure were pregnant (33 in their third trimester). In 47 of these pregnant women, the liver failure was due to HEV infection.⁹ In a case series from India, 33 to 43% of pregnant women with HEV infection had severe disease or infection that led to fulminant hepatic failure.¹⁰ A review indicated that the case fatality rate among pregnant women with HEV infection is between 15% and 25%, as compared with a range of 0.5 to 4% in the population overall.¹¹ Among 220 consecutive pregnant women presenting with jaundice caused by acute viral hepatitis, fulminant hepatic failure and death were more common among women with HEV infection than among those without HEV infection (relative risk of fulminant hepatic failure, 2.7; relative risk of death, 6.0).¹²

Pregnant women with primary HSV infection have an increased risk of dissemination and hepatitis (an otherwise rare complication in immunocompetent adults), particularly during the third trimester. To date, 27 cases of HSV hepatitis during pregnancy have been reported.¹³ After patients with immunosuppression, pregnant women are the largest group of adults with disseminated HSV infection; in one review, the mean gestational age at presentation was 31 weeks, and the case fatality rate was 39% for both mothers and neonates.¹⁴ Other reviews have confirmed a high burden of HSV hepatitis among pregnant women^15,16; however, data on the incidence of primary HSV infection among pregnant women are limited. Recurrences of genital HSV infection increase in frequency during pregnancy,¹⁷ although the clinical characteristics of recurrent genital HSV infection are similar in pregnant women and nonpregnant women.

The severity of (and susceptibility to) Plasmodium falciparum malaria is determined by the level of immunity, which depends mainly on the intensity and stability of malaria transmission. In areas of low or unstable transmission, infected women become symptomatic, and, if untreated, the infection can progress rapidly to complications, with a high case fatality rate. In three districts in India, 23% or more of maternal deaths between 2004 and 2006 were attributable to malaria, which was the most common cause of maternal death during pregnancy.¹⁸ Pregnant women have a risk of severe malaria that is three times as high as that among nonpregnant women; a median maternal mortality of 39% has been reported in studies in the Asia–Pacific region. Maternal death also has been reported in association with P. vivax infection.¹⁸

In areas of high transmission, most women harboring parasites do not present with symptoms. It was thought that, in such areas, cases of severe or fatal malaria during pregnancy were rare. However, the numbers of maternal deaths from malaria in sub-Saharan Africa may have been underestimated, and malaria during pregnancy may be an important direct cause of maternal complications and death.^19,20 Of pregnant women who are symptomatic, the majority are women having their first pregnancy; women who have been pregnant more than once and who live in areas where malaria is highly endemic are less likely to present with clinical signs or symptoms of malaria, even if they have high parasite loads.^20,21 The predominant theory to explain this phenomenon is that P. falciparum parasites accumulate selectively in the placenta, and particular anti-genic variants interact with syncytiotrophoblastic chondroitin sulfate A.²² Women have a malaria episode caused by chondroitin sulfate A–binding parasites during their first pregnancy because they lack immunity to antigenic variants presented by these strains (even though they may be immune to other antigenic variants of parasites that bind endothelial receptors from previous infections) and are thus highly susceptible to the new infection.

Several reports and case series have suggested that pregnancy is a risk factor for the development of severe and disseminated coccidioidomycosis, particularly during the third trimester and the immediate postpartum period, with an estimated rate of 7.7 to 11 cases per 10,000 pregnancies.^23-25 However, the rate of disease during pregnancy was much lower than expected in a large 1988 survey of records from three delivery centers in Tucson, Arizona, covering more than 47,000 deliveries.²⁶ During the 1993 epidemic in Kern County, California, only 32 cases were identified among pregnant women, a lower number than expected; disseminated disease occurred in 3 of these cases, with no maternal deaths,²⁷ which suggested that many pregnant women have asymptomatic or clinically mild disease. Taken together, these data suggest that the incidence of coccidioidomycosis is decreasing and that pregnant women may not be at increased risk for dissemination.

Early studies postulated that pregnancy, particularly in the third trimester, is a risk factor for severe varicella. These studies involved mostly case reports or small case series.^28-30 In a 1990 review of 34 published cases of varicella pneumonia, mortality among pregnant women was 35%,²⁸ higher than that among nonpregnant adults, reported as 11.4% in another study.³¹ Paryani and Arvin reported a varicella pneumonia rate of 9%, with one death among 43 pregnant women with varicella.³⁰ A review of reports published from 1965 to 1989 on varicella pneumonia in adults showed that of 99 cases, 46 were in women; 28 of these women were pregnant (21 in the third trimester). This suggested an increased rate of varicella pneumonia during pregnancy; however, mortality among pregnant women (10%) was not higher than that among men and non-pregnant women.²⁹ Other studies do not support the idea that illness due to varicella is more severe during pregnancy. In a New York City survey for the period from 1957 to 1964, only 1 of 144 women with varicella died.³² In a study from Britain and Germany, in which 1373 women with varicella were followed during pregnancy, no maternal deaths were reported.³³

The harmful effects of malaria (mainly due to P. falciparum) during pregnancy — maternal anemia, low birth weight, and preterm birth — have long been recognized.¹⁹ In areas of stable endemic transmission (e.g., sub-Saharan Africa), up to 25% of pregnant women have acute infection, leading to placental malaria³⁴; this frequency is higher than that among nonpregnant women.^35,36 In several studies in Africa and Asia, the prevalence of malarial parasitemia was found to be higher among pregnant females than among nonpregnant females 15 to 45 years of age.^18,37,38 P. falciparum is the only species associated with placental sequestration, which is believed to be the cause of many of the manifestations of P. falciparum disease during pregnancy. Many studies have shown decreasing susceptibility to malaria with increasing parity,^37-39 probably as a result of acquisition of immunity to parasites expressing pregnancy-specific variant surface antigens.¹⁹ This association is most pronounced in areas where malaria is highly endemic.²⁰ Young maternal age may be an additional and independent risk factor for malaria during pregnancy. The third trimester of gestation has been associated with the highest risk of clinical malaria in some studies⁴⁰ but not others.³⁹ However, maternal parasitemia, placental parasite burden, and episodes of clinical malaria may be expressions of disease severity rather than of initial susceptibility in areas with a high prevalence of malaria.

Limited data suggest that P. vivax infections also are more severe during pregnancy.¹⁸ These data, however, are difficult to interpret because most areas where P. vivax is the predominant cause of malaria have low or unstable transmission and therefore increased disease severity in all parity groups.⁴¹ Accumulation of P. vivax in the placenta has not been reported.⁴²

Primarily a foodborne pathogen, listeria can contaminate a variety of raw foods, such as uncooked meats and vegetables, unpasteurized milk, and soft cheeses. Infection may be asymptomatic or may be manifested as an influenza-like illness; severe infection is rare during pregnancy, and no maternal deaths due to listeriosis have been reported among pregnant women who are hospitalized.⁴³ L. monocytogenes infections most commonly occur during the third trimester and seem to be rare earlier in pregnancy.⁴⁴ However, listeria has a predilection for the placenta and fetus, and, depending on the stage of pregnancy, listeriosis can lead to pregnancy loss, stillbirth, preterm birth, or serious neonatal disease. Active, population-based surveillance showed that 17% of 762 listeriosis cases reported in 10 U.S. sites between 2004 and 2009 were in pregnant women.⁴⁵ Hispanic women seemed to be particularly at risk.^45-47 It has been estimated that invasive listeriosis during pregnancy is 13 times to more than 100 times as frequent as in the general population.^45,46,48 However, in one study, surveillance data indicated that more than 50% of listeriosis cases during pregnancy were associated with a neonatal case,⁴⁵ which suggests that neonatal disease leads to recognition of listeria infections during pregnancy in a substantial proportion of cases and may therefore bias estimates of pregnancy-conferred risk.