Immune and hormonal changes during pregnancy worsen or reactivate certain infections

The fetus may be considered as an immunologically incompatible transplant that must not be rejected by the mother. Reasons for the failure to reject the fetus include:

A severe or generalized immunosuppression in the mother would be undesirable because it would mean potentially disastrous susceptibility to infectious disease. Certain infections, however, are known to be more severe (Table 23.1), and certain persistent infections reactivate during pregnancy (Table 23.2). The hormonal changes that accompany pregnancy can also increase susceptibility. The picture is further complicated when there is malnutrition, which in itself impairs host defences by weakening immune responses, decreasing metabolic reserves and interfering with the integrity of epithelial surfaces.

Table 23.1 The effect of pregnancy on the severity of infectious disease

Table 23.2 Reactivation of persistent infections during pregnancy

The fetus has poor immune defences

Once the fetus is infected, it is exquisitely susceptible because:

Most microorganisms have sufficient destructive activity to kill the fetus once it is infected, leading to spontaneous abortion or stillbirth. Here, our interests focus on the few microorganisms that are capable of more subtle, non-lethal effects. They overcome the placental barrier by infecting it so that the infection then spreads to the fetus. They can then interfere with fetal development or cause lesions so that a live but damaged baby is born.

Intrauterine infection may result in death of the fetus or congenital malformations

After primary infection during pregnancy, certain microorganisms enter the blood, establish infection in the placenta, and then invade the fetus. The fetus sometimes dies, leading to abortion, but when the infection is less severe, as in the case of a relatively non-cytopathic virus, or when it is partially controlled by the maternal IgG response, the fetus survives. It may then be born with a congenital infection, often showing malformations or other pathologic changes. The infant is generally small and fails to thrive. It produces specific antibodies, but often, for instance with CMV, fails to generate an adequate virus-specific cell-mediated immune response, remaining infected for a long period. Hence, the lesions may progress after birth. It is a striking feature of these infections that they are generally mild or unnoticed by the mother.

Important causes of congenital infections are shown in Table 23.3. Viruses that induce fetal malformations (i.e. act as teratogens) share certain characteristics with other teratogens such as drugs or radiation (Table 23.4). The fetus tends to show similar responses (e.g. hepatosplenomegaly, encephalitis, eye lesions, low birth weight) to different infectious agents, and the diagnosis is difficult on purely clinical grounds. Most of these infections, HSV, rubella, CMV and syphilis, can also, at times, kill the fetus. They generally follow primary infection of the mother during pregnancy, so their incidence depends upon the proportion of non-immune females of childbearing age.

Table 23.3 Maternal infections that are transmitted to the fetus

a This figure is for resource-poor countries with no intervention (no antiretroviral drugs, no caesarean section, or avoidance of breastfeeding).

b Infection also occurs during and immediately after birth.

c Protection of newborn by hepatitis B vaccine plus specific immunoglobulin.

Table 23.4 Comparison between teratogenic viruses and other teratogens

Routine antenatal screening for rubella antibody, treponemal antibody (which includes syphilis, yaws, pinta or bejel, which cannot be identified individually by serology), hepatitis B surface antigen and HIV antibody is being carried out to differing degrees worldwide. These tests help identify women who are infected with hepatitis B or HIV, infected or have been exposed in the past to treponemal infections, the most important of which is syphilis in this setting, or are susceptible to rubella.

Routine screening programmes lead to clinical management issues for both the mother and child. For example, HIV diagnosis will lead to consideration of antiretroviral therapy for the mother and, immediately on birth, the child, offering a caesarean section delivery, and advising against breastfeeding to reduce the risk of vertical transmission. In addition, the child will then be followed up for at least 12    months using sensitive tests to determine whether HIV has been transmitted vertically. Diagnosis of chronic hepatitis B infection will result in determination of the maternal level of infectivity, and subsequently offering an accelerated course of hepatitis B vaccine alone or, if the mother is highly infectious, vaccine and HBV-specific immunoglobulin to the baby. In addition, there are antiviral drugs for chronic hepatitis B that might be offered, together with long-term follow-up, to the mother. Rubella-susceptible women are offered rubella immunization postnatally. Women found to have been exposed to treponemal infection in pregnancy are offered antibiotic treatment and the baby is followed up for the first year using serology to identify active infection, as congenital syphilis can result from earlier untreated infection of the mother. In the case of CMV, which is not part of routine antenatal screening in the UK and USA, for example, a primary infection, reinfection or reactivation of the latent virus during pregnancy can lead to fetal infection (see next section).

The likelihood of fetal infection is increased when the mother develops a poor immune response, when the concentration of infectious agents in her blood is high (primary or secondary syphilis, e antigen positive hepatitis B carrier, HIV), or in a primary infection.

There is no good evidence to suggest that maternal mumps, influenza or poliovirus infection during pregnancy leads to harmful effects in the fetus, but the human parvovirus (see Ch. 26) occasionally causes fetal damage or death in 5–10% of cases following maternal infection in early pregnancy. The infected fetus develops severe anaemia with ascites and hepatosplenomegaly (hydrops fetalis) as the virus infects progenitor erythroid stem cells. Intrauterine exchange blood transfusion is used to manage hydrops fetalis.