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Congenital Infections

Pregnant women have a lot of infections and fortunately only a few of those affect the fetus. A number of years ago - actually many many years ago - we did a study and just in a six week period 30% of the women had some infectious illness during that time. So fortunately most of these aren’t transmitted to the fetus newborn infections, congenital infections. The thing that bothers me is that a lot of the workup of what are likely congenital infections is either not done or done poorly. Epidemiologic aspects of infections are overlooked, and serologic tests are used inappropriately to make diagnoses. Or, more frequently they are done and you will see on the record TORCH titers done. Negative. And what were done were not adequate to make a diagnosis. So these are what we are going to concentrate on today. The only addition, which I am not going to talk about, would be hepatitis C, which probably should be added to the list although its transmission, compared to hepatitis B, is far less.

The pathogenesis of congenital infections; there are a number of possibilities and the first is that the pregnant woman is infected and transmission to the fetus can be either by the blood, by the placenta, or occasionally ascending infections - frequently with ruptured membranes or leakage of membranes - and then ascending infection.

What I’ll do now is go through the individual infectious illnesses. The first is CMV and this, actually as far as frequency of major problems, is the most frequent. There are two events. One is perinatally acquired infection, which is exceedingly common but not too important as far as damage to the baby. Then congenital acquisition which occurs in 0.5 to 2.7% of births. But this results by and large from primary infection in the mother and some 50-90% of women have been previously infected.

Okay, now to switch over to rubella. This is something that we really shouldn’t need to talk about today. Rubella should be gone, and yet there are a number of young adults who weren’t vaccinated and who have been protected by herd immunity and who are susceptible, particularly adults who travel who are serologically susceptible can still get rubella. The last major outbreak in California was nine years ago, but it is still a risk, a small risk. The risk period with rubella and the timing of maternal infection is greatest in the first eight weeks of pregnancy, in fact even if infection occurs a few weeks before onset of pregnancy. Here we have 16% from 13-20 weeks, but these abnormalities in general are not so clear cut, and the main risk really is in the first 12 weeks, or at most, 16 weeks. The risk after 20 weeks is zero. The main manifestations by percent occurrence is in utero death, in utero growth retardation and deafness.

Now we will go to hepatitis B. The major transmission risk factors for infection in the infant are listed here. First of all, presence of E antigen. The mother is surface antigen positive and also E antigen positive. In those circumstances there is an 80-95% transmission rate to the fetus. Asians have a higher attack rate than non-Asians. Acute hepatitis B in the third trimester has a higher rate. Then the transmission can be directly correlated with the number of surface antigen particles in the mother’s blood. There are five possible manifestations with congenital or neonatally acquired hepatitis B from the mother. The first is; asymptomatic transient antigenemia followed by recovery and antibody. This is the minority; only about 10%. Asymptomatic but persistent antigenemia, and this is unfortunately all too common. Hepatitis with clearing of antigen, and this is actually quite rare. And hepatitis which becomes chronic persistent or chronic active. These two really shouldn’t be separated because persistent antigenemia leads to bad outcome eventually. Then fulminant hepatitis with death. All of you know this, and we’ve been very successful, all pregnant women should be screened for active hepatitis B surface antigen and exposed in any situation where the mother is positive, in fact any situation where she is likely to be positive, the baby should be treated with HBIG within 12 hours of birth and then receive vaccine.

Next is herpes and this is a newspaper from right after acyclovir was first licensed. The main situation with herpes is that the congenital infection is only a small part. The major problem with herpes is acquisition of virus infection during the birth process. So the congenital infection is actually rare but it is virtually always severe and almost never without residual. The important thing is a vesicular rash at birth and I’ve seen some real tragedies.

Next is congenital infection with varicella and there are two events. Early infection in pregnancy and then infection right before birth, maternal infection right before birth. The infections of the mother early in pregnancy, first of all is not too common and transmission to the baby is relatively rare.

As far as treatment … I should go back. I realize I didn’t say anything about treatment with CMV and the babies with congenital CMV; you would like to treat them and with recent successes with toxoplasmosis it makes this more likely. A better idea. However a national study using ganciclovir failed to show benefit. Having said that, any severe baby with CMV I would treat with ganciclovir.

Coming back to varicella infection; there is no data on treatment if they have any evidence of activity, which you don’t usually see, that I would treat these babies with acyclovir.

The second aspect is infection near term and the risk period is very clear and it’s at a time when the mother is infected and the baby gets infected in utero but gets no antibody. This period is five days or less before delivery, or two days after delivery. These babies will have a congenital infection and will have an illness that looks like smallpox. That is the lesions come all at once, and the mortality, untreated, is very high; 30%. So any babies with these criteria should receive varicella zoster immune globulin at birth. They shouldn’t get prophylactic acyclovir, but as soon as any symptoms develop, they should be treated with acyclovir.

The next are enteroviruses and again enterovirus infections are exceedingly common in pregnant women in the summer. Fortunately, even though infection probably gets to the fetus, the majority of these are not a problem. However, infections in the last two weeks percentage-wise, most are mild but can lead at birth to severe meningoencephalitis and myocarditis and sepsis-like illness, with hepatitis and disseminated intravascular coagulation. The diagnosis again for enteroviruses is culture and now PCR of CSF and actually now PCR can be done on stool, throat and urine specimens as well.

Treatment; there is no specific treatment. In nursery outbreaks that end in severe disease, giving IVIG makes sense, although there is little evidence of benefit. Lastly there is a new drug, not licensed yet, called proconerol which is in trial for neonatal infection but has been shown to be effective in older patients with meningitis.