A common scenario in private practice is the pregnant woman presenting with, or exposed to, a viral illness. Generally there are four infectious agents I like to exclude Rubella, CMV, Parvovirus B19 and Toxoplasmosis (see also article on Varicella). Furthermore, serology for all these agents needs to be repeated 3-4 weeks post-illness or exposure to confidently exclude them from causing infection. If at all possible, in the case of an exposure, it is useful to make the definitive diagnosis in the contact.
Acute Rubella has a 40-60% chance of causing severe disease during the first eight weeks of pregnancy (the syndrome includes deafness, cataract, retinopathy, and heart disease). Congenital disease is usually restricted to first 20 weeks of pregnancy.
Of increasing importance is re-infection with Rubella. The majority of women under 35 years have vaccine induced immunity. It is becoming increasing clear that vaccine induced immunity can wane (and requires boosters). Patients with a low level of immunity (reflected by a Rubella antibody level of less than 40 IU/L) can still acquire Rubella infection. The chances of delivering a baby with a congenital Rubella syndrome is low (less than 2%) in this clinical scenario but can occur and has been the subject of litigation in Australia.
Rubella vaccine contains live (attenuated) virus. Although congenital infection occurs in approximately 2% of vaccinated women all the babies appear normal and no cases of congenital disease have been ascribed to the vaccine strain.
Diagnosis:
For immune status, it is clear that greater than 40 IU/L is protective, any levels below 30 IU/L and I suggest vaccination (post-partum).
Rubella serology is very reliable in detecting acute primary infection, although a patient may be Rubella IgG and IgM negative in very early disease.
Unfortunately Rubella IgM may not appear in re-infection so we need to look for rising rubella antibody levels. We always need to have a repeat bleed 3-4 weeks post a suspected Rubella exposure.
Case study
A 29 year old pregnant lady was exposed to a confirmed case of (wild type) Rubella at eight weeks gestation. A serum sample taken around the time of exposure was sent for Rubella serology. The result was Rubella IgM negative and a Rubella IgG antibody level of 26 IU/L. The comment was a low level of Rubella immunity was detected and re-vaccination was suggested post-partum. The general parctitioner subsequently requested further Rubella serology four weeks later. The result was Rubella IgM negative and the Rubella IgG antibody level was greater than 100 IU/L. This patient had clearly been re-infected with Rubella. A subsequent ultrasound demonstrated foetal abnormalities consistent with congenital Rubella syndrome.
CMV is the commonest cause of viral congenital disease in developed countries. Acute CMV in adults ranges from asymptomatic to a mononucleosis syndrome. Although routine antenatal screening is currently not indicated many doctors are performing it as part of routine antenatal serology. This is fraught with difficulties, in particular the chances of detecting a false positive CMV IgM is very high in this low risk group. There are valid indications for investigation of suspected CMV infection during pregnancy, such as a mononucleosis syndrome. A typical story is a mother who acquires CMV from her child, who attends day care, during her second pregnancy.
Following primary CMV infection during pregnancy approximately 40-50% of infants are infected. Four per cent will be born with severe disease (hearing loss, intrauterine growth retardation, hepatosplenomegaly, microcephaly, intracebral calcifications) and 10-15% will have long term sequelae, most commonly hearing loss. Primary infection during the first half of pregnancy is probably worse than during the second half. Also, if the mother is already CMV IgG positive (ie she has been exposed in the past) there is still a small risk that the baby will acquire congenital CMV infection.
Diagnosis
Serology is the mainstay of diagnosis. A positive CMV IgM without a change in the IgG level does not necessarily indicate recent primary CMV infection, so, it is important to obtain a follow-up bleed 10-14 days later to detect a rise in CMV IgG levels. Furthermore CMV IgM can persist for up to a year post infection - and if detected in the first half of pregnancy could simply represent prenatal infection. Neither culture or polymerase chain reaction (PCR) are particularly useful to diagnose acute CMV infection in adults.
I do not recommend amniocentesis. It has been suggested that amniocentesis (and chorionic villous sampling [CVS]) with culture and PCR for CMV will increase the ability to predict fetal damage. However published algorithms are based on, as yet, unproven assumptions. It is argued that by finding amniotic fluid positive for CMV increases the risk of delivering a severely affected baby to 8% and that a negative culture excludes CMV disease.
Unfortunately, it appears that infection of the fetus may be missed by amniocentesis before or after 20 weeks. In one study 25% (4 of 16) of CMV infected babies were negative for CMV by amniotic fluid culture and PCR prior to 20 weeks gestation. Possible reasons for the false negatives are that transplacental transmission occurs late, that the virus is less likely to be excreted by the fetus into the amniotic fluid during the first 20 weeks or that iatrogenic infection results from amniocentesis by breaching the maternal and fetal circulations. The latter possibility is plausible, although difficult to prove, particularly when PCR, as well as culture, has been initially negative for CMV despite subsequent congenital infection of the child.
Contamination of PCR and false positive results is possible even with careful technique and could be due to even a minute amount of maternal blood contaminating amniotic fluid. In addition, the culture immunofluorescence technique is relatively rapid and sensitive and the high degree of specificity of culture immunofluorescence is currently an advantage over PCR. CVS may be more prone to maternal contamination.
The risks and limitations of amniocentesis must be considered when counselling women with suspected primary CMV infection during pregnancy If a baby is born with suspected congenital CMV urine culture within 14 days of birth provides definitive evidence of intrauterine CMV infection. Interestingly, it appears that antivirals (for example, ganciclovir) given to babies with congenital CMV disease benefit from the therapy post-partum.
It is worth noting that Parvovirus B19 is species specific ie although related to the canine Parvovirus, the canine virus does not cause disease in humans.
Parvovirus B19 is often considered exotic and yet it is a very common childhood exanthem. It was discovered by an Australian (Yvonne Cossart) in the early 1970s, however it has only been recently that diagnostic assays have become widely available. B19 is endemic all year round with the highest activity in late spring and early summer with epidemics every 3-5 years. Most adults are immune. There is a less than 10% risk of fetal death after maternal infection. Parvovirus infects the haemopoetic cells of the foetus, transiently shutting down red blood cell production. This results in fetal hydrops in the baby. Often the baby will recover as the infection resolves. Inevitably there have been successful reports of treatment with intra-uterine blood transfusion. A congenital syndrome has not been described (ie the baby either lives or dies).
Diagnosis
There are suggestions that parvovirus IgG should be added to the antenatal screen but it is probably not worthwhile screening until a vaccine becomes available.
To diagnose infection Parvovirus IgG and IgM should be tested for, however, the IgM response can wane after four weeks and if the patient is IgG positive and IgM negative then one should perform PCR on the serum since clinically apparent foetal hydrops may not present until six weeks after the mother's acute illness. If maternal infection is detected then the mother should have serial ultrasounds and alpha fetoprotein measured.
It is likely that in the future the approach to Parvovirus B19 will be like rubella i.e. use of a vaccine and reliable screening.
This is relatively rare in Australia. The common presentation is a mononucleosis type syndrome. The congenital syndrome includes hearing loss, intrauterine growth retardation, hepatosplenomegaly microcephaly and hepatosplenomegaly The risks are stratified by trimester. During the first trimester 10-25% of foetuses become infected and the majority have severe disease. In the second trimester 30-50% are infected but 70% are normal. While in the third trimester 60% are infected and over 90% are normal. Spiramycin is a useful treatment and is given to the mother as soon as possible during pregnancy.
Diagnosis
Serology for Toxoplasma IgG and IgM are the mainstays of diagnosis. Culture and PCR may have a role in babies born with suspected congenital disease.