The risk of different rash illnesses in pregnancy
Rubella
The clinical features and consequences for the fetus of primary rubella in pregnancy are well established ( 5). The unreliability of a clinical diagnosis of rubella is accepted (6). The risk to the fetus of primary rubella in the first 16 weeks gestation is substantial ( Table 1: Characteristics of rubella, parvovirus B19 and varicella-zoster virus infections in the UK), with major and varied congenital abnormalities being associated with infection in the first trimester, and a lesser risk, limited to deafness, in the fourth month (5). Rubella infection prior to the estimated date of conception or after 20 weeks carries no documented risk (5, 7), and rubella between 16 and 20 weeks gestation a minimal risk of deafness only (8).
A rubella reinfection is defined as rubella infection in someone who has previously had either documented natural rubella virus infection or successful rubella immunisation (9). Maternal reinfection is usually subclinical and diagnosed by changes in antibody concentration (IgG and/or IgM) only. The risk to the fetus of subclinical maternal reinfection in the first 16 weeks gestation has not been precisely determined, but an overview would suggest the risk of congenital damage is less than 10%, and probably less than 5% (10). Maternal rubella reinfection with fetal infection and damage made a substantial contribution to the incidence of congenital rubella in the UK in the late 1980s and early 1990s (10 ), but has declined as the incidence of rubella has fallen. Maternal reinfection with a rash is very rare, but can be presumed to present a significant, but not quantified, risk to the fetus as viraemia will have occurred.
Before rubella vaccine became available, an estimated 200-300 babies were born each year with Congenital Rubella Syndrome (CRS) in the UK . Routine rubella vaccination for schoolgirls was introduced in England and Wales in 1970, and subsequently for susceptible women post-partum. This selective policy was effective in reducing the number of children born with CRS and rubella-associated pregnancy terminations but rubella continued to circulate and remaining non-immune women were exposed via their own or other young children. Measles, mumps and rubella (MMR) vaccine was introduced in 1988 for all children in the second year of life with a catch-up campaign for pre-school children at that time, with the aim of interrupting circulating rubella. A national measles/rubella vaccine campaign targeted all school aged children (5 to 16 years) in 1994, a routine second MMR immunisation at 4 years of age was subsequently introduced in 1996, and the schoolgirl vaccination programme was discontinued.
The epidemiology of rubella in England and Wales changed after the introduction of MMR vaccine with a considerable fall in rubella in young children. However, in 1993 there was a large increase in both notified and laboratory confirmed cases of rubella (link to graph). Most of these cases occurred in males in colleges and universities, who had not been offered either MMR or single rubella vaccine (11, 12). There was a concomitant rise in reports of rubella infection in pregnant women. Outbreaks of rubella have continued, predominantly in young males with a small number of cases in pregnant women through contact with young men in this country, who acquired their infection or abroad. Between 1999 and 2005, there have been four infants with CRS born to women whose infection occurred in the UK .
MMR coverage fell from around 92% in 1997 to 80% in 2003 due to adverse publicity about unproven associations between MMR vaccine, bowel disease and autism and had risen slightly to around 82% by mid-2005. Following the publication of many studies which did not support an association between MMR vaccine and these conditions, coverage rose slightly to around 82% by mid-2005. The lack of circulating rubella in the UK cannot be maintained with this low coverage in the longer term.
Table detailing breakdown of laboratory reports of rubella
It is now more than 10 years since the report of the last Working Party which considered diagnosis of rubella (1), and it was in 1996 that the last guidance was issued (4).
There are a wide range of potential consequences of parvovirus B19 infection, ranging from minor febrile illness to erythema infectiosum (Fifth disease, slapped cheek syndrome), generalised rash illness clinically indistinguishable from rubella, aplastic crises in patients with shortened red cell life, arthralgia, and persistent infection in the immunocompromised (14). Infection in the first 20 weeks of pregnancy can lead to intrauterine death (risk 15% c.f. 5% in control group; excess risk 9%) and hydrops fetalis (risk 3%, of which about half die, and are included in the excess risk of 9%, if infection between 9-20 weeks gestation) (15). These consequences usually occur some 3-5 weeks after the onset of maternal infection, but can be later. Permanent congenital abnormality has not been identified as a consequence of intrauterine infection, although persistent neonatal infection and anaemia can occur rarely (16).
Parvovirus B19 reinfection and reactivation has been shown in volunteer studies (17) and in the immunocompromised, but there is no evidence to suggest reinfection is a risk to the fetus. Parvovirus B19 infection is common with some 50-60% of adults having been infected (18). No vaccine or preventive measures are available, and an increased incidence occurs every 3-4 years, largely in schoolchildren.
In 1998, guidance on the management of parvovirus B19 infection was issued by PHLS after consultation with a range of authorities (2). A number of areas in relation to management in pregnancy are outwith the scope of that guidance, however.
Disseminated primary varicella-zoster virus infection ( chickenpox; varicella ) presents as a characteristic vesicular rash, and clinical diagnosis is highly specific, although not very sensitive as sub clinical and mild cases occur. Infection during the first 20 weeks of pregnancy can lead to intrauterine infection with characteristic fetal damage ( Table 1: Characteristics of rubella, parvovirus B19 and varicella-zoster virus infections in the UK) at an incidence of some 1% (19). Maternal infection at 20-37 weeks gestation can lead to intrauterine infection and herpes zoster in childhood. Maternal infection with onset within one week pre- or post-delivery can lead to neonatal varicella, which is potentially life-threatening if untreated; the degree of risk cannot be quantitated given that immunoglobulin prophylaxis and antiviral treatment is now accepted practice, and early studies, which showed a risk up to 30%, are likely to have been biased by selective reporting.
Localised varicella-zoster virus infection ( shingles; zoster ) reflects reactivation of latent virus, and is usually dermatome restricted. There is no observed risk to the fetus or neonate of localised maternal herpes zoster (19), although it is uncertain whether dissemination of herpes zoster, as may occur in the immunocompromised, carries a fetal/neonatal risk.
Varicella-zoster virus reinfection has been described, but is rare (20).
Varicella-zoster virus is endemic within the UK, with some 90% of young adults having been infected (21). Although an attenuated live varicellazoster virus vaccine has been available for many years, it is not licenced as yet in the UK (22). Its use on a named patient basis only in the UK has been limited to specific groups at significant risk, primarily immunocompromised susceptible children.
Guidance on the management of varicella-zoster virus infection in pregnancy and the newborn was published in 1998 (3).
The clinical features and complications of measles in the child and adult are well-established and include disseminated rash, coryza, conjunctivitis, pneumonia, otitis media, encephalitis, etc (23). Infection in pregnancy can lead to intrauterine death and preterm delivery (24), but is not associated with congenital infection or damage.
Indigenous measles is rare in the UK following introduction of MMR vaccine in 1988 and the MR vaccine campaign of 1994 (link to graph Fig 18, p53 but add coverage) (25) except in the unvaccinated or in communities with low coverage (26). Most cases are now noted in people who move to the UK from countries where measles is still endemic. Recent falls in vaccine coverage have contributed to a rise in susceptible individuals which may eventually accumulate to the point where an epidemic will occur as seen in Dublin in 1999/2000 (27). Human normal immunoglobulin (HNIG) may not prevent measles, but has been shown to attenuate the illness. There is no evidence that it prevents intrauterine death or pre-term delivery.
Enteroviruses ( coxsackievirus A, B; echovirus; enterovirus 68-71 ) can cause a wide range of manifestations such as meningitis, hand, foot and mouth disease, febrile illness, myocarditis and Bornholm disease. Infection during pregnancy is not associated with any particular fetal consequence, although rarely can result in abortion (as can any febrile illness) (28). Neonatal infection is usually acquired from the mother or by cross-infection. Neonatal infection, particularly with selected echoviruses, can have multisystem life-threatening complications (29).
Sporadic enterovirus infection is not uncommon, but major summer epidemics have not been seen in the UK for some years. Except for poliovirus, no vaccines are available. Immunoglobulin has been advised for prophylaxis in exposed neonates (29).
Hand, foot and mouth disease is characterised by vesicular lesions of hands, feet, and mouth; the latter soon break down to ulcers. It is a commonly recognised manifestation of enterovirus infection. Pregnant women presenting with the characteristic features may be investigated by viral cultures of faeces and throat swab (serology of little value), but can be reassured that there is no adverse consequence for the fetus. Pregnant women in contact with cases of hand, foot and mouth disease should be reassured.
Infectious mononucleosis (IM) is a common presentation of primary Epstein-Barr virus (EBV) in young adults. IM is characterised by generalised lymphadenopathy, fever, sore throat and typical haematological and serological findings, including the detection of heterophil antibody. A generalised maculopapular rash is an associated accompanying feature, however (30), particularly if ampicillin, or a similar antibiotic, has been taken.
Primary EBV infection in pregnancy (whether clinically-apparent as IM or asymptomatic) carries no specific risk to the fetus (31). EBV infection results in a latent infection with persistent excretion in the throat of a proportion (c. 20%) of individuals. Hence exposure to EBV can occur irrespective of whether the contact patient has IM, and exposure to IM does not require investigation and the patient can be reassured.
Some 50% of young adults are susceptible to EBV, with higher rates in more affluent social groups, and some 2% or more of those susceptible become infected annually. About 50% of these infections will present with IM.
Cytomegalovirus (CMV) can cause an IM-like syndrome with a generalised maculopapular rash, and must be considered if heterophil antibody is not detected. Primary infection with CMV may lead to intrauterine infection (32).It is not considered further as occurrence of a rash is very rare and no effective intervention exists.
