Proven infection
If a vertically transmissible infection is confirmed or cannot be
excluded in a pregnant woman, the risk to the fetus depends on the stage of
pregnancy and the type of infection. For some infections, it may be appropriate
to determine whether the fetus has been infected (eg, CMV infection,
toxoplasmosis and, in some circumstances, varicella). This requires specialised
tests, such as culture or nucleic acid testing of amniotic fluid. Expert advice
and appropriate investigations are essential before interventions such as
termination of pregnancy or administration of potentially toxic drugs are
considered.
Rubella
Although rubella is generally preventable by
vaccination, congenital rubella still occurs in Australia.11 Up to 10% of women of child-bearing age are
susceptible, as they have not been vaccinated, vaccination has failed, or
vaccine-induced immunity has waned. Although the Australian Measles Control
Campaign raised the proportion of school children immune to rubella to over 95%
in 1998, 15%–20% of young men remain susceptible and a potential source of
infection for pregnant women with inadequate immunity.
If infection occurs in the first trimester of pregnancy, the risk of
fetal infection and damage is high (about 90% in the first two months of
pregnancy, and 50% in the third), and termination of pregnancy is usually
recommended. Risk of fetal damage falls steeply after the first trimester and is
negligible after 16 weeks; between 12 and 16 weeks, deafness has been reported.
If a pregnant woman has close contact with or develops rubella-like
illness, her IgG and IgM titres should be measured, even if she was previously
positive for rubella IgG — rarely, women with apparently adequate immunity can
be reinfected (although the risk of fetal abnormality is probably less than 5%,
even in the first trimester12). If contact is in the second or third
trimester and rubella IgG was detected in the
first trimester, further investigation is not necessary. Women who remain
susceptible to rubella should receive MMR vaccine post
partum, unless two previous attempts at immunisation have
failed.
Cytomegalovirus infection
Cytomegalovirus is the most common cause of congenital infection and
non-hereditary deafness. Currently, there is no vaccine or treatment that can be
given during pregnancy (ganciclovir is used to treat serious CMV infection
associated with conditions such as organ transplantation or HIV/AIDS). CMV
infection is transmitted by contact with saliva, urine or genital secretions and
often causes mild hepatitis, atypical lymphocytosis and non-specific symptoms
during the self-limiting primary infection. The virus then becomes latent, but
is reactivated periodically during episodes of mild immunosuppression caused by
intercurrent infection, pregnancy or stress. Reactivation is asymptomatic,
except in severely immunocompromised individuals.
Primary maternal infection occurs in about 1 per 300 pregnancies in
Australia and results in fetal infection in about 40% of cases (affecting 1 per
1000 infants); fetal damage is most likely early in pregnancy. Most congenitally
infected infants are apparently normal at birth, but long-term sequelae, most
commonly deafness and mild intellectual impairment, occur in up to 40% (10%–15%
of all infants of women with primary infection during pregnancy). Symptomatic
multisystem disease, characterised by growth retardation, microcephaly,
intracranial calcification, thrombocytopenia and hepatitis, is uncommon.13
Reactivation of maternal infection during pregnancy can also cause
fetal or perinatal infection (about 1% of infants), but sequelae are uncommon
and usually mild.14 It is
usually difficult to distinguish asymptomatic primary maternal infection from
reactivation or to determine precisely when infection occurred.
If primary maternal CMV infection is suspected because of close
contact or a compatible illness, serological and liver function tests and a
blood film will usually confirm the diagnosis (case report, Box 5). More often, primary CMV infection is
suspected because of a positive CMV IgM result in routine antenatal screening.
False positive CMV IgM results are common, because of cross-reactions, viral
reactivation or persistent low-level IgM after past primary infection. IgG
avidity testing will help distinguish recent from long-past infection.15 Ideally, women who believe
they are at risk of CMV infection, such as childcare workers, should be tested
for IgG before conceiving.
If recent CMV infection is likely or cannot be excluded, especially
in the first trimester, amniocentesis should be considered to determine whether
the fetus is infected. It should be done at about 19 weeks' gestation, or at
least six weeks after the likely time of infection. CMV isolation or positive
nucleic acid test results from amniotic fluid indicate fetal infection, but not
necessarily morbidity, while negative results indicate that severe fetal
morbidity is extremely unlikely. If fetal infection is confirmed, the stage of
pregnancy at which it occurred, viral load in the amniotic fluid and evidence of
fetal abnormality or growth retardation on ultrasound examination may aid in
considering termination of pregnancy
Toxoplasmo
Lisiske CMV infection, toxoplasmosis is usually asymptomatic or has
mild, non-specific symptoms. Primary infection during pregnancy can cause
serious fetal effects. However, unlike CMV infection, toxoplasmosis during
pregnancy can be treated, potentially reducing the fetal effects.
Although asymptomatic women with perceived risk (eg, contact with
cats) are often tested for toxoplasma IgG, pre-pregnancy or antenatal screening
is not recommended. There is no clearly defined group of women at increased
risk, about 75% of women are susceptible,16 and seroconversion during pregnancy is
uncommon. False positive toxoplasma IgM results are not uncommon (case report,
Box 6), and low levels of IgM
may persist for many months or years after primary infection. Like CMV,
toxoplasma infection remains latent for life, but clinical reactivation is
confined to severely immunosuppressed individuals. Infants of women who are
seropositive before conception are not at risk.
Toxoplasmosis is acquired through eating raw or undercooked meat or
ingesting soil contaminated with toxoplasma oocysts, which are excreted in the
faeces of infected cats. Pregnant women should be specifically advised to avoid
these exposures (see Pre-pregnancy testing and
counselling). Direct contact with cats is rarely a source of infection
(they are usually infected as kittens and excrete oocysts for a relatively short
time).
Investigation of suspected acute toxoplasmosis is similar to that of
suspected CMV infection. If maternal infection is confirmed or cannot be
excluded, antibiotic treatment appears to reduce the risk of fetal infection and
sequelae,8 although this has
not been confirmed by randomised controlled trials.17 For maternal infection in the first
trimester, it is particularly important to determine whether the fetus is
infected,18 as likelihood of
fetal infection is low (about 15%), but, if it occurs, fetal damage is likely to
be severe. Later in pregnancy, infection is more likely, but fetal damage is
less likely and, if it occurs, less severe.19
Varicella (chickenpox)
Fetal infection occurs in 10%–15% of cases of varicella (chickenpox)
in pregnant women but is usually transient and asymptomatic. The most common
clinical manifestation, if any occurs, is shingles in the first year of life.
However, 2%–3% of infants of women who have chickenpox in the first half of
pregnancy develop fetal varicella syndrome, with potentially severe defects,
including skin scarring in a dermatomal distribution, ipsilateral limb
hypoplasia, visceral, neurological and eye lesions20 (Box 7). Maternal varicella within a few days
before or after delivery can result in potentially severe varicella in the
infant,21 who should be given
zoster immune globulin (ZIG) as soon as possible after birth.
More than 90% of women of child-bearing age in Australia are immune
to varicella virus,9,16 with a
history of infection providing reliable evidence of immunity. If in doubt when
contact occurs, pregnant women should be tested for varicella IgG as soon as
possible (including those who have been vaccinated, if seroconversion has not
been confirmed). If seronegative, they should be offered ZIG, preferably within
48 hours of contact (maximum, 72 hours). ZIG may not prevent infection but
reduces illness severity
The diagnosis of chickenpox is usually obvious. The disease is more
likely to be severe in adults than in children and may be complicated by
pneumonia, especially in smokers and in the latter half of pregnancy, and is
occasionally fatal. Use of aciclovir is not recommended during pregnancy, but
evidence is accumulating that it has no adverse fetal effects.22 Given during the incubation period or
within 24 hours of rash onset, it can reduce risk of infection or illness
duration and severity. Its use should be considered during the incubation period
for women who have not received ZIG, or soon after rash onset, especially in
women with risk factors for severe disease, such as chronic lung disease,
smoking or impaired immunity, or in the latter half of pregnancy.9 If disease progresses,
admission to hospital and intravenous aciclovir are indicated.
The recommended use of varicella vaccine in susceptible women of
child-bearing age will reduce the incidence of congenital and neonatal varicella
in Australia.2
Parvovirus B19 infection
Parvovirus B19 causes erythema infectiosum, or fifth disease, which
occurs in epidemic waves lasting two to three years, mainly among
primary-school-aged children. Infection is often asymptomatic, but, like
rubella, can cause rash and arthralgia or arthritis, particularly in adults.
Complications of parvovirus infection during pregnancy are excess fetal loss in
the first 20 weeks (up to 10% excess) and hydrops (about 3%) if maternal
infection occurs between nine and 20 weeks' gestation23 (Box 9). Hydrops is caused by severe fetal
anaemia and presents about five weeks after maternal infection. About a third of
cases resolve spontaneously, and outcome is significantly improved in the
remainder by intrauterine transfusion.24
About 60% of Australian women of child-bearing
age are susceptible to parvovirus B19,25 and the annual seroconversion rate varies
from about 1%–2% during non-epidemic years to 10%–15% during epidemics.26 Household and occupational
contact (eg, in a schoolteacher) lead to seroconversion in about 50% and
20%–30%, respectively, of those susceptible.7
Routine antenatal screening for parvovirus antibody is not indicated,
nor is it generally recommended that susceptible pregnant women with
occupational exposure to the virus stay away from work. Epidemics are
protracted, infection is prevalent in the community, and infectivity precedes
rash onset. If contact occurs during pregnancy, IgG tests should be done to
determine susceptibility and, if seronegative, repeated two to three weeks
later.
If infection is confirmed during pregnancy, the fetus should be
monitored for signs of hydrops by ultrasound examination over the next six to 12
weeks, with appropriate specialist referral if it occurs. PCR examination of
amniotic fluid is not recommended after proven maternal parvovirus infection,
but it can be helpful during investigation of non-immune hydrops of unknown
cause.
Enterovirus infection
Many different enteroviruses circulate in the community, especially
during summer. They cause a variety of syndromes, mainly in children, including
non-specific febrile illness; maculopapular, petechial or vesicular rash (hand,
foot and mouth disease); upper respiratory tract infection; and aseptic
meningitis. Infection is usually benign, but can be transmitted to the infant if
it occurs late in pregnancy and, rarely, can cause life-threatening
meningoencephalitis, cardiomyositis or hepatitis.27 No specific intervention is available for
pregnant women, but a history of relevant symptoms may aid diagnosis of severe
neonatal infection.
Other infections
Many other maternal infections can be transmitted to the fetus or
infant.
Listeriosis is an uncommon foodborne
illness caused by Listeria monocytogenes. Pregnant
women are particularly susceptible to the disease, which can result in fetal
death or chronic intrauterine and congenital or perinatal infection.4,28 Investigation of symptoms
such as headache, myalgia and fever associated with relatively inconspicuous
gastrointestinal symptoms in a pregnant woman should include a recent dietary
history and blood culture (Box
4). It is treatable with penicillin.
Gonorrhoea and chlamydial infection can be
transmitted to the infant during delivery and initially cause superficial
infection (conjunctivitis) or upper respiratory tract colonisation. Gonococcal
infection may become disseminated, while chlamydial infection may cause
pneumonia at four to six weeks of age.
Herpes simplex virus (HSV) causes neonatal
HSV sepsis syndrome and encephalitis, which are often
fatal or produce long-term sequelae, but are rare in Australia.29 The risk of vertical
transmission of HSV (types 1 and 2) is greatest during primary maternal
infection, which is often associated with viraemia. Primary genital herpes
(usually type 2) may be clinically severe, with heavy and prolonged viral
excretion, and higher risk of transmission to the infant during vaginal delivery
than recurrent disease. Treatment with aciclovir and, if lesions are present at
term, caesarean section should be considered in primary genital HSV infection.
Caesarean section is not routinely recommended in women with recurrent genital
herpes, as the risk of vertical transmission is small. It should be considered
only if active genital lesions that cannot be covered are present at the onset
of labour.30
Conclusions
Some vertically transmissible infections can be prevented or treated
if detected by routine antenatal screening. Appropriate investigation and
management of other suspected infections can reduce unnecessary intervention,
prevent or moderate adverse outcomes and relieve anxiety. However, antenatal
screening that is not based on accepted criteria or a well-defined plan of
action can cause unnecessary anxiety and potentially dangerous intervention.
Evidence-based recommendations
-
HIV antibody testing should be offered to all pregnant women, and any who are seropositive should be offered antiretroviral therapy1 (E2).
-
Non-pregnant women of childbearing age should be tested for immunity to varicella and offered vaccine if non-immune9 (E2).
-
Suspected infection or contact with infections known to be vertically transmissible in early pregnancy should be investigated. Intervention should be based on laboratory-confirmed maternal and, if appropriate, fetal infection and consideration of known risks of fetal damage (E3–E4, depending on infection).15,18
-
Aciclovir treatment of varicella and herpes simplex virus during pregnancy can significantly reduce morbidity in the mother and potentially in the infant9 (E2). Aciclovir is not recommended in pregnancy, although there is no evidence of adverse fetal effects22 (E3). Its use should be considered when it is judged that benefits outweigh risks.SOURCE: MJU.COM
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