Vaccinations and viral infections in pregnancy
Viral infections and
vaccinations remain a grey area as far as obstetritians are
concerned. Given below is an overview of some common viral
infections, that can complicat3e pregnancy, importance being
given to period of infectivity, vaccinations available etc
The table below gives an
overall idea of the safety of vaccines in pregnancy.
Immunizations in pregnancy
Considered safe if
Contraindicated during pregnancy or
safety not established
Tetanus and diphtheria toxoids (Td)
Typhoid (parenteral and Ty21a*)
*--Live, attenuated vaccine. BCG = bacille
Calmette-Guérin; IPV = inactivated polio virus. Adapted from
Guidelines for vaccinating pregnant women. Recommendations of
the Advisory Committee on Immunization Practices (ACIP).
Atlanta, Ga.: Centers for Disease Control and Prevention,
Hepatitis A virus replicates in the liver, is
excreted in the bile, and is shed in the stool. Peak
infectivity of infected persons occurs during the 2-week
period before the onset of jaundice or elevation of liver
enzymes, when the concentration of virus in the stool is
highest. Chronic shedding does not occur. Viremia occurs soon
after infection and persists through the period of liver
enzyme elevation .
women are at risk if there is an infected household member, if
they work in close physical contact with infected persons.
Transmission of hepatitis A from an acutely infected woman to
her fetus has not been established.
A infection during pregnancy can cause the woman to be at
increased risk for severe systemic infection, spontaneous
abortion, and premature delivery.
pregnant women exposed to the hepatitis A virus,
immunoglobulin, 0.02 mg/kg intramuscularly, and hepatitis A
virus vaccine are recommended for postexposure prophylaxis. A
second dose of vaccine is required 6 months later. Although
formal studies of hepatitis A vaccine in
have not been conducted, the vaccine has been used extensively
in pregnancy without adverse outcomes.
Hepatitis B infection is caused by a DNA-containing virus and
is transmitted through contact with infected blood, sexual
activity, and sharing of intravenous needles. Hepatitis B
infection may be asymptomatic, or it may result in fulminant
Risk factors for a pregnant woman include having had sex with
a man who has sex with men, having multiple sexual partners,
using or abusing intravenous drugs, having occupational
exposure, and being a household contact of acutely infected
persons or persons with a chronic carrier state. Women who
have husbands who have recently contracted the disease may
Because it contains noninfectious hepatitis B surface antigen
particles and should cause no risk to the fetus, neither
pregnancy nor lactation is a contraindication to vaccination.
Antibody testing for Hepatitis B:
HBsAg (hepatitis B surface antigen), surface antigen and
the IgM antibody to the core antigen
for identifying carriers or making the diagnosis of acute or
chronic HBV infections.
in the blood 30 to 50 days after exposure and seven to 21 days
prior to the onset of jaundice.
disappear with the onset of jaundice or persist for weeks.
Anti-HBsAg (antibody to hepatitis B surface antigen), or
IgM antibodies to HBcAg
Indicates clinical recovery and subsequent immunity to HBV,
except in cases of passive transfer of anti-HBsAg through
Appearance is indicative of resolution of acute infection and
signals that patient is considered immune and noninfectious.
Indicates patient has received vaccine and developed passive
Anti-HBc (antibody to hepatitis B core antigen)
early indicator of acute infection.
life-long marker of past infection.
3) In the
absence of HBsAg and anti-HBsAg, this marker is an important
indicator of recent infection.
HBeAg (hepatitis B “e” antigen)
early in HBV infection and indicates the patient is more
likely to be infectious.
Persists days to weeks and even indefinitely in some cases.
Blood level serves as marker for degree of
contagiousness; persistence beyond ten weeks may indicate
progression to a chronic carrier state and probable liver
pregnant women should be screened for HBsAg early in pregnancy
special situations (such as when acute hepatitis is suspected,
when there is a history of exposure, or when the mother has a
particular high-risk behavior such as substance abuse and
prostitution), an additional HBsAg test should be performed
later in pregnancy or prior to delivery.
Women who present for delivery without prenatal care or
without documentation of HBsAg results should have the HBsAg
performed as soon as possible after admission.
Preventive measures in women who have contracted the disease.
of intimate contact with household members and sexual partners
until those individuals receive appropriate prophylaxis.
Vaccination: individuals who have risk factors should be
vaccinated against infection
vaccine should be given in the deltoid muscle.
Individuals who have been exposed to the virus before the
vaccine should receive passive immunization with Hepatitis B
immune globulin in the contralateral arm.
0.5ml administered IM at a site different from the site used
for the vaccination.
Susceptible pregnant women who are at risk for Hepatitis B
infection should be specifically targeted for vaccination.
*Pregnancy is NOT a contraindication for vaccination.
combination of passive and active immunization has been
effective in reducing frequency of perinatal transmission of
Hepatitis B virus.
Acute Disease in the infant
When maternal infection is within the first trimester, up to
10% of neonates will be seropositive for HBsAg.
mothers acutely infected in the third trimester, 80% of
newborns will be infected.
Infants who are born to women who are HBsAg positive at
the time of delivery should receive both Hepatitis B immune
globulin (HBIG) and Hepatitis B vaccine.
postexposure immunoprophylaxis for exposure to Hepatitis B
Vaccination + HBIG *
acute infection HBIG +/-
contact -- None unless known exposure
contact -- acute
known exposure HBIG +/-
(<12 months) --
case in primary HBIG +
Inadvertent -- percutaneous/
Vaccination +/- HBIG
* HBIG = Hepatitis B immune
Recommended schedule of Hepatitis B immunoprophylaxis to
prevent perinatal transmission of Hepatitis B virus infection
born to mother known to be HBsAg * positive
Recommended Schedules of Hepatitis B vaccination for infants
born to HBsAg negative mothers
Hepatitis B vaccine Age of infant
Dose 1 Birth -- before
Dose 2 1-2 months
Dose 3 6-18 months
studies of healthy adults and children indicate that hepatitis
B vaccine protects against chronic HBV infection for at least
15 years, even though antibody levels might decline below
Vaccinations to prevent all three of the above viral
infections are live attenuated vaccines and should be avoided
during pregnancy. Ideally,women of childbearing age should
be immunized against poliomyelitis, measles, mumps, rubella,
varicella, tetanus, and diphtheria before becoming pregnant.
This is particularly important for rubella because of the
consequences of infection for the developing fetus.
When compared with uninfected women,
women with mumps during pregnancy have no increase in the risk
of delivering an infant with congenital malformations. The
rate of spontaneous abortion in women who acquire mumps during
the first trimester of pregnancy is increased. Gestational
mumps infection has been implicated in the development of
endocardial fibroelastosis (EFE) in offspring. Perinatal
mumps infection with parotid swelling and pneumonia has been
Infective period:Patients are considered noninfectious 9 days
after the onset of parotid swelling.
Vaccination in pregnancy: Vaccine virus has been isolated from
the placenta of nonimmune women immunized 7 to 10 days before
Virus has not been isolated from the fetal tissue of immunized
women, and no cases of mumps vaccine–associated embryopathy
have been reported. However, because of theoretical risks to
the fetus, pregnant women should not be immunized, and
conception should be avoided for 3 months after vaccination.
Mumps vaccine is not transmitted from vaccinees to contacts
and can be given to children whose mothers are pregnant.
Vaccination in non pregnant women:
Immune globulin preparations interfere with the serologic
response to live-attenuated virus vaccines. Mumps vaccine
should be given at least 2 weeks before or 3 months after
standard administration of immunoglobulin preparations or
Rubeola or measles is caused by a paramyxovirus that commonly
attacks children. The viral syndrome arises after an
incubation period of 10-14 days from respiratory droplet
pregnancy: There may be increased uterine activity, leading to
premature delivery. Because occurrence of measles in
pregnancy increases the risk for premature labor and
spontaneous abortions, susceptible pregnant women exposed to
measles should receive immunoglobulin intramuscularly within 6
days of exposure. They then should be given the measles,
mumps, and rubella vaccine after delivery, at least 5 months
after receipt of immunoglobulin.
Teratogenicity: There is no specific syndromes attributed to
intra-uterine rubeola infection. However, the newborn
delivered to a woman with active disease may develop severe
Vaccination: Pregnant women should not
receive measles vaccine However, accidental vaccination with
rubeola vaccineis not a cause for alarm or an indication for
pregnancy termination. Immune serum globulin (ISG) may be
given to susceptible pregnant women exposed to rubeola in an
attempt to prevent or modify the clinical expression of the
disease. The intramuscular preparation (0,25ml/kg,maximum 15
ml) should be given within six days of exposure.
German measles (Rubella):
Rubella is caused by a single-stranded
RNA virus of the togavirus family. It causes only mild or
subclincal illness, with fever lasting only 3 days. However,
it can produce many fetal abnormalities. Defects involving
virtually every organ have been reported.
Risk of fetal infection : The risk of
fetal infection and congenital anomalies may be over 90% in
the first trimester and is in the order of 25% in the early
second trimester. The risk of severe abnormalities due to
infection probably declines through the second trimester. The
rate of neonatal seropositivity increases again with third
trimester maternal infection, probably due to increased fetal
If a woman is exposed to rubella
during the first 20 weeks of pregnancy, a serologic test
should be performed to determine immunity. If she is found to
be susceptible, she should be retested in 2 to 4 weeks. If
infection has occurred, she should receive counseling
regarding her options. If rubella is contracted during the
first 20 weeks of pregnancy, fetal or early neonatal death
occurs in 15% to 20% of cases. Among infants who survive, 20%
to 50% have evidence of congenital rubella syndrome (eg,
cataracts, deafness, and congenital heart disease). If a
pregnant woman exposed to rubella decides not to terminate her
pregnancy, immunoglobulin can be given in the same timing and
dosage as for measles, although current evidence has not
proved that this treatment is protective.
Congenital rubella can be diagnosed by
fetal blood sampling by cordocentesis for measurement of fetal
levels of rubella-specific IgM.,reverse transcription
polymerase chain reaction (RT-PCR) and virus isolation from a
maternal pharyngeal swab and productsof conception.However,
the accuracy of amniotic fluid culture, assessment of fetal
blood for specific IgM, or use of PCR is very low. In very
precious pregnancies, the couple will have to weigh the risks
of foetal blood sampling, the chances of inaccurate reports,
and the chance of anomalies mentioned in literature ,
trimester wise. No treatment other than abortion is
Effect of vaccination:
Vaccination produces long-term immunity
in 95% of vaccines, and as implimentation of MMR vaccination
to all new borns has been going on in Kerala since a long
time, the incidence of Rubeola in the coming generation of
pregnant women is likely to be very low. For women who are
not yet immunized, it is best to give the rubella vaccine soon
after delivery, so that she is immune before the next
Vaccination in pregnancy:
The rubella vaccine is a live virus
preparation and should not be administered to pregnant women
for theoretic reasons. A woman who has taken rubella vaccine
should not get pregnant for one month.
Inadvertent vaccination during
pregnancy should not be a reason for medical termination as
the risk of fetal effects is negligible.
Breast-feeding does not adversely affect the response to any
of the recommended vaccines for adults. No current recommended
vaccine is contra indicated in breast-feeding mothers.
virus (VZV) is a DNA virus in the herpes family. Clinical
chickenpox develops 10-20 days after respiratory exposure.
Patients are contagious from 48 h before the onset of the rash
untilall of the ruptured vesicles
abnormalities associated with congenital varicella infection:
scarring, limb hypoplasia, missing/hypoplastic digits, limb
paralysis/muscle atrophy, psychomotor retardation,
chorioretinal scarring, optic disc hypoplasia, Horner’s
childhood zoster. The period of highest risk is stated to be
present only in the first half of pregnancy. The reports cite
variying inceidences, between 9% in some repots to 2% in other
reports. Children infected with VZV in utero may develop
zoster within the first two years of life. Maternal infection
within four days of delivery poses a 30% risk to infants of
developing disseminated varicella. If the infection had taken
place earlier, the mother would have developed antibodies,
which would have been passed to the fetus along with the
infection. This would perceptibly reduce the severity of
the pregnant woman:
women in whom primary varicella develops have an increased
risk for serious complications (eg, pneumonia and premature
labor) compared with other noninfected women. Susceptible
women who are exposed to varicella zoster may be given
varicella zoster immunoglobulin within 96 hours, which may
prevent or modify serious maternal illness, but no evidence
exists that it prevents intrauterine infection.
should be reserved for severe maternal varicella infection.
Doses of 5-10mg/kg intravenously every 8 h may be given
without untoward maternal or fetal effects. The medication is
discontinued typically after 7 days when the patient is
clinically improved. Infants born to mothers in whom
varicella develops within 5 days before or 48 hours after
delivery should receive varicella zoster immunoglobulin to
reduce the likelihood of serious or fatal neonatal varicella
infection. Neither VZIG nor acyclovir demonstrably reduce the
risk of congenital malformations.
of the infant:
Treatment with VZIG is recommended for all exposed neonates if
the mother had chickenpox within 5 days before and up to 2
days after delivery. The appropriate dose is 125 U (1 vial).
In addition, VZIG should be given to all exposed neonates who
are delivered at or before 28 weeks' gestation, because of the
poor antibody transfer at early gestational ages.
Unfortunately, VZIG does not prevent 100% of cases of neonatal
varicella. In one series, half of the infants who received
prophylaxis developed chickenpox, though the severity of the
infection was reduced.
Vaccination: A live attenuated varicella vaccine is available
and is recommended for susceptible nonpregnant adults. Two
doses are recommended, with the second dose being given 4 to 8
weeks after the first dose. Persons who receive the varicella
vaccine should not become pregnant for 1 month after
Although vaccination during pregnancy with live virus vaccines
is not recommended, inadvertent vaccinations during pregnancy
have occurred. More than 600 vaccinations during pregnancy
have been reported, with no increased adverse effects to the
mother and fetus recorded.
If a child
in the home has chickenpox, it is prudent to evaluate the
maternal history. If, however, the mother is not immune, it is
reasonable to keep the mother and newborn isolated from the
infected child. Another option is to give VZIG to mother and
Rabies is a viral infection transmitted most commonly by the
saliva of infected animals.
There have been no identified associations between rabies
vaccination and fetal abnormalities. Considering the potential
maternal and fetal consequences of untreated rabies exposure,
similar guidelines should be used for postexposure prophylaxis
in pregnant and nonpregnant patients.
Immunoglobulins are proteins produced by B lymphocytes and
plasma cells. All immunoglobulin preparations are of the IgG
class. Immunoglobulins for clinical use are administered
intramuscularly and intravenously, and hyperimmune
preparations are available against specific diseases such as
tetanus, rabies, hepatitis B, and varicella zoster
(Table ) .
immunoglobulin in pregnancy
ABY, antibody; HBGI, hepatitis B immunoglobuin; HRIG,
human rabies immune globulin; VZIG, varicella zoster
immunoglobulin.Modified from Guide for adult
Immunization American College of Physicians 1994. p. 86.
Family contacts sexual contacts, day
care outbreak international traveler
0.02 mL/kg up to second 0.02 mL/kg to
2 mL for 3 mo or less
0.06 mL/kg up to 5 mL for 6 mo
Percutaneous or mucosal exposure
0.5 mL at birth vaccinate with HBV
Sexual contacts of person with acute
or chronic HBV
0.06 mL/kg vaccinate with HBV vaccine
Nonimmune contacts of acute cases
exposed less 6 days previously
0.25 mL/kg up to 15 mL for normal
hosts. 0.5 mL/kg up to 15 mL for immunocompromised
Persons exposed to rabid or
potentially rabid animal
Immunosuppressed, pregnant, or
125 U/10 kg up to 624 U
zoster, or shingles, represents reactivation of latent
infection due to the VZV. Reactivation occurs in approximately
3% of infected patients; thus this complication is rare in
pregnancy. The new
mother who has an outbreak of shingles can be allowed to
breast-feed, provided that the skin lesions do not involve the
breast. Viral cultures obtained on breast milk from women who
had zoster and acute varicella have been negative.
herpes can be caused by either HSV-1 or HSV-2, and is
transmitted through direct sexual contact. Transmission
requires physical contact of the susceptible mucosal surfaces
or small cracks in the skin of the genital tract with the
virus. The rate of recurrence for genital herpes is higher in
pregnant compared with nonpregnant women, and is more common
with HSV-2 than HSV-1. The most significant risk of genital
herpes infection during pregnancy is transmission of the virus
to the fetus or newborn. This transmission occurs more
commonly during delivery as the fetus comes into contact with
infected vaginal secretions. In-utero transmission occurs less
women who have preterm premature rupture of membranes and
active genital lesions, there are published case reports
supporting conservative management in the setting of recurrent
HSV infection. It is important to note that in this setting,
administration of antiviral therapy has not been proven to
shorten the duration of active lesions.
percent of neonatal HSV infections are caused by HSV-2. Most
of the neonatal infections caused by HSV-1 are associated with
the acquisition of primary HSV-1 late in pregnancy, and
subsequent exposure of the fetus to secretions in the genital
tract at time of delivery. In 1988, the
of Obstetricians and
Gynecologists (ACOG) recommended that in the absence of
prodromal symptoms at the onset of labor, vaginal delivery
acceptable. Furthermore, even in the presence of membrane
rupture for more than 4 hours, cesarean delivery was still
appropriate in the presence of active genital herpes lesions.
Acyclovir prophyalxis should be considered for women at or
beyond 36 weeks who had a first episode of HSV occurring
during the current pregnancy, and could be considered for
women at risk for recurrent disease. Acyclovir may be
administered orally to pregnant women who have first episode
genital herpes or severe recurrent herpes, and should be
administered intravenously (IV) to pregnant women who have
severe HSV infection,
of systemic acyclovir, valacyclovir, and famciclovir in
pregnant women has not been established. Prospective pregnancy
registries established by Glaxo Wellcome (Triangle
Park, North Carolina) indicate no increase in teratogenicity
to gravidas exposed to acyclovir in the first trimester.