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Vaccinations and viral infections in pregnancy

Dr.Shobhana Mohandas (Article published in TOGS bulletin)

 

 

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 otherwise indicated.

Contraindicated during pregnancy or safety not established

 

Special recommendations pertain

Tetanus and diphtheria toxoids (Td)

Hepatitis B

Influenza

Meningococcal

Rabies

BCG*

Measles*

Mumps*

Rubella*

Varicella*

Anthrax

Hepatitis A

Japanese encephalitis

Pneumococcal

Polio (IPV)

Typhoid (parenteral and Ty21a*)

Vaccinia*

Yellow fever*

*--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, 2002.

 

Hepatitis A:

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 .

Pregnant 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.

Hepatitis A infection during pregnancy can cause the woman to be at increased risk for severe systemic infection, spontaneous abortion, and premature delivery.

Vaccination:  For 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 pregnancy have not been conducted, the vaccine has been used extensively in pregnancy without adverse outcomes.

Hepatitis B: 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 hepatitis.

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 request vaccination.

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:

Available Tests

a. HBsAg (hepatitis B surface antigen), surface antigen and the IgM antibody to the core antigen

1) Used for identifying carriers or making the diagnosis of acute or chronic HBV infections.

2) Present in the blood 30 to 50 days after exposure and seven to 21 days prior to the onset of jaundice.

3) May disappear with the onset of jaundice or persist for weeks.

b. Anti-HBsAg (antibody to hepatitis B surface antigen), or IgM antibodies to HBcAg

1) Indicates clinical recovery and subsequent immunity to HBV, except in cases of passive transfer of anti-HBsAg through blood products.

2) Appearance is indicative of resolution of acute infection and signals that patient is considered immune and noninfectious.

3) Indicates patient has received vaccine and developed passive immunity.

c. Anti-HBc (antibody to hepatitis B core antigen)

1) An early indicator of acute infection.

2) A life-long marker of past infection.

3) In the absence of HBsAg and anti-HBsAg, this marker is an important indicator of recent infection.

d. HBeAg (hepatitis B “e” antigen)

1) Appears early in HBV infection and indicates the patient is more likely to be infectious.

2) Persists days to weeks and even indefinitely in some cases.

3) Blood level serves as marker for degree of contagiousness; persistence beyond ten weeks may indicate progression to a chronic carrier state and probable liver disease.

 

a. All pregnant women should be screened for HBsAg early in pregnancy

b. In 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.

c.  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.

Avoidance of intimate contact with household members and sexual partners until those individuals receive appropriate prophylaxis.

a. Vaccination: individuals who have risk factors should be vaccinated against infection       

a) The vaccine should be given in the deltoid muscle.

b)    Individuals who have been exposed to the virus before the vaccine should receive passive immunization with Hepatitis B immune globulin in the contralateral arm.

c) HBIG- 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.              

      The combination of passive and active immunization has been effective in reducing frequency of perinatal transmission of Hepatitis B virus.

 

      Acute Disease in the infant

1.     When maternal infection is within the first trimester, up to 10% of neonates will be seropositive for HBsAg.

2.     To mothers acutely infected in the third trimester, 80% of newborns will be infected.

a.  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.

 

Guide to postexposure immunoprophylaxis for exposure to Hepatitis B virus

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Type of Exposure                                  Immunoprophylaxis                                           

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Perinatal                                                 Vaccination + HBIG *                                         

 

Sexual -- acute infection                      HBIG +/- Vaccination                                         

 

Sexual -- chronic carrier                       Vaccination                                          

 

Household contact --

  chronic carrier                                     Vaccination                                          

 

Household contact --                          None unless known exposure

  acute case                                                                          

 

Household contact -- acute

  case, known exposure                       HBIG +/- vaccination                                          

 

Infant (<12 months) --

  acute case in primary                         HBIG + vaccination                                            

  care-giver

                                                       

Inadvertent -- percutaneous/

  permucosal                                          Vaccination +/- HBIG                                         

---------------------------------------------------------------------------------------

* HBIG = Hepatitis B immune globulin

 

 

 

 

 

 Recommended schedule of Hepatitis B immunoprophylaxis to prevent perinatal transmission of Hepatitis B virus infection

===========================================================================

--------------------------------------------------------------------------------------

Infant 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

----------------------------------------------------------------------------------

      Option 1

        Dose 1                                  Birth -- before hospital discharge

        Dose 2                                  1-2 months

        Dose 3                                  6-18 months


Long-term 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 detectable levels.

 

Mumps, Measles, Rubella:

 

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.

 

Mumps:

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 reported.

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 therapeutic abortion. 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 blood transfusions.

 

Measles:

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 inoculation.

Effect on 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 neonatal measles. 

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 immunocompetence.

Prenatal management:

 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 available. 

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 pregnancy. 

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.

 

Varicella:

Varicella-zoster 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 have crusted over. 

Fetal abnormalities associated with congenital varicella infection:

Cutaneous scarring, limb hypoplasia, missing/hypoplastic digits, limb paralysis/muscle atrophy, psychomotor retardation, convulsions, microcephaly, cerebral cortical atrophy, chorioretinitis, cataracts, chorioretinal scarring, optic disc hypoplasia, Horner’s syndrome, and early 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 infection. 

Effects on the pregnant woman:

Pregnant 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.

Acyclovir 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. 

Treatment 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 vaccination. 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.

Contact with varicella:

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 newborn.

 

 

Rabies:

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

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 ) .

 

   Indications for immunoglobulin in pregnancy

Abbreviations: 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.

Infection

Indication

Preparations

Dose

Hepatitis A

Family contacts sexual contacts, day care outbreak international traveler

Ig

0.02 mL/kg up to second 0.02 mL/kg to 2 mL for 3 mo or less

 

 

Ig

0.06 mL/kg up to 5 mL for 6 mo

Hepatitis B

Percutaneous or mucosal exposure

HBIG

0.5 mL at birth vaccinate with HBV vaccine

 

Sexual contacts of person with acute or chronic HBV

HBIG

0.06 mL/kg vaccinate with HBV vaccine

Measles

Nonimmune contacts of acute cases exposed less 6 days previously

Ig

0.25 mL/kg up to 15 mL for normal hosts. 0.5 mL/kg up to 15 mL for immunocompromised

Rabies

Persons exposed to rabid or potentially rabid animal

HRIG

20 IU/kg

Varicella zoster

Immunosuppressed, pregnant, or newborn contact

VZIG

125 U/10 kg up to 624 U

 

Herpes zooster:

Herpes 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 simplex:

Genital 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 frequently.

In 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.

Seventy 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 American College of Obstetricians and Gynecologists (ACOG) recommended that in the absence of visible lesions or prodromal symptoms at the onset of labor, vaginal delivery was 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,

The safety 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. 

 

 

 

 

 

 

 

 

 

 

 

 

 

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