Transcript Slide 1

Immunization
Recommendations
Pregnant and Breastfeeding
Women
Natali Aziz, MD, MS
Department of Obstetrics, Gynecology and Reproductive Sciences
University of California at San Francisco
Antepartum and Intrapartum Management
June 5, 2008
Opportunity for Immunization
during Pregnancy
In the US, ~ 4 million live births each year
In the US, >98% of women have at least 1
prenatal visit
– Health care opportunity for vaccination!
– Immunization effective in pregnant women
Protection for
– Pregnant woman
– Fetus
– Neonate
– Young infant
Obstetric Immunization Challenges
Limited well-controlled studies in pregnant cohorts
Theoretical concerns about efficacy
Theoretical concerns about safety in pregnancy/BF
– Vaccine type (e.g., live vaccines)
– Additives/adjuvants/preservatives (e.g., thimerosal)
– Timing of vaccination
Interruption of breastfeeding
Impaired newborn/infant immune response to
childhood series concerns
Lack of harmonization with FDA labels and indications
Public perception/risks and legal liability
Logistic issues for office-based practice
ACIP April 2008
Overview
Immune Considerations during Pregnancy
Types of Immunizations
Immune Globulins
Immunization Recommendations
– Prior to Conception
– During Pregnancy
– Postpartum
Special Considerations
– Traveling during Pregnancy
– Immunocompromised Pregnant Women
– Vaccine Controversy
Summary
Immune Considerations
in Pregnancy
Pregnant women
– Altered immune response
– Increased risk of some
infections
– Increased risk of severe
outcomes of some
infections
Fetus, newborn, infant
– Immature immune
response
– Increased risk of some
infections
– Increased risk of severe
outcomes of some
infections
– Infection sequelae can
result in lifelong disability
Immunization Types
Inactivated vaccines, toxoids, immune globulins
– No evidence of harmful effects on fetus/pregnancy
– Generally considered safe in pregnancy
Live Vaccines
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Theoretical risk of infecting fetus
No reports of teratogenicity or classic congenital infections!!!
Subclinical infections reported
Use discouraged during pregnancy unless high risk
Administration during/within 4 wks of pregnancy DOES NOT
warrant termination
Counsel patient about potential theoretical risks
Lack of cases demonstrating harmful effects to fetus!
Vaccinations: Inactivated
Considered safe if otherwise indicated
– Hepatitis B
– Influenza
– Meningococcal (MPSV4)
– Rabies
– Tetanus and diphtheria toxoids (Td)
CDC May 2007: Guidelines for Vaccinating Pregnant Women
Vaccinations: Live-Attenuated
Contraindicated during pregnancy or safety
not established
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BCG*
Influenza* (LAIV, FluMist- intranasal)
Measles*
Mumps*
Rubella*
Vaccinia*
Varicella*
Zoster*
*Live, attenuated vaccine.
CDC May 2007: Guidelines for Vaccinating Pregnant Women
Vaccinations:
Special Considerations
Special Recommendations
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Anthrax
Hepatitis A
HPV
Japanese encephalitis
Meningococcal (MCV4)
Pneumococcal
Polio (IPV)
Typhoid (parenteral and oral Ty21a*)
Vaccinia* (high risk exposure only)
Yellow fever*
Tdap/Pertussis (acellular)
*Live, attenuated vaccine.
CDC May 2007: Guidelines for Vaccinating Pregnant Women
Immune Globulins
Considered safe if otherwise indicated
– Post-exposure prophylaxis same in pregnancy
Hepatitis A and B
Measles
Rabies
Tetanus
– Varicella PEP recommended in pregnancy
Varicella-zoster immune globulin (VZIG)
Purified human immune globulin (VariZIG)
Immune globulin intravenous (IVIG)
Immunizations
Prior to Conception
Human Papillomavirus
Indication: Girls/women aged 9 to 26 years old
Timing: Preconception
Dosing: 3-dose series
– 0, 2, 6 months
Quadrivalent inactivated viral vaccine
– HPV 6, 11, 16, 18
– Duration of immunity unknown
Category B
Animal studies
– 300x human dose
– No impaired fertility or fetal harm in rats
Human studies
– Limited safety evidence in pregnancy
– No difference in congenital anomalies/SAB in vaccine-exposed
pregnancies
Use in pregnancy not recommended – despite category B
Merck 2006; ACIP 2007; ACOG 2007
Measles, Mumps, Rubella
Indication: No evidence of immunity to rubella
– Immunity determined by rubella IgG antibody titer or vax documentation
– Determination of measles/mumps immunity not needed
Timing: Preconception
Dosing: Single-dose in low-risk and 2-dose in high-risk women
– MMR versus rubella vaccination recommended!!!
– 0 and 1 month for individuals at high risk for mumps/measles
Live-attenuated vaccine
– Immunity: rubella 90% >15 years, ?lifelong; measles 99% lifelong; mumps
75-95% >30 years
No rubella congenital defects reported in offspring of women
vaccinated just before or during pregnancy!
Avoid conception for 28 days after administration
Use in pregnancy not recommended
– Termination not recommended for inadvertent exposure
MMWR 1989; ACIP 1989, 2006; Bar-Oz 2004; Badilla 2007
Varicella
Indication: No evidence of immunity to varicella
– Immunity determined by varicella IgG antibody titer,
vaccination documentation, or clinical history verification
Timing: Preconception
Dosing: 2-dose series
– 0 and 4-8 weeks
Live-attenuated vaccine
No varicella congenital defects reported in offspring of
women vaccinated just before or during pregnancy!
Immunization of close contacts of pregnant women safe
Avoid conception for 28 days after administration
Use in pregnancy not recommended
– Termination not recommended for inadvertent exposure
Zoster (live) vaccine not recommended in pregnancy
ACIP 2006
Tetanus, Diphtheria, Pertussis
(Tdap)
Indication: No previous dose of Tdap and > 2 years
elapsed since last dose of Td
Timing: Preconception (Postpartum)
Dosing: Single-dose series
– Then resume Td series Q 10 years
Tetanus and diphtheria toxoids
Acellular pertussis inactivated vaccine
Limited safety and immunogenicity data in pregnancy!
Use in pregnancy not recommended
– Termination not recommended for inadvertent exposure
ACIP 2005, 2008
Immunizations
During Pregnancy
Tetanus and Diphtheria
Indication:
– Not received Primary Td 3-dose series
– Last Td booster > 10 years ago
– Major/contaminated wound and last Td booster > 5 years ago
Timing: Pregnancy (any trimester!)
Dosing:
– Primary series/3-dose: 0, 1 month, 6-12 months
– Booster/Single-dose series Q 10 years
– Booster/Single-dose if major/contaminated wound and last Td
> 5 years ago; then resume booster/single-dose Q 10 years
Tetanus and diphtheria toxoids
May consider deferring until PP to administer Tdap if
sufficient tetanus protection during pregnancy
ACIP 2008; MMRW 2008
Influenza
Indication: Influenza season (October-May)
Timing: Pregnancy (any trimester!)
Dosing: Single-dose series
Infection associated with morbid infection during
pregnancy
Use inactivated vaccine for pregnant women
No adverse fetal effects or pregnancy outcomes!
Intranasal vaccine (LAIV, FluMist): live-attenuated
– NOT recommended for use in pregnant women!!!
California mandate of thimerosal-free vaccine for
pregnant women
Harper 2004; Munoz 2005; Pool 2006
Hepatitis B
Indication: Completing hepatitis B vaccination
series or at high risk for acquiring infection
Timing: Pregnancy
Dosing: 3-dose series
– 0, 1-2, 4-6 months
Inactivated vaccine
No adverse fetal effects or pregnancy outcomes!
Hepatitis B
Efficacy
– >80% efficacy after 3 doses in general population
– 49% after 2 of 3 doses (HIV-negative pregnant women)
vs. 59-70% in non-pregnant
Factors assoc with failure to seroconvert (pregnancy)
– Smoking OR 7.5 (2.0-27.7)
– BMI  34 OR 16.2 (1.7-154.7)
– Age  25 year-old OR 3.9 (1.1-14.4)
Pre-vaccination testing (anti-HBc Ab)
– Cost-effective if prevalence > 20%
Post-vaccination testing for certain groups/revax prn
Double dose in immunocompromised
Levy 1991; Ingardia 1998; CDC 2005
Hepatitis A
Indication: Completing hepatitis A vaccination series,
PEP, or at high risk for acquiring infection
Timing: Pregnancy
Dosing: 2-dose series
– 0 and 6-12 months (Havrix) or 0 and 6-18 months (Vaqta)
Inactivated vaccine
Pre-exposure and Post-exposure prophylaxis
Pre-vaccination testing recommended in select group
Post-vaccination testing not recommended
– 94-100% effective
Limited safety data in pregnancy
– No adverse fetal effects or pregnancy outcomes reported
ACIP 2007
Immunizations
Postpartum
Postpartum Immunization
Vaccinations
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MMR
Varicella
Tdap
Influenza
Hepatitis A and B
HPV
Anti-D-immune globulin does not generally reduce the
response to MMR or varicella vaccines
– CONSIDER serologic testing 6-8 weeks after vaccination to
assure that seroconversion has occurred
May administer multiple vaccines at same time
Inactivated and live vaccines are safe in breastfeeding
– Exception: smallpox vaccine!
– Breastfeeding does not adversely affect vax success/safety
Special Considerations
Pneumococcal
Indication: High risk individuals
– Chronic diseases or immunocompromised
Timing: Preconception, pregnancy, postpartum
Dosing: Single series
– *Immunocompromised*: single revaccination if > 5
years since receipt of first dose
Inactivated vaccine
Limited safety data in pregnancy
– No reported adverse events
MMWR 2005
Pregnant Patient with
Splenectomy
Indication: Splenectomy
Timing: Preconception, pregnancy, postpartum
– Ideally 14 days prior to procedure
Vaccines
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Pneumococcal
H. influenzae
Meningococcal (MPSV4)
Influenza
Dosing:
– H. influenzae and Meningococcal (MPSV4)- Single series
– Pneumococcal- Single revaccination > 5 years from first dose
– Annually: Influenza
ALL inactivated vaccines
Immunocompromised/HIV +
Pregnant Women
Per routine pregnancy recommendations
– MMR, Tdap, and influenza
Routinely recommended
– Hepatitis A, Hepatitis B, pneumococcal
– Double Hepatitis B dose!
Not recommended unless indicated otherwise
– Meningococcal and H. influenzae
Use live-attenuated vaccines cautiously
– MMR not recommended in severely immunocompromised
(CD4 <200)
– Varicella vaccine generally not recommended, especially in
severely immunocompromised (CD4 <200)
Avoid vaccinations in 3rd trimester due to possible viral
load increase!
Traveling During Pregnancy
Yellow Fever
Indication: Travel to endemic area
– Waiver letter required during pregnancy
Timing: Avoided during pregnancy if possible
– Avoid pregnancy for 4 weeks after vaccination
Dosing: Single series
Live-attenuated vaccine
Limited safety data in pregnancy
– No increase in adverse pregnancy outcomes
– No in crease in congenital anomalies
Robert 1999; ACIP 2002; Cavalcanti 2007
Traveling During Pregnancy
Poliovirus
Indication: Travel to endemic area
Timing: Avoided during pregnancy if possible
Dosing: Primary or single booster series
– Primary/3-dose series: 0, 1-2 months, 6-12 months
– Booster/single dose if immunized
Inactivated vaccine (IPV)
Limited safety data in pregnancy
Traveling During Pregnancy
Typhoid
Indication: Travel to endemic area
Timing: Avoided during pregnancy if possible
Dosing: Single series
Inactivated vaccine
Limited safety data in pregnancy
Other Vaccines
Miscellaneous
Rabies
– Inactivated vaccine
– Pre- and post-exposure prophylaxis deemed safe
Japanese encephalitis, plague, cholera
– Inactivated vaccines
– May be considered in pregnancy
Anthrax
– Inactivated vaccine
– Vaccination in pregnancy recommended in high risk
Malaria
– Vaccines in development
Bacillus Calmette Guerin (BCG)
– Live-attenuated vaccine
– Not recommended in pregnancy
– No harmful effects demonstrated
Smallpox (Vaccinia Virus)
Contraindicated during pregnancy
– Any trimester and breastfeeding period
– Within 28 days of conception
– Close contacts
Live-attenuated vaccine
Not associated with teratogenicity
“Fetal or neonatal vaccinia infection”
– Rare (<50 cases), but lethal
– Vaccinia IG not recommended for fetal infection treatment
Case reports of maternal transmission to fetus or
infant via breast milk following vaccination
– Stop breastfeeding until area heals if vaccination indicated!!!
Wharton 2003; Garde 2004; ACIP 2001; MMRW 2001; CDC 2007
Vaccine Controversy
Autism prevalence has increased
– Changes in case definition and increased awareness
– ?Actual increase in incidence of autism
Multiple large, well-designed studies and
systematic reviews have not demonstrated link
between vaccines/MMR and autism
Studies do not demonstrate association between
vaccines and multiple sclerosis or type 1 DM
Immunization Safety Review 2004
Vaccine Controversy
Multiple large, well-designed epidemiologic
studies and systematic reviews have not
demonstrated association between thimerosal
and autism or other developmental disorders
No association b/w thimerosal and CV disease
Mercury poisoning and autism DIFFER
WHO advisory committee concluded it is safe to
continue using thimerosal in vaccines
Yoshizawa 2002; WHO 2002; Hviid 2003; Thompson 2007
Thimerosal-Containing
Adult Vaccines
DTap (Tripedia)
– Tdap- thimerosal free!!!
DT
Td
– Except 1 of 2 Sanofi Pasteur vaccines (thimerosal-free)
TT
Hep A/Hep B combined vaccine (Twinrix)
Influenza
– Except Fluzone (thimerosal-free; used in CA in pregnancy)!!!
– Except FluMist (thimerosal-free; live attenuated)
Japanese encephalitis
Meningococcal (Menomune A, C, AC, A/C/Y/W-135)
CDC 2007
Summary
Preconception Immunizations
HPV
MMR
Varicella
Tdap
Summary
Pregnancy Immunizations
Td
Influenza
Hepatitis B
Hepatitis A
Others
– Pneumococcal
– Meningococcal
– H. Influenzae
Summary
Postpartum Immunizations
MMR
Varicella
Tdap
Influenza
Hepatitis A and B
HPV
Summary
Travel Immunizations
Tetanus and diphtheria
Hepatitis A and B
Measles
Influenza
Meningococcus
Japanese and tick-borne encephalitis
Yellow Fever
Poliovirus (IPV)
Typhoid
Rabies
General Summary
Live-attenuated vaccinations
– Little or no data demonstrating harm to fetus
– Termination not recommended for inadvertent
exposure!
Vaccinations (live-attenuated and inactivated)
generally safe during breastfeeding
Smallpox vaccine only reserved for emergency
indications during pregnancy or breastfeeding
Studies do not demonstrate association
between vaccinations/thimerosal to autism or
other diseases
Immunization Resources
http://www.cdc.gov/vaccines
http://www.cdc.gov/nip/vacsafe/concerns/autism
http://www.cdc.gov/vaccines/recs/ACIP
– Advisory Committee on Immunization Practices (ACIP)
http://www.immunize.org/vw
– Immunization Action Coalition (IAC)
– IAC Express email notices, “Vaccinate Women” publication
– Ob/Gyn providers
http://www.ca-siis.org
– California Immunization Registry (CAIR)
California Immunization Registry
CAIR = Statewide Immunization Information System
CA statewide immunization registry network
9 multi-county regional immunization registries
Computerized registry system for provider entered info
– Assist providers to track patient records
– Reduce missed opportunities
– Fully immunize all children in California
Schools, childcare centers, and WIC can link into
regional registries
Ultimate goal to integrate 9 regional district
http://www.ca-siis.org
Vaccine Registries
Inadvertent Immunizations During Pregnancy
All vaccinations (general)
– VAERS: Vaccine Adverse Event Reporting System
– 800-822-7967; www.vaers.org
HPV Quadrivalent Vaccine
– Gardasil/Merck
– 1-800-986-8999
Rubella Vaccine in Pregnancy Registry- discontinued in 1989
Varicella
– VARIVAX Pregnancy Registry
– 800-986-8999
Tdap
– BOOSTRIX/GlaxoSmithKline Biologicals (1-888-825-5249)
– ADACEL/Sanofi Pasteur at (1-800-822-2463 or 1-800-VACCINE)
Smallpox
– Centers for Disease Control and Prevention
– Smallpox Vaccine in Pregnancy Registry
– 404-639-8253
UCSF Reproductive Infectious Disease
Consult Service
1-415-719-8726
Free
24-hour availability
For medical providers seeking assistance
in management of reproductive infectious
disease and perinatal HIV issues
Acknowledgements
Julian Parer, MD, PhD
Tekoa King, CNM, MPH
Judith Bishop, CNM, MSN, MPH
Aaron Caughey, MD, MPP, MPH, PhD
Irené Merry and UCSF CME office
Deborah Cohan, MD, MPH