1. Vaccines, Pregnancy and Breast-feeding Support for this program is made possible by the AAFP Foundation through a grant from Pfizer Inc.

2. Vaccines, Pregnancy and Breast-feeding Developed for AFMRD by Gail Colby, M.D. and Wendy Biggs, M.D. Midland Family Medicine Residency 2010 Ehab Molokhia, MD and Gerald Liu, MD University of South Alabama Family Medicine Residency Updated 2012

3. Vaccines, Pregnancy and Breast-feeding Objectives Medical knowledge –List 3 most common live attenuated vaccines –State vaccines that are CONTRAINDICATED for administration during pregnancy –List the vaccine that Advisory Committee on Immunization Practices (ACIP) recommends be given to all pregnant patients –Recognize vaccines high-risk women should receive

4. Vaccines, Pregnancy and Breast-feeding Objectives Patient care –Assess a pregnant woman’s immunization status –Administer indicated tetanus-diphtheria- pertussis vaccination Interpersonal communication –Recognize the prenatal visit as an opportunity to discuss vaccine indications with patient

5. Vaccines, Pregnancy and Breast-feeding Vaccines in Pregnancy The pregnant woman is at increased risk for severe illness from some vaccine-preventable illnesses –Example: H1N1 influenza in 2009-10 Pregnant women who contracted H1N1 in 2009 were more likely to need hospitalization and had increased morbidity and mortality MMWR Morb Mortal Wkly Rep. 2010 Mar 26;59(11):321-6. 2009 pandemic influenza A (H1N1) in pregnant women requiring intensive care – New York City, 2009..

6. Vaccines, Pregnancy and Breast-feeding Vaccines in Pregnancy Pre-conception counseling on immunizations is ideal If pre-conception counseling not done, prenatal visits are opportunity to discuss and administer recommended vaccinations

7. Vaccines, Pregnancy and Breast-feeding Vaccines in Pregnancy Passive immunity by trans-placental transfer of antibodies may protect vulnerable neonates –Vaccinating pregnant women in third trimester for influenza Decreased respiratory illness with fever 36% within first 6 months of life Infants born to vaccinated women had 63% decreased incidence of lab-confirmed influenza Zaman Z, et al. Effectiveness of maternal influenza immunization in mothers and infants. N Engl J Med; 2008; 359:1555-64.

8. Vaccines, Pregnancy and Breast-feeding Vaccine Benefits in Pregnancy Benefits outweigh risks when –Likelihood of disease exposure is high Example: Pertussis in the household –Infection would pose a risk to mother Example: H1N1 influenza –Infection would pose a risk to fetus Example: Maternal hypoxia from severe influenza –Vaccine is unlikely to cause harm Example: Inactivated vaccines

9. Vaccines, Pregnancy and Breast-feeding Obstacles to Vaccines in Pregnancy Mothers may refuse vaccinations –Wish to avoid any potential “exposures” to fetus in utero –Public misconception of vaccines Perceived as “dangerous” –e.g. H1N1 influenza vaccine in 2009 –Thimerosal ACOG states (2009) “benefits of vaccines outweigh any unproven potential concerns about traces of thimerosal preservative”

10. Vaccines, Pregnancy and Breast-feeding Obstacles to Vaccines in Pregnancy Public perception that only “FDA- approved” vaccines for pregnancy should be given –None are pregnancy category A –Only bivalent HPV is pregnancy category B –Anthrax is category D –All others are category C H1N1 and seasonal influenza are category C

11. Vaccines, Pregnancy and Breast-feeding Guidelines for Vaccinating Pregnant Women For most vaccines –Recommendations from the Advisory Committee on Immunization Practices (ACIP) Published update May 2007 Available at www.cdc.gov/vaccines/pubs/pregguide.htm www.cdc.gov/vaccines/pubs/pregguide.htm Updates for specific vaccines published on-line –e.g. H1N1 influenza (www.cdc.gov/h1n1flu)www.cdc.gov/h1n1flu

12. Vaccines, Pregnancy and Breast-feeding ACIP Vaccine Recommendations in Pregnancy Vaccines classified as –“Recommended” –“Consider if otherwise indicated” –“Recommended to avoid”

13. Vaccines, Pregnancy and Breast-feeding Vaccine Safety in Pregnancy Live vaccines are CONTRAINDICATED by ACIP during pregnancy However, risk of live vaccines is theoretical –No direct evidence against transmission of any common live vaccines (e.g. MMR, Varicella, nasal influenza) Ref: www.cdc.gov/vaccines/pubs/preg-guide.htm#19www.cdc.gov/vaccines/pubs/preg-guide.htm#19 –Smallpox (vaccinia) only vaccine proven to be transmitted to fetus (vaccine not distributed) –Avoidance of live vaccines is based on theory only

14. Vaccines, Pregnancy and Breast-feeding Vaccine Safety in Pregnancy No evidence of fetal risk with –Inactivated vaccines e.g.Inactivated influenza –Bacterial vaccines e.g. Meningococcal –Toxoid vaccines e.g. Td (tetanus-diphtheria)

15. Vaccines, Pregnancy and Breast-feeding Live Vaccines Measles, Mumps and Rubella (MMR) Varicella (chickenpox) Live attenuated influenza (intranasal spray flu vaccine) Zoster (for shingles) BCG (for tuberculosis, not done in U.S.) Vaccinia (smallpox)

16. Vaccines, Pregnancy and Breast-feeding Live Vaccines and Pregnancy Avoid pregnancy for 28 days after MMR and/or varicella vaccine If found to be pregnant when vaccine given, counsel patient on theoretical risk –Not an indication for termination

17. Vaccines, Pregnancy and Breast-feeding 25 year old G2P1 woman presents for her first prenatal visit. Your nurse ordered routine prenatal lab tests. Her blood type is A negative. She is rubella non-immune. She tells you she was rubella immune last pregnancy. You review her immunization history. Case

18. Vaccines, Pregnancy and Breast-feeding What questions do you need to ask her? Case

19. Vaccines, Pregnancy and Breast-feeding 1.Did she have routine childhood immunizations? –Yes, most states require children to have up-to- date immunizations prior to school entry 2.Did she get booster shots as an adolescent? Which ones? –Got tetanus-diphtheria (Td) at 14 years old Case Questions

20. Vaccines, Pregnancy and Breast-feeding 3.Did she have chickenpox as a child? –Yes –If she was unsure about her chickenpox status, Varicella IgG should be checked –If negative – varicella vaccine postpartum at same time as MMR and Anti-D (Rhogam ® ) Case Questions

21. Vaccines, Pregnancy and Breast-feeding 4.Why is the patient non-immune to rubella? –Responded to MMR but antibody titer now at low level Rubella antibody may decline over time below detection level of standard tests –If non-immune in her first pregnancy, perhaps failed to respond to original immunization series Occurs 1-2/1000 even with proper timing of series Case Questions

22. Vaccines, Pregnancy and Breast-feeding 5.Is she at increased risk for rubella? –Most likely NOT –Even with waning immunity, increased susceptibility to rubella does not occur Studies of people with “lost” detectable rubella antibody –Most had antibody levels with more sensitive tests –Respond with rapid IgG antibody rise to booster after re-vaccination with MMR Case Questions

23. Vaccines, Pregnancy and Breast-feeding Measles, Mumps and Rubella (MMR) She is Rh negative, received Anti-D Immunoglobuin (Rhogam ® ) at 28 weeks, and now needs Rhogam ® post-partum How does this affect giving MMR? –Anti-D Immunoglobuin (Rhogam ® ) can be administered in a different limb simultaneously with MMR –If not given simultaneously, then MMR should be given 3 months after Anti-D Immunoglobuin (Rhogam ® )

24. Vaccines, Pregnancy and Breast-feeding Measles, Mumps and Rubella (MMR) Your patient receives Rhogam ® and an MMR simultaneously after delivery Should you do any follow-up? –Yes. Rubella IgG antibody titers should be checked 3 months later for immunity.

25. Vaccines, Pregnancy and Breast-feeding Measles, Mumps and Rubella (MMR) How does an Rh negative infant change the mother’s management? –She does not need Anti-D Immunoglobulin (Rhogam ® ) post-partum –She still needs MMR –Titers for rubella IgG should be checked 6 weeks after MMR given

26. Vaccines, Pregnancy and Breast-feeding What about Tetanus- Diphtheria (Td)? Health care providers should assess a pregnant woman’s tetanus immunization status. Your patient got a tetanus shot at 14 years old (11 years ago) –Indications to update tetanus immunization No Td vaccination within the last 10 years No completed primary childhood series (4 or 5 doses of pediatric tetanus-diphtheria)

27. Vaccines, Pregnancy and Breast-feeding What about Tetanus- Diphtheria (Td)? Is your patient’s tetanus protection “presumed sufficient? ” “Presumed sufficient” if –Younger than 31 years and received complete childhood series and at least 1 booster of Td as an adolescent or adult –Older than 31 years and received complete childhood series and at least 2 Td boosters. –Tetanus titer protective (>0.1 IU/ml by ELISA)

28. Vaccines, Pregnancy and Breast-feeding What about Pertussis? Pertussis incidence is increasing Use of Tdap to booster tetanus, diphtheria, and pertussis is a “consider if otherwise indicated” recommendation by ACIP Pregnancy is NOT a contraindication for use of Tdap

29. Vaccines, Pregnancy and Breast-feeding What about Pertussis? Should your patient get Tdap or Td during pregnancy? What other information do you need to know? –Where does she work? –How old is her other child? –Is there pertussis in the community?

30. Vaccines, Pregnancy and Breast-feeding Pertussis Considerations Consider giving Tdap to pregnant women at high-risk of pertussis exposure –Health care providers –Child care providers –Caregiver of infant younger than 12 months –Community has known pertussis activity –Adolescents

31. Vaccines, Pregnancy and Breast-feeding Pertussis Considerations Waiting until second trimester of pregnancy to give Tdap is reasonable precaution to minimize patients’ concerns of risks –Acellular pertussis is not-live –Presumed safe in pregnancy –However, patients may be concerned recalling whole cell pertussis vaccine previously available

32. Vaccines, Pregnancy and Breast-feeding Pertussis Considerations Passive immunity to pertussis (trans- placental transfer of antibodies) from Tdap may be insufficient to protect infant Theoretically, maternal Tdap could interfere with neonatal pertussis vaccine response –No studies proving this occurs

33. Vaccines, Pregnancy and Breast-feeding Tetanus-Diphtheria and Pertussis Women with incomplete childhood series –2 doses of Td separated by 4 weeks –Tdap postpartum 6 to 12 months after the second Td dose http://www.cdc.gov/vaccines/pubs/preg-guide.htm#19

34. Vaccines, Pregnancy and Breast-feeding Tetanus-Diphtheria and Pertussis If >2 years and <10 years since last Td –Give Tdap immediately postpartum If >10 years since last Td and “presumed sufficient” tetanus immunity –Give Tdap immediately postpartum There is an increased risk of local reactions if Tdap given <2 years from previous Td

35. Vaccines, Pregnancy and Breast-feeding 6.Based on this information, are you going to give your patient Td or Tdap? –Tdap 7.When? –Post-partum 8.Why? –This patient is presumed to have sufficient tetanus protection because she is younger than 31 years old, had a complete childhood series and had a booster of Td at age 14. Case Questions

36. Vaccines, Pregnancy and Breast-feeding Recommended Vaccine in Pregnancy Only one vaccine is in the Advisory Committee on Immunization Practice’s (ACIP’s) “recommended” category. –Which is it? INFLUENZA –Should this patient get it? YES

37. Vaccines, Pregnancy and Breast-feeding Recommended Vaccination Influenza vaccine is RECOMMENDED for women who are pregnant or may become pregnant during flu season –Seasonal influenza – H1N1 –NOT THE LIVE-ATTENUATED INFLUENZA VACCINE (nasal spray)

38. Vaccines, Pregnancy and Breast-feeding According to Advisory Committee on Immunization Practices (ACIP) Other vaccines “Should be considered if otherwise indicated” –Hepatitis B –Meningococcal –Rabies

39. Vaccines, Pregnancy and Breast-feeding Hepatitis B Hepatitis B vaccine should be considered for high-risk pregnant women Risk factors for Hepatitis B –More than one sexual partner in the previous 6 months –Current or past history of sexually transmitted infection –Recent or current injection drug use –Having a Hepatitis B Ag-positive sex partner

40. Vaccines, Pregnancy and Breast-feeding Meningococcal No data available Bacterial vaccine presumed safe If a woman is pregnant at the time of vaccination, a registry for pregnancy outcome surveillance exists

41. Vaccines, Pregnancy and Breast-feeding Human Papilloma Virus (HPV) Quadrivalent HPV (Gardasil ® ) is not recommended for use in pregnancy If a quadrivalent HPV vaccine given, delay remainder of series until after delivery Bivalent HPV (Cervarix ® ) is category B and may be used in pregnancy

42. Vaccines, Pregnancy and Breast-feeding Rabies No indication of fetal adverse effects to rabies vaccines 90-95% mortality to untreated rabies Pregnant women bitten by potentially rabid animal should receive post- exposure rabies prophylaxis

43. Vaccines, Pregnancy and Breast-feeding Recommended to Avoid Live-attenuated viruses –MMR –Varicella (Varivax ® ) –Zoster (Zostavax ® ) –Vaccinia (Smallpox) –Yellow Fever

44. Vaccines, Pregnancy and Breast-feeding Recommended to Avoid Inactivated Polio –Vaccination should be avoided on theoretical grounds –If a woman requires immediate protection against polio, administer IPV according to recommended schedules

45. Vaccines, Pregnancy and Breast-feeding Yellow Fever Only if travel to an endemic area is unavoidable Antigen appears to cross placenta in low level, but no congenital anomalies associated

46. Vaccines, Pregnancy and Breast-feeding Breast-Feeding No vaccines affect breast-feeding safety Breast-feeding does not diminish vaccines’ effectiveness Giving a vaccine during breast-feeding theoretically may protect infant Any routine vaccine can be given –(except smallpox)

47. Vaccines, Pregnancy and Breast-feeding Summary Medical knowledge –ACIP recommends influenza vaccine (both seasonal and H1N1) during pregnancy –No live-attenuated vaccines should be administered to pregnant women (MMR, varicella, nasal spray influenza) –High-risk women should receive Hepatitis B vaccine

48. Vaccines, Pregnancy and Breast-feeding Summary Medical knowledge –Bivalent HPV (Cervarix ® ) is category B and may be given during pregnancy –Quadrivalent HPV (Gardasil ® ) is currently not approved for use during pregnancy

49. Vaccines, Pregnancy and Breast-feeding Summary Patient care –Tetanus-diphtheria (Td) should be up-to-date (within 10 years) or booster should be given –Delay Td and give Tdap immediately post-partum if >10 years since last Td and “presumed sufficient” tetanus immunity –If Td series is incomplete, it should be updated during pregnancy –If >2 years but <10 years since last Td, give Tdap (Tetanus-diphtheria and acellular pertussis) immediately postpartum

50. Vaccines, Pregnancy and Breast-feeding Summary Patient care –Prenatal visits are an excellent time to assess immunization status –Update necessary vaccines at prenatal visits Interpersonal communication –Physicians should discuss all immunization risks and benefits, especially Tdap, with patients