1. Perinatal Hepatitis B Program: How Far Have We Come? Eric E. Mast, MD, MPH Chief, Prevention Branch Division of Viral Hepatitis 41 st National Immunization Conference Kansas City, MO March 8, 2007

2. Outline Progress implementing perinatal hepatitis B prevention programs Existing program gaps New ACIP recommendations Next steps

3. Background ~23,000 infants born to HBsAg-positive mothers in 2003 Without immunoprophylaxis: – ~6300 chronically infected with HBV (most asymptomatic) – ~1550 expected to die of chronic liver disease Postexposure immunization beginning at birth is 85%-95% effective in preventing perinatal HBV transmission Perinatal HepB prevention programs very cost-effective: – $3 saved (medical and work-loss costs) for every $1 spent (program costs) – 1 death prevented for every 15 infants of HBsAg-positive mothers who are identified and given post-exposure immunoprophylaxis

4. National Immunzation Program funding since 1990 61 projects (50 states, 6 cities, 5 territories) Identification of HBsAg-positive pregnant women Case-management and tracking infants born to HBsAg positive mothers to assure: –HBIG and hepatitis B vaccine at birth –completion of vaccination by 6 months of age –post-vaccination serologic testing Identification/vaccination of susceptible HH/sex contacts Perinatal Hepatitis B Prevention Programs

5. Prevent perinatal HBV transmission Universal infant vaccination, beginning at birth Catch-up vaccination of all children and adolescents <19 years Vaccination of adults in high risk groups Advisory Committee on Immunization Practices Strategy to Eliminate HBV Transmission

6. Percent of Pregnant Women Screened Prenatally, 2004 ≥95% (n=37) 90-94% (n=8) <90% (n=7) unknown (n=12) NYC Philadelphia Houston San Antonio Chicago D.C. Am. Samoa Guam N. Mariana Is. Puerto Rico Virgin Islands National estimate: 93%-97%

7. Completion of Follow-up For Infants of HBsAg Positive Mothers, 1993-2004 Source: National Immunization Program, CDC HBIG/vaccine at birth 3 doses by 6-8 months Postvaccination testing 95% 70% 52%

8. Estimated New Perinatal Chronic HBV Infections United States, 1990-2005 >85% decline

9. Perinatal Hepatitis B Prevention Program Gaps Identification of HBsAg-positive mothers ~50% of expected infants born to HBsAg-positive mothers identified for case-management Higher rates of administration of HBIG at birth, completion of vaccine series among infants who receive case management Management of infants of mothers w/unknown HBsAg status Failure to test for HBsAg at time of delivery Failure to administer hepatitis B vaccine at birth Tracking infants born to identified HBsAg-positive mothers Failure to administer appropriate post-exposure prophylaxis

10. Identified and Expected Births to HBsAg-Positive Mothers, United States, 1993-2003 Expected number Percent identified Source: National Immunization Program, CDC

11. Estimated New Chronic HBV Infections by Place of Acquisition, United States, 1990-2005 United States Immigrants from other countries

12. Post-Exposure Immunization by Receipt of Case Management State (yrs) Case managementNo.(%) HBIG and HepB at birth No. (%) Complete series by 8 mo No. (%) AlabamaYes982 (78)905 (92)828 (90) (1990-2002)No318 (22)212 (67)189 (59) ConnecticutYes64 (52)64 (100)52 (90) (1994-1995)No58 (48)52 (90)189 (48) Sources:Brian Wheeler, Alabama Department of Public Health, 2004 MMWR 1996;45:584-7

13. HepB Birth Dose Coverage among Infants Born to Women with Unknown HBsAg Status StudyYear No. of infants identified Vaccinated at birth, (%) National1993640(22) Washington1994125(53) California1995200(20) Florida199538(29) Ohio199535(66) Oregon200043(19) Michigan200057(14)

14. HBsAg Prevalence among Pregnant Women by Prenatal Screening Status, Philadelphia, 1991 Prenatal Screening No. of Women TestedNo. (%) HBsAg-positive Yes155512 (0.8) No20814 (6.7) Source: JAMA 1991;266:2852-5

15. Medical Errors in Prevention of Perinatal HBV Transmission July 1999-October 2002: >500 medical errors in prevention of perinatal HBV transmission reported by state/local heath departments Examples: ― Infants born to HBsAg-positive mothers did not receive HepB and HBIG within 12 hrs of birth ― Infants born to mothers with unknown HBsAg status did not receive HepB within 12 hrs of birth ― HBsAg screening test results misordered, misinterpreted, mistranscribed, or miscommunicated ― Ordering wrong hepatitis B screening test Source: Immunization Action Coalition

16. Perinatal Hepatitis B Death - Michigan Baby girl; DOB: 9/99 Died: 12/99; Cause - fulminant hepatitis B Mother tested HBsAg-positive during pregnancy Prenatal care provider – Made a transcription error and reported mother as “hepatitis negative” to the hospital – Used prenatal record form from 1966 – Did not report HBsAg-positive test (Michigan law) Hospital staff – Relied on written record from prenatal provider – Did not have a copy of mother’s laboratory result – Had suspended administration of HepB birth dose for all newborns because of thimerosal concern

17. New ACIP Hepatitis B Vaccine Recommendations for Infants, Children, and Adolescents Standing orders for HepB at birth Delivery hospital policies/procedures and case management programs to ensure: −All pregnant women tested for HBsAg −Identification and management of infants of HBsAg positive mothers infants of mothers w/unknown HBsAg status

18. Next Steps For Perinatal Hepatitis B Prevention Programs I Work with hospitals to achieve: Universal birth dose coverage; documentation of birth dose in an immunization information system Policies and procedures for identification and management of infants born to – HBsAg positive mothers – mothers w/unknown HBsAg status Improve identification of HBsAg-positive pregnant women: Incorporation of HBsAg testing in standard prenatal panels Reporting of HBsAg-positive laboratory results Universal reporting mechanisms (e.g., Newborn metabolic screening card, birth certificate)

19. Next Steps For Perinatal Hepatitis B Prevention Programs II Strengthen case management of HBsAg positive mothers and their infants Increase rates of postvaccination testing Referral of HBsAg-positive women for medical care Strengthen monitoring and evaluation: Reasons for discrepancies between expected and identified HBsAg-positive pregnant women Appropriate care of infants born to mothers with unknown HBsAg status Reporting of HBsAg-positive infants

20. Summary and Conclusions Substantial progress has been made in implementing perinatal hepatitis B prevention programs – >85% decline in perintatal HBV infections There will be ongoing need for these programs for the forseeable future – number of HBsAg-positive mothers increasing as a result of immigration from countries with high endemicity Prevention gaps: – identification of HBsAg-positive mothers – management of infants of mothers w/unk HBsAg status – tracking infants born to HBsAg-positive mothers Need for renewed focus on perinatal hepatitis B prevention

21. Hepatitis B Vaccine Birth Dose Coverage*, 2004 <30 30-39 9 No. of states Coverage % 7 40-49 50-59 5 60-6915 70-795 >802 *0-2 days after delivery 7

22. Evaluation Needs Perinatal Hepatitis B Prevention Program Requirements 5.1 Establish a mechanism to identify all HBsAg-positive pregnant women. – Conduct case management of all identified infants at risk of acquiring perinatal hepatitis B infection which includes administration of appropriate immunoprophylaxis is administered to all infants born to HBsAg-positive women [including hepatitis B immune globulin (HBIG), hepatitis B vaccine birth dose, and complete vaccine series]. completion of post-vaccination serologic testing of all infants born to HBsAg-positive women and reporting of all HBsAg-positive infants to CDC through the National Notifiable Disease Surveillance System (NNDSS). – Evaluate completeness of identification of HBsAg-positive pregnant women, case management, reporting of HBsAg-positive infants, and appropriate care of infants born to HBsAg-unknown status mothers based on methodology provided by CDC. – Establish and examine feasibility to implement a state plan to implement a universal reporting mechanism with documentation of maternal HBsAg test results for all births. – Work with hospitals to achieve universal birth dose coverage and documentation of the birth dose in an IIS.

23. Hepatitis B Vaccine Birth Dose Coverage by State Universal Birth Dose Policy, 2004 Universal Birth Dose Policy No. of States* Birth Dose Coverage Median (range) Yes28 64% (23% - 83%) No20 38% (5% - 69%) *Unknown for 2 states

24. Perinatal Hepatitis B Prevention Historical Perspective 1965 – Blumberg et al - Discovery of Austrailia antigen 1972 – Schwietzer et al – Natural history study demonstrates HBV transmission from mother to infant – 1976, Okada et al: 90% transmission from HBeAg-positive mothers, XX% transmission from HBeAg negative mothers 1974 – Kohler et al – Administration of anti-HBs prevents chronic HBV infection in infants born to HBsAg postive mothers – 1983 – Beasley et al - Postexposure prophylaxis with HBIG demonstrated to prevent perinatal HBV transmission – 1984 – Wong et al

25. Hospital Survey Findings

26. Chronology of ACIP Perinatal Hepatitis B Prevention Recommendations 1977 – Infants born to mothers with acute hepatitis B in the third trimester of pregnacy and HBsAg seropositivity at the time of delivery may be given either HBIG or IG within 7 days of birth 1981 – All infants born to HBsAg-positive mothers should receive HBIG within 24 hours after birth 1982 – Infants born to HBsAg-positive mothers should receive HBIG at birth and HepB vaccine beginning at 3 months of age 1985 – – Mothers belonging to risk groups should be tested for HBsAg – HBIG and HepB vaccine within 12 hours of birth 1988 – All pregnant women should be screened for HBsAg 1991 – Routine infant hepatitis B vaccination recommended 2002 – Preference for birth dose recommended 2005 – Universal birth dose recommended

27. Hepatitis B Vaccination Coverage 19-35 Months of Age United States, 1992-2003 Source: National Immunization Survey, CDC Routine infant vaccination recommended

28. Perinatal Hepatitis B Prevention Programs Year 2000 Disease Reduction Goals 90% of pregnant women screened for HBsAg 90% of births to HBsAg-positive mothers identified 90% of infants born to HBsAg-positive mothers –receive HBIG and HepB at birth –complete HepB series by age 6-8 mo

29. Effectiveness of Case-Management For Infants Born to HBsAg-Positive Mothers, Alabama, 1990-2002 Case ManagementNo. (%) HBIG and HepB vaccine within 24 h No. (%) Completion of 3-dose series by 8 mo No. (%) Yes982 (78)905 (92.2)828 (89.8) No (Linkage of all birth certificates with HBsAg registry) 318 (22)212 (66.7)189 (59.2) Source: Brian Wheeler, Alabama Department of Public Health

30. Rationale for Identification of HBsAg Positive Persons Primary prevention Enhance immunization strategies to eliminate HBV transmission by vaccinating at risk contacts Prevent transmission in health care settings – blood, organ, tissue donors – dialysis patients Secondary prevention Reduce risks for chronic liver disease in infected persons by providing medical management and antiviral therapy

31. Delivery hospital standing orders to ensure identification of and immunoprophylaxis for –infants born to HBsAg-positive mothers –infants born to mothers with unknown HBsAg status Case management programs to assure: –HBsAg testing of all pregnant women –Reporting and tracking of HBsAg-positive women and their infants Standing orders for administration of hepatitis B vaccine as part of routine medical care for all medically stable infants weighing ≥2,000 grams at birth. New ACIP Recommendations New Implementation Recommendations

32. Proportion of Infants Receiving Hepatitis B Vaccine Birth Dose, 1999-2003 0-7 days 0-2 days Source: National Immunization Survey

33. Perinatal Hepatitis B Prevention Program Evaluation Partnership with DHAP – Perinatal ID screening assessment project (RTI) sampling frame: 15 states, live births in 2003 ~24,000 maternal medical records for 3 states, neonatal medical records will be examined status: piloting in first state Partnership with DBMD – Evaluation of adherence to 2002 perinatal Group B Strep disease prevention guidelines project secondary objective: evaluate adherence to screening recommendations for other infections, including HBV sampling frame: 10 Active Bacterial Core (ABCs) surveillance locations, live births in 2003 and 2004 ~5000 maternal labor and delivery records status: obtaining human subjects approvals/HIPAA waivers

34. National Survey of Perinatal Hepatitis B Prevention Policies and Practices in Hospitals, 2005-2006 Objectives: Evaluate maternal HBsAg screening and newborn HepB vaccination policies/practices Assess factors associated with lack of screening and vaccination Data collection: Random sample of 242 hospitals w/ ≥100 annual births Questionnaire mailed March 2006 to obstetric nurse managers −perinatal hepatitis B prevention policies/practices Review of 25 paired maternal/infant medical records: −maternal HBsAg screening results −administration of HepB vaccine and HBIG to infants Findings: Scheduled to be presented at 2007 National Immunization Conference (March 5-8, Kansas City)

35. Estimated HBsAg Positive Pregnant Women Among Women Not Tested Prenatally, 2003 HBsAg prevalence in women not tested prenatally Estimated HBsAg Prevalence, % Estimated HBsAg positive No. (%) Same as pregnant women tested prenatally 0.6%1,191 (5) 8X higher than pregnant women tested prenatally* 3.6%7,244 (30) Total23,827 *JAMA 1991;266:2852-5

36. Live Births, All Races and Asian/Pacific Islander United States, 1985-2002 All Races Asian/Pacific Islanders 210,907 5.2% 104,606 2.8%

37. Newborn 18% Children 18% Adolescent 6% Adult 59% Sources: National Health and Nutrition Examination Survey III N Engl J Med 1989;321:1301-5 Pediatrics 1992;89:269-73 Pediatrics 1995;96:1113-6 Estimated Age at Infection of Persons With Chronic HBV Infection Before Childhood Vaccination, United States