The National Perinatal Hepatitis B Prevention Program, 19942008 Emily A. Smith, Lisa Jacques-Carroll, Tanja Y.

Walker, Barry Sirotkin and Trudy V. Murphy Pediatrics 2012;129;609; originally published online March 26, 2012; DOI: 10.1542/peds.2011-2866

The online version of this article, along with updated information and services, is located on the World Wide Web at:
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2012 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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The National Perinatal Hepatitis B Prevention Program, 19942008

AUTHORS: Emily A. Smith, MPH,a Lisa Jacques-Carroll, MSW,b Tanja Y. Walker, MPH,a Barry Sirotkin, MS,c and Trudy V. Murphy, MDa
aDivision of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, bImmunization Services Division, National Center for Immunization and Respiratory Diseases, and cOfce of the Director, Ofce of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia

WHATS KNOWN ON THIS SUBJECT: Infants born to women who are hepatitis B surface antigenpositive have a 90% risk of chronic hepatitis B virus infection, which may cause premature death from liver failure or cancer. Postexposure prophylaxis in infancy prevents 85% to 95% of perinatal infections. WHAT THIS STUDY ADDS: The Perinatal Hepatitis B Prevention Program was created to identify and manage infants born to women who are hepatitis B surface antigenpositive. We provide, for the rst time since 1996, national-level data on the outcomes of the Perinatal Hepatitis B Prevention Program.

KEY WORDS hepatitis B, immunization programs, infant, newborn diseases, infectious disease transmission, pregnancy complicationsinfectious, United States ABBREVIATIONS ACIPAdvisory Committee on Immunization Practices APIAsian/Pacic Islander CDCCenters for Disease Control and Prevention HBIGhepatitis B immunoglobulin HBsAghepatitis B surface antigen HBVhepatitis B virus HepBhepatitis B vaccine NHANESNational Health and Nutrition Examination Survey PHBPPPerinatal Hepatitis B Prevention Program Ms Smith analyzed the data from Perinatal Hepatitis B Prevention Programs, calculated estimated births to Hepatitis B surface antigenpositive women, and drafted and revised the article; Ms Jacques-Carroll collected and analyzed the data from Perinatal Hepatitis B Prevention Programs, calculated estimated births to Hepatitis B surface antigenpositive women, and revised the article; Ms Walker collected and analyzed the data from Perinatal Hepatitis B Prevention Programs and revised the article; Mr Sirotkin collected and analyzed birth data from the National Center for Health Statistics for the calculation of estimated births to Hepatitis B surface antigenpositive women; and Dr Murphy initiated the project, assisted in data analysis, and critically revised the article for publication. www.pediatrics.org/cgi/doi/10.1542/peds.2011-2866 doi:10.1542/peds.2011-2866 Accepted for publication Dec 14, 2011 Address correspondence to Emily A. Smith, MPH, Centers for Disease Control and Prevention/NCHHSTP, 1600 Clifton Rd NE, MS G-37, Atlanta, GA 30329. E-mail: esmith6@cdc.gov PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright 2012 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no nancial relationships relevant to this article to disclose. FUNDING: This research was supported in part by an appointment to the Research Participation Program at the Centers for Disease Control and Prevention administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the Centers for Disease Control and Prevention.

abstract
OBJECTIVE: To determine the trends and outcomes of the national Perinatal Hepatitis B Prevention Program (PHBPP) for infants born from 1994 to 2008. METHODS: PHBPPs in state and city public health jurisdictions annually submitted program outcome reports to the Centers for Disease Control and Prevention. The annual number of births to hepatitis B surface antigen (HBsAg)-positive women was estimated and used to evaluate the percentage of PHBPP-identied HBsAg-positive pregnant women. PHBPP reports were used to assess program objectives achieved, and infant outcomes by 12 to 24 months of age. RESULTS: From 1994 to 2008, the estimated number of annual births to HBsAg-positive women increased from 19 208 to 25 600 (P , .001). The annual number of PHBPP-managed infants increased (P , .001), comprising 40.8% to 50.5% of the estimated number. On average, 94.4% of PHBPP-managed infants received hepatitis B immunoglobulin and hepatitis B vaccine within 1 day of birth. The percentage of infants who completed the vaccine series by age 12 months decreased from 86.0% to 77.7% (P = .004), but the percentage who received postvaccination testing increased from 25.1% to 56.0% (P , .001). Incidence of chronic hepatitis B virus infection among tested infants decreased from 2.1% in 1999 to 0.8% in 2008 (P = .001). CONCLUSIONS: The PHBPP achieved substantial progress in preventing perinatal hepatitis B virus infection in the United States, despite an increasing number of at-risk infants. Signicant gaps remain in identifying HBsAg-positive pregnant women, and completing management and assessment of their infants to ensure prevention of perinatal hepatitis B virus transmission. Pediatrics 2012;129:609616

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Infants born to women who are hepatitis B surface antigen (HBsAg)-positive are at high risk of hepatitis B virus (HBV) infection.1,2 Perinatally infected infants have a 90% risk of chronic HBV infection,3 which results in progressive, asymptomatic damage to the liver. Approximately 15% to 25% of chronically infected infants risk premature death from liver failure or hepatocellular carcinoma.4 Postexposure prophylaxis, consisting of hepatitis B immunoglobulin (HBIG) and hepatitis B (HepB) vaccine administered at birth, followed by 2 to 3 additional doses of HepB vaccine, is 85% to 95% effective in preventing perinatal chronic HBV infection.5 Since 1984, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) has recommended that infants of HBsAg-positive women receive HBIG and HepB vaccine within 12 hours of birth.6 In 1988, ACIP recommended that all pregnant women receive HBsAg screening to ensure that infants born to HBsAg-positive women are identied for postexposure prophylaxis.7 In 1990, ACIP recommended that these infants receive serologic testing (HBsAg and antibody to hepatitis B surface antigen) 1 to 2 months after completing the HepB vaccine series to determine their outcomes (hepatitis B immunity by vaccination, nonresponse to vaccination, or chronic HBV infection) and future management.8 ACIP recommends the small percentage (,10%) of infants who fail to respond to an initial HepB vaccine series and remain uninfected9 receive an additional HepB vaccine series and repeat postvaccination serology.10,11 The CDC created the US Perinatal Hepatitis B Prevention Program (PHBPP) in 1990 to accelerate progress toward the eliminationofperinatalHBVtransmission. The PHBPP aimed to ensure screening of all pregnant women for HBsAg, and that infants born to HBsAg-positive women
610 SMITH et al

receive timely postexposure prophylaxis and serologic testing after completion of the HepB series. Table 1 outlines the timeline of activities performed by the national PHBPP since its inception in 1990. National PHBPP outcomes for infants born in 1993 were published in 1996.12 Since then, outcomes have not been reported for the estimated $20 000 infants born annually to HBsAg-positive women in the United States. In this article, we summarize PHBPP outcomes as reported by grantees from 1994 to 2008.

METHODS
Data Collection The CDC provides funds to grantees through the Public Health Service Section 317 Immunization Grants Program, a portion of which are expected to be allocated to PHBPPs, in jurisdictions throughout the United States. The requirements and recommendations for 2008 to 2012 grant recipients can be found online.13 PHBPPs in state and city jurisdictions submit annual reports of program outcomes, which include the number of
TABLE 1 Timeline of PHBPP Reporting Activities
1990

identied (reported to local PHBPP) births to HBsAg-positive women and the number of case-managed (tracked by the local PHBPP) infants born to HBsAgpositive women. Of case-managed infants, PHBPPs report the number who receivedHBIG anda dose of HepBvaccine (birth dose) within 1 day of birth (data are not collected for birth dose within 12 hours of birth), who completed the HepB vaccine series by 8 and 12 months of age, and who received postvaccination serologic testing and their outcomes. Postvaccination serologic testing data are collected only from infants who completed the HepB vaccine series. In 2004, PHBPPs began reporting the number of case-managed infants lost to followup, and in 2005 categorized the reasons (moved out of state, moved out of country, infant death, family refused, or inability to locate) (Table 1). Annual PHBPP outcomes were aggregated to create a report covering the national cohort of infants born 2 calendar years before (eg, outcomes of infants born in 2000 were reported in 2002). For each report, the total number of case-managed infants formed the

PHBPP began - No. of identied (reported to local program) births to HBsAg-positive women within jurisdiction - No. of case-managed infants born to HBsAg-positive women - No. of case-managed infants given HBIG and rst dose of HepB within 1 calendar day of birth - No. of case-managed infants who completed the HepB series by 8 mo of age - No. of case-managed infants who completed the HepB series by 12 mo of age - No. of case-managed infants who received postvaccination serologic testing - No. of tested infants who were HBsAg-positive Maternal HBsAg status and/or birth dose administration recorded on state birth certicate No. of birthing hospitals participating in Vaccines for Children programa - No. of case-managed infants lost to follow-up Reasons for loss to follow-up Birth dose supply policy (local prevention program supplies HepB birth dose to birthing hospitals, regardless of Vaccines for Children participation)

2001 2004

2005 2006

a Vaccines for Children is a federal program that purchases and distributes vaccines to enrolled providers, who administer the vaccines to eligible children (ie, uninsured, Native American/Alaska Native) at no cost.

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denominator to calculate the percentages of infants who received HBIG and a HepB birth dose within 1 day of birth, completed the HepB vaccine series by 8 and 12 months of age, and received postvaccination serologic testing. The number of infants who received postvaccination serologic testing was used as the denominator to calculate the percentages of infant outcomes. We analyzed data for infants born from 1994 to 2008 from 49 US states (excludes Alaska), 5 cities (Chicago, Houston, New York City, Philadelphia, San Antonio), and the District of Columbia. Electronic Annual Assessment data les were available from 1999 to 2008. Data from 1994 to 1998 were available as archived summaries. General outcome data from the past 15 years (1994 to 2008) were used to evaluate program trends. Estimating Births to HBsAg-positive Women The CDC estimates the annual number of births to HBsAg-positive women in the United States by using deidentied natality data, provided by the National Center for Health Statistics, and HBsAg seroprevalenceestimates among women of child-bearing age, by race and ethnicity. Natality data were available from 1994 to 2007; 2008 estimates used 2007 natality data. HBsAg seroprevalence among US- and foreign-born Asian/Pacic Islander (API) women of child-bearing age was estimated from the medical literature1416; for all other race/ethnicities, seroprevalence was determined from the National Health and Nutrition Examination Survey (NHANES) III (19881994) or NHANES 1999 to 2006 data.17 Hispanic seroprevalences were derived from averages of Mexican American seroprevalences from NHANES III and NHANES 1999 to 2006 data. Owing to small sample sizes in NHANES, the national average HBsAg seroprevalence was used for women who identied as Native American/other.
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By using the above data sources, estimates from 1994 to 2004 were generated by using the following race/ethnicityspecic HBsAg seroprevalence rates among women of child-bearing age: non-Hispanic whites 0.11%, non-Hispanic blacks 0.5%, Hispanics 0.09%, Native American/other 0.5%, foreign-born APIs 8.9%, and US-born APIs 0.14%. Estimates for 2005 to 2008 were generated by using the following HBsAg seroprevalence rates: non-Hispanic whites 0.08%, nonHispanic blacks 0.71%, Hispanics 0.03%, Native American/other 0.19%, foreignborn APIs 8.9%, and US-born APIs 0.14%. Statistical Analysis Statistical analyses were conducted by using SAS 9.2 (SAS Institute, Inc, Cary, NC). To quantify changes in the main outcomes over time, we used leastsquares linear regression on the unadjusted annual rates. We used the slope to measure the change in value each year and tested whether the slope was signicantly different from 0 (P , .050).

at 50%, although the number of estimated births continued to rise (Fig 1). Each year, the percentage by jurisdiction ranged from 0% to .100% (Table 2). A percentage .100 was obtained if HBsAgpositive births exceeded the estimated number of HBsAg-positive births. Outcomes of Case-managed Infants Born to HBsAg-positive Women, 19942008 Almost all (91.8% to 100.5%) births to HBsAg-positive women that were annually identied by PHBPPs were case managed (data not shown). A total of 152 128 (98.1% of identied) infants were case managed from 1994 to 2008. During this period, the annual number of case-managed infants increased by 62%, from 7415 to 12 033 (P , .001). The number of infants case managed by a jurisdiction ranged from 0 to 2668 infants each year (Table 2). From 1994 to 2008, 92.1% to 96.8% of case-managed infants annually received HBIG and a HepB birth dose within 1 day of birth. Each year, about 70% of case-managed infants completed the HepB vaccine series by 8 months of age, and almost 80% completed the series by 12 months of age; however, the percentage who completed the series by 12 months of age decreased from 86.0% in 1994 to 77.7% in 2008 (P = .004) (Fig 2). The percentage of case-managed infants who received postvaccination serologic testing more than doubled, from 25.1% in 1994 to 55.7% in 2008 (P , .001) (Fig 2). Infant serologic test results were documented from 1999 to 2008, during which an average of 49.3% of case-managed infants received serologic testing. On average, 91.6% of infants tested positive for antibody to hepatitis B surface antigen, indicating immunity to HBV, and 1.3% tested HBsAg-positive, indicating chronic HBV infection. The incidence of chronic HBV infection among tested infants decreased from 1.9% in 1999 to 0.8% in
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RESULTS
Estimated and Identied Births to HBsAg-positive Women, 19942008 The estimated annual number of births to HBsAg-positive women increased from 19 208 in 1994 to 25 600 in 2008 (P , .001) (Fig 1). By jurisdiction, the estimate ranged from 11 to 5871 (Table 2). From 1994 to 2008, a total of 155 081 births to HBsAg-positive pregnant women were identied by PHBPPs. The annual number increased from 8080 to 12 260 (P , .001) over this period, and ranged from 0 to 2884 by jurisdiction (Table 2). The percentage of identied (out of estimated) births to HBsAg-positive women increased from 42.1% in 1994 to 47.9% in 2008 (P = .002) (Fig 1). From 2000 to 2008, this percentage stabilized

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To optimize elimination of perinatal HBV transmission, all infants born to HBsAgpositive women should receive HBIG and a HepB birth dose within 12 hours of birth.10 By 2000, PHBPPs exceeded the 1996 program goal that 90% of infants born to HBsAg-positive women receive HBIG and a HepB birth dose at birth.12 Only 83.0% of case-managed infants received HBIG and a HepB birth dose in 1993,12 compared with 95.5% of casemanaged infants in 2008. Given the increasing numbers of infants born to HBsAg-positive women, this represented major progress. Infants born to HBsAg-positive women who do not complete the HepB vaccine series, or who have delays in completing the series, are signicantly more likely to develop chronic HBV infection than infants who receive timely postexposure prophylaxis.19,20 In a retrospective review of 426 children born to HBsAg-positive women, incompletely vaccinated children were almost 8 times more likely than fully vaccinated children to develop chronic HBV infection, and were half as likely to be immune through vaccination.19 In another investigation of perinatal infections, receiving HBIG more than 12 hours after birth was the only factor signicantly associated with HBV infection.21 According to 2008 National Immunization Survey data, 93.5% of all infants in the United States completed the HepB vaccine series by 19 to 35 months of age.22 Annual completion timelines among case-managed infants, which were more stringent than general immunization recommendations for infants in the United States, had yet to meet the program goal delineated in 1996 (90% completion of the HepB series by 68 months of age).12 PHBPP completion rates may have been underestimated because of the time frame in which data were collected and reported, as the oldest age possible for PHBPPs to report vaccine completion was 12 months.

FIGURE 1

Estimated and identied births to HBsAg-positive women in the United States, 19942008. Data from PHBPPs.

2008 (P = .001) (Table 2). Serologic results were not reported for 7.1% of tested infants. An average of 51.7% of case-managed infants had not received postvaccination serologic testing at the time of the report because of loss to follow-up or incomplete case management. The percentage of case-managed infants lost to follow-up decreased from 26.4% in 2004 to 13.0% in 2008, but the difference was not signicant (P = .126) (Table 2). From 2005 to 2008, the reason for loss to follow-up was reported annually for 72.0% to 88.3% of case-managed infants (data not shown). On average, the most common reasons for loss to follow-up were inability to locate (33.1%) and moved out of country (24.4%), and the least common reason was infant death (2.0%). Family refused was the only category that signicantly increased, from 10.8% in 2005 to 17.9% in 2008 (P = .020).

PHBPPs were successful in executing the many steps to prevent perinatal HBV transmission. From 1994 to 2008, the numbers of identied HBsAg-positive pregnant women and case-managed infants increased and program outcomes improved. In addition, PHBPPs extended their activities to evaluate hospital perinatal hepatitis B prevention practices in 2001 (Table 1), working with hospitals to increase HepB birth dose coverage as a safety net for infants at risk who were not identied,10,18 and to the identication and management of household and sexual contacts of HBsAg-positive women. In 2008, 13.0% of case-managed infants were lost to follow-up and 44.3% did not receive HBsAg serologic testing. Although the annual percentage of casemanaged infants who were lost to followup decreased over time, it is problematic that family refused as a reason for loss to follow-up signicantly increased. The reasons are unclear but need to be better understood. Continued efforts are needed to prevent loss to follow-up and ensure complete case management of these infants, as it is key to eliminating perinatal HBV transmission.10

DISCUSSION
For the rst time since 1996,12 we report the outcomes of the national PHBPP over a 15-year period, 1994 to 2008. Overall,
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TABLE 2 Infants Born to HBsAg-positive Women in the United States,a 19942008

Total, n Range by Jurisdiction (min, max) Year 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 Pk
a

Case-Managed Infants, n (%f ) HepB Administration Case Managede 7415 (0, 1733) 7538 (0, 1921) 8148 (0, 2116) 9017 (0, 2535) 8541 (0, 2042) 9368 (0, 2295) 10 332 (0, 2330) 10 509 (0, 2647) 10 869 (0, 2668) 11 253 (0, 2644) 11 719 (0, 2558) 11 896 (0, 2368) 11 462 (0, 2168) 12 028 (0, 2249) 12 033 (0, 2280) ,.001 HBIG & HepB at birthg 6975 (94.1) 6964 (92.4) 5132j (63.0) 8302 (92.1) 8133 (95.2) 8456 (90.3) 9779 (94.6) 10 082 (95.9) 10 415 (95.8) 10 852 (96.4) 11 347 (96.8) 11 157 (93.8) 10 996 (95.9) 11 435 (95.1) 11 497 (95.5) .126 3 doses by 68 mo 4999 (67.4) 5399 (71.6) 5926 (72.7) 6650 (73.7) 6160 (72.1) 6678 (71.3) 7400 (71.6) 7277 (69.2) 7755 (71.3) 8171 (72.6) 8335 (71.1) 8409 (70.7) 8197 (71.5) 8441 (70.2) 8445 (70.2) .734 3 doses by 12 mo 6375 (86.0) 6136 (81.4) 6694 (82.2) 6918 (76.7) 6981 (81.7) 7496 (80.0) 8342 (80.7) 8250 (78.5) 8794 (80.9) 8991 (79.9) 9282 (79.2) 9240 (77.7) 9016 (78.7) 9306 (77.4) 9352 (77.7) .004 Postvaccination HBsAg test Received 1860 (25.1) 1807 (24.0) 2450 (30.1) 3175 (35.2) 3420 (40.0) 3826 (40.8) 4488 (43.4) 4725 (45.0) 5054 (46.5) 5757 (51.2) 6268 (53.5) 6292 (52.9) 5930 (51.7) 6325 (52.6) 6697 (55.7) ,.001 Tested HBsAg+h Lost to Follow-upi

Estimatedb 19 208 (12, 5395) 19 105 (11, 5189) 19 841 (11, 5135) 19 772 (11, 5116) 20 246 (11, 4934) 20 056 (11, 4917) 21 773 (12, 5517) 21 663 (12, 5371) 21 932 (13, 5226) 23 269 (13, 5661) 23 919 (13, 5730) 23 743 (11, 5501) 24 623 (14, 5652) 25 600 (11, 5871) 25 600 (11, 5871) ,.001

Identiedc 8080 (0, 1733) 7793 (0, 1921) 8416 (0, 2116) 9035 (0, 2535) 8498 (0, 2042) 9505 (0, 2295) 10 488 (0, 2330) 10 944 (0, 2884) 11 020 (0, 2668) 11 356 (0, 2644) 11 832 (0, 2558) 11 890 (0, 2368) 11 671 (0, 2185) 12 293 (0, 2262) 12 260 (0, 2302) ,.001

Identied/ Estimatedd 0.421 (0.0, 1.612) 0.408 (0.0, 1.116) 0.424 (0.0, 1.074) 0.457 (0.0, 1.229) 0.420 (0.0, 0.987) 0.474 (0.0, 1.114) 0.482 (0.0, 1.122) 0.505 (0.0, 1.130) 0.502 (0.0, 1.076) 0.488 (0.0, 1.085) 0.495 (0.0, 1.362) 0.501 (0.0, 1.149) 0.474 (0.0, 1.087) 0.480 (0.0, 1.072) 0.479 (0.0, 1.220) .002

71 (1.9) 93 (2.1) 113 (2.4) 97 (1.9) 77 (1.3) 84 (1.3) 86 (1.4) 85 (1.4) 71 (1.1) 56 (0.8) .001

3122 (26.4) 1916 (16.1) 1703 (14.9) 2109 (17.5) 1570 (13.0) .126

Includes 49 US states (all but Alaska), 5 cities (Chicago, Houston, New York City, Philadelphia, San Antonio), and the District of Columbia. by CDC by using NHANES Hepatitis B seroprevalence data and seroprevalence data from medical literature review applied to National Center for Health Statistics birth data; 2008 estimates are based on 2007 birth data. c Reported to local jurisdiction. d Proportion greater than 1.00 if identied births to HBsAg-positive mothers exceeded estimated births to HBsAg-positive mothers. e By state or city PHBPP. f Percent out of case-managed infants unless otherwise stated. g Within 1 calendar day of birth. h Not reported 19941998; percent out of case-managed infants who received postvaccination HBsAg testing. i Not reported 19992003. j Does not include data from city jurisdictions. k Calculated by using linear regression on unadjusted annual percent (if available) or gure.
b Calculated

PHBPP data would not capture outcomes of exposed infants whose case management was completed after the annual reporting deadline. Although most infants could have completed vaccination and serology at ,12 months of age, infants receiving the hepatitis BHaemophilus inuenzae type b combination vaccine Comvax (Merck Vaccine, Whitehouse Station, NJ) would not complete the series until 12 to 15
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months of age.23 From 2006 to 2008, 50% of jurisdictions reported Comvax administration rates to case-managed infants, and indicated that 2.5% or fewer case-managed infants received the Comvax series annually. Although the percentage of casemanaged infants who completed the HepB series by 12 months of age decreased from 1994 to 2008, the percentage who received postvaccination

serologic testing increased. This indicates that the percentage of infants who fully completed case management (received the 3-dose vaccine series and postvaccination serologic testing) by age 12 to 24 months increased over time. Test results also suggested that HBV prevention was successful for 91% of these infants, and that the incidence of HBV infection likely decreased from 1999 to 2008.
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FIGURE 2

Outcomes of case-managed infants born to HBsAg-positive women, 19942008. *City jurisdiction data were unavailable in 1996; excluding city data, 5132 (63%) received HBIG and HepB birth dose within 1 day of birth.

commonly, these HBsAg-positive women had been identied but were not referred to the PHBPP, or did not have a serologic test reported during pregnancy.32 A comparison of national cases of perinatal HBV infections (US-born, 1 24 months old, HBsAg-positive) in 2005 yielded similar results.33 Cases reported to the national PHBPP were reconciled with cases reported to the CDC via the National Notiable Diseases Surveillance System.33 Before reconciliation, only 58% of unique cases were captured by both reporting systems; after reconciliation, this increased to 84%.33 Coordination between PHBPPs and enhanced HBV infection surveillance improved identication of HBsAgpositive pregnant women, in both total number and accuracy. Errors in the documentation of maternal HBsAg status have also been noted in several studies.27,34 Infants born to women with unknown or discrepant HBsAg results were less likely to receive HBIG or a HepB birth dose, compared with infants born to women with documented HBsAg status, whether positive or negative.27,28,35 ACIP recommends women with unknown HBsAg status receive HBsAg testing on presentation for delivery and that their infants weighing $2000 g receive a HepB birth dose within 12 hours of birth, if the test result is still unknown.10 ACIP recommends infants with lower birth weights receive both HepB and HBIG if at 12 hours the test result is still unknown. A study of hospital practices revealed that 37% of delivery hospitals lacked policies regarding documenting HBsAg status among women admitted with unknown status.27 Identication early in pregnancy has become more important to evaluate for possible treatment of HBsAg-positive women with high HBV load, which may further reduce perinatal HBV transmission. Despite completion of timely postexposure prophylaxis, between

Gaps Rates of postvaccination testing comprised a signicant gap in case management. In 2008, only one-half of case-managed infants and only onequarter of the CDCs 25 600 estimated infants born to HBsAg-positive women had known serologic outcomes. Serologic testing identies infants who remain susceptible after vaccination and might benet from revaccination,9,24 conrms vaccine-induced protection, and detects HBsAg-positive children in need of referral for evaluation and care of chronic HBV infection. The other major gap lay in the identicationofHBsAg-positivepregnantwomen. The Council of State and Territorial Epidemiologists recommends that all HBsAg-positive pregnant women are reported to public health departments in all states25; however, fewer than 50% of the annual estimated births to HBsAgpositive women were identi ed and case managed by a PHBPP. In contrast, screening estimates across several studies indicated that about 95% of pregnant women received prenatal HBsAg serologic testing.2628 This indicates that
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not all HBsAg-positive pregnant women were reported to and identied by a PHBPP. Although the CDCs estimated number of births to HBsAg-positive women has not been validated and the percentage of identied (out of estimated) births to HBsAg-positive women varied by jurisdiction, some jurisdictions identifed and case managed more infants born to HBsAg-positive women than the CDC estimated. Several PHBPPs implemented enhanced case management to increase identication of HBsAg-positive pregnant women.29,30 New York State used multiple reporting mechanisms to increase identication of HBsAgpositive pregnant women and achieved 96% completeness in reporting.31 Metabolic screening cards (required by New York State law) were also used to nd additional cases in the event that the maternal HBsAg status was not reported (ie, delivery outside the hospital). By matching birth certicates with HBV infection surveillance data and PHBPP records, the Philadelphia PHBPP identied an additional 129 births (57%) to HBsAg-positive women in 2008.32 Most

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1% and 10% of infants born to HBsAgpositive women develop chronic HBV, or breakthrough, infection.36,37 Breakthrough infections are strongly associated with high maternal viral load (HBV DNA), with transmission rates as high as 32% among infants born to women with HBV DNA concentrations more than 108 copies/mL.3739 Limitations This study has several limitations. The CDCs annual number of estimated births to HBsAg-positive women was largely dependent on NHANES seroprevalence estimates, which were not available for Hispanic women (we substituted Mexican American seroprevalence).40 Further, CDC estimates accounted only for foreign-born API women. Using country of birth data of all foreign-born persons (particularly those from HBVendemic countries) and country-specic HBsAg seroprevalence produced a higher number of estimated births to HBsAg-positive women than the CDCs estimate.40,41 HBsAg seroprevalence rates throughout the world may also change over time owing to vaccination efforts.4244 The data reported here came from unveried annual reports from PHBPP grantees and would capture women

and infants case managed only if they were reported to a PHBPP (by physician, hospital, or laboratory); however, as indicated by the discrepancy between the CDCs estimated and PHBPP-identied HBsAg-positive women, some maternal HBsAg results undoubtedly went unreported. Similarly, the infants of some HBsAg-positive women received postexposure prophylaxis with completion of vaccination, without notication or assistance by public health. These unreported rates of maternal HBsAg screening and outcomes of infants are largely unknown. All data reported were aggregate data, and did not contain individual identiers. Maternal country of birth, HBV genotype, and hepatitis B e-antigen status play a vital role in perinatal HBV transmission.1,2,45 Enhanced surveillance with collection of these data would have provided further insight into risk of perinatal HBV transmission and program effectiveness; however, most PHBPPs lacked the resources to collect and report these data.

numbers of infants born to HBsAgpositive women. A high percentage of infants received timely postexposure prophylaxis, and the incidence of chronic HBV infections among tested infants decreased. Despite reportedly high levels of screening, approximately half of the estimated births to HBsAg-positive women were identied and managed each year by public health. Vaccination rates and chronic hepatitis B incidence rates among unidentied infants were unknown, and likely, would have affected perinatal hepatitis B infection rates in the United States. Stronger effortswould ensure identication of HBsAg-positive pregnant women and that their infants receive appropriate postexposure prophylaxis, assessment, and, if needed, long-term evaluation and care.

CONCLUSIONS
Overall, perinatal hepatitis B prevention programs have increased identication and management of the growing

ACKNOWLEDGMENTS We gratefully acknowledge data contributions from the PHBPP coordinators and the National Center for Health Statistics, and review and suggestions on the manuscript by Ms Nancy Fasano, Nancy Fenlon RN, MS, and Sarah Schillie MD, MPH, MBA (CDC, National Center for Immunization and Respiratory Diseases, and National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention).

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The National Perinatal Hepatitis B Prevention Program, 19942008 Emily A. Smith, Lisa Jacques-Carroll, Tanja Y. Walker, Barry Sirotkin and Trudy V. Murphy Pediatrics 2012;129;609; originally published online March 26, 2012; DOI: 10.1542/peds.2011-2866
Updated Information & Services References including high resolution figures, can be found at: http://pediatrics.aappublications.org/content/129/4/609.full.ht ml This article cites 34 articles, 9 of which can be accessed free at: http://pediatrics.aappublications.org/content/129/4/609.full.ht ml#ref-list-1 One P3R has been posted to this article: http://pediatrics.aappublications.org/cgi/eletters/129/4/609 This article, along with others on similar topics, appears in the following collection(s): Infectious Disease & Immunity http://pediatrics.aappublications.org/cgi/collection/infectious _disease Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://pediatrics.aappublications.org/site/misc/Permissions.xh tml Information about ordering reprints can be found online: http://pediatrics.aappublications.org/site/misc/reprints.xhtml

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