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Postvaccination Serologic Testing Results for Infants Aged ≤24 Months Exposed to Hepatitis B Virus at Birth — United States, 2008–2011
An estimated 25,000 infants are born to hepatitis B surface antigen (HBsAg)-positive women annually in the United States (1). With no intervention, 40%–90% of these infants will acquire hepatitis B virus (HBV) infection (2,3). Approximately 90% of infected infants develop chronic HBV infection, with a 15%–25% risk for premature death from cirrhosis or cancer of the liver (4). To prevent perinatal HBV transmission, the Advisory Committee on Immunization Practices (ACIP) recommends that infants born to HBsAg-positive women receive postexposure prophylaxis with hepatitis B vaccine (HepB) and hepatitis B immune globulin (HBIG) within 12 hours of birth, and complete the 3-dose HepB series. To determine infant outcomes after postexposure prophylaxis, ACIP recommends postvaccination serologic testing (PVST) at age 9–18 months (4). To evaluate the implementation of these recommendations, CDC assessed outcomes at age 24 months (through 2011) among infants born to HBsAg-positive women enrolled during 2008–2009 in Enhanced Perinatal Hepatitis B Case Management Projects (EPHBP). Of 4,214 EPHBP-managed infants who completed ≥3 HepB doses, 63.7% had reported PVST results, 13.3% had reported PVST results but infant age was unknown, and 23.0% had no reported PVST results. Of 2,683 infants with PVST results by age 24 months, 93.3% were protected, 1.2% were infected, 3.2% remained susceptible, and 2.3% had indeterminate results. ACIP-recommended postexposure prophylaxis was highly effective among infants who completed vaccination and received PVST. PVST is critical for guiding medical management of infants born to HBsAg-positive women, identifying infants with HBV infection and in need of further care, and monitoring progress toward the elimination of perinatal HBV transmission.
In 2007, CDC funded EPHBP to characterize HBsAg-positive pregnant women and assess outcomes among their infants. Five project sites, in Florida, Michigan, Minnesota, New York City, and Texas (excluding cities of Houston and San Antonio), collected and reported data to CDC. Data of women enrolled in EPHBP during 2008–2009 were reviewed; maternal characteristics from the first pregnancy on record were used. Records of all infants born to these women were reviewed to age 24 months; PVST records were examined for infants who completed ≥3 HepB doses (with and without HBIG). Of infants with reported PVST results and date, HBV serology status was categorized as "protected" (anti-HBs-positive, HBsAg-negative), "HBV-infected" (anti-HBs-negative, HBsAg-positive; anti-HBs-positive, HBsAg-positive; or anti-HBs unreported, HBsAg-positive), "susceptible" (anti-HBs-negative, HBsAg-negative), or "indeterminate" (all other result combinations). A protective anti-HBs result was defined as ≥10 mIU/mL. Records of susceptible infants were reviewed for revaccination and repeat PVST. Bivariate analysis of mother/infant pairs was used to examine associations between maternal characteristics (age, race/ethnicity, place of birth, primary language) and infant outcomes (≥3 HepB doses, PVST receipt); significant variables were evaluated further in a multivariable logistic regression model.
EPHBP managed 5,075 infants born to 4,938 HBsAg-positive women in 2008–2009. Most of the women were aged 20–39 years, self-identified as Asian/Pacific Islander (API) or non-Hispanic black, were foreign-born, and almost half indicated a primary language other than English (Table 1). Maternal characteristics were not significantly associated with infant receipt of ≥3 HepB doses. Infants born to women who were Hispanic (odds ratio [OR] = 0.43; 95% confidence interval [CI] = 0.31–0.61), U.S.-born (OR = 0.60; CI = 0.47–0.75), or whose primary language was English (OR = 0.66; CI = 0.56–0.78) were significantly less likely to receive PVST compared to infants born to women who were non-Hispanic, foreign-born, and whose primary language was non-English, respectively. Infants born to API women (OR = 1.50; CI = 1.29–1.74) were significantly more likely to receive PVST compared to infants born to non-API women. After controlling for maternal place of birth (U.S.-born versus foreign-born) and primary language (English versus non-English), infants born to API women were slightly more likely to receive PVST than infants of non-API women (OR = 1.09, p<0.001).
By age 24 months, 4,214 EPHBP-managed infants received ≥3 HepB doses (Table 2). Although 3,244 (77.0%) of these infants received PVST, 412 (9.8%) received incomplete PVST, either anti-HBs only (41) or HBsAg only (371). Among the 4,214 EPHBP-managed infants, 2,073 (49.1%) were tested at age 9–18 months; 259 (6.2%) were tested before age 9 months and 351 (8.4%) were tested after age 18 months. Age at testing was unknown (not reported) for 561 (13.3%) infants. Most (355) incomplete results were from one site where infants were tested only for HBsAg and test dates were not reported (Table 3).
Of the 2,683 infants with reported PVST dates and results, 114 remained susceptible after initial vaccination and PVST. Of these infants, 29 received three additional HepB doses and repeat PVST, as recommended by ACIP; 27 were protected and two remained susceptible. Overall, 93.3% of tested infants were protected, 1.2% were infected, 3.2% remained susceptible, and 2.3% had indeterminate results (Table 4).
Ruthie Benson, Texas Dept of State Health Svcs. Susan A. Crowley, Minnesota Dept of Health. Cristina Dusek, Florida Dept of Health. Julie Lazaroff, MPH, New York City Dept of Health and Mental Hygiene, New York. Kenneth Onye, MPH, Michigan Dept of Community Health. Emily A. Smith, MPH, Tanja Y. Walker, MPH, Sarah F. Schillie, MD, Trudy V. Murphy, MD, Div of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention; Jane Zucker, MD, Immunization Services Div, National Center for Immunization and Respiratory Diseases, CDC. Corresponding contributor: Emily A. Smith, email@example.com, 404-718-8514.
ACIP-recommended postexposure prophylaxis for infants born to HBsAg-positive mothers protects 85%–95% of infants from perinatally acquired HBV infection (4). Since 1990, CDC has funded perinatal hepatitis B prevention programs to identify HBsAg-positive pregnant women and ensure that their infants receive postexposure prophylaxis, including PVST. PVST identifies infants who are protected, remain susceptible after a primary HepB series, or develop HBV infection and should be referred for continuing medical care (4–6).
Among infants born to HBsAg-positive mothers and managed by perinatal hepatitis B prevention programs in the United States, and who received ≥3 HepB doses, PVST rates by age 15–27 months increased from 25% in 1994 to 56% in 2008 (1). In another study, 57% of infants born to HBsAg-positive mothers during 2003–2005 received HBsAg testing (7). In comparison, 77.0% of EPHBP-managed infants received PVST, and 63.7% had known serologic outcomes (Table 3). Although rates of PVST have increased, this analysis highlights areas in need of improvement. Strategies are needed to increase the rates for overall testing and testing for both anti-HBs and HBsAg, which are required to confirm outcomes. Of infants in EPHBP, 9.8% received only one of the two recommended serologic tests. An anti-HBs result <10 mIU/mL is insufficient to determine whether the infant is susceptible or is HBV-infected. Alone, an anti-HBs result ≥10 mIU/mL does not confirm that the infant is protected; the HBsAg result also must be negative. A negative HBsAg test result by itself does not indicate whether the infant is protected by vaccination or remains susceptible.
ACIP recommends PVST at age 9–18 months (4). Infants should be tested starting at age 9 months, if at least 1 month has passed since the last HepB dose, to ensure that all HBV-infected infants are identified* (4,8). Of EPHBP-managed infants, 14.6% received PVST outside of the recommended time frame, and 13.3% had an unknown age at testing. Infants who remain susceptible after an initial HepB series without timely PVST to prompt revaccination have continuing risk for transmission from household contacts with chronic HBV infection. Intervals ≥4 months between the final HepB dose and PVST have been associated with waning of anti-HBs titers, which might fail to confirm protection and result in unnecessary revaccination (6,9).
In this analysis, infants born to API women were significantly more likely to receive PVST. Previous studies have yielded mixed results (5,6,10). A study examining data from 1992–2000 found that infants whose mothers were non-Hispanic white, were aged <20 years, were U.S.-born, or had a household income <$15,000 were less likely to receive PVST (6,10). In another study, however, PVST did not differ significantly by maternal age or race among infants managed by the Louisiana Office of Public Health (5).
The results of this study are subject to at least two limitations. First, results from the EPHBP sites might not be representative of all births to HBsAg-positive women in the United States; EPHBP-managed women and infants comprise about 25% of CDC's estimated births to HBsAg-positive women. Second, the completeness of reporting PVST results to CDC was not examined. However, overall PVST rates of EPHBP-managed infants were high compared with rates reported in other studies (1,7).
To achieve optimal prevention of perinatal HBV infection, HBsAg-positive pregnant women must be identified before delivery, and their infants must complete appropriate and timely postexposure prophylaxis. PVST (anti-HBs and HBsAg) as soon as age 9 months and at least 1 month after the last HepB dose has been given determines if infants are susceptible and should be revaccinated and retested, or are infected and require additional medical care. Although universal recommendations for HepB vaccination have been published (4), no universal recommendations for HBV screening of infants or children have been issued. HBV infection usually is asymptomatic, and therefore is unlikely to be detected without testing, until complications arise. Conducting timely PVST and reporting results to public health officials ensures that infants born to HBsAg-positive women receive appropriate follow-up, and is a key element of surveillance to monitor progress toward the elimination of perinatal HBV transmission.
Immunization Svcs Div, National Center for Immunization and Respiratory Diseases, CDC.
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* Infants who complete the HepB series with the Haemophilus influenzae type b combination product (COMVAX, Merck & Co.) at age 12–15 months are eligible for PVST 1 month after the last dose (2).
What is already known on this topic?
Infants born to hepatitis B surface antigen-positive women have a 40%–90% chance of acquiring hepatitis B virus (HBV) infection. Infected infants have a 90% risk of chronic HBV infection, which can result in premature death from liver failure or cancer. Postexposure immunoprophylaxis in infancy prevents 85% to 95% of perinatal infections. To determine infant outcomes, including whether infants require additional vaccination for protection, postvaccination serologic testing is recommended 1 month after completing the hepatitis B vaccine series (age 9–18 months).
What is added by this report?
Among infants with reported outcomes, postvaccination serologic testing data from Enhanced Perinatal Hepatitis B Case Management Projects indicated that timely postexposure prophylaxis might be 93% effective in protecting infants from perinatal hepatitis B infection. However, 23.0% of infants had no reported postvaccination serologic testing.
What are the implications for public health practice?
Postvaccination serologic testing (hepatitis B surface antigen [HBsAg] and hepatitis B surface antigen antibody) for infants born to HBsAg-positive women is important to determine appropriate infant medical follow-up. Test results should be reported to perinatal hepatitis B program coordinators who can assist families in assuring infant protection and who monitor progress toward elimination of perinatal hepatitis B virus transmission.
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