National Perinatal Hepatitis B Prevention Program: 2009-2017.

OBJECTIVES: To assess trends and programmatic outcomes among infants born to hepatitis B surface antigen (HBsAg)-positive women from 2009 to 2017 and case-managed by the Centers for Disease Control and Prevention's national Perinatal Hepatitis B Prevention Program (PHBPP). METHODS: We analyzed 2009-2017 annual programmatic reports submitted by 56 US jurisdictions funded through the Centers for Disease Control and Prevention's PHBPP to assess characteristics of maternal-infant pairs and achievement of objectives of infant hepatitis B postexposure prophylaxis, vaccine series completion, and postvaccination serologic testing (PVST). We compared the number of maternal-infant pairs identified by the program with the number estimated born to HBsAg-positive women from 2009 to 2014 and 2015 to 2017 by using a race and/or ethnicity and maternal country of birth methodology, respectively. RESULTS: The PHBPP identified 103 825 infants born to HBsAg-positive women from 2009 to 2017, with a range of 10 956 to 12 103 infants annually. Births estimated annually to HBsAg-positive women increased nonsignificantly from 24 804 in 2009 to 26 444 in 2014 (P = .0540) and 20 678 in 2015 to 20 832 in 2017 (P = .8509). The proportion of infants identified annually increased overall from 48.1% to 52.6% (P = .0983). The proportion of case-managed infants receiving postexposure prophylaxis, at least 3 vaccine doses, and PVST increased overall from 94.7% to 97.0% (P = .0952), 83.1% to 84.7% (P = .5377) and 58.8% to 66.8% (P = .0002), respectively. CONCLUSIONS: The PHBPP has achieved success in managing infants born to HBsAg-positive women and ensuring their immunity to hepatitis B. Nonetheless, strategies are needed to close gaps between the number of infants estimated and identified, increase vaccine series completion, and increase ordering of recommended PVST for all case-managed infants.

Estimating Annual Births to Hepatitis B Surface Antigen-Positive Women in the United States by Using Data on Maternal Country of Birth.

OBJECTIVE: A national estimate of births to hepatitis B surface antigen (HBsAg)-positive women can help public health programs plan surveillance, educational, and outreach activities to improve identification and management of at-risk women and infants. Stratifying mothers by country of birth allows for the application of region-specific HBsAg prevalence estimates, which can more precisely estimate the number of at-risk infants. The objective of our study was to estimate the number of births to HBsAg-positive women in the United States with more granularity than previous models. METHODS: We developed a model that incorporated maternal country of birth (MCOB) and updated HBsAg prevalence estimates. We assessed birth certificate data by MCOB, and we stratified US-born mothers by race/ethnicity, US territory-born mothers by territory, and non-US-born mothers by region. We multiplied and summed data in each subcategory by using HBsAg prevalence estimates calculated from the 2009-2014 National Health and Nutrition Examination Surveys or Perinatal Hepatitis B Prevention Program. We compared the findings of our MCOB model with a race/ethnicity model. RESULTS: In 2015, an estimated 20 678 infants were born to HBsAg-positive women in the United States, representing 0.5% of all births. Births to US-born and non-US-born women comprised 77.2% and 21.5% of all births, respectively, and 40.1% and 57.9% of estimated births to HBsAg-positive women, respectively. The estimated contribution of births to HBsAg-positive women varied by MCOB region, from 4 (0.03%) infants born to women from Australia/Oceania to 5795 (28.0%) infants born to women from East Asia. Our MCOB model estimated 5666 fewer births to HBsAg-positive women than did the race/ethnicity model. CONCLUSIONS: As global vaccine programs reduce HBsAg prevalence, the MCOB model can incorporate evolving HBsAg prevalence estimates for women from various regions of the world.

Hepatitis B Surface Antigen Testing Among Pregnant Women, United States 2014.

BACKGROUND: Post-exposure prophylaxis administered to infants shortly after birth prevents approximately 90% of cases of perinatal hepatitis B virus (HBV) transmission. The Advisory Committee on Immunization Practices recommends that all pregnant women be tested for hepatitis B surface antigen (HBsAg) at an early prenatal visit during each pregnancy to detect active infection with HBV. This study sought to determine the proportion and characteristics of pregnant women tested\not tested according to Advisory Committee on Immunization Practices recommendations. METHODS: We analyzed MarketScan databases to assess prenatal HBsAg testing among women with commercial and Medicaid health care coverage according to demographic and clinical characteristics. Pregnant women 15-44 years of age continuously enrolled in a health plan in the MarketScan database during 2013 and 2014 and with a live birth in 2014 were included. RESULTS: Among commercially insured women, 239,955 (87.7%) received HBsAg testing and 59.6% were tested during their first trimester. Among Medicaid-enrolled women, 57,268 (83.6%) received HBsAg testing and 39.4% were tested during their first trimester. Among women with high risk pregnancies, HBsAg testing occurred in 87.3% of those with commercial insurance and 84.8% with Medicaid. Testing also varied by maternal age; among women with commercial insurance, testing was greatest among women 26-44 years of age, and among women with Medicaid, testing was greatest among younger women (15-25 years). Testing was lowest among women residing in the Northeast (commercial insurance only). CONCLUSIONS: Prenatal HBsAg testing identifies HBV-infected pregnant women so their infants can receive timely immunoprophylaxis. Efforts to optimize HBsAg testing among all pregnant women are needed to further prevent perinatal HBV transmission.

Assessment of State Perinatal Hepatitis B Prevention Laws.

INTRODUCTION: Identifying pregnant women with hepatitis B virus (HBV) infection for post-exposure prophylaxis of their infants is critical to preventing mother-to-child transmission of HBV infection. HBV infection in infancy results in premature death from chronic liver disease or cancer in 25% of affected infants. Universal screening of pregnant women for HBV infection is the standard of care, and in many states is supported by laws for screening and reporting these infections to public health. No recent assessment of state screening and reporting laws for HBV infection has been published. METHODS: In 2014, the authors analyzed laws current through December 31, 2013 from U.S. jurisdictions (50 states and the District of Columbia) related to HBV infection and hepatitis B surface antigen screening and reporting requirements generally and for pregnant women specifically. RESULTS: All states require reporting of cases of HBV infection. Twenty-six states require pregnant women to be screened. Thirty-three states require public health reporting of HBV infections in pregnant women, but only 12 states require reporting pregnancy status of women with HBV infection. CONCLUSIONS: This assessment revealed significant variability in laws related to screening and reporting of HBV infection among pregnant women in the U.S. Implementing comprehensive HBV infection screening and reporting laws for pregnant women may facilitate identifying HBV-infected pregnant women and preventing HBV infection in their infants.

Characteristics of Pregnant Women With Hepatitis B Virus Infection in 5 US Public Health Jurisdictions, 2008-2012.

OBJECTIVE: We estimated the prevalence of hepatitis B surface antigen (HBsAg), a serologic marker of active hepatitis B virus (HBV) infection, among pregnant women, and estimated the proportion HBsAg-positive pregnant women who had received additional recommended testing. METHODS: From 2008 through 2012, Perinatal Hepatitis B Prevention Programs (PHBPPs) in Florida, Michigan, Minnesota, New York City, and Texas prospectively collected data on demographic characteristics of HBsAg-positive pregnant women. We estimated the prevalence of HBsAg positivity among pregnant women by demographic characteristics using natality data. PHBPPs (excluding Texas) collected additional recommended testing (for hepatitis B e antigen [HBeAg] and/or HBV deoxyribonucleic acid [DNA]) among HBsAg-positive pregnant women to measure levels of viremia. RESULTS: During the study period, 15,205 HBsAg-positive women were case-managed. The median age of HBsAg-positive women was 29 years; prenatal HBsAg screening was at a median of 27 weeks pre-delivery. Of 15,205 HBsAg-positive women, 11,293 (74.3%) were foreign-born. In four PHBPPs with 14,098 pregnancies among 12,214 HBsAg-positive women, HBeAg and/or HBV DNA testing was documented for 2,794 (19.8%) pregnancies. The estimated prevalence of HBsAg positivity among pregnant women was 0.38% (17,023 of 4,468,773). HBsAg prevalence was highest among foreign-born women from most regions in Asia (2.0% to 8.7%; with the exception of South Asia, 0.4%) and Africa (3.4%). CONCLUSION: One-fifth of HBsAg-positive pregnant women had documentation for HBeAg and/or HBV DNA, and about one-third reported receiving care for HBV infection during a case-managed pregnancy. Greater emphasis is needed on prenatal evaluation for HBV liver disease care and treatment among pregnant women with HBV infection.

Estimated Annual Perinatal Hepatitis B Virus Infections in the United States, 2000-2009.

BACKGROUND: Ninety percent of perinatal hepatitis B virus (HBV) infections result in chronic HBV (CHBV), which carries 25% risk of premature death from progressive liver injury, cirrhosis, and liver cancer. In 1990, the Centers for Disease Control and Prevention (CDC) funded Perinatal Hepatitis B Prevention Programs (PHBPP) to ensure postexposure prophylaxis for exposed infants and accelerate elimination of perinatal CHBV in the United States. From 2000 to 2009, the annual rates of perinatal CHBV reported by PHBPP (0.8%-2.4%) were consistently lower than expected rates from CDC models (3.0%-4.1%), suggesting that rates of CHBV might be higher among infants whose outcomes were not identified by PHBPP. To better understand the factors impacting modeled expected number and rates of perinatal CHBV, we examined historic CDC models, applied updated inputs to the 2009 CDC model, and performed sensitivity analyses over a range of parameter values. METHODS: Models employed estimates of the annual number of births to hepatitis B surface antigen (HBsAg)-positive pregnant women, and data from PHBPP and National Immunization Surveys. Published literature provided prenatal HBsAg screening rates, efficacy of postexposure prophylaxis (PEP), and perinatal HBV transmission rates. RESULTS: The updated 2009 model predicted 952 perinatal CHBV infections, equivalent to a baseline rate of 3.84%, among infants of HBsAg-positive women. Sensitivity analyses yielded a possible range of perinatal CHBV rates between 0.60% and 15.41%. The proportion of infants receiving timely PEP, the efficacy of PEP, and perinatal HBV transmission rate were major "drivers" of CHBV rates. Three-way sensitivity analysis yielded possible perinatal CHBV rates between 0.79% and 13.64%. CONCLUSIONS: Modeling provided useful programmatic goals for achieving elimination of perinatal CHBV in the United States. Limitations of data inputs likely contributed to discrepancies between predicted and reported rates.

Update: Shortened Interval for Postvaccination Serologic Testing of Infants Born to Hepatitis B-Infected Mothers.

Infants born to hepatitis B-infected mothers receive postexposure prophylaxis to reduce their risk for perinatal hepatitis B virus (HBV) infection. Postexposure prophylaxis consists of hepatitis B (HepB) vaccine and hepatitis B immune globulin administered within 12 hours of birth, followed by completion of the 3-dose or 4-dose HepB vaccine series. Postvaccination serologic testing (PVST) assesses an infant's response to HepB vaccination and has typically occurred at age 9-18 months. This report provides a CDC update recommending shortening the interval for PVST from age 9-18 months to age 9-12 months. Providers should order PVST (consisting of hepatitis B surface antigen [HBsAg] and antibody to HBsAg [anti-HBs]) for infants born to HBsAg-positive mothers at age 9-12 months (or 1-2 months after the final dose of the vaccine series, if the series is delayed). This recommendation was prompted by the discontinuation of production of Hib/HepB vaccine (Comvax) and new data from the Enhanced Perinatal Hepatitis B Prevention Program supporting PVST 1・2 months after receipt of the last HepB vaccine dose, and at age ≥9 months.

Outcomes of infants born to women infected with hepatitis B.

BACKGROUND AND OBJECTIVES: Perinatal exposure is an important mode of hepatitis B virus (HBV) transmission, resulting in chronic disease in ∼ 90% of infected infants. Immunoprophylaxis recommended for infants born to hepatitis B surface antigen-positive mothers reduces up to 95% of perinatal HBV infections. We sought to identify factors associated with perinatal HBV transmission. METHODS: We analyzed prospectively collected data from 5 of 64 US-funded Perinatal Hepatitis B Prevention Programs during 2007-2013. We examined effects of maternal demographic and laboratory results, infant gestational age and birth weight, and immunoprophylactic management on perinatal HBV infection. RESULTS: Data from 17,951 mother-infant pairs were analyzed. Among 9252 (51.5%) infants for whom hepatitis B surface antigen testing results were available, 100 (1.1%) acquired perinatal HBV infection. Both hepatitis B (HepB) vaccine and hepatitis B immune globulin were administered within 12 hours of birth for 10,760 (94.9%) of 11,335 infants with information. Perinatal HBV infection was associated with younger maternal age (P = .01), Asian/Pacific Islander race (P < .01), maternal hepatitis B e-antigen positivity (P < .01), maternal antibody to hepatitis B e-antigen negativity (P < .01), maternal viral load ≥ 2000 IU/mL (P = .04), and infant receipt of <3 HepB vaccine doses (P = .01). Four infants born to 429 mothers with viral load testing were infected; all 4 were born to mothers with viral loads in the ninth or tenth decile. CONCLUSIONS: Perinatal HBV infection occurred among 1% of infants, most of whom received recommended immunoprophylaxis. Infants at greatest risk of infection were those born to women who were younger, hepatitis B e-antigen positive, or who had a high viral load or those infants who received <3 HepB vaccine doses.

Discrepant hepatitis B surface antigen results in pregnant women screened to identify hepatitis B virus infection.

OBJECTIVE: To resolve discrepant hepatitis B surface antigen (HBsAg) results for pregnant women screened for hepatitis B virus (HBV) infection. STUDY DESIGN: A case was defined as discrepant HBsAg (reactive followed by non-reactive) result during the same pregnancy. The Centers for Disease Control and Prevention examined a convenience sample of cases passively reported by US Perinatal Hepatitis B Prevention Programs. Using a standard form, available results were obtained for hepatitis B tests and vaccination histories. Results were independently reviewed by 3 viral hepatitis experts and a clinical virologist to resolve discrepancies. The initial HBsAg result was classified as probable true positive, probable false positive, or unresolved. RESULTS: From April 2009-December 2011, 142 (75.9%) of 187 reported discrepant cases met the case definition. Of the 142 initial reactive HBsAg results, 113 (79.5%) were laboratory-confirmed, and 89 (62.7%) were resolved. Among these 89 cases, the initial test was a probable true positive in 14 (15.7%), and a false positive in 75 (84.3%). Total antibody to hepatitis B core antigen was positive for 11 (78.6%) of the true positive cases and negative for 67 (89.3%) of the false positive cases. True positives included 2 cases of resolving acute HBV infection and one case recently given hepatitis B vaccination. CONCLUSIONS: In this retrospective analysis of discrepant HBsAg-reactive screening results from pregnant women, the majority were false positives, but true positives occurred. Testing for total hepatitis B core antibody, an indicator of past or current HBV infection, was useful for resolving discrepancies.

Hepatitis B vaccine response among infants born to hepatitis B surface antigen-positive women.

PURPOSE: Annually, an estimated 25,000 infants are born to hepatitis B surface antigen (HBsAg)-positive women in the United States. Hepatitis B (HepB) vaccine and hepatitis B immune globulin (HBIG) are recommended at birth, followed by completion of vaccine series and post-vaccination serologic testing (PVST). In a large cohort of infants born to HBsAg-positive women, factors influencing vaccine response were evaluated. METHODS: Data were from HBsAg-negative infants born to HBsAg-positive women in the Enhanced Perinatal Hepatitis B Prevention Program (EPHBPP) from 2008 to 2013. Vaccine non-responders were defined as infants with antibody to hepatitis B surface antigen (anti-HBs) <10mIU/mL at PVST after receiving ≥3 vaccine doses. Multivariable analyses modeled statistically significant predictor variables associated with non-response. RESULTS: A total of 17,951 maternal-infant pairs were enrolled; 8654 HBsAg-negative infants born to HBsAg-positive mothers received ≥3 doses of vaccine with anti-HBs results. 8199 (94.7%) infants responded to a primary HepB series; 199 (94.8%) to a second series. Factors associated with anti-HBs <10mIU/mL included gestational age <37 weeks, vaccine birth dose >12h after birth, timing of final vaccine dose <6 months after birth, receipt of 3 vs. 4 vaccine doses, and PVST interval >6 months from final vaccine dose in bivariate analysis. PVST interval >6 months from final vaccine dose (OR=2.7, CI=2.0, 3.6) was significantly associated with anti-HBs <10mIU/mL; the proportion increased from 2% at 1-2 months to 21.6% at 15-16 months after the final dose. Receipt of a 4th dose improved the response rate (OR=0.5, CI=0.3, 0.8). CONCLUSIONS: Ninety-five percent of a large cohort of uninfected infants born to HBsAg-positive mothers in the United States responded to primary HepB vaccine series. The proportion of infants with anti-HBs <10mIU/mL increased with longer interval between the final vaccine dose and PVST. Optimal timing of PVST is within 1-2 months of final vaccine dose to avoid unnecessary revaccination.

Cost-effectiveness analysis of the national Perinatal Hepatitis B Prevention Program.

OBJECTIVE: To analyze the cost-effectiveness of the national Perinatal Hepatitis B Prevention Program (PHBPP) over the lifetime of the 2009 US birth cohort and compare the costs and outcomes of the program to a scenario without PHBPP support. PHBPP's goals are to ensure all infants born to hepatitis B (HepB) surface antigen-positive women receive timely postexposure prophylaxis, complete HepB vaccine series, and obtain serologic testing after series completion. METHODS: A decision analytic tree and a long-term Markov model represented the risk of perinatal and childhood infections under different prevention alternatives, and the long-term health and economic consequences of HepB infection. Outcome measures were the number of perinatal infections and childhood infections from infants born to HepB surface antigen-positive women, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost per QALY gained. The health outcomes and total costs of each strategy were compared incrementally. Costs were evaluated from the health care system perspective and expressed in US dollars at a 2010 price base. RESULTS: In all analyses, the PHBPP increased QALYs and led to higher reductions in the number of perinatal and childhood infections than no PHBPP, with a cost-effectiveness ratio of $2602 per QALY. In sensitivity analyses, the cost-effectiveness ratio was robust to variations in model inputs, and there were instances where the program was both more effective and cost saving. CONCLUSIONS: This study indicated that the current PHBPP represents a cost-effective use of resources, and ensuring the program reaches all pregnant women could present additional public health benefits.