National Perinatal Hepatitis B Prevention Program: 2009–2017

The CDC PHBPP-funded jurisdictions collect data on maternal-infant pairs case managed by the program and include data for receipt of PEP, hepatitis B vaccine series, and PVST. Each jurisdiction submits aggregate data annually for specific birth cohorts for selected time periods (eg, the reporting period for the 2017 birth cohort was January 1, 2017, through December 31, 2018, and submitted in 2019) via an electronic form to the CDC, and all data are compiled into an annual report.¹²  This report is reviewed annually, and the collection form is revised as needed to address programmatic issues. In this article, we analyze PHBPP aggregate data from 56 jurisdictions (50 US states, the District of Columbia, Chicago, Houston, New York City, Philadelphia, and San Antonio) to assess outcomes for case-managed infants for birth cohorts 2009–2017.

The number of infants case managed was the denominator for the percentage of infants who received PEP at birth, completed ≥3 doses of the hepatitis B vaccine by age 8 to 12 months or after 12 months of age during the reporting period, and received PVST after series completion. PVST results were also assessed.

Between reporting periods for birth cohorts 2009–2017, questions were added to address programmatic issues identified during the annual report review. The following additional data were collected and assessed for years available: indeterminate PVST (defined as either a single test [HBsAg or anti-HBs only] performed or an inconclusive laboratory result) and number of single tests received, underweight infants (defined as <2000 g at birth), infants who moved out of the country before series or PVST completion and were closed to the program, and infant insurance status at birth.

The CDC provides the PHBPP-funded jurisdictions with annual national and jurisdictional-level estimates of the number of births to HBV-infected women using natality data from the National Center for Health Statistics (National Center for Health Statistics, unpublished observations).¹²  This estimate provides a programmatic goal for identifying HBV-infected pregnant women and their infants. Natality data were assessed for maternal characteristics, including race and/or ethnicity and country of birth, input into a multiplier model,^11–13  and summed to generate an annual estimate of births to HBV-infected women. For cohort years 2009–2014, the CDC used a race and/or ethnicity model first categorizing infants by maternal race and/or ethnicity and then multiplying by category-specific prevalences derived from medical literature for Asian–Pacific Islanders only and derived from the NHANES 1999–2006 for other racial and ethnic groups.¹¹  Prevalence estimates used for the race and/or ethnicity model are as follows: non-Hispanic white persons, 0.08%; non-Hispanic Black persons, 0.71%; Hispanic persons, 0.03%; Native American or other persons, 0.19%; foreign-born Asian–Pacific Islander patients, 8.9%; and US-born Asian and/or Pacific Islander persons, 1.4%.^11,13  For cohort years 2015–2017, the CDC incorporated maternal country of birth into the multiplier model.¹²  Infants were categorized primarily by maternal country of birth and subcategorized: US-born, then subcategorized by race and/or ethnicity; US territory-born, then subcategorized by territory; non-US-born, then subcategorized by geographic region, and unknown country of birth. Prevalence estimates were derived from NHANES 2009–2014, PHBPP Annual Reports, or Enhanced Perinatal Hepatitis B Case Management and are detailed by Koneru et al.¹²  Both methodologies calculate a point and lower limit estimate for infants born to HBsAg-positive women each year.^11,12  In this article, we present annual national-level point estimates with jurisdictional-level ranges for birth cohorts 2009–2017.

We performed analyses using SAS versions 9.3 to 9.4 (SAS Institute, Inc, Cary, NC) and Microsoft Excel (Microsoft Corporation, Redmond, WA). Least squares linear regression was used to examine changes in programmatic outcomes for cohorts 2009–2017, and significance was set as P < .05. Because of the low power of the statistical analyses, we will discuss both significant and nonsignificant effects because these outcomes have program-planning implications for achieving PHBPP objectives of identifying HBV-infected pregnant women and case management of their infants. Review by the CDC’s institutional review board was not required because deidentified data from annual reports and natality data sets were used.

The national PHBPP identified a total of 103 825 (range by year: 10 956–12 103) infants born to HBsAg-positive women from 2009 to 2017. Identified births ranged from 0 to 2615 by jurisdiction annually. Nearly 97% (100 372 of 103 825) of all infants identified were case managed by the PHBPP (Table 1).

A total of 96 629 (mean per year: 10 737) case-managed infants received PEP within 1 calendar day of birth. The proportion of infants receiving PEP ranged from 94.7% to 96.6% (P = .0952) from 2009 to 2017. A total of 85 421 (mean per year: 9491) case-managed infants received ≥3 hepatitis B vaccine doses by 8 to 12 months of age, and the proportion slightly increased overall from 83.1% to 84.7% (P = .5377). An additional 1578 infants received ≥3 doses after 12 months of age, yielding a total of 86 999 infants receiving ≥3 doses during the case-management period (Table 1). A total of 917 underweight infants (<2000 g) of 44 293 case-managed infants were identified during 2014–2017, with 78.7% receiving the 4 recommended vaccine doses before close-out from case management (data not shown). The proportion of infants receiving PVST increased significantly overall from 58.8% for birth cohort 2009 to 66.8% (P = .0002) for cohort 2017, with an annual range of 6637 to 7499 infants. The proportion of infants who tested positive for HBsAg decreased overall from 0.9% for cohort 2009 to 0.4% for cohort 2017 (P = .0006), with 63 and 29 HBsAg-positive infants in cohorts 2009 and 2017, respectively. For birth cohort 2009, 5552 infants tested anti-HBs positive (≥10 mIU/mL), and for cohorts 2010–2017, a mean of 6694 tested anti-HBs positive by cohort year (Table 1).

A total of 754 indeterminate PVST results were reported for 2014–2017, with 81.2% because of the infant receiving a single HBsAg or anti-HBs test only (Table 2). For cohorts 2010–2017, 12.4% of infants were closed out from case management before vaccine series or PVST completion, and for cohorts 2016–2017, 50.0% of infants were closed out (ie, the PHBPP ceased follow-up of the infant for programmatic outcomes) because they moved out of the country (data not shown). Infant insurance status was collected for cohorts 2010–2017, and up to 57.1% of infants identified during this time period were insured (29.6% publicly, 27.5% privately) (data not shown).

Over 2009–2017, there was an estimated annual mean of 23 785 infants born to HBsAg-positive women, with a notable decrease of 5558 from 2014 through 2015 after a change in methodology for estimating births. Overall, births estimated annually to HBsAg-positive women decreased from 24 804 in 2009 to 20 832 in 2017 (P = .0581); however, estimated births increased from 24 804 in 2009 to 26 444 in 2014 (P = .0540) and 20 678 in 2015 to 20 832 in 2017 (P = .8509). Estimated births ranged from 13 to 6243 by jurisdiction annually. The percentage of PHBPP-identified births of the estimated total number of births among HBsAg-positive women increased overall from 44.0% in 2009 to 52.6% in 2017 (P = .0983) but decreased during 2009–2014 from 48.1% to 44.0% and during 2015–2017 from 55.6% to 52.6% (Table 1). Annual trends in the number of infants estimated born to HBsAg-positive women, infants identified by PHBPPs, infants who received PEP within 1 calendar day of birth, and infants who received PVST are shown (Figs 1 and 2).

This article reports programmatic outcomes of infants born during 2009–2017 and enrolled in the national PHBPP for prevention of MTCT of HBV infection and reflects changes to the estimated birth methodology and data reported to the CDC in the annual report.

Historically, the national PHBPP has identified less than one-half of infants estimated to be born to HBsAg-positive women each year.¹¹  HBV infection disproportionately impacts population subgroups in the United States, with higher HBsAg prevalence observed in non-Hispanic Asian and non–US-born persons.¹  After adoption of a newer model incorporating both race and ethnicity and maternal country of birth as well as updated HBsAg prevalence estimates,¹²  the program achieved an average of 54.2% identification over 2015–2017. Previous studies indicate that gaps in identification of HBsAg-positive women (and subsequently, their infants) might result from women’s limited access to and receipt of prenatal care, inadequate receipt and documentation of prenatal HBsAg screening during all pregnancies,^3,14  and challenges in reporting HBsAg-positive pregnant women to appropriate PHBPPs, including by laboratories, by clinicians, and within health departments.¹⁵  One PHBPP jurisdiction, Philadelphia, was able to increase the number of HBV-positive pregnant women identified using a novel capture-recapture protocol that assessed multiple data sources¹⁶ ; similar protocols should be considered by other PHBPPs.

Most case-managed infants (96.3%) received recommended PEP at birth. To encourage high rates of PEP, many PHBPPs assist birthing facilities in enrolling in the Immunization Action Coalition’s “Birth Dose Honor Roll,” which recognizes institutions that have >90% hepatitis B birth dose coverage for a 12-month period and written policies on administration of hepatitis B vaccine and PEP to newborns.¹⁷  Ensuring PEP for infants born outside of the hospital setting (eg, birthing centers, home births) poses additional challenges. These settings might not be equipped to provide the birth dose, and providers caring for infants in these settings (eg, midwives) might delay the birth dose. The PHBPP and pediatric providers should educate birthing facility administrators and parents on the importance of following ACIP-recommended HBV management.

Overall, 85.1% of case-managed infants completed the hepatitis B vaccine series by 12 months of age, and 63.6% received PVST by the end of the reporting period, with a statistically significant increase (P = .0002) in the proportion receiving PVST from 58.8% to 66.8% for birth cohort years 2009–2017 (Table 1). However, 33.2% of case-managed infants did not receive PVST, leaving them at potential risk of disease burden. Additional efforts are needed to increase series completion and PVST rates among case-managed infants. One jurisdictional PHBPP has achieved and maintained higher-than-national PHBPP outcomes using performance-based contracts with target outcomes specified in key contracts (National Center for Immunization and Respiratory Disease, unpublished observations). For the current funding period from July 1, 2019, through June 30, 2024, the CDC has set targets for each PHBPP: (1) 80% of the lower limit of estimated births to HBsAg-positive women will be identified, (2) 98% of identified infants will receive PEP at birth, (3) 90% of case-managed infants will receive PEP and complete the series by 12 months of age, and (4) 85% of infants will receive PVST.

Of the infants who received PVST, the number of HBsAg-positive infants significantly decreased for birth cohort years studied from 63 HBsAg-positive infants in the 2009 cohort to 29 HBsAg-positive infants in the 2017 cohort, indicating decreased disease burden and premature death. However, the number of HBsAg-positive infants identified is thought to be many-fold lower than the number estimated to be chronically infected. Ko et al¹⁵  estimated that, in the 2009 cohort, 1058 infants were infected perinatally, and, of those, 952 infants became chronically infected. Ko et al¹⁵  reported that the final estimate of chronic HBV-infected infants is driven by the number of infants receiving timely PEP, the efficacy of PEP, and the perinatal HBV transmission rate. The discrepancy in identified HBsAg-positive infants and the annual estimate of chronically infected infants highlight the need to increase the proportion of infants who are identified and who receive PEP, complete the vaccine series, and receive PVST each year.

Insurance status has been reported annually by PHBPPs since the 2010 cohort. A majority of case-managed infants were reported to be insured either by public or private entities. PHBPPs should explore how they can work collaboratively with insurers to ensure HBV-exposed infants receive recommended interventions to prevent HBV MTCT. Collaborations could range from sharing immunization and PVST histories to assisting with case management of insured infants. PHBPPs would need to identify and work with the state Medicaid and large insurers in their local jurisdictions to determine the feasibility of this type of collaboration.

ACIP recommends HBV-exposed infants with birth weights of <2000 g receive 3 additional doses of hepatitis B vaccine after the birth dose. Ko et al¹⁸  reported, in their enhanced study of 5 PHBPPs, that 83.3% of underweight infants did not receive the recommended 4 doses of hepatitis B vaccine. Others have reported that underweight infants have a lower response to vaccine with lower mean antibody titers after vaccination.¹⁹ 

Since 2014, 917 underweight infants have been case managed. However, 21.3% of infant cases were closed out before the infant received 4 doses. These findings demonstrate the continued need for PHBPPs to focus on provider and parental education on the specialized vaccine schedule to prevent perinatal HBV transmission in underweight infants.

PHBPPs have recently had the option to report PVST results as indeterminate. Indeterminate results are discrepant, do not allow for a clear interpretation, and may result from either a single test (HBsAg or anti-HBs only) performed or an inconclusive test result. The report allows PVSTs in which only 1 of the 2 tests were conducted to be reported separately in this category. Of 754 indeterminate tests reported, the majority (81.2%) were indeterminate because only 1 of the 2 recommended tests were ordered. This finding reveals another opportunity for both provider and parental education on PVST. For PVST to meet the ACIP recommendations, both HBsAg and anti-HBs tests must be conducted. To assist providers with ordering both recommended tests more easily and eliminating erroneous ordering of tests such as a hepatitis B core antibody test, the CDC has encouraged laboratories to offer PVST panels specifically for infants born to HBV-infected women.²⁰ 

Since 2010, infants who were lost to follow-up for various reasons have been reported as “closed prior to completion of series and/or PVST.” The annual number of infants reported in this category ranged from 1070 to 1536 overall. These infants represent 10.9% of all case-managed infants, which is an improvement over the 13% previously reported as lost to follow-up (National Center for Health Statistics, unpublished observations).

Annual report data are aggregate and self-reported by each grantee and subject to error. Limited built-in checks on data were available within the annual report electronic form. Data analyzed included birth cohorts followed for 2 calendar years, with potential for missing data on vaccine doses and PVST (eg, for an infant born on December 31, 2017, data would be available through December 31, 2018, and potentially data would be missing from January 1, 2019, forward). Additionally, there are limitations to the methodologies for estimating births to HBV-infected women, as previously published by Smith et al,¹¹  and Koneru et al.¹² 

The national PHBPP identified a total of 103 825 infants, ∼49% of the estimated number of infants born to HBsAg-positive women, and case managed 100 372 infants, with ∼96% receiving PEP, 87% receiving ≥3 vaccine doses, and 64% receiving PVST. The program has achieved success in managing a considerable number of infants born to HBV-infected women and ensuring their immunity to HBV infection. Despite this success, there continues to be opportunity for improvement, including closing the gap between the number of infants estimated and identified; vaccine series completion, especially for underweight infants; and conducting recommended PVST for all case-managed infants.

ACIP

Advisory Committee on Immunization Practices

anti-HBs

antibody to hepatitis B surface antigen

CDC

Centers for Disease Control and Prevention

HBIG

hepatitis B immune globulin

HBsAg

hepatitis B surface antigen

HBV

hepatitis B virus

MTCT

mother-to-child transmission

PEP

postexposure prophylaxis

PHBPP

Perinatal Hepatitis B Prevention Program

PVST

postvaccination serological testing