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.

What’s Known on This Subject:

Perinatal transmission of the hepatitis B virus is highly preventable by administering postexposure prophylaxis shortly after birth, followed by a complete vaccine series. Center for Disease Control and Prevention–funded public health jurisdictions identify and case-manage infants born to hepatitis B virus–infected women to prevent perinatal transmission.

What This Study Adds:

We provide national-level programmatic outcomes of 56 funded jurisdictions for birth cohorts 2009–2017 to assess characteristics of maternal-infant pairs and achievement of objectives of infant hepatitis B postexposure prophylaxis, hepatitis B vaccine series completion, and postvaccination serological testing.

Chronic hepatitis B infection is estimated to impact >850 000 people in the United States,1  and perinatal or mother-to-child transmission (MTCT) of hepatitis B virus (HBV) contributes disproportionally to new infections in infants.2  MTCT of HBV infection is highly preventable by administering postexposure prophylaxis (PEP) shortly after birth, followed by a complete hepatitis B vaccine series. The Advisory Committee on Immunization Practices (ACIP) recommends the following: (1) screening pregnant women early in pregnancy for hepatitis B surface antigen (HBsAg), (2) administering PEP, defined as hepatitis B vaccine and hepatitis B immune globulin (HBIG), to infants born to HBV-infected women within 12 hours of birth, (3) completion of the hepatitis B vaccine series by age 6 months, and (4) conducting infant postvaccination serological testing (PVST), consisting of both HBsAg and antibody to hepatitis B surface antigen (anti-HBs) after completion of the vaccine series.35  Since 2015, ACIP has recommended a shortened interval for PVST at age 9 to 12 months (or 1–2 months after the final dose of the vaccine series, if the series is delayed),4  as opposed to the previous recommendation of 9 to 18 months.5 

Without intervention (vaccine and/or HBIG), ∼90% of infants born to women who are both HBsAg-positive and hepatitis B e antigen–positive and ∼32% of infants born to women who are both HBsAg-positive and hepatitis B e antigen–negative become infected with HBV.68  PEP and a complete hepatitis B vaccine series is up to 95% effective in preventing MTCT of HBV infection.6,7,9  Delayed PEP markedly reduces vaccine effectiveness in preventing MTCT.7,10  Among HBV-infected infants, 90% develop chronic HBV infection with a 25% lifetime risk of premature death from complications such as liver failure and liver cancer, perpetuating the cycle of risk for MTCT.3,5 

Since 1990, the Centers for Disease Control and Prevention (CDC) has funded public health jurisdictions (regions managed by state or local public health agencies) to identify HBV-infected (defined as positive for HBsAg) pregnant women and case manage their infants to prevent MTCT of HBV infection.11  This national Perinatal Hepatitis B Prevention Program (PHBPP) aims to ensure infants born to HBV-infected women receive timely PEP, complete a full series of hepatitis B vaccine, and receive PVST after a complete series to confirm immunity, identify infants needing revaccination, and identify infected infants. PHBPP-funded jurisdictions follow these infants for up to 24 months to monitor completion of these recommended interventions. In this article, we describe the PHBPP programmatic outcomes for birth cohorts 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,1113  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).

TABLE 1

Outcomes of Infants Case Managed by PHBPP, 56 US Jurisdictions, Birth Cohorts 2009–2017

Birth CohortTotal, nCase-Managed Infants, n (%)
Range by Jurisdiction (Minimum, Maximum)Hepatitis B Administration PVSTa
EstimatedIdentified% Identified/EstimatedCase ManagedHBIG + Hepatitis B at Birth (%)3 Doses by 8–12 mo (%)3 Doses After 12 mob (%)Total 3 Doses (%)Received, n (%)HBsAg-positive, n (%)Anti-HBs ≥10 mIU/mL, n (%)
Total 214 064 (136, 46 744) 103 825 (9, 20 955) 48.5 (6.6, 44.8) 100 372 (8, 19 605) 96 629 (96.3) 85 421 (85.1) 1578 (1.6) 86 999 (86.7) 63 858 (63.6) 376 (0.6) 59 105 (92.6) 
2009 24 804 (14, 5481) 11 930 (1, 2138) 48.1 (7.1, 105.8) 11 551 (1, 2122) 10 937 (94.7) 9597 (83.1) — (—) 9597 (83.1) 6792 (58.8) 63 (0.9) 5552 (81.7) 
2010 24 223 (13, 5253) 11 456 (1, 2184) 47.3 (7.7, 102.0) 11 054 (0, 2015) 10 580 (95.7) 9534 (86.2) 231 (2.1) 9765 (88.3) 6637 (60) 47 (0.7) 5991 (94.4) 
2011 24 589 (14, 5297) 11 430 (0, 2173) 46.5 (0.0, 94.9) 11 018 (0, 1944) 10 650 (96.7) 9519 (86.4) 164 (1.5) 9683 (87.9) 6852 (62.2) 47 (0.7) 6200 (90.5) 
2012 25 912 (14, 5833) 12 103 (0, 2549) 46.7 (0.0, 103.7) 11 687 (0, 2343) 11 333 (97) 10 127 (86.7) 168 (1.4) 10 295 (88.1) 7433 (63.6) 60 (0.8) 7024 (94.5) 
2013 25 268 (16, 5715) 11 249 (0, 2295) 44.5 (0.0, 94.4) 10 769 (0, 2013) 10 402 (96.6) 9329 (86.6) 134 (1.2) 9463 (87.9) 7053 (65.5) 36 (0.5) 6652 (94.3) 
2014 26 444 (14, 6243) 11 632 (1, 2615) 44.0 (3.0, 91.7) 11 186 (1, 2404) 10 726c (95.9) 9475 (84.7) 254 (2.3) 9729 (87) 7276 (65) 34 (0.5) 6916 (95.1) 
2015 20 678 (17, 4134) 11 498 (2, 2365) 55.6 (9.5, 107.5) 11 000 (2, 2156) 10 627 (96.6) 9149 (83.2) 331 (3) 9480 (86.2) 7135 (64.9) 30 (0.4) 6756 (94.7) 
2016 21 314 (17, 4473) 11 571 (3, 2442) 54.3 (13.6, 106.3) 11 350 (3, 2432) 10 980 (96.7) 9583 (84.4) 181 (1.6) 9764 (86) 7499 (66.1) 30 (0.4) 7143 (95.3) 
2017 20 832 (17, 4315) 10 956 (1, 2194) 52.6 (5.3, 96.0) 10 757 (1, 2176) 10 394 (96.6) 9108 (84.7) 115 (1.1) 9223 (85.7) 7181 (66.8) 29 (0.4) 6871 (95.7) 
Pd 0.0581 0.1498 0.0983 0.2886 0.5238 (0.0952) 0.1826 (0.5377) 0.9092 (0.9492) 0.1896 (0.9442) 0.0315 (0.0002) 0.0029 (0.0006) 0.0056 (0.0390) 
Birth CohortTotal, nCase-Managed Infants, n (%)
Range by Jurisdiction (Minimum, Maximum)Hepatitis B Administration PVSTa
EstimatedIdentified% Identified/EstimatedCase ManagedHBIG + Hepatitis B at Birth (%)3 Doses by 8–12 mo (%)3 Doses After 12 mob (%)Total 3 Doses (%)Received, n (%)HBsAg-positive, n (%)Anti-HBs ≥10 mIU/mL, n (%)
Total 214 064 (136, 46 744) 103 825 (9, 20 955) 48.5 (6.6, 44.8) 100 372 (8, 19 605) 96 629 (96.3) 85 421 (85.1) 1578 (1.6) 86 999 (86.7) 63 858 (63.6) 376 (0.6) 59 105 (92.6) 
2009 24 804 (14, 5481) 11 930 (1, 2138) 48.1 (7.1, 105.8) 11 551 (1, 2122) 10 937 (94.7) 9597 (83.1) — (—) 9597 (83.1) 6792 (58.8) 63 (0.9) 5552 (81.7) 
2010 24 223 (13, 5253) 11 456 (1, 2184) 47.3 (7.7, 102.0) 11 054 (0, 2015) 10 580 (95.7) 9534 (86.2) 231 (2.1) 9765 (88.3) 6637 (60) 47 (0.7) 5991 (94.4) 
2011 24 589 (14, 5297) 11 430 (0, 2173) 46.5 (0.0, 94.9) 11 018 (0, 1944) 10 650 (96.7) 9519 (86.4) 164 (1.5) 9683 (87.9) 6852 (62.2) 47 (0.7) 6200 (90.5) 
2012 25 912 (14, 5833) 12 103 (0, 2549) 46.7 (0.0, 103.7) 11 687 (0, 2343) 11 333 (97) 10 127 (86.7) 168 (1.4) 10 295 (88.1) 7433 (63.6) 60 (0.8) 7024 (94.5) 
2013 25 268 (16, 5715) 11 249 (0, 2295) 44.5 (0.0, 94.4) 10 769 (0, 2013) 10 402 (96.6) 9329 (86.6) 134 (1.2) 9463 (87.9) 7053 (65.5) 36 (0.5) 6652 (94.3) 
2014 26 444 (14, 6243) 11 632 (1, 2615) 44.0 (3.0, 91.7) 11 186 (1, 2404) 10 726c (95.9) 9475 (84.7) 254 (2.3) 9729 (87) 7276 (65) 34 (0.5) 6916 (95.1) 
2015 20 678 (17, 4134) 11 498 (2, 2365) 55.6 (9.5, 107.5) 11 000 (2, 2156) 10 627 (96.6) 9149 (83.2) 331 (3) 9480 (86.2) 7135 (64.9) 30 (0.4) 6756 (94.7) 
2016 21 314 (17, 4473) 11 571 (3, 2442) 54.3 (13.6, 106.3) 11 350 (3, 2432) 10 980 (96.7) 9583 (84.4) 181 (1.6) 9764 (86) 7499 (66.1) 30 (0.4) 7143 (95.3) 
2017 20 832 (17, 4315) 10 956 (1, 2194) 52.6 (5.3, 96.0) 10 757 (1, 2176) 10 394 (96.6) 9108 (84.7) 115 (1.1) 9223 (85.7) 7181 (66.8) 29 (0.4) 6871 (95.7) 
Pd 0.0581 0.1498 0.0983 0.2886 0.5238 (0.0952) 0.1826 (0.5377) 0.9092 (0.9492) 0.1896 (0.9442) 0.0315 (0.0002) 0.0029 (0.0006) 0.0056 (0.0390) 

—, not applicable.

a

PVST includes all infants case managed, including both those who did and did not receive PEP. Because of data limitations, PVST is defined here as a test for HBsAg, a test for anti-HBs, or both.

b

Three doses after 12 mo and by the end of reporting period 1; this category can include infants who received a 4-dose series.

c

PEP (HBIG + hepatitis B birth dose) data from 1 jurisdiction (Philadelphia) were limited because of the exclusion of infants who did not have documented PEP from the birthing facility.

d

P values in parentheses reflect trends in proportions shown in the column.

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).

TABLE 2

Indeterminate Infant PVST and Single Tests, Birth Cohorts 2014–2017

Birth CohortIndeterminate PVSTaHBsAg Test OnlyAnti-HBs Test Only% of Indeterminate Tests due to Single Test Performed
2014 166 45 84 77.7 
2015 198 70 104 87.9 
2016 197 59 98 79.7 
2017 193 72 80 78.8 
Total 754 246 366 81.2 
Birth CohortIndeterminate PVSTaHBsAg Test OnlyAnti-HBs Test Only% of Indeterminate Tests due to Single Test Performed
2014 166 45 84 77.7 
2015 198 70 104 87.9 
2016 197 59 98 79.7 
2017 193 72 80 78.8 
Total 754 246 366 81.2 
a

Indeterminate PVST is defined as either a single test (HBsAg or anti-HBs only) performed or an inconclusive laboratory test result.

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).

FIGURE 1

Infants born to HBsAg-positive women and identified, birth cohorts 2009–2017, United States. Birth estimates, number of infants estimated to be born to HBsAg-positive women for each birth cohort year; PHBPP identified, number of infants identified by the PHBPP born in a birth cohort year. a Estimated births were calculated by using the race and ethnicity model for birth cohorts 2009–2014 and the maternal country of birth model for cohorts 2015–2017. The dashed line indicates the transition to changed methodology.

FIGURE 1

Infants born to HBsAg-positive women and identified, birth cohorts 2009–2017, United States. Birth estimates, number of infants estimated to be born to HBsAg-positive women for each birth cohort year; PHBPP identified, number of infants identified by the PHBPP born in a birth cohort year. a Estimated births were calculated by using the race and ethnicity model for birth cohorts 2009–2014 and the maternal country of birth model for cohorts 2015–2017. The dashed line indicates the transition to changed methodology.

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FIGURE 2

Programmatic outcomes of infants born to HBsAg-positive women, birth cohorts 2009–2017, United States. PHBPP identified, number of infants identified by the PHBPP; case managed, number of infants case managed by the PHBPP; PEP, number of infants who received PEP for HBV; PVST, number of infants who received PVST after hepatitis B vaccine series completion.

FIGURE 2

Programmatic outcomes of infants born to HBsAg-positive women, birth cohorts 2009–2017, United States. PHBPP identified, number of infants identified by the PHBPP; case managed, number of infants case managed by the PHBPP; PEP, number of infants who received PEP for HBV; PVST, number of infants who received PVST after hepatitis B vaccine series completion.

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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.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Ms Koneru conceptualized and designed the study, collected data, conducted the analyses, interpreted data and results, and drafted the initial manuscript; Ms Fenlon conceptualized the study, designed a data collection instrument, collected data, and assisted with the analyses and initial manuscript; Drs Schillie, Williams, and Nelson provided subject matter expertise and assisted in interpretation of data; Dr Weng assisted in interpretation of data; and all authors reviewed and revised the manuscript, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.

FUNDING: No external funding.

COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2020-037549.

     
  • 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

1
Patel
EU
,
Thio
CL
,
Boon
D
,
Thomas
DL
,
Tobian
AAR
.
Prevalence of hepatitis B and hepatitis D virus infections in the United States, 2011–2016
.
Clin Infect Dis
.
2019
;
69
(
4
):
709
712
2
Schweitzer
A
,
Horn
J
,
Mikolajczyk
RT
,
Krause
G
,
Ott
JJ
.
Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013
.
Lancet
.
2015
;
386
(
10003
):
1546
1555
3
Schillie
S
,
Vellozzi
C
,
Reingold
A
, et al
.
Prevention of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices
.
MMWR Recomm Rep
.
2018
;
67
(
1
):
1
31
4
Schillie
S
,
Walker
T
,
Veselsky
S
, et al
.
Outcomes of infants born to women infected with hepatitis B
.
Pediatrics
.
2015
;
135
(
5
):
e1141
e1147
5
Mast
EE
,
Margolis
HS
,
Fiore
AE
, et al.;
Advisory Committee on Immunization Practices
.
A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. [published correction appears in MMWR Morb Mortal Wkly Rep. 2006;55(6):158–159 and MMWR Morb Mortal Wkly Rep. 2007;56(48):1267]
.
MMWR Recomm Rep
.
2005
;
54
(
rr
):
1
31
6
Lee
C
,
Gong
Y
,
Brok
J
,
Boxall
EH
,
Gluud
C
.
Effect of hepatitis B immunisation in newborn infants of mothers positive for hepatitis B surface antigen: systematic review and meta-analysis
.
BMJ
.
2006
;
332
(
7537
):
328
336
7
Beasley
RP
,
Hwang
LY
,
Lee
GC
, et al
.
Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine
.
Lancet
.
1983
;
2
(
8359
):
1099
1102
8
Beasley
RP
,
Trepo
C
,
Stevens
CE
,
Szmuness
W
.
The e antigen and vertical transmission of hepatitis B surface antigen
.
Am J Epidemiol
.
1977
;
105
(
2
):
94
98
9
Wong
VC
,
Ip
HM
,
Reesink
HW
, et al
.
Prevention of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg by administration of hepatitis-B vaccine and hepatitis-B immunoglobulin. Double-blind randomised placebo-controlled study
.
Lancet
.
1984
;
1
(
8383
):
921
926
10
Marion
PL
.
Use of animal models to study hepatitis B virus
.
Prog Med Virol
.
1988
;
35
:
43
75
11
Smith
EA
,
Jacques-Carroll
L
,
Walker
TY
,
Sirotkin
B
,
Murphy
TV
.
The national Perinatal Hepatitis B Prevention Program, 1994-2008
.
Pediatrics
.
2012
;
129
(
4
):
609
616
12
Koneru
A
,
Schillie
S
,
Roberts
H
, et al
.
Estimating annual births to hepatitis B surface antigen-positive women in the United States by using data on maternal country of birth
.
Public Health Rep
.
2019
;
134
(
3
):
255
263
13
Ko
SC
,
Fan
L
,
Smith
EA
,
Fenlon
N
,
Koneru
AK
,
Murphy
TV
.
Estimated annual perinatal hepatitis B virus infections in the United States, 2000–2009
.
J Pediatric Infect Dis Soc
.
2016
;
5
(
2
):
114
121
14
Kolasa
MS
,
Tsai
Y
,
Xu
J
,
Fenlon
N
,
Schillie
S
.
Hepatitis B surface antigen testing among pregnant women, United States 2014
.
Pediatr Infect Dis J
.
2017
;
36
(
7
):
e175
e180
15
Centers for Disease Control and Prevention
.
Laboratory reporting of pregnancy status for hepatitis B-positive women
.
2015
. Available at: https://www.cdc.gov/hepatitis/hbv/pregstatuslabreporting.htm. Accessed October 1, 2019
16
Kuncio
DE
,
Newbern
EC
,
Ma
L
, et al
.
Capture-recapture: using existing data sources to improve perinatal hepatitis B surveillance, Philadelphia, 2008–2014
.
Public Health Rep
.
2017
;
132
(
3
):
376
380
17
Immunization Action Coalition
.
Hepatitis B birth dose honor roll
. Available at: https://www.immunize.org/honor-roll/birthdose/. Accessed October 10, 2019
18
Ko
SC
,
Schillie
SF
,
Walker
T
, et al
.
Hepatitis B vaccine response among infants born to hepatitis B surface antigen-positive women
.
Vaccine
.
2014
;
32
(
18
):
2127
2133
19
Schillie
SF
,
Murphy
TV
.
Seroprotection after recombinant hepatitis B vaccination among newborn infants: a review
.
Vaccine
.
2013
;
31
(
21
):
2506
2516
20
Centers for Disease Control and Prevention
.
Post-vaccination serologic testing (PVST) panels for infants born to hepatitis B virus (HBV)-infected women
.
2016
. Available at: https://www.cdc.gov/hepatitis/hbv/pvst.htm. Accessed September 27, 2019

Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.