Discrepant Hepatitis B Surface Antigen Results in Pregnant Women Screened to Identify Hepatitis B Virus Infection Steven L. Veselsky, MPH1,*, Tanja Y. Walker, MPH1,†, Nancy Fenlon, MS2, Chong-Gee Teo, MD, PhD1, and Trudy V. Murphy, MD1 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. (J Pediatr 2014;165:773-8).


erinatal hepatitis B virus (HBV) transmission is an important source of new chronic HBV infections. Up to 90% of infants infected with HBV develop chronic infection and 25% risk premature death from liver failure or hepatocellular carcinoma.1-3 Completion of postexposure prophylaxis starting with hepatitis B vaccination and hepatitis B immunoglobulin administered within 12 hours of birth can prevent 85%-95% of perinatal HBV infections.1,2 In 2008, an estimated 25 000 infants in the US were at risk for perinatal HBV transmission by virtue of being born to a woman infected with HBV.4 To identify pregnant women infected with HBV and prepare postexposure prophylaxis for their infants, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) recommends screening for HBV infection at the first prenatal visit of each pregnancy.2,5 Most women will receive hepatitis B surface antigen (HBsAg) screening only once during each pregnancy, but repeat screening may be indicated at the discretion of the provider (eg, when the initial results are inconsistent with the vaccination history, for medical indications, when the patient is high risk for HBV infection, or during care for acute or From the Division of Viral Hepatitis, National Center for chronic HBV infection).2,6 The Advisory Committee on Immunization Practices HIV/AIDS, Viral Hepatitis, Sexually Transmitted Diseases, also recommends rescreening at delivery if women are at increased risk for HBV and Tuberculosis Prevention, and Immunization Services Division, National Center for Immunization and infection.2 In Texas, state code requires HBsAg testing twice during each pregRespiratory Diseases, US Centers for Disease Control and Prevention, Atlanta, GA nancy, at the first prenatal visit and again at delivery.7 *S.V. currently works in the Division of Global HIV/AIDS, HBsAg is the serologic test recommended for screening pregnant women and Center for Global Health, US Centers for Disease Control and Prevention, Atlanta, GA. will identify women with either acute or chronic HBV infection. If the results of †T.W. currently works in the Division of HIV/AIDS initial and subsequent tests are discordant, resolution of the discrepancy becomes Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, US Centers for Disease Control a priority to ensure appropriate postexposure management of the infants at birth. 1


and Prevention, Atlanta, GA.


Antibody to hepatitis B core antigen Antibody to hepatitis B surface antigen Centers for Disease Control and Prevention Food and Drug Administration Hepatitis B surface antigen Hepatitis B virus Hepatitis B viral DNA Perinatal Hepatitis B Prevention Program

Supported by 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 (ORISE Interagency Agreement [12FED1209578]) between the US Department of Energy and the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the Centers for Disease Control and Prevention. The authors declare no conflicts of interest. Portions of the study were presented as an abstract at the Pediatric Academic Societies’ meeting, May 3-6, 2014, Vancouver, Canada. 0022-3476/$ - see front matter. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jpeds.2014.06.043




We evaluated discrepant HBsAg screening results from pregnant women whose initial test result was reactive, and report how the discrepancies were resolved.

Methods Since 1990, the US Perinatal Hepatitis B Prevention Programs (PHBPPs) in 64 public health jurisdictions were funded by CDC immunization grants to support and accelerate elimination of perinatal HBV infection.2,4 PHBPPs identify pregnant women with HBV infection to educate and assist the women, and ensure timely initiation and completion of postexposure prophylaxis for their infants.2 From April 1, 2009 to December 31, 2011, PHBPP coordinators were invited to voluntarily report to the CDC discrepant HBsAg results from pregnant women screened for HBV infection. This project was determined to be program evaluation and, therefore, exempt from institutional review board review and approval. A case of discrepant HBsAg results was defined as a woman with reactive HBsAg result when initially screened during pregnancy, followed by a nonreactive HBsAg result when subsequently tested during the same pregnancy. A standard definition of a reactive HBsAg test is a value $10 mIU/mL, but is assay dependent. Cases were excluded if they did not meet the case definition or if the subject was a child or nonpregnant woman. PHBPP coordinators received a uniform data collection form and protocols defining eligibility for report of discrepant cases. De-identified data were sent to the CDC via electronic submission to a secure e-mail account and by mail. Information about the pregnant women included age, race/ethnicity, expected and actual date of delivery, hepatitis B vaccination history including dates of vaccination, and other major medical conditions (eg, chronic liver disease, HIV, and other immunocompromising conditions). Laboratory information included all HBsAg and confirmatory tests (Food and Drug Administration [FDA]-approved neutralization assays), dates, and results during the current pregnancy, the type of HBsAg assay, the assay manufacturer, signal-to-cut-off ratio (a measure of the strength of the reaction in the test sample relative to the control sample) when available, and test results and dates of additional HBV serologic markers (eg, total antibody to hepatitis B core antigen [anti-HBc], IgM anti-HBc, hepatitis B viral DNA [HBV DNA], hepatitis B e antigen, antibody to hepatitis B e antigen, and antibody to HBsAg [anti-HBs]). Liver function test results were not requested. Perinatal coordinators provided de-identified copies of original laboratory reports when requested to clarify information on the data collection form. Perinatal coordinators and the CDC contacted laboratories to complete missing information using unique identification numbers created by the local health department, and laboratory identification numbers so that case information remained de-identified. Data were abstracted and stored in a secure database. To resolve discrepancies, available results were reviewed by 3 viral hepatitis experts and a clinical virologist for 774

Vol. 165, No. 4 agreement on a resolution category. Cases were categorized into 3 distinct groups based on the initial HBsAg-test results—probable true positive, probable false positive, and unresolved. Probable true positive was defined as an initial reactive HBsAg result with evidence of acute or chronic HBV infection, including detectable HBV DNA, and/or positive total anti-HBc and/or IgM anti-HBc. A history of hepatitis B vaccination within 1 month of HBsAgtesting without serologic evidence of HBV infection was also defined as a true positive; detection of vaccinederived HBsAg has been reported for up to 3 days in adults and 18 days in infants after vaccination.8,9 The initial HBsAg result was defined as probable false positive when available tests lacked specific markers for HBV infection (ie, no detectable HBV DNA, or negative tests for total anti-HBc or both total and IgM anti-HBc). Cases were deemed unresolved if no additional serology (with or without relevant vaccination history) was available, or if additional serology was insufficient to confirm or exclude HBV infection or recent vaccination (eg, negative IgM anti-HBc without total anti-HBc). Analysis was based on summary frequencies. The test date relative to the actual or expected date of delivery was calculated backward in weeks. Statistical analyses were conducted using SAS 9.3 (SAS Institute, Cary, North Carolina).

Results Testing results from 187 cases of discrepant HBsAg results were submitted. Ten cases were excluded because the subject was a child or a nonpregnant woman; 35 additional cases failed to meet the case definition, and 23 (65.7%) of these with an initial reactive HBsAg result were nonreactive on confirmatory testing. Twenty-nine cases with no or unknown confirmatory testing were included. The final sample consisted of 142 cases. Discrepant HBsAg-test results were submitted from 9 states (Arizona, California, Florida, Maryland, Massachusetts, Michigan, North Dakota, Oregon, and Texas) (Table I). Forty-three (30.2%) cases that were resolved locally by PHBPP coordinators prior to submission were independently reassessed for this evaluation. Coordinators requested CDC input to resolve 69 (48.6%) pending cases; the status of the remaining 30 cases was not reported. The majority of initial HBsAg testing was performed by national commercial or hospital laboratories (Table I). The median age of cases was 27 (range 17-49) years at initial HBsAg test (Table II); more than 50% were among women aged 20-29 years. The largest proportion of cases (38.7%) was among Hispanic women; 57.4% of cases in Hispanic women were reported by Texas. Asian-Pacific Islander women accounted for less than 10% of cases. The median time of the initial HBsAg test before the expected or actual date of delivery was approximately 24 weeks (range, 0 week [delivery]-36 weeks). Chronic medical conditions including hepatitis C were uncommon (Table II). Information on hepatitis B vaccination was available for Veselsky et al


October 2014

Table I. Cases of discrepant HBsAg results from 142 passively reported cases in pregnant women, by state and laboratory type Characteristics State Texas Florida California Michigan Massachusetts Maryland North Dakota Arizona Oregon Types of laboratory performing initial test National commercial Hospital State public health Regional/local Not reported

No. (%) 57 (40.1) 27 (19.0) 26 (18.3) 20 (14.1) 6 (4.3) 2 (1.4) 2 (1.4) 1 (0.7) 1 (0.7) 73 (51.4) 53 (37.3) 8 (5.6) 7 (5.0) 1 (0.7)

62 women; 25 (41%) women with information reported receiving 1 or more doses, including one woman who received the first dose of vaccine 3 days before the initial HBsAg test. All HBsAg assays were FDA-approved (Table III). The HBsAg result was confirmed in 79.5% of initial HBsAg tests; the confirmatory test was performed by neutralization in more than one-half of initial specimens. The average and median number of days between the initial reactive and nonreactive test was 69.5 and 32 days, respectively. The same assay was used for initial and subsequent HBsAg tests

Table II. Characteristics of 142 pregnant women with discrepant HBsAg results Characteristics Age #19 y 20-29 y 30-39 y $40 y Race/ethnicity Hispanic Black, non-Hispanic White, non-Hispanic Asian/Pacific Islander Unknown Hepatitis C Yes No Unknown Other major medical condition Yes No Unknown History of hepatitis B vaccine Yes No Unknown Vaccination in month before initial HBsAg test Yes No Unknown

No. (%) 16 (11.2) 78 (55.0) 44 (31.0) 4 (2.8) 55 (38.7) 25 (17.6) 25 (17.6) 12 (8.5) 25 (17.6) 2 (1.4) 115 (81.0) 25 (17.6) 0 (0) 105 (73.9) 37 (26.1) 25 (17.6) 37 (26.1) 80 (56.3) 1 (0.7) 61 (43.0) 80 (56.3)

Table III. HBsAg assays Initial HBsAg assay CIAs* Chemiluminometric microparticle immunoassay Chemiluminescent EIA Chemiluminescent microparticle Immunoassay EIAs† Microparticle EIA EIA or ELISA Not reported Confirmatory test Yes No Not reported Confirmation method Neutralization Other/unknown Not reported

No. (%) 21 (14.8) 27 (19.1) 10 (7.0) 5 (3.5) 5 (3.5) 74 (52.1) 113 (79.5) 15 (10.5) 14 (10.0) 80 (56.3) 33 (23.2) 29 (20.5)

Subsequent HBsAg assay Same Different Unknown/not reported

47 (33.1) 17 (11.9) 78 (55.0)

CIA, chemiluminescent immunoassay; EIA, enzyme immunoassay; ELISA, enzyme-linked immunosorbent assay. *Includes Advia Centaur (Siemens Healthcare Diagnostics, Inc, Tarrytown, New York), Ortho Vitros ECi (Ortho-Clinical Diagnostics, Inc, Rochester, New York), Abbott Architect (Abbott Laboratories, Abbott Park, Illinois), Abbott Prism (Abbott Laboratories), and Immulite 1000/2000 (Siemens Healthcare Diagnostics, Inc). †Includes Ortho ELISA (Ortho-Clinical Diagnostics, Inc), GS HBsAg EIA 3.0 (Bio-Rad Laboratories, Redmond, Washington), ETI-MAK 2 Plus EIA (DiaSorin, Inc, Stillwater, Minnesota), and Abbott AxSYM (Abbott Laboratories).

in 33.1% of cases. Signal-to-cutoff ratio information was incomplete or unavailable for most cases and was, therefore, not considered in the evaluation. Resolution of Discrepant HBsAg Results Sufficient information was available to resolve the discrepant HBsAg results in 89 (62.7%) cases (Table IV). The remaining 53 unresolved cases lacked key laboratory information. All cases with total anti-HBc antibody results were resolved. Total anti-HBc results were available for 78 (87.6%) of the 89 resolved cases and for none of the cases that remained unresolved. True Positives Fourteen HBsAg-discrepant cases, which constituted 9.8% of overall cases and 15.7% of resolved cases, were probable true positive. The majority (11) of the cases had a positive total anti-HBc result subsequent to the initial reactive HBsAg result. Two women were positive for IgM anti-HBc only, suggesting they were recovering from acute HBV infection, particularly as the subsequent HBsAg result was nonreactive. Another woman received hepatitis B vaccination 3 days before the specimen was obtained for HBsAg testing; her initial reactive HBsAg result could have resulted from vaccine-derived HBsAg, which was no longer detectable on subsequent testing. One woman with positive total antiHBc reported past vaccination, although dates and number of doses were not available; for this woman, her initial reactive HBsAg was interpreted as a probable initial true positive HBsAg result.

Discrepant Hepatitis B Surface Antigen Results in Pregnant Women Screened to Identify Hepatitis B Virus Infection




Table IV. Interpretation of initial reactive HBsAg from pregnant women with discrepant HBsAg results Resolution of initial HBsAg-result

No. (%)

Probable true positive

14 (9.8)

Additional information

Positive total anti-HBc Positive IgM anti-HBc Vaccination 3 days before HBsAg testing* Probable false positive 75 (52.8) Negative total anti-HBc No HBV DNA detected Technical error reported by laboratory Unresolved 53 (37.4) No additional serology, no history of vaccination Negative IgM anti-HBc Negative IgM anti-HBc, negative anti-HBs Negative IgM anti-HBc, negative HBeAg Negative anti-HBs Negative anti-HBs, negative HBeAg Positive anti-HBs, unknown vaccination history

No. (%) 11 (78.6) 2 (14.3) 1 (7.1) 67 (89.3) 6 (8.0) 2 (2.7) 28 (52.8) 17 (32.1) 3 (5.7) 1 (1.9) 1 (1.9) 2 (3.8) 1 (1.9)

HBeAg, hepatitis B e antigen. *HBsAg in vaccine is reported to be detectable for $18 days after vaccination.

False Positives More than one-half (n = 75, 52.8%) of the 142 discrepant cases were resolved as probable initial false positive HBsAg. Most (n = 67, 89.3%) had a negative total anti-HBc result, indicating no past or current HBV infection. Eleven (16.4%) of these cases also had history of hepatitis B vaccination (3 doses [n = 8], 2 doses [n = 1], and unknown number of doses [n = 2]). Six cases were resolved by tests indicating no detectable HBV DNA; 1 of the 6 women had previously received 3 doses of hepatitis B vaccine. A laboratory reported technical error accounted for 2 initially reactive HBsAg results; 1 woman had received 3 doses of hepatitis B vaccine, and the vaccine history was unknown for the other woman. Unresolved Of 53 cases that remained unresolved, more than one-half had no additional serology; 4 had a history of 3 doses of hepatitis B vaccine. Approximately one-third were tested for IgM anti-HBc, presumably to determine if they had acute HBV infection; 2 of the cases reported past hepatitis B vaccination (1 with 1 dose, and 1 with an unknown number of doses). None was tested for total anti-HBc.

Discussion Discrepant HBsAg results in pregnant women screened for HBV infection pose a challenge to ensuring optimal prevention of perinatal HBV transmission and require prompt attention for resolution. Accurate resolution informs women of their HBV infection status, assists in determining appropriate care, and allows time to prepare for neonatal postexposure 776

Vol. 165, No. 4 prophylaxis, if necessary.2,10 Additional training on interpretation of discrepant HBsAg results and on selection of follow-up serology might be useful for persons who regularly interpret HBV serologic results to avoid unnecessary prenatal visits, the costs of blood draws and testing, and generating unwarranted concern. Misunderstanding of results or misinterpretation of HBV serological markers is a common reason for failure to resolve discrepancies.11 Although guidance is generally available for interpreting serologic results for HBV infection, little or no guidance is available for resolving discrepant HBsAg results, including results from pregnant women screened for HBV infection.2,12 We found that more than 50% of cases already had a negative total anti-HBc or no detectable HBV DNA result indicating no HBV infection. Less than 16% of resolved discrepant cases were true HBsAg positives. A positive total anti-HBc indicates current or past HBV infection, is not elicited by vaccination, and usually persists for life.13,14 However, without other HBV markers, discrepant cases require additional testing to confirm acute HBV infection, resolved infection, or chronic infection. The presence of IgM anti-HBc usually indicates acute or recent infection and can persist for more than 6 months. A subsequent nonreactive HBsAg result suggests recovery from the infection. However, IgM anti-HBc can persist at low levels during viral replication in chronically infected persons, become transiently elevated during reactivation, or be a false positive result, thereby complicating interpretation.15-18 HBV DNA, like HBsAg, is a marker of active HBV replication and its detection confirms that the initial HBsAg result is a true positive. Moreover, HBV DNA assays can detect HBV at levels below those of HBsAg assays (eg, in “occult HBV infection,” or when a mutant HBV strain results in a nonreactive test for HBsAg).15,16 Evidence for perinatal transmission from pregnant women with occult HBV infection is inconclusive, and no recommendation addresses HBV prophylaxis for infants in this situation, which would generally not be detected by HBsAg testing alone.19 For this reason, administering the first dose of hepatitis B vaccine within 12 hours of birth might be warranted for infants born to pregnant women with unresolved discrepant HBsAg results. When identified, maternal infection with a mutant HBV strain constitutes an indication for postexposure prophylaxis for the infant, although efficacy is uncertain if such mutants confer vaccine escape.20,21 The absence of detectable HBV DNA and a nonreactive HBsAg result at follow-up testing indicates very low or no risk for perinatal HBV transmission, even in the presence of positive total anti-HBc.16 Testing for anti-HBs was not helpful for resolving discrepant cases whose follow-up samples were negative for HBsAg, HBV DNA and anti-HBc. In 1 woman with a positive anti-HBs result, detection likely excluded a true reactive HBsAg but did not discriminate between HBV infection and hepatitis B vaccination.16 During 2009-2011, at least 11 HBsAg assays were FDAapproved for HBsAg testing (http://www.cdc.gov/hepatitis/ Partners/PeriHepBCoord.htm). Specimens with reactive Veselsky et al

October 2014 results are routinely retested, and if reactive on repeat testing, the results should be confirmed by an FDA-approved neutralization assay. Not all laboratories routinely confirm reactive HBsAg, especially when the laboratory is not informed that the specimen is from a pregnant woman. Providers should be aware that they may have to request confirmatory testing for reactive HBsAg results if not done. The results of at least 10% of initial reactive HBsAg tests in our study sample were not confirmed. Confirmatory testing allows for identification of true positives when the level is substantially above the limit of detection. Although highly sensitive, HBsAg assays and confirmatory tests have limited sensitivity at the lower limits of detection (near the cut-off value for low HBsAg levels). When results are in that so-called “gray zone,” repeat testing of the same or subsequent specimens can result in discrepancies. We speculate that a substantial proportion of unresolved and false positive cases had results in the “gray zone.” Clinical and management dilemmas can arise when discrepant HBsAg screening results represent a false negative or a false positive. The clinical consequences of false negative HBsAg results include failure to manage the women for their liver disease and failure to administer postexposure prophylaxis for their infants. Clinical consequences of false positive HBsAg results might result in unnecessary infant postexposure prophylaxis, additional costs, and the psycho-social consequences of misdiagnosis. Ideally, discrepant results are resolved soon after they are recognized, and before pregnant women deliver. If not, infants born to women with unresolved discrepant results might be managed as recommended for women with unknown maternal screening results.2 Although the discrepant cases in this series consisted of a nonrepresentative convenience sample, the proportion of cases among Asian/Pacific Islander women (50% of pregnant women infected with HBV in the US, and constitute the race/ethnic group with the highest prevalence of HBsAg-positivity.22,23 Asian/Pacific Islander women infected with HBV often are infected with HBV genotype B or C, which is associated with persistence of high HBsAg load, and therefore, might be less likely to have discrepant HBsAg-test result than women with lower HBsAg load.15 The largest proportion of cases in our study sample was from Hispanic women. Hispanic women from the Americas generally are infected with HBV genotype A or H, which is associated with lower levels of HBV viremia by childbearing age than with genotypes B and C.24 In Texas, the population is roughly one-third Hispanic, and all pregnant women were routinely tested twice during each pregnancy. These factors likely increased the chance that women who had results in the “gray zone” could manifest discrepant HBsAg test outcomes. Laboratory errors were uncommonly reported among our discrepant cases. Although the specific types of errors were not reported, possible errors might have included procedural or technical problems (eg, improper dilution techniques), failure to confirm initially reactive specimens, or use of a

ORIGINAL ARTICLES defective test kit. We did not identify assays that generated excess discrepant cases. This evaluation has several limitations. The sample was based on passive, voluntary reporting, and therefore, was not representative of the population, or possible to estimate how often discrepant cases arose. Given the retrospective approach of the analysis, we could not validate an algorithm for resolving discrepant HBsAg test results. The retrospective approach also limited determination of sensitivity and specificity of HBsAg screening tests. Our evaluation was restricted to cases with an initial reactive HBsAg result followed by a nonreactive result during the same pregnancy; other sequences of discrepant results would have been possible. In addition, the completeness of the data was inconsistent, as some reports included de-identified original laboratory results, and other reports included data abstracted by health department personnel. We requested signal-to-cut off ratios from the participating laboratories but were not able to obtain this information in the majority of cases. Laboratories reported that they retain this information for only a few days after the assay is performed. Without these ratios, it was not possible to determine which of the discrepant cases resulted from weakly reactive or weakly nonreactive HBsAg readings, which could have contributed to, respectively, false positive or false negative results. Finally, misclassification error was possible depending on the amount of information known for each case. Some cases considered probable true positives based on a positive total anti-HBc might have been considered unresolved by others. In conclusion, although the majority of discrepant HBsAgreactive screening results from this retrospective analysis of pregnant women were false positives, true positives occurred. Total anti-HBc was the most useful single test to resolve HBsAg discrepancies. Validation of a testing algorithm for resolving discrepant results will require prospective studies. n We acknowledge the valuable contributions of Jan Drobeniuc, MD, PhD, Emily A. Smith, MPH, and Susan Wang, MD, MPH (Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, Sexually Transmitted Disease, and Tuberculosis Prevention; US Centers for Disease Control and Prevention), Lisa Jacques-Carroll, MSW (National Center for Immunization and Respiratory Diseases, US Centers for Disease Control and Prevention), and Perinatal Hepatitis B Prevention, Program coordinators from Arizona, California, Florida, Massachusetts, Maryland, Michigan, North Dakota, Oregon, and Texas. Submitted for publication Dec 9, 2013; last revision received Apr 15, 2014; accepted Jun 12, 2014. Reprint requests: Steven L. Veselsky, MPH, Division of Global HIV/AIDS, Centers for Disease Control and Prevention, MS E-30, 1600 Clifton Rd, Atlanta, GA 30333. E-mail: [email protected]

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Discrepant Hepatitis B Surface Antigen Results in Pregnant Women Screened to Identify Hepatitis B Virus Infection




2. Mast EE, Margolis HS, Fiore AE, Brink EW, Goldstein ST, Wang SA, et al. 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. MMWR Recomm Rep 2005;54:1-31. 3. McMahon BJ, Bulkow LR, Singleton RJ, Williams J, Snowball M, Homan C, et al. Elimination of hepatocellular carcinoma and acute hepatitis B in children 25 years after a hepatitis B newborn and catch-up immunization program. Hepatology 2011;54:801-7. 4. Smith EA, Jacques-Carrol L, Walker TY, Sirotkin B, Murphy TV. The National Perinatal Hepatitis B Prevention Program, 1994-2008. Pediatrics 2012;129:609-16. 5. Centers for Disease Control and Prevention. Prevention of perinatal transmission of hepatitis B virus: prenatal screening of all pregnant women for hepatitis B surface antigen. MMWR Morb Mortal Wkly Rep 1988;27:341-6. 351. 6. Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP, Finelli L, et al. 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 II: immunization of adults. MMWR Recomm Rep 2006;55:1-33. 7. Texas Department of State and Health Services [www.dshs.state.tx.us/] Austin: State of Texas. [updated 2013 Sept 23]. Texas Health and Safety Code Chapter 81, Subchapter E., x 81.090. Available at: http://www.dshs. state.tx.us/idcu/disease/hepatitis/hepatitis_b/reporting/. Accessed July 23, 2013. 8. Lunn ER, Hoggarth BJ, Cook WJ. Prolonged hepatitis B surface antigenemia after vaccination. Pediatrics 2000;105:e81. 9. Kloster B, Kramer R, Eastlund T, Grossman B, Zarvan B. Hepatitis B surface antigenemia in blood donors following vaccination. Transfusion 1995;35:475-7. 10. Apuzzio J, Block JM, Cullison S, Cohen C, Leong SL, London T, et al. Chronic hepatitis B in pregnancy. A workshop consensus statement on screening, evaluation, and management, Part 2. Female Patient 2012; 37:30-4. 11. Girard A, Moreau-Gaudry A, Reseau PA, Hilleret MN. Analysis of medical prescribing practices for hepatitis B serology tests. Gastroenterologie Clinique et Biologique 2010;34:8-15. 12. Loo NM, Pryce DJ. Exploring hepatitis B: a neglected disease. Minn Med 2012;95:37-40.


Vol. 165, No. 4 13. Weinbaum CM, Williams I, Mast EE, Wang SA, Finelli L, Wasley A, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep 2008;57:1-20. 14. Ponde RA, Cardoso DD, Ferro MO. The underlying mechanisms for ‘anti-HBc alone’ serological profile. Arch Virol 2010;155:149-58. 15. Locarnini S. Interpretation and application of virological testing including resistance in chronic hepatitis B. Med J Malaysia 2005; 60(Suppl B):41-51. 16. Torbenson M, Thomas DL. Occult hepatitis B. Lancet Infect Dis 2002;2: 479-86. 17. Kao JH, Chen PJ, Lai MY, Chen DS. Acute exacerbations of chronic hepatitis B are rarely associated with superinfection of hepatitis B virus. Hepatology 2001;34:817-23. 18. Orenbuch-Harroch E, Levy L, Ben-Chetrit E. Acute hepatitis B or exacerbations of chronic hepatitis B-that is the question. World J Gastroenterol 2008;14:7133-7. 19. Walz A, Wirth S, Hucke J, Gerner P. Vertical transmission of hepatitis B virus (HBV) from mothers negative for HBV surface antigen and positive for antibody to HBV core antigen. J Infect Dis 2009;200: 1227-31. 20. Sa-nguanmoo P, Tangkijvanich P, Tharmaphornpilas P, Rasdjarmrearnsook A, Plianpanich S, Thawornsuk N, et al. Molecular analysis of hepatitis B virus associated with vaccine failure in infants and mothers: a case-control study in Thailand. J Med Virol 2012;84: 1177-85. 21. Ngui SL, O’Connell S, Eglin RP, Heptonstall J, Teo CG. Low detection rate and maternal provenance of hepatitis B virus S gene mutants in cases of failed postnatal immunoprophylaxis in England and Wales. J Infect Dis 1997;176:1360-5. 22. Euler GL, Wooten KG, Baughman AL, Williams WW. Hepatitis B surface antigen prevalence among pregnant women in urban areas: implications for testing, reporting, and preventing perinatal transmission. Pediatrics 2003;111:1192-7. 23. Koumans EH, Rosen J, van Dyke MK, Zell E, Phares CR, Taylor A, et al. Prevention of mother-to-child transmission of infections during pregnancy: implementation of recommended interventions, United States, 2003-2004. Am J Obstet Gynecol 2012;206:e1-11. 24. Ott JJ, Stevens GA, Wiersma ST. The risk of perinatal hepatitis B virus transmission: hepatitis B e antigen (HBeAg) prevalence estimates for all world regions. BMC Infect Dis 2012;12:131.

Veselsky et al

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

To resolve discrepant hepatitis B surface antigen (HBsAg) results for pregnant women screened for hepatitis B virus (HBV) infection...
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