Draft Recommendation Statement
Hepatitis B Virus Infection in Pregnant Women: Screening
This opportunity for public comment expires on February 4, 2019 at 8:00 PM EST
Note: This is a Draft Recommendation Statement. This draft is distributed solely for the purpose of receiving public input. It has not been disseminated otherwise by the USPSTF. The final Recommendation Statement will be developed after careful consideration of the feedback received and will include both the Research Plan and Evidence Review as a basis.
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Send Us Your Comments
In an effort to maintain a high level of transparency in our methods, we open our draft Recommendation Statements to a public comment period before we publish the final version.
The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific clinical preventive services for patients without obvious related signs or symptoms.
It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.
The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decisionmaking to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.
Screening for HBV infection during pregnancy identifies women whose infants are at risk of perinatal transmission. Data from a nationally representative sample showed a prevalence of maternal HBV infection of 85.8 cases per 100,000 deliveries from 1998 to 2011 (0.09% of live-born singleton deliveries in the United States).1, 2 Although there are guidelines for universal infant HBV vaccination, rates of maternal HBV have increased annually by 5.5% since 1998.1, 2 Persons infected with HBV during infancy or childhood are more likely to progress to chronic infection. Chronic HBV infection increases long-term morbidity and mortality by predisposing infected persons to cirrhosis of the liver and liver cancer.
In 2009, the USPSTF reviewed the evidence for screening for HBV infection in pregnant women and issued an A recommendation.3 The USPSTF has decided to use a reaffirmation deliberation process to update this recommendation. The USPSTF uses the reaffirmation process for well-established, evidence-based standards of practice in current primary care practice for which only a very high level of evidence would justify a change in the grade of the recommendation.4 In its deliberation of the evidence, the USPSTF considers whether the new evidence is of sufficient strength and quality to change its previous conclusions about the evidence.
The USPSTF previously reviewed the evidence on serologic testing for HBV (hepatitis B surface antigen [HBsAg]) in pregnancy and found adequate evidence of its accuracy (sensitivity and specificity >98%).
Benefits of Early Detection and Interventions
The USPSTF found convincing evidence that universal prenatal screening for HBV infection substantially reduces perinatal transmission of HBV and the subsequent development of chronic HBV infection. The USPSTF found adequate evidence that vaccination of all infants against HBV infection and providing postexposure prophylaxis with hepatitis B immune globulin (HBIG) at birth to infants of mothers infected with HBV substantially reduce the risk for acquisition of HBV infection in infants.
Harms of Screening and Interventions
The USPSTF found limited evidence on the harms of screening for HBV infection in pregnant women but bound the potential harms of screening as no greater than small based on the high accuracy of screening and the low likelihood of harms from preventive interventions.
Using a reaffirmation process, the USPSTF concludes with high certainty that the net benefit of screening for HBV infection in pregnant women is substantial.
Draft: Clinical Considerations
Patient Population Under Consideration
This recommendation applies to all pregnant persons.
The principal screening test for detecting maternal HBV infection is the serologic identification of HBsAg. Screening should be performed in each pregnancy, regardless of previous HBV vaccination or previous negative HBsAg test results.1
A test for HBsAg should be ordered at the first prenatal visit. At the time of admission to a hospital or other delivery setting, women with unknown HBsAg status or with new or continuing risk factors for HBV infection (e.g., injection drug use, sexually transmitted infection) should be screened.
Interventions to prevent perinatal transmission of HBV infection include screening all pregnant women for HBV, vaccinating infants born to HBV-negative mothers within 24 hours of birth, and completing the HBV vaccination series by age 18 months for infants. For HBV-positive mothers, case management during pregnancy includes HBV DNA viral load testing and referral to specialty care for counseling and medical management of HBV infection. For infants born to mothers positive for HBsAg, current guidelines for case management include HBV vaccination and HBIG within 12 hours of birth, completing the vaccine series, and serologic testing for infection and immunity by age 9 to 12 months. For infants born to mothers with unknown HBsAg status, current guidelines for case management include HBV vaccination within 12 hours of birth followed by HBIG.7
The USPSTF has made recommendations on screening for other sexually transmitted infections, including chlamydia and gonorrhea,8 HBV in nonpregnant adults and adolescents,9 genital herpes,10 HIV,11 and syphilis in pregnant women.12
Draft: Other Considerations
Universal screening for HBV infection in women during pregnancy is standard clinical practice in the United States. Presently, 26 states have laws mandating prenatal HBV screening.15 Although rates of maternal screening for HBV infection range from 84% to 88%, screening rates during the first trimester are lower, with 60% of commercially-insured and 39% of Medicaid-enrolled women screened during the first trimester.16 Seventy-one percent of infants receive HBV vaccination within 3 days of birth.1, 17 Primary care clinicians and delivery settings must establish effective systems for the accurate and timely transfer of maternal HBsAg test results to labor, delivery, and newborn medical records to maximize benefit.1
Research Needs and Gaps
The USPSTF has identified areas of needed research. Continued research on effective implementation of case management in vulnerable populations most at risk for perinatal transmission of HBV infection is needed. Additional studies on the effectiveness of prenatal antiviral medication to reduce perinatal transmission are needed. Analyses of recent data from existing case management programs, such as the Perinatal Hepatitis B Prevention Program (PHBPP) program, would be helpful in understanding program performance and research needs.1
Burden of Disease
Hepatitis B is a viral infection of the liver transmitted through contact with the bodily fluids or blood of an infected individual. In the United States, prevalence estimates of chronic HBV infection range from approximately 850,000 to more than 2 million cases.1, 18-20 In the United States, new cases of HBV among adults are largely transmitted through injection drug use or sexual intercourse, but most prevalent cases of HBV infection are chronic infections from exposure occurring in infancy or childhood. Another major risk factor for HBV infection is country of origin. In the United States, adults with HBV born in high-prevalence countries were commonly infected during childhood.19 In children, the primary source of infection is perinatal transmission at birth.21 According to the CDC, 800 to 1,000 cases of perinatal transmission occurred yearly (3.8% of infants born to HBV-positive women) from 2000 to 2009.22
Since 1988, rates of maternal HBV infection have increased annually by 5.5%.1, 2 Older maternal age, race/ethnicity (non-Hispanic black and Asian), lower education, higher poverty levels, and lack of insurance coverage are risk factors for HBV infection among women.2, 23
Persons infected with HBV during infancy or childhood are more likely to develop chronic HBV infection and have poor long-term health outcomes (e.g., chronic hepatitis, cirrhosis, or hepatocellular carcinoma) compared to persons who are infected later in life.1 Acute HBV infections progress to chronic disease in 80% to 90% of infected infants, 30% of acute infections progress before age 6 years, and less than 1% to 12% of acute infections progress in older children or adults. Approximately 25% of persons who become chronically infected during childhood and 15% of those infected as adults will die from cirrhosis or hepatocellular carcinoma.1, 7, 24
Scope of Review
To reaffirm its 2009 recommendation on screening for HBV infection in pregnant women, the USPSTF commissioned a reaffirmation evidence update. The aim of this update is to identify substantial new evidence that is sufficient enough to change the prior recommendation. Case management is the standard intervention in the United States for all HBV-positive pregnant women. As a result, the USPSTF targeted its evidence review to focus on the effectiveness and potential harms of screening and the effectiveness and harms of case management to prevent perinatal transmission.
Accuracy of Screening Tests
The primary screening test for detecting maternal HBV infection is the serologic identification of HBsAg. Serological immunoassays for detecting HBsAg have a reported sensitivity and specificity greater than 98%.25, 26
Effectiveness of Early Detection and Treatment
No studies were identified that directly assessed the benefits or harms of universal HBV screening during pregnancy. Two fair-quality observational studies reported perinatal transmission rates (primary outcome) over time.1, 27, 28
One study reported outcomes of case management from 1994 to 2008 for 155,081 infants born to HBV-positive women in the national PHBPP, administered by the CDC.1, 27 From 1994 to 2008, the estimated number of infants born to HBV-positive women increased in the United States (from 19,208 to 25,600; p<0.001). The proportion of infants born to HBV-positive women enrolled in the PHBPP for case management also increased during this period (from 42.1% to 47.9%; p=0.002). The number of infants receiving case management increased from 7,415 in 1994 to 12,033 in 2008 (p<0.001).1, 27
Perinatal transmission outcomes were reported for infants born from 1999 to 2008 who received serologic testing (n=55,362). There was a statistically significant decrease in the perinatal transmission rate (p=0.001). In 1999, 1.9% of infants with serologic testing were infected with HBV; the rate had decreased to 0.8% (p=0.001) by 2008.1, 16
The second observational study was conducted in a large regional health care system in the United States (Kaiser Permanente Northern California).1, 28 The case management program reported on 4,446 infants born to HBV-positive women from 1997 to 2010. More than 97% of the infants received HBV vaccination and HBIG within 12 hours of birth. Overall rates of perinatal transmission were very low (0.75%), and a decreasing trend in perinatal transmission was reported (incidence rate ratio, 0.90 [95% confidence interval (CI), 0.82 to 1.00]).1, 28
The results on historical trends from the observational studies are at risk of bias due to changes in case management program implementation, other interventions (e.g., antiviral medication), cultural or secular changes (e.g., universal vaccination), changes in reporting methods, and differences in data collection procedures.1
Potential Harms of Screening and Treatment
No studies were identified that reported the potential harms of universal HBV screening during pregnancy or case management. Screening has a low false-positive rate, and treatment is rarely harmful.1
Estimate of Magnitude of Net Benefit
The USPSTF considered the evidence using a reaffirmation process. It previously found adequate evidence that serologic testing for HBsAg accurately identifies HBV infection. Interventions are effective for preventing perinatal transmission, based on foundational evidence and observational studies of U.S. case management programs. In addition, there is evidence that over time, perinatal transmission has decreased among woman and infants enrolled in case management, providing an overall substantial health benefit. Therefore, the USPSTF reaffirms its previous conclusion that there is convincing evidence that screening for HBV infection in pregnant women provides substantial benefit.
Draft: Reaffirmation of Previous USPSTF Recommendation
This recommendation is a reaffirmation of the USPSTF 2009 recommendation statement. In 2009, the USPSTF reviewed the evidence for screening for HBV infection in pregnant women and found that the benefits of screening substantially outweighed the harms.3 For the current recommendation, the USPSTF commissioned a targeted review to look for new and substantial evidence on the benefits and harms of screening and determined that the net benefit of screening for HBV infection in pregnant women continues to be well established. The USPSTF found no new substantial evidence that would change its recommendation and, therefore, reaffirms its recommendation to screen for HBV infection in pregnant women.
Draft: Recommendations of Others
The American College of Obstetricians and Gynecologists recommends HBV screening (HBsAg and anti-HBs) in every pregnant patient at the earliest prenatal visit.29 These tests should be designated as “prenatal.” The CDC Advisory Committee on Immunization Practices recommends testing for HBsAg in all pregnant women during an early prenatal visit (e.g., in the first trimester) and HBV DNA testing for pregnant women who test positive for HBsAg.7 The American Academy of Family Physicians recommends screening for HBV infection in pregnant women at their first prenatal visit.30 The American Association for the Study of Liver Diseases recommends screening in all pregnant women using HBsAg and anti-HBs.24
Send Us Your Comments
In an effort to maintain a high level of transparency in our methods, we open our draft Recommendation Statements to a public comment period before we publish the final version.
1. Henderson JT, Webber EM, Bean SI. Screening for Hepatitis B Virus Infection in Pregnant Women: An Updated Systematic Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 179. AHRQ Publication No. 19-05248-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2019.
2.Salemi JL, Spooner KK, Mejia de Grubb MC, Aggarwal A, Matas JL, Salihu HM. National trends of hepatitis B and C during pregnancy across sociodemographic, behavioral, and clinical factors, United States, 1998-2011. J Med Virol. 2017;89(6):1025-32.
3. U.S. Preventive Services Task Force. Screening for hepatitis B virus infection in pregnancy: U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med. 2009;150(12):869-73, W154.
4. U.S. Preventive Services Task Force. Procedure manual. https://www.uspreventiveservicestaskforce.org/Page/Name/procedure-manual. Updated 2018. Accessed December 27, 2018.
5. del Canho R, Grosheide PM, Mazel JA, et al. Ten-year neonatal hepatitis B vaccination program, The Netherlands, 1982-1992: protective efficacy and long-term immunogenicity. Vaccine. 1997;15(15):1624-30.
6. Chen HL, Zha ML, Cai JY, Qin G. Maternal viral load and hepatitis B virus mother-to-child transmission risk: a systematic review and meta-analysis. Hepatol Res. 2018;48(10):788-801.
7. 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.
8. U.S. Preventive Services Task Force. Screening for chlamydia and gonorrhea: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161(12):902-10.
9. U.S. Preventive Services Task Force. Screening for hepatitis B virus infection in nonpregnant adolescents and adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161(1):58-66.
10. US Preventive Services Task Force. Serologic screening for genital herpes infection: US Preventive Services Task Force recommendation statement. JAMA. 2016;316(23):2525-30.
11. U.S. Preventive Services Task Force. Screening for HIV: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159(1):51-60.
12. U.S. Preventive Services Task Force. Screening for syphilis infection in pregnant women: US Preventive Services Task Force reaffirmation recommendation statement. JAMA. 2018;320(9):911-7.
13. Centers for Disease Control and Prevention. Perinatal transmission. https://www.cdc.gov/hepatitis/hbv/perinatalxmtn.htm. Accessed December 27, 2018.
14. Centers for Disease Control and Prevention. Viral hepatitis. https://www.cdc.gov/hepatitis/hbv/index.htm. Accessed December 27, 2018
15. Culp LA, Caucci L, Fenlon NE, Lindley MC, Nelson NP, Murphy TV. Assessment of state perinatal hepatitis B prevention laws. Am J Prev Med. 2016;51(6):e179-e85.
16. 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-e80.
17. Hill HA, Elam-Evans LD, Yankey D, Singleton JA, Kang Y. Vaccination coverage among children aged 19-35 months: United States, 2016. MMWR Morb Mortal Wkly Rep. 2017;66(43):1171-7.
18. Roberts H, Kruszon-Moran D, Ly KN, et al. Prevalence of chronic hepatitis B virus (HBV) infection in U.S. households: National Health and Nutrition Examination Survey (NHANES), 1988-2012. Hepatology. 2016;63(2):388-97.
19. Kowdley KV, Wang CC, Welch S, Roberts H, Brosgart CL. Prevalence of chronic hepatitis B among foreign-born persons living in the United States by country of origin. Hepatology. 2012;56(2):422-33.
20. Gish RG, Sollano JD Jr, Lapasaran A, Ong JP. Chronic hepatitis B virus in the Philippines. J Gastroenterol Hepatol. 2016;31(5):945-52.
21. Society for Maternal-Fetal Medicine (SMFM), Dionne-Odom J, Tita AT, Silverman NS. #38: Hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission. Am J Obstet Gynecol. 2016;214(1):6-14.
22. 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):114-21.
23. Miller GK, Barker L, Taylor A, et al. Hepatitis B vaccination among U.S. women of reproductive age. J Womens Health. 2017;26(4):A29.
24. Terrault NA, Lok AS, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-99.
25. Centers for Disease Control and Prevention (CDC). Sensitivity of the test for antibody to hepatitis B surface antigen--United States. MMWR Morb Mortal Wkly Rep. 1993;42(36):707-10.
26. World Health Organization. Hepatitis B Surface Antigen Assays: Operational Characteristics (Phase I). Geneva: World Health Organization; 2001.
27. Smith EA, Jacques-Carroll L, Walker TY, Sirotkin B, Murphy TV. The national Perinatal Hepatitis B Prevention Program, 1994-2008. Pediatrics. 2012;129(4):609-16.
28. Kubo A, Shlager L, Marks AR, et al. Prevention of vertical transmission of hepatitis B: an observational study. Ann Intern Med. 2014;160(12):828-35.
29. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 86: viral hepatitis in pregnancy. Obstet Gynecol. 2007;110(4):941-56.
30. American Academy of Family Physicians. Clinical preventive service recommendation: hepatitis. https://www.aafp.org/patient-care/clinical-recommendations/all/hepatitis.html. Accessed December 27, 2018.
Internet Citation: Draft Recommendation Statement: Hepatitis B Virus Infection in Pregnant Women: Screening. U.S. Preventive Services Task Force. January 2019.