Hepatitis B immunization in postpartum women

CLINICAL OPINION

Hepatitis B immunization in postpartum women Marcus W. Jurema, MD, Margaret Polaneczky, MD, and William J. Ledger, MD New York, NY OBJECTIVE: To investigate the acceptance and efficacy of hepatitis B immunization in women during the postpartum period. STUDY DESIGN: A group of 157 consecutive women who were delivered of neonates between 1994 and 1999 under the care of a private, full-time faculty-based practice of obstetrics and gynecology participated in the study. All patients were screened for hepatitis B surface antigen and antibody during their pregnancy. Susceptible patients eligible for hepatitis B immunization were offered the vaccine in the immediate postpartum period. The planned vaccine administration was a series of 3 intramuscular injections, with the second injection given 4 weeks later and the third given 6 months after the initial injection. Rescreening for hepatitis B surface antibody titers was performed at a visit after the last injection. Response to the immunization series was evaluated according to rate of acceptance, compliance, and achievement of seroprotection. RESULTS: Thirteen (8%) patients had been immunized previously and had antibodies, whereas 8 (5%) patients had serologic evidence of a previous infection. Of the 136 patients eligible for the study, 113 (83%) agreed to participate, 16 (12%) declined, and 7 (5%) moved away from New York right after delivery. Of the 113 participants, 104 (92%) patients received at least 2 vaccine injections, with 80 (71%) completing 3 injections. Among patients who had postvaccinal antibody titers, 66 of 69 (96%) of the group that received 3 injections and 9 (75%) of 12 of the group that received 2 injections were found to have antibodies. CONCLUSION: Hepatitis B immunization in the postpartum period is feasible and effective. (Am J Obstet Gynecol 2001;185:355-58.)

Key words: Hepatitis B, vaccine, acceptance, compliance, seroprotection

Hepatitis B infection is a communicable disease with serious and potentially fatal complications that include liver failure, chronic liver disease, and hepatocellular carcinoma in those who remain antigen positive. More than 360 million people are affected worldwide by this viral infection.1 In the United States, 1.25 million people are chronically infected with hepatitis B and 5000 people die annually of its complications.2 In addition, 200,000 to 300,000 new cases of hepatitis B infection occur each year.2, 3 A safe, cost-effective, and efficient recombinant vaccine against hepatitis B has been available for 2 decades.3-5 However, the effectiveness of efforts to eradicate hepatitis

From the New York and Presbyterian Hospital–Weill Medical College of Cornell University. Reprint requests: William J. Ledger, MD, Department of Obstetrics and Gynecology, New York and Presbyterian Hospital–Weill Medical College of Cornell University, 525 East 68th St, J-130, New York, NY 10021. Copyright © 2001 by Mosby, Inc. 0002-9378/2001 $35.00 + 0 6/1/116092 doi:10.1067/mob.2001.116092

B or significantly reduce its incidence has fallen short of expectations.6, 7 This shortfall has been caused by underutilization of vaccination by health care providers and by a lack of public awareness and education about hepatitis B infection. Most patients are unaware that hepatitis B can be transmitted through sexual contact or that it is about 100 times more infectious than the human immunodeficiency virus. In the United States, hepatitis B mostly affects people between 15 and 39 years old, with the highest incidence between ages 20 to 29 years. 8, 9 This epidemiologic cluster represents a major component of the patients seen at centers for women’s health. Yet women’s health practitioners have played a minor role to date in preventing propagation of hepatitis B infection. Margolis et al10 showed that physicians of obstetrics and gynecology were less likely than primary care physicians to counsel their patients about hepatitis B prevention. This is unfortunate because preventive health care for women, especially in infectious diseases, has been strongly emphasized in academic centers during the last decade.11 355

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Standard care in obstetrics and gynecology currently includes routine screening of hepatitis B surface antigen (HepBsAg) in all pregnant women. Infants born to mothers who are positive for this antigen are given active and passive hepatitis B immunizations. This strategy has significantly reduced the incidence of hepatitis B infection among infants, but it does not prevent hepatitis B infection in all newborns. This treatment strategy accepts the fact that some susceptible young mothers will acquire hepatitis B and become future carriers. This pattern of care exposes future newborns to the risk of infection. In addition, it ignores the potential health risks of this virus to the mother. Additional testing for hepatitis B surface antibody (HepBsAb) can identify mothers susceptible to hepatitis B infection who are eligible for immunization. However, vaccination of such individuals during pregnancy has encountered several obstacles. First, despite its demonstrated safety in pregnancy,12-14 some patients, as well as physicians, perceive vaccination as the introduction of a foreign substance that long-term follow-up studies may show causes some future health problems. Second, lower rates of seroconversion have been reported when the vaccine is administered during pregnancy.14, 15 There are a number of possible reasons for this, including the added weight of a pregnant woman and antenatal changes in immunologic response. As one solution, we designed a hepatitis B vaccination schedule that began in the postpartum period. The postpartum period confers close patient-physician contact to aid in compliance, to increase acceptance by eliminating fear of harm to the fetus, and to improve efficacy by avoiding the added weight and the immunosuppression of pregnancy. Material and methods A group of 157 consecutive women who were delivered of neonates between 1994 and 1999 under the care of a private, full-time faculty-based practice of obstetrics and gynecology participated in the study. All patients were screened for HepBsAg and HepBsAb during their pregnancies. They were also screened for other sexually transmitted diseases, including syphilis, gonorrhea, and chlamydia. Susceptible patients were offered hepatitis B immunization beginning in the postpartum period, and consent was obtained for vaccination. Women who were not offered vaccination included those who had been previously immunized, had evidence of previous infection, or had plans to move out of the practice area shortly after delivery. The vaccination schedule consisted of a series of 3 intramuscular (deltoid) injections given at the first postpartum visit, with the second injection given 4 weeks later and the third given 6 months after the initial injection. This paralleled the pattern in place of seeing patients twice within the first 8 weeks of delivery and again 6

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months after the first postpartum visit. The vaccine was given in the form of 20-µg doses of Engerix-B (SmithKline Beecham, Philadelphia, Pa). Patients had postvaccinal HepBsAb titers drawn at their first visit after the last injection. Efficacy of the vaccine was evaluated in terms of acceptance as the percentage of patients who accepted the vaccine. Compliance was defined as the percentage of patients who received at least 2 injections, because most immunogenicity is achieved after 2 injections (the third acts as a “booster”).2 The rate of seroprotectiveness was also evaluated, defined as the percentage of patients who achieved postvaccinal HepBsAb titers greater than 10 mU/mL. The Student t test was used to compare rates of seroconversion according to age and weight at time of first injection. Results A total of 157 patients participated in this study. Study subjects ranged in age from 18 to 44 years and had a mean body weight of 137.2 pounds (postpartum). One hundred forty-three of the subjects were white. The average gestational age at delivery was 39 weeks. One hundred fifteen patients were born in the United States, and only 14 foreign-born patients came from areas endemic for hepatitis B virus (Middle East, Asia, Africa, Pacific Islands, and parts of Central and South America). Only 4 patients occupied employment positions at risk for hepatitis B infection (all health care–related jobs). Twenty patients reported that they had previously had a sexually transmitted disease, and 2 reported that they had been treated for pelvic inflammatory disease in the past. No patient tested positive for gonorrhea or syphilis, and only 1 patient tested positive for chlamydia during the pregnancy. All patients denied any history of intravenous drug use. Information on sexual orientation and number of sexual partners was not uniformly recorded. Maternal human immunodeficiency virus status was not directly obtained in all cases but was inferred from the results of newborn screening. All were negative. All 157 women in this study were screened for HepBsAg and HepBsAb during their pregnancies. A total of 113 (72%) women found to be susceptible to hepatitis B infection agreed to begin immunization in the postpartum period. Of these, 104 (92%) received at least 2 vaccine injections, with 80 (70.8%) patients receiving all 3 injections and 24 (21.2%) receiving 2 injections. Nine (8.0%) patients received only 1 injection. The other 44 patients did not begin vaccination for the following reasons: 16 declined vaccination, 13 had been immunized previously and had hepatitis B antibodies, 5 were HepBsAb positive, 3 were HepBsAg positive, and 7 had plans to move out of the practice area shortly after delivery (5 to Europe and 2 elsewhere in the United States). Postvaccinal HepBsAb titers were obtained in 69 patients who completed all 3 injections. A seroprotective-

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ness rate of 95.7% (66 of 69) was obtained for this group. The seroprotectiveness rate was 75.0% (9 of 12) for the patients who received 2 injections. The average time interval between delivery and the start of immunization treatment was 3.4 weeks. The second injection was given an average of 5.4 weeks after the first one. For those who received the third injection, the average time between the second and third injections was 26.4 weeks. The mean interval between the end of vaccination and antibody rescreening was 54.9 weeks. The opportunity to test for postimmmunization antibody status was often lost because many new parents moved out of the area. Independent t test analysis showed that there was a statistically significant difference between the group of patients that seroconverted and the group that did not with respect to average body weight (129.5 vs 159 pounds, respectively; P = .005) but not to average age (34 vs 36 years; P = .335). Among those who received only 2 injections, there was no difference between converters and nonconverters with respect to average age (30 vs 34 years; P = .465) or to average body weight (128 vs 136 pounds; P = .664). Among those who received 3 shots, there was also a statistically significant difference between converters and nonconverters with respect to body weight (129.6 vs 174 pounds; P = .001) but not to average age (34 vs 37 years; P = .264). Comment Hepatitis B infection is a serious and potentially fatal disease that affects millions of people worldwide. It is also a preventable disease. A safe and efficacious vaccine has been available for 2 decades. Unfortunately, the initial strategy of immunization of persons at high risk for acquiring hepatitis B infection had little impact on the overall incidence of hepatitis B. Since the early 1990s, therefore, the major approach to hepatitis B eradication has been to perform routine immunization of infants and “catch-up” immunization of children and adolescents.16 However, in countries such as the United States, with low endemicity of chronic hepatitis B infection, most new infections continue to occur in adults. In this study population, 8 (5.1%) women had serologic evidence of a previous hepatitis B infection: 3 were HepBsAg positive and 5 were HepBsAb positive. Five of these 8 women had been born in countries in which hepatitis B virus is endemic. The other 3 women were born in the United States and had no high-risk characteristics. It is quite likely that they acquired hepatitis B through unprotected sexual intercourse, underscoring the reality that this is a sexually transmitted disease with a potentially serious outcome for American women. American physicians have failed to organize programs directed toward immunization of adults, and many opportunities are missed in the office setting. Currently, screening for HepBsAg in adults occurs routinely only

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during pregnancy for the purpose of identifying the newborns at risk of acquiring hepatitis B. In our study we considered the health risks to the mother by also screening for HepBsAb, identifying susceptible mothers, and offering them hepatitis B vaccination. Our strategy to vaccinate in the postpartum period achieved an overall compliance rate of 92.0% and a seroprotectiveness rate of 75.0% among women who received 2 injections and as high as 95.7% among women who received all 3 injections. These rates are higher than those reported for vaccination during pregnancy. Ingardia et al15 reported a rate of 49% (39 of 80) seroconversion during pregnancy, with 80% of patients receiving 2 shots and 11% receiving 3 shots. Grosheide et al13 reported a seroconversion rate of 75% after 3 injections in pregnant patients compared with 92% in patients who were not pregnant. Our rates are within the expected range (90% to 100%) of seroconversion observed in healthy adults.1, 11 We found a statistically significant difference in seroconversion rates with respect to average body weight. Women with higher body weights were less likely to become immunized, probably because the vaccine was injected into the subcutaneous space instead of intramuscularly. Age (usually >40 years) has also been reported to affect the efficacy of the vaccine.4 In our study, the age of the subjects did not influence seroconversion rates, probably because the majority of patients were younger than 40 years old. Sixteen of our patients declined immunization, most commonly because they were married and monogamous, and because they perceived themselves to be in a low-risk category. In fact, the majority of the women in this study belonged to this low-risk category, according to their histories. However, it is important to remember that at least 50% of marriages end in divorce in the United States. Divorce often is followed by sexual activity with 1 or more partners. These women may therefore be at risk for acquiring hepatitis B virus in the future and should be offered vaccine protection. As women reach reproductive age and become sexually active, they distance themselves from their pediatric caregivers and seek guidance from practitioners of obstetrics and gynecology who become, in most cases, their primary caregivers. Practitioners of obstetrics and gynecology are therefore in a privileged position to help diminish the propagation of hepatitis B infection. The postpartum period provides an opportune time to accomplish vaccination against hepatitis B because most new mothers are made aware of the vaccine as their newborns are also receiving it and because they are perhaps more inclined to visit their obstetrician on a frequent enough basis to complete the vaccine as scheduled. In this group of postpartum women, hepatitis B immunization was shown to be feasible and effective, with high acceptance, compliance, and seroprotectiveness

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rates. As the specialty of obstetrics and gynecology assumes a greater role in primary care, prevention should be emphasized more than treatment alone. The goal of eradication of hepatitis B can be achieved if obstetriciangynecologists assume an active role in counseling and offering vaccination to this young adult patient population.

REFERENCES

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7. Francis DP. The public’s health unprotected: reversing a decade of underutilization of hepatitis B vaccine [editorial]. JAMA 1995;274:1242-3. 8. Moore-Caldwell SY, Werner MJ, Powell L, Greene JW. Hepatitis B vaccination in adolescents: knowledge, perceived risk, and compliance. J Adolesc Health 1997;20:294-9. 9. Hollinger FB. Comprehensive control (or elimination) of hepatitis B virus transmission in the United States. Gut 1996;38(suppl 2):S24-30. 10. Margolis HS, Handsfield HH, Jacobs RJ, Gangi JE. Evaluation of office-based intervention to improve prevention counseling for patients at risk for sexually acquired hepatitis B virus infection. Hepatitis B-WARE Study Group. Am J Obstet Gynecol 2000;182:1-6. 11. Ledger WJ. Preconceptual preventive health care for women: infectious diseases in clinical practice. Infectious Disease in Clinical Practice 1993;2:222-6. 12. Levy M, Koren G. Hepatitis B vaccine in pregnancy: maternal and fetal safety. Am J Perinatol 1991;8:227-32. 13. Grosheide PM, Schalm SW, van Os HC, Fetter WP, Heijtink RA. Immune response to hepatitis B vaccine in pregnant women receiving post-exposure prophylaxis. Eur J Obstet Gynecol Reprod Biol 1993;50:53-8. 14. Ayoola EA, Johnson AO. Hepatitis B vaccine in pregnancy: immunogenicity, safety and transfer of antibodies to infants. Int J Gynaecol Obstet 1987;25:297-301. 15. Ingardia CJ, Kelley L, Steinfeld JD, Wax JR. Hepatitis B vaccination in pregnancy: factors influencing efficacy. Obstet Gynecol 1999;93:983-6. 16. Update: recommendations to prevent hepatitis B virus transmission—United States. MMWR Morb Mortal Wkly Rep 1999;48:33-4.