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Intrapartum hepatitis B screening in a low-risk population
Intrapartum hepatitis B screening in a low-risk population J. M. Ernest, MD: Laurence B. Givner, MD,b and Robert Pool, MD· Winston-Salem, North Carolina Intrapartum hepatitis B surface antigen testing was performed on all laboring patients admitted to Forsyth Memorial Hospital in Winston-Salem, North Carolina from December, 1988 through November, 1989. Of the 5580 patients tested, eight patients had test results positive for hepatitis B surface antigen (overall prevalence rate of 0.14%). HBsAg was present in 0.3% of public patients and 0.08% of private patients. Of the seven patients who were not known to be positive for hepatitis B surface antigen before pregnancy, three had identifiable risk factors for hepatitis B virus. The time interval from birth to administration of hepatitis B immune globulin in the newborn averaged 13.3 hours. Patient cost per new case detected was $13,203. Intrapartum hepatitis B surface antigen screening with an assay performed once daily allows for timely administration of hepatitis B immune globulin to the newborn in accordance with recommendations of the American College of Obstetricians and Gynecologists, although some newborns receive hepatitis B immune globulin after the 12-hour birth-to-administration interval recommended by the Centers for Disease Control. (AM J OBSTET GVNECOl 1990;163:978-80.)
Key words: Hepatitis B virus, intrapartum screening, hepatitis B surface antigen
Vertical transmission of hepatitis B virus represents one of the most efficient modes of hepatitis B virus infection. In the United States an esimated 16,500 women who are positive for hepatitis B surface antigen (HBsAg) give birth yearly and approximately 3500 of their infants become chronic hepatitis B virus carriers. 1 Treatment of these newborns soon after birth with hepatitis B immune globulin and subsequently hepatitis B virus vaccine would prevent 85% to 90% of exposed infants from becoming chronic carriers.2 In June 1988 the Advisory Committee on Immunization Practices of the Centers for Disease Control recommended universal screening of all pregnant women early in the prenatal period 1 because studies from large inner-city hospitals found that only 35% to 65% of HBsAg-positive patients were identified by limiting screening to women considered high-risk by Advisory Committee on Immunization Practices guidelines. 3•5 These universal screening recommendations are based in part on prevalence rates in large inner-city hospitals. Although universal screening has been estimated to be cost effective in areas where the prevalence of hepatitis B virus infection is at least 0.06%: many practitioners in hospitals outside inner-city areas remain reluctant to add the additional costs of routine hepatitis B virus screening to prenatal care. Practitioners are also conFrom the Department of Obstetrics and Gynecolcgy" and the Department of Pediatrics/ Bowman Gray School of Medicine of Wake Forest University, and the Department of Pathology,' Forsyth Memorial Hospital. Presented at the Tenth Annual Meeting of the Society of Perinatal Obstetricians, Houston, Texas, January 23-27, 1990. Reprint requests: J. M. Ernest, MD, Department of Obstetrics and Gynecology, Bowman Gray School of Medicine, 300 South Hawthorne Road, Winston-Salem, NC 27103.
6/6/22581
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cerned that maternal hepatitis B virus test results performed early in gestation are not available to the pediatrician early in the newborn period and are concerned about untested patients who are transferred at the onset of labor and patients who receive no prenatal care. Because of these concerns we examined the feasibility and cost of universal hepatitis B virus screening at the time oflabor in a non-inner-city population in western North Carolina by addressing three questions. (1) What is the prevalence of HBsAg-positive women in this population? (2) Will screening for HBsAg at the time of labor allow for timely immunization of the newborn? (3) What is the cost per case detected in this population? Methods and material Since December 1988 all patients in labor who came to Forsyth Memorial Hospital in Winston-Salem, North Carolina, have been screened for HBsAg. Approximately 5000 births per year occur at Forsyth Memorial Hospital to Forsyth county residents (which includes 94% of the total births from Forsyth County) and an additional 300 to 400 births per year occur at Forsyth Memorial Hospital to women transferred from the 19-county referral area surrounding Forsyth county. Patients are transferred to Forsyth Memorial Hospital to receive high-risk obstetric care from the Obstetrics Department of Bowman Gray School of Medicine of Wake Forest University. Winston-Salem has a population of 150,000. The largest city from which referrals are received, Greensboro, North Carolina, has a population of 200,000. Approximately 70% of the obstetric patients who are delivered at Forsyth Memorial Hospital are white, and 70% of the overall pa-
Intrapartum hepatitis B virus screening
Volume 163 Number 3
979
Table I. Patients with positive HBsAg and neonatal hepatitis B immune globulin administration Intervals (hr) Patient No.
Type of prenatal care
Maternal risk factor
Known positivity before admission
Admission-result known
Admission-birth
Birth-hepatitis B immune globulin given
1 2 3
Private Public Public
No No No
22.5 19.0 17.0
31.0 4.0 137.0
4.0 18.0 0.5
4 5 6 7
Private Public Private Public
No No Yes Yes
29.5 17.0
12.5 6.0 30.5 4.0
23.0 13.0 1.0 7.0
8
Public
Filipino None Intravenous drugs None None Korean Multiple sexually transmitted diseases None
No
32.0
14.0
21.0
tient population receive their care from private physicians. Eighty percent of patients who receive care from a private physician are white, and the majority of the remainder are black. The prevalence of illicit drug use and sexually transmitted diseases in the private group is unknown. Except for selected situations, all Medicaid patients are seen and followed through local health departments by resident physicians from Bowman Gray School of Medicine. Therefore all patients seen by private physicians have private third-party coverage or are able to self-pay the physician'S fee and hospital costs of delivery. Of the 30% of patients who receive their care through local health departments, approximately 55% are white, and the remainder black, with an occasional patient of Hispanic, Oriental, or Native American background as in the private population. The admitted use of illicit parenteral drugs is increasing in our public health department patients and currently appears to be in the 5% to 15% range. The prevalence of Neisseria gonorrhoeae infection at the first prenatal visit is 2% to 3%, and Chlamydia trachomatis 5% to 6%. Patients were screened for HBsAg with the AUSRIA 11-125 radioimmunoassay (Abbott Laboratories, North Chicago). The assay was performed once daily and positive results (defined as counts 2:2.1 times the mean of the negative controls) were confirmed with standard hepatitis B profiles including hepatitis B e antigen (HBeAg), and antibodies to hepatitis B core, surface, and e antigens. Patients with a positive test for HBsAg were referred for infectious disease consultation and their infants received hepatitis B immune globulin (and hepatitis B virus vaccine) as soon after birth as test results were available.
Results During the 12 months from Dec. 1, 1988, through Nov. 30, 1989, 5580 laboring patients were screened for HBsAg. Eight patients were found to be HbsAg-
positive (prevalence of 0.14%). The rate in public patients was 0.3% and in private patients was 0.08%. One of the eight patients was Korean and a known chronic hepatitis B virus carrier and one had been found to be HBsAg-positive at a previous admission for preterm labor (patients 6 and 7, respectively, Table I). The remaining six were not known to be positive for HBsAg before labor. Four of the six (67%) had no known risk factors for hepatitis B virus infection as defined by the Advisory Committee on Immunization Practices.' Three of these four previously unknown HBsAg-positive patients were public health department patients and one was a private patient. In the six patients not known to be positive for HBsAg at the time of admission, the average time from admission in labor until HBsAg results were known was 23 hours (range, 17-32 hours) (Table I). The time interval from birth to administration of hepatitis B immune globulin averaged 13.3 hours (range, 0.5 to 23.0 hours). The actual hospital cost of each HBsAg assay was $12.90, for a total cost of $71,982 for the 12 months studied. Actual cost per new case detected (excluding the one patient previously known to be a chronic carrier) was $10,283. The cost to the patient of the HBsAg test used for screening was $15 per patient for the first 6 months, and $18 for the last 6 months, for a total cost of $94,421 for the 12-month period. The cost per new case detected (excluding the one patient previously known to be a chronic carrier) was $13,488 per case.
Comment Infants born to women positive for HBsAg (and hepatitis B e antigen) have a 90% risk of hepatitis B virus infection. Ninety percent of infected infants become chronic carriers at risk for the development of cirrhosis and hepatocellular carcinoma. I The development of the carrier state can be prevented in 85% to 90% of infants born to HBsAg-positive mothers by prompt administration of hepatitis B immune globulin after birth
980
Ernest, Givner, and Pool
and a series of hepatitis B virus vaccine injections. 2 Whereas infants are at highest risk for hepatitis B virus infection when the mother is both HBsAg- and HBeAgpositive,7 fatal cases of hepatitis B virus infection have been reported in infants of HBsAg-positive, HBeAgnegative mothers,S and infants born to HBsAg-positive women should receive immunization regardless of maternal HBeAg status. Current Centers for Disease Control recommendations include universal screening of all pregnant women for hepatitis B virus infection early in gestation as well as availability of HBsAg results within 24 hours for women admitted in labor who have not had prenatal screening.! Prompt treatment of the infant after birth then can occur. In large inner-city populations with high prevalence rates of hepatitis B virus, these recommendations are generally considered appropriate. In other areas where the prevalence of hepatitis B virus is lower, the cost effectiveness of universal screening may be questioned because of the presumed low likelihood of positive results. Logistically, transmitting HBsAg information from the maternal physician's office to the pediatrician at the time of birth may impede timely hepatitis B immune globulin administration to the infant, and centers that receive transfer patients or patients without prenatal care may have substantial numbers of patients in labor who have not been screened early in gestation. An occasional HBsAgnegative patient in early pregnancy may acquire hepatitis B virus during pregnancy with minimal symptoms. On the basis of the 5580 patients in this study, intrapartum HBsAg testing of all patients with an assay performed once daily, while obviating the need for screening in early pregnancy, will not allow reporting of every patient'S HBsAg status within 24 hours of admission nor will it allow for administration of hepatitis B immune globulin to exposed infants within 12 hours of birth as recommended by the Centers for Disease ControL! Two of the six infants born to women not known to be HBsAg-positive at the onset of labor received hepatitis B immune globulin within 12 hours of birth and four received hepatitis B immune globulin more than 12 hours (13, 18,21, and 23 hours, respectively) after birth (Table I). The apparent decline in efficacy of hepatitis B immune globulin as the interval from birth to administration increases was the basis for the Centers for Disease Control recommendation of administration of hepatitis B immune globulin within 12 hours of birth. The population base and regional characteristics of
September 1990 Am J Obstet Gynecol
our patients would suggest a low-risk group for hepatitis B virus infection, and the 0.14% prevalence is slightly lower than the national average of 0.2%.6 When the prevalence is at least 0.06%, direct and indirect costs of universal antepartum screening as well as immunization of the newborn allow for a cost-effective prevention program. s Shifting the time of screening to the intrapartum period allows for continued cost effectiveness while obviating the logistic problems described above. Universal intrapartum HBsAg screening in this lowrisk population identified seven previously undetected HBsAg-positive women (four without any identifiable risk factors for hepatitis B virus). This approach permitted timely immunization of their infants with hepatitis B immune globulin (and subsequently hepatitis B virus vaccine). However, once-daily performance ofthe HBsAg assay did not permit strict adherence to the Centers for Disease Control recommendations to obtain all HBsAg test results within 24 hours of admission or administration of hepatitis B immune globulin to the infant within 12 hours of birth. These findings must be considered in planning of policies for screening pregnant women for hepatitis B virus infection. Hospitals without daily HBsAg testing capabilities should continue to consider prenatal testing of their obstetric patients. REFERENCES 1. Recommendations of the Immunization Practices Advisory Committee. Prevention of perinatal transmission of hepatitis B virus: prenatal screening of all pregnant women for hepatitis B surface antigen. MMWR 1988;37:341-6. 2. Stevens CE, Toy PT, Tong MJ, et al. Perinatal hepatitis B virus transmission in the United States: prevention by passive-active immunization. J AMA 1985 ;253: 1740-5. 3. Summers PR, Biswas MK, Pastorek JG II, Pernoll ML, Smith LG, Bean BE. The pregnant hepatitis B carrier: evidence favoring comprehensive antepartum screening. Obstet Gynecol 1987;69:701-4. 4. Jonas MM, SchiffER, O'Sullivan MJ, et al. Failure ofCenters for Disease Control criteria to identify hepatitis B infection in a large municipal obstetrical population. Ann Intern Med 1987;107:335-7. 5. Kumar ML, Dawson NV, McCullough AJ, et al. Should all pregnant women be screened for hepatitis B? Ann Intern Med 1987;107:273-7. 6. Arevalo JA, Washington AE. Cost-effectiveness of prenatal screening and immunization for hepatitis B virus. JAMA 1988;259:365-9. 7. Tong MJ, Sinatra FR, Thomas DW, Nair PV, Merritt RJ, Wang DW. Need for immunoprophylaxis in infants born to HBsAg-positive carrier mothers who are HBeAg negative. J Pediatr 1984;105:945-7. 8. Delaplane D, Yogev R, Crussi F, Shulman ST. Fatal hepatitis B in early infancy: the importance of identifying HBsAgpositive pregnant women and providing immunoprophylaxis to their newborns. Pediatrics 1983;72: 176-80.
Key words: Hepatitis B virus, intrapartum screening, hepatitis B surface antigen
Vertical transmission of hepatitis B virus represents one of the most efficient modes of hepatitis B virus infection. In the United States an esimated 16,500 women who are positive for hepatitis B surface antigen (HBsAg) give birth yearly and approximately 3500 of their infants become chronic hepatitis B virus carriers. 1 Treatment of these newborns soon after birth with hepatitis B immune globulin and subsequently hepatitis B virus vaccine would prevent 85% to 90% of exposed infants from becoming chronic carriers.2 In June 1988 the Advisory Committee on Immunization Practices of the Centers for Disease Control recommended universal screening of all pregnant women early in the prenatal period 1 because studies from large inner-city hospitals found that only 35% to 65% of HBsAg-positive patients were identified by limiting screening to women considered high-risk by Advisory Committee on Immunization Practices guidelines. 3•5 These universal screening recommendations are based in part on prevalence rates in large inner-city hospitals. Although universal screening has been estimated to be cost effective in areas where the prevalence of hepatitis B virus infection is at least 0.06%: many practitioners in hospitals outside inner-city areas remain reluctant to add the additional costs of routine hepatitis B virus screening to prenatal care. Practitioners are also conFrom the Department of Obstetrics and Gynecolcgy" and the Department of Pediatrics/ Bowman Gray School of Medicine of Wake Forest University, and the Department of Pathology,' Forsyth Memorial Hospital. Presented at the Tenth Annual Meeting of the Society of Perinatal Obstetricians, Houston, Texas, January 23-27, 1990. Reprint requests: J. M. Ernest, MD, Department of Obstetrics and Gynecology, Bowman Gray School of Medicine, 300 South Hawthorne Road, Winston-Salem, NC 27103.
6/6/22581
978
cerned that maternal hepatitis B virus test results performed early in gestation are not available to the pediatrician early in the newborn period and are concerned about untested patients who are transferred at the onset of labor and patients who receive no prenatal care. Because of these concerns we examined the feasibility and cost of universal hepatitis B virus screening at the time oflabor in a non-inner-city population in western North Carolina by addressing three questions. (1) What is the prevalence of HBsAg-positive women in this population? (2) Will screening for HBsAg at the time of labor allow for timely immunization of the newborn? (3) What is the cost per case detected in this population? Methods and material Since December 1988 all patients in labor who came to Forsyth Memorial Hospital in Winston-Salem, North Carolina, have been screened for HBsAg. Approximately 5000 births per year occur at Forsyth Memorial Hospital to Forsyth county residents (which includes 94% of the total births from Forsyth County) and an additional 300 to 400 births per year occur at Forsyth Memorial Hospital to women transferred from the 19-county referral area surrounding Forsyth county. Patients are transferred to Forsyth Memorial Hospital to receive high-risk obstetric care from the Obstetrics Department of Bowman Gray School of Medicine of Wake Forest University. Winston-Salem has a population of 150,000. The largest city from which referrals are received, Greensboro, North Carolina, has a population of 200,000. Approximately 70% of the obstetric patients who are delivered at Forsyth Memorial Hospital are white, and 70% of the overall pa-
Intrapartum hepatitis B virus screening
Volume 163 Number 3
979
Table I. Patients with positive HBsAg and neonatal hepatitis B immune globulin administration Intervals (hr) Patient No.
Type of prenatal care
Maternal risk factor
Known positivity before admission
Admission-result known
Admission-birth
Birth-hepatitis B immune globulin given
1 2 3
Private Public Public
No No No
22.5 19.0 17.0
31.0 4.0 137.0
4.0 18.0 0.5
4 5 6 7
Private Public Private Public
No No Yes Yes
29.5 17.0
12.5 6.0 30.5 4.0
23.0 13.0 1.0 7.0
8
Public
Filipino None Intravenous drugs None None Korean Multiple sexually transmitted diseases None
No
32.0
14.0
21.0
tient population receive their care from private physicians. Eighty percent of patients who receive care from a private physician are white, and the majority of the remainder are black. The prevalence of illicit drug use and sexually transmitted diseases in the private group is unknown. Except for selected situations, all Medicaid patients are seen and followed through local health departments by resident physicians from Bowman Gray School of Medicine. Therefore all patients seen by private physicians have private third-party coverage or are able to self-pay the physician'S fee and hospital costs of delivery. Of the 30% of patients who receive their care through local health departments, approximately 55% are white, and the remainder black, with an occasional patient of Hispanic, Oriental, or Native American background as in the private population. The admitted use of illicit parenteral drugs is increasing in our public health department patients and currently appears to be in the 5% to 15% range. The prevalence of Neisseria gonorrhoeae infection at the first prenatal visit is 2% to 3%, and Chlamydia trachomatis 5% to 6%. Patients were screened for HBsAg with the AUSRIA 11-125 radioimmunoassay (Abbott Laboratories, North Chicago). The assay was performed once daily and positive results (defined as counts 2:2.1 times the mean of the negative controls) were confirmed with standard hepatitis B profiles including hepatitis B e antigen (HBeAg), and antibodies to hepatitis B core, surface, and e antigens. Patients with a positive test for HBsAg were referred for infectious disease consultation and their infants received hepatitis B immune globulin (and hepatitis B virus vaccine) as soon after birth as test results were available.
Results During the 12 months from Dec. 1, 1988, through Nov. 30, 1989, 5580 laboring patients were screened for HBsAg. Eight patients were found to be HbsAg-
positive (prevalence of 0.14%). The rate in public patients was 0.3% and in private patients was 0.08%. One of the eight patients was Korean and a known chronic hepatitis B virus carrier and one had been found to be HBsAg-positive at a previous admission for preterm labor (patients 6 and 7, respectively, Table I). The remaining six were not known to be positive for HBsAg before labor. Four of the six (67%) had no known risk factors for hepatitis B virus infection as defined by the Advisory Committee on Immunization Practices.' Three of these four previously unknown HBsAg-positive patients were public health department patients and one was a private patient. In the six patients not known to be positive for HBsAg at the time of admission, the average time from admission in labor until HBsAg results were known was 23 hours (range, 17-32 hours) (Table I). The time interval from birth to administration of hepatitis B immune globulin averaged 13.3 hours (range, 0.5 to 23.0 hours). The actual hospital cost of each HBsAg assay was $12.90, for a total cost of $71,982 for the 12 months studied. Actual cost per new case detected (excluding the one patient previously known to be a chronic carrier) was $10,283. The cost to the patient of the HBsAg test used for screening was $15 per patient for the first 6 months, and $18 for the last 6 months, for a total cost of $94,421 for the 12-month period. The cost per new case detected (excluding the one patient previously known to be a chronic carrier) was $13,488 per case.
Comment Infants born to women positive for HBsAg (and hepatitis B e antigen) have a 90% risk of hepatitis B virus infection. Ninety percent of infected infants become chronic carriers at risk for the development of cirrhosis and hepatocellular carcinoma. I The development of the carrier state can be prevented in 85% to 90% of infants born to HBsAg-positive mothers by prompt administration of hepatitis B immune globulin after birth
980
Ernest, Givner, and Pool
and a series of hepatitis B virus vaccine injections. 2 Whereas infants are at highest risk for hepatitis B virus infection when the mother is both HBsAg- and HBeAgpositive,7 fatal cases of hepatitis B virus infection have been reported in infants of HBsAg-positive, HBeAgnegative mothers,S and infants born to HBsAg-positive women should receive immunization regardless of maternal HBeAg status. Current Centers for Disease Control recommendations include universal screening of all pregnant women for hepatitis B virus infection early in gestation as well as availability of HBsAg results within 24 hours for women admitted in labor who have not had prenatal screening.! Prompt treatment of the infant after birth then can occur. In large inner-city populations with high prevalence rates of hepatitis B virus, these recommendations are generally considered appropriate. In other areas where the prevalence of hepatitis B virus is lower, the cost effectiveness of universal screening may be questioned because of the presumed low likelihood of positive results. Logistically, transmitting HBsAg information from the maternal physician's office to the pediatrician at the time of birth may impede timely hepatitis B immune globulin administration to the infant, and centers that receive transfer patients or patients without prenatal care may have substantial numbers of patients in labor who have not been screened early in gestation. An occasional HBsAgnegative patient in early pregnancy may acquire hepatitis B virus during pregnancy with minimal symptoms. On the basis of the 5580 patients in this study, intrapartum HBsAg testing of all patients with an assay performed once daily, while obviating the need for screening in early pregnancy, will not allow reporting of every patient'S HBsAg status within 24 hours of admission nor will it allow for administration of hepatitis B immune globulin to exposed infants within 12 hours of birth as recommended by the Centers for Disease ControL! Two of the six infants born to women not known to be HBsAg-positive at the onset of labor received hepatitis B immune globulin within 12 hours of birth and four received hepatitis B immune globulin more than 12 hours (13, 18,21, and 23 hours, respectively) after birth (Table I). The apparent decline in efficacy of hepatitis B immune globulin as the interval from birth to administration increases was the basis for the Centers for Disease Control recommendation of administration of hepatitis B immune globulin within 12 hours of birth. The population base and regional characteristics of
September 1990 Am J Obstet Gynecol
our patients would suggest a low-risk group for hepatitis B virus infection, and the 0.14% prevalence is slightly lower than the national average of 0.2%.6 When the prevalence is at least 0.06%, direct and indirect costs of universal antepartum screening as well as immunization of the newborn allow for a cost-effective prevention program. s Shifting the time of screening to the intrapartum period allows for continued cost effectiveness while obviating the logistic problems described above. Universal intrapartum HBsAg screening in this lowrisk population identified seven previously undetected HBsAg-positive women (four without any identifiable risk factors for hepatitis B virus). This approach permitted timely immunization of their infants with hepatitis B immune globulin (and subsequently hepatitis B virus vaccine). However, once-daily performance ofthe HBsAg assay did not permit strict adherence to the Centers for Disease Control recommendations to obtain all HBsAg test results within 24 hours of admission or administration of hepatitis B immune globulin to the infant within 12 hours of birth. These findings must be considered in planning of policies for screening pregnant women for hepatitis B virus infection. Hospitals without daily HBsAg testing capabilities should continue to consider prenatal testing of their obstetric patients. REFERENCES 1. Recommendations of the Immunization Practices Advisory Committee. Prevention of perinatal transmission of hepatitis B virus: prenatal screening of all pregnant women for hepatitis B surface antigen. MMWR 1988;37:341-6. 2. Stevens CE, Toy PT, Tong MJ, et al. Perinatal hepatitis B virus transmission in the United States: prevention by passive-active immunization. J AMA 1985 ;253: 1740-5. 3. Summers PR, Biswas MK, Pastorek JG II, Pernoll ML, Smith LG, Bean BE. The pregnant hepatitis B carrier: evidence favoring comprehensive antepartum screening. Obstet Gynecol 1987;69:701-4. 4. Jonas MM, SchiffER, O'Sullivan MJ, et al. Failure ofCenters for Disease Control criteria to identify hepatitis B infection in a large municipal obstetrical population. Ann Intern Med 1987;107:335-7. 5. Kumar ML, Dawson NV, McCullough AJ, et al. Should all pregnant women be screened for hepatitis B? Ann Intern Med 1987;107:273-7. 6. Arevalo JA, Washington AE. Cost-effectiveness of prenatal screening and immunization for hepatitis B virus. JAMA 1988;259:365-9. 7. Tong MJ, Sinatra FR, Thomas DW, Nair PV, Merritt RJ, Wang DW. Need for immunoprophylaxis in infants born to HBsAg-positive carrier mothers who are HBeAg negative. J Pediatr 1984;105:945-7. 8. Delaplane D, Yogev R, Crussi F, Shulman ST. Fatal hepatitis B in early infancy: the importance of identifying HBsAgpositive pregnant women and providing immunoprophylaxis to their newborns. Pediatrics 1983;72: 176-80.