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ORIGINAL RESEARCH |
From the Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas and the Dallas County Health Department, Dallas, Texas.
Address reprint requests to: James B. Hill, MD, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9032; E-mail: james.hill{at}utsouthwestern.edu.
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ABSTRACT |
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METHODS: Since 1992, information on women with HBV during pregnancy has been collected in a prospective longitudinal study. Those HBV carriers and their infants participating in a county HBV immunoprophylaxis program were identified. Infants were followed for up to 15 months and examined for hepatitis B infection by hepatitis B surface antigen (HBsAg).
RESULTS: A total of 369 infants born to women with chronic HBV met the inclusion criteria and received hepatitis B immune globulin at birth and the full course of the hepatitis B vaccine series. We compared 101 breast-fed infants with 268 formula-fed infants. There was no significant difference between the two groups with respect to the number of women who were positive for hepatitis B e antigen (HBeAg) (22% versus 26%, P = .51). Three women in the breast-feeding group had liver transaminase abnormalities, compared with six women in the formula-feeding group (P = .29). Overall, there were nine cases of HBV infection transmission (2.4%). None of the 101 breast-fed infants and nine formula-fed infants (3%) were positive for HBsAg after the initial vaccination series (P = .063). The mean length of time for breast-feeding was 4.9 months (range 2 weeks to 1 year).
CONCLUSION: With appropriate immunoprophylaxis, including hepatitis B immune globulin and hepatitis B vaccine, breast-feeding of infants of chronic HBV carriers poses no additional risk for the transmission of the hepatitis B virus.
Hepatitis B virus (HBV) is readily transmitted from the mother to the fetus. Most of this transmission occurs to asymptomatic HBV carriers during labor and delivery. Although the mechanism of transmission is not known, it is presumed to result from exposure to maternal blood, secretions, or both1–5 and is more common in women with the hepatitis B e antigen (HBeAg).2,5–7
Transmission of HBV through breast milk has been reported in several studies ( Linnemann CC, Goldberg S. HBAg in breast milk [letter]. Lancet 1974;2:155; Boxall EH, Flewett TH, Dane DS. Hepatitis B surface antigen in breast milk [letter]. Lancet 1974;2:1007–8).2,8 Several groups have recommended against breast-feeding on the basis of those data.5,9,10 The proscription of breast-feeding appears justified, if it is associated with any increased risk of HBV transmission and its long-term consequences. The majority of these breast-fed infected infants become chronic hepatitis B carriers and develop sequelae of chronic infection, such as cirrhosis and hepatocellular carcinoma.11 However, the mechanism and risks of transmission of hepatitis B in breast milk are not well understood.
In the United States, infants of mothers with the hepatitis B surface antigen (HBsAg) receive both hepatitis B immune globulin at birth and the hepatitis B vaccine series. There has been considerable success with these programs, with reports of less than a 5% transmission rate when infants completed the full HBV vaccination protocol.12 That protocol theoretically reduces the risk of neonatal transmission during breast-feeding.5,13 However, breast-feeding in chronic hepatitis B carriers has not been studied after use of passive immunoprophylaxis and active vaccination regimen at birth.14 Many clinicians have not encouraged breast-feeding in this population; however, many women remain motivated to breast-feed despite the potential risk. In this study, we compared the risk of HBV transmission from chronic HBV carriers to infants who were and were not breast-fed.
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MATERIALS AND METHODS |
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Newborn infants of known chronic carrier mothers were administered hepatitis B immunoglobulin at birth along with the first dose of the hepatitis B recombinant vaccine series. The remaining doses of vaccine were given at 1 and 6 months of age. Infants were then followed up to 9–15 months of age and tested for hepatitis B surface antibody and antigen. The presence of HBsAg indicated immunoprophylaxis failure, whereas an antibody titer greater than 10 mIU in the absence of antigen indicated immunity. Uninfected infants with an inadequate antibody response were administered repeat vaccinations. Information on breast-feeding and its duration was obtained.
Beginning in 1992, these data have been collected prospectively and entered into a computerized database. Women who were chronic carriers of HBV and who breast-fed for at least 2 weeks were compared with chronic carriers who chose not to breast-feed. Formula-fed infants were fed exclusively with formula. Only infants who successfully completed the vaccination protocol were included for analysis.
Statistical analysis was performed with EpiInfo 6.04a (Centers for Disease Control and Prevention, Atlanta, GA). Means were compared using Student t test. Categorical data were compared using 
2 analysis or Fischer exact test where appropriate. A P value less than .05 was considered significant.
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RESULTS |
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We analyzed the remaining 101 breast-fed infants and 268 formula-fed infants with complete follow-up data. The maternal demographic characteristics of the study group are shown in Table 1
. One hundred sixty-two women delivered at Parkland Hospital, and 207 women delivered at other Dallas County hospitals. The mothers who breast-fed were older (29.0 versus 25.6 years, P = .004). There was a significant difference in ethnicity between the two groups (P = .006). In the breast-fed group, most infants were Asian (37%), followed by black (32%), Hispanic (12%), white (9%), African (7%), and other (2%). There were more blacks (49%) in the formula fed group. The average duration of breast-feeding was 4.9 months (range 2 weeks to 1 year).
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. Two hundred forty-nine women (67%) had liver chemistry or serologic test results available. Almost all missing data were from prenatal care at other Dallas County Hospitals. In the breast-fed group, three of 43 (7%) women tested had liver transaminase abnormalities; one of these women had primary hepatocellular carcinoma. In the formula-fed group, six of 175 (3%) women tested had liver transaminase abnormalities (P = .29). There was no significant difference in women positive for HBeAg in the formula fed group (26%) compared with the breast-fed group (22%) (P = .51). Four women in the formula-fed group had human immunodeficiency virus infection, and none were identified in the breast-fed group.
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The overall infection rate in this cohort of infants of women with chronic HBV was 2.4% (95% CI, 1.1, 4.6). For women who breast-fed, the vertical transmission rate was 0% (95% CI, 0, 3.6), and for women who formula-fed it was 3% (95% CI, 1.5, 6.3). These results did not differ significantly (P = .063). We were unable to examine the rate of HBV transmission by length of breast-feeding, without any observed transmission in this cohort. Of the nine formula-fed infants who were infected with HBV, five were born to the 41 women who were positive for HBeAg (Table 2
). Thus overall, HBeAg-positive HBV carriers accounted for over half of the cases of HBV transmission in this cohort. HBeAg antigen status conferred a significantly higher risk (9.6% versus 1.9%, P = .01) of HBV transmission among women with available HBeAg tests (Table 3).
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DISCUSSION |
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Other studies have found various rates of HBV transmission in women who breast-fed. Beasley et al13 examined two cohorts of patients. In the first cohort, 92 infants of asymptomatic chronic HBV carriers who were breast-fed were compared with 55 formula-fed infants. When infants were tested at 3 or more months of age, with a mean age at last follow-up of 11 months, no difference was seen in the HBV infection rate (53% versus 60%). These infants did not undergo immunoprophylaxis or vaccination. The authors concluded that there was no evidence for a relationship between breast-feeding and subsequent development of hepatitis B in these infants.
A study from Hong Kong4 described 97 women who were HBsAg positive. Only four mothers in this cohort breast-fed their infants. None of the infants were immunized or received vaccine. However, 72% of breast milk samples examined contained HBsAg. Although there were a small number of breast-fed infants, the authors advised against breast-feeding and proposed that the most important measure of prevention of HBV infection was immunization with hepatitis B immune globulin.
DeMartino et al8 described a cohort of 22 breast-fed infants and 63 formula-fed infants who were born to asymptomatic mothers in Italy who were HBsAg positive. These infants received hepatitis B immune globulin at birth followed by three injections of vaccine. The authors concluded that breast-fed infants are not at higher risk of contracting HBV infection than formula-fed infants.
Recommendations against breast-feeding have pointed to the shortcomings of the above-mentioned reports, the small number of patients, and inconsistent results. We believe that our larger series provides useful clinical information regarding counseling patients who are highly motivated to breast-feed. We cannot conclusively say that breast-feeding is safe, but we can state that the risk of transmission is low and comparable for both breast-fed and formula-fed infants. Although we found no cases of HBV transmission in our breast-fed cohort, the 95% CI of the estimate of risk extends to 3.6%.
In mothers positive for HBeAg, the risk of vertical transmission from chronic HBV carriers is higher. Although no breast-fed infants of HBeAg-positive mothers seroconverted, our data are limited by the small number of HBeAg carriers. Therefore, it is difficult to draw conclusions about the effect of HBeAg on the risk of transmission through breast-feeding.
There are several limitations to our study and its conclusions. First, the cohorts were not randomly assigned. There were possibly some biases against breast-feeding that might have led high-risk women to bottle-feed and lower-risk women to breast-feed. The overall sizes of the cohorts limits the confidence intervals for the infection rates observed. We do not know the newborn HBsAg status to determine which were infected at birth and which were infected during breast-feeding. Finally, we do not have quantitative HBV polymerase chain reaction data to estimate maternal infectivity; instead, we relied on HBeAg status as a surrogate for increased infectivity. The power for the observed difference in the incidence of vertical transmission from chronic HBV carriers under these sample sizes is 0.28. Keeping the sample size in the same proportion, we would need 275 breast-fed infants and 729 formula-fed infants to achieve 80% power to detect similar differences as observed.
In summary, breast-feeding in a United States cohort of HBV carriers with a low prevalence of HBeAg did not increase the risk of HBV transmission. When combined with neonatal hepatitis B immunoprophylaxis and vaccination, chronic carriers of HBV who are contemplating breast-feeding can be counseled about a low risk (less than 4%) of HBV transmission. Women with HBeAg and high infectivity should be counseled that the risk for HBV transmission with breast-feeding could be higher but is currently unknown.
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Footnotes |
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Received October 29, 2001. Received in revised form January 22, 2002. Accepted February 14, 2002.
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REFERENCES |
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2. Lee AKY, Henrietta MH, Wong VC. Mechanisms of maternal-fetal transmission of hepatitis B virus. J Infect Dis 1978;138:668–71.[Medline]
3. Stevens CE, Beasley RP, Tsui J, Lee W. Vertical transmission of hepatitis B antigen in Taiwan. N Engl J Med 1975;292:771–4.[Abstract]
4. Wong VC, Lee AKY, Henrietta MH. Transmission of hepatitis B antigens from symptom free carrier mothers to the fetus and the infant. Br J Obstet Gynaecol 1980;87: 958–65.[Medline]
5. Woo D, Cummins M, Davies PA, et al. Vertical transmission of hepatitis B surface antigen in carrier mothers in two west London hospitals. Arch Dis Child 1979; 54:670–5.[Abstract]
6. Beasley RP, Trepo C, Stevens CE, Szmuness W. The e antigen and vertical transmission of hepatitis B surface antigen. Am J Epidemiol 1977;105:94–8.
7. Schweitzer IL. Vertical transmission of the hepatitis B surface antigen. Am J Med Sci 1975;270:287–91.[Medline]
8. De Martino M, Appendino C, Resti M, Rossi ME, Muccioli AT, Vierucci A. Should hepatitis B surface antigen positive mothers breastfeed? Arch Dis Child 1985;60: 972–4.[Abstract]
9. American Academy of Pediatrics and American College of Obstetricians and Gynecologists. Guidelines for perinatal care. 4th ed. Elk Grove Village, IL: American Academy of Pediatrics; Washington, DC: American College of Obstetricians and Gynecologists; 1997.
10. Chen DS, Hsu NH, Sung JL, Hsu TC, Hsu ST, Kuo YT, et al. The Hepatitis Steering Committee and the Hepatitis Control Committee. A mass vaccination program in Taiwan against hepatitis B virus infection in infants of hepatitis B surface antigen-carrier mothers. JAMA 1987;257: 2597–603.[Abstract]
11. Maupas P, Chiron JP, Barin F, Coursaget P, Goudeau A, Perrin J, et al. Efficacy of hepatitis B vaccine in prevention of early HBsAg carrier state in children: Controlled trial in an endemic area (Senegal). Lancet 1981;1:289–92.[Medline]
12. Stevens CE, Toy PT, Tong MJ, Taylor PE, Vyas GN, Nair PV, et al. Perinatal hepatitis B virus transmission in the United States: Prevention by passive-active immunization. JAMA 1985;253:1740–5.[Abstract]
13. Beasley RP, Stevens CE, Shiao IS, Meng HC. Evidence against breastfeeding as a mechanism for vertical transmission of hepatitis B. Lancet 1975;2:740–1.[Medline]
14. Moi MT, Targonski PV, Stoll BJ, Albert GP, Margolis HS. Prevention of perinatal transmission of the hepatitis B virus: Outcome of infants in a community prevention program. Am J Dis Child 1992;146:793–6.[Abstract]
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