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order to improve infant prophylaxis. This screening program involved tracking women with HBsAg by test-ing at enrollment for prenatal care. Women who deliv-ered at Parkland Hospital and who were positive forHBsAg had carrier status established by serologic testing for the presence of hepatitis B core immunoglobulin (Ig)G antibody and the absence of hepatitis B core IgM

antibody. Each woman also had testing for liver func-tion, human immunodeficiency virus antibody, and hep-atitis B e antigen, if available. No quantitative testing forHBV by polymerase chain reaction (PCR) was per-formed. Women delivering at other Dallas County hos-

pitals did not uniformly undergo any immunologic orhepatic function testing.

Newborn infants of known chronic carrier motherswere administered hepatitis B immunoglobulin at birthalong with the first dose of the hepatitis B recombinantvaccine series. The remaining doses of vaccine weregiven at 1 and 6 months of age. Infants were then

followed up to 9 –15 months of age and tested for hepa-titis B surface antibody and antigen. The presence of HBsAg indicated immunoprophylaxis failure, whereasan antibody titer greater than 10 mIU in the absence of antigen indicated immunity. Uninfected infants with aninadequate antibody response were administered repeatvaccinations. Information on breast-feeding and its du-ration 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. Onlyinfants who successfully completed the vaccination pro-tocol 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. Cate-gorical data were compared using

2 analysis or Fischerexact test where appropriate. A P value less than .05 wasconsidered significant.

RESULTS

Three hundred ninety women who were chronic carri-ers of HBV were identified from January 1992 throughSeptember 1998. Three infants in the breast-fed groupwere excluded because there were insufficient bloodsamples and lack of follow-up. Eighteen infants in theformula-fed group were excluded. Sixteen did not haveadequate samples, and two infants were lost to follow-up.

We analyzed the remaining 101 breast-fed infants and268 formula-fed infants with complete follow-up data.

The maternal demographic characteristics of the study

group are shown in Table 1. One hundred sixty-twowomen delivered at Parkland Hospital, and 207 womendelivered at other Dallas County hospitals. The motherswho 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-fedgroup, most infants were Asian (37%), followed by black(32%), Hispanic (12%), white (9%), African (7%), andother (2%). There were more blacks (49%) in the for-mula fed group. The average duration of breast-feeding was 4.9 months (range 2 weeks to 1 year).

The number of women with abnormal laboratory

findings is given in Table 2. Two hundred forty-ninewomen (67%) had liver chemistry or serologic test re-sults available. Almost all missing data were from prena-tal care at other Dallas County Hospitals. In the breast-fed group, three of 43 (7%) women tested had livertransaminase abnormalities; one of these women had

primary hepatocellular carcinoma. In the formula-fedgroup, six of 175 (3%) women tested had liver transam-inase abnormalities (P .29). There was no significant

Table 1. Characteristics of the Study Population

CharacteristicBreast-fed(n 101)

Formula-fed(n 268) P

Maternal age (y) .004Mean SD 29.0 (6.2) 25.6 (6.3)Range 15–41 13–43

Ethnicity .006

Asian 38 (37) 84 (31)Black 33 (32) 132 (49)Hispanic 12 (12) 21 (8) White 9 (9) 20 (7) African 7 (8) 3 (1)Other 2 (2) 8 (3)

Nulliparous 37 (36) 93 (35) .48Infant sex

Male 56 (55) 136 (51) .25Female 45 (45) 132 (49)

SD standard deviation.Data are n (%), except for maternal age.

Table 2. Women With Abnormal Laboratory Findings

Laboratory findingBreast-fed(n 101)

Formula-fed(n 268) P

AST/ALT 3/43 (7) 6/175 (3) .29 Anti-HCV 2/52 (4) 7/131 (4) .93HIV-1 0/51 (0) 4/170 (3) .25HBeAg 11/51 (22) 41/157 (26) .51HBc IgG 56/59 (95) 176/190 (93) .54HBc IgM 2/52 (4) 15/179 (8) .27

AST aspartate aminotransferase; ALT alanine aminotransferase; Anti-HCV hepatitis C antibodies; HIV-1 human immunodefi-ciency virus 1; HBeAg hepatitis B e antigen; HBc hepatitis B core;IgG immunoglobulin G; IgM immunoglobulin M.

1 05 0 H il l et a l Hepatitis B and Breast-feeding OBSTETRICS & GYNECOLOGY



difference in women positive for HBeAg in the formulafed group (26%) compared with the breast-fed group(22%) (P .51). Four women in the formula-fed grouphad human immunodeficiency virus infection, and nonewere identified in the breast-fed group.

Five (5%) infants in the breast-fed group requiredadditional vaccine. Each infant seroresponded after re-ceiving the additional vaccine doses. Fourteen (5%) for-mula-fed infants required additional doses of vaccine

with subsequent immunity. This difference was not sig-nificant (P .91).

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 ratewas 0% (95% CI, 0, 3.6), and for women who formula-fed it was 3% (95% CI, 1.5, 6.3). These results did notdiffer significantly (P .063). We were unable to exam-ine the rate of HBV transmission by length of breast-feeding, without any observed transmission in this co-hort. Of the nine formula-fed infants who were infectedwith 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 thecases of HBV transmission in this cohort. HBeAg anti-gen status conferred a significantly higher risk (9.6%versus 1.9%, P .01) of HBV transmission among women with available HBeAg tests (Table 3).

DISCUSSION

In this prospective cohort study of chronic carriers of hepatitis B who successfully completed our immunopro-

phylaxis protocol, the overall transmission rate was

2.4%. Our findings indicate that the risk of HBV trans-mission is low after breast-feeding in a United Statescohort. Tseng et al (Tseng RYM, Lam CWK, Tam J.Breastfeeding babies of HBsAg positive mothers [letter].Lancet 1988;2:1032) reported similar results in a cohortof women in Hong Kong. They found HBsAg in 0 of 14(0%) breast-fed infants and in four of 156 (3%) bottle-fedinfants. These infants were immunized with hepatitis Bimmune globulin and then vaccinated at 1 day, 1 monthand 6 months of age.

Other studies have found various rates of HBV trans-mission in women who breast-fed. Beasley et al13 exam-ined two cohorts of patients. In the first cohort, 92 infantsof asymptomatic chronic HBV carriers who were breast-fed were compared with 55 formula-fed infants. Wheninfants were tested at 3 or more months of age, with amean 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 orvaccination. The authors concluded that there was noevidence for a relationship between breast-feeding andsubsequent development of hepatitis B in these infants.

A study from Hong Kong 4 described 97 women whowere HBsAg positive. Only four mothers in this cohort

breast-fed their infants. None of the infants were immu-nized or received vaccine. However, 72% of breast milksamples examined contained HBsAg. Although therewere a small number of breast-fed infants, the authorsadvised against breast-feeding and proposed that the

most important measure of prevention of HBV infectionwas immunization with hepatitis B immune globulin.

DeMartino et al8 described a cohort of 22 breast-fedinfants and 63 formula-fed infants who were born toasymptomatic mothers in Italy who were HBsAg posi-tive. These infants received hepatitis B immune globulinat birth followed by three injections of vaccine. Theauthors concluded that breast-fed infants are not athigher risk of contracting HBV infection than formula-fed infants.

Recommendations against breast-feeding have pointedto the shortcomings of the above-mentioned reports, the

small number of patients, and inconsistent results. We believe that our larger series provides useful clinical infor-mation regarding counseling patients who are highly moti-vated 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 andformula-fed infants. Although we found no cases of HBVtransmission in our breast-fed cohort, the 95% CI of theestimate of risk extends to 3.6%.

In mothers positive for HBeAg, the risk of verticaltransmission from chronic HBV carriers is higher. Al-though no breast-fed infants of HBeAg-positive mothers

seroconverted, our data are limited by the small numberof HBeAg carriers. Therefore, it is difficult to drawconclusions about the effect of HBeAg on the risk of transmission through breast-feeding.

There are several limitations to our study and itsconclusions. First, the cohorts were not randomly as-signed. 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 overallsizes of the cohorts limits the confidence intervals for the

Table 3. Hepatitis B Transmission by Feeding and Hepa-

titis B e Antigen Status

HBeAgBreast-fed(n 101)

Formula-fed(n 268)

Total(n 369)

Positive 0/11 5/41 5/52Negative 0/40 3/116 3/156*Not done 0/50 1/111 1/161

HBeAg hepatitis B e antigen.* P .002 compared with HBeAg-positive women (Fisher exact

test).

1051VOL. 99, NO. 6, JUNE 2002 Hill et al Hepatitis B and Breast-feeding



infection rates observed. We do not know the newbornHBsAg status to determine which were infected at birthand which were infected during breast-feeding. Finally,we do not have quantitative HBV polymerase chainreaction data to estimate maternal infectivity; instead, werelied on HBeAg status as a surrogate for increasedinfectivity. The power for the observed difference in the

incidence of vertical transmission from chronic HBVcarriers under these sample sizes is 0.28. Keeping thesample size in the same proportion, we would need 275

breast-fed infants and 729 formula-fed infants to achieve80% power to detect similar differences as observed.

In summary, breast-feeding in a United States cohortof HBV carriers with a low prevalence of HBeAg did notincrease the risk of HBV transmission. When combinedwith neonatal hepatitis B immunoprophylaxis and vac-cination, chronic carriers of HBV who are contemplating

breast-feeding can be counseled about a low risk (lessthan 4%) of HBV transmission. Women with HBeAg

and high infectivity should be counseled that the risk forHBV transmission with breast-feeding could be higher

but is currently unknown.

REFERENCES

1. Gilbert GL. Vertical transmission of hepatitis B: Review of the literature and recommendations for management. Med J Aust 1981;1:280 –5.

2. Lee AKY, Henrietta MH, Wong VC. Mechanisms of maternal-fetal transmission of hepatitis B virus. J Infect Dis1978;138:668–71.

3. Stevens CE, Beasley RP, Tsui J, Lee W. Vertical transmis-sion of hepatitis B antigen in Taiwan. N Engl J Med1975;292:771–4.

4. Wong VC, Lee AKY, Henrietta MH. Transmission of hepatitis B antigens from symptom free carrier mothers tothe fetus and the infant. Br J Obstet Gynaecol 1980;87:958–65.

5. Woo D, Cummins M, Davies PA, et al. Vertical transmis-sion of hepatitis B surface antigen in carrier mothers in twowest London hospitals. Arch Dis Child 1979; 54:670–5.

6. Beasley RP, Trepo C, Stevens CE, Szmuness W. The eantigen and vertical transmission of hepatitis B surfaceantigen. Am J Epidemiol 1977;105:94– 8.

7. Schweitzer IL. Vertical transmission of the hepatitis Bsurface antigen. Am J Med Sci 1975;270:287–91.

8. De Martino M, Appendino C, Resti M, Rossi ME, Muc-cioli AT, Vierucci A. Should hepatitis B surface antigen

positive mothers breastfeed? Arch Dis Child 1985;60:972–4.

9. American Academy of Pediatrics and American College of Obstetricians and Gynecologists. Guidelines for perinatalcare. 4th ed. Elk Grove Village, IL: American Academy of Pediatrics; Washington, DC: American College of Obste-tricians and Gynecologists; 1997.

10. Chen DS, Hsu NH, Sung JL, Hsu TC, Hsu ST, Kuo YT,et al. The Hepatitis Steering Committee and the HepatitisControl Committee. A mass vaccination program in Tai-wan against hepatitis B virus infection in infants of hepati-tis B surface antigen-carrier mothers. JAMA 1987;257:2597–603.

11. Maupas P, Chiron JP, Barin F, Coursaget P, Goudeau A,Perrin J, et al. Efficacy of hepatitis B vaccine in preventionof early HBsAg carrier state in children: Controlled trial inan endemic area (Senegal). Lancet 1981;1:289–92.

12. Stevens CE, Toy PT, Tong MJ, Taylor PE, Vyas GN,Nair PV, et al. Perinatal hepatitis B virus transmission inthe United States: Prevention by passive-active immuniza-tion. JAMA 1985;253:1740–5.

13. Beasley RP, Stevens CE, Shiao IS, Meng HC. Evidenceagainst breastfeeding as a mechanism for vertical transmis-sion of hepatitis B. Lancet 1975;2:740–1.

14. Moi MT, Targonski PV, Stoll BJ, Albert GP, Margolis HS.

Prevention of perinatal transmission of the hepatitis Bvirus: Outcome of infants in a community prevention program. Am J Dis Child 1992;146:793– 6.

Address reprint requests to: James B. Hill, MD, Department of Obstetrics and Gynecology, University of Texas SouthwesternMedical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9032; E-mail: [email protected].

Received October 29, 2001. Received in revised form January 22, 2002. Accepted February 14, 2002.

1 05 2 H il l et a l Hepatitis B and Breast-feeding OBSTETRICS & GYNECOLOGY

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