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Evaluation of the Compliance With Recommended Procedures in Newborns Exposed to HBsAg-Positive Mothers

A Multicenter Collaborative Study

Heininger, Ulrich MD*; Vaudaux, Bernard MD; Nidecker, Myriam cand.med.; Pfister, Riccardo E. MD, PhD; Posfay-Barbe, Klara M. MD, MS; Bachofner, Marius MD*; Hoigné, Irene MD§; Gnehm, Hanspeter E. MD§

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The Pediatric Infectious Disease Journal: March 2010 - Volume 29 - Issue 3 - p 248-250
doi: 10.1097/INF.0b013e3181bd7f89
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Abstract

It has been estimated for the year 2000 that 620,000 persons would die worldwide from hepatitis B virus (HBV) related diseases: 580,000 (94%) from cirrhosis and hepatocellular cancer related to chronic HBV infection and 40,000 (6%) from acute hepatitis B.1 The model further estimated that, in the absence of immunization, 64.8 million infants of a yearly birth cohort would be infected with HBV and 1.4 million would die of HBV-related disease. Most sequelae from chronic HBV infection result from maternal-infant transmission of HBV during birth. Development of chronic disease is approximately 90% in unvaccinated children born to hepatitis B surface antigen (HBsAg) and hepatitis B envelope antigen positive mothers and 40% in those born to HBsAg positive/hepatitis B envelope antigen negative mothers.2,3

Currently, the frequency of HBsAg carriers is estimated to be approximately 1% in women of child-bearing age in Switzerland.4,5 The Swiss Federal Office of Public Health recommends antenatal HBsAg screening in all pregnant women preferably in the third trimester (and intra-/postnatal catch-up if not done before) followed by active and passive immunization for newborns of HBsAg-positive mothers.4 This procedure has a demonstrated success rate of 90% to 97% and provides long-lasting immunity.6–8 To complete the immunization series, further doses of HBV vaccine are recommended at 1 and 6 months or 1, 2, and 12 months of age. Furthermore, serological control of successful immunization of the infant is recommended preferably 4 (to 8) weeks after the last dose of HBV vaccine, ie, at 7 (to 15) months of age. Successful immunization has been defined as an anti-HBs antibody value of ≥100 IU/L in Switzerland.4

In a single center study, we previously found that physicians' compliance with official recommendations was suboptimal.5 The goal of the present collaborative multicenter study was to determine current compliance, with official recommendations for prevention of perinatal hepatitis B transmission in a large cohort of mothers and their infants with the aim to improve the management of HBV-exposed infants.

METHODS

This retrospective study was performed in maternity units of large teaching hospitals in 4 regions of Switzerland which are listed as follows: Aarau, Basel, Geneva, and Lausanne. Records of all women admitted for delivery to the participating centers between January 1, 2005 and December 31, 2006, were screened for documentation of HBsAg testing during pregnancy. The total numbers of births during the study period were extracted from the study centers' birth records. In HBsAg-positive mothers and their offspring, data were obtained from patient charts after informed consent: maternal nationality, mother's and child's dates of birth, names, address and phone number, child's pediatrician, time interval from birth to administration of hepatitis B immunoglobulins, and/or hepatitis B vaccine. A standardized questionnaire was sent to pediatricians for information on subsequent hepatitis B immunizations and results of subsequent serological tests in each child.

In accordance with Swiss national guidelines,4 procedures performed were categorized as “complete and on time” if:

  • Hepatitis B immunoglobulines was administered within the first 24 hours of birth.
  • HBV vaccine was administered within 24 hours and was followed by further doses of HBV (0-, 1-, and 6-month or 0-, 1-, 2-, and 12-month schedule).
  • Serum was tested for anti-HBs antibodies between 7 and 15 months of age. If <100 IU/mL, further dose(s) of HBV vaccine had to be administered until ≥100 IU/mL was reached.

Ethical approval was obtained. Informed consent was requested from all HBsAg-positive mothers to contact their child's pediatrician.

RESULTS

Of 27,226 women giving birth, 95 (0.35%) had missing records. Of the remaining 27,131 women, 26,750 (98.6%) were tested for HBsAg during pregnancy, and 194 (0.73%) were positive including 1 woman who delivered twice during the study period and 2 women delivering twins (Table 1). Of 196 HBsAg-exposed infants, 53 (27%) were excluded because of refused study participation, change of address, or still births. Inclusion rates were similar at the 4 study sites: 39 (72%) of 54 newborns (site A), 11 (73%) of 15 newborns (site B), 55 (74%) of 74 newborns (site C), and 38 (72%) of 53 newborns (site D). Of the 141 mothers of these 143 children, 84% were foreign born. The likelihood for timely completion of infant immunizations was higher in Swiss born mothers than in foreign born mothers (17/24, 71%, vs. 52/119, 44%; P = 0.015) whereas maternal age did not play a role in this regard.

TABLE 1
TABLE 1:
General Maternal Characteristics by Study Regions

In 141 (98.6%) newborns, active and passive anti-HBV immunization within 24 hours of birth could be verified and in all of 76 newborns for whom the exact hour of immunization was recorded this was done within 24 hours of birth. In 2 newborns birth records could not be retrieved. In 83% of HBsAg exposed newborns, the immunization series was completed with at least 2 further doses of hepatitis B vaccine but, unfortunately, frequently not in a timely fashion (Table 2). Delayed administration of dose 2 was the most frequently observed deviation and there was significant site to site variation with proportions of complete immunizations ranging from 54% to 100% (data not shown).

TABLE 2
TABLE 2:
Procedures in 143 HBsAg Exposed Infants After Discharge From Maternity Wards

Similarly, serological control of successful immunization was not performed frequently according to recommendations: 38% of children were tested at all and 22% of children were tested in a timely fashon as recommended. The likelihood for timely serology was similar in infants of Swiss born and foreign born mothers (29% vs. 21%; P = 0.38); maternal age did not play a role in this regard. In several cases serological testing was only prompted by participation in this study. Finally, anti-HBs antibody values ≥100 IU/L were documented in 27% of infants. All infants with antibody values <100 IU/L at least had values >10 IU/L (low responders) and no chronically infected child was identified.

Analysis of hospital discharge letters revealed quality problems with either lack of advice to primary care pediatricians on the need to administer further doses of hepatitis B vaccine and/or missing information on the need to perform serological testing after the last dose of hepatitis B vaccination. Again, significant site-to-site variability was noted with generally better compliance with recommended procedures when these were specifically mentioned in the discharge letter.

DISCUSSION

Although compliance with HBsAg screening in pregnant women and administration of active and passive HBV immunization in HBsAg exposed newborns was excellent (>98%), compliance with application of further doses of active immunization and serological success control was far from optimal. The need for additional doses of HBV vaccine in low responders (anti HBs antibody value, ≥10–99 IU/L) was disregarded in 6 of 19 such infants and final serological documentation of success was only achieved in 3 of 19 low responders. No nonresponders (anti HBs antibody value, <10 IU/L) and no HBV infections were found among 55 of 143 tested infants. However, the number of nonresponders and HBV infections among the remaining 88 infants is unknown.

There was no evidence that postponing HBV vaccine dose 2 from 1 month of age, as recommended, to 2 months of age would be detrimental in terms of prevention of HBV infection. Although postponing would make administration easier as a licensed hexavalent diphtheria-tetanus-pertussis-inactivated poliomyelitis-Hib-HBV vaccine could be used, we would not encourage delaying dose 2 to 2 months of age as current efficacy data are primarily on the basis of the conventional 0-, 1-, and 6-month or 0-, 1-, 2-, and 12-month schedules.9

Similar results as those which we observed were encountered in comparable other studies.10–13 In a study from the United Kingdom, failure rates to reach second and third doses and serological testing were 7%, 18%, and 33%, respectively.10 Corresponding rates in a US study were 2%, 11%, and 20%.11 A recent study from Zurich, Switzerland, revealed a failure rate of 6% for active and passive immunization in exposed newborns and failure rates of 10% and 15% for the second and third doses and significant delays in administration of immunizations; compliance with serological testing was not reported.12 In contrast, a dedicated Dutch team established a program with electronic data management and an assigned public health nurse who manages cases by home visits.13 From 1993 to 1998, 691 HBsAg exposed children were followed. Although administration of the first dose of HBV vaccine was frequently delayed, 99.7% of these newborns completed the full immunization series and 95% of those eligible were serologically tested. All 78 neonates with anti-HBs antibody value <100 IU/L were revaccinated.

Strengths of our study were its large sample size and the performance of all study procedures in a standardized fashion. As limitations, only 73% of eligible families could be enrolled and final clinical outcome in exposed children (chronic hepatitis B or not) was not conclusively studied. Nevertheless, we identified important shortcomings in the management of these high risk children. The quality of discharge letters in terms of communicating the need for completion of the immunization series as well as serological success control needs improvement. Active follow-up, for example, by sending regular reminding letters from the neonatal wards to parents and pediatricians of HBsAg-exposed infants, possibly supported by central or local patient registries, should therefore be considered. Alternatively, if appropriate care for HBsAg exposed infants cannot be achieved, universal newborn hepatitis B immunization should be discussed.14,15.

ACKNOWLEDGMENTS

The authors thank the staff of the neonatal and obstetrical departments, pediatricians in private practices, and the families for their contributions and participation in this study. Special thanks to N. Bürki, MD (Hospital Liestal); F. deTechtermann, MD (Hôpital de Vevey); P. Dolivo, MD (Hôpital d'Yverdon); S. Heinzl, MD (Hospital Bruderholz); I. Hösli, MD (University Hospital Basel); and A. Zemmouri, MD (Hôpital de Morges) for their valuable contributions.

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Keywords:

hepatitis B; HBs antigen; newborn; vaccine

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