Copyright 2001 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2001
Routine use of hepatitis B vaccine for low-risk newborns was suspended on July 7, 1999, because of concern about the potential risk of thimerosal, a mercury-containing vaccine preservative. Reinstatement of the birth dose was recommended when a thimerosal-free vaccine became available.
To explore changes in hepatitis B vaccination practices for newborns related to the revised recommendations for low-risk infants (in this study, the terms newborn and infant are used interchangeably).
A telephone survey of a random sample of 1000 US hospitals.
Nurse managers, nursery directors, and staff nurses of the newborn nurseries.
Main Outcome Measures
Nursery vaccination practices before and after July 7, 1999, and the availability and use of thimerosal-free vaccine.
Interviews were conducted with 773 (87%) of 886 eligible hospitals. Before July 7, 1999, 78% of the hospitals reported vaccination practices that were consistent with recommendations at that time, although only 47% vaccinated all low-risk infants at birth. After July 7, 1999, almost all hospitals discontinued vaccination of low-risk infants, in accordance with the recommendation change; however, there was a 6-fold increase in the number of hospitals that were not vaccinating all high-risk infants. After the introduction of thimerosal-free vaccine, only 39% of the hospitals reported vaccinating all low-risk infants.
Most hospital nurseries altered their newborn hepatitis B vaccination practices consistent with changes in national recommendations. However, unintended consequences included the failure of some hospitals to continue vaccinating all high-risk infants and the delay in reintroducing vaccination for low-risk newborns after the introduction of a thimerosal-free vaccine. Assessments of the appropriateness of this country's response to the threat of thimerosal in vaccines should consider these findings.
THIMEROSAL, an organic mercury-containing preservative, has been used for more than 60 years in vaccines to prevent contamination. A 1999 report from the US Agency for Toxic Substances and Disease Registry suggested that infants who receive thimerosal-containing vaccines in the first 6 months of life may be exposed to mercury levels exceeding some federal guidelines, and on July 7, 1999, the US Public Health Service (PHS) and the American Academy of Pediatrics (AAP) published a joint statement regarding thimerosal.1 Concern about the potential risk related to thimerosal led the PHS and AAP to change their hepatitis B vaccination recommendation for low-risk infants, ie, those born to mothers whose test result for hepatitis B surface antigen (HBsAg) was negative: physicians were encouraged to postpone the first dose of hepatitis B vaccine from birth until 2 to 6 months of age. The statement clarified that, due to the high risk of infection, infants born to mothers who are HBsAg positive or whose HBsAg status is unknown should continue to receive the first dose of hepatitis B vaccine at birth. This recommendation was published in Pediatrics,1Morbidity and Mortality Weekly Report,2 and the AAP News; presented on the National Immunization Program Web site; and disseminated via state immunization programs and the AAP's electronic membership mailing list. In addition, the American Academy of Family Physicians issued its own similar recommendation3 about thimerosal and hepatitis B vaccine. A follow-up statement4 from the PHS stated that a return to the recommended practice of vaccinating newborns was anticipated as soon as adequate supplies of thimerosal-free vaccine became available.
On September 10, 1999, a subsequent statement5 was published in Morbidity and Mortality Weekly Report, announcing the availability of a thimerosal-free hepatitis B vaccine. The Morbidity and Mortality Weekly Report statement5 indicated that a single-antigen thimerosal-free hepatitis B vaccine should be prioritized for newborns, and that routine hepatitis B vaccination policies for all newborns should be reintroduced immediately in hospitals in which such policies and practices had been discontinued. At that point, thimerosal-free vaccine could be ordered directly from the manufacturer but was not yet available through the PHS or state immunization programs; supplies of this vaccine were insufficient at that time to vaccinate all newborns in the United States. In mid-October 1999, thimerosal-free vaccine became available through the PHS; states were able to order limited quantities of the vaccine, prioritized for hospital nurseries only. By December 1999, there was sufficient vaccine supply to cover the 0- to 6-month age group in all states.
To explore changes in hepatitis B vaccination practices in hospital nurseries related to the recommendation changes, a telephone interview study was designed and conducted in late 1999. Specifically, we sought to characterize nursery vaccination practices at 3 points: time 1, from January to June 1999, before any thimerosal-related announcements; time 2, from July to October 1999, during the period that newborn hepatitis B vaccination was suspended for infants born to HBsAg-negative mothers; and time 3, from November to December 1999, after thimerosal-free vaccine became available in sufficient supply for all US newborns.
A standardized 10-minute telephone interview protocol was designed for use with nurse managers and/or other knowledgeable staff of hospital newborn nurseries. Specific questions focused on the 3 periods of interest. To estimate hepatitis B vaccination practices in each period studied, interviewers asked hospital respondents to indicate whether none, some, or all infants born to mothers who were HBsAg positive, HBsAg negative, or HBsAg unknown received hepatitis B vaccine in the newborn nursery before hospital discharge. Other items focused on the availability of thimerosal-free vaccine; whether resumption of hepatitis B vaccination was met by any resistance from physicians, nursing staff, or parents; and demographic variables.
Interview protocols were pilot tested for clarity and ease of use with nurse managers from a convenience sample of 10 hospitals in 4 states. For 5 of those hospitals, identical interview protocols were used with physician directors of the newborn nursery. Information provided by nurse managers was validated by physician nursery directors using identical interview protocols.
Data collection occurred in December 1999, 2½ to 3 months after publication of the PHS recommendation to resume newborn vaccination; by this time, there was a sufficient supply of thimerosal-free vaccine available to vaccinate all US newborns. Six trained interviewers telephoned a national random sample of 1000 hospitals, drawn from the database of all hospitals maintained by the Hospital Management Research Institute. Interviewers asked to speak with the nurse manager in charge of the normal newborn nursery. If a nurse manager was unavailable, interviewers asked to speak with the nursery director or a charge nurse. If that respondent felt unable to provide reliable information (eg, had worked in the nursery <6 months or had administrative oversight rather than day-to-day involvement), she or he recommended a staff nurse knowledgeable about nursery vaccination practices to complete the interview. When the appropriate individual was located, interviewers obtained verbal consent to participate and then conducted the interview.
Data analysis included general descriptive statistics, followed by bivariate analysis to explore associations between hospital demographic characteristics and hepatitis B vaccination practices. Analyses were performed using SAS statistical software, version 6.0 (SAS Institute Inc, Cary, NC). The study protocol was approved by the institutional review boards of the University of Michigan Medical Center, Ann Arbor, and the Centers for Disease Control and Prevention, Atlanta, Ga.
From our original sample of 1000 hospitals, we excluded 114 ineligible hospitals (those that had closed or that were not delivering newborns). Interviews were conducted with 773 of 886 eligible hospitals, for a response rate of 87%. Of the nonparticipating hospitals, 86 (10%) cited inadequate time to complete the interview and 27 (3%) declined participation.
Most interviews were completed with the normal newborn nursery's nurse manager (64%); other interviewees included charge nurses (12%), staff nurses (16%), or physician nursery directors (8%). The demographic characteristics of hospitals with completed interviews are shown in Table 1. These hospitals represented all 50 states, plus the District of Columbia.
As shown in Table 2, 88% of the hospitals in the study gave hepatitis B vaccine to all infants born to HBsAg-positive mothers, with an additional 9% reporting no mothers who were HBsAg positive during time 1. Vaccination of other infant groups at time 1 was less consistent, with only 47% of hospitals vaccinating all low-risk infants (those born to mothers who were HBsAg negative). At time 2, most hospitals altered their vaccination practices in accordance with the PHS/AAP revised recommendations; however, a small but significant number of hospitals reported vaccination practices for high-risk infants that were inconsistent with the time 2 recommendations. Specifically, 7% of hospitals reported vaccinating none of the infants born to HBsAg-positive mothers, and 19% of hospitals reported vaccinating none of the infants born to mothers of unknown HBsAg status; these time 2 figures represent a 6-fold increase over the time 1 rates. In addition, many more hospitals reported that they had no mothers whose HBsAg status was positive or unknown during time 2 compared with time 1.
At the time of the interview, only 223 hospitals had obtained thimerosal-free vaccine for their nursery. Among the 405 hospitals that did not have thimerosal-free vaccine, 61% either were unaware that the product was available or had not made a decision about its use; for another 7%, the hospital had decided not to reinstitute hepatitis B vaccination. Twenty-seven percent of hospitals had ordered vaccine and were awaiting delivery from either the vaccine manufacturer or the state vaccine program.
For the 223 hospitals using thimerosal-free vaccine available at the time of the interview, respondents were asked whether there was resistance from physicians, parents, or nursing staff to the resumption of hepatitis B vaccination in the nursery. Sixteen percent believed there was some or a lot of resistance from physicians, 9% believed there was resistance from parents, and 7% believed there was resistance from nursing staff. Nineteen percent reported that confusion about the changes in hepatitis B vaccine recommendations may have affected their nursery's vaccination practices. In addition, 27% of hospital respondents indicated there were one or more "other" factors affecting the use of hepatitis B vaccine in the newborn nursery. The factors described most frequently were physician preference to administer all doses of hepatitis B vaccine in the outpatient setting (n = 29), the high cost of thimerosal-free vaccine and/or reimbursement problems in the hospital setting (n = 20), and concerns about insufficient supply of thimerosal-free vaccine (n = 10).
Hepatitis B vaccination practices at time 3 for the 223 hospitals with thimerosal-free vaccine are shown separately for each risk group in Table 2. These data demonstrate that, for infants born to HBsAg-positive mothers, 95% of hospitals either vaccinated all such infants or had no infants in this group; this is comparable to the time 1 rates. However, the proportion of hospitals vaccinating all low-risk infants was smaller at time 3 than at time 1.
Bivariate analyses were conducted to explore associations between vaccination practices for low-risk infants at times 1 and 3. Among hospitals that were vaccinating all low-risk infants at time 1 and that had thimerosal-free vaccine available at time 3, those that reported physician resistance to resumption of newborn vaccination were less likely to be vaccinating all low-risk infants at time 3 (38% vs 62%; P = .02), as were those that reported some confusion related to the policy change (45% vs 55%; P = .02).
Table 3 classifies hospitals' hepatitis B vaccination practices at all 3 periods. At time 1, most hospitals had vaccination practices that were consistent with PHS/AAP recommendations at that time (ie, vaccinating all infants born to mothers with positive or unknown hepatitis B status). The recommendation did not require that infants receive a birth dose of hepatitis B vaccine, only that the first dose be received at or by the age of 2 months; therefore, hospitals that were not vaccinating all low-risk infants were not categorized as inconsistent with recommendations. At time 2, only 55% of the reported vaccination practices were consistent with PHS/AAP recommendations (ie, vaccinating all infants born to mothers with positive or unknown hepatitis B status but none of the low-risk infants). The primary reason for this decrease was failure to vaccinate all infants born to mothers of unknown hepatitis B status (34% of hospitals); in addition, 6% of hospitals were categorized as inconsistent because they continued vaccinating all low-risk newborns. At time 3, only 37% of hospitals with thimerosal-free vaccine available reported vaccination practices consistent with PHS/AAP recommendations for universal vaccination of all newborns. Of the 63% of hospitals that were inconsistent at time 3, each reported vaccinating none or some—but not all—infants of unknown status; not one hospital in this group had resumed universal vaccination of low-risk newborns.
Data from this study suggest that changes in hospital hepatitis B vaccination practices in response to revised PHS/AAP recommendations had some unintended and potentially harmful effects. Although more than 90% of hospitals suspended the use of thimerosal-containing vaccine for infants born to HBsAg-negative mothers, some hospitals discontinued routine vaccination practices for high-risk infants and for infants at unknown risk. The proportion of hospitals vaccinating none of the infants born to HBsAg-positive mothers increased from 1% at time 1 to 7% at time 2; the proportion of hospitals vaccinating none of the infants born to mothers whose HBsAg status was unknown also increased during this period, from 3% to 19%. This finding is extremely concerning, considering the significant medical implications resulting from failure to administer hepatitis B vaccine to high-risk infants in the first 12 hours of life. During data collection for this study, interviewers verified responses of inappropriate vaccination practices for high-risk infants through follow-up questions (eg, "So none of the infants born to HBsAg-positive mothers were vaccinated?"). This study's reported increase in inappropriate vaccination practices for a small group of high-risk infants parallels anecdotal reports to the PHS that, following publication of the thimerosal-related recommendations, some high-risk infants did not receive hepatitis B vaccine within 12 hours of birth.5
Our data do not clarify whether reported nonvaccination of all high-risk infants was due to misinterpretation of new recommendations, breakdowns in communication from nursery director to nurse managers or other nursing staff, or human error. Although one fifth of the respondents thought that confusion about the changing hepatitis B vaccine recommendations affected their nursery's vaccination rate, the question was not specific to high-risk patients; however, other reports6 also have indicated that physicians were confused by the recommendation changes. In our study, many hospital respondents made unsolicited or follow-up comments that not all attending physicians were well-informed about thimerosal issues and the revised recommendations. This was most problematic in hospitals in which different attending physicians maintained different standing orders or vaccination preferences; the result was a situation in which some, but not all, infants were vaccinated. Lack of information or understanding of the recommendation must be suspected as a possible factor in the reported failure to vaccinate all high-risk infants, an unfortunate and unintended consequence of the publicity and recommendation changes related to thimerosal.
These results serve as a cautionary tale: the policy changes prompted by the theoretical risk of thimerosal appear to be associated with an increase in inappropriate vaccination practices for infants who had a real risk of hepatitis B infection. While this study's methods do not allow for the determination of a causal link between lack of information or understanding about the recommendation change and reported failure to vaccinate all high-risk infants, the 6-fold reported increase in inappropriate vaccination practices for high-risk infants cannot be discounted. Although such an increase in inappropriate vaccination practices for high-risk infants was unintended, it could have been predicted. Previous studies7,8 have shown that outpatient primary care physicians can be confused about changes in childhood immunization recommendations. A somewhat greater level of confusion would be expected for newborn hepatitis B vaccine, as a broader array of parties—physician nursery directors, nurse managers, hospital pharmacists, and outpatient primary care physicians—are involved in vaccination decisions, and then those decisions must be conveyed consistently and accurately to staff responsible for vaccinating individual patients.
Also concerning is the decreased rate of hepatitis B vaccination for low-risk newborns in the study's time 3 period, among hospitals that had thimerosal-free vaccine. The proportion of hospitals vaccinating all low-risk infants decreased from 47% at time 1 to 39% at time 3. Certainly, this study was conducted at a time when vaccination practices at many hospitals were in flux, and we would expect that some hospitals that had not yet resumed universal newborn vaccination did so as thimerosal-free vaccine became more widely available. However, it is also possible that this lower vaccination rate may signal a long-term shift toward administration of the initial dose of hepatitis B vaccine in the outpatient setting. Comments from the respondents in this study indicate that many primary care physicians prefer to begin the hepatitis B vaccine series in the outpatient office setting, because of the convenience of record keeping, the ability to use combined hepatitis B and Haemophilus influenzae type b vaccine, and increased reimbursement. Although these preferences likely existed before the thimerosal-related policy changes, the July 7, 1999, recommendation to shift the first hepatitis B vaccine dose to the outpatient setting provided the impetus to implement the change and "opened the door" to allowing physicians to realize the benefits of giving all doses in the outpatient setting. Afterward, resumption of newborn vaccination required not only the availability of thimerosal-free vaccine but also the convincing of outpatient primary care physicians that the benefits of newborn vaccination outweighed the convenience of beginning the series at the age of 2 months.
Furthermore, the introduction of thimerosal-free vaccine did not happen in a timely fashion. In this study, at time 3—when the nation's vaccine supply was sufficient for all infants aged 0 to 6 months—61% of hospitals that were not using thimerosal-free vaccine either did not know the vaccine was available or had not gotten around to making a decision regarding its use. This lack of information and/or action extended the period during which low-risk newborns were not vaccinated.
The suspension of routine vaccination for low-risk infants, and the delay in its resumption, appears even more problematic in the face of inaccurate or inconsistent communication of information between prenatal providers and birthing facilities. Such was the case of a December 1999 death of a 3-month-old Michigan infant, born to an HBsAg-positive woman whose HBsAg status was communicated incorrectly to the birthing hospital.9 The hospital had not resumed routine vaccination of low-risk newborns, even though thimerosal-free vaccine was available. The infant received neither hepatitis B immunoglobulin nor hepatitis B vaccine during the hospital stay, and died less than 2 weeks after the onset of acute hepatitis B infection. While the cause of death was directly linked to the error in information transfer about the mother's hepatitis B status, the suspension of universal newborn vaccination for low-risk infants served to remove what would have been a "safety net" protection for this infant.
This situation illustrates a tension between establishing a protection against a theoretical risk and the possible unintended consequences of that action that carry an actual risk. When setting a policy, and when evaluating its impact, the counterplay between theoretical and actual risk, and the potential tradeoffs that any policy change can inspire, must be studied. In this case, the policy change driven by a theoretical risk from thimerosal produced an indirect and unintended—but still clinically significant—risk of hepatitis B infection in a small but significant number of infants. Knowing that policy changes cause disruptions that lead to problems of implementation, the known and potential impacts of policy changes, positive and negative, should be factored into policy decisions. This perspective is already used in other policy arenas, such as environmental impact statements that are called for before making important environmental policy changes. Future immunization policy changes should strive to incorporate assessment of possible unintended consequences into the policy's benefit equation.
This study has several limitations that may affect its ability to draw definitive conclusions. First, responses consisted solely of respondent self-report. Verification of hospital policies, vaccination rates, and demographic characteristics was not performed. However, we believe that the hospital respondents in this study were well-informed about nursery vaccination practices, and our results are consistent with another report9 from the Centers for Disease Control and Prevention regarding changes in hepatitis B vaccination policies and standing orders after the PHS/AAP recommendation changes. More important, individual reports of inappropriate vaccination practices, such as the failure to administer hepatitis B vaccine to an infant of an HBsAg-positive mother, were not examined, thus prohibiting us from demonstrating any causal link between reported inappropriate vaccination practices and other factors, including lack of information or understanding of hepatitis B vaccination recommendations. Finally, we did not attempt to characterize nonrespondent hospitals; however, the study's high response rate (87%) and low number of refusals (n = 27) allow us to conclude that the sample is representative of all US hospitals.
Most hospital nurseries altered their newborn hepatitis B vaccination policies and practices in ways that were consistent with changes in national recommendations from the PHS and national physician groups. However, unintended consequences of these recommendation changes include the reported failure of some hospitals to continue to vaccinate all high-risk infants after the policy change, even though all PHS and AAP statements clearly indicated that vaccination should continue for such infants. A further consequence is the reluctance of some hospitals to resume universal vaccination of low-risk newborns after thimerosal-free vaccine became available. Such unintended consequences must be included in any assessment of the appropriateness and relative success of this country's response to the threat of thimerosal in vaccines.
The suspension of newborn hepatitis B vaccination for low-risk infants was a controversial policy, related to a theoretical risk of mercury exposure. The Centers for Disease Control and Prevention and physician specialty societies had no direct means to identify and inform hospital decision makers for nursery vaccination issues, to ensure appropriate and consistent response to the policy change. This study describes the implementation of the recommendation to suspend, and then resume, newborn hepatitis B vaccination. The variability of hospital responses and the delayed resumption of newborn vaccination point to the need for better methods of communication about policy changes and a more thoughtful balance between theoretical risk and actual risks related to inconsistent implementation.
Accepted for publication April 1, 2001.
This study was funded by the Centers for Disease Control and Prevention, Atlanta, through a cooperative agreement with the Association of Teachers of Preventive Medicine, Washington, DC.
The 2 authors affiliated with the Centers for Disease Control and Prevention, Ms Malik and Dr Yusuf, participated as individuals in the design of the study, the interpretation of results, and the review/revision of the manuscript.
Corresponding author and reprints: Sarah J. Clark, MPH, Division of General Pediatrics, University of Michigan, 300 N Ingalls Bldg, Room NI6E06, Ann Arbor, MI 48109-0456 (e-mail: firstname.lastname@example.org).
Clark SJ, Cabana MD, Malik T, Yusuf H, Freed GL. Hepatitis B Vaccination Practices in Hospital Newborn Nurseries Before and After Changes in Vaccination Recommendations. Arch Pediatr Adolesc Med. 2001;155(8):915-920. doi:10.1001/archpedi.155.8.915