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OBJECTIVES. Thimerosal is a mercurial preservative that was widely used in multidose vaccine vials in the United States and Europe until 2001 and continues to be used in many countries throughout the world. We conducted a pharmacokinetic study to assess blood levels and elimination of ethyl mercury after vaccination of infants with thimerosal-containing vaccines. METHODS. Blood, stool, and urine samples were obtained before vaccination and 12 hours to 30 days after vaccination from 216 healthy children: 72 newborns (group 1), 72 infants aged 2 months (group 2), and 72 infants aged 6 months (group 3). Total mercury levels were measured by atomic absorption. Blood mercury pharmacokinetics were calculated by pooling the data on the group and were based on a 1-compartment first-order pharmacokinetics model. RESULTS. For groups 1, 2, and 3, respectively, (1) mean ± SD weights were 3.4 ± 0.4, 5.1 ± 0.6, and 7.7 ± 1.1 kg; (2) maximal mean ± SD blood mercury levels were 5.0 ± 1.3, 3.6 ± 1.5, and 2.8 ± 0.9 ng/mL occurring at 0.5 to 1 day after vaccination; (3) maximal mean ± SD stool mercury levels were 19.1 ± 11.8, 37.0 ± 27.4, and 44.3 ± 23.9 ng/g occurring on day 5 after vaccination for all groups; and (4) urine mercury levels were mostly nondetectable. The blood mercury half-life was calculated to be 3.7 days and returned to prevaccination levels by day 30. CONCLUSIONS. The blood half-life of intramuscular ethyl mercury from thimerosal in vaccines in infants is substantially shorter than that of oral methyl mercury in adults. Increased mercury levels were detected in stools after vaccination, suggesting that the gastrointestinal tract is involved in ethyl mercury elimination. Because of the differing pharmacokinetics of ethyl and methyl mercury, exposure guidelines based on oral methyl mercury in adults may not be accurate for risk assessments in children who receive thimerosal-containing vaccines.

* Abbreviations: UNEP — : United Nations Environmental Programme WHO — : World Health Organization Vaccines remain one of the most effective ways to prevent infectious disease and deaths globally.1 Universal childhood immunization provides herd immunity against many infectious agents and is a policy that has achieved dramatic reductions in common childhood illnesses. Thimerosal, which contains ethyl mercury, has been used as a preservative in vaccines to prevent contamination of multidose vials from bacteria and fungi since the 1930s.2 Although there are clear neurotoxic effects of methyl mercury absorption, ethyl mercury has not been associated with those consequences. Nevertheless, before data were available on risks of thimerosal in vaccines, in 1999 the American Academy of Pediatrics and the US Public Health Service recommended moving toward removing thimerosal use in preservatives as a precautionary measure.3 Thus, thimerosal as … Address correspondence to Walter A. Orenstein, MD, 1462 Clifton Rd, Suite 446, Atlanta, GA 30322. E-mail: worenst{at}emory.edu

* Abbreviations: HICs — : high-income countries LMICs — : low- and middle-income countries Thimerosal is an ethyl mercury–containing compound that has been used safely for >60 years as a preservative in multidose vials of vaccines to prevent bacterial and fungal contamination of those vials when they are repeatedly entered to withdraw doses.1,2 In the late 1990s, preservative-free single-dose vials were widely introduced into high-income countries (HICs). This was a precautionary move in response to theoretical concerns, now known to be unfounded, that ethyl mercury in thimerosal could build up in vaccine recipients’ bodies at a rate to similar methylmercury (a known toxin) causing toxicity.3 For low- and middle-income countries (LMICs), where the burdens of vaccine-preventable deaths are most profound, multidose vials of thimerosal-preserved vaccines are a critical part of immunization programs. Extensive additional resources associated with increased manufacturing, shipping, cold-chain storage, administration, and waste-handling infrastructure would be required by a move away from multidose vaccines; for example, a shift to single-dose vials would increase the annual cost of Pan American Health Organization– or UNICEF–supplied vaccines by >$300 million.4 In January 2013, governments are set to finalize the products and processes that will be prohibited in a multilateral environmental treaty, backed by the United Nations Environment Programme, which aims to restrict human and environmental exposure to mercury.5 As a mercury derivative, thimerosal could potentially be included within the treaty. Although supportive of the objectives of reducing human and environmental exposure to mercury, the World … Address correspondence to Shane K. Green, PhD, Sandra Rotman Centre, MaRS Building, South Tower, 101 College St, Suite 406, Toronto, ON, Canada, M5G1L7. E-mail: shane.green{at}srcglobal.org

Objective. There is an established link between exposure to mercury and impaired childhood cognitive development and early motor skills. Thimerosal (also known as thiomersal), a preservative used in a number of children's vaccines, contains ethylmercury (an organic compound of mercury), and there has been concern that this exposure to mercury may be of some detriment to young children. The aim of this research was to test in a large United Kingdom population–based cohort whether there is any evidence to justify such concerns.Methods. We used population data from a longitudinal study on childhood health and development. The study has been monitoring >14 000 children who are from the geographic area formerly known as Avon, United Kingdom, and were delivered in 1991–1992. The age at which doses of thimerosal-containing vaccines were administered was recorded, and measures of mercury exposure by 3, 4, and 6 months of age were calculated and compared with a number of measures of childhood cognitive and behavioral development covering the period from 6 to 91 months of age.Results. Contrary to expectation, it was common for the unadjusted results to suggest a beneficial effect of thimerosal exposure. For example, exposure at 3 months was inversely associated with hyperactivity and conduct problems at 47 months; motor development at 6 months and at 30 months; difficulties with sounds at 81 months; and speech therapy, special needs, and “statementing” at 91 months. After adjustment for birth weight, gestation, gender, maternal education, parity, housing tenure, maternal smoking, breastfeeding, and ethnic origins, we found 1 result of 69 to be in the direction hypothesized—poor prosocial behavior at 47 months was associated with exposure by 3 months of age (odds ratio: 1.12; 95% confidence interval: 1.01-1.23) compared with 8 results that still supported a beneficial effect.Conclusions. We could find no convincing evidence that early exposure to thimerosal had any deleterious effect on neurologic or psychological outcome.

Concern has been expressed over the possibility that the mercury-containing compound thimerosal in vaccines may cause autism.1–4 Thimerosal is sodium ethylmercury thiosalicylate, an organic compound of ethyl mercury, included in certain vaccines to protect multiple dose ampules from bacterial and fungal contamination. Mercury in sufficient dose is neurotoxic, and probably more toxic in the immature brain. It is reasonable to ask whether thimerosal in childhood vaccine increases risk of chronic childhood neurologic disability and specifically of autism. The available data with which to address the question are very limited and largely inferential. Most of the information we have about mercury toxicity is related to exposure to methyl rather than ethyl mercury. Bernard et al1 offered an hypothesis that autism is an expression of mercury toxicity resulting from thimerosal in vaccines. They base this hypothesis on their views2 that the clinical signs of mercury toxicity are similar to the manifestations of autism, that the onset of autism is temporally associated with immunization in some children, that the recent increase in diagnosis of autism parallels exposure to thimerosal, and that there are higher levels of mercury in persons with than without autism. This review will examine these issues and others to ask whether, according to evidence now available, thimerosal is a probable cause of autism. We will not discuss which, if any, of the differing guidelines designed to limit exposure to mercurials is appropriate for deciding whether thimerosal in vaccines is in all regards safe for children. Our focus is on a narrower but important question: whether current evidence indicates that mercury at any known dose, form, duration, age, or route of exposure leads to autism. Bernard et al1 present a table listing ∼95 clinical findings they consider to be shared by autism and mercury poisoning. …

Background. On July 7, 1999, the American Academy of Pediatrics and the US Public Health Service issued a joint statement calling for removal of thimerosal, a mercury-containing preservative, from vaccines. This action was prompted in part by a risk assessment from the Food and Drug Administration that is presented here. Methods. The risk assessment consisted of hazard identification, dose-response assessment, exposure assessment, and risk characterization. The literature was reviewed to identify known toxicity of thimerosal, ethylmercury (a metabolite of thimerosal) and methylmercury (a similar organic mercury compound) and to determine the doses at which toxicity occurs. Maximal potential exposure to mercury from vaccines was calculated for children at 6 months old and 2 years, under the US childhood immunization schedule, and compared with the limits for mercury exposure developed by the Environmental Protection Agency (EPA), the Agency for Toxic Substance and Disease Registry, the Food and Drug Administration, and the World Health Organization. Results. Delayed-type hypersensitivity reactions from thimerosal exposure are well-recognized. Identified acute toxicity from inadvertent high-dose exposure to thimerosal includes neurotoxicity and nephrotoxicity. Limited data on toxicity from low-dose exposures to ethylmercury are available, but toxicity may be similar to that of methylmercury. Chronic, low-dose methylmercury exposure may cause subtle neurologic abnormalities. Depending on the immunization schedule, vaccine formulation, and infant weight, cumulative exposure of infants to mercury from thimerosal during the first 6 months of life may exceed EPA guidelines. Conclusion. Our review revealed no evidence of harm caused by doses of thimerosal in vaccines, except for local hypersensitivity reactions. However, some infants may be exposed to cumulative levels of mercury during the first 6 months of life that exceed EPA recommendations. Exposure of infants to mercury in vaccines can be reduced or eliminated by using products formulated without thimerosal as a preservative.

Objective. To determine the impact of the American Academy of Pediatrics/US Public Health Service (AAP/USPHS) joint statement on thimerosal in vaccines on hospital infant hepatitis B vaccination policies in Wisconsin. Methods. The nurse managers of hospital newborn nurseries (n = 110) were surveyed by mail. Nonresponders were resurveyed. Twelve hospitals no longer provided obstetric services. Of the remaining 98 hospitals, 84 (86%) responded to the initial mailing and 14 (14%) responded to the second mailing. The number of hospitals that offered hepatitis B vaccine to infants before July 1999 was compared with that in March 2000. The number of hospitals that had policies in place to vaccinate infants whose mothers' hepatitis B surface antigen status (HBsAg) was positive or unknown during the thimerosal alert (July 1999 through November 1999) was compared with that in March 2000. Results. Before July 1999, 81% of the hospitals representing 84% of reported Wisconsin births routinely offered hepatitis B vaccine to all infants. By March 2000, 50% of hospitals, representing 43% of births, had resumed routine infant hepatitis B vaccination. Physician decision to use a combination Haemophilus influenzae type b hepatitis B vaccine was the most frequently given reason for not reinstituting infant hepatitis B vaccination. During the thimerosal alert, 23% of hospitals did not have policies to vaccinate infants whose mothers were HBsAg-positive and 51% did not have policies to vaccinate infants whose mothers' HBsAg status was unknown. By March 2000, 6% of hospitals still did not have policies to vaccinate infants whose mothers were HBsAg-positive and 24% did not have policies to vaccinate infants whose mothers' HBsAg status was unknown. Conclusion. The AAP/USPHS joint statement on thimerosal in vaccines has resulted in a 38% decrease in the number of hospitals routinely offering infants hepatitis B vaccine. Although thimerosal-free hepatitis B vaccine is now available, some hospitals still do not have appropriate policies in place for vaccinating infants whose mothers' HBsAg status is positive or unknown. In the future, policymakers should include anticipated consequences that may result from changes in immunization policy in their recommendations.

The Advisory Committee on Immunization Practices (ACIP) has established the hepatitis B vaccine birth dose as the preferred time for administering the first dose of hepatitis B vaccine in infants (J. Modlin, personal communication, December 2001). This recommendation comes on the heels of the Institute of Medicine’s (IOM) report, “Immunization Safety Review: Thimerosal Containing Vaccines and Neurodevelopmental Disorders,” which correctly concluded that there is still no evidence to prove (or disprove) a causal relationship between thimerosal-containing vaccines and adverse neurodevelopmental events.1 The IOM has further recommended more research not only into the biological controversy regarding thimerosal but into the public health issues surrounding policy-making in the face of uncertainty.1 This is also the same issue being addressed by the National Vaccine Advisory Committee, which will shortly undertake a “review of how public health policy decisions are made under uncertainty” and a “review of strategies used to communicate rapid changes in vaccine policy” using the disruption of the hepatitis B birth dosing program as an example (G. Peter, personal communication, December 2001). With ACIP recognition of the many benefits of initiating hepatitis B vaccination at birth and with the availability of hepatitis B vaccines with little or no thimerosal content, it seems instructive to continue to pose this question: did our knowledge of thimerosal in July 1999 and concerns about its theoretical toxicity when delivered in pediatric vaccines call for the emergent disruption of the hepatitis B immunization program recommended at that time by the American Academy of Pediatrics (AAP) and the US Public Health Service (USPHS).2 In comments made by one of us (R.S.D.) at a conference sponsored by the National Vaccine Advisory Committee3 and in a previous commentary in Pediatrics ,2 our view on this issue, that disruption of the hepatitis B vaccination program …

OBJECTIVE: Exposure to thimerosal, a mercury-containing preservative that is used in vaccines and immunoglobulin preparations, has been hypothesized to be associated with increased risk of autism spectrum disorder (ASD). This study was designed to examine relationships between prenatal and infant ethylmercury exposure from thimerosal-containing vaccines and/or immunoglobulin preparations and ASD and 2 ASD subcategories: autistic disorder (AD) and ASD with regression. METHODS: A case-control study was conducted in 3 managed care organizations (MCOs) of 256 children with ASD and 752 controls matched by birth year, gender, and MCO. ASD diagnoses were validated through standardized in-person evaluations. Exposure to thimerosal in vaccines and immunoglobulin preparations was determined from electronic immunization registries, medical charts, and parent interviews. Information on potential confounding factors was obtained from the interviews and medical charts. We used conditional logistic regression to assess associations between ASD, AD, and ASD with regression and exposure to ethylmercury during prenatal, birth-to-1 month, birth-to-7-month, and birth-to-20-month periods. RESULTS: There were no findings of increased risk for any of the 3 ASD outcomes. The adjusted odds ratios (95% confidence intervals) for ASD associated with a 2-SD increase in ethylmercury exposure were 1.12 (0.83–1.51) for prenatal exposure, 0.88 (0.62–1.26) for exposure from birth to 1 month, 0.60 (0.36–0.99) for exposure from birth to 7 months, and 0.60 (0.32–0.97) for exposure from birth to 20 months. CONCLUSIONS: In our study of MCO members, prenatal and early-life exposure to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to increased risk of ASDs.

BACKGROUND. The prevalence of pervasive developmental disorders has increased in recent years. Links with the measles component of the measles-mumps-rubella vaccine and the cumulative exposure to thimerosal through other vaccines have been postulated. OBJECTIVES. The purpose of this work was to estimate the pervasive developmental disorder prevalence in Montreal, Canada, in cohorts born from 1987 to 1998 and evaluate the relationship of trends in pervasive developmental disorder rates with: (1) changes in cumulative exposure to ethylmercury (thimerosal) occurring through modifications in the immunization schedule of young children and (2) trends in measles-mumps-rubella vaccination use rates and the introduction of a 2–measles-mumps-rubella dosing schedule during the study period. METHODS. We surveyed 27749 children born from 1987 to 1998 attending 55 schools from the largest Anglophone school board. Children with pervasive developmental disorders were identified by a special needs team. The cumulative exposure by age 2 years to thimerosal was calculated for 1987–1998 birth cohorts. Ethylmercury exposure ranged from medium (100–125 μg) from 1987 to 1991 to high (200–225 μg) from 1992 to 1995 to nil from 1996 onwards when thimerosal was entirely discontinued. Measles-mumps-rubella coverage for each birth cohort was estimated through surveys of vaccination rates. The immunization schedule included a measles-mumps-rubella single dose at 12 months of age up to 1995, and a second measles-mumps-rubella dose at 18 months of age was added on after 1996. RESULTS. We found 180 children (82.8% males) with a pervasive developmental disorder diagnosis who attended the surveyed schools, yielding a prevalence for pervasive developmental disorder of 64.9 per 10000. The prevalence for specific pervasive developmental disorder subtypes were, for autistic disorder: 21.6 of 10000; for pervasive developmental disorder not otherwise specified: 32.8 of 10000; and for Asperger syndrome: 10.1 of 10000. A statistically significant linear increase in pervasive developmental disorder prevalence was noted during the study period. The prevalence of pervasive developmental disorder in thimerosal-free birth cohorts was significantly higher than that in thimerosal-exposed cohorts (82.7 of 10000 vs 59.5 of 10000). Using logistic regression models of the prevalence data, we found no significant effect of thimerosal exposure used either as a continuous or a categorical variable. Thus, thimerosal exposure was unrelated to the increasing trend in pervasive developmental disorder prevalence. These results were robust when additional analyses were performed to address possible limitations because of the ecological nature of the data and to evaluate potential effects of misclassification on exposure or diagnosis. Measles-mumps-rubella vaccination coverage averaged 93% during the study interval with a statistically significant decreasing trend from 96.1% in the older birth cohorts (1988–89) to ∼92.4% in younger birth cohorts (1996–1998). Thus, pervasive developmental disorder rates significantly increased when measles-mumps-rubella vaccination uptake rates significantly decreased. In addition, pervasive developmental disorder prevalence increased at the same rate before and after the introduction in 1996 of the second measles-mumps-rubella dose, suggesting no increased risk of pervasive developmental disorder associated with a 2–measles-mumps-rubella dosing schedule before age 2 years. Results held true when additional analyses were performed to test for the potential effects of misclassification on exposure or diagnostic status. Thus, no relationship was found between pervasive developmental disorder rates and 1- or 2-dose measles-mumps-rubella immunization schedule. CONCLUSIONS. The prevalence of pervasive developmental disorder in Montreal was high, increasing in recent birth cohorts as found in most countries. Factors accounting for the increase include a broadening of diagnostic concepts and criteria, increased awareness and, therefore, better identification of children with pervasive developmental disorders in communities and epidemiologic surveys, and improved access to services. The findings ruled out an association between pervasive developmental disorder and either high levels of ethylmercury exposure comparable with those experienced in the United States in the 1990s or 1- or 2-dose measles-mumps-rubella vaccinations.

* Abbreviations: AAP — : American Academy of Pediatrics FDA — : Food and Drug Administration TCV — : thimerosal-containing vaccine USPHS — : US Public Health Service A draft treaty under consideration by the United Nations Environmental Program has been prepared to greatly reduce global health hazards from environmental mercury.1 In response to the draft treaty, the World Health Organization urges removal of a provision in the treaty that calls for a ban on thimerosal (which contains ethyl mercury) in vaccines, a position recently endorsed by the American Academy of Pediatrics (AAP) and the US Public Health Service (USPHS). Removal of the ban on thimerosal-containing vaccines (TCVs) represents a significant reversal of the position expressed in an AAP/USPHS joint statement in 1999 that called for elimination of mercury in vaccines and the subsequent actions taken in the United States.2 Understanding the circumstances that led 14 years ago to the 1999 statement and the knowledge accumulated in these subsequent years can reinforce the importance of the 2012 AAP/USPHS position. AAP representatives and other members of national pediatric societies within the International Pediatric Association advocating for deletion of the provision banning TCVs need to know why the elimination of thimerosal was initially called for in 1999 but is no longer indicated. This commentary … Correspondence to Louis Z. Cooper, MD, 80 Central Park W, Apt 11F, New York, NY 10023. E-mail: lzcooper{at}verizon.net

Objective. After concerns about the possible toxicity of thimerosal-containing vaccines in the United States, this study was designed to investigate whether there is a relationship between the amount of thimerosal that an infant receives via diphtheria-tetanus-whole-cell pertussis (DTP) or diphtheria-tetanus (DT) vaccination at a young age and subsequent neurodevelopmental disorders. Methods. A retrospective cohort study was performed using 109 863 children who were born from 1988 to 1997 and were registered in general practices in the United Kingdom that contributed to a research database. The disorders investigated were general developmental disorders, language or speech delay, tics, attention-deficit disorder, autism, unspecified developmental delays, behavior problems, encopresis, and enuresis. Exposure was defined according to the number of DTP/DT doses received by 3 and 4 months of age and also the cumulative age-specific DTP/DT exposure by 6 months. Each DTP/DT dose of vaccine contains 50 μg of thimerosal (25 μg of ethyl mercury). Hazard ratios (HRs) for the disorders were calculated per dose of DTP/DT vaccine or per unit of cumulative DTP/DT exposure. Results. Only in 1 analysis for tics was there some evidence of a higher risk with increasing doses (Cox's HR: 1.50 per dose at 4 months; 95% confidence interval [CI]: 1.02–2.20). Statistically significant negative associations with increasing doses at 4 months were found for general developmental disorders (HR: 0.87; 95% CI: 0.81–0.93), unspecified developmental delay (HR: 0.80; 95% CI: 0.69–0.92), and attention-deficit disorder (HR: 0.79; 95% CI: 0.64–0.98). For the other disorders, there was no evidence of an association with thimerosal exposure. Conclusions. With the possible exception of tics, there was no evidence that thimerosal exposure via DTP/DT vaccines causes neurodevelopmental disorders.

To the Editor .— I am the first author of a recent article on a study undertaken by the Centers for Disease Control and Prevention (CDC) to screen for a potential link between thimerosal-containing vaccines and neurodevelopmental delays.1 The article has been subject to heavy criticism from antivaccine lobbyists. Their criticism basically comes down to the following two claims: the CDC has watered down the original findings of a link between thimerosal-containing vaccines and autism, and GlaxoSmithKline (GSK) has hired me away from the CDC so as to convince me to manipulate the data further before publication. Because I was responsible for nearly all aspects of this study, including study design, data gathering, data analysis, and writing of the article, I wish to give my opinion on these claims. These are my personal opinions and do not represent the opinion of the CDC or GSK. Did the CDC water down the original results? It did not. This misconception comes from an erroneous perception of this screening study and other epidemiological studies. The perception is that an epidemiological study can have only 1 of 2 outcomes: either an …

Vaccines often contain preservatives, adjuvants, additives, or manufacturing residuals in addition to pathogen-specific immunogens. Some parents, alerted by stories in the news media or information contained on the World Wide Web, are concerned that some of the substances contained in vaccines might harm their children. We reviewed data on thimerosal, aluminum, gelatin, human serum albumin, formaldehyde, antibiotics, egg proteins, and yeast proteins. Both gelatin and egg proteins are contained in vaccines in quantities sufficient to induce rare instances of severe, immediate-type hypersensitivity reactions. However, quantities of mercury, aluminum, formaldehyde, human serum albumin, antibiotics, and yeast proteins in vaccines have not been found to be harmful in humans or experimental animals.

To assess the possible toxicity of thimerosal-containing vaccines (TCVs) among infants.A 2-phased retrospective cohort study was conducted using computerized health maintenance organization (HMO) databases. Phase I screened for associations between neurodevelopmental disorders and thimerosal exposure among 124 170 infants who were born during 1992 to 1999 at 2 HMOs (A and B). In phase II, the most common disorders associated with exposure in phase I were reevaluated among 16 717 children who were born during 1991 to 1997 in another HMO (C). Relative risks for neurodevelopmental disorders were calculated per increase of 12.5 micro g of estimated cumulative mercury exposure from TCVs in the first, third, and seventh months of life.In phase I at HMO A, cumulative exposure at 3 months resulted in a significant positive association with tics (relative risk [RR]: 1.89; 95% confidence interval [CI]: 1.05-3.38). At HMO B, increased risks of language delay were found for cumulative exposure at 3 months (RR: 1.13; 95% CI: 1.01-1.27) and 7 months (RR: 1.07; 95% CI: 1.01-1.13). In phase II at HMO C, no significant associations were found. In no analyses were significant increased risks found for autism or attention-deficit disorder.No consistent significant associations were found between TCVs and neurodevelopmental outcomes. Conflicting results were found at different HMOs for certain outcomes. For resolving the conflicting findings, studies with uniform neurodevelopmental assessments of children with a range of cumulative thimerosal exposures are needed.

Objective. Hepatitis B vaccine is recommended for all infants, and the series may be started during the delivery admission. For infants who are born either to women who are positive for hepatitis B surface antigen (HBsAg) or to women whose HBsAg status is unknown, vaccination should be started within 12 hours of birth to prevent perinatal and early childhood hepatitis B virus infection. Because of concerns about mercury exposures from vaccines that contain thimerosal, the United States Public Health Service (USPHS) and the American Academy of Pediatrics (AAP) recommended in July 1999 that the first dose of hepatitis B vaccine be deferred until 2–6 months of age but only for infants who are born to HBsAg-negative women. To assess the impact on birth-dose vaccine coverage for infants who are born to women with unknown HBsAg status, we measured coverage before and after July 1999. Methods. A sample of Michigan infants who were born to women whose HBsAg status was either unknown or missing were identified by reviewing newborn screening cards for infants who were born during 1) March–April 1999 (before recommendation changes [T1]); 2) July 15–September 15, 1999 (immediately after recommendation changes [T2]); and 3) March–April 2000 (6 months after resumption of pre-1999 practices were recommended [T3]). We verified maternal HBsAg screening and newborn hepatitis B vaccination by reviewing infant and maternal hospital records. Results. Of 1201 infants who were born to women whose HBsAg status was indicated as unknown or missing on the newborn screening card during the 3 time periods, 216 (18%) were born to women whose status was truly unknown at the time of delivery, as determined by medical record review. During T1, 53% of these 216 infants received hepatitis B vaccine before hospital discharge, compared with 7% of infants who were born during T2 and 57% of infants who were born during T3. During T1, 19% of these infants received hepatitis B vaccine within 12 hours of birth compared with 1% of infants who were born during T2 and 14% of infants who were born during T3. Conclusions. Hepatitis B vaccine birth-dose coverage for infants who were born to women whose HBsAg status was unknown at the time of delivery was already low in Michigan before the July 1999 USPHS/AAP Joint Statement but decreased significantly during the 2 months after the USPHS/AAP Joint Statement. Abrupt changes in established vaccination recommendations for lower risk children may lead to decreased coverage among higher risk children. Increases in hepatitis B vaccine coverage at birth are necessary to reduce the risk of perinatal infection for infants who are born to women with unknown HBsAg status.

Effective immunization programs have markedly diminished the incidence of vaccine-preventable diseases. As a result, there now exists in society a lower awareness of the actual risks associated with the diseases themselves and a greater prominence of the potential risks of adverse effects associated with vaccines. Concern regarding public reactions to new vaccine safety issues may place pressure on policymakers and/or health care providers to act quickly in response to new information. However, this concern must be tempered by the necessary caution required to assess the intended and unintended risks and benefits of any action undertaken. The interplay of these potentially competing demands is well illustrated by the recent safety concern involving the use of thimerosal in vaccines. Thimerosal is a mercury-containing compound that has been widely used as an antimicrobial agent in vaccines for over 60 years. Human exposure to mercury may have potentially significant health consequences. By mid-1999, the Food and Drug Administration (FDA) had discovered that children could be exposed to an amount of mercury from vaccines that exceeded 1 of 3 existing federal safety thresholds. After this realization, the organized medical and public health communities in the United States became involved in a series of urgent and intense discussions to determine an appropriate response to the issue. This manuscript describes and analyzes the process that led to the July 7, 1999, joint American Academy of Pediatrics (AAP)/US Public Health Service (PHS) statement on thimerosal,1 with the goal of suggesting improvements for managing similar vaccine safety concerns in the future. We conducted structured interviews with over 15 individuals involved in the discussions and negotiations leading to the joint AAP/PHS statement on thimerosal. The individuals represented both the governmental agencies and nongovernmental organizations involved, including the FDA, the Environmental Protection Agency (EPA), the Centers for Disease Control and …

To the Editor .— In their article, Drs Shete and Daum criticize the AAP and USPHS for recommending suspension of the hepatitis B vaccine birth dose because these organizations “placed the theoretical risk of thimerosal toxicity above the real public health burden of failing to immunize children at risk of hepatitis B … beginning at birth.1” In defense of …

The commentary by Seal and Daum entitled “What Happened to Primum non nocere?” 1 that appeared in the May 2001 issue of Pediatrics criticized the July 1999 recommendation of the American Academy of Pediatrics (AAP) and US Public Health Service (USPHS) to delay the birth dose of hepatitis B vaccine for infants born to hepatitis B surface antigen (HBsAg)-negative women to reduce infant exposure to thimerosal.2 The commentary contains incorrect statements and oversimplifies the complex process of balancing multiple risks and benefits when formulating vaccine policy as summarized in the excellent article by Feudtner and Marcuse3 in the same issue. Some professionals had difficulty understanding the need for the July 1999 recommendations because they didn't fully understand the risks from organomercury exposure and the amounts of ethylmercury present in vaccines. Several developments in the past 2 years have reinforced the wisdom of the recommendations made in July 1999. Seal and Daum stated that methylmercury “might” be harmful to the developing fetal central nervous system. Methylmercury is neurotoxic at all ages, and the developing fetal brain is at least 10-fold more sensitive than the adult brain.4 They also incorrectly stated that “no data existed that implicated ethylmercury” as a cause of neurotoxicity. As reviewed by Ball et al,5 ethylmercury from thimerosal has caused significant neurotoxicity in infants, children, and adults. Such data were available at …

On July 7, 1999, the American Academy of Pediatrics (AAP) and the US Public Health Service (USPHS) jointly indicated that the first dose of hepatitis B vaccine (HBV), often given in the first days after birth, be deferred until infants are about 6 months of age in instances when the infant is born to a hepatitis B-seronegative mother.1,2The rationale for this changed recommendation was concern about the safety of thimerosal, a preservative used in many vaccine preparations since 1930. More than 30 vaccines on the market today (10/00) contain thimerosal, an ethyl mercury compound with a mercury content of 49.6%. Although the Food and Drug Administration (FDA) had reviewed thimerosal safety in 1976 and concluded that there were no harmful effects, the FDA Modernization Act, passed by Congress in 1997, mandated testing and analyzing of mercury-containing products. After passage of the FDA Modernization Act, interaction between the FDA and vaccine manufacturers was underway with the aim of encouraging manufacturers to remove thimerosal from all licensed vaccines, as is evidenced from the thorough assessment of the use of thimerosal in vaccine preparations that appears concurrently in this month's issue of Pediatrics .3 To many, the statement issued by the AAP and the USPHS on July 7, 1999, seemed precipitous and caught the medical, scientific, industrial, and regulatory communities by surprise. Although some studies suggested that low-level, frequent exposure to another mercury salt, methyl mercury, might be harmful to the developing fetal central nervous system,4 other research efforts provided conflicting data on this point5 and no data existed that implicated ethyl mercury, the mercury moiety found … Address correspondence to Robert S. Daum, MD, University of Chicago, Department of Pediatrics, Section of Pediatric Infectious Disease, MC 6054, 5841 S Maryland Ave, Chicago, IL 60637-1470. E-mail:rsd2{at}midway.uchicago.edu.