Delayed acquisition of neonatal reflexes in newborn primates receiving A thimerosal-containing hepatitis B vaccine: Influence of gestational age and birth weight

Laura Hewitson, Lisa A. Houser, Carol Stott, Gene Sackett, Jaime L. Tomko, David Atwood, Lisa Blue, E. Railey White

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


This study examined whether acquisition of neonatal reflexes in newborn rhesus macaques was influenced by receipt of a single neonatal dose of hepatitis B vaccine containing the preservative thimerosal (Th). Hepatitis B vaccine containing a weight-adjusted Th dose was administered to male macaques within 24 h of birth (n = 13). Unexposed animals received saline placebo (n = 4) or no injection (n = 3). Infants were tested daily for acquisition of nine survival, motor, and sensorimotor reflexes. In exposed animals there was a significant delay in the acquisition of root, snout, and suck reflexes, compared with unexposed animals. No neonatal responses were significantly delayed in unexposed animals. Gestational age (GA) and birth weight (BW) were not significantly correlated. Cox regression models were used to evaluate main effects and interactions of exposure with BW and GA as independent predictors and time-invariant covariates. Significant main effects remained for exposure on root and suck when controlling for GA and BW, such that exposed animals were relatively delayed in time-to-criterion. Interaction models indicated there were various interactions between exposure, GA, and BW and that inclusion of the relevant interaction terms significantly improved model fit. This, in turn, indicated that lower BW and/or lower GA exacerbated the adverse effects following vaccine exposure. This primate model provides a possible means of assessing adverse neurodevelopmental outcomes from neonatal Th-containing hepatitis B vaccine exposure, particularly in infants of lower GA or BW. The mechanisms underlying these effects and the requirements for Th requires further study.

Original languageEnglish
Pages (from-to)1298-1313
Number of pages16
JournalJournal of Toxicology and Environmental Health - Part A: Current Issues
Issue number19
StatePublished - 2010

Bibliographical note

Funding Information:
The authors thank Dr. Andrew Wakefield for assistance with the study design and for critical review of the article; Drs. Saverio Capuano and Mario Rodriguez for veterinary assistance; and Amanda Dettmer, Daniel Hollenbeck, Carrie Redinger, Dave McFarland, Melanie O’Malley, and Megan Rufle for technical support. We express our gratitude to Robert Sawyer, Troy and Charlie Ball, and Dr. Jeff Bradstreet. We are indebted to the late Gerald Ruppenthal, who assisted in the study design, training, and implementation of the infant primate developmental measures prior to his death in 2005. This work was supported by the Johnson Family, the late Liz Birt, SafeMinds, the Autism Research Institute, the Ted Lindsay Foundation, the Greater Milwaukee Foundation, David and Cindy Emminger, Sandy McInnis, Elyse Roberts, and Vivienne McKelvey. L.H. designed the study and was also responsible for coordinating all aspects of the study. L.A.H. was responsible for newborn primate care and neurodevelopmental assessments. C.S. and G.S. were responsible for data analyses; J.L.T. was responsible for ultrasounds of pregnant dams and newborn injections; and D.A., L.B., and E.R.W. were responsible for the production of thimerosal-containing hepatitis B vaccines. Prior to 2005, C.S. acted as a paid expert in MMR-related litigation on behalf of the court retained by plaintiff lawyers. L.H. has a child who is a petitioner in the National Vaccine Injury Compensation Program. For this reason, L.H. was not involved in any data collection or statistical analyses to preclude the possibility of a perceived conflict of interest.

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis


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