Cortisol is a well-known glucocorticoid that can be used as a biomarker of hypothalamic-pituitary-adrenocortical activity. To explore basal cortisol physiology during pregnancy and infancy in Macaca nemestrina monkeys, hair was collected from a convenience sample of 22 healthy mother-infant dyads. Adult females were housed in pairs as part of a small breeding colony at the Washington National Primate Research Center and infants were reared in a specialized nursery. Maternal samples were collected from females during a pregnancy-detection ultrasound and immediately following labor and delivery. Infant samples were collected at birth, 20 days, 4, 6, 8 and 10 mos. of age. Hair cortisol concentrations (HCCs) were determined using an enzyme immunoassay in washed and ground hair samples. Like human mothers, macaque HCCs rose during pregnancy (paired t=5.8, df=16, p<.001). Maternal HCCs at pregnancy-detection (114.2 ± 12.07 picogram/milligram (pg/mg)) were highly predictive of maternal HCCs at delivery (144.8 ± 13.60 pg/mg), suggesting a trait-like quality (r=0.90, P<.001). When maternal HCCs were viewed on a continuum, the absolute rise in cortisol over the course of pregnancy was significantly related to newborn HCCs (r=0.55, P=.02). Infant birth HCCs (1027.4.3 ± 97.95 pg/mg) were seven times higher than maternal HCCs at delivery (paired t = 19.1, df = 16, P<0.001). Higher birth HCCs were strongly associated with larger decreases in infant hair cortisol until 6 months of postnatal age when infant HCCs converged on values indistinguishable from adults. Overall, study results demonstrate a marked degree of fetal cortisol exposure during the latter part of gestation and suggest that the rise in maternal cortisol over pregnancy may play an influential role on HCCs in the newborn.

BackgroundIn the 1990s, the mercury-based preservative thimerosal was used in most pediatric vaccines. Although there are currently only two thimerosal-containing vaccines (TCVs) recommended for pediatric use, parental perceptions that vaccines pose safety concerns are affecting vaccination rates, particularly in light of the much expanded and more complex schedule in place today.ObjectivesThe objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model.MethodsWe administered vaccines to six groups of infant male rhesus macaques (n = 12–16/group) using a standardized thimerosal dose where appropriate. Study groups included the recommended 1990s Pediatric vaccine schedule, an accelerated 1990s Primate schedule with or without the measles–mumps–rubella (MMR) vaccine, the MMR vaccine only, and the expanded 2008 schedule. We administered saline injections to age-matched control animals (n = 16). Infant development was assessed from birth to 12 months of age by examining the acquisition of neonatal reflexes, the development of object concept permanence (OCP), computerized tests of discrimination learning, and infant social behavior. Data were analyzed using analysis of variance, multilevel modeling, and survival analyses, where appropriate.ResultsWe observed no group differences in the acquisition of OCP. During discrimination learning, animals receiving TCVs had improved performance on reversal testing, although some of these same animals showed poorer performance in subsequent learning-set testing. Analysis of social and nonsocial behaviors identified few instances of negative behaviors across the entire infancy period. Although some group differences in specific behaviors were reported at 2 months of age, by 12 months all infants, irrespective of vaccination status, had developed the typical repertoire of macaque behaviors.ConclusionsThis comprehensive 5-year case–control study, which closely examined the effects of pediatric vaccines on early primate development, provided no consistent evidence of neurodevelopmental deficits or aberrant behavior in vaccinated animals.CitationCurtis B, Liberato N, Rulien M, Morrisroe K, Kenney C, Yutuc V, Ferrier C, Marti CN, Mandell D, Burbacher TM, Sackett GP, Hewitson L. 2015. Examination of the safety of pediatric vaccine schedules in a non-human primate model: assessments of neurodevelopment, learning, and social behavior. Environ Health Perspect 123:579–589; http://dx.doi.org/10.1289/ehp.1408257

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Domoic Acid (DA) is a naturally-occurring marine neurotoxin that is increasingly recognized as an important public health issue. Prenatal DA exposure occurs through the maternal consumption of contaminated shellfish/finfish. To better understand the fetal risks associated with DA, we initiated a longitudinal, preclinical study focused on the reproductive and developmental effects of chronic, low-dose oral DA exposure. To this end, 32 adult female Macaca fascicularis monkeys were orally dosed with 0, 0.075 or 0.15 mg/kg/day DA on a daily basis throughout breeding and pregnancy. The doses included the proposed human Tolerable Daily Intake (TDI) (0.075 mg/kg/day) for DA. Adult females were bred to nonexposed males. To evaluate behavioral development during early infancy, offspring were administered a neonatal exam modeled after the human Neonatal Behavior Assessment Scale and a series of visual recognition memory problems. Results indicated that DA does not impact early survival reflexes or responsivity to the environment during the neonatal period. Findings from recognition memory tests showed that exposed and control infants demonstrated robust novelty scores when test problems were relatively easy to solve. However, infants in the 0.15 mg/kg DA group failed to demonstrate a novelty response when problems became more challenging. This study is the first to evaluate the offspring neurodevelopmental effects of prenatal DA exposure in a translational primate model and results indicate subtle but significant consequences on emerging memory processes.