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Pediatr Res. 2017 Aug;82(2):244-252. doi: 10.1038/pr.2017.57. Epub 2017 May 24.

Beyond the uterine environment: a nonhuman primate model to investigate maternal-fetal and neonatal outcomes following chronic intrauterine infection.

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Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon.
Advanced Imaging Research Center and Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon.
Division of Comparative Medicine, Oregon National Primate Research Center, Beaverton, Oregon.
Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama.
Department of Pediatrics, Division of Neonatology, Oregon Health and Science University, Portland, Oregon.
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon.


BackgroundIntrauterine infection is a significant cause of early preterm birth. We have developed a fetal-neonatal model in the rhesus macaque to determine the impact of chronic intrauterine infection with Ureaplasma parvum on early neonatal reflexes and brain development.MethodsTime-mated, pregnant rhesus macaques were randomized to be inoculated with U. parvum (serovar 1; 105 c.f.u.) or control media at ~120 days' gestational age (dGA). Neonates were delivered by elective hysterotomy at 135-147 dGA (term=167d), stabilized, and cared for in our nonhuman primate neonatal intensive care unit. Neonatal reflex behaviors were assessed from birth, and fetal and postnatal brain magnetic resonance imaging (MRI) was performed.ResultsA total of 13 preterm and 5 term macaque infants were included in the study. Ten preterm infants survived to 6 months of age. U. parvum-infected preterm neonates required more intensive respiratory support than did control infants. MRI studies suggested a potential perturbation of brain growth and white matter maturation with exposure to intra-amniotic infection.ConclusionWe have demonstrated the feasibility of longitudinal fetal-neonatal studies in the preterm rhesus macaque after chronic intrauterine infection. Future studies will examine long-term neurobehavioral outcomes, cognitive development, neuropathology, and in vivo brain imaging to determine the safety of antenatal antibiotic treatment for intrauterine infection.

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