The proposed study will assess the effects of in utero exposure to HIV and of malarial co-infection on children's neurobehavioral development across the first two years of life. The importance of this research is that there is a growing population of children who are exposed to maternal HIV in utero in the presence of other co-infections. However, we have limited knowledge of the consequences of that exposure for the early development of the children born to these women. The central hypothesis of this study is maternal HIV increases risks for birth of children with low birth weight (LBW). These risks are especially high in women who are co-infected with malaria and are mediated by pre-term birth, intrauterine growth retardation (IUGR) and placenta! abnormalities, including chorioamnionitis. LBW and placenta! abnormalities, in turn, lead to developmental delays and to a slowed rate of development across the first two years of life, even when controlling for vertical transmission of HIV. The study will also examine measures of the family environment as moderators of adverse developmental consequences of maternal HIV. Unique features of the study include the use of child assessments that have been standardized on the target population, examination of the independent and conjoint effects of maternal HIV and malaria co-infection, recruitment of local controls with social and economic backgrounds similar to those of the infected women, and the measurement of the pre-natal environment as a risk factor using placental histology. Women will be recruited early in their second semester from the antenatal clinics at two district hospitals in Coast Province, Kenya. They will be seen at regular intervals until delivery and they and their children then followed until the children are 24 months of age. The proposed project will be conducted by a multidisciplinary team from: Case Western Reserve University, Kenya Medical Research Institute, The Kenyan Ministry of Health, International Centre for Reproductive Health, and the African Mental Health Foundation/University of Nairobi. The project also provides the framework for a program of training in pediatric HIV research that will build the technical and research capacity of the collaborating Kenyan institutions.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1-ICP2-B (50))
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Brouwers, Pim
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Case Western Reserve University
Other Health Professions
Schools of Medicine
United States
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Kalayjian, Benjamin C; Malhotra, Indu; Mungai, Peter et al. (2013) Marked decline in malaria prevalence among pregnant women and their offspring from 1996 to 2010 on the south Kenyan Coast. Am J Trop Med Hyg 89:1129-34
Steiner, Kevin L; Malhotra, Indu; Mungai, Peter L et al. (2012) In utero activation of fetal memory T cells alters host regulatory gene expression and affects HIV susceptibility. Virology 425:23-30
Malhotra, Indu; Dent, Arlene; Mungai, Peter et al. (2009) Can prenatal malaria exposure produce an immune tolerant phenotype? A prospective birth cohort study in Kenya. PLoS Med 6:e1000116