Project Abstract/Summary The two-phased research mechanism will permit us to design, pilot test, and validate the efficacy of innovative new multivariate protocols for estimating actual risk for the birth of a child with fetal alcohol spectrum disorders (FASD). In the R61 Phase we will research, create, design, and pilot test new protocols for: 1) interviewing mothers (with biomarker validation) to determine maternal alcohol consumption on a daily/weekly basis across pregnancy and postpartum alcohol use during breastfeeding to assess their specific contributions to child traits and severity of FASD outcomes; 2) determining maternal experience with stress, trauma, and mental health status during pregnancy and their contribution to the severity of effect on FASD diagnostic traits; 3) interviewing fathers regarding paternal traits that contribute to the risk for FASD from exposure to teratogens such as alcohol, other drugs, and environmental toxins during pre-conception; and 4) establishing a comprehensive, summary FASD risk score from the above innovations when combined with multiple other empirically-established proximal and distal variables of risk. The R33 Phase will then initiate an exploration of a multivariate, comprehensive approach to FASD risk via two applications for better understanding FASD etiology. One application is prospective and the other retrospective. In the prospective study, 200 women (and as many of their partners as we can consent) will be recruited from prenatal clinics, and their offspring will be assessed at six weeks and nine months postpartum and diagnosed by pediatric dysmorphologists and a multidisciplinary team. The second application of the new methods will gather the new data retrospectively and link the data to two existing cohorts of maternal/child dyads whom we have followed over time to assess their FASD status and the severity of their physical, neurodevelopmental, and behavioral traits. Both of these studies will add new insight to our long-term quest to understand more completely the respective contributions of a broad range of host, agent, and environmental factors to the etiology of FASD. This R33 Phase will provide substantial validation of the weekly alcohol use data, mental health status assessments, paternal questionnaire, and FASD risk score innovations via the clinical assessment of the offspring of each pregnancy. In developing this more comprehensive approach to FASD risk, both study phases draw on our existing clinical epidemiology infrastructure, the experience of our multi- disciplinary team, and the participants in existing longitudinal cohorts.