Brain and Cognitive Development in the PASS Cohort: The Impact of PrenatalAlcohol Exposure - This is a competitive renewal application for R01-AA025653. Over the last 6 years, we have conducted neuroimaging studies in over 400 South African (SA) youth [8-12-years-old; ~300 with prenatal alcohol exposure (PAE) and ~100 non-exposed Controls (NC); 50% girls] from the Prenatal Alcohol, SIDS and Stillbirth (PASS) prospective birth cohort. The PASS cohort is comprised of ~6,000 SA children (born 2008- 2014; now ~8-15-years-old) whose mothers reported on drinking behavior during pregnancy. With pseudo- random selection criteria for the PAE participants recruited during the 1st funding period, the quantity of total drinks during pregnancy was (on average) quite low (range: ~1-611 drinks, M = 27.6, SD = 59.2 ). During this renewal period, we have the opportunity to extend recruitment to over-sample youth with much higher PAE quantities (range: ~32-817 drinks, M = 123.9, SD = 110.8). For renewal, we have developed a novel cohort- sequential cross-sectional/longitudinal study design, in which we would bring back ~50% of participants recruited during the 1st funding period (~150 PAE, ~50 NC) for longitudinal assessment of brain, cognition, and facial morphology (BCF), plus recruitment of ~250 new PASS participants (~200 PAE, ~50 NC). This will permit 1) recruitment of more highly exposed PAE participants to span the range of exposure, 2) study of a broader age range across adolescence among PAE and NC from 8 to 17 years during which dramatic brain development continues, and 3) utilization of data collected during the 1st 6 years both in the longitudinal component and with newly recruited participants in the cross-sectional component. Notably, most children with heavy PAE experience greater early life adversity than NC children, and early intervention is believed to be key in attenuating PAE-effects, the latter of which may depend, in part, on understanding the impact of quantity, frequency and timing (QFT) and early life experiences. Our history of productive team-work and existing infrastructure, coupled with experienced staff and collaborators in South Africa over the last 6 years, bode well for renewal, putting us in an exceptional position to further understanding how QFT of PAE independently, or interactively, impacts associations between (1) brain and cognition/behavior, (2) brain and early life environment, and (3) brain and facial morphology as function of environmental/maternal factors. We will use identical measures of brain structure/function, 3D facial imaging, cognition (WISC-V), early life experience (e.g., maternal age, nutrition, parity, mental health, substance use both perinatally and currently) and environmental risk factors (e.g., multiple measures of SES, access to resources, stress), measured perinatally and during childhood. Both cross-sectional and longitudinal quantitative measures from 3D facial imaging will be utilized in parallel with neuroimaging and cognitive assessments. Using the entire range of PAE, we expect independent and interactive (e.g., quantity by timing) effects of QFT on brain/cognition/face associations, with the largest effects driven by quantity, followed by frequency, and then timing of PAE.
