CIFASD Progress Ukraine Clinical Project February 1-2, 2011 Christina Chambers Kenneth Lyons Jones Claire Coles Julie Kable Andy Hull Lyuba Yevtushok Natalya Zymak Wladimir Wertelecki

Specific Aims Measure birth prevalence and range of alcohol-related physical features and neurobehavioral impairment relative to dose, timing of exposure to alcohol Evaluate contribution of maternal nutritional status to outcomes Baseline and third trimester blood levels RCT with MMN supplements with or without choline Provide resources for prenatal ultrasound study

Progress: Recruitment and Evaluations in Phase II 7,026 pregnant women screened in two oblasts 390 have completed first interview 596 ultrasounds performed 241 outcome interviews completed 185 Bayley tests completed 157 dysmorphology exams for unique children;280 dysmorphology exams by Ukrainian physicians 514 blood samples received at UC Davis

5/11 7/11 12/11 7/12 Aim 1 - Exposure v Physical Features (+ pilot) ✓ Aim 2 Baseline Nutrition v Physical Features Aim 1,2,3 – Neurobehavior 6M 12M Aim 3 – Exposure v Physical Features (+ pilot)

Specific Aim 2: Baseline Mineral Status and Physical Features Exposure Classification OR (95% CI) For Cardinal Features of FAS* p-value AA per day conception 4.430 (1.338, 14.664) 0.015 Fe lower quartile 5.447 (1.721, 17.237) 0.004 Zn lower quartile 1.736 (0.570, 5.285) 0.331 Cu lower quartile 0.149 (0.031, 0.720) 0.010 Folic acid supplements 0.271 (0.043, 0.869) 0.018 *Adjusted for smoking, gestational age at enrollment, and CP activity

DSMB Met January, 2011 Feedback to participants Reviewed data Fe levels for subjects in exposed and treated group; determined no evidence of a safety signal Reviewed progress report and recommended a revision to the analysis plan to allow for a formal interim analysis when sample size of 300 subjects achieved for neurobehavior

This Year Added 1 FTE statistician Post-doc nutritional epidemiologist PhD Math/Stats student Bringing Smriti up to speed

5 questions 7 children with 4 modes of evaluation 35 children with 3 of 4 Laterality of physical features across modalities?

Palpebral Fissure Length Category R = L N = 361 % R > L N = 27 L > R N = 47 FAS 90.3 4.2 5.6 No FAS 82.6 7.7 9.7 Deferred 80.1 5.1 14.7 Deferred: Robinson 68.2 9.1 22.7 Deferred: Hoyme 73.8 4.9 21.3 Deferred: Jones 88.1 4.5 7.5

This Year Modify the startle response protocol to mirror the infant heart rate monitoring paradigm Population-based estimate of incidence of FAS based on screened sample and rate of affected in exposed sample Enhance retention and implement a plan to retain the cohort beyond 12 months Obtain agreement to use selected samples for mRNA biomarker collaboration Re-consent to use archived blood samples for DNA? R01 application focused on nutrition PA-10-239 Longer term neurobehavior measures for the cohort Infant nutrition measures Post-natal intervention