1. 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

2. 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

3. 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

4. Flow of Subjects Alcohol Group N = 300 No Alcohol Group N = 300*
Screening and Enrollment
Alcohol Group
N = 300
No Alcohol Group
N = 300*
Randomization within Site and Within Alcohol Group by Smoking Status
75 MMN; 75 MMN + choline; 150 treatment as usual
Baseline and Third Trimester Blood Sampling, Two Interviews
Birth Outcome, Photographs, Dysmorphology Examination, Neurobehavioral Testing 6 and 12m
*Additional ‘questionable’ group recruited and randomized with same procedures

5. Sample Size for Primary Endpoint for RCT
Projected Sample Size 12-Month Bayley with 75% Retention
Alcohol vs. no alcohol
225
Among alcohol exposed
MMN vs. No MMN
112
MMN+Choline vs. No MMN 56
MMN+Choline vs. MMN

6. Specific Aim 1 Preliminary Classification Exposed N = 83 Unexposed
FAS
6 (7.2%)
Deferred
20 (24.1%)
16 (21.6%)
No FAS
58 (69.9%)
58 (78.4%)
Revised Classification
N = 49
N = 43
FAS/FASD
14 (28.6%)
2 (4.7%)*
Bayley Score >1SD Below Mean – No Features
5 (10.2%)
5 (11.6%)
Total
19 (38.7%)
7 (16.3%)
Some Features –
Normal Bayley
4 (8.2%)
10 (23.3%)
*some features with neurobehavioral impairment
** neurobehavioral impairment

7. Specific Aim 1: Timing and Dose Relative to FAS Classification
Exposure Classification
OR (95% CI)
For FAS/FASD Revised Classification
p-value
AA per day conception
3.069 (1.089, 8.689)
0.035
AA per drinking day in pregnancy (most recent two weeks at enrollment mid-pregnancy)
2.708 (1.164, 6.301)
0.021
Range of Exposure Among Affected Infants
Minimum
Maximum
0.1351
2.201
AA per drinking day conception
0.4730
5.180
AA per day pregnancy
0.000
0.7481
AA per dinking day pregnancy
3.491

8. Specific Aim 1: Physical Features Relative to Neurobehavior by Alcohol Group
Dysmorphology Classification
Alcohol Exposed Group
N = 44
6 Month Bayley
MDI
Mean (SD)
p-value
6 Month
Bayley
PDI
FAS
75.0
<0.001
62.0
<0.002
Deferred
83.6 (15.8)
83.7 (16.4)
No FAS
97.3 (5.1)
97.2 (11.9)
Initial Dysmorphology Classification
Unexposed Group
N = 43
---
0.343
0.549
98.1 (4.5)
100.5 (8.9)
95.2 (10.1)
98.4 (10.6)

9. Specific Aim 2: Selected Baseline Measures by Alcohol Group
Alcohol Unexposed
Mean ± SD
N = 103
Alcohol Exposed
N = 114
p-value
Zn (ų/mL)
0.65 ± 0.12
0.61 ± 0.10
0.053
Cu (ų/mL)
1.79 ± 0.29
1.72 ± 0.30
0.075
Mg (ų/mL)
16.35 ± 1.50
16.26 ± 1.46
0.656
Ca (ų/mL)
86.29 ± 9.60
84.45 ± 7.26
0.115
Fe (ų/mL)
0.87 ± 0.32
0.90 ± 0.38
0.523
Ferritin (ng/mL)
28.44 ± 23.13
36.60 ± 33.67
0.037
TfR
16.25 ± 4.78
15.88 ± 6.92
0.649
Cp activity (Units/L)
± 51.29
± 50.27
0.151
HsCRP (mg/L)
4.80 ± 7.39
3.18 ± 3.74
0.047

10. Uriu-Adams J & Keen CL, BDRB 89 (2010)

11. 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, )
0.015
Fe lower quartile
5.447 (1.721, )
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

12. Specific Aim 2: Intent to Treat Analysis: Balance on Selected Covariates Associated with Outcome in the Exposed
Characteristic
Associated with FAS Status in Exposed
No Supplement
MMN
MMN + Choline
P-value
Gestational Age at Enrollment – Mean (SD)
20.6 (5.3)
19.5 (5.9)
20.2 (7.1)
0.723
Current Smokers - %
17.2%
18.5%
23.3%
0.989

13. Specific Aim 2: Intervention Group Relative to FASD Classification
Vitamin Group
In Exposed
FAS/FASD Revised Classification
No intervention (n = 51)
9 (15.0%)
4 (12.5%)
MMN (n = 28)
1 (3.3%)
MMN + Choline (n = 29)
Deferred to FAS/FASD among Exposed
Deferred to No FAS
Among Exposed
No intervention
5 (83.3%)
1 (16.7%)
MMN or MMN + Choline
2 (40.0%)
3 (60.0%)