Progress Report Moscow Region Infant Study June 22, 2005 Santa Barbara, CA

Objectives To measure the birth prevalence and range of alcohol-related features and neurobehavioral impairment among children born to women who report moderate to heavy amounts of alcohol by utilizing methods to permit earlier diagnosis of alcohol-related effects To evaluate the contribution of maternal nutritional factors to increased risk for prenatal growth deficiency, neurobehavioral impairment, and alcohol-related physical features in infants prenatally exposed to moderate to heavy amounts of alcohol by conducting a trial of supplement intervention and measuring micronutrient levels in maternal blood

Progress Jan 05-June 05 March, 2005, Carl Keen completed site visit to Center for Biotech Medicine (minerals), Laboratory of Anna Kalinina (vitamins), Friendship University (biomarkers, DNA banking) Resolved problems with CRDF Completed and tested screener database; completed and implemented use of extended alcohol and control database Completed ultrasound data collection tool and data dictionary Mentor training for infant testers – 2 full day sessions with each of four testers – ongoing practice sessions Initiated recruitment of subjects

Screening results 4 ladies consultation services have performed preliminary interviews with 413 pregnant women Data has been entered into the screening database as of April, 2005 Based on initial screening guidelines for subject selection 12 percent of women are meeting the criteria for exposed, and 27 percent are meeting the criteria for unexposed

Characteristics of the sample population Nationality Russian 377 (91.3%) Maternal Age (yrs) 25.20  5.52 (Range 15-44) Paternal Age (yrs) 28.87  6.65 (Range 17-63) Marital Status Married Unmarried;living with partner Unmarried;not living with partner 225 (54.5%) 153 (37.0%) 35 (8.5%) Gestational Age at Screening (wks) 14.70  6.7 (Range 3-37)

Demographics and pregnancy history Maternal Education (yrs) < 9 years 9 - 11 years 12 - 15 years > 15 years 10 (2.4%) 102 (24.7%) 215 (52.0%) 86 (20.8%) Gravidity Primigravid Range 1-14 201 (48.7%) Parity Primiparous Range 0-5 284 (68.8%) Previous spontaneous abortion or stillbirth (among multigravid) Range 0-9 47 (22.2%) Previous pregnancy termination 147 (69.3%)

Medication and illicit drug use Any medication vitamins analgesics, antihistamines, antifungal antiretrovirals, tuberculosis drugs thyroid medication oral steroids herbs 84 (20.3%) 56 (13.6%) 15 (3.6%) 4 (0.9%) 3 (0.7%) Illicit drugs marijuana amphetamine cocaine opiates inhalants other 2 (0.5%)

Smoking in the last month *smoking among exposed 63%; smoking among controls 23%

Alcohol history 372 (90.1%) of women interviewed report being ever-drinkers Among ever-drinkers, mean age at onset of drinking 17.44  2.33 yrs (range 5-32)

Quantity/frequency

Quantity/frequency 94% of ever drinkers report some alcohol in pregnancy 52% of ever drinkers report some alcohol after recognition of pregnancy

Tolerance

Signs of abuse in the last year

Validity of maternal report in Russia?

Alcohol consumption by pregnant women in Russia 1022 pregnant women in one Northwest Russian maternity house who delivered live born singletons completed a questionnaire at first prenatal visit Alcohol consumption reported by 26% of responders (40% non-responders) Most reported drinking in very small quantities-primarily beer and wine Drinkers had higher birth weight babies than non-drinkers (occasional drinkers adjusted birth weight 65 grams higher than non-drinkers; 95% CI, 2 - 129) Grjibovski A et al, (2002) Paediatric and Perinatal Epidemiology;16:255-62 Grjibovski A et al, (2004) Acta Obstet Gynecol Scand;83:1159-66

Alcohol consumption by pregnant women in Russia Preliminary data from 78 women interviewed at time of delivery in one birthing hospital in Moscow 2004-5 (Nemtsov et al – Moscow Institute of Psychiatry) 96.1% reported being ever drinkers 49.4% reported consuming some alcohol during pregnancy

Alcohol consumption by pregnant women in Russia Alcohol Group Adj. Mean BW ± SE 95% CI Abstainer in pregnancy 3290 ± 66 3158, 3421 <1 drink/day in any week 3367 ± 69 3228, 3506 >4 drinks at least one occasion 2709 ± 200 2309, 3109 Adjusted for pre-pregnancy weight, smoking, sex of infant

Alcohol consumption by pregnant women in Russia Alcohol Group Adj. Mean BL ± SE 95% CI Abstainer in pregnancy 51.4 ± 0.4 50.7, 52.2 <1 drink/day in any week 52.0 ± 0.4 51.2, 52.8 >4 drinks at least one occasion 48.9 ± 1.1 46.8, 51.1 Adjusted for pre-pregnancy weight, smoking, sex of infant

Alcohol consumption by pregnant women in Russia Alcohol Group Adj. Mean BOFC ± SE 95% CI Abstainer in pregnancy 34.8 ± 0.2 34.3, 35.3 <1 drink/day in any week 34.7 ± 0.3 34.2, 35.2 >4 drinks at least one occasion 33.7 ± 0.7 32.3, 35.2 Adjusted for pre-pregnancy weight, smoking, sex of infant

Knowledge regarding FAS among pregnant women in Russia Alcohol Group Heard of FAS Abstainer in pregnancy 33% <1 drink/day in any week 20% > 4 drinks at least one occasion 0%

Plans for coming year Continue recruitment and evaluate projected sample size through Year 3 Submit manuscript on screening data Preliminary analysis of micronutrient measures at enrollment, and biomarker measures at enrollment v. maternal report