The Epidemiology of FASD in Italy: Progress Report Philip A. May, Ph.D. The University of New Mexico Daniela Fiorentino La Sapienza, The University of Rome

Specific Aims Determine prevalence & characteristics of FASD children (vs. controls) in select towns in the Lazio Region. Screen suspects for FASD in first grade classes in public schools. Determine any substrate differences in the population.

Specific Aims (2) Identify maternal risk factors for FASD in a European population. Identify children for neuropsychological tests. Provide epidemiologic data in Italy for designing targeted prevention programs.

Funding Pilot money from CIFASD pays for travel for American members of the team. Bulk of the money for the study comes from the Italian government.

Background No population-based epidemiologic study published to date for Italy or other Western European countries. Few articles on prenatal drinking in Italy. Clinical literature from Italy documents a total of 24 cases of FAS in 5 articles located.

Insights into Italian Perceptions about Drinking Bonati and Fellin (1991) were careful to distinguish between drinking with meals and drinking between meals. Between meal drinkers are the Italian “alcohol abusers” (<1% of those in the study). Birth weight is affected only by abuse. Drinking during meals and the diet are believed to be protective.

Further Insights: Prenatal Drinking Primatesta et al., (1993) in Milan found binge drinking (no definition cited) during pregnancy in 1.4% of their sample. Yet, 2% had 23 or more drinks (277g) per wk., and, 7% had 11.5 to 23 drinks per wk. Therefore, substantial risk for FASD (by US standards) for 9%. During pregnancy, 29% of women continued to drink daily.

Italian Study Population: Wave I 68 schools (two districts) in this part of the Lazio Region, Province of Rome. District covers 15 towns about one hour southeast of the City of Rome. 25 schools (jurisdictions) picked randomly.

Wave I Sample (2) 1086 in 1st grade classes in the schools. 543 (50%) received consent to participate. 181 children picked for full dysmorphology screen because of: Growth, <25th centile (hgt., wgt. or OFC). Behavioral problems. 72 randomly-selected controls picked.

Wave I Final Dysmorphology Sample 253 (suspects and controls) picked for full screen. 233 examined by dysmorphology team

Wave I - Psychological Testing Total referred for testing = 147 Reason for testing: 15 preliminary FAS (6.4% of those screened) 79 deferred (26.6%) 53 controls ( 19 or 26.4% were deferred from blinded examinations)

Psychological Testing 140 evaluated; 7 parents did not provide consent for testing. Tests administered: Ravens Colored Matrices. Italian TROG judged not suitable because of small Italian samples which are not validated and published. (One similar one too long.) Rustioni’s Evaluation of Language Comprehension (Italian norms standardized on 2622 children). Behavioral measures (e.g. PBCL-36, parent and teacher ratings).

Maternal Interviews 517 administered by three very persistent interviewers. Form originally a version of our South African questionnaire with: reproductive, social and dietary history; and time line follow-back Q,F,T measures of drinking. Have now found out that many key measures were cut out when questionnaire was shortened, e.g. binge drinking.

Wave I Maternal Interviews: Sample Completed Interviews completed with mothers of: Preliminary FAS children --14/15 (93.3%). Deferred Children -- 72/79 (91.1%). Controls – 47/53 (95.9%). But the questionnaires have lost so much in the shortening that they are not as rich in detail about drinking pattern as they should be.

Parental Feedback Individual meetings scheduled with all parents of children tested at the school. Not all came. All were provided with a report of growth, teacher’s report on behavior and performance, and the psychological evaluation. No mention of alcohol-related issues mentioned.

Wave I Final Case Conferences Final diagnoses made for children in case conference January, 2005. Case conferences include data and professional representation/analysis of: Dysmorphology. Psychological and behavioral evaluation. Maternal interviews.

Case Conference Results Diagnosis prel. dx n of def. of cat. FAS 15 4 2.7% 26.7% Deferred 132 4 2.7% Partial FAS X 17 11.6% 13.6% ARND X 1 0.7% or 15% Not FASD X 121 82.3% Total 147 147 100.0%

Wave I: Selected Dysmorphology Results Variable FASD* Controls** p Dysm. Score 12.5 3.3 <.001 OFC (cm) 50.8 51.9 <.001 PFL (cm) 2.4 2.5 <.003 PL (cm) 1.5 1.4 <.003 Smooth Philtrum 90.0% 10.4% <.001 Alt. Pal. Crease 45.5% 19.5% <.02 * n=22 **n= 67

Wave I: Selected Psychological and Developmental Results Test FASD Controls p Raven CPM 17.9 21.8 .002 Raven %tile 55.0 72.0 .002 Rustoni (tot. errors) 7.9 5.3 <.001 Rustioni Qualitative 3.4 4.9 .002 Teachers’s DBD rating: attention 4.3 0.6 <.001 hyperact./impul. 2.1 0.7 .005 PBCL-36 7.9 3.8 <.001

Wave I: Selected Maternal Variables Variable FASD Controls p Educ.< hs. 58.8% 31.8% .014 Parity 2.5 1.9 .016 Cur. drinker * 91.7% 100.0 % ns Cur. drks*.- mo. 41.9 8.0 .007 Drk.before p.g. 64.7% 66.7% ns Drk. dur. p.g. 50.0% 27.4% ns Drks.-30 days p.g.** 6.1 1.2 .024 Body size (no sig. difference on any variables) * consumed alcohol in past yr. - current drinkers ** 2nd and 3rd trimesters

Italy Wave II Carried out in March, 2003. Another 25 schools in the Lazio region picked via random number table. Utilized a similar international team for dysmorphology, Italians for psychological testing and maternal data. Lead dysmorphologists: Luther Robinson and Gene Hoyme.

Italy Wave II 910 was the total number of children in random-sample schools. 435 (47.8%) were provided consent to participate. 185 selected from first tier screening (hgt. wgt., OFC, and/or developmental probs). After dysmorphology screening: 35 children (18.9%) were selected for further testing. 48 controls were selected.

Italy Wave II Further consent to participate gained for all 83 children (100%). Tests used: WISC

Wave II Psychological Testing and Maternal Interviews Psychological testing was completed for all 83 children except one control.* 408 mothers of the 435 mothers (93.7%) were interviewed with an improved questionnaire. * who became very tired and his mother requested that the WISC not be given.

Wave II Maternal Interviews The question remains as to how much the questionnaire was improved and how the mothers responded (with seemingly more forthcoming answers?). Specific analyses of particular FASD and control mothers from both waves will be insightful. Total mothers interviewed in both waves is 925.

Italy: Lessons Learned Parental consent was a substantial issue. Logistics are complicated by small schools, narrow roads, and heavy traffic in urban areas. Our Italian colleagues are extremely hard working, very efficient, and persistent. Maternal questionnaire from Wave I needed revision to achieve the most useful and accurate information. Sensitivity to stigma is an issue.

Italy: Lessons Learned (2) The mothers in Italy may be no more forthcoming with candid and accurate information on drinking than those in the United States or other developed countries. The psychological tests used in Wave I were not the best at discriminating the children. Psychological battery was improved and lengthened for Wave II. The PBCL was not used the same in Italy as in the U.S. – they are not as problem oriented.

Future Plans for Italy Case conference for final diagnosis for Wave II children: January, 2006. We have proposed to test all FASD children and controls with the complete CIFASD battery. 45 to 50 FASD and 115 controls are candidates for testing: From Wave I: 22 FASD and 67 controls. From Wave II: ~25 FASD and 48 controls.