1. Adverse Outcomes From Prenatal Alcohol Exposure By: Larry Burd, Ph.D. Director North Dakota Fetal Alcohol Syndrome Center

2. 3.9 Million Births 1,560,000 Exposed 137,000 Frequent heavy drinking 39,000 FASD The National Center on Addiction and Substance Abuse, 1999

3.  Lost productivity due to FAS: Adults - $1,000,000,000/annually $2,739,000/day  Health care costs due to FAS: Children and adults - $2,000,000,000/annually $5,479,000/day The National Center on Addiction and Substance Abuse, 1999

4. North Dakota Alcohol Income (2000) Wholesale tax$ 5,500,000 Sales tax$14,500,000 Total$20,000,000

5. Family History Maternal Risk Factors

6. Family History Familial Multigenerational Genetic Factors

7. Increased Probability of a Previous Child with Fetal Alcohol Syndrome Total number of live births prior to birth of FAS child Number of children with FAS in prior births Estimated incidence of FAS per 1,000 live births Incidence of FAS in previous births per 1,000 live births Risk increased by 13523.97170.4172x Source: E.L> Abel, Fetal Alcohol Syndrome in Families, Neurotoxicity and Teratology (1988), 10, pp.1-2. Copyright 1988 by Elsevier Science, Adapted with permission of the publisher.

8. Increased Risk of Having a Second Child with Fetal Alcohol Syndrome Total number of live births after birth of FAS child Number of children with FAS in subsequent births Estimated incidence of FAS per 1,000 live births Incidence of FAS in subsequent births per 1,000 live births Risk increased by 3527.97771795x Source: E.L> Abel, Fetal Alcohol Syndrome in Families, Neurotoxicity and Teratology (1988), 10, pp.1-2. Copyright 1988 by Elsevier Science, Adapted with permission of the publisher.

10. THE MOMS Age27.4 Education10.6 Unmarried63% Smoker82% Alcoholic10+ years Heavy Drinker> 10 day + Treatment> 3 (45%) Minority73% Poor+ Poor Diet+ Parity3 Prenatal (1 st )1 Prenatal visits<3 Maternal Deaths FAE4.1% FAS4.5% Number of prenatal complications Number of prenatal visits Monthly prenatal care starts Birth weight Number of malformations

11. THE DADS Age30.8 Education10.9 Unmarried63% Alcoholic12 + years Heavy Drinker+ Treatment> 3 Minority60% Poor+ Other terminations Number of prenatal visits Number of prenatal complications

12. THE CHILDREN Age Diagnosis7.1 years Older Sibs2 Younger2 Birth Defects20% Cerebral Palsy6% Mental Retardation30% ADHD60% Out of Home85% Head Injury25% Dead Sibling FAS/FAE Controls 11% 2%

13. THE DADS Age30.8 Education10.9 Unmarried63% Alcoholic 12+ years Heavy Drinker + Poor + THE MOMS Age27.4 Education10.6 Unmarried63% Smoker82% Alcoholic 10+ years Heavy Drinker> 10 day Treatment >3 times (45%) Poor + Poor Diet + Parity 3 Prenatal (1 st ) 1 Prenatal visits< 3 Maternal deaths FAE4.1% FAS4.5% THE CHILDREN Age diagnosis7.1 years Older sibs2 Younger2 Birth defects20% Cerebral Palsy6% Mental retardation30% ADHD60% Out of Home85% Head Injury25% Dead Sibling FAS/FAE11.4% Controls2.0%

14. Mortality in a Ten-Year Follow-Up of FAS Children 18% cases 27% of the Mothers (Streissguth, 1985)

15. MATERNAL RISK SCORE SCORE ____ Age Over 25 years ____Unmarried, Divorced, Widow, Living with PartnerCheck any one, ____On AFDC, WIC, Social Security or Income < $16,000 Per Year Add 5 ____Did not Graduate From High School ____Poor Diet ____Smokes More Than ½ Pack per Day ____Drinks less than 2 days/week & less thanCheck here, 2 drinks /drinking day Add 20 ____Age First Drunk Less Than 15 years ____In Treatment Over Three Times ____In Treatment in Last 12 MonthsCheck any one, ____Previous Child With FAS, FAE, Birth Defect, Add 35 or Developmental Disability ____Previous Child Died ____Children Out of Home (Foster Care or Adopted) Check any one, ____Heavy Drinker (3 or more days per week or over 3 drinks Add 45 per drinking day) ____Uses Inhalants, Sniffs or Illegal Drugs Score Risk Category Recommendations 0 None Standard Prenatal Care 5 Low Standard Prenatal Care 20-40 Moderate Standard Prenatal Care and Patient Education on FAS 45-50 High High Risk pregnancy, Alcohol-Drug Abuse Treatment 55-85 Very HighHigh Risk Pregnancy, Inpatient Treatment Total Score Prenatal Copyright 2000

16. Exposure

17. Exposure Rates: BRFSS:4% Birth Certificates:3% FAS Case Registry:2% (low) 8% (moderate) 90% (heavy) Prenatal Screening:39%

18. Adverse Outcomes Due to Prenatal Alcohol Exposure Did mom drink? Did she drink enough? Abnormal signs or disorders Yes or No

19. SCREENING FOR ALCOHOL ABUSE TWEAK Test (Russell 1984) TOLERANCEHow many drinks can you hold? If more than 5 drinks = 2 points WORRYHave close friends or relatives worried or complained about Your drinking in the past year? Yes = 2 points EYE-OPENERDo you sometimes take a drink in the morning when you first get up? Yes = 1 point AMNESIAHas a friend or family member ever told you about things you said or did while you were drinking that you could not remember? Yes = 1 point K/CUT DOWNDo you sometimes feel the need to cut down on your drinking? Yes = 1 point A score of 2 or above places the woman in a risk category and requires further assessment.

20. Fetal Alcohol Exposure: Could increase severity of other disorders Could cause other disorders to occur – lower susceptibility Could cause FAS with other disorders FAS could obscure other disorders Could be irrelevant to phenotype

21. Assessment of Exposure During Pregnancy On average how many days per week did you drink during pregnancy? _____(a) What is the most you had to drink on any one day during pregnancy? _____ On an average drinking day during pregnancy how many drinks did you have? _____(b) Exposure Parameters (Cumulative exposure during pregnancy)  Pregnancy Drinking Days = ( a x 40 ) = _____(c)  Estimate of number of drinking days during pregnancy.  Percent of Days Exposed During Pregnancy = ( c ÷ 280 ) =  Estimate of days exposed during pregnancy. _____  Number of Drinks During Pregnancy = ( a x b x 40 ) =  Estimate of number of drinks during pregnancy. _____(d)  Ounces of absolute alcohol = ( d ÷ 2 ) = _______  Estimate of exposure to absolute alcohol during pregnancy.

23. Mortality

24. Two Hundred and Fifty-Eight Cases of Suffocation of Infants By Charles Templeman, M.D., B.Sc. (Pub. Health), Surgeon of Police; Surgeon to the Royal Infirmary, Dundee. (Read before the Medico-Chirurgical Society of Edinburgh, 1 st June 1892.)

25. If drinking over 2 years prior to pregnancy, mortality rate 62.7%  46% deaths occur on Saturday night and Sunday morning

26. Mortality and Alcohol Use Increased risk of SIDS Sibling mortality FAS/FAE10% Controls2% Increased risk of death Saturday and Sunday

27. Rate Mothers:8% Cases:FAS 4.1% Partial 4.5% Dead – Siblings:+530%

28. Diagnosis

29. Diagnosis of People with Adverse Outcome from Prenatal Alcohol Exposure Specific Pattern of Malformations. Confirmed History of Maternal Alcohol Use-Abuse. Specific Pattern of Neurocognitive Deficits.

30. DIAGNOSTIC CRITERIA FAS AND ALCOHOL RELATED EFFECTS (3, 4, and 5 require the presumption that the finding is due to prenatal alcohol exposure) 1.FAS confirmed alcohol exposure A.confirmed maternal alcohol exposure B.characteristic facial anomalies C.growth retardation D.neurodevelopmental abnormalities 2.FAS without confirmed maternal alcohol exposure B, C, and D above 3.Partial FAS with confirmed maternal alcohol exposure A.confirmed maternal alcohol exposure B.some or partial characteristic facial features C.growth retardation D.neurodevelopmental abnormalities E.behavioral or cognitive abnormalities presumed due to prenatal alcohol exposure 4.Alcohol-Related Birth Defects (ARBD) Cardiac Ocular-Auditory Other Skeletal Renal 5.Alcohol-Related Neurodevelopmental Disorder (ARND) A.CNS neurodevelopmental abnormalities B.Complex pattern of behavior or cognitive abnormalities

31. Signs of Prenatal Alcohol Exposure Vision Hearing ADHD Mental Disorders Cognitive Impairment Height Weight Head Circumfrence < 10 th Cleft Palate 3 or more facial features: –Short palpebral fissions –Absent philtrum –Thin vermilion border upper lip –Epicanthal Folds Neurological Abnormalities Cardiac Deficits Organ Abnormalities

32. Growth Weight Diagnosis < 10 Height 100% Diagnosed Cases 100% Diagnosed Cases

33. Diagnosis of Adverse Outcomes from Prenatal Alcohol Exposure Pattern Malformations –All are common –Many appear together Maternal Alcohol Use-Abuse –Only 10-15% moms accompany children –Moms rarely interviewed –Cousin, aunt, friend, neighbor, police Neurocognitive Deficits –I Q - normed –V-P split Neuropsychological Findings –Cutoff – Abnormal test only –% present in population with FAS without FAS

34. Syndromal Variation Phenotype Variation # Highly Variable Phenotype Classic Severe

35. Syndromal Variation Phenotype Variation # Highly Variable Phenotype Classic Severe Currently Diagnosed

36. Syndromal Variation Highly Variable Phenotype Number of Cases Classic Severe ADHD Hearing Impairment Cognitive Deficits Learning Disabilities Mental Disorders Infectious Illness Mortality CL & P Pregnancy Losses Fertility Birth Defects Increased Severity Visual Impairment Phenotype Variation

37. Inaccurate Diagnosis: Stigmatization of Mother Labeling of Child Diagnostic Imprecision Parents Schools Doctors Epidemiologist Apathy

38. Public Health  Inaccurate Prevalence Outcome  Causal Factors  Cost Estimates  Service Systems Consequences of Misdiagnosis

39. Mothers  Recurrence  Health  Death  Guilt  Search for what’s wrong Consequences of Misdiagnosis

40. Child  Misunderstood Behavior  Inappropriate Treatment  Secondary Disabilities  Jail  Substance Abuse  Multiple Foster Homes  Unnecessary testing Consequences of Misdiagnosis

41. Society  Cost  Low Priority for funding  Recurrence  Loss of Potential  Infant-child Mortality Rate  Increased Severity Consequences of Misdiagnosis

43. The Brain

46. Examination of the developing mouse brain following alcohol exposure shows cells that have been killed. Apoptotic cells Nile blue stained in two of the pictures and dark brown at bottom right. Kindly provided by Dr. K Sulik and Dr. W Dunty, Univ of North Carolina

47. Ikonomidou C, et al. Science 287:1056-1060, 2000.

48. Impairments in: Memory Attention Adaptive behavior Use of social rules Sleep Behavior regulation

50. Treatment

51. Treatment of FAS Start early-Avoid Abuse Avoid multiple foster homes Treat in community Make a place in the community Avoid problem peers Use legal system Long term treatment-more than 10 years

53. A Developmental Management Model for Children and Adults With FAS and Related Disorders _____________________________________________________________________________ Newborn Management: 1.Diagnostic assessment of both physical and neurologic anomalies 2.Early involvement of child protective services. 3.Referral to the Department of Human Services for initiation of infant stimulation. 4.Prevention of secondary disabilities, specific to age group; abuse, vision/hearing deficits. 5.Referral of mother to substance abuse treatment program. 6.Sensory evaluation (vision and hearing). Childhood Management: 1.Head Start Program with special learning environment, addressing specific learning disabilities. 2.Annual developmental assessment. 3.Referral for services to address neurologic deficits and psychosocial delays. 4.Prevention of secondary disabilities.

54. Monitoring social skill development Adolescent Management: 1.Prevention of secondary disabilities, specifically drug and alcohol use. Prevention of school failure, social problems and institutionalization. 2.Vocational training, preparation for future employment. 3.Continuation of developmental assessments. 4.Develop long term plan (10 years). 5.Social skill development and monitor peer group. Adult Management: 1.Employment services (vocational rehabilitation). 2.Social services and long-term support. 3.Monitor for substance abuse. 4.Enhance awareness in adult service systems: mental health, substance abuse, corrections. ________________________________________________________________________

55. Common Recommendations Annual Evaluation Positive Behavior Management Program Respite Care IEP Monitor Peers Schedule Plan Ahead Evaluate All Siblings Find the Mom

56. Prevention of FAS 10-18 cases of FAS born each year in ND. Treatment 50% Effective Alcohol Use & Other Risk Factors Risk of FAS Women Treated Women Quit * Cases Prevented Cost per Case Prevented Daily Alcohol Use 0.01%20,00010,0001$100,000,000 Heavy drinkers, middle class, non-smokers.29%69034413,450,000 Heavy drinkers, low in- come, smokers, poor diet 4.3%47231235,000 Women who have had a previous child with FAS 75%31115,000 * Quit after one year.

58. Cumulative Cost Savings from Preventing One Case of FAS per Year for 20 Consecutive Years