Fetal Alcohol Spectrum Disorder: Prevalence, Comorbidity, and Economic Cost. Presented by Svetlana (Lana) Popova, MD, PhD, MPH

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1 Fetal Alcohol Spectrum Disorder: Prevalence, Comorbidity, and Economic Cost Presented by Svetlana (Lana) Popova, MD, PhD, MPH Centre for Addiction and Mental Health, University of Toronto, PAHO/WHO Collaborating Centre Toronto, Canada Training on FASD Santiago, Chile April 26-28, 2017

2 OVERVIEW Prevalence of alcohol consump7on and binge drinking during pregnancy, FAS/FASD in different popula7ons of different countries (including countries of La7n America and the Caribbean), World Health Organiza7on (WHO) regions and globally. Es7mated global incidence of children born with FAS and FASD annually Co- morbidity Economic cost

3 Fetal Alcohol Spectrum Disorder (FASD) What is FASD? An umbrella term describing the range of effects that can occur in a person whose mother drank alcohol during pregnancy What are the effects of FASD? Physical and mental disabilities Problems associated with behaviour and learning Problems with memory, speech, attention, problem solving Trouble with the law, school, drug abuse etc. Irreversible and lifelong FASD is preventable!

4 Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term that covers several alcohol- related diagnoses FASD Fetal Alcohol Syndrome (FAS) Partial Fetal Alcohol Syndrome (pfas) Fetal Alcohol Effects (FAE) Alcohol- Related Neurodevelopmental Disorder (ARND) Alcohol- Related Birth Defects (ARBD)

Alcohol- related neurodevelopmental disorder Alcohol- related

5 What are Fetal Alcohol Spectrum Disorder (FASD)? Fetal alcohol syndrome (most severe) Par$al FAS (some defects) Alcohol- related neurodevelopmental disorder Alcohol- related birth defects In the normal range, but never reach their poten$al (largest number of cases)

6 Prevalence of Alcohol Use During Pregnancy and FAS/FASD 1) Popova S, Lange S, Probst C, Gmel G, & Rehm J (2017). Lancet Global Health 2) Lange S, Probst C, Gmel G, Rehm J, Popova S (accepted). JAMA, Pediatrics Objec7ve: To es$mate the prevalence of alcohol use and binge drinking during pregnancy and FAS/FASD by country, WHO region, and globally Methodology: Comprehensive Literature search: not limited geographically/language Meta- analyses: Pooled prevalence for countries with 2+ studies, assuming a random- effects model Data predic@on: For countries with one or no studies: a) For AC: using frac$onal response regression modelling and; b) For FAS/FASD: based on the propor$on of women who gave birth to a child with FAS/FASD among women who consumed alcohol during pregnancy Es$mated WHO regional and global averages of FAS/FASD prevalence weighted by the number of live births in each country

7 Prevalence of Alcohol Use During Pregnancy in General Popula7on for select Countries (any amount of alcohol consumed and at any point during pregnancy) % % 45.8% % 36.5% 36.3% 35.6% 34.0% 33.1% 32.7% 30.5% 29.7% 28.3% 26.7% 27.0% 25.8% % 18.0% 15.2% 15.0% 14.8% 13.2% 13.0% 12.7% 10.6% 10.0% 10.0% 9.4% 8.1% 0

8 Five Countries with the Highest Prevalence of Binge Drinking During Pregnancy in General Popula7on Es7mated propor7on of women who binge drank during pregnancy out of all women who used any amount of alcohol during pregnancy (% shown on the top of bars) 70.0% 60.0% 17.4% 50.0% 40.0% 30.0% 20.0% 25.9% 35.8% 42.0% 77.7% 10.0% 0.0% Ireland Czech Republic Moldova Lithuania Paraguay binge drinking any amount

9 Prevalence of Alcohol Use During Pregnancy in General Population by WHO Region, 2012 EUR 25.2% (95% CI: 21.6% 29.6%) AMR 11.2% (95% CI: 9.4% 12.6%) EMR 0.2% (0.1% 0.9%) SEAR 1.8% (95% CI: 0.9% 5.1%) AFR 10.0% (95% CI:8.5% 11.8%) WPR 8.6% (95% CI: 4.5% 11.6%) AFR=African Region, AMR=Region of the Americas, EMR=Eastern-Mediterranean Region, EUR=European Region, SEAR=South-East Asia Region, WPR=Western Pacific Region

10 Prevalence of Alcohol Use and Binge Drinking During Pregnancy in General Popula7on by WHO Region and Globally, % 25.0% 25.2% 20.0% Prevalence 15.0% 10.0% 11.2% 10.0% 8.6% 9.8% 5.0% 0.0% 2.7% 2.8% 3.1% 1.8% 0.2% 1.8% 2.0% EUR AMR AFR WPR SEAR EMR Worldwide binge drinking any amount AFR=African Region, AMR=Region of the Americas, EMR=Eastern-Mediterranean Region, EUR=European Region, SEAR=South-East Asia Region, WPR=Western Pacific Region

Prevalence of Alcohol Use During Pregnancy in 70.0% Canada (any amount, and at any point during pregnancy) 60.0% 60.5% 50.0% 50.8% 48.8% 46.0% 40.0% 34.5% 30.0% 30.1% 26.3% 24.3% 25.3% 22.

11 Prevalence of Alcohol Use During Pregnancy in 70.0% Canada (any amount, and at any point during pregnancy) 60.0% 60.5% 50.0% 50.8% 48.8% 46.0% 40.0% 34.5% 30.0% 30.1% 26.3% 24.3% 25.3% 22.3% 20.0% 10.0% 10.0% 14.6% 17.0% 7.5% 17.5% 14.4% 10.5% 10.5% 11.2% 10.8% 16.8% 9.9% 0.0% 2.0% 0.5% 2.0% 0.6% General Population Northern Communities (Range: 0.5% to 30.1%) (Range: 24.3% to 60.5%)

12 Prevalence of Any Amount of Alcohol Use During Pregnancy in General Popula7on of La7n America and the Caribbean in 2012 Lange, Probst, Heer, Roerecke, Rehm, Monteiro, Shield, de Oliveira & Popova. In press. Rev Panam Salud Publica [Pan American Journal of Public Health] Data from published studies on the prevalence of alcohol consump7on during pregnancy were available from 5 of the 33 countries in La7n America and the Caribbean: Brazil [n=17], Chile [n=2], Guatemala [n=1], Mexico [n=3], and Uruguay [n=1]; no studies from the Caribbean. Meta- analysis for Brazil and Mexico, based on the criterion of three available studies per country. The prevalence of alcohol consump7on during pregnancy was predicted for 31 countries.

Prevalence of Any Amount of Alcohol Use During Pregnancy in General Popula7on of La7n America and the Caribbean in 2012 25% 20% 23% 22% 18% 18% Lange, Probst, Heer, & Popova. In press.

13 Prevalence of Any Amount of Alcohol Use During Pregnancy in General Popula7on of La7n America and the Caribbean in % 20% 23% 22% 18% 18% Lange, Probst, Heer, & Popova. In press. Rev Panam Salud Publica 15% 10% 5% 0% 15% 15% 15% 15% 15% 13% 13% 12% 12% 12% 11% 11% 11% 10% 10% 10% 10% 10% 9% 9% 9% 9% 9% Grenada St. Lucia Guyana Paraguay Brazil Hai7 St. Vincent and Grenadines Barbados Dominica Argen7na Peru Dominican Republic Bahamas Panama Chile Honduras Bolivia Suriname Venezuela An7gua and Barbuda Belize St. Kijs and Nevis Jamaica Colombia Ecuador Nicaragua Uruguay Costa Rica El Salvador Guatemala Trinidad and Tobago Cuba Mexico Global 8% 8% 7% 6% 5% 1% 10% Es7mate of alcohol use (any amount) during pregnancy based on a meta- analysis of the current literature

14 Prevalence of Any Amount of Alcohol Use During Pregnancy in General Popula7on of La7n America and the Caribbean in 2012 Lange, Probst, Heer & Popova. In press. Rev Panam Salud Publica

15 *Es7mate of binge drinking during pregnancy based on a meta- analysis of the current literature 16% 14% Prevalence of Binge Drinking During Pregnancy in General Popula7on of La7n America and the Caribbean in % 12% 10% 8% 6.7% 6% 4% 2% 3.6% 3.6% 3.0% 3.3% 2.7% 3.0% 2.4% 2.3% 2.7% 2.7% 2.2% 2.4% 2.3% 2.0% 2.3% 1.9% 1.9% 1.5% 2.8% 2.3% 2.2% 2.0% 1.9% 1.9% 1.8% 1.6% 1.6% 1.5% 1.4% 1.2% 1.4% 1.2% 0%

16 Prevalence of Alcohol Use During Pregnancy (cont ) Alcohol consump7on during pregnancy is a significant public health concern worldwide and an established cause of FASD FASD is theore7cally, largely preventable However, globally, FASD may increase in the near future due to two reasons: 1) the rates of alcohol use, binge drinking and drinking during pregnancy appear to be increasing among young women in a number of countries; and 2) a vast majority of pregnancies are unplanned

17 Prevalence of FAS/FASD in General Popula7on Flow chart for systema7c literature search on prevalence of FAS/FASD 11,089 records iden$fied through database searching 21 addi$onal records iden$fied through other sources 11,110 records found 5,965 records screened 430 full- text ar$cles assessed for eligibility 5,145 duplicates removed 5,535 records excluded 368 full- text ar$cles excluded; lack of relevant data or did not meet the inclusion criteria 62 ar$cles iden$fied as including relevant data from 19 countries [African Region (South Africa, 9 studies), European Region (Croa$a, 2 studies; Denmark, 1 study; France, 7 studies; Germany, 1 study; Ireland, 1 study; Italy, 3 studies; Netherlands, 1 study; Portugal, 1 study; Spain, 1 study; Sweden, 2 studies; Switzerland, 1 study; and United Kingdom, 3 studies), Region of the Americas (Canada, 2 studies; United States, 24 studies; and Uruguay, 1 study), and Western Pacific Region (Australia, 7 studies; New Zealand, 1 study; and Republic of Korea, 1 study)]

Prevalence of FAS in General Popula7on by WHO Region, 2012 EUR 37.4 per 10,000 (95% CI: 24.7 54.2 per 10,000) AMR 16.6 per 10,000 (95% CI: 11.0 24.0 per 10,000) EMR 0.2 per 10,000 (0.2 0.

18 Prevalence of FAS in General Popula7on by WHO Region, 2012 EUR 37.4 per 10,000 (95% CI: per 10,000) AMR 16.6 per 10,000 (95% CI: per 10,000) EMR 0.2 per 10,000 ( per 10,000) SEAR 2.7 per 10,000 AFR (95% 14.8 per CI: ,000 per 10,000) (95% CI: per 10,000) WPR 12.7 per 10,000 (95% CI: per 10,000) AFR=African Region, AMR=Region of the Americas, EMR=Eastern-Mediterranean Region, EUR=European Region, SEAR=South-East Asia Region, WPR=Western Pacific Region

19 Prevalence of FAS in General Popula7on by WHO Region and Globally, Prevalence (per 10,000) % EUR AMR AFR WPR SEAR EMR Worldwide AFR=African R, AMR=R of the Americas, EMR=Eastern-Mediterranean R, EUR=European R, SEAR=South-East Asia R, WPR=Western Pacific R

20 Prevalence of FASD in General Popula7on by WHO Region, 2012 EUR per 10,000 (95% CI: per 10,000) EMR 1.3 per 10,000 ( per 10,000) SEAR 14.1 per 10,000 CI: 10, per 10,000) AFR (95% 78.3 per (95% CI: per 10,000) AMR 87.9 per 10,000 (95% CI: per 10,000) WPR 67.4 per 10,000 (95% CI: per 10,000) AFR=African Region, AMR=Region of the Americas, EMR=Eastern-Mediterranean Region, EUR=European Region, SEAR=South-East Asia Region, WPR=Western Pacific Region

21 Prevalence of FASD in General Popula7on by WHO Region and Globally, 2012 Prevalence (per 10,000) % % EUR AMR AFR WPR SEAR EMR Global AFR=African Region, AMR=Region of the Americas, EMR=Eastern-Mediterranean Region, EUR=European Region, SEAR=South-East Asia Region, WPR=Western Pacific Region

22 Five Countries with the Highest Prevalence of FASD 120 in the General Popula7on Prevalence (per 1,000) South Africa* Croa7a* Ireland Italy* Belarus *Based on actual data

23 Prevalence of FAS and FASD in La7n America and the Caribbean in 2012 Prevalence (per 1,000) Grenada 17.2 St Lucia FASD FAS Guyana Paraguay Brazil Hai7 St Vincent and Grenadines Barbados Dominica Argen7na Peru Bahamas Dominican Republic Panama Honduras Bolivia Chile Suriname Venezuela An7gua and Barbuda Belize St Kijs and Nevis Jamaica Colombia Ecuador Nicaragua Uruguay Costa Rica El Salvador Guatemala Trinidad and Tobago Cuba Puerto Rico 1.0 Mexico 7.7 Global FAS FASD

24 Global Incidence of FAS and FASD Fetal Alcohol Syndrome Globally, one out of 67 women who consume alcohol during pregnancy in the general popula7on delivered a child with FAS, which translates to about 119,000 children born with FAS in the world each year Fetal Alcohol Spectrum Disorder One out of 13 pregnant women who consumed alcohol while pregnant delivered a child with FASD Over 1,700 cases of FASD are born every day 630,000 cases of FASD are born every year globally

Comparison FASD prevalence among special popula7ons, based on select studies, to the global prevalence among the general popula7on 600.0 500.0 400.0 300.0 200.0 100.0 0.0 Prevalence (per 1,000) 521.

25 Comparison FASD prevalence among special popula7ons, based on select studies, to the global prevalence among the general popula7on Prevalence (per 1,000) Adoptees from Eastern Europe, Sweden (Landgren et al. 64) As compared to the global FASD prevalence among the general popula7on: 5 to 68 7mes higher among children in care 16 to 25 7mes higher among Aboriginal popula7ons 19 7mes higher among a psychiatric care popula7on 24 7mes higher in a low socioeconomic status popula7on 30 7mes higher in a correc7onal popula7on _Foster and adopted youth referred to a children s mental health centre, USA (Chasnoff et al.65) /Correctional population, Canada (Fast et al.66) 1Aboriginal population, Canada (Robinson et al. 67) RRural population with a low socioeconomic status, South Africa (de Vries et al.68) >Children residing in an orphanage, Brazil (Strömland et al. 69) 3Psychiatric care population, USA (Bell & Chimata70) 7Aboriginal population, Australia (Fitzpatrick et al. 71) & foster care children, Israel (Tenenbaum et al. 72) 7.73 General population, Globally

26 INTRODUCTION Comorbidity of FASD FASD is related to numerous comorbidities due to the permanent effects of prenatal alcohol exposure on the fetus However, the existing comorbid conditions and their prevalence among individuals with FASD remained to be established Popova, S., Lange, S., Shield, K., Mihic, A., Chudley, A. E., Mukherjee, R. A. S., Bekmuradov, D., & Rehm, J. (2016). Comorbidity of fetal alcohol spectrum disorder: a systematic review and meta-analysis. The Lancet, 387, DOI:

27 OBJECTIVES The objectives of the current study were to: 1) Identify the comorbid conditions that occur among individuals with FASD, and 2) Estimate the pooled prevalence of comorbid conditions found to occur among individuals with FAS The latter objective was limited to FAS because FAS is the only expression of FASD in the International Classification of Diseases (ICD): ICD, version 9 Alcohol affecting foetus or newborn via placenta or breast milk ICD, version 10 Fetal alcohol syndrome (dysmorphic) - Q86.0

28 METHODS Systematic Literature Review A systematic literature search was performed in multiple electronic bibliographic databases in order to locate original published studies that reported on the comorbidity among individuals with diagnosed FASD The search was not limited geographically All comorbid conditions were coded according to the ICD-10 Meta-analyses were performed, assuming a random-effects model

29 RESULTS Systematic Literature Review Records identified through database searching (n = 5,016) Additional records identified through other sources (n = 52) Duplicates removed (n = 2,144) Records screened (n = 2,924) Records excluded (n = 2,625) Full-text articles assessed for eligibility (n = 299) Articles included in qualitative synthesis (n = 127) Full-text articles excluded; lack of relevant data/did not meet the inclusion criteria (n = 172) Studies included in quantitative synthesis (meta-analyses; n = 33) Canada (6); Germany (4); Ireland (1); Italy (1); Norway (1); Portugal (1); Scotland (1); South Africa (3); Sweden (3); USA (12)

30 RESULTS (Con t) Systematic Literature Review 428 comorbid conditions, spanning across 18 (out of 22) chapters of the ICD-10 The most prevalent disease conditions were: - Congenital malformations, deformities and chromosomal abnormalities (Q00-Q99; Chapter XVII), and - Mental and behavioural disorders (F00-F99; Chapter V)

31 RESULTS (Con t) Percentage of conditions found to occur among individuals with FASD by ICD-10 chapter

32 RESULTS (Con t) Meta-analyses 33 studies reported data on frequency of at least one disease condition and were eligible to be included in the meta-analyses Contained 1,728 subjects with diagnosed FAS Reported frequencies for 183 comorbid conditions coded in ICD-10 In order to estimate pooled prevalence, 183 metaanalyses were performed; one for each comorbid condition found to occur among individuals with FAS

33 Comorbid conditions with a pooled prevalence over 50% among individuals with FAS 100.0% 90.0% 80.0% 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% 90.7% 81.8% 76.2% 69.2% 67.2% 54.5% 51.2% 71.4% 61.9% 77.3% 57.9% 56.8% 51.2% 72.2% 65.3% 54.1% 52.6% 50.0% 90.9% 50.0% Conduct/behavioural problems/disruptive behaviour/impulsivity (F91) Receptive language deficit (F80.2) Expressive language deficit (F80.1) Developmental/cognitive disorder; developmental delay(s) (F89) Speech/language delay/disorder/retarded speech development/speech defects/ acquisition (F80.9) Alcohol dependence/drug dependence (F10.2/F19.2) Attention deficit hyperactivity disorder/ attention deficit disorder (F90.0) Refractive error(s) (H52.6) Subnormal/decreased visual acuity/ problems/visual impairment (H54) Chronic/recurrent (serous) otitis media (H65.2) Central hearding disorder (H90.5) Conductive hearing loss (H90.2) (Acute/serous/serousmucous) otitis media (H65.0) Intrauterine growth retardation (P05.9) Pre-mature birth/born prematurally/ preterm birth (P07.3) Coccygeal fovea (Q14.1) Congenital fusion of cervical vertebrae/ cervical spin fusion (Q76.4) Hypertelorism (Q75.2) Abnormal retinal function - ERG records (R94.1) Failure to thrive (R62.8) Mental and behavioural disorders (F00-F99) Diseases of the eye and adnexa (H00-H59) Diseases of the ear and mastoid process (H60-H95) Certain conditions originating in the perinatal period (P00-P99) Congenital malformations, (Q00-Q99) Symptoms, signs and abnormal clinical and lab findings (R00-R99)

34 RESULTS (Con t) Pooled prevalence of comorbid conditions in individuals with FAS vs the general population of the USA 9.5 times 10.3 times times times 97.5 times 5.6 times 31 times times times 4.4 times 7.6 times FAS General population

35 Cost of FASD in Canada Percentage of main cost components attributable to FASD in Canada in 2013 Total annual cost: $1.3 B - $2.3 B Health Care 10.2% $128.5 M-$226.3 M Productivity Losses Due to Morbidity and Mortality 42.2% $532 M - $1.2 B Corrections 30.0% $378.3 M Prevention and Research 0.6% Special Education 4.3% Children in Care 4.7% Supportive Housing 1.8% Long-term Care 6.2% Popova et al. (2015). Available at:

36 Popova et al (2012) Journal of Population Therapeutics and Clinical Pharmacology, Incorporating Fetal Alcohol Research, 19(1), e51-e65. Available from

37 If Not Now, When? The presented data will raise awareness of harmful effects of PAE and draw attention to the need for screening and early diagnosing Improving screening and diagnosis would promote access to interventions and resources that may subsequently reduce burden and cost The harmful effects of alcohol on a fetus, representing many cases of preventable disability, should be recognized globally as a large public health problem. The presented results clearly demonstrate the need for such recognition

38 ACKNOWLEDGEMENTS This work was supported by the Public Health Agency of Canada Many people worked on these projects!

39 CONTACT INFORMATION Svetlana (Lana) Popova Senior Scientist, Associate Professor Social & Epidemiological Research Department Centre for Addiction & Mental Health, University of Toronto, WHO Collaborating Centre 33 Russell Street, room T507 Toronto, Ontario, Canada M5S 2S1 Tel. (416) ext

Prevalence of Alcohol Consumption during Pregnancy and Fetal Alcohol Spectrum Disorder

Prevalence of Alcohol Consumption during Pregnancy and Fetal Alcohol Spectrum Disorder Presented by Svetlana (Lana) Popova, MD, PhD, MPH Centre for Addiction and Mental Health, University of Toronto, PAHO/WHO