FASD Isn’t Just About the Brain

Dr Caron Byrne Health and Wellbeing in DD 2018

Learning ObjectivesRe-evaluate and modify your current knowledge and assumptions about FASD:

diagnostic terminology, affected populations/prevalence, epigenetics and neuroimmune function, adaptive function/IQ,

nutrition, misdiagnosis, stigma/blamehealth monitoring

Conflict of Interestthe author has no conflict of interest to disclose

Quick review of Diagnostic Terms in FASD• Fetal Alcohol Syndrome (FAS)• Partial FAS (pFAS)• Alcohol Related Neurodevelopmental Disorder (ARND)• Static encephalopathy • Neurobehavioural Disorder associated with Prenatal

Alcohol Exposure (ND-PAE)• Fetal Alcohol Spectrum Disorder (FASD)

FASD Assessment and Diagnosis• No universal agreement on assessment and

diagnostic criteria (yet!)• different diagnostic terms used in different

countries (1, 2, 3)

• DSM5 • International Classification of Diseases (ICD)• Canadian FASD Diagnostic Guidelines (1)

Assessment• Multidisciplinary team assessment is best• Physical, cognitive, behavioural, adaptive and history

searching for prenatal alcohol exposure (PAE)• cognitive function and IQ is important to assess but

adaptive function and how someone manages in real life is essential to design realistic supports and interventions

Missed diagnoses and misdiagnosis• prenatal alcohol exposure (PAE) is imposed on basic

genetics of the fetus • FASD can co-occur with other syndromes (ie Down

Syndrome, autism etc) if PAE occurs but not all may be diagnosed

• FASD may be and is often missed-stigma and shame play a role, challenges getting alcohol use history

Prevalence of FASD-CAMH Study (4)

• Prevalence: how many people across the lifespan have the condition at any one time

• Recent study of age 7-9 years old in Greater Toronto• 5/10 school districts agreed to participate (4)

• 2555 students were assessed with consent• Population was mainly Caucasian, middle class• Living with partners 94.8%; employed 89.5%

CAMH Study (4)

• Mothers of children with suspected FASD vs control group: lower level of education, 3 xs more likely to be getting financial support form family, fathers had less secondary education

• planned pregnancy- controls 83.8 % vs 63.2%• No one said they had an alcohol problem or had

sought help

Mothers of children with suspected FASD

• alcohol consumption prior to pregnancy recognition: high risk intake 63.2%, some risk 36.8%

• alcohol use after preg recognition (PR): 10.5%• more smoked before pregnancy recognition and

more smoked daily • Substance use before PR- 68.4% vs 27% controls• No drug use after PR

Prevalence of FASD• Results of CAMH study- prevalence 2%-3% which is

more than previous assumed prevalence of 1% • BUT 2%-3% still likely an underestimate• Prevalence in Croatia: 4-7%; Italy: 4-5%; South Africa: 6-

21%; depends on rates of alcohol use, nutritional status • FASD is not restricted to disadvantaged groups and is

spread throughout society regardless of socioeconomic status, age or ethnicity (4)

Epigenetics and FASD• Epigenetics-’stable but potentially reversible

alterations of genetic information that result in changes in gene expression, but do not involve changes in the DNA sequence itself’ (6)

• PAE can reprogram neurobiological systems, altering developmental trajectories and resulting in increased vulnerability to adverse neurobiological, behavioural and health outcomes. (5)

Epigenetics and FASD• Adverse neurodevelopmental outcomes of children

with FASD often persist well into adulthood, including metabolic changes, autoimmune dysfunction and altered stress responsivity (5)

• More studies will help to develop epigenetic biomarkers of PAE which will help in early diagnosis but also may help discover targeted interventions (5)

Neuroimmune Function and FASD• Emerging data support that low to moderate levels of

PAE may reprogram the developing nervous system leading to altered neuroimmune and neuroglia signalling during adulthood (6)

• Moderate level= 1 drink a day (14 gms of ethanol)• PAE may lead to proinflammatory response

(hypersensitive) in adulthood after even mild physical trauma or infection and could lead to chronic pain, autoimmune disorders and cognitive impairment (6)

Maternal Nutrition and Prenatal Alcohol Exposure (PAE)

• maternal iron deficiency without PAE can lead to persistent neurodevelopmental deficits (7)

• Iron deficiency + PAE will magnify FASD symptoms • Maternal iron deficiency worsens PAE fetal outcomes• Maternal use of drugs and alcohol will disrupt her

absorption of many essential nutrients and therefore reduce availability to the fetus (8). Poor diet will intensify this and compound effects of PAE

Stigma• We know that Mothers do not want to deliberately hurt

their unborn babies

• Positive support from fathers, partners, family, society, doctors and government to encourage no drinking during pregnancy is required.

• Education of all is needed

Stigma/Blame• Culture of drinking, unplanned pregnancies and lack of

awareness of effects of alcohol on the fetus are major contributors to babies being born with FASD

• For some teens and women, alcohol addiction +/-poverty, abusive situations (past and present) can make stopping ETOH very difficult, at times impossible

• More is needed than just being told to stop drinking • Assigning blame to mothers is never helpful, nor fair

it is our collective responsibility

Health Monitoring and Education about FASD

• Good personal health record keeping from infancy onwards, including adverse responses to medications will help foster better health care into adulthood for those with FASD

• Education of the health community about the increased risks those with FASD have for early onset chronic illness is crucial for early intervention and treatment

References

1. Cook, J. L., Green, C. R., Lilley, C. M., Anderson, S. M., Baldwin, M. E., Chudley, A. E.,…Rosales, T. (2016a). Fetal alcohol spectrum disorder:

A guideline for diagnosis across the lifespan. Canadian Medical Association Journal, 188(3), 191-1972. Hoyme, H.E. et al (2016). Updated Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders.

Pediatrics. 2016 Aug;138(2):e20154256

3. Kable, J.A., Mukherjee, R.A.S. (2016). Neurodevelopmental disorder associated wit prenatal alcohol exposure(ND-PAE): A proposed diagnostic method of capturing the neurocognitive phenotype of FASD. European Journal of Medical Genetics, September 2016 http://dx.doi.org/10.1016/j.ejmg.2016.09.013

4. Popova, S. et al (2018). World Health Organization International Study on the Prevalence of Fetal Alcohol Spectrum Disorder (FASD) Canadian Component. CAMH April 2018 (www.camh.ca )

5. Lussier, A.A., Weinberg, J., Kobor, M.S. (2017).Epigenetics studies of fetal alcohol spectrum disorder: where

are we now? Epigenomics (2017) 9(3), 291-311. [reprints@futuremedicine.com]6. Noor, S., Milligan, E.D. (2018)

Lifelong Impacts of Moderate Prenatal Alcohol Exposure on Neuroimmune Function. Frontiers in Immunology, May 2018 www.frontiersin.org

7. Helfrich, K. K., Saini, N., Kling, P.J., Smith, S. (2018).Maternal Iron Nutriture as a Critical Modulator of FASD Risk in Alcohol-Exposed Pregnancies. Biochem Cell Biol. 2018 April; 96(2): 204-212. doi:10.1139/bcb-2017-02068. Sebastiani, G. et al. (2018). The Effects of Alcohol and Drugs of Abuse on Maternal Nutritional Profile during Pregnancy.Nutrients 2018, 10, 1008;doi:10.339/nu10081008 www.mdpi.com/journal/nutrients