Neurodevelopmental Disorders Associated with Prenatal Exposure to Alcohol

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Presentation from December 18, 2013 Chicago Board of Health Meeting by Carl C. Bell, M.D on Neurodevelopmental Disorders Associated with Prenatal Exposure to Alcohol.

Presentation from December 18, 2013 Chicago Board of Health Meeting by Carl C. Bell, M.D on Neurodevelopmental Disorders Associated with Prenatal Exposure to Alcohol.

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  • 1. Neurodevelopmental Disorders associated with Prenatal Exposure to Alcohol Carl C. Bell, M.D. Staff Psychiatrist – Jackson Park Hospital Family Practice Clinic Staff Psychiatrist – St. Bernard Hospital Inpatient Psychiatry Unit Former Director of the Institute for Juvenile Research (Birthplace of Child Psychiatry) Professor Psychiatry and Public Health Director of Public & Community Psychiatry – Department of Psychiatry University of Illinois at Chicago
  • 2. Triadic Theory of Influence         Sociological theories of social control and social bonding (Akers et al., 1979; Elliott et al., 1985) Peer clustering (Oetting & Beauvais, 1986) Cultural identity (Oetting & Beauvais, 1990-91) Psychological theories of attitude change & behavioral prediction (Fishbein & Ajzen, 1975; Ajzen, 1985) Personality development (Digman, 1990) Social learning (Akers et al., 1979; Bandura, 1977, 1986) Integrative theories (e.g., Jessor & Jessor's, Problem Behavior Theory; Brook’s Family Interaction Theory, Hawkins’ Social Development Theory) See Petraitis, Flay and Miller (1995).
  • 3. Cultural/ Attitudinal Stream Social/ Normative Stream Intrapersonal Stream
  • 4. Community Psychiatry Protective Factor Field Principles      Rebuilding the Village/Constructing Social Fabric Access to Modern and Ancient Technology Connectedness Social and Emotional Skills Self Esteem - Activities that create a sense of power; Activities that create a sense of connectedness; Activities that create a sense of models; Activities that create a sense of uniqueness   Reestablish the Adult Protective Shield/Safety Minimize the Effects of Trauma/Mastery
  • 5. Risk Factor - Culture Destroys Canada's monocultural ethnocentric culture had little value for First Nation culture.  Thus, First Nation children were removed from their families and told them their culture was not acceptable, resulting in First Nation people having to give up their cultural protective factors which ultimately led to many First Native people engaging in the risky behaviors of suicide and intra-group homicide. 
  • 6. Risk Factor - Culture Destroys Within these communities, alcoholism is common and for every one child in Canadian juvenile detention centers without fetal alcohol syndrome there are 19 children with fetal alcohol spectrum disorders (Popova et al, 2011).  Bell (2012) has proposed many disruptive behaviors leading to incarceration results from fetal alcohol exposure (FAE). 
  • 7. Risk Factor - Culture Destroys  Fetal Alcohol Exposure is the leading cause of speech and language disorders, ADHD, Specific Learning Disorders, & Mild Mental Retardation which are often responsible for affect dysregulation leading to disruptive behaviors leading to incarceration. Stratton et al. (1996). Fetal Alcohol Syndrome: Diagnosis, Epidemiology, Prevention, and Treatment. Washington, D.C. National Academy of Sciences, Institute of Medicine.
  • 8. ADHD on the Rise?    In 2011, 11% of children/adolescents aged 4 to 17 years had ever received an ADHD diagnosis (6.4 million children). Among those with a history of ADHD diagnosis, 83% were reported as currently having ADHD (8.8%); 69% of children with current ADHD were taking medication for ADHD (6.1%, 3.5 million children). A parent-reported history of ADHD increased by 42% from 2003 to 2011. Prevalence of a history of ADHD, current ADHD, medicated ADHD, & moderate/severe ADHD increased significantly from 2007 estimates. Prevalence of medicated ADHD increased by 28% from 2007 to 2011.
  • 9. ADHD on the Rise?    Conclusions: Approximately 2 million more U.S. children/adolescents aged 4 to 17 years had been diagnosed with ADHD in 2011, compared to 2003. More than two-thirds of those with current ADHD were taking medication for treatment in 2011. Visser, et al. Trends in the Parent-Report of Health Care Provider-Diagnosed and Medicated AttentionDeficit/Hyperactivity Disorder: United States, 2003– 2011. JOURNAL OF THE AMERICAN ACADEMY OF CHILD & ADOLESCENT PSYCHIATRY, in press – 2013 http://www.jaacap.com/article/S0890-8567(13)00594-7/a
  • 10. Risk Factor - Culture Destroys  Youth Risk Behavior Surveillance  The prevalence of having carried a weapon in general was higher among white males (27.2%) than among their black counterparts (21%).  The prevalence of having carried a weapon onto school property was higher among white males (7.8%) than black males (6.7%).
  • 11. Risk Factor - Culture Destroys The prevalence of having ever used cocaine was higher among white males (7.6%) than black males (4.2%).  Yet, people of color make up a higher proportion of children and young adults who are incarcerated.  In fact, in 2010, the imprisonment rate for black non-Hispanic males (3,074/100,000 U.S. black male residents) was almost seven times higher than it was for white non-Hispanic males (459/100,000) U.S. Bureau of Justice Statistics 
  • 12. Protective Factor - Culture Protects  While doing HIV prevention work in Durban, South Africa it was striking that 40 percent of the Zulu people were HIVpositive, 6 percent of the white South African people were HIV-positive, but only 1 percent of the Indian South African people were HIV-positive.
  • 13. The Critical Role of Self-Regulation   Neuroscience and behavioral research are converging on the importance of self-regulation for successful development Children who do not develop the capacity to inhibit impulsive behavior, to plan, and to regulate their emotion are at high risk for behavioral and emotional difficulties Bell CC & McBride DF. Affect Regulation and the Prevention of Risky Behaviors. Journal of the American Medical Association, Vol. 304, No. 5: 565 –566, August 4, 2010
  • 14. Prevalence of FASD  Fetal Alcohol Syndrome (FAS) occurs far more frequently than generally believed: FAS: 1 per 1000 live births  Although estimates vary widely, when combined with the milder afflictions of Fetal Alcohol Spectrum Disorders (FASD), the Centers for Disease Control puts the frequency of FAS/FASD as high as one in 100.
  • 15. Prevalence of Drinking while Pregnant In the US 13% knowingly drink while pregnant  1% drink heavily while pregnant  3-4% binge drink during pregnancy (SAMHSA)  12% of pregnant women consume 5 or more drinks per month  50% of pregnancies are unplanned 
  • 16. Case History A 31 year old Black male presented with a CC of being handicapped all of his life and more recently he has gotten out of control (per mother’s report as patient was too intellectually disabled and suffering from speech preservation so he could not give a revealing HPI much less any PH. I had seen the patient last year and tried some Sertraline and Benadryl but they did not help. Mother reports that she recently picked up a foster son and her 31-year old son is jealous (she does not know why) and he is seriously choking
  • 17. The Case History patient has previously been on Clonidine 0.1mg BID, Propranolol 10mg BID, Olanzapine 10mg BID, and Clonazepam 0.5mg BID without any positive change in the patient’s behavior or mentation. He was groomed, cooperative but confused. His mood was bland & his affect was flat. He had perseveration, was easily distractible, & had severe memory impairment. DX – Pervasive Developmental Disorder and Intellectual disability from fetal alcohol exposure. Mother drank while pregnant.
  • 18. Case History The mother called to report that her son had really gotten violent & agitated – kicking over chairs and choking the 14-year old I told her to give him Omega – 3 twice a day; she reported she knew what that was because she and her husband were taking it for their health. Three months later the patient returned and presented continuing to have poor insight, and perseveration (the Miami Heath beat the Bulls) – however he was no longer violent 
  • 19. The Critical Role of Self-Regulation     1979 – 55% (151) of the 274 children in Pupil Service Center on Chicago’s Southside FAE 1985 – 20% of inmates in Texas Department of Corrections were “mentally retarded.” 2011 - chart audit on 162 children in several nursebased school clinics estimates 39% (63) of those children met the DSM-5 Condition for Further Study “Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (NDA-PAE) 2012 prior to the closure of the Community Mental Health Council, Inc. - chart audit of 330 randomly selected patients revealed that 12% (39 of 330 patients) met criteria for NDA-PAE.
  • 20. The Critical Role of Self-Regulation   2013 - work on an inpatient psychiatric unit at St. Bernard Hospital (in the heart of Englewood - one of the poorest African-American communities in Chicago) reveals of 93 patients consecutively admitted patients, 32% (30) meet the criteria for NDA-PAE. 2013 - a random sample of 20% of consecutively seen outpatients in Jackson Park Hospital's Family Practice Clinic reveals that out of 100 patients, 29% (29) fit the criteria for NDA-PAE
  • 21. Prenatal Choline     Newborn rats prenatally exposed to alcohol exhibited reduced birth weight and brain weight, delays in eye opening and incisor emergence, and alterations in the development of all behaviors. Choline supplementation significantly attenuated ethanol’s effects on birth and brain weight, incisor emergence, and most behavioral measures. In fact, behavioral performance of ethanol-exposed subjects treated with choline did not differ from that of controls. Thomas et al. Prenatal choline supplementation mitigates the adverse effects of prenatal alcohol exposure on development in rats Neurotoxicol Teratol. 2009 ; 31(5): 303–311.
  • 22. Postnatal Choline Animal Model Thomas J et al. (2007). Choline Supplementation Following Third-TrimesterEquivalent Alcohol Exposure Attenuates Behavioral Alterations in Rats. Behavioral Neuroscience  Giving choline to infants who were exposed in the womb to alcohol may mitigate some of the resulting problems. 
  • 23. Postnatal Choline Animal Model At San Diego State University, research led by Jennifer Thomas, PhD, is using an animal model to assess the potential therapeutic value of choline.  Because scientists have been unable to determine a safe threshold for alcohol consumption during human pregnancy, abstention is the only sure means of prevention.  However, warnings about the dangers of drinking during pregnancy either don’t reach or 
  • 24. Postnatal Choline Animal Model As a result, researchers are seeking effective remedies to give after birth, when health professionals may be better able to intervene.  Choline plays a number of roles in brain development & is a precursor to acetylcholine, a neurotransmitter involved in learning and cognition, among other functions.  Choline is available in many foods, such as eggs and liver, and sold over the counter in well-tolerated forms such as lecithin, choline bitartrate or chloride, and phosphatidylcholine. 
  • 25. Postnatal Choline Animal Model The current study of 170 rats found that giving choline to rat pups exposed to alcohol during the equivalent of the third trimester, when there’s a spurt in brain growth, significantly reduced the severity of alcohol-related overactivity and spatial learning deficits.  The benefits lasted months after choline treatment, suggesting that choline’s effects are long-lasting, say the authors. 
  • 26. Postnatal Choline Animal Model Various doses of choline were equally effective, so the researchers think that at least for the rat, as little as 10 mg/kg of weight per day could be effective.  Thomas and her colleagues would next like to determine how choline helps and to assess how late in development it can reduce fetal alcohol effects.  If choline is to be used clinically, it’s important to know when treatment works best. 
  • 27. Postnatal Choline Animal Model The current study demonstrates the benefits of postnatal choline in rats, making it potentially more useful given the realities of drinking during pregnancy.  Thomas and her colleagues are conducting clinical studies of postnatal choline on humans affected by prenatal alcohol exposure.  If the current results with rats are replicated in humans, then infants born to mothers who drank when pregnant might benefit from supplemental choline. 
  • 28. Postnatal Choline Animal Model The authors conclude that extra choline "can alter brain development following a developmental insult.  Early dietary interventions may reduce the severity of some fetal alcohol effects, even when administered after birth."  Importantly, the animal data suggest that although early postnatal choline can reduce learning deficits and hyperactivity following early alcohol exposure, it doesn’t help reduce motor coordination deficits. 
  • 29. Postnatal Choline Animal Model Thomas cautions, "Choline is not going to be a panacea for all symptoms of fetal alcohol spectrum disorders. Women need to be continually reminded of the damaging effects of alcohol on the developing fetus."  Previous studies by other researchers have shown that prenatal choline supplementation in rats influences development of the nervous system, especially the brain’s cortex and hippocampus. 
  • 30. Postnatal Choline Animal Model Due to choline’s beneficial effects on nervoussystem development, women are advised to consume 450 mg a day while pregnant and 550 mg a day while breast feeding (the tolerable upper limit has been set at 3.5 g per day).  For infants, 125-150 mg/day is considered adequate during the first year, rising as the child grows older.  Choline is added to some prenatal vitamins and baby formulas, and is now added to some children’s multivitamins and cereals. 
  • 31. Postnatal Choline Wozniak et al. Post-Natal Choline Supplementation in Children with FASD: Preliminary Safety and Efficacy Results; University of Minnesota  Pilot study of 20 children with FASD, ages 2.5 to 5 years, who were randomly assigned (double blind) to placebo or 500mg choline supplementation per day for 9 months  Plasma choline levels increased by 105% at month 1 and remained elevated at 6 months (105%) and 9 months (102)  Tolerability was high with 17 participants completing the study. 
  • 32. Postnatal Choline By 6 months, the choline group showed a 9.9% increase in delayed sequential memory (a hippocampally dependent measure) compared to the placebo group which showed only a 2.2% increase (effect size 0.42).  In the choline group, earlier age at enrolment was associated (non-significantly ) withy greater improvement in memory.  At 9 months, global cognitive functioning (Mullen Scales) was increased by 8.6 points in the choline group vs. 4.3 points in the placebo group (effect size = 0.29). 
  • 33. Postnatal Choline  The greatest improvement on the Mullen was in fine motor skill (7.1 points for the active group vs 1 point for the placebo group, effect sixe = 0.59).
  • 34. Postnatal Choline Thomas J, et al. Choline Supplementation in Children With Fetal Alcohol Spectrum Disorders; San Diego State University  Randomized, Control Trial in 5 – 10 year olds  Changes in cognitive function as measured by performance on neuropsychological tasks of learning/memory, executive functions, and attention  Children's Behavior Checklist (CBCL), Behavioral Rating Inventory of Executive Function (BRIEF) - Baseline and 6 weeks; Parent questionnaires about children's behavioral functioning will assess changes. 
  • 35. The Critical Role of Self-Regulation     1979 – 55% (151) of the 274 children in Pupil Service Center on Chicago’s Southside FAE 1985 – 20% of inmates in Texas Department of Corrections were “mentally retarded.” 2011 - chart audit on 162 children in several nursebased school clinics estimates 39% (63) of those children met the DSM-5 Condition for Further Study “Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (NDA-PAE) 2012 prior to the closure of the Community Mental Health Council, Inc. - chart audit of 330 randomly selected patients revealed that 12% (39 of 330 patients) met criteria for NDA-PAE.
  • 36. The Critical Role of Self-Regulation   2013 - work on an inpatient psychiatric unit at St. Bernard Hospital (in the heart of Englewood - one of the poorest African-American communities in Chicago) reveals of 93 patients consecutively admitted patients, 32% (30) meet the criteria for NDA-PAE. 2013 - a random sample of 20% of consecutively seen outpatients in Jackson Park Hospital's Family Practice Clinic reveals that out of 100 patients, 29% (29) fit the criteria for NDA-PAE
  • 37. People with fetal alcohol exposure (FAE) have several characteristics Mild mental retardation, specific learning disorders, speech and language deficits and ADHD as evidenced by special education in grammar and high school (FAE is the leading cause of such problems).  Explosive emotionality - quick to get frustrated and sometimes with an explosive temper yet these affective outbursts do not last long and are wrongfully referred to as moods when the reality is their mood is 
  • 38. People with fetal alcohol exposure (FAE) have several characteristics Most of the time such folk are very childlike and naïve and they really want people to like them because they have been ostracized most of their lives because they are "slow.“  Patients have very poor judgment, planning ability, capacity to foretell consequences of their behavior, etc.  Patients have difficulty doing simple math, e.g. serial 7s - you know 100-7=; 93-7=; 867=; 79-7=; 72-7=; 65-7. 
  • 39. People with fetal alcohol exposure (FAE) have several characteristics Patient often complains of being diagnosed as bipolar, depressed, and schizophrenic.  Patients are often on a wide variety of medications that may or may not be helpful.  Patients may continue to have the characteristic facial characteristics of FAE wide apart set eyes, epicantal folds in their eye lids, flat mid face, short palpebral fissures, no philthrum or a very indistinct philthrum, small chin, funny shaped ears, and a small head - of course these features go away as the child 
  • 40. People with fetal alcohol exposure (FAE) have several characteristics The range of fetal alcohol exposure varies widely in people so that is why the growing way of describing it as FASD (Fetal Alcohol Spectrum Disorder).  You have to remember that the fetal brain is developing for 9 months so there are multiple opportunities for the alcohol to denature the choline, Vitamin A, and folate in the body that causes the lack of these nutrients to damage DNA, chromatin and RNA causing various forms of brain damage. 
  • 41. People with fetal alcohol exposure (FAE) have several characteristics  There is growing evidence that by having a good diet with choline bitartrate 650 ucg BID (Puritan’s Pride 200 for $10.99), Vitamin A 25,000 IU daily (Swanson 300 for $5.69), and folate 800 mcg (Swanson Ultra 30 for $5.00), the effects of FAE may be reversed in utero, possibly may also be ameliorated post delivery, and may even correct some of the problems in adults who had FAE when fetuses.
  • 42. DSM – 5: Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure  A. More than minimal exposure to alcohol during gestation, including prior to pregnancy recognition – Confirmation of gestational exposure to alcohol may be obtained from maternal self-report of alcohol use in pregnancy, medical or other records, or clinical observation.  B. Impaired neurocognitive functioning as manifested by one or more of the following: 1.Impairment in global intellectual performance (i.e. IQ of 70 or below) 2.Impairment in executive functioning (e.g. poor planning and organization, inflexibility, difficulty with behavioral inhibition)
  • 43. DSM – 5: Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure  B - Impaired neurocognitive functioning as manifested by one or more of the following: 3. Impairment in learning (e.g. lower academic achievement than expected for intellectual level; specific learning disability) 4. Memory impairment (e.g. problems remembering information learned recently; repeatedly making the same mistakes; difficult remembering lengthy verbal instructions) 5. Impairment in visual-spatial reasoning (e.g. disorganized or poorly planned drawings or constructions; problems differentiating left from right)
  • 44. DSM – 5: Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure  C. Impaired self-regulation manifested by one or more of the following: 1. Impairment in mood or behavioral regulation (e.g. mood liability,; negative affect or irritability ], frequent behavioral outbursts). 2. Attention deficit (e.g. difficulty shifting attention; difficulty sustaining mental effort). 3. Impairment in impulse control (e.g. difficulty waiting turn; difficulty complying with the rules).  D. Impairment in adaptive functioning as manifested by two or more of the following, one of which must be (1) or (2): 1. Communication deficit (e.g. delayed acquisition of language; difficulty understanding spoken language) 2. Impairment in social communication and interaction (e.g., overly friendly with strangers, difficulty reading social cues; difficulty understanding social consequences)
  • 45. DSM – 5: Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure  D. Impairment in adaptive functioning as manifested by two or more of the following, one of which must be (1) or (2): 3. Impairment in daily living skills (e.g. delayed toileting, feeding, or bathing; difficulty managing daily schedule) 4. Impairment in motor skills (e.g., fine motor development; delayed attainment of gross motor milestones or ongoing deficits in gross motor function; deficits in coordination and balance.  E. Onset of disorder (symptoms in Criteria B, C, and D) occurs in childhood.
  • 46. DSM – 5: Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure   F. The disturbance causes clinically significant distress or impairment in social, academic, occupational or other important areas of functioning. G. The disorder is not better explained by the direct physiological effects associated with postnatal use of a substance (e.g. medication, alcohol or other drugs); medical condition (traumatic brain injury, delirium, dementia);
  • 47. IDEAS TO COMBAT THE EFFECTS OF FAE Do public service announcements to grandmothers who are care giving for grandchildren who have learning disorders, mild intellectual disability, ADHD, speech and language disorders, explosive tempers and who know their daughters or daughters-in-law were drinking during pregnancy.  Have correctional facilities who incarcerate pregnant women screen those women for drinking while pregnant before they knew they were pregnant. 
  • 48. IDEAS TO COMBAT THE EFFECTS OF FAE Psychiatric Services (11-15-13) “less than half of American teens with mental health disorders receive treatment, and those who do get help rarely see a mental health specialist.”  “analysis of data from more than 10,000 teens aged 13 to 17 across the” US revealed that “teens with ADHD, conduct disorder or oppositional defiant disorder received mental health care more than 70 percent of the time, while those with phobias or anxiety disorders were least likely to be treated.” 
  • 49. OTHER ROUTES OF TRANSMISSION?  I was talking to a woman who did not drink when pregnant but who's son has all the signs of fetal alcohol exposure (I am now asking parents who are patients about their children to see if they drank while pregnant) and she told me that the father of her child (who is now dead) also had all the symptoms that her son has and how she learned that he was in special education after they had had their son.
  • 50. OTHER ROUTES OF TRANSMISSION? That sparked off a much more scary idea that it is possible that if the father of her child had fetal alcohol exposure and it damaged his DNA, RNA and histones whether or not that acquired biologic genetic damage might not be transmitted from father to son in his sperm?  If so then the question of the mother's drinking while pregnant is important but there may be another route of transmission. 
  • 51. OTHER ROUTES OF TRANSMISSION? Paternal alcohol consumption – expression of a key enzyme catalyzing DNA methyelation – called DNA methyltransferase 1 (DNMT1) was reduced in the sperm of paternal rats after 9 weeks of chronic alcohol exposure.  Analysis of methylation patterns of sperm DNA from human volunteers showed a correlation between chronic alcohol use and demethylation of DNA regions that normally show particularly high methylation.. 
  • 52. OTHER ROUTES OF TRANSMISSION?  Transmission of these epigenetic changes to the offspring through fertilization possibly could alter gene expression in the fetus, thus affecting prenatal development. – Kobor MS, Weinberg J. Epigenetics and Fetal Alcohol Spectrum Disorders. Alcohol Research and Health, Vol. 34 (No. 1): http://pubs.niaaa.nih.gov/publications/arh341/29-37.h – Ramsay M. Genetic and epigenetic insights into FASD. Genome Medicine 2012, 2:27 http://www.biomedcentral.com/content/pdf/gm148.pdf
  • 53. IDEAS TO COMBAT THE EFFECTS OF FAE Educate Obstetricians about the damage FAE can do and suggest to them that choline supplements may decrease the outcome of FAE exposed children (let them know that prenatal vitamins do not have choline in them).  Work with Chicago Public Schools to identify children in special education who have the characteristic histories of FAE, and have their parents supplement those children’s nutrition with choline, folate, and vitamin A. 
  • 54. IDEAS TO COMBAT THE EFFECTS OF FAE Work with Cook County Detention Center to identify children in their facility who have the characteristic histories of FAE, and supplement those children’s nutrition with choline, folate, and vitamin A.  Get in touch with the Illinois Department of Children and Family Services and have them to identify children in their facility who have the characteristic histories of FAE, and supplement those children’s nutrition with choline, folate, and vitamin A. 
  • 55. IDEAS TO COMBAT THE EFFECTS OF FAE Get vitamin companies to put choline in their prenatal vitamins.  Get Walgreens to supply choline supplements in their stores.  Get Phillip Jackson of the Black Star project on it.  Others? 