Fetal Alcohol Spectrum Disorders

1. Fetal Alcohol Spectrum Disorders Beth Conover, MS, APRN Genetic Counselor and Nurse Practitioner Assistant Professor, MMI Director Nebraska Teratogen Information Service 402-559-5071 bconover@unmc.edu

2. Disclosure Information 2018 Speaking of Children Conference Fetal Alcohol Syndrome Disorders Beth Conover • I have no financial relationships to disclose.

3. Munroe Meyer Institute, UNMC

4. Nebraska TIS @MotherToBaby NE • Service– Toll-free phone consultation to patients or health care providers about exposures during pregnancy • Education– to public and academic groups, including medical, nursing, genetic counseling, pharmacy and others • Research – collaborative projects looking at outcomes of exposures to specific agents

5. Alcohol • Pregnancy loss • Fetal Alcohol Syndrome: • Growth retardation • Central nervous system anomalies and dysfunction • Characteristic facial features • Malformations • Binge drinking (4 or more drinks on occasion may be at least as risky as daily use of moderate amounts • Concentration in breastmilk is equal to maternal blood concentrations; more than one drink a day may cause infant drowsiness & delays Conover EA, Jones KL. 2012. Safety concerns regarding binge drinking in pregnancy. Birth Defects Research (Part A) 94:570-575.

7. Prenatal Case • A 21 year-old pregnant woman, Lisa, comes to clinic for her first prenatal visit. She found out she was pregnant one week ago by using an at-home pregnancy test. The first day of her last menstrual cycle was 5 weeks ago. • She is concerned because she was at a party 3 weeks ago and consumed 6 mixed drinks, predominantly rum mixed with coca-cola.

8. Questions: Do the timing and level of drinking in this case meet the threshold for dangerous prenatal alcohol exposure? How would you counsel the patient regarding the risk to the embryo in this scenario? If the event was repeated in the first trimester, how would the risk change? If the event was repeated in the second trimester, how would the risk change?  

9. A 3 year-old female, Maria, is brought in for evaluation for possible FASD. She is accompanied by a foster parent who has limited knowledge regarding Maria’s mother and her pregnancy. She brings records that state the following: • “Maria was removed from the home at age 2 years after it was witnessed that the mother and father were using methamphetamine in her presence. Hair samples from Maria tested positive for the drug. Maria was then returned to the parents’ care after a drug monitoring plan was put in place. At 2 years 3 months, during a home visit, a case worker observed the biological mother giving Maria a bottle that was later determined to contain vodka. The mother was tested and found to have a blood alcohol concentration of 0.385 mg/L. Maria was then removed for the final time from the home. Maria’s mother then entered a substance abuse program. Unfortunately, she failed to complete the program and continues to abuse alcohol and methamphetamine. Maria has a brother whose cord blood was positive for methamphetamines (Maria did not have cord blood testing). Maria’s mother has mental health issues and needed extra help in school; little is known of Maria’s father except that he died unexpectedly of unknown causes. • Maria walked at 14 months, but has speech and language delays and is receiving speech therapy. She reportedly has ‘meltdowns’ when she does not get what she wants. • Growth parameters for Maria (height, weight, and head circumference) are normal. Physical examination shows no abnormalities. Palpebral fissure length is at the 25th centile. Lip is a grade 3 and philtrum is a grade 2.

10. Goals for today’s presentation: • Review principles of teratogenesis (agent, dose, timing) • Define Fetal Alcohol Syndrome Disorders and their prevalence • Explore prenatal risk assessment associated with maternal drinking • Explain the process of evaluating a child who may have a FASD • Explore cognitive and behavioral aspects of FASD including risk for involvement in the criminal justice system • Consider strategies for treatment • Apply your knowledge to case examples

11. Variables Affecting Teratogenic Impact • Timing of exposure • 1st trimester—miscarriage, malformations (high sensitivity days 18-60) • 2nd and 3rd trimester—pregnancy viability, CNS growth and maturation, fetal growth • Perinatal—problems with newborn adaptation • Dose • Some drugs have a threshold of teratogenicity • As a general rule, the higher the dose, the higher the risk to the fetus

12. Paternal Exposures • Sperm develop over 90 day time period • Possible effects: • -DNA mutations or chromosome breaks (chemo, radiation) • -Alterations to fertility • -Excreted in semen, absorbed by woman, directly affects fetus • -??? Affects methylation • Poorly studied, but little evidence male exposures cause birth defects

13. Constraints in Teratogen Risk Assessment • 3% background risk • Bias of ascertainment • Difficulty extrapolating from animal data • Few agents studied in combination • Confounding factors: poor prenatal care, maternal nutrition, maternal illness, polytherapy

14. Methamphetamine • Animal studies regarding malformations and behavioral alterations are inconsistent. • In humans, most studies do not show a significant risk for malformations • 3rd trimester use associated with low birth weight, prematurity, and withdrawal symptoms (jitteriness, drowsiness, and respiratory distress) • Possible long term impact on cognition and behavior; area of study.

15. Marijuana • Today’s mj may be up to 20x more potent than in the past. Very little data on high potency exposures! • Conflicting reports with regard to teratogenicity--minimal risk for birth defects, but some evidence of subtle behavioral changes • Chronic use in 3rd trimester may cause problems with newborn adaptation • In some cases is "cut" with more dangerous agents • THC excreted in breast milk

16. Prescription Narcotics • The number of painkiller-addicted newborns tripled between 2000 and 2009 • Methadone • Oxycontin • Vicodin • Risk for malformations low, but Neonatal Abstinence Syndrome (tremors, irritability, respiratory distress, diarrhea) is a big problem

17. Inheritance of Addiction • Biological reason for addiction poorly understood • Many studies have observed that addiction “runs in the family”. May be “addiction genes” or related to depression, bipolar disease, or ADHD • 25% risk for male children of alcoholics to develop addiction • 5-10% risk for female children of alcoholics to develop addiction

18. Prevalence of Prenatal Alcohol Exposure • Almost 40% of American women are abstinent • ~14% of women drink more than 6 drinks when they drink (“bingeing”) • ~4% have alcohol abuse or alcohol dependence problems. • 2016 MMWR Report: The weighted prevalence of alcohol-exposed pregnancy risk among U.S. women aged 15–44 years was 7.3%. During a 1-month period, approximately 3.3 million women in the United States were at risk for an alcohol-exposed pregnancy. Morbidity and Mortality Weekly Report. 2016;65(4):91-97

20. CDCFAS Criteria

21. Fetal Alcohol Spectrum Disorders (FASD) • FASD are conditions caused by the mother's intake of alcohol during pregnancy. These disorders can be mild or severe, and can affect physical and intellectual/behavioral problems. The spectrum of alcohol-related diagnoses includes: • Fetal Alcohol Syndrome (FAS) • PFAS (Partial Fetal Alcohol Syndrome) • ARND (Alcohol Related Neurodevelopmental Disorder) • ARBD (Alcohol Related Birth Defects • All of these birth defects are entirely preventable and can happen to anyone, regardless of age, race or socioeconomic status.

23. Why is there a spectrum of effects? • Timing and Dose • Higher levels of alcohol early in pregnancy (ex. binge drinking) increase the chances for facial changes and birth defects • Chronic low level alcohol use can also result in FASD • Exposure later in pregnancy is more likely to affect growth and brain development • Genetic factors affecting metabolism of alcohol • Maternal nutritional status

24. Prevalence of FASD

25. Assessment for FASD • Pregnancy history and maternal risk factors • Developmental and medical history • Height, weight and head circumference • Dysmorphology exam • Neurocognitive testing • In some cases, genetic testing to rule out other conditions

26. ½ Oz. Absolute Alcohol = Standard Drink . .

27. How much is too much?

28. Forebrain development induces development of facial features derived from neural crest

29. Palpebral Fissure Length • Plot measurements • Short PFL defined as <10th centile • Avoid gestalt diagnosis (you can be fooled)

30. Lip and Philtrum Assessment • Ensure the patient has a neutral expression • Smiling will falsely increase the score • Place guide alongside face • Score lip and philtrum separately • 4 or 5 is considered positive

32. CNS Abnormalities • Structural: • Structural brain abnormalities (MRI) • Head circumference less than 10th percentile • Non-febrile seizures • Cognitive/Behavioral: • Below average intelligence • Hyperactivity • Attention deficits • Language dysfunction • Perceptual difficulties

33. Using Artificial Intelligence in the Diagnostic Evaluation

34. Face2Gene in Clinic

35. What about ARND? • ARND (requires both A and B, cannot be diagnosed in children less than 3 years) • A. Documented prenatal alcohol exposure • B. Neurobehavioral impairment • With cognitive impairment • With behavioral impairment without cognitive impairment

37. FASD is a ‘diagnosis of exclusion’ • The characteristics seen in alcohol are not unique to FASD, and are seen in individuals with genetic conditions or other non-alcohol related causes • Thus far, none of the characteristic features of FASD are ONLY seen in FASD • In most cases, especially if there is significant intellectual disability, it is necessary to first rule out other conditions that would better explain the features seen in the child.

38. Genetic Testingkaryotype, microarray, gene sequencing

39. Behavior and Cognition

41. Infants and Children with FASD • Difficult to feed • Poor sleeper • Highly irritable • Hyperactive • Developmental delays

42. Children with FASD: learning and behavioral problems • Deficiencies in learning language and language use, especially receptive language • Difficulty generalizing information • Problems with mastering new or recently learned skills • Issues with memory (ie. remembering something from a year ago but not from yesterday) • Difficulty predicting outcomes or cause and effect • Problems distinguishing fact from fantasy • Challenges in distinguishing friends from strangers • Lack of learning from experience because they may not understand cause and effect, behavior and experience

43. Characteristics of Teens/Adults with FAS • Poor judgment • Poor impulse control • Criminal behavior • Sexual promiscuity • Restlessness • Poor problem-solving skills • Resistance to change • Difficulty forming relationships • Naiveté, gullibility Difficulty concentrating on tasks • Poor understanding of social norms

44. Adults with FASD • Adults with FASD continue to have the same learning difficulties they had as youth, and may also often have difficulty with: • the legal and court system, due to lack of understanding of cause and effect • controlling alcohol consumption • maintaining custody of their children • mental health issues

45. FASD: Co-occurring Conditions • Most persons with FASD have some degree of attention deficit and attachment disorders. • Sometimes individuals with FASD are diagnosed with other conditions, such as Asperger's Syndrome (mild Autism), depression, Tourette's syndrome, pervasive developmental disorder (PDD), Oppositional Defiant Disorder (ODD), Obsessive-Compulsive Disorder (OCD), Sensory Integration Disorder (SID), Reactive Attachment Disorder (RAD), Bipolar disease, or other psychiatric conditions. • These could be misdiagnoses, or these conditions might occur along with FASD. When FASD is diagnoses, sometimes other conditions are missed.

46. www.thearc.org/NCCJD

47. FASD and the Criminal Justice System www.nofas.org

48. FASD Treatment • There is no cure for FAS. However, treatment for symptoms is encouraged. “Treat the child not the diagnosis” (interventions are rarely specific to FASD). • Treatments for FASD include: • a loving and stable home situation • medical care • appropriate use of medication (antidepressants, stimulants, neuroleptics, antianxiety drugs) • educational and behavioral services. • Prevention is cheaper, easier, and more compassionate!

50. Medications • Treatment in FAS may include SSRI’s such as Prozac or Zoloft, and stimulants such as Ritalin. • Little is known about whether certain medications work better in individuals diagnosed with FAS • Herbal products such as St. John’s Wort have been poorly studied with regards to treating symptoms of FAS