Kenneth Lyons Jones University of California, San Diego Dysmorphology Core Kenneth Lyons Jones University of California, San Diego

Aim #1 Aim #1: To assure consistency as well as accuracy in recognition of Fetal Alcohol Spectrum Disorders (FASD) at all CIFASD project sites throughout the world. Deliverables: Since July 2013 I have examined 578 subjects in 5 different CIFASD sites including Atlanta, Georgia, Minneapolis, Minn., Los Angeles, CA, San Diego, CA, and 2 sites in Ukraine. To accomplish this goal the previously established CIFASD physical examination protocol and classification system is used to perform and/or validate physical examinations of all infants and children who were participants in the CIFASD renewal project and who were not previously examined by the Core examination team. On-going training and re-training of local pediatricians/neonatologists/geneticists who are performing preliminary examination at some CIFAS sites was done at all sites. In some sites, over the last year I have worked face-to-face with the local examiners to maintain quality of their physical examinations. In addition trainees at all the sites were frequently involved

Aim #1 Publications: Coles CD, Kable JA, Keen CL, Jones KL, Wertelecki W, Granovska IV, Pashtepa AO, Chambers CD; CIFASD. Dose and timing of prenatal alcohol exposure and maternal nutritional supplements: Developmental effects on 6-Month-Old Infants. Matern Child Health J. 2015 Dec;19(12):2605:14. Migliorini R, Moore EM, Glass L, Infante MA, Tapert SF, Jones KL, Mattson SN, Riley EP. Anterior cingulate cortex surface area relates to behavioral inhibition in adolescents with and without heavy prenatal alcohol exposure. Behav Brain Res. 2015 Oct 1;292:26-35. doi: 10.1016/j.bbr.2015.05.037. Epub 2015 May 27 Kable JA, Coles CD, Keen CL, Uriu-Adams JY, Jones KL, Yevtushok L, Kulikovsky Y, Wertelecki W, Pedersen TL, Chambers CD; CIFASD. The impact of micronutrient supplementation in alcohol-exposed pregnancies on information processing skills in Ukrainian infants. Alcohol. 2015 Nov; 49(7):647-56. doi: 10.1016/j.alcohol.2015.08.005. Epub 2015 Sep 25 Gautam P, Lebel C, Narr KL, Mattson SN, May PA, Adnams CM, Riley EP, Jones KL, Kan EC, Sowell ER. Volume changes and brain-behavior relationships in white matter and subcortical gray matter in children with prenatal alcohol exposure. Hum Brain Mapp. 2015 Jun;36(6):2318-29. doi: 10.1002/hbm.22772 Glass L, Ware AL, Crocker N, Deweese BN, Coles CD, Kable JA, May PA, Kalberg WO, Sowell ER, Jones KL, Riley EP, Mattson. Neuropsychological deficits associated with heavy prenatal alchohol exposure are not exacerbated by ADHD Neuropsychology. 2013 Nov;27(6):713-24

Aim #2 Aim #2: To develop a training DVD that could be used to teach physicians and other health care professionals with little or no experience in diagnosis of FASD to correctly identify the characteristic structural features of FAS through a physical examination and to successfully diagnose or rule out this disorder on that basis. Deliverables: - Eight 15 minute DVDs of children with the fetal alcohol syndrome - One DVD which focuses on diagnosis of (ND-PAE). - 10 question FAS Quiz given to five pediatric residents who completed their training by using the DVD exclusively and five who completed hands-on live training done by me. There was no difference between the two groups. - The AAP has agreed to provide a copy of the DVD to all 500 members of the San Diego Chapter for their review and comments. They have asked and we have agreed to transcribe it by streaming. . This will be streamed to them in mid-March and we are hoping to get feed-back from them by mid-April. -

FAS QUIZ 5. All but one of the following are non-cardinal features of FAS, but are seen more frequently In children with FAS than in the general population: - Hockey stick crease - Ptosis - Pre-auricular pit -- Railroad track ears   6.When measuring the left palpebral fissure it is helpful for the examiner to close her/his left eye. - True - False 7. In order to make a diagnosis of FAS, you need: - All 3 of the cardinal facial features - 2 of the 3 cardinal facial features - Just one of the 3 cardinal facial features 8. A feature that occurs more frequently in children with FAS , but is not one of the cardinal features of the disorder. Pick one: - Strabismus - Low set ears - Ocular hyperteloroism - Aberrant frontal hair pattern 9 .Evaluation of the effect of alcohol on fetal development can be solely accomplished through a careful physical examination by a pediatrician. 10. The effect of alcohol on fetal development occurs almost exclusively in the first trimester of pregnancy. 1. Which of the following are true? - Prenatal exposure to alcohol can result in a spectrum of defects. On one end of the spectrum is the fetal alcohol syndrome while on the other end of the spectrum are children who lack the physical features of FAS , but who have specific neurodevelopmental abnormalities referred to as alcohol related neurobehavioral defects (ARND). This is referred to as Fetal Alcohol Spectrum Disorders (FASD) - The primary effect of alcohol exposure on the developing fetus is the effect of alcohol on brain development - Many of the cardinal features of FAS are secondary to the effect of alcohol on brain development - All of the above 2. All but one of the following are critical for the diagnosis of Fetal Alcohol Syndrome (FAS): - Short palpebral fissures - Decreased innercanthal distance - Smooth philtrum - Thin vermillion border of upper lip 3. Measurement of the palpebral fissure is best done using a rigid ruler. - True - False 4 .Head circumference <3rd centile is required for a diagnosis of FAS.

FAS QUIZ Exclusively Hands on Training Exclusively From DVD 5/5 All the above 5/5 All the above 5/5 Decreased 5/5 Decreased inner-canthal inner-canthal distance distance 5/5 True 5/5 True 4/5 False 5/5 False 1. Which of the following are true? - Prenatal exposure to alcohol can result in a spectrum of defects. On one end of the spectrum is the fetal alcohol syndrome while on the other end of the spectrum are children who lack the physical features of FAS , but who have specific neurodevelopmental abnormalities referred to as alcohol related neurobehavioral defects (ARND). This is referred to as Fetal Alcohol Spectrum Disorders (FASD) - The primary effect of alcohol exposure on the developing fetus is the effect of alcohol on brain development - Many of the cardinal features of FAS are secondary to the effect of alcohol on brain development - All of the above 2. All but one of the following are critical for the diagnosis of Fetal Alcohol Syndrome (FAS): - Short palpebral fissures - Decreased innercanthal distance - Smooth philtrum - Thin vermillion border of upper lip 3. Measurement of the palpebral fissure is best done using a rigid ruler. - True - False 4 .Head circumference <3rd centile is required for a diagnosis of FAS.

Exclusively Hands on Training Exclusively DVD 5 Exclusively Hands on Training Exclusively DVD 5. 4/5 - pre-auricular pit 5/5 - pre-auricular pit 6. 4/5 - True 4/5 - True 7. 5/5 - 2 of the 3 cardinal 5/5 - 2 of the 3 cardinal facial features facial features 8. 5/5 – Strabismus 5/5 – Strabismus 9. 5/5 – False 4/5 - False 10. 5/5 – False 5/5 - False 5. All but one of the following are non-cardinal features of FAS, but are seen more frequently In children with FAS than in the general population: - Hockey stick crease - Ptosis - Pre-auricular pit -- Railroad track ears   6. When measuring the left palpebral fissure it is helpful for the examiner to close her/his left eye. - True - False 7. In order to make a diagnosis of FAS, you need: - All 3 of the cardinal facial features - 2 of the 3 cardinal facial features - Just one of the 3 cardinal facial features 8. A feature that occurs more frequently in children with FAS , but is not one of the cardinal features of the disorder. Pick one: - Strabismus - Low set ears - Ocular hyperteloroism - Aberrant frontal hair pattern 9 .Evaluation of the effect of alcohol on fetal development can be solely accomplished through a careful physical examination by a pediatrician. 10. The effect of alcohol on fetal development occurs almost exclusively in the first trimester of pregnancy.

Aim #3 Two phases: Deliverables: Aim #3: To develop a methodology whereby long-distance consultation can be provided to physicians and other health care providers in outlying areas throughout the world. Deliverables: Two phases: 1. Pilot Consultations: The remote physicians have the capability to film the physical exam and securely transmit them via the internet to me in San Diego for review and thereafter to schedule a consultation. For this consultation, the remote clinicians look at the participant documents and video at their site and I look at the same information on the secure repository at my site. In July 2015 this phase was successfully completed at the University of Minnesota where we are collaborating with Dr. Jeff Wozniak and was outlined in our last report.

Aim #3 Aim #3: Phase 2. Real-Time Consultations: This phase gives physicians and healthcare providers the capability to perform the examination and consult with me during a live session at the remote site in order to make the diagnosis of FAS or successfully rule out this disorder. Real-time consultations give clinicians in remote sites the benefit of interactive consultation with the patient present. We plan to have our first group of real-time consultations this spring. - Minnesota: The equipment was set up at the University of Minnesota site in September 2015. The equipment is portable and will be suitable for use at various sites served by the clinical staff working with Dr. Jeffrey Wozniak including Minneapolis as well as site in a remote area of the state of Minnesota. - Northern San Diego: We have had discussions with Dr. Dan Calac who is the Medical Director of the Indian Health Council (IHC) clinic in Northern San Diego County. Our discussions have been positive and we hope to use telemedicine to examine approximately one-hundred children as part of a Native-America prevalence study of FASD. The children will be evaluated at the IHC Clinic with a hand-held camera that we have already purchased. The images will be sent back to me in real-time in San Diego.

Aim #4 Aim #4: To document the prevalence of major malformations in children prenatally exposed to alcohol , and in so doing, delineate the extent of Alcohol Related Birth Defects (ARBD) Deliverables: Circumstances in Ukraine where we had planned to do this study have made this aim impossible to carry out. We are not able to collect information in the project timeframe to complete the aim

How Project Has Interacted with Rest of Consortium Specific Aim #1: To assure consistency as well as accuracy in recognition of Fetal Alcohol Spectrum Disorders at all CIFASD project sites throughout the world. - Relates to the aims of all other clinical projects in the CIFASD consortium. Without an accurate diagnosis it is impossible for the clinical projects to confidently interpret their data.

Novel Innovative Aims To assure consistency as well as accuracy in recognition of Fetal Alcohol Spectrum Disorders at all CIFASD project sites throughout the world. The telemedicine project will continue to require much time as I will now be a source for various projects set up in this iteration as well as others that I suspect will want to be included.

Three Priority Areas Prevention: Prevention of FASD involves pregnancy and I think we need to continue to have a cohort study to allow us to investigate ways to prevent this disorder Intervention: We need to investigate epigenetic factors that could lead to treatment as well  as other strategies that focus on intervention Stigma: Without decreasing stigma we will never get anywhere with helping parents (both biologic and adoptive), and children with this disorder. In addition we will never change the mind-set of obstetricians, and pediatricians so they will diagnose it appropriately, and we will never be able to change the mind-set of educators so they will be able to appropriately teach children with it.