25th미국기형학회 보고 - 한정열 센터장

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25th미국기형학회 보고 - 한정열 센터장

  1. 1. 25th International Conference Organization of Teratology Information Specialists Korean Motherisk Program JUNG YEOL HAN In Baltimore 2012
  2. 2. Contents 25th OTIS Conference Visit of Motherisk Program Vision of KMRP
  3. 3. 25th OTIS Conference
  4. 4. Patient’s Perception of Teratogenicrisks- Effects on Compliance By G.Koren Dental x-ray VAS EDPS > 13 : high risk of Termination of pregnancy Depression: 3-5% of pregnancy, suicide think : 32%
  5. 5. EDPS(Edinburgh postnatal depression scale)
  6. 6. TIS adapting to New Economic Realities and How it will Affect Research by Dee Quinn  History of TIS : 1979 : 1st TIS at UCSD 1985 : 1st meeting in Philadelphia 1990 : Formation of OTIS in Salt Lake City 1999 : Incorporation of OTIS in Montreal 2003 : Start of OTIS national Program 2011 : OTIS & ENTIS Collaboration  Economic evaluation & study : asthma, autoimmune ds Low dose MTX study  1992 : 38 in USA & Canada / 2000 - 2012 : 10 closed  Source funding?
  7. 7. An Epidemiological Enterprise : From Fluoride to Folate by JD Ericson of CDC Vietnam war veterans: herbicides(Agent orange) & Spina bifida ( 1996 law ) Interview : multivitamin use – lower risk Periconception multivitamine study : S. bifida, VSD, ASD, CL+CL
  8. 8. An Epidemiological Enterprise : From Fluoride to Folate Intervention Study in China : USFDA : require fortification of folic acid (25 states National birth defect prevention networks) Increased colorectal cancer : decrease by adjusting age Cognitive issues Methylation & epigenetics
  9. 9. The All or None Phenomenon : How should we counsel ?By Dr. BrentMouse vs Human Preimplantation period (수정 후 2주 이내) Usually not susceptible period to teratogen Some highly susceptible period to teratogen Surviving embryo : similar outcome
  10. 10. 예외: Long half life Teratogenic infectious agent Maternal effect(large exposure) Epigenetic effect Mutagenic effectMouse data 이용 상담 : no thanks by Brent.
  11. 11. By JM Friedman6days : implantation begin Very little data Chronic exposure Few accumulative exposure situationCzeizel : Hofpp study 24-42days of LMP : Exposure vs Non-exposure Live birth 92% - BW 3,222 3,268 Anomaly 3.3% -
  12. 12. IVF/ICSIAngelman SD/ Beckwith-Wiedemann syndrome -- inconsistent , absolute risk <1%동물 :Most agents : no effectSome agents : increased malformation
  13. 13.  Zygotic induced anomaly hydrops 22% Bent limbs 24% Abdominal wall defect 17% ---- multifactorial birth defects strikingly absence of other common anormaly ( NTD, CHD…) hydrops may be pathogenic , but mechanism is unknown Post-zygotic period : zygote와 다름 , Death more commonAnswer by JD Friedman: We don’t know Counseling : never say : “All or none” But, risk is very low
  14. 14. Strategies of Reducing the impact of Known teratogen The potential benefit of a Multi-micronutrient Supplementation in Pregnant women who consume Alcohol by Christina D. Chambers : Choline (precursor molecule for the neurotransmitter acetylcholine) Alcohol : CNS의 acetylcholine inhibitor RCT : Alcoholic pregnant women 300(control)/150(choline) f/u : 6mo, 12mo FASD : decreased in choline group Next step “ 5세 (preschool neurobehavioral test)
  15. 15.  Thyroid Hormone to Reduce Impact of Gestational Alcohol use in the rat by EE Redei 가설 : Thyroid function abnormal--- like FASD Maternal T4 administration – FASD 경감 Dio3 gene : epigenetic effect  Antiepileptic drugs : Cellular, Physiological, and behavioral evidence of developmental Neurotoxicity by KN Gale Phenobarbital, phenytoin, lamotrigine --- neurobehavioral abnormal - brain growth에 영향(neuronal cell death induction) , But FA 완화 Future direction : “Antidote” Epilepsy + AED + Antidote : reduce of risk of Adverse pregnancy outcome === AED use 증가( more compliance)
  16. 16. Thomas Sheperd Lecture“ The future of Research : The View of NICHD “ by AE Guttmacher (NICHD director)NICHD : 50 yrs celebration ( 1962 : President Kennedy sign) The mission :  every person is born healthy  women suffer no harmful effects from reproductive processes  all children have the chance to achieve their full potential for healthy and productive lives, free from disease or disability,  health, productivity, independence, and well-being of all people through optimal rehabilitation
  17. 17. NICHD study : Reproduction Developmental biology Pregnancy : biomarker Early origin of health and disease, growth, development : association is not equal to mechanism placenta , multigenerational effect Conduct of science trans -disciplinary science omics( genome, epigenome) training
  18. 18. OTIS 25th Anniversary SessionBy G. Koren : OTIS early challenges & future opportunities Abuse of drugs and alcohol Folic acid Occupational exposure Infection Pharmacogenomics methyl mercury Drugs & breastfeeding Biomarker : hair/meconiumBy Tina : OTIS & NOFAS: partners in preventing birth defectBy M Kisor : Parents & OTIS – One mother’s experience with OTISBy L Morrison : Birth defects prevention, risk reduction, and Awareness ActBy G. Koren : A model of industry-Academia collaboration for drugs in pregnancy
  19. 19. Pregnancy registry workshop What should pregnancy registries use for a comparison group(s)? Pregnancy registries and REMS: opportunities for collaboration risk (Risk Evaluation and Mitigation Strategy : to enhance labeling) Conducting Global pregnancy registries- Challenges and opportunities How can pregnancy registries Work with/Complement other sources of Clinical and observational information? How does a registry fit in an overall plan to obtain information? Interpreting Data from pregnancy registries: Who, When, How?
  20. 20. Pregnancy registryAdvantage : Aim of pregnancy registry : major birth defect, Birth defect trend Used to generate hypothesisLimitations : Exposure의 classification - lack Outcome(birth defect , developmental disability)의 universal determination - lack Representation : voluntary Loss to f/u : limit interpretation
  21. 21. Congenital malformation studies in Chernobyl Impacted Regions of Ukraine: Lessons learned by W. Werterlecki Thyroid cancer NTD increase Birth weight decrease
  22. 22. 2012 Teratogen Update : ART by JL Simpson (March of Dimes)IVF alone (<1993) vs ICSI (>1993 대략 50%)IVF alone : 1979-1993 : 2.9%ICSI : De novo chromosomal abnormality - 1.66% ( 0.45% in general) Hypospadias : RR 3.0( 1.09-6.50) Beckwith-Wiedemann syndrome (BWS) : epigenetic perturbation( MTHFR, IGF2) Reasons : Underlying reasons for ART old age genetic disorder balanced translocation Limitation : no true comparison group
  23. 23. Education Lunchbox Session1. Diagnostic radiation2. Influenza vaccine3. Binge drinking ---
  24. 24. Motherisk Calls for 2011Lines : Motherisk general help line : 31,201 calls Alcohol and substance abuse line : 1,317 calls NVP help line : 2,035 calls82% : women & their partners , 18% : health care provider34,553 calls : 63% regarding pregnancy , 37% regarding breastfeedingMotherisk general help line : mc question : psychotropics(19-25%)417 : clinical fellow on call149 : in clinic ( 45% psychotropic)
  25. 25. A review of calls to MotherSafe regarding exposures during lactation: 2000-2010 by Kennedy D.(Ausralia)79% call : consumers but, midwives & early childhood nursesConsumer call : increaseRepeat caller : 35% in 2000 and 55% in 2010Commonest concern exposure : antihistamines, cold, flu preparations and antibioticsBefore contacting (79%) : 38% family doctor, 35% internet, 9% medical specialist, 9% pharmacistF/U of breastfeeding practice ( 100 women) : positive with no women stopping breastfeeding in order to take medication
  26. 26. - Abstracts -E-teratogens: a case-report and a glance at the availability of Isotretinoin on the Web : “buy isotretinoin” on GoogleSafety of levetriacetam in pregnancy : 2.2%(20/897)Are change in Steroid hormones associated with smoke exposure responsible for pregnancy outcome? SA in cortisol high/ estrogen& progesterone level lower, but not related cigarette smokeUnplanned pregnancies and contraceptive utilization among women calling the California TIS regarding exposure to category D or X medication : 99% no contraceptive methodsPregnancy outcome and factors associated with voluntary termination ofpregnancy in Korean women inadvertently exposed to Isotretinoin: 25% ToP, by 1st contact physician Adj OR : 2.06Pregnancy outcome after Licorice exposure in pregnancy : Stillbirth 2.3% vs 0.3%
  27. 27.  Free Thyroid Hormone levels, Second-Hand Smoke, and pregnancy outcome: SA 48 vs successful pregnancy outcome Cotinine levels : no difference FT4 : slightly higher/ FT3 : lower ---- may contribute to adverse pregnancy outcome including SA Is lithium only a cardiovascular teratogen? A prospective comparative multicenter observational study : in 219 lithium exposure vs 812 control major anomaly : 8.6% in 1st exposure (2.6%) CV anomaly : 3.9%(0.6%) non-CV anomaly : 6.6%(2.0%) Preterm delivery : 15.2%(6.2%)
  28. 28. Japan Drug Information Institute of pregnancy 2012
  29. 29. Visit of Motherisk Program
  30. 30. Motherisk Program 2012
  31. 31. Motherisk Program 2012
  32. 32. Motherisk Program 2012
  33. 33. Motherisk Program 2012
  34. 34. Motherisk Program 2012
  35. 35. Gidi’s office door 2012
  36. 36.  OTIS Conference Visit of Motherisk Program Vision of Korean MRP
  37. 37.  Insight Networks Concentration
  38. 38. In Toronto 2012

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