1. 25th International Conference
Organization of Teratology
Information Specialists
Korean Motherisk Program
JUNG YEOL HAN
In Baltimore 2012

2. Contents
 25th OTIS Conference
 Visit of Motherisk Program
 Vision of KMRP

3. 25th OTIS Conference

4. Patient’s Perception of Teratogenic
risks- 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. EDPS(Edinburgh postnatal depression scale)

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. 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. 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

10. The All or None Phenomenon :
How should we counsel ?
By Dr. Brent
Mouse vs Human
 Preimplantation period (수정 후 2주 이내)
Usually not susceptible period to teratogen
Some highly susceptible period to teratogen
 Surviving embryo : similar outcome

11. 예외:
Long half life
Teratogenic infectious agent
Maternal effect(large exposure)
Epigenetic effect
Mutagenic effect
Mouse data 이용 상담 : no thanks by Brent.

12. By JM Friedman
6days : implantation begin
 Very little data
 Chronic exposure
 Few accumulative exposure situation
Czeizel : Hofpp study
24-42days of LMP :
Exposure vs Non-exposure
Live birth 92% -
BW 3,222 3,268
Anomaly 3.3% -

13. IVF/ICSI
Angelman SD/ Beckwith-Wiedemann syndrome
-- inconsistent , absolute risk <1%
동물 :
Most agents : no effect
Some agents : increased malformation

14.  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 common
Answer by JD Friedman: We don’t know
Counseling : never say : “All or none”
But, risk is very low

15. 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)

16.  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)

17. 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

18. 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

19. OTIS 25th Anniversary Session
By G. Koren : OTIS early challenges & future opportunities
 Abuse of drugs and alcohol
 Folic acid
 Occupational exposure
 Infection
 Pharmacogenomics
 methyl mercury
 Drugs & breastfeeding
 Biomarker : hair/meconium
By Tina : OTIS & NOFAS: partners in preventing birth defect
By M Kisor : Parents & OTIS – One mother’s experience with OTIS
By L Morrison : Birth defects prevention, risk reduction, and Awareness Act
By G. Koren : A model of industry-Academia collaboration for drugs in
pregnancy

20. 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?

21. Pregnancy registry
Advantage :
 Aim of pregnancy registry : major birth defect, Birth defect trend
 Used to generate hypothesis
Limitations :
 Exposure의 classification - lack
 Outcome(birth defect , developmental disability)의
universal determination - lack
 Representation : voluntary
 Loss to f/u : limit interpretation

22. Congenital malformation studies in Chernobyl Impacted
Regions of Ukraine: Lessons learned
by W. Werterlecki
 Thyroid cancer
 NTD increase
 Birth weight decrease

23. 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

24. Education Lunchbox Session
1. Diagnostic radiation
2. Influenza vaccine
3. Binge drinking
---

25. Motherisk Calls for 2011
Lines : Motherisk general help line : 31,201 calls
Alcohol and substance abuse line : 1,317 calls
NVP help line : 2,035 calls
82% : women & their partners , 18% : health care provider
34,553 calls : 63% regarding pregnancy , 37% regarding breastfeeding
Motherisk general help line : mc question : psychotropics(19-25%)
417 : clinical fellow on call
149 : in clinic ( 45% psychotropic)

26. A review of calls to MotherSafe regarding exposures
during lactation: 2000-2010 by Kennedy D.(Ausralia)
79% call : consumers
but, midwives & early childhood nurses
Consumer call : increase
Repeat caller : 35% in 2000 and 55% in 2010
Commonest concern exposure : antihistamines, cold, flu preparations
and antibiotics
Before contacting (79%) : 38% family doctor, 35% internet,
9% medical specialist, 9% pharmacist
F/U of breastfeeding practice ( 100 women) : positive with no women
stopping breastfeeding in order to take medication

27. - Abstracts -
E-teratogens: a case-report and a glance at the availability of
Isotretinoin on the Web : “buy isotretinoin” on Google
Safety 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 smoke
Unplanned pregnancies and contraceptive utilization among women
calling the California TIS regarding exposure to category D or X
medication : 99% no contraceptive methods
Pregnancy outcome and factors associated with voluntary termination of
pregnancy in Korean women inadvertently exposed to Isotretinoin
: 25% ToP, by 1st contact physician Adj OR : 2.06
Pregnancy outcome after Licorice exposure in pregnancy : Stillbirth 2.3% vs 0.3%

28.  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%)

29. Japan Drug Information Institute of pregnancy 2012

30. Visit of Motherisk Program

33. Motherisk Program 2012

34. Motherisk Program 2012

35. Motherisk Program 2012

36. Motherisk Program 2012

37. Motherisk Program 2012

38. Gidi’s office door 2012

39.  OTIS Conference
 Visit of Motherisk Program
 Vision of Korean MRP

40.  Insight
 Networks
 Concentration

41. In Toronto 2012