25th International Conference Organization of Teratology

Information Specialists

Korean Motherisk Program JUNG YEOL HAN

In Baltimore 2012

Contents

25th OTIS Conference Visit of Motherisk Program

Vision of KMRP

25th OTIS Conference

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%

EDPS(Edinburgh postnatal depression scale)

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?

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

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

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

Mouse data 이용 상담 : no thanks by Brent.

예외:

Long half life

Teratogenic infectious agent

Maternal effect(large exposure)

Epigenetic effect

Mutagenic effect

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% -

IVF/ICSI

Angelman SD/ Beckwith-Wiedemann syndrome -- inconsistent , absolute risk <1% 동물 :

Most agents : no effect

Some agents : increased malformation

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

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)

Strategies of Reducing the impact of Known teratogen

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)

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

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

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

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?

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

Pregnancy registry

Congenital malformation studies in Chernobyl Impacted

Regions of Ukraine: Lessons learned

by W. Werterlecki

Thyroid cancer NTD increase

Birth weight decrease

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

Education Lunchbox Session

1. Diagnostic radiation

2. Influenza vaccine

3. Binge drinking

---

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)

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

- 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%

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%)

Japan Drug Information Institute of pregnancy 2012

Visit of Motherisk Program

Motherisk Program 2012

Motherisk Program 2012

Motherisk Program 2012

Motherisk Program 2012

Motherisk Program 2012

Gidi’s office door 2012

OTIS Conference Visit of Motherisk Program

Vision of Korean MRP

Insight

Networks

Concentration

In Toronto 2012