1. Motherisk Program in Canada
June Seek Choi, M.D., PhD.
The Korean Motherisk Program,
Div. of Maternal-Fetal Medicine,
Dept. of OB & GYN,
Cheil General Hospital and Women’s Healthcare Center,
Kwandong University School of Medicine

2. The Hospital for Sick Children

3. The Hospital for Sick Children

4. The Hospital for Sick Children

5. Contents
• Organization Chart
• Motherisk Program (Clinic and Call Center)
• Laboratory Studies in Motherisk
• Studies in Canada

6. Organization Chart

7. Organization Chart (1)
• Dr. Gideon Koren- Director of Motherisk
• Dr. Ito Shinya- Head of Division of
Clinical Pharmacology & Toxicology
• Dr. Irena Nulman- Associate Director of
Motherisk, Alcohol & Drugs in
Pregnancy

8. Organization Chart (2)
Adverse Drug
Reaction
Clinical
Pharmacology &
Toxicology
Breast Feeding
Sickkids Motherisk Call
Hospital Center
Clinic
Motherisk
Program
Placental Study
Hair Test

9. Organization Chart (3)
• 11 Fellows
• 6-8 Graduate students
• 10 Counselors

10. Organization Chart (4)
• Case Round (Shinya’s Round)
• Fellow’s Lecture
• Review Round (Gidi’s Round)
• Breast Feeding Round
• Clinical Pharmacology Tutorial
• Toxicology Round
• Pre-clinic Meeting
• Motherisk Round
• Motherisk Clinic

11. Motherisk Program
(Call Center and Clinic)

12. Motherisk Program (Call Center) (1)
1
MR General
Line
2
Motherisk
Helpline Alcohol
1
Line
NVP Line 1

13. Motherisk Program (Call Center) (2)
Total
number of
call: 34,558
Alcohol and
MR general NVP line:
Substance
line: 31,206 2,035
use: 1,317
Motherisk 2011

14. Motherisk Program (Call Center) (3)
Caller Type Number of Questions per Call
on the MR General Line
Motherisk 2011

15. The Most Called About Exposures during Pregnancy
on the Motherisk General Line
Frequency of Question (%)
Motherisk 2011

16. The Most Called About Exposures during Lactation on
the Motherisk General Line
Frequency of Question (%)
Motherisk 2011

17. Motherisk Clinic (1)
• Every Friday Afternoon
• Conducted by Fellow & Staff

18. Motherisk Clinic (2) Reasons for Clinic Visit
Frequency of Question (%)
Motherisk 2011

19. Motherisk Clinic (3) Return Mail

21. Laboratory Studies in Motherisk
Hair Test

22. Hair Test (1)

23. Hair Test (1) Alcohol
FAEE concentration Classification Interpretation
> 1.0 ng/mg (positive) Chronic Alcohol -100% specific for regular, excessive alcohol
Abuser consumption
-25% of chronic alcohol abusers will test below
this level
0.50-0.99 ng/mg Chronic Alcohol -90% specific for regular, excessive alcohol
(positive) Abuser consumption
-10% of chronic alcohol abusers will test below
this range
-10% of moderate drinkers will show result in
this range
< 0.49 ng/mg Moderate/Non-drinker -No evidence of excessive alcohol consumption
(negative) (Up to 20g of alcohol per day; ~2drinks)
< 0.20 – 0.040 ng/mg Non-Drinker (abstainer) -No evidence of alcohol consumption
(negative)
The Hospital for Sick Children 2007

24. Hair Test (2) Methamphetamine
• Half of a million people using this drug
weekly in the USA
• 8% of individuals with positive drug test in
Motherisk database are positive for
methamphetamine
• 85% of the individuals positive for
methamphetamine are positive for at least
one other drug abuse, most commonly
cocaine

25. Hair Test (3) Drugs in Adult Hair
COCAINE OPIATES CANNABIS AMPETAMINE METHAMPHETAMINE
ng/mg ng/mg ng/mg ng/mg ng/mg
(n = 1,532) (n = 426) (n = 597) (n = 97) (n =243)
median 2.38 0.65 0.33 0.60 1.03
VERY LOW < 0.23 < 0.16 < 0.11 < 0.13 < 0.16
(5th percentile)
LOW 0.23-0.71 0.16-0.33 0.11-0.18 0.13-0.30 0.16-0.37
(5-25th percentile)
MEDIUM 0.72-8.58 0.34-1.77 0.19-0.70 0.31-1.44 0.38-3.87
(25-75th percentile)
HIGH 8.59-39.47 1.78-8.22 0.71-2.86 1.45-9.72 3.88-24.51
(75-95th percentile)
VERY HIGH > 39.47 > 8.22 > 2.86 > 9.72 > 24.51
(95th percentile)
The Hospital for Sick Children 2006

26. Laboratory Studies in Motherisk
Placental Perfusion Study

27. Placental Perfusion Study (1)
• Human placental perfusion, first
designed by Schneider et al (1972)
• To investigate drug transfer from
the maternal to the fetal circulation
• Placental perfusion study has been
conducted in Motherisk since 2004

28. Placental Perfusion Study (2)
• Exclusion Criteria
- Preterm placenta
- Extremely fibrotic changed placenta
- Many defects in cotyledon
- Hepatitis, HIV
• Failure Rate: 90%

30. Studies in Canada
Fetal outcomes in women taking domperidone
during pregnancy
June-Seek Choi,*,† Jung-Yeol Han,*,† Hyun-Kyong Ahn,*,† Hyun-Mee RYU,†
Moon-Young KIM,† Jae-Hyug YANG,† Alejandro A. Nava-Ocampo‡,§ and Gideon Koren¶

31. Fetal outcomes in women taking domperidone during
pregnancy
Cases (n= 120) Controls (n=212) 95% CI for the difference P value
Gestational age at birth (weeks) 39.1 ± 1.4 39.2 ± 2.0 -0.5, 0.4 0.81
Birth weight (g) 3,308.4 ± 529.1 3,273.0 ± 485.0 -77.2, 148.1 0.54
Birth length (cm) 49.5 ± 2.5 46.6 ± 2.2 -0.7, 1.4 0.51
Head circumference at birth (cm) 34.4 ± 3.7 34.2 ± 3.8 -0.6, 1.6 0.58
Apgar score, 1 min 8.3 ± 1.3 8.2 ± 1.3 -0.2, 0.2 0.80
Apgar score, 5 min 9.0 ± 1.3 8.9 ± 1.4 -0.1, 0.3 0.36
Malformationsa 3 (2.5) 3 (1.4) OR= 0.6 (0.1, 2.8) 0.38
Meconium staining at birth - 1 (0.5) - 0.69
Neonatal jaundice 1 (0.8%) 4 (1.9) OR= 2.3 (0.3, 20.7) 0.41
aIn the case group: a baby born with bilateral equino varus and right calcaneal deformity, another with megacisterna magna, and a
third one with right inguinal hernia.
In the control group: a baby born with skin tag on the left nipple and a spot on left knee, another with left dysplastic kidney, and a third
one with left pyelectasis

32. Studies in Canada
Pregnancy and isotretinoin therapy
June Seek Choi, Gideon Koren, Irena Nulman

33. Pregnancy and isotretinoin therapy
• Oral isotretinoin was introduced in the USA
in 1982 and Canada in 1983.
• 20-35% risk for congenital defects
232 types of generic
(craniofacial, central nervous system, and original
cardiovascular, and thymic malformations) isotretinoin made in
36 countries around
• 30-60% of children prenatally exposed to
the world
isotretinoin have been reported to
demonstrate neurocognitive impairment,
even without physical defects.

34. Pregnancy and isotretinoin therapy
Pregnancy Preventio System to Manage Accu iPLEDGE
n Program(PPP) tane Related Teratogeni
city (SMART)
• 1988 • 2002 • 2006
• 34% failing to receive the • Monthly pregnancy tes
• 36% failed to required two pregnancy ts,
tests before beginning • Documentation of
receive a treatment contraceptive use,
pregnancy test • 54% of women of child- • Patient education
bearing age failing to use reinforcing key safety
two methods of birth- messages
control • Registered in a single
database

35. Pregnancy and isotretinoin therapy

36. Pregnancy and isotretinoin therapy
• We propose that every physician and pharmacist
who prescribes or dispenses isotretinoin should
complete a mandatory online certification program
involving proper education about contraceptive
methods and the therapeutic and fetotoxic effects
of this drug.
• With improved education of patients and healthcare
providers, improved patient adherence with
established safety protocols, and proper control of
isotretinoin distribution, one can hope that more
women will use isotretinoin safely.

37. Studies in Canada
Fetal and neonatal outcomes in women reporting
ingestion of licorice (Glycyrrhiza uralensis) during
pregnancy
June-Seek Choi1,2, Jung-Yeol Han1,2, Hyun-Kyeong Ahn1,2, Hyun-Mee Ryu2,
Moon-Young Kim2, Jin-Hoon Chung2, Alejandro A. Nava-Ocampo3,4,5, Gideon Koren4,5,6

38. Fetal and neonatal outcomes in women reporting ingestion of
licorice (Glycyrrhiza uralensis) during pregnancy
• The roots and rhizomes of licorice species have long
been used worldwide as a natural remedy and
sweetener in candies, liquor, and teas.
• A large number of chemicals has been isolated from
licorice, including triterpene saponins, flavonoids,
isoflavonoids and chalcones, and glycyrrhizin, the
latter of which is considered to be the main
biologically active component of licorice.
• In Republic of Korea, licorice is present in over
2,000 OTC formulations, and in more than 200
galenic formulations.

39. Fetal and neonatal outcomes in women reporting ingestion of
licorice (Glycyrrhiza uralensis) during pregnancy
Cases (n= 180) Controls (n= 350) 95% CI for the difference P value
Stillbirths, n (%) 4 (2.2) 1 (0.3) OR= 7.9 (0.9 to 71.5) 0.048
Live births, n (%) 176 (97.8) 349 (99.7) OR= 0.1 (0.0 to 1.1) 0.048
Preterm births, n (%) 17 (9.4) 22 (6.3) OR= 1.5 (0.8 to 3.0) 0.19
Gestational age (weeks; mean ± SD) 39.0 ± 2.5 39.3 ± 1.7 -0.007, 0.7 0.05
Birth weight (g; mean ± SD) 3,294.1 ± 522.0 3,287.9 ± 457.6 -93.0., 80.5 0.89
Birth length (cm; mean ± SD) 49.7 ± 2.3 49.6 ± 1.9 -0.5, 0.3 0.60
Head circumference (cm; mean ± 34.6 ± 1.5 34.5 ± 1.3 -0.3, 0.2 0.62
SD)
Apgar score, 1 min (mean ± SD) 8.4 ± 0.9 8.6 ± 3.9 -0.4, 0.8 0.45
Apgar score, 5 min (mean ± SD) 9.0 ± 0.7 9.1 ± 0.9 -0.4, 0.8 0.37
Major malformations, n (%) 2 (1.1)a 1 (0.3)b OR= 3.9 (0.4 to 43.5) 0.27
Minor malformations, n (%) - 2 (0.6)c - 0.44
Meconium staining at birth, n (%) - 5 (1.4) - 0.13
Neonatal jaundice, n (%) 3 (1.7) 8 (2.3) OR= 0.7 (0.2 to 2.8) 0.46
aA baby born with megacisterna magna, and another born with dysplastic changes in the left kidney, left ectopic ureteral insertion, and hydroureter and
mild pyelectasis in the right kidney.
bA baby born with mild forefoot adduction, varus deformity of left foot and calcaneal deformity of right foot, and is being followed up by a pediatric orthopedist.
cA baby born with a single umbilical artery, and another baby born with left pyelectasis

40. Fetal and neonatal outcomes in women reporting ingestion of
licorice (Glycyrrhiza uralensis) during pregnancy
• The rate of stillbirths was marginally higher among
women who took licorice than those who did not
(OR= 7.9; 95%CI 0.9-71.5; P=0.048), and
significantly higher when compared to the general
population in Republic of Korea (OR= 13.3; 95% CI
4.9-35.8; P<0.001).

41. Fetal and neonatal outcomes in women reporting ingestion of
licorice (Glycyrrhiza uralensis) during pregnancy
25th International Conference of the Organization of
Teratology Information Specialists
Marriott Baltimore Waterfront

42. Studies in Canada
Fetal and neonatal outcomes in pregnant women exposed to
abdominal or lumbar radiodiagnostic procedures without
administration of radionucleotides
June-Seek Choi1,2, Jung-Yeol Han1,2, Hyun-Kyeong Ahn1,2, Hyun-Mee Ryu2,
Moon-Young Kim2, Jin-Hoon Chung2, Gye-Hyeong An2, and Alejandro A. Nava-Ocampo3,4,5

43. Fetal and neonatal outcomes in pregnant women exposed to abdominal or
lumbar radiodiagnostic procedures without administration of
radionucleotides
Characteristics n (%)
A) Radiological study
Lumbar spine radiography 40 (34.5)
Plain abdominal radiography 19 (16.4)
Upper gastrointestinal tract radiography 18 (15.5)
Abdominal CT scan without contrast 13 (11.2)
Contrast-enhanced abdominal CT scan 6 (5.2)
Urinary tract X-ray 6 (5.2)
Barium enema 5 (4.3)
Pelvis radiography 5 (4.3)
Intravenous pyelogram 2 (1.7)
Lumbar CT scan 2 (1.7)
B) Indications
Low back pain 33 (28.4)
Check-up 32 (27.6)
Abdominal pain 16 (13.8)
Functional gastrointestinal disorders 15 (12.9)
Evaluation post-car accident 10 (8.6)
n= 115
Upper respiratory tract infection 1 (0.9) aBased on the estimates for selected
procedures published elsewhere10
Others 9 (7.8) 1 mSv = 1 mGy = 0.1 rad
bMedian (ranges)
C) Fetal dose (mSv)a 7.2 (0.3 – 66.6)b

44. Fetal and neonatal outcomes in pregnant women exposed to abdominal or
lumbar radiodiagnostic procedures without administration of
radionucleotides
Fetal and neonatal outcomes Exposed (n= 105) Controls (n= 485) 95% CI for the difference P value
Gestational age at birth (weeks) 39.5 ± 1.1 39.2 ± 1.6 -0.6, 0.1 0.13
Birth weight (g) 3,321.2 ± 422.6 3,300.6 ± 428.7 -111.5., 70.1 0.66
Birth length (cm) 49.5 ± 2.6 49.5 ± 1.9 -0.5, 0.4 0.96
Head circumference at birth (cm) 34.7 ± 1.9 34.6 ± 1.7 -0.4, 0.3 0.83
1-min Apgar score 8.4 ± 0.6 8.3 ± 0.8 -0.3, 0.1 0.30
5-min Apgar score 9.0 ± 0.6 9.1 ± 0.7 -0.1, 0.2 0.41
IUFD (%) 1 (1.0) 1 (0.2) OR= 4.7 (0.3, 75.0) 0.33
Malformationsa (%) 2 (1.9) 2 (0.4) OR= 4.7 (0.7, 33.6) 0.15
NICU admission (%) 5 (4.8) 8 (1.7) OR= 2.9 (1.0, 9.3) 0.062
Duration at NICU (days) 6.0 ± 3.0 6.3 ± 7.4 -10.2, 10.8 0.95
Meconium stain at birth (%) - 2 (0.4) - 0.68
Neonatal jaundice (%) 2 (1.9) 11 (2.3) OR= 0.8 (0.2, 3.8) 0.59
aInthe case group: a baby born with left cerebral mild ventriculomegaly and infantile spasm, second one with small pulmonary artery. In the control group: a
baby born with cleft palate, second one with mega cistern magna.

45. Future Works
• Paper for Individual Herbal Medicine
• Establish Placental Perfusion Study
in Korean Motherisk Program
• Improvement of Korean Motherisk
Database

46. Thank you for your attention!!

47. Elements
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