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

The Hospital for Sick Children

The Hospital for Sick Children

The Hospital for Sick Children

Contents

• Organization Chart

• Motherisk Program (Clinic and Call Center)

• Laboratory Studies in Motherisk

• Studies in Canada

Organization Chart

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

Organization Chart (2)

Sickkids Hospital

Clinical

Pharmacology &

Toxicology

Adverse Drug Reaction

Breast Feeding

Motherisk Program

Motherisk Call Center

Clinic

Placental Study

Hair Test

Organization Chart (3)

• 11 Fellows

• 6-8 Graduate students

• 10 Counselors

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

Motherisk Program

(Call Center and Clinic)

Motherisk Program (Call Center) (1)

Motherisk Helpline

MR General Line

1

2

Alcohol Line

1

NVP Line 1

Motherisk Program (Call Center) (2)

Total number of

call: 34,558

MR general line: 31,206

Alcohol and Substance use: 1,317

NVP line: 2,035

Motherisk 2011

Motherisk Program (Call Center) (3)

Caller Type

Motherisk 2011

Number of Questions per Call

on the MR General Line

The Most Called About Exposures during Pregnancy

on the Motherisk General Line

Motherisk 2011

Frequency of Question (%)

The Most Called About Exposures during Lactation on

the Motherisk General Line

Frequency of Question (%)

Motherisk 2011

Motherisk Clinic (1)

• Every Friday Afternoon

• Conducted by Fellow & Staff

Motherisk Clinic (2)

Frequency of Question (%)

Motherisk 2011

Reasons for Clinic Visit

Motherisk Clinic (3) Return Mail

Laboratory Studies in Motherisk

Hair Test

Hair Test (1)

Hair Test (1)

FAEE concentration Classification Interpretation

> 1.0 ng/mg (positive) Chronic Alcohol

Abuser

-100% specific for regular, excessive alcohol

consumption

-25% of chronic alcohol abusers will test below

this level

0.50-0.99 ng/mg

(positive)

Chronic Alcohol

Abuser

-90% specific for regular, excessive alcohol

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

(negative)

Moderate/Non-drinker -No evidence of excessive alcohol consumption

(Up to 20g of alcohol per day; ~2drinks)

< 0.20 – 0.040 ng/mg

(negative)

Non-Drinker (abstainer) -No evidence of alcohol consumption

The Hospital for Sick Children 2007

Alcohol

Hair Test (2)

• 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

Methamphetamine

Hair Test (3)

COCAINE

ng/mg

(n = 1,532)

OPIATES

ng/mg

(n = 426)

CANNABIS

ng/mg

(n = 597)

AMPETAMINE

ng/mg

(n = 97)

METHAMPHETAMINE

ng/mg

(n =243)

median 2.38 0.65 0.33 0.60 1.03

VERY LOW (5th percentile)

< 0.23 < 0.16 < 0.11 < 0.13 < 0.16

LOW (5-25th percentile)

0.23-0.71 0.16-0.33 0.11-0.18 0.13-0.30 0.16-0.37

MEDIUM (25-75th percentile)

0.72-8.58 0.34-1.77 0.19-0.70 0.31-1.44 0.38-3.87

HIGH (75-95th percentile)

8.59-39.47 1.78-8.22 0.71-2.86 1.45-9.72 3.88-24.51

VERY HIGH (95th percentile)

> 39.47 > 8.22 > 2.86 > 9.72 > 24.51

The Hospital for Sick Children 2006

Drugs in Adult Hair

Laboratory Studies in Motherisk

Placental Perfusion Study

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

Placental Perfusion Study (2)

• Exclusion Criteria

- Preterm placenta

- Extremely fibrotic changed placenta

- Many defects in cotyledon

- Hepatitis, HIV

• Failure Rate: 90%

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¶

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

Studies in Canada

Pregnancy and isotretinoin therapy

June Seek Choi, Gideon Koren, Irena Nulman

Pregnancy and isotretinoin therapy

• Oral isotretinoin was introduced in the USA

in 1982 and Canada in 1983.

• 20-35% risk for congenital defects

(craniofacial, central nervous system,

cardiovascular, and thymic malformations)

• 30-60% of children prenatally exposed to

isotretinoin have been reported to

demonstrate neurocognitive impairment,

even without physical defects.

232 types of generic

and original

isotretinoin made in

36 countries around

the world

Pregnancy Prevention Program(PPP)

• 1988

• 36% failed to

receive a

pregnancy test

System to Manage Accutane Related Teratogenicity (SMART)

• 2002

• 34% failing to receive the required two pregnancy tests before beginning treatment

• 54% of women of child- bearing age failing to use two methods of birth- control

iPLEDGE

• 2006

• Monthly pregnancy tests,

• Documentation of contraceptive use,

• Patient education reinforcing key safety messages

• Registered in a single database

Pregnancy and isotretinoin therapy

Pregnancy and isotretinoin therapy

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.

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

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.

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 ±

SD)

34.6 ± 1.5 34.5 ± 1.3 -0.3, 0.2 0.62

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

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).

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

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

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)

Upper respiratory tract infection 1 (0.9)

Others 9 (7.8)

C) Fetal dose (mSv)a 7.2 (0.3 – 66.6)b

n= 115 aBased on the estimates for selected

procedures published elsewhere10

1 mSv = 1 mGy = 0.1 rad bMedian (ranges)

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

aIn the 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.

Future Works

• Paper for Individual Herbal Medicine

• Establish Placental Perfusion Study

in Korean Motherisk Program

• Improvement of Korean Motherisk

Database

Thank you for your attention!!

Elements www.animationfactory.com