Measuring Drugs in Mothers and Neonates

1
Measuring Drugs in Mothers and Neonates

• Joey Gareri
• Motherisk Laboratory
• Division of Pharmacology and Toxicology
• Hospital for Sick Children, Toronto

2
Physiology of the Hair Shaft
3
Routes of Drug Entry Into Hair

• Capillary blood supply to follicle
• Transport via sebacious gland
• Transport via sweat gland
• Adsorption via passive exposure

4
General Model for Drug Incorporation and Removal
Sweat
ingested drugs
Drugs appear in sweat and sebum
Blood Ingested Drugs appear in blood
Drugs/metabolites incorporated into hair
External Exposure
Hair exposed to drugs from environment
Hair wetted by sweat or normal hygiene
5
Routes of Drug Entry Into Neonatal Hair

• Transplacental transfer of drugs into fetus
• Deposition of drugs into hair via follicle
• Evacuation of fetal urine into amniotic fluid
• External adsorption of drug onto hair via
  amniotic fluid

6
Prenatal Exposures

• Neonatal hair starts forming at approximately
  20-22 weeks gestation
• small quantities available
• low concentration of drugs
• timing of collection not critical

7
Hair Testing in Adults

• Chronic exposure
• Behaviour patterns
• Acute exposures (history)
• Abstinence
• Dose information uncertain

8
Meconium Analysis

• Meconium babys first bowel movements
• A matrix unique to the developing fetus that is
  already commonly used in neonatal drug screening
• Best collected within 72 hours of birth
• Extremely low birth weight infants may be longer
• Superior to blood and urine
• Discarded material
• Collection is easy and non-invasive

9
Routes of Drug Entry Into Meconium

• 12 weeks gestation fetal swallowing
• Transplacental transfer of drugs into fetus
• Evacuation of fetal urine into amniotic fluid
• Swallowing of amniotic fluid
• Deposition of drugs into meconium

10
Prenatal Exposures

• Meconium starts forming at approximately 13 weeks
  gestation
• large quantities available
• high concentration of drugs
• timing of collection IS critical
• 1-2 days post-natal

11
Motherisk LaboratoryIllicit Drugs

• Phencylidine
• (i.e. angel dust)
• Methamphetamine
• Amphetamine
• LSD

• Cocaine
• Benzoylecgonine (cocaine metabolite)
• Cannabis
• Opiates (heroin)

12
Motherisk LaboratoryLicit Drugs

• Benzodiazepines
• ativan, diazepam, midazolam, rohipnol etc.
• Barbiturates
• Nicotine
• Cotinine
• (nicotine metabolite)
• Fatty Acid Ethyl Esters (FAEE)
• (i.e. alcohol)

• Opiates
• morphine, codeine
• Methadone
• Meperidine
• Demerol
• Oxycodone
• Oxycontin , Percocet, Percodan

13
Ethanol Metabolism
Oxidative
ADH and MEOS (CYP 2E1)
ACETALDEHYDE
FATTY ACYL CoA
ETHANOL
Microsomal FAEE Synthase
FAEE
FATTY ACIDS
Cytosolic FAEE Synthase
Non-Oxidative
14
Motherisk Laboratory

• RESEARCH IN FETAL AND NEONATAL TOXICOLOGY
• Adult/child hair testing
• Determine trends in illicit drug use/exposures
• Neonatal hair/meconium testing
• Establish prenatal exposures
• Tool in correlation of developmental outcomes
• Assist in FASD diagnoses

15
The Ideal Neonatal Biomarker..

• would include non-invasive sampling
• reveal an extensive history of in utero exposure
• be independent of maternal report

16
Motherisk Laboratory Research

• Meconium Analysis
• Prevalence of Fetal Alcohol Exposure
• Grey Bruce, Ontario
• 682 samples analyzed
• 2.5 confirmed rate of prenatal ethanol exposure
• Montevideo Study
• Montevideo, Uruguay
• 900 samples
• FAEE, cocaine, opiates, cannabis, etc
• Outcome analysis

17
Motherisk Laboratory Research

• Hair Analysis
• Methamphetamine/Cocaine
• Extensive placental transfer
• Maternal methamphetamine associated with polydrug
  use

18
Clinical Use of Hair Testing

• Child protection
• Conclusively determine drug use/abstinence in
  caregivers
• Determine presence of contaminated home
  environment
• To determine long-term exposures and recognize
  extraordinary situations

19
Possible Factors Affecting Uptake of Drugs into
Hair

• Ethnicity (hair colour, metabolism)
• Type of Hair (dry, oily, hair color)
• Type of Drug
• Dose

20
Hair Sampling

• Vertex Posterior Scalp
• Area of highest growth consistency
• 85 growth phase / 15 resting phase

21
Segmental Analysis

• Growth rate 1.0 centimetre / month
• 2-3 week time delay
• By performing segmental hair analysis a diary
  of drug use can be established
• For example
• 0-3cm from scalp 1-4 months prior to sampling
• 3-6cm from scalp 4-7 months prior to sampling

22
CASE 1

• 8 centimetres (whole length)
• Sampled August 10, 2005
• Cocaine 9.00 ng/mg medium
• Benzoylecgonine 0.43 ng/mg
• Opiates 0.68 ng/mg low
• Oxycodone 1.84 ng/mg
• TIME PERIOD mid-November 2004 to mid-July 2005

23
CASE 1

• Segmental Analysis (sampled August 31, 2005)
• 0-1cm (July 2005)
• Cocaine 0.66 ng/mg low
• 1-2cm (June 2005)
• Cocaine 0.72 ng/mg low
• Opiates lt 0.10 ng/mg trace
• 2-3cm (May 2005)
• Cocaine 2.04 ng/mg low/medium
• Opiates lt 0.10 ng/mg trace
• 3-4cm (April 2005)
• Cocaine 3.68 ng/mg medium
• Benzoylecgonine 0.10 ng/mg
• Opiates lt 0.10 ng/mg trace

24
CASE 1

• Segmental Analysis
• 4-5cm (March 2005)
• Cocaine 2.77 ng/mg medium
• Benzoylecgonine 0.13 ng/mg
• Opiates 0.18 ng/mg low
• 5-6cm (February 2005)
• Cocaine 2.23 ng/mg medium
• Benzoylecgonine 0.18 ng/mg
• Opiates 0.10 ng/mg low
• 6-7cm (January 2005)
• Cocaine 1.09 ng/mg low
• Benzoylecgonine 0.14 ng/mg
• Opiates 1.56 ng/mg medium
• 7-8cm (December 2004)
• Cocaine 0.93 ng/mg low
• Benzoylecgonine 0.17 ng/mg
• Opiates 0.64 ng/mg low

25
CASE 1
26
CASE 2

• 15 centimetres (whole length)
• Sampled August 9, 2005
• Segmental Analysis
• 0-1cm (mid-June to mid-July 2005)
• Cocaine 8.37 ng/mg medium
• Benzoylecgonine 0.47 ng/mg
• 1-15cm (mid-April 2004 to mid-June 2005)
• Cocaine 41.00 ng/mg very high
• Benzoylecgonine 4.43 ng/mg

27
Case 2
28
When an adults hair contains cocainewhat of
households have cocaine in a childs hair?
29
Family Ties Parent and Childrens Hair Test
Results
30

• THANK YOU
• ?
• THE END

31
Portrait of the Addicted Mother

• Unemployed (93)
• Annual Income lt 15,000/yr (CAD) (96)
• Grade 12 education or less (92)
• Single/Divorced/Separated (74)
• No permanent residence (23)
• Multiple pregnancies (87)
• Apprehended children (25)
• Children living with other family members (74)
• Abused by partner (60)
• Depressed (78)
• Suicidal thinking (25)

32
OVERVIEWNeonatal Screening for Fetal Alcohol
Exposure

• PROS
• maximize diagnosis/intervention across
  socioeconomic lines
• opportunity to initiate therapy at earliest
  possible time in development (improved prognosis
  for outcome)
• avoids marginalization of high-risk women (as
  opposed to targeted screening)
• birth provides a window of opportunity in
  engaging high-risk women
• optimal intervention timing for behaviour changes
  in mother
• can provide adoptive parents with valuable
  background information
• enormous research potential in engaging an
  elusive study population

• CONS
• potential labeling/stigmatization of mother and
  child
• potential for conflict due to perceived or
  potential implications of a positive test
• low disease specificity associated with alcohol
  exposure (lt60 unaffected)
• not diagnostic for specific treatment
• intensive follow-up required, high cost
• can potentially decrease the likelihood of
  adoption for exposed infants

33
Prevention by Intervention

• NEONATAL INTERVENTION CANNOT PREVENT PRIMARY
  ALCOHOL-INDUCED DAMAGE
• Mothers of alcohol-affected children are
  significantly more likely to produce subsequent
  alcohol affected children
• Substance-addicted women have an 85 incidence of
  multiple pregnancies (average 4) and 25
  incidence of child apprehension by social
  services
• EARLY MATERNAL INTERVENTION (e.g. 1st pregnancy)
  can potentially prevent future cases of FASD

34
Prevention by Intervention

• In FASD
• 50-70 incidence of substance addiction
• 50 incidence of inappropriate or promiscuous
  sexual behaviour
• FASD INTERVENTION is capable of alleviating
  secondary disabilities which perpetuate FASD

35
Ranges of Drug Concentration in Hair Adults
36
Ranges of Drug Concentration in HairInfants