FINAL teratogenisis

Question 1

Significance of Birth Defects

Answer 1

Responsible for:
up to 50% of hospital admissions
10% of deaths in newborn period
40% of death within 1st year of life
15-20% of stillborn infants have a major malformation
Present in 3% of newborns ( to 5-8% at 5 years)
14% of newborns have minor malformations

Question 2

Causes of Congenital Malformations

Answer 2

20% single gene disorder
10% chromosomal disorders
5% teratogen
65%: unknown

Question 3

Principles of Teratology

Answer 3

The risk of abnormal development varies with the developmental stage of the fetus at the time of exposure
brain is sensitive all the way through

Question 4

Manifestations of Teratogenesis

Answer 4

Death (miscarriage, stillbirth)
Malformation
Growth retardation
Functional abnormalities
• behavioral                • cognitive
• metabolic                 • immune

Question 5

The manifestations of teratogenesis are dose-dependent
!!

The risk for abnormal development is dependent on the interplay between the genetic makeup of the fetus and the environmental insult

Teratogenic agents act in specific ways to initiate abnormal development

Answer 5

i love you

Question 6

the ergogenic periode

Answer 6

the first 12 weeks
this is when all the organs are developing
(beofre this time its all pluripotential cell where they can divid into anything - no affects can be seen)
after that the the fetal periode (extra toes…) this is when the malformations appear

Question 7

grwthe retardations is in —– trimester

Answer 7

third

Question 8

is there a no effect zone

Answer 8

probably not

Question 9

anything the mom is exposed to has a potential for birth defects

Answer 9

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Question 10

Recreational Drug Use in Canada

Answer 10

Alcohol is the most commonly used and abused drug

Cannabis and hashish are the most commonly used illegal drugs

Question 11

Substances of Abuse

Answer 11

Lifetime use of 8 drugs: 45.2%
Hallucinogens*
Cocaine*
Speed*
Ecstasy*
Inhalants
Heroin*
Steroids
Cannabis 
Lifetime use of 5 drugs (*): 16.5%

Question 12

Women with Substance Use Issues

Answer 12

History of trauma
Come from child welfare system
Experienced homelessness and deep poverty
Survivors of domestic or relational violence, including physical and sexual abuse
Involvement with the Criminal Justice System

Question 13

Women with Substance Abuse Problems

Answer 13

More likely to have:
Fewer resources at their disposal
Living with a partner with substance abuse problems
Mental health problems

Question 14

Substance Abuse During Pregnancy

Answer 14

2.3 – 5.5% of pregnant women reported use of an illegal drug
Characteristics of abusers:
Lower socioeconomic status/living in poverty
Less formal education
Single, separated, divorced or widowed
No permanent residence

Women with significant substance use typically use more than one drug
Vancouver study:
23% used cocaine
18% used hallucinogens
10% used intravenous drugs
8% used opiates
92% used alcohol

Question 15

Selected Substances of Abuse

Answer 15

Alcohol
Solvents 
Cocaine
Methadone
Cannabis
Methamphetamines

Question 16

Canadian Addiction Survey (2004)

Answer 16

Abstainer: 7.3%
Light infrequent: 38.7%
Less than 5 drinks, less than once per week
Light frequent: 27.7%
Less than 5 drinks, more than once per week
Heavy infrequent: 5.6%
5 drinks or more, less than once per week
Heavy frequent: 7.1%
5 drinks or more, more than once per week

Question 17

Alcohol Use/Abuse

Answer 17

Past year drinking:
Lifetime abstainers: 7.2%
Former drinkers: 13.5%
15 years or older consuming alcohol: 79.3%
44% at least once per week
9.9% ≥ 4 times per week

Past year drinkers:
1 – 2 drinks/drinking day: 63.7%
≥ 5 drinks/drinking day: 16%

Heavy drinking at least once/week: 6.2%
Heavy drinking at least once /month: 25.5%

Low risk drinking guidelines:
Females: 9 drinks/week
Males: 14 drinks /week
and a limit of 2 drinks/day
Meet low risk guidelines: 77.4%
Exceed low risk guidelines: 22.6%

Question 18

alcohol use

Answer 18

67% of adolescent girls drink alcohol
80% of 17 year old girls drink
Use increases in street involved youth

Question 19

Drinking Behavior

Answer 19

Binge drinking during pregnancy
15 – 17 years: 7%
18 – 25 years: 4.8%
26 – 44 years: 3.1%
Teens and young adults tend to recognize pregnancy later
Result: increased risk for binge drinking during pregnancy

Question 20

Incidence of FASD

Answer 20

0.5 - 3.0/1000 general population
Incidence may vary in specific groups
No change in incidence in Saskatchewan over past 20 years: 0.59/1000
Health Canada – estimates the incidence of FASD to be 1/100

Question 21

2016 Health Canada Diagnostic Guidelines

Answer 21

Use of FASD as a diagnostic term
Recognition that growth parameters may not be significant in terms of discriminating morbidity 
Assess:
Prenatal exposure to alcohol
Sentinel facial features
Neurodevelopmental dysfunction

CMAJ February 16, 2016; 188 (3)

Question 22

FASD Diagnostic Categories

Answer 22

FASD with Sentinel Facial Features
FASD without Sentinel Facial Features
At Risk for Neurodevelopmental Dysfunction and FASD

Question 23

Neurodevelopmental Dysfunction

Answer 23

Prenatal alcohol exposure is among the most commonly known causes of intellectual disability
Can cause a range of disability from invisible changes in executive function to learning disability to intellectual disability
The brain is the most sensitive organ to the teratogenic effects of prenatal alcohol exposure
Motor skills
Neuroanatomy/ neurophysiology
Cognition
Language
Academic achievement
Memory

Attention
Executive functioning including impulse control and hyperactivity
Affect regulation
Adaptive behavior, social skills, social communication

Question 24

Cost of FASD

Answer 24

The comprehensive lifetime cost of just one baby with FASD could be as much as $6 million
The cost to Canadian taxpayers for Fetal Alcohol Syndrome is estimated to be $300 million each year

Question 25

Fetal Solvent Syndrome

Answer 25

Also known as toluene embryopathy
Aromatic hydrocarbon organic solvent
Component of gasoline, glue, paint, lacquer thinner
Popularity due to relative ease of accessibility, low cost and misperceived lack of addictive qualities

Denver study:
Prematurity
Birth weight, length, head circumference
Dysmorphic features
Narrow bifrontal diameter, short palpebral fissures, midface hypoplasia, wide nasal bridge
Abnormal palmar creases
Blunt fingertips

Neonatal complications:
Polycythemia, acidosis, hypocalcemia 
Follow-up evaluations:
Persistent weight and length <5th % and microcephaly
38% cognitive or motor delays
38% speech delay
Behavioral disturbances:
Jittery and irritable in neonatal period
Hyperactivity, aggressiveness, head banging

Question 26

Cocaine

Answer 26

Risk of congenital malformations is greater with larger (more frequent, higher dose) exposures
Defects associated with CNS hemorrhage or infarction
Intestinal atresia, gastroschisis, sirenomelia, limb-body wall complex, limb reduction defects
Vascular disruption is a particular hazard with 2nd or 3rd trimester use
** placental disruption

Is there a Fetal Cocaine Syndrome?
Low birth weight, microcephaly, prominent glabella, periorbital and eyelid edema, low nasal bridge, short nose and toenails
Association with neonatal necrotizing enterocolitis (less blood to intestines and can get holes in it)

Prenatal growth retardation
Effects of concomitant alcohol and tobacco use
Normalizes by school age
Neonatal behavioral abnormalities
Attention, arousal, affect and action
No neonatal withdrawal syndrome
Increased risk for SIDS

In utero cocaine exposed boys:
Lower IQ scores
Lower abstract/visual reasoning
Deficits in short term memory
Deficits in verbal reasoning

Women who used cocaine:
Less sensitive to their infants’ cues at 6 ½ months and 12 months
At 6 ½ months heavy users were less responsive to their infants than light users
Prenatal cocaine use plus lower intellectual functioning adversely affected maternal-infant interactions

Question 27

Methadone

Answer 27

Unlikely to pose a substantial teratogenic risk if part of supervised program
Potential effects of concomitant use of other drugs as well as adverse nutritional, infectious and psychosocial factors
No increase in malformations
Decreased fetal growth but not persistent into childhood

At risk for visual problems:
Reduced acuity: 95%
Nystagmus: 70%
Delayed visual maturation: 50%
Strabismus:(crossed eyed) 30%
Refractive errors: 30%
Cerebral visual impairment: 25%

Withdrawal symptoms may occur in newborn infants
Mild but persistent deficits on psychometric and behavioral tests
Increased risk of SIDS

Question 28

Cannabis

Answer 28

Widely used as “recreational” drug
Principal ingredient:
delta-9-tetrahydrocannabinol
Frequency of major malformations no greater than expected
No association with decreased birth weight and length or spontaneous abortions

Many of published studies confounded by variables such as alcohol and tobacco use, timing and duration of exposure, race and socioeconomic status
Increased risk for depressive and anxious symptoms at age 10

Question 29

Methamphetamines

Answer 29

Decreased birth weight and head circumference
Effects on growth greater when exposure during all of pregnancy vs. 1st or 2nd trimester use
Significantly decreased growth with associated smoking

4% of infants with withdrawal symptoms
Symptoms of agitation, vomiting and tachypnea
MRI: smaller putamen, globus pallidus, caudate and hippocampus volumes
Changes in energy metabolism in brains of children with prenatal exposure

Neurodevelopmental assessments
Decreased visual motor integration, attention, verbal memory and long term spatial memory
No difference in motor skills, short term spatial memory and measures of non-verbal intelligence

Question 30

Conclusions:
Prenatal exposure to recreational and illicit drugs can impact the developing fetus
Cost of these exposures can have significant effects not only on the fetus but on society in lost productivity and costs related to disability
Important to look at the underlying reasons for substance abuse and their impact on the social determinants of health

Answer 30

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