FINAL teratogenisis Flashcards
Significance of Birth Defects
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
Causes of Congenital Malformations
20% single gene disorder
10% chromosomal disorders
5% teratogen
65%: unknown
Principles of Teratology
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
Manifestations of Teratogenesis
Death (miscarriage, stillbirth) Malformation Growth retardation Functional abnormalities • behavioral • cognitive • metabolic • immune
The manifestations of teratogenesis are dose-dependent
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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
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the ergogenic periode
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
grwthe retardations is in —– trimester
third
is there a no effect zone
probably not
anything the mom is exposed to has a potential for birth defects
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Recreational Drug Use in Canada
Alcohol is the most commonly used and abused drug
Cannabis and hashish are the most commonly used illegal drugs
Substances of Abuse
Lifetime use of 8 drugs: 45.2% Hallucinogens* Cocaine* Speed* Ecstasy* Inhalants Heroin* Steroids Cannabis Lifetime use of 5 drugs (*): 16.5%
Women with Substance Use Issues
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
Women with Substance Abuse Problems
More likely to have:
Fewer resources at their disposal
Living with a partner with substance abuse problems
Mental health problems
Substance Abuse During Pregnancy
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
Selected Substances of Abuse
Alcohol Solvents Cocaine Methadone Cannabis Methamphetamines
Canadian Addiction Survey (2004)
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
Alcohol Use/Abuse
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%
alcohol use
67% of adolescent girls drink alcohol
80% of 17 year old girls drink
Use increases in street involved youth
Drinking Behavior
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
Incidence of FASD
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
2016 Health Canada Diagnostic Guidelines
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)
FASD Diagnostic Categories
FASD with Sentinel Facial Features
FASD without Sentinel Facial Features
At Risk for Neurodevelopmental Dysfunction and FASD
Neurodevelopmental Dysfunction
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
Cost of FASD
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
Fetal Solvent Syndrome
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
Cocaine
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
Methadone
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
Cannabis
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
Methamphetamines
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
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
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