Ch 21 Toxic exposure in utero Flashcards
Alcohol
teratogen that passes through the placental barrier and affects the developing fetus throughout gestation
fetal alcohol spectrum syndrome (FASD) is a diagnostic term T or F?
False, it’s not a diagnostic term, it’s an umbrella term
FASD describes
craniofacial
cardiovascular
skeletal
neurological deficits
FASD includes what syndromes
Fetal alcohol syndrome
Partial FAS (PFAS)
alcohol-related birth defects (ARBD)
alcohol-related neurodevelopmental disorder (ARND)
Leading cause of preventable ID
Fetal alcohol syndrome
Small amount of alcohol consumption is safe during pregnancy. T or F
False - no level of alcohol consumption is safe during pregnancy
prenatal alcohol exposure leads to alterations in
size and structure across brain regions
during 1st and 2nd trimester, prenatal alcohol consumption interferes with what?
migration, proliferation, organization of brain cells
results in varying craniofacial and brain malformations
during the 3rd trimester, prenatal alcohol consumption interferes with what?
damage to the cerebellum, hippocampus, prefrontal cortex
neurochemical effects of alcohol
increased turnover of norepinephrine and dopamine
decreased transmission of acetylcholine
increased transmission in GABA system
increased production of beta endorphin in the hypothalamus
Which part of the brain is affected in FASD?
white matter!!
Structural abnormalities in FASD
microcephaly
migrational anomalies
disproportionate reduction in gray and white matter volume (frontal, parietal, temporal)
white matter hypoplasia > gray matter hypoplasia
Diagnosis of FAS (4 criteria)
growth deficiency
craniofacial features
CNS dysfunction
prenatal alcohol exposure
FAS Criteria 1 - growth deficiency
below average height and or weight
small for gestational age
show growth deficiency as adolescents and adults
FAS Criteria 2 - craniofacial features
short palpebral fissures (eye width decrease with increase prenatal alcohol) flat midface short upturned nose smooth or long philtrum (ridges between lip and nose) thin vermilion (upper lip thinner with more alcohol)
FAS Criteria 3 - CNS dysfunction
microcephaly (2+ SD below the mean) callosal agenesis cerebellar hypoplasia seizure fine and gross motor problems hearing loss cognitive deficits (memory, EF, attention, LD)
FAS Criteria 4 - Prenatal Alcohol Exposure
confirmed ur unknown
no biochemical marker can confirm consumption
Alcohol-related birth defects (ARBD)
congenital anomalies in cardiac skeletal renal ocular auditory
alcohol related neurodevelopmental disorder (ARND)
A. CNS abnormalities such as structural brain abnormalities
B. behavior or cognitive abnormalities inconsistent with development
ND-PAE (neurodevelopmental disorder associated with prenatal alcohol exposure)
some exposure to alcohol
impaired neurocognitive fx, self regulation, adaptive fx
prevalence of FAS
10%
USA prevalence of FAS higher than Europe by
2x
FASD rates in USA
9/1000 births
Risk factors of FAS in USA
Race and SES are confounded higher maternal age low education low econ background MH issues social isolation abuse hx
which racial group has the highest FAS rate
Black or native americans
10x more than whites or high SES
factors that determine severity of FAS
quantity consumed pattern of exposure timing of exposure additional risk factors - multiple drugs - high maternal age - maternal Health issues - lower education, reduced access, nutrition, stress, abuse
quantity consumed definition
no consensus but 3 risk levels
- high risk - BAC > 100mg/dL (average size woman drinking 6-8 beers in one sitting)
- some risk - use less than high risk
- unknown risk
- no risk (no use)
pattern of exposure
chronic consumption (4-5 drinks daily) binge drinking (5 or more standard drinks) 9 or more a week
timing of exposure
drinking in 1st trimester - increases FASD by 12x
drinking in 1st and 2nd trimester - increases FASD by 61x
drinking in ALL trimester - increases FASD 65x
children with FAS have CNS damage, true or false
TRUE
FASD NP - IQ
great variability, IQ 20-120
more dysmorphic features = lower IQ
25% FAS and 10% ARND IQ <70
FASD NP LD
learning difficulties, reading and spelling and math
low school performance
school attendance
FASD NP Attention
60-95%ADHD
3-9x higher than normal kids
impaired visual sustained attention, auditory verbal attention
FASD NP processing speed
deficits on challenging tasks and complex
working memory deficits
FASD NP speech and language
oral motor function and speech production
naming
expressive and receptive language disorder
comprehension higher level
pragmatics
FASD visuospatial
deficits in local vs global analysis of visual stimuli
VS construction deficits (maybe due to motor deficits)
FASD Executive function
deficits many domains
FASD sensorimotor
delay motor development
deficits in fine motor (reduced cerebellar size)
tremor, weak grasp, poor eye hand coordination
balance
sensory integration
FASD emotion and personality
restless, impulsive, disruptive, aggressive, delinquent antisocial behaviors juvenile delinquency sleep disturbance adaptive behavior
% of cases that get diagnosed with FASD
only 25% due to limited expertise
only 11% diagnosed by age 6
early intervention is important with diagnosis because it can..
mitigate development of secondary disability
have appropriate intervention, counseling
get support
comorbid dx with FASD
ADHD
CD
ODD
OCD
protective factors for FASD
early dx
services
stable home
protection from violence
how does cocaine affect the CNS in utero exposure?
effects on monoamine system
dopamine
exposure in early gestation affects neural proliferation and migration
exposure in late gestation affects neuronal maturation and synaptogenesis
brain abnormalities 2/2 cocaine exposure in utero?
abnormalities in frontocingulate cortex
anterior cingulate gyrus
% of pregnant women worldwide using cocaine
0.5-3%
consequences of maternal cocaine use on infants?
Small head circumference low birth weight Poor sleep cycle abnormal startle response abnormal brain stem evoked potential impulsivity emotional lability low frustration tolerance
NP results for cocaine exposure in utero
Lower overall IQ
Deficits in academic achievement (parent education, SES)
Impairment in sustained and selective attention
Slow processing speed (due to poor attention regulation)
Language delay (esp expressive)
visual spatial deficits
working memory and executive function
marijuana
psychoactive and medicinal use
Predominant psychoactive constituent in marijuana
THC
What pathway is associated with the rewarding property of cannabis
Meso cortical limbic dopamine system
What changes are produced by THC use
mood perception motor coordination short-term and working memory concentration
Does THC cross the placenta during gestation?
yes
It is secreted in maternal milk during lactation
8x higher concentration in breast milk than in plasma
Effects of prenatal cannabis exposure
Fetal growth restriction in mild in late pregnancy Low birth weight Increased risk of stillbirth altered sleep patterns irritability excitability and arousal
Infants exposed to cannabis in utero have increased risk of birth defects, true or false
false
Heavy marijuana exposure effects
Delay in visual maturation and visual attentiveness
Heightened tremors
exaggerated startle and visual responses
poor habituation to novel stimuli
exaggerated moro reflex
athetoid movements
disinhibition in motor tests (like in narcotic withdrawal)
Which is the third most used drug after alcohol and tobacco during pregnancy
Marijuana
Percentage of pregnant women using marijuana during pregnancy
2-6%
Heavy marijuana use has been associated with what changes in length of gestation
Reduction in length of gestation by one week
Which gender is more vulnerable on testing after prenatal cannabis exposure
male
Neuropsychological assessment results for prenatal cannabis exposure (PCE)
IQ unaffected
underachievement in reading, spelling math
problems with attention and concentration (could be confounded by alcohol use
hyperactivity, inattention, impulsivity
executives functions deficit, working memory
Visual spatial processing
sensorimotor - unaffected by age 1 but
- decreased rate of visual habituation
- increased tremor (4 day olds)
mood:
delinquent behavior in middle adolescence
depression
behavioral dysregulation
Primary human exposure of methylmercury
eating contaminated fish (shark, tuna, swordfish)
shellfish
Consumption of mercury can be done through what ways
Ingested
inhaled
absorbed through the skin
Organs commonly affected in mercury exposure
Neurologic
gastrointestinal
renal systems
How does methyl mercury gain access to brain tissues
By active transport into the endothelial cells in the blood brain barrier
Methylmercury destroys neurons and causes cerebral atrophy in both hemisphere
Deadliest of the Mercury compounds
dimethylmercury
What happens when exposed to dimethylmercury
It can cause acute mercury poisoning by permeating the skin, getting into the bloodstream, and depositing in the brain, kidneys and other organs
Symptoms of exposure to dimethylmercury
Paresthesia deterioration in fine motor coordination restriction of visual fields severe ataxia dementia death
which barrier can methylmercury cross
placenta barrier
blood brain barrier
prenatal exposure to mercury results in
atrophy of cerebral cortex and corpus callosum dysmyelination of pyradmidal tract ID poor motor coordination blindness seizure inability to speak progressive cortical degenerative disease cerebral palsy sensory deficits microcephaly limf malformationlumb
common exposure to mercury
fish consumption
vaccine
dental amalgams
why do fetuses have greatest risk to mercury exposure?
because they can’t secrete it
which brain structures are affected in infants or children when mother is exposed to mercury
occipital cortex
cerebellum
Neuropsych assessment results in mercury exposure
deficits in attention motor skills language VS memory expressive language overall IQ reduction in activity level in boys
Environmental toxicant - polychlorinated biphenyl (PCB))
used in transformers, adhesives, tapes, plastic and rubber products, oil based pain, electrical devices, carbonless copy paper
primary human exposure of PCB
highly contaminated fish and sea mammals
neuropathology of PCB
disruption of endocrine system
changes in thyroid hormone level in infants
decreased size of splenium of corpus callosum
effects of PCB in utero exposure
low birth weight
delays in sensorimotor and cognitive abilities
NP results of PCB
deficit in verbal ability
EF
Inorganic lead exposure through what means
drinking water from lead pipes
imported candies, toys, cosmetics, pottery
paint chips and paint dust
lead can pass through what barrier
blood brain barrier
what happens after lead reaches CNS?
CNS -> interferes with neurulation, migration, synaptogenesis, neurotransmission
what happens when lead reaches the fetus
crosses the placenta and accumulates in fetal organs
how is the brain impacted by lead exposure
decreased cerebral volume in: frontal gray matter ACC prefrontal cortex possible neuronal loss
incidence rate of lead exposure up or down
declined sharply but high in low income areas, minority
determinants of severity of lead exposure
ACTION LEVEL = blood lead level of 5 mg/dl or higher
different lead levels and classification of deficits
<30 low lead level
>44 pharmacological intervention CHELATION Therapy
>80 can lead to lead encephalopathy
signs of elevated lead level?
headache irritability abdominal pain vomiting weight loss attention problems hyperactivity learning problems slowed speech
NP results in lead exposure
decline in IQ decline in academic achievement EXECUTIVE FUNCTION most affected visual spatial skills restless, impulsivity, inattentive, aggressive ADHD ODD antisocial behaviors
% of lead that can be absorbed by children
50%
% of lead that can be ingested by adults
10-15%
more severe effects are seen when lead is exposed during what stage of development?
in utero and infancy (more severe than later childhood and adulthood)!
What is chelation therapy
treatment for children whose blood lead level is >44
trap lead in the blood and remove it through urine
helps with reducing lead level but NOT reverse cog deficits
in utero exposure to Nicotine and Tobacco results
reduced fetal oxygen supply
fetal undernourishment
vasoconstrictor effects on placenta and umbilical cord
in utero exposure to amphetamine results in
motor deficits during infancy
EF deficits in childhood
poor emotional regulation
in utero exposure to opiates results in
decrease in neural plasticity increase in cell death lower birth weight motor deficits in infancy deficits in EF and ADHD in childhood
in utero exposure to pesticides results in
enzymes that regulate acetylcholine
in utero exposure to air pollution results in
lower IQ
poorer academics
behavioral problems
in utero exposure to antiepileptic meds in 1st trimester
major anatomical birth defects
in utero exposure to antiepiletic meds in 3rd trimester
behavioral and cognitive deficits
in utero exposure to valporic acide and polytherapy
verbal deficits
increased risk for adhd, ASD
in utero exposure to Coumadin/blood thinner
developmental delay
dandy walker syndrome
in utero exposure to accutane (acne meds)
birth defect
ID
in utero exposure to SSRI
neonatal abstinence syndrome
-excessive crying, irritability, hyperactive reflex, seizure, increased muscle tone
Acrodynia
affects young children exposed to mercury
misdiagnosed as measles, kawasaki disease
sx = irritability, photophobia, pink discoloration, edema of hands and feet, hair loss…
reference dose
exposure without recognized adverse effects
Lead NP
EF!!!
Tobacco NP
Adhd
Externalizing
Cocaine NP
Attention
PCB potentiates by
Mercury!
Alcohol
Affects parietal > temporal and occipital
