Toxic Exposure in Utero Flashcards
What is fetal alcohol spectrum disorder (FASD)?
An umberlla term that describes the craniofacial, cardiovascular, skeletal, and neurologic effects that can occur when alcohol is consumed during pregnancy.
What are the diagnostic classifications that comprise FASD?
- Fetal alcohol syndrome (FAS)
- Partial FAS
- Fetal alcohol effects (FAE)
- Alcohol related birth defects (ARBD)
- Alcohol related neurodevelopmental disorder (ARND)
What are the leading cause of preventable ID in the Western hemisphere?
Fetal alcohol spectrum disorders
What is the neuropathology of fetal alcohol exposure?
- Alterations in size and structure w/in frontal, temporal, and parietal brain regions
- During 1st and 2nd trimester: interferes w/ migration, proliferation, and organization of brain cells which results in craniofacial and brain malformations
- During 3rd trimester damages the cerebellum, hippocampus, and prefrontal cortext
What are the neurochemical effects of alcohol?
- Increased turnover of NE and DA
- Decreased transmission in acetylcholine systems
- Increased transmission in GABA systems
- Increased production of beta-endorphin in the hypothalamus
What is observed on structural neuroimaging studies in those with prenatal alcohol exposure?
- Microcephaly
- Migrational anomalies
- Relative increases in gray matter but decreases in gray matter in perisylvian cortices
- Thinning or agenesis of corpus collosum
- Reduced brain growth in the ventral portions of the frontal lobes (L>R)
- Reduced cerebellar size
- Reduced basal ganglia (CN and LN)
- L hippocampus < R hippocampus
- Reduced parietal volumes
- WM hypoplasia
What are typical EEG findings in those w/ prenatal alcohol exposure?
50% w/ FAS exhibit reductions in alpha frequencies (when individuals are relaxed)
What are typical PET findings in those w/ prenatal alcohol exposure?
Reduced metabolic activity in the caudatenucleus and thalamus in children w/ FAS
What are typical SPECT findings in those w/ prenatal alcohol exposure?
Those w/ FAS show similar metabloic activity in both hemispheres
Typically developing children show > resting activity in L hemisphere
What are typical fMRI findings in those w/ prenatal alcohol exposure?
Disproportionate reductions in WM (parietal and temporal lobes)
Increased gray matter density in the parietal cortex
What are the diagnostic classifications for FASD?
FAS w/ confirmed maternal alcohol exposure
A. Confirmed maternal alcohol exposure
B. Evidence of characteristic facial abnormalities
C. Evidence of growth retardation
D. Evidence of CNS abnomralities
FAS w/out confirmed maternal alcohol exposure= C and D above
Partial FAS w/ confirmed maternal alcohol exposure- A, C, D above, plus some components of facial characteristics and behavior/cognitive abnormalities
What are the diagnostic classifications for alcohol related effects?
Alcohol Related Birth Defects
- Congenital anomalies, including malformations & dysplasias
- Includes various cardiac, skeletal, renal, ocular, and auditory defects
Alcohol-related neurodevelopmental disorder
-Evidence of CNS abnormalities
OR
-Evidence of behavioral/cognitive abnormalities
What 4 criteria must be met for a diagnosis of FAS?
1) Growth deficiency
2) Craniofacial features
3) CNS dysfunction: microcephaly (2 or more SD below the mean), callosal agenesis, cerebellar hypoplasia, seizures, motor problems, cognitive deficits
4) Prenatal alcohol exposure: confirmed or unknown
What are the characteristic craniofacial features of FAS?
- Short palpebral fissures
- Flat midface
- Short upturned nose
- Smooth or long philtrum
- This vermilion
Is the incidence of FAS higher in the US or Europe?
-It is more than 2X higher in the US compared to Europe
What are risk factors associated with FAS?
- In the US: low SES and race are confounded
- In Europe: low SES rather than race
What level of alcohol exposure is considered high risk, some risk, and an unknown risk?
- High risk: BAC greater than 100 mg/dL weekly early in pregnancy (121 lb woman drinking 6-8 beers at a time)
- Some risk: confirmed use of alcohol during pregnancy
- Unknown risk: unknown use of alcohol during pregnancy
Is chronic consumption (4-5 drinks daily) or binge drinking (5 or more standard drinks in a sitting or >9 a week) associated with FAS?
Both. Lesser quantities are associated with ARBD and ARND
During what trimester are the most significant risks associated with consumption?
First and second
What are additional risk factors associated with FAS besides SES and race?
- Polydrug use
- Higher maternal age
- Maternal mental health issues
- Lower educational attainment
- Reduced pre/postnatal care
- Inadequate nutirtion
- Stress, abuse, neglect
What is the typical disease course for children and adolescents/adults with FAS?
Children: CNS damage that leads to lifelong neurocog and behavioral problems
Adolescents/Adults: School failure, unemployment, mental health issues, and delinquency
What are the typical neuropsychological findings from those with FASD?
- Average IQ from 65-72 with great variability
- Those w/ more dysmorphic features have lower IQ scores
- 60-95% qualify for ADHD
- Pervasive deficits in visual sustained attention
- Deficits in complex reaction time
- Poor naming, and expressive and receptive language disorders
- Reduced oral motor function and speech production d/t craniofacial abnormalities
- Deficits in local analysis of visual stimuli
- Difficulties acquiring verbal information rather than retention deficit
- EF deficits
- Delayed motor development and fine motor deficits
- Poor balance
- Restless, impulsive, inattentive, disruptive, and aggressive
- Elevated levels of internalizing/externalizing disorders
Why is early diagnosis essential for those with FASD?
Because early interventions and resources may
1) Mitigate the development of secondary disabilities
2) Allow intervention and counseling to the mother to prevent the birth of additional affected children
3) Seek diagnosis and support for siblings who may be affected
What diagnoses is FASD typically comorbid with?
ADHD, CD, ODD, and OCD
What are protective factors against FASD?
1) Early diagnosis
2) Services from governmental developmental disabilities programs
3) Living in a stable home
4) Protection from violence
Through what medium does in utero exposure to cocaine typically occur?
Crack cocaine
How does cocaine affect the CNS?
It effects the monoamine system (especially DA)
In early gestation: Affects neural proliferation and migration
In later gestation: affects neuronal maturation and synaptogenesis
May lead to abnormalities in the frontocingulate cortex, including the anterior cingualte gyrus
What are physical characteristics of infants prenatally exposed to cocaine?
Small head circumference and low birth weight
In infants exposed to cocaine there is a dose response relationship between amount of in utero exposure and what?
Later neurobehavioral problems
What are neurobehavioral characteristics of those exposed to cocaine in the neonatal period and toddler/preschool stage?
Infant: poor sleep cycles, abnormal startle response, abnormal brainstem evoked potentials
Toddlers: impulsivity and emotional lability
What are expectations for neuropsych findings in infants exposed prenatally to cocaine?
- Lower overall IQ
- Deficits in attention and arousal
- Slower reaction times
- Language delays
- Deficits in working memory
- Executive dysfunction
- Impulsive and poor emotional controll
What effects does heavy marijuana exposure have in utero?
- Delay in infant visual maturation and visual attentiveness
- Heightened tremors and startles
- Exaggerated Moro reflex
- Increased occurrence of athetoid movements
- Disinhibition on motor tasks
What percentage of woman report using marijuana during their first trimester?
3%
Use 6 or more times per week is associated with a reduction in length of gestation.
After controlling for _________ many neurobehavioral consequences of prenatal exposure to marijuana do not remain significant.
Maternal risk factors
What are expectations for neuropsych findings for those exposed to marijuana in utero?
- Possible increased hyperactivity, inattention, and impulsivity
- Altered neural functioning during visuospatial working memory processing
- Decreased rates of visual habituation
- Risk of delinquent behavior in adolesence
What are common sources of mercury?
- Fungicides and pesticides
- Cosmetics
- Dental fillings
- Commercial thermometers
- CFL bulbs
- Coal fired power plants
- Fish contaminated w/ mercury
What are the symptoms of acute mercury poisoning?
- Parasthesia, deterioration in fine motor coordination, restriction of visual fields
- Progresses to severe ataxia, dementia, and death
- Caused by dimethylmercury exposure
What are the neuropathological effects of mercury in fetal cases?
- Atrophy and hypolasia of the cerebral cortex and corpus callosum
- Abnormal cytoarchitecture
- Demyelnation of pyramidal tract
-Results in brain damage, ID, incoordination, blindness, seizures, and inability to speak
What is the reference does for methylmercury?
5.8mg/L
8% of childbearing women have blood mercury concentrations greater than this level
What are the biggest areas of concern to the general population with regard to mercury exposure?
- Fish and shellfish: FDA recommends that pregnant women, breastfeeding mothers, and young children avoid fish with high mercury content
- Vaccines: thimerosal (50% mercury) used to be used as a preservative but has since been removes
- Dental amalgams: Public Health Service concluded that dental amalgams do not pose a health risk of mercury exposure
Why do fetuses have the greatest risk to mercury exposure?
They are unable to excrete mercury
Methylmercury most readily passes through the placenta
What are outcomes of offspring of women exposed to significant mercury?
- Cortical degenerative disease
- Cerebral palsy
- ID
- Severe sensory deficits
- Microcephaly
- Limb malformations
What are expectations for neuropsychological assessment results in fetuses exposed to high levels of mercury?
- Reduced activity level in boys
- Deficits in motor skills, attention, language, visuospatial skills, and memory
- Lower overall intelligence scores
What are PCBs and how does primary human exposure occur?
- Polychlorinated biphenyls- organic chemical
- Exposure occurs through highly contaminated fish and sea mammals
How do PCBs affect the developing fetus?
- They are endocrine disruptors and change thyroid hormone levels
- Decreased size of spelnium of corpus collosum
- Neurotoxic effect on DA activity
What are the physical and neuropsych findings for infants exposed to PCBs?
- Low birth weight and delays in sensorimotor/cognitive abilities
- Reduced verbal abilities and deficits in executive functions
What are sources of exposure to inorganic lead (Pb)?
Drinking water from lead pipes, and imported candies, toys, cosmetics, and pottery
Paint chips and/or paint dust during renovations
Maternal occupational exposure is the most likely cause of in utero exposure
What effect does Pb have on the CNS?
Passes the BBB by mimicing calcium
Interferes with neurulation, migration, synaptogenesis, and neurotransmission
May affect the DA system
MRI demonstrates reduced volume in the frontal gray matter, anterior cingulate, and prefrontal cortex
What is the current “action level” of Pb at which public health actions are recommended?
5mg/dL
<30 mg/dL = low lead level
>80 mg/dL = lead encephaloapathy
>44 mg/dL = pharmacologic intervention
What are signs of elevated lead levels?
Headache, irritability, abdominal pain, vomiting, weight loss, attention problems, hyperactivity, learning problems, and slowed speech development
What are the expectations for neuropsych results in someone with high Pb levels?
- Declines in IQ and academic achievement
- Attention and executive function deficits
- Impaired visuospatial skills
- Restless, impulsive, inattentive, aggressive
- Higher levels of internalizing and externalizing disorders
What percent of lead to adults versus children absorb?
Children absorb 50% of ingested lead and adults absorb only 10-15%
What is chelation therapy?
The use of a chemical substance that removes excess or toxic metals before they cause damage to the body
Children with blood lead levels greater than 44 mg/dL are treated with chelation
It may not be effective in reversing cognitive declines
What are the neuropsych effects of in utero exposure to tobacco/nicotine?
Equivocal findings but there may be increased rates of disruptive behavior disorders such as ADHD
What are neuropsych findings of antieplieptic medications, blood thinners (warfarin), acne medications (isoretinoin), and SSRIs in utero?
Antiepileptic meds: major birth defects such as neural tube defects, especially w/ valproic acid and polytherapy
Warfarin: Developmental delays and Dandy-Walker malformation
Isoretinoin: Birth defects and ID
SSRIs: can lead to neonatal abstinence syndrome
What is acrodynia?
Rare disease that affects young children exposed to mercury.
Symptoms: irritability, photophobia, pink discoloration and edema of hands and feet, hair loss, irritability, anorexia, insomnia, poor muscle tone, profuse sweating, and polyneuritis
Often misdiagnosed as measles, another virus, or Kawasaki disease
What is neonatal abstinence syndrome?
A nonspecific group of symptoms that can be displayed by some newborns whose mothers used illicit or prescription drugs during pregnancy.
Symptoms: excessive crying, irritability, hyperactive reflexes, seizures, and increased muscle tone
What is a reference dose?
An exposure without recognized adverse effects
