Teratology Flashcards
(30 cards)
1
Q
Teratology
A
Teratology is the science of:
- Congenital developmental disorders
-Overt or latent defects of the organism resulting from effect of internal and external factors on developmental processes.” (Ujházy et al, 2012)
2
Q
Teratology- Etymology
A
Terat = sign sent by the gods, portent, marvel, monster
Ology = doctrine, theory, science of (Mirriam-Webster)
3
Q
Signal to noise ratio
A
High signal-noise ratio means easier to detect he signal
Low signal- noise ratio means it is harder to detect the signal
4
Q
Bradford Hill Criteria
A
- Temporality: cause must precede the outcome
- Strength: strong relationship between variables
- Biological gradient: dose-response effect: More exposure leads to more outcome
- Consistency: relationship is consistent in different studies and populations
- Specificity: single cause for single effect
- Plausibility: biological rationale for relationship
- Coherence: relationship consistent with previous knowledge
- Analogy: relationship synonymous with other, similar, relationships
-Experiment/intervention: randomly assigned treatment changes the outcome
5
Q
Some known teratogens
A
Medications:
- SSRIS
- Statins
- Anticonvulsants
- Thalidomide
Drugs:
- Alcohol
- Tobacco
- Cocaine
- Amphetamines/meth/MDMA
Opiates (eg: heroin)
Conditions and infections:
- Hypotension
- Toxoplasmosis
- Rubella
- Diabetes
Environmental exposures:
- Heavy metals
- Radiation
- Pesticides
- Fluoride
6
Q
Thalidomide – the first famous teratogen
A
- Anti-nausea drug developed in 1950s, and sold in UK as treatment for symptoms, including morning sickness in pregnancy
- Sold under brand name Distaval among others
- Took 5 years for authorities to realise the drug was causing birth defects
- Prenatal exposure to thalidomide can cause damage to limbs, internal organs and the brain
7
Q
Prenatal exposure to medications
A
- Studies on the neurodevelopmental impact of prenatal exposure to antidepressants tend to find null results, but some evidence of impaired motor function (Review: Gentile &Galbally, 2011)
- Broader literature review onimpact of psychotropic medications (antidepressants, benzodiazepines, mood stabilizers) found antidepressants linked to reduced IQ and impaired language performance
- Same review warned that research on the neurodevelopmental impact of psychotropic medications is limited and focuses on physical birth defects (Gentile, 2021)
- Some studies show an effect of prenatal paracetamol exposure and asthma (Barańska etal, 2023), and neurodevelopmental outcomes including ADHD, ASD, or lower IQ (Baueret al, 2018)
-The NHS advice is that paracetamol is safe to use in pregnancy but should be used sparingly
8
Q
Sodium Valproate
A
- An anticonvulsant medication used mostly for epilepsy, seizures, bipolar and migraines
- Contraindicated in pregnancy and carried a warning label
- In some with epilepsy is the only effective medication so doctor might recommend they continue to use it in pregnancy
- Exposure to valproate in pregnancy associated with a range of physical birth defects and developmental problems (Foetal Valproate Spectrum Disorder(FVSD)
- Not all people with prenatal exposure to valproate will develop FVSP – dose-response relationship, where higher exposure carries a higher riskof FVSD
9
Q
Foetal Valproate Spectrum Disorder- Developmental features
A
- Cognitive delay/low IQ
- Academic delay
- Sensory processing difficulties
- Motor control/ movement difficulties
- Language and communication difficulties
- Autism very common
10
Q
Foetal Valproate Spectrum Disorder- Facial features
A
- Hypotelorism
- Flat midface
- Small upturned nose
- Shallow philtrum
- Low set ears
- Smal mouth
11
Q
Impact of maternal prenatal stress on the foetus- mechanisms
A
- When we experience stress, stress hormones (adrenaline, cortisol, corticotropin-releasing hormone (CRH), adrenocorticotropin-releasing hormone (ACTH)) are released into our blood
-The placenta acts as a barrier, protecting foetus from many harmful compounds, but stress hormones (and all teratogens) pass through and into the blood of foetus
12
Q
The impact of maternal prenatal stress on the foetus – physical conditions
A
- Spontaneous abortion
- Structural malformations
- Preeclampsia
-Preterm birth
-Low birth weight
13
Q
The impact of maternal prenatal stress on the foetus – animal models
A
Experiments using rats and monkeys showed prenatal stressors delivered to the pregnant mother (such as being tied up, or given an electric shock) lead to changes in offspring:
- Delayed motor development
- Reduced exploration and adaptive behaviour
- More emotional and anxious reactions to unfamiliar stimuli
- Impaired cognitive function
- Alterations in social and sexual behaviour
(Mulder et al, 2002; Beydoun & Saftlas, 2008
14
Q
The impact of maternal prenatal stress on the foetus – human functional development
A
Such studies in humans have found prenatal stress is related to:
- Externalising behavioural problems
- Anxiety
- Low mood / emotional problems
- ADHD symptoms
- Motor difficulties
- Low IQ Speech and language difficulties
- Impulsivity
(Beydoun & Saftlas, 2008; Talge et al, 2007
15
Q
Heavy metals (HMs)
A
- Elements having an atomic number greater than 20 and atomic density above 5 g cm− 3
- Can be ingested in food, breathed in though air or from metal-based pesticides,tobacco smoke, and other environmental exposures
16
Q
What do studies of the impact of prenatal heavy metal exposure focus on?
A
- Lead,mercury, cadmium, chromium, arsenic (metalloid), zinc, selenium, manganese, and copper
17
Q
Prenatal exposure to heavy metals
A
Traces of metals can enter bloodstream and cross the blood-brain barrier
- Metal ions can interact with neurotransmitters, receptors, ion pumps, enzymes and amino acid, leading to altered brain development
- Literature review (Heng et al, 2022) found prenatal exposure to several heavy metals associated with neurodevelopmental changes…
18
Q
Prenatal exposure to heavy metals- Heng et al 2022
A
- Arsenic, cadmium, lead, manganese, and mercury all associated with neurodevelopmental changes
- Most evidence for lead and manganese
- Lead associated with poor academic achievement, low IQ score, externalizing behavioural problems, difficulties with memory, motor skills, language, visual-spatial ability
19
Q
Other environmental teratogens and genetic complications
A
- Organophosphate pesticides linked to increase in Autism and ADHD, but literature is mixed
- Strong evidence that Zika virus infection in pregnancy responsible for increase in microcephaly (reduced brain size) in Brazil
- Ionising radiation from nuclear bomb testing, the Chernobyl disaster,radioactive waste, and background environmental radiation linked to increase in schizophrenia
- Complex interaction between several genes and teratogenic exposures
20
Q
Cocaine
A
- Typically used with other substances so difficult to isolate the impact
- Mixed results, indicating a low signal-to-noise ratio
- In large, well-designed studies, there is a detectable effect of prenatal cocaine exposure (PCE) on visual memory, information processing, executive functions, arousal, inhibitory control, especially when theres an emotionally salient distractor
- People with PCE may have to rely on different brain structures or use more natural resources to suppress emotional responses during everyday cognitive tasks
- Children and young people with PCE show heightened stress response,frustration, disruptive behaviour in school and effects stronger in boys
21
Q
Cannabis
A
- Studies into prenatal cannabis exposure had yielded mixed results
- Typically used with tobacco so difficult to isolate the impact
- Many studies investigated them together, effectively treating them as one exposure
- Some evidence of impact on visual-spatial and motor functioning, early language development, impulsivity, hyperactivity, aggression and attention problems
22
Q
Opiates
A
- Studies difficult and tend to be of low quality with high risk of bias (small sample sizes, little control of confounding variables
- Access to users is easier in treatment, and often a mix of prescription opiates (e.g. methadone) and illegal opiates (e.g.heroin) which are more difficult to measure
- Brain studies, including animal models, show an effect on basalganglia, thalamus, and cerebellar white matter – linked to deficits in motor control and sensory function
- Neurobehavioural studies shown differences in general cognition, language and motor functioning but risk of bias is high
23
Q
Tobacco
A
- Fairly consistent evidence that prenatal tobacco exposure leads to difficulties with emotional and cognitive functioning, especially executive functioning
- Children with prenatal tobacco exposure score lower on measures of attention,orientation, attention, inhibitory control, task initiation, and metacognition
- More likely to suffer from low mood and heightened stress response,especially in boys
- In neurological studies, they show reduced volume in the frontal lobe, lateral ventricular system, and cerebellum lack of consistency in findings)
- Increased task-related brain activity, indicates having to compensate with greater brain activation to achieve same behavioural and cognitive outcomes
- Older children and teens prenatally exposed have higher rates of antisocial behaviour, conduct disorder, and addictions, even when controlling for genetic differences
24
Q
Caffine
A
- Caffeine identified as potential cause of developmental problems when consumed in pregnancy
- Findings in human epidemiological studies are inconsistent
- Lots of confounding variables
- Low signal to noise ratio
- No identifiable syndrome or phenotype
- Difficult to confirm the level of exposure -
- Experiments using animals show birth defects but not the same one reported in human studies and only at very high doses
25
Sandy’s law, Ontario
As of February 1, 2005, all establishments in Ontario that serve or sell liquor were required to display signs cautioning women who are pregnant that the consumption of alcohol during pregnancy is the leading cause of FASD
26
FASD – mechanisms of damage
- Alcohol passes though placenta into amniotic fluid
- Fetus does not metabolise alcohol
- Alcohol can kill cells via several mechanisms
- Can disrupt or reduce cell division and migration
- Can disrupt fetal sleep cycle
- Can alter functioning of neurotransmitter systems, especially glutamate and serotonin
- Can disrupt gene expression and these changes can be inherited –transgenerational epigenetics
27
Presentation- Physical signs
- Low birth weight
-Small head/brain – microcephaly
- Small stature
- Craniofacial anomalies including 3-4 facial features
- Problems with organs, joints
-Compromised immune system
28
Presentation- Neurodevelopmental
- Poor academic achievement
- Sensory dysfunction
- Problems with emotional regulation/arousal
- Executive dysfunction (planning, attention)
- Hyperactivity, impulsivity
- Difficulty with mathematics and other abstract reasoning
- Difficulty with daily living, adaptive functioning
- Problems with social communication
29
Estimated prevalence of FASD
- Problem with quality of evidence in UK
- Best data from analysis of longitudinal cohort – McQuire et al(2018)
- Estimates prevalence of FASD somewhere between 6% and17%
- Active case ascertainment (ACA) – gold standard
-Study by University of Salford found about 2-4%
- Small scale – Greater Manchester only
30
Eiden et al (2023)developmental-transactional mode
-Regards neurological, psychological, and social development as dynamic processes resulting from complex interactions between child and caregiving environment
- Developmental health dependent on child and parent adapting to each other as developmental change progresses.
