Prenatal substance use Flashcards
epidemiology of substance use by pregnant women (5)
- tobacco and alcohol most common substances used
- illicit and licit drugs lower, but significant
- cannabis most common psychoactive substance used
- many use more than one substance
- substances used vary by race and ethnicity
epidemiological trend of tobacco use in pregnant women (3)
- use is decreasing
- younger women (<24) more likely (also more likely to report use)
- higher rate with lower socioeconomic status
epidemiological trend of alcohol use in pregnant women (2)
- higher rates in older women
- higher rate with lower socio economic status
epidemiological trend of cannabis use in pregnant women (3)
- rates have increased (higher since legalization)
- because more reports or think it’s safe?
- higher rates amongst 15-24 years
risk factors for substance use during pregnancy (7)
- history of drug/alcohol related problems
- family history (genetic and environmental factors)
- frequent encounters with law enforcement
- partner who abuses substances
- history of sexual abuse
- poverty and homelessness
- psychiatric illness - anxiety, depression, PTSD
exposure in different trimesters
trimester 1 -> most likely to have teratogenic effects
trimester 2/3 -> more likely to see cognitive or behavioral effects (affects brain, neurobiology)
pharmacokinetic principles of drugs (4)
- absorption: how does drug enter
- distribution: where does drug go
- metabolism: how is drug broken down
- elimination: how is drug eliminated
ex of how pregnancy can affect ADME
A -> nausea/vomiting: drug less absorbed
D -> more fat, more distribution
M -> fast/slow metabolizers: length of exposure to drug
E -> kidney filtering rate
placenta (2)
- drugs transferred from mother to fetus via placenta (same route taken by O2 and nutrients)
- placenta is temporary organ that attaches to wall of uterus, where umbilical cord arises from
functions of placenta (4)
- provide O2 and nutrients
- remove harmful waste products
- produce hormones
- pass immunity
ability of drug to cross placenta depends on (2)
- physical properties of placenta
- specific physiochemical drug properties
properties affecting drug transfer across placenta: placental properties (7)
- placenta surface area
- placenta thickness
- pH of maternal and fetal blood
- placenta metabolism
- uteroplacental blood flow
- presence of placental drug transporters
- concentration gradient across placenta
drug properties increasing transfer across placenta (4)
- < 500-1000 Da
- uncharged
- high lipophilicity
- no protein binding (smaller molecule)
properties affecting drug transfer across placenta: drug properties (4)
- molecular weight
- lipid solubility
- ionization/charge
- protein binding
which drugs are most likely to pass into breast milk
drugs with same physiochemical properties as those that pass through placenta
mechanisms of fetal harm: general (4)
- direct harm: to fetus itself (teratogen)
- via placenta (indirect): impaired function
- via mother’s physiological response (indirect)
- poor nutritional health secondary to substance use (indirect)
mechanism of fetal harm: tobacco (2)
- increase of nicotine and CO2: vasconstriction + reduction of O2 levels to fetus
- nicotine increases other chemicals that cause deregulation in normal fetal development (catecholamines)
obstetrical complications: tobacco (5)
- spontaneous abortion
- placenta abruption
- placenta previa
- premature rupture of membranes
- uterine infections
neonatal outcomes: tobacco (6)
- premature birth
- stillbirth
- low birth weight
- increased risk of SIDS
- fetal growth restriction
- cleft lip/palate
childhood outcomes: tobacco (5)
- SIDS
- increased risk of asthma
- congenital heart defects
- diabetes mellitus
- impaired cognitive ability
breast milk and tobacco (8)
- nicotine readily absorbed in breast milk
- can possibly decrease milk supply
- reduced appetite
- diarrhea, vomiting
- sleep disturbances
- high risk of SIDS
- increased HR and respiratory illness
- obesity and thyroid problems
impact of alcohol (2)
- crosses placenta
- anxiolytic that causes CNS depression
mechanism of fetal harm: alcohol (4)
- damages cells by ROS: interact with DNA, proteins, lipids
- ethanol and acetaldehyde responsible for biological effects
- underdeveloped fetus liver: unable to metabolize/eliminate alcohol, goes back into mom until she metabolizes it (prolonged exposure)
- prolonged exposure -> teratogenic effects (esp in 1st trimester)
obstetrical complications: alcohol (3)
- IUGR
- increased risk of stillbirth
- increased risk of miscarriage
neonatal complications: alcohol (4)
- FAS
- withdrawal symptoms at birth
- fetal death
- reduced birth weight
childhood outcomes: alcohol (6)
- poor growth
- attention problems like ADHD
- delinquent and criminal behaviors
- SUDs
- impaired learning, memory, IQ
- language and communication disabilities
FAS physical outcomes at birth (3)
- inadequate growth before or after birth
- birth defects of face
- microencephaly
FAS outcomes in childhood development (4)
- intellectual disability
- abnormal behavioral development
- joint abnormalities and heart defects
- increased risk of ADHD, antisocial behavior
breast-milk and alcohol (3)
- newborns metabolize alcohol at 1/2 rate of adults
- decrease in milk intake
- interference with sleep/wake cycle
why pregnant women use cannabis (3)
- anxiety
- insomnia
- morning sickness
mechanism of fetal harm: cannabis (3)
- cross placenta (high lipophilicity) and distribute into fetal brain
- CB1R and CB2R found as soon as 14 weeks gestation (deregulation of development of endocannabinoid system associated with adverse outcomes)
- long half-life (low fetal clearance)
when is THC measurable in fetal brain after maternal exposure
within 15 minutes
obstetrical complications: cannabis (4)
- premature delivery
- risk of miscarriage
- IUGR
- reduced blood flow to placenta
neonatal outcomes: cannabis (5)
- neonatal death
- premature birth
- smaller head circumference
- neurobehavioral outcomes: ex ASP
- congenital abnormalities (only correlations exist)
childhood outcomes: cannabis (7)
- attention deficits
- hyperactivity/impulsivity
- depressive/anxious symptoms
- aggressive behaviors
- deficits in verbal, perceptual, social, cognitive skills
- delinquency
- smoking/substance use
*some conditions are genetic so is it really the substance or the genetics/environment
breast milk and cannabis (4)
- THC and CBD accumulate in breast milk
- increased sedation and lethargy
- reduced appetite
- reduced maternal bonding
effects of opioids binding to opioid receptors (3)
- pain relief
- euphoria
- dysphoria
response of activation of each opioid receptor (3)
mu -> analgesia, respiratory depression, miosis, euphoria, reduced GI motility
delta -> analgesia
kappa -> analgesia, respiratory depression, miosis, dysphoria, psychotomimetic effects
mechanism of fetal harm: opioids (3)
- low molecular weight, low protein binding, high lipophilicity -> readily crosses placenta
- infants born have passive dependency -> when umbilical cord cut, supply disrupted -> withdrawal symptoms in baby
- repetitive patterns of withdrawal reduces blood flow to placenta, lowers O2 supply and interferes with fetal development
obstetrical complications: opioids (7)
- premature birth
- premature rupture of membranes
- miscarriage
- placenta abruption
- intrauterine infection
- preeclampsia
- postpartum hemorrhage
neonatal outcomes: opioids (6)
- premature birth
- poor fetal growth
- low birth weight
- prolonged hospital stays
- birth defects? (associations)
- neonatal abstinence syndrome (NAS)
what is NAS
group of conditions that can occur when newborns withdraw from certain substances that they were exposed to before birth
withdrawal symptoms of NAS: CNS (6)
- inconsolable crying
- high pitch crying
- skin irritation
- hyperactive reflexes
- tremor
- seizures
withdrawal symptoms of NAS: GI (4)
- poor feeding
- excessive sucking
- feeding intolerance
- loose or watery stools
withdrawal symptoms of NAS: autonomic (5)
- sweating
- nasal stuffiness
- sneezing
- fever
- trachypnea
timeline of NAS withdrawal symptoms (2)
- onset within 24-72h after birth
- preterm infants have a later onset and less severe symptoms
why do preterm infants have a later onset of NAS and less severe symptoms (2)
- developmental immaturity of nervous system
- reduced total drug exposure (shortened gestation)
childhood outcomes: opioids (4)
- lower IQ/intellectual difficulties
- behavioral problems
- poor language development
- hyperactivity
*adverse neurocognitive, behavioral and developmental outcomes
breast milk and opioids (5)
- present in breast milk
- CNS depression
- lethargy
- reduced clearance in baby, prolonged exposure
- reduced appetite
impact of cocaine (3)
- lipophilic: crosses placenta
- inhibits NE and epi reuptake (increases DA in synapse: pleasurable effects)
- differences between inhalation, IV and intranasal
mechanism of fetal harm: cocaine (4)
- BP increases
- increased HR
- vasoconstriction
- blood flow to placenta decreased
obstetrical complications: cocaine (7)
- miscarriage
- premature birth
- placental abruption
- spontaneous abortion (via reduced blood flow)
- IUGR
- hypertension
- cardiovascular cocaine toxicity
neonatal outcomes: cocaine (3)
- low birth weight
- low head circumference
- possible abnormalities (reduced blood flow during critical periods of development)
physical childhood outcomes: cocaine (4)
- CVD
- cleft palate
- polydactyl (abnormal # of fingers/toes)
- swelling or malformation of kidney
neurodevelopmental childhood outcomes: cocaine (6)
- impaired adolescent functioning (school, behavior, brain)
- impaired perceptual reasoning and procedural learning
- symptoms of oppositional defiant disorder
- ADHD
- impaired memory and executive function
- problems with language development
impact of amphetamines (2)
- powerful CNS stimulant (euphoria, paranoia, delusions, hallucinations)
- releases large amounts of NE and DA (euphoria, increased alertness, irritability, aggression)
mechanism of fetal harm: amphetamines
increases maternal HR and BP, limiting O2 to fetus
obstetrical complications: amphetamines (3)
- high BP
- increased HR
- reduced O2 flow to placenta
neonatal outcomes: amphetamines (2)
- premature birth
- low birth weight
*(no known congenital abnormalities)
breast milk and amphetamines
breast milk [amphetamine] = 2.8-7.5x maternal plasma [amphetamine]
main takeaways (4)
- substance use during pregnancy = multiple health problems for mother and child
- screening for substance use should be part of routine care
- drugs pass through placenta based on physiochemical properties
- adverse outcomes depend on substance ingested, timing of exposure and amount of maternal consumption
what do adverse outcomes secondary to substance exposure in utero depend on (3)
- substance ingested
- timing of exposure
- amount of maternal consumption
associated major abnormalities (a) cocaine (b) cannabis (c) opioids (d) amphetamines (e) alcohol (f) tobacco
(a) limb reduction syndrome
(b) none
(c) congenital heart defects
(d) hypoplastic fetal putamen, hippocampus and globus pallidus
(e) hydrocephaly, heart abnormalities
(f) heart defects, limb reduction defects, abnormal # of digits, growth restricition
