The Infant of Drug Dependent Mother Ma. Teresa C. Ambat, MD TTUHSC-Neonatology 9/12/2008 Objectives Describe strategies how to identify neonates in whom substance abuse is suspected Recognize.
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Transcript The Infant of Drug Dependent Mother Ma. Teresa C. Ambat, MD TTUHSC-Neonatology 9/12/2008 Objectives Describe strategies how to identify neonates in whom substance abuse is suspected Recognize.
The Infant of
Drug Dependent Mother
Ma. Teresa C. Ambat, MD
TTUHSC-Neonatology
9/12/2008
Objectives
Describe strategies how to identify neonates in whom
substance abuse is suspected
Recognize perinatal and long term complications
associated with fetal exposure to major drugs of abuse
Recognize signs and symptoms of neonatal abstinence
syndrome
Identify treatment strategies for NAS
Question
1.
The National Household Survey on Drug Abuse: indicated that
45% of women of childbearing age in the United States have
used an illicit drug over their lifetime. Of the following, the annual
estimate of prenatal exposure to a substance of abuse is highest
for:
A.
Alcohol
Marijuana
Nicotine
Cocaine
Heroin
B.
C.
D.
E.
Epidemiology
Prevalence of gestational use of drugs of abuse varies
ranges from 1% to 27%
Significant number remain regular users, even in the
third trimester
Tobacco [19.8%], Ethanol [13%], cannabis [9.3%], cocaine
[10%], heroin [1%])
Identification of substance use
Maternal self-reports, and few confounders
Identify medical, obstetric, and behavior patterns suggestive
of substance use
Obtain history of past and present substance use in a
nonjudgmental manner
Questions limited to frequency and amount of specific
substances
Patterns suggestive of substance use
Identification of substance use
Maternal interview usually underestimates the extent of
exposure
Rates of alcohol and illicit drug use varied with the use of
different validated screening instruments: MAST, CAGE, TACE
Physicians’ records yielded the lowest prevalence estimates
suggesting lack of attention devoted to addiction disorders
Question
2.
The duration of time for detecting a drug of abuse in the
maternal urine varies, depending on the time of intake,
dose and mode of administration, and metabolism of the
drug. Of the following, the duration of time after birth for the
detection of a drug of abuse in the maternal urine is longest
for:
A.
Amphetamine
Benzodiazepine
Methadone
Opiate
Marijuana
B.
C.
D.
E.
Identification of substance use
Indication for toxicology screening
Self-reporting of substance use
Multiple characteristics suggesting substance use
Compliance requirements with treatment recommendations
Urine is the preferred source for drug testing - easily
available and in large quantities
Most substances are measurable in urine for < 72 hours
after use, except for marijuana
Identification of substance use
Time interval before drug elimination in urine
Drug
Detectable in urine
Alcohol
<24h
Amphetamines
<48h
Barbiturates: Short acting
Long acting
<48h
<7days
Benzodiazepines
<72h
Cocaine
<72h
Marijuna:
Single use
Chronic use
Opiates:
Morphine, Heroin
Methadone
<72h
<30days
<48h
<96h
Question
3. Various matrices for the detection of fetal exposure to drugs
of abuse have been developed and tested for their
sensitivities and specificities. Of the following, the matrix
that is most sensitive for the detection of fetal exposure to
benzoylecgonine is neonatal:
A.
B.
C.
D.
E.
Blood
Gastric aspirate
Hair
Meconium
Urine
Question
4. Testing of neonatal meconium for a drug of abuse depends
on deposition of the drug into the meconium that begins at
the commencement of fetal swallowing and continues until
after delivery. Of the following, the earliest gestational age
at which exposure to cocaine has been detected in
meconium in a fetus is:
A.
B.
C.
D.
E.
12 weeks
16 weeks
20 weeks
24 weeks
E. 28 weeks.
Identification of substance use
Meconium testing 93% sensitive (82% PPV) compared
with combined maternal and neonatal urine testing
Meconium and hair analyses - highest sensitivities in
detecting use of cocaine and opiates (80-100%),but not
cannabis (20%)
Fetal exposure to cocaine detected by meconium
testing was documented as early as 16 wks
Other matrices: hair and nail, blood/cord blood, amniotic
fluid
Identification of substance use
Perinatal pharmacology
Any substance unbound to proteins passes freely from the maternal
compartment placenta fetal compartment
Concentrations in the fetal circulation > the maternal serum
Effects from any substance depend on the gestational timing and
the extent of drug distribution
Toxic or teratogenic effects expressed as fetal demise,
dysmorphism, growth restriction, or behavioral changes
Except for maternal alcohol, a birth defect syndrome has not been
described for other illicit substances
Perinatal pharmacology
Substances of abuse may be intentionally or
inadvertently taken at toxic doses
Difficult to ascribe specific effects to a certain drug due
to impurity of most illicit drugs and use of multiple
substances
Accurate evaluation of dosage and the exact period of
exposure are rarely possible
Alcohol
Alcohol use during pregnancy: 12.9%, binge drinkers:
4.6%
Difficult to assess by laboratory tests
Alcohol
Ethanol - an anxiolytic analgesic with CNS
depressant effect
Impairs placental function
Interferes with transport of AA
Alters placental expression of EGF and PGF
Inhibits DNA and protein synthesis
Inhibits phospholipase A2, decreases PGI production,
increases HCG production
Complications of Fetal Alcohol Exposure
Antenatal
SAB
Aneuploidy
Stillbirth
Breech
IUGR
Abnormal HR
pattern
fetal breathing,
movement
Intrapartum
Abruptio
Premature labor
Neonatal
Prematurity
LBW, SGA
Abstinence
syndrome
FAS
FAE
Abnormal EEG
Long term
Post natal growth
restriction
Low Bayley/Fagan
scores
ADHD
Language problem
Behavior problem
Poor academic
performance
Adolescent:
difficulty in
memory,
calculation
Question
5. Fetal alcohol syndrome is the leading identifiable
nonhereditary cause of mental retardation and
neurologic deficit. Define the 3 specific criteria to qualify
for a diagnosis of FAS.
A. growth retardation
B. specific mid-facial features,
C. non-specific developmental aberrations
Fetal Alcohol Syndrome
FAS – leading identifiable nonhereditary cause of
mental retardation and neurologic deficit
Diagnostic criteria: 1. growth retardation, 2. specific midfacial features, 3. non-specific developmental
aberrations
Smooth philtrum, thin upper lip and short palpebral fissure
– 100% sensitivity
Diagnostic criteria (FAS and Alcohol
related effects
1.
FAS + confirmed maternal alcohol exposure
A.
Confirmed maternal alcohol exposure
Characteristic facial anomalies: short palpebral fissures, flat
upper lip, flat philtrum, flat midface
Growth restriction: LBW/SGA, decelerating weight over time not
due to nutrition, disproportional weight to height
CNS neurodevelopmental anomalies: decreased HC at birth,
structural brain anomalies, neurologic hard or soft signs (impaired
fine motor skills, NSHL, poor tandem gait, poor eye-hand
coordination)
B.
C.
D.
Diagnostic criteria (FAS and Alcohol
related effects
2.
FAS without confirmed maternal alcohol exposure
B, C and D as above
3.
Partial FAS + confirmed maternal alcohol exposure
A.
Confirmed maternal alcohol exposure
Some components of characteristic facial anomalies
C or D as above or
Evidence of complex pattern of behavior or cognitive anomalies
inconsistent with developmental level and cannot be explained by
familial background or environment alone
B.
C.
D.
Diagnostic criteria (FAS and Alcohol
related effects
4. Alcohol-Related Birth Defects (ARBD)
A.
Confirmed maternal alcohol exposure + 1 or more congenital
anomalies (Cardiac, skeletal, renal, ocular, auditory, others)
Every malformation has been described in patients with FAS.
Etiologic specificity to alcohol teratogenesis remains uncertain.
5. Alcohol-related neurologic disorder (ARND)
A.
Confirmed maternal exposure and D and or E
Tobacco
Prevalence during pregnancy: 20%
Nicotine – primary psychoactive chemical
Central effects
Binds to nicotinic Ach receptors release of neurotransmitters (Ach,
NE, GABA, glutamate)
Dopamine release in mesolimbic dopaminergic pathway
Peripheral effects
Releases epinephrine from adrenal cortex physiologic response
flight or fight reaction
Suppresses insulin release hyperglycemia, affects appetite
Tobacco
Fetal Effects
Poor maternal nutrition affects growth and development
Nicotine a vasoconstrictor reduces placental blood flow
decreased fetal O2 hypoxia/ischemia
CO + Hb carboxyhemoglobin hinder O2 delivery to
fetus
Nicotine readily crosses placental barrier
Nicotine Ach receptors are present early in gestation
affecting brain development (neurotoxic)
Complications of Fetal Exposure to Tobacco
Fetal
SAB
Stillbirth
Placental
decidual
necrosis
Intrapartum
Neonatal
Long term
Abruptio
Premature labor
IUGR
CHD
Deformities of
extremities,
polycsyctic
kidneys,
gastroschisis,
skull deformities
PPHN
Low test scores
(cognitive,
language,
general
academic
achievement)
Conduct disorder
Adolescentonset drug
dependence
SIDS
Marijuana
Dried material from hemp plant, Cannabis sativa
Smoked in cigarette or pipe passes rapidly into blood
rapid high
d-9-tetrahydrocannabinol (THC) - primary psychoactive
component
THC binds to cannabinoid receptors (CB1) modify
release of neurotransmitters
Marijuana
Fetal and Neonatal Effects
THC crosses placenta easily and present in amniotic fluid
High lipid solubility, slow elimination prolonged fetal exposure
Cannabinoid receptors present in early gestation modify
neurotransmitters (serotonin, dopamine, GABA) altered
neuronal growth, maturation and differentiation structural or
functional abnormalities
Impact generally subtle, adverse outcomes usually associated
with heavy or frequent use
Question
6. Children who have been exposed prenatally to substances of
abuse may have physical deformities as well as
neurodevelopmental deficits. Of the following, the substance
of abuse most associated with intestinal atresia, infarction
and necrotizing enterocolitis is:
A.
B.
C.
D.
E.
Alcohol
Heroin
Marijuana
Cocaine
Nicotine.
Complications of Fetal Exposure to Marijuana
Antenatal
Intrapartum
Neonatal
Long term
Precipitous or
dysfunctional
labor
Meconium
stained AF
Prematurity
Fine tremors
Disrupted sleep
Poor abstract,
visual reasoning,
Poor memory
and verbal skills
Poor motor skills
Abnormal
attention
behavior
Small risk for
SIDS
Cocaine
Alkaloid extracted from leaves of Erythroxylon coca
bush
Chemical name: methylbenzoylecgonine
Forms
Coca paste – 1st extraction product, 80% cocaine
Cocaine HCl – powder soluble in water, can be snorted and
injected
Alkaloidal base (free-basing)
Crack cocaine – most popular abused form
Cocaine - Pharmacology
Affects 3 neurotransmitters: norepinephrine,
dopamine, serotonin
Inhibits reuptake of NE, D accumulation at synapse
prolonged stimulation of receptors
NE stimulation: tachycardia, HTN, diaphoresis, tremors
Dopamine stimulation: increased alertness, euphoria,
enhanced feeling of well-being, sexual excitement,
heightened energy
Cocaine - Pharmacology
Decreases reuptake of tryptophan affecting
serotonin biosynthesis
Dec serotonin: decreased need for sleep (serotonin
regulates sleep-wake cycle)
Cocaine-Pharmacology
Low molecular weight, high lipid solubility crosses
placenta by simple diffusion
Elimination of cocaine and metabolites slow
increased fetal toxicity
Decreases placental perfusion
Congenital malformation not increased
Complications of Fetal Exposure to Cocaine
Antenatal
Stillbirth
Abortion
Inc uterine
vascular
resistance
Infection/STD
Placental infarcts
IUGR
Abnormal fetal
breathing
Intrapartum
Abruptio
Premature labor
PROM
Shortened labor
Meconium stained
amniotic fluid
Neonatal
PT, LBW, SGA
Small HC
Postnatal growth
restriction
CNS: cerebral
infarction,
seizures, cortical
atrophy, IVH
Abnormal EEG
and BAER
NEC
Intestinal
perforation
Long term
Expressive/
receptive
language problem
Low verbal
comprehension
Poor recognition,
memory, info
processing
visual attention
Behavior problem
(distractibility,
ADHD)
Amphetamines
Methyphenyethylamine – stimulant of norepinephrine,
dopamine and serotonin release
Metamphetamine (meth, speed, ice, crystal) – N-methyl
homologue of amphetamine
Higher CNS stimulation, less PNS and cardiovascular
stimulation
Euphoria, aggressive behavior, arrhythmias, anxiety,
seizures, shock, stroke, abdominal cramps, insomnia,
death
Complications of Fetal Exposure to
Amphetamines / Methamphetamines
Antenatal
Fetal death
Retroplacental
hemorrhage
Intrapartum
Neonatal
Long term
Prematurity
Neonatal death
Drug intoxication
(abnormal sleep,
tremors, poor
feeding,
hypertonia,
sneezing, highpitched cry,
loose stools,
fever, yawning,
hyperreflexia,
excoriation)
Dec IQ
Aggressive
behavior/peer
related problems
Poor academic
performance
Club drugs
Methylene-dioxymethamphetamine or MMDA (ecstasy)
Gamma hydroxybutyrate (GHB)
Ketamine hydrochloride
Used by young people during all-night dance parties
Few data on fetal and neonatal effects
One study indicated increased risk of congenital defects
(musculoskeletal, CVS)
Opioids
Opiate or narcotic – any natural or synthetic drug
that has morphine like pharmacologic actions
Natural opiates – morphine, codeine
Synthetic opiates – heroin, methadone,
propoxyphene, pentazocine, meperidine, oxycodon,
hydromorphone, fentanyl
Neonatal Abstinence Syndrome
Generally associated with withdrawal from heroin or
methadone
Similar signs associated with other narcotics, alcohol,
benzodiazepines and barbiturates
Associated with noradrenergic hyperactivity
CNS, respiratory, GI, vasomotor and cutaneous systems
manifestations
CNS signs predominate and appear early
Neonatal Narcotic Withdrawal or
Abstinence Syndrome
Onset within 72 hrs (usually within 24-48 hrs)
Factors influencing onset: amount of narcotics, timing of the
last dose before delivery, character of labor, type of
analgesia/anesthesia, maturity and nutritional status of infant
Peaks by the 3rd day
Decreases in intensity by 5th – 7th day, but may not
completely disappear until 8-16 weeks
Manifestations of Neonatal Narcotic
Withdrawal
CNS
Hyperactivity, hyperirritability, excessive crying, highpitched cry, increased muscle tone, exaggerated reflexes,
tremors, sneezing, hiccups, yawning, short, non-quiet
sleep, fever
Respiratory
Tachypnea, excess secretions
Manifestations of Neonatal Narcotic
Withdrawal
GI
Vasomotor system
Disorganized sucking, vomiting, drooling, sensitive gag,
hyperphagia, diarrhea, abdominal cramps
Stuffy nose, flushing, sweating, sudden circumoral pallor
Cutaneous
Excoriated buttocks, scratches, pressure-point abrasions
Complications of Neonatal Narcotic
Withdrawal
Abnormalities in serum pH/electrolytes and dehydration
Weight loss
Aspiration pneumonia
Respiratory alkalosis
Convulsion
Mortality – 27/1000 LB
Causes: immaturity, prematurity, HMD, MAS, PPHN,
congenital malformations
Non-narcotic Hypnosedatives
Hypnosedatives
Barbiturates
Non-barbiturate sedatives/tranqulizers
Bromide, Chloral hydrate, chlordiaxepoxide, diazepam,
ethchlorvynol, glutethimide, ethanol
Non-narcotic abstinence syndrome
Passive addiction even with therapeutic doses (e.g.
phenobarbital)
Manifestations of withdrawal can be intense and life
threatening
Convulsion more frequent
Observed 7-10 days after birth as a result of slow
clearance
Question
7.
A 4 day old, SGA presented with generalized tonic, clonic
seizure. There was no prenatal care. On exam, he was
found to be irritable, inconsolable, weak suck and swallow
and uncoordinated. He was also noted to be hypertonic
with tremors. What significant maternal history could have
contributed to the above findings?
A.
Use of amphetamines
Use of marijuana
Use of SSRI for depression
Maternal seizure disorder
Use of cocaine
B.
C.
D.
E.
SSRI
Prescribed for depression
Inhibits serotonin reuptake at presynaptoic junction
increased concentrations at the synaptic cleft
potentiates serotonergic transmission
No major birth defects
Prenatal exposure and withdrawal associated with
neurobehavioral effects (behavioral changes, altered
autonomic activity)
Diagnosis of Neonatal Abstinence
Syndrome
Scoring tools
Lipsitz scale
Finnegan scale
Neonatal abstinence score
Score at first appearance of NAS symptoms then q3-4 hrs
Specific to narcotic withdrawal
Differential diagnoses: hypoglycemia, hypocalcemia,
hypomagnesemia, sepsis, meningitis
Treatment of NAS
Supportive
Quiet, dimly lit environment, comfortable side lying position,
swaddled
Nutrition and fluid and electrolyte balance
IV fluids may be required
Pharmacotherapy
Average scores >8 over 3 scoring intervals or >12 over 2
scoring intervals
Goal: decreased irritability, feeding tolerance, sleeping bet
feeding without sedation
Treatment of NAS
Diluted tincture of opium (DTO) – 0.4mg/ml morphine
equivalent
Phenobarbital
Starting dose 0.1ml/kg (2 drops/kg) q4 hrs
Increment of 2 drops/kg q3-4 hrs until desired effect
Taper gradually after 3-5 days of stabilization
2nd line drug
Anticonvulsant, NAS by sedatives or hypnotics
Paregoric
Deleterious additives: camphor, ethanol, glycerin, benzoic acid,
isoquinolones
Other concerns
Maternal support
Breast feeding – generally discouraged if noncompliant
Drug-dependent mothers as caregivers
Social service referral
Potential child abuse
Follow-up
References
Chasnoff IJ. Prenatal Substance Exposure: Maternal Screening and
Neonatal Identification and Management. NeoReviews 4 (9), 2003.
Chan D, Klein J, Koren G. New Methods for Neonatal Drug
Screening. NeoReviews 4 (9), 2003.
Rayburn WF. Maternal and Fetal Effects from Substance Use. Clin
Perinatol 34, 2007.
Ostrea EM. The infant of drug dependent mother.