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



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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.
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The Infant of Drug Dependent Mother