The Infant of Drug Dependent Mother

Ma. Teresa C. Ambat, MDTTUHSC-Neonatology9/12/2008

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

Question1. 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. AlcoholB. MarijuanaC. NicotineD. CocaineE. Heroin

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, T-ACE

Physicians’ records yielded the lowest prevalence estimates suggesting lack of attention devoted to addiction disorders

Question2. 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. AmphetamineB. BenzodiazepineC. MethadoneD. OpiateE. Marijuana

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 useTime 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

<72h

<30days

Opiates: Morphine, Heroin

Methadone

<48h

<96h

Question3. 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. BloodB. Gastric aspirateC. HairD. MeconiumE. Urine

Question4. 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. 12 weeksB. 16 weeksC. 20 weeksD. 24 weeksE. 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 Intrapartum Neonatal Long term

SAB

Aneuploidy

Stillbirth

Breech

IUGR

Abnormal HR pattern

fetal breathing, movement

Abruptio

Premature labor

Prematurity

LBW, SGA

Abstinence syndrome

FAS

FAE

Abnormal EEG

Post natal growth restriction

Low Bayley/Fagan scores

ADHD

Language problem

Behavior problem

Poor academic performance

Adolescent: difficulty in memory, calculation

Question5. 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 retardationB. 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 mid-facial 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 exposureA. Confirmed maternal alcohol exposure

B. Characteristic facial anomalies: short palpebral fissures, flat upper lip, flat philtrum, flat midface

C. Growth restriction: LBW/SGA, decelerating weight over time not due to nutrition, disproportional weight to height

D. 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)

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 exposureA. Confirmed maternal alcohol exposure

B. Some components of characteristic facial anomalies

C. C or D as above or

D. Evidence of complex pattern of behavior or cognitive anomalies inconsistent with developmental level and cannot be explained by familial background or environment alone

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 Intrapartum Neonatal Long termSAB

Stillbirth

Placental decidual necrosis

Abruptio

Premature labor

IUGR

CHD

Deformities of extremities, polycsyctic kidneys, gastroschisis, skull deformities

PPHN

Low test scores (cognitive, language, general academic achievement)

Conduct disorder

Adolescent-onset drug dependence

SIDS

Marijuana Dried material from hemp plant, Cannabis sativa

Smoked in cigarette or pipe passes rapidly into blood rapid high

-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

Question6. 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. AlcoholB. HeroinC. MarijuanaD. CocaineE. 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 Intrapartum Neonatal Long termStillbirth

Abortion

Inc uterine vascular resistance

Infection/STD Placental infarcts

IUGR

Abnormal fetal breathing

Abruptio

Premature labor

PROM

Shortened labor

Meconium stained amniotic fluid

PT, LBW, SGA

Small HC

Postnatal growth restriction

CNS: cerebral infarction, seizures, cortical atrophy, IVH

Abnormal EEG and BAER

NECIntestinal perforation

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 Intrapartum Neonatal Long termFetal death

Retroplacental hemorrhage

Prematurity

Neonatal death

Drug intoxication (abnormal sleep, tremors, poor feeding, hypertonia, sneezing, high-pitched 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, high-pitched 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

Disorganized sucking, vomiting, drooling, sensitive gag, hyperphagia, diarrhea, abdominal cramps

Vasomotor system 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

Question7. 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 amphetaminesB. Use of marijuanaC. Use of SSRI for depressionD. Maternal seizure disorderE. Use of cocaine

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 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

Phenobarbital 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.