Neonatal drug withdrawal is a common problem in populations in which drugs taken for therapeutic, recreational, or addiction purposes are readily available to pregnant women. However, the incidence is difficult to determine because of unreliable histories of maternal drug abuse and limited health provider skills in eliciting drug histories and diagnosing nonopiate drug exposure in the newborn period. In addition, maternal use of more than one drug makes ascribing a given effect on the neonate to a specific drug difficult.
Overall the incidence of drug-exposed newborns is reportedly 3-50%, depending on the specific patient population, with urban centers usually reporting higher rates. An estimated 10–11% of the 4.1 million live births (in 2005) involved prenatal exposure to alcohol or illegal drugs. When tobacco data are included more than one million children are affected by prenatal exposure. Among offspring exposed to opioids or heroin in utero, withdrawal signs develop in 55-94%.
Death is rarely associated with withdrawal alone but occurs as a consequence of prematurity, infection, and severe perinatal asphyxia.
Long-term mortality rate is likely to be extremely low, although the risk for SIDS is significantly higher among infants who are exposed to opiates. Infants exposed to methadone have a 3.7-fold higher risk of SIDS compared with controls. Infants exposed to cocaine have a 2.3-fold higher risk for SIDS compared with infants with no exposure. This increased risk is related to a complex interplay of factors; the compromised home environment associated with a mother who is drug addicted is an important variable.
When assessing potential neonatal abstinence syndrome (NAS), the most reliable method of determining the extent of drug use in pregnancy is maternal history as part of routine antenatal assessment, with a structured interview providing a greater yield than an informal interview.
The amount of information obtained from the mother about prenatal drug exposure widely varies and may not be reliable. How the mother is questioned and the specificity of the questions are the most important factors. Maternal interviews have been reported to be the least sensitive method of identifying drug use in pregnancy when compared with maternal hair and meconium drug testing. Maternal self-report was found to underestimate in utero drug exposure by as much as 44% when compared with data from meconium analyses.
[15]Despite concerted efforts by health care professionals to promote prenatal care, the mother may not have received such care and the delivery hospitalization may be the only opportunity to elicit information on the nature and extent of the infant's in utero exposure to drugs and alcohol. The mother's concern for her infant's health may encourage valid responses; conversely, fear of legal reprisals or loss of custody of the infant may cause the mother to deny drug use.
The Committee on Substance Abuse of the American Academy of Pediatrics recommends obtaining a comprehensive medical and psychological history that includes specific information regarding maternal drug use as part of every newborn evaluation.
[16]The relationship between maternal cocaine use and placental abruption is well established. Therefore, a perinatal history of abruption should alert the medical caretaker that prenatal exposure to cocaine is a possibility.
PHYSICAL
A thorough physical examination of the neonate should include accurate assessment of weight, length, and head circumference and a standardized assessment of gestational age. Special attention should be paid to signs of intrauterine growth retardation (IUGR), microcephaly, prematurity, congenital infection, and major and minor congenital malformations.
Infants are suspected of having neonatal abstinence syndrome if they exhibit any of the following signs:
CNS dysfunction
- High-pitched cry
- Restlessness, with sleep duration less than 1-3 hours after feeding
- Hyperactive reflexes
- Jitteriness
- Tremors
- Hypertonia
- Myoclonic jerks
- Generalized convulsions
Metabolic, vasomotor, and respiratory disturbances
- Sweating
- Fever
- Mottling
- Frequent yawning
- Sneezing (>3 times per interval)
- Nasal flaring
- Respiratory rate greater than 60 breaths per minute without retractions
- Apnea
GI dysfunction
- Excessive (frantic) sucking or rooting
- Poor feeding
- Hyperphagia, usually associated with poor weight gain
- Regurgitation or projectile vomiting
- Loose or watery stools
Alcohol-specific symptoms
- Withdrawal that presents within the first 24 hours of life is reported among infants with the dysmorphic features of fetal alcohol syndrome.
- Neonates also exhibit irritability, tremors, seizures, opisthotonus, and abdominal distention.
Lysergic acid (LSD) symptoms
- The effect of LSD on the fetus is clouded by the high incidence of polydrug abuse.
- Withdrawal symptoms manifest as hypertonia, tremors, poor feeding, and abnormal feeding patterns.
Other symptoms
- Nicotine may produce withdrawal symptoms in infants, including increased excitability and hypertonicity.
- Caffeine withdrawal includes feeding difficulties, vomiting, excessive crying, irritability, and poor sleep patterns. Onset of symptoms may occur as long as 5 days after birth and persist for weeks or months.
The timing of onset of the symptoms gives an indication of the maternal drug abuse. Withdrawal from high levels of maternal alcohol can occur within a day or 2 of birth. Heroin has a short half-life and withdrawal also occurs within 48–72 h of birth, whereas methadone withdrawal occurs at 7–14 days.
Different scoring systems have been developed for assessing the severity of neonatal abstinence syndrome, such as those by Finnegan, Ostrea, Lipsitz, Rivers, and the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS).
[17, 18, 19] These are based on opiate withdrawal and may not be entirely appropriate for the infant exposed to cocaine or other drugs.
The most widely used system is the Finnegan scoring system, in both its original and modified forms. A neonatal abstinence syndrome scoring form is shown below.
Neonatal abstinence syndrome scoring form.The Finnegan scale assesses 21 of the most common signs of neonatal drug withdrawal syndrome and is scored on the basis of pathological significance and severity of the adverse symptoms, which sometimes requires pharmacological treatment. Despite the number of items that can be scored, it is nevertheless a relatively easy and reliable system to use once staff have been adequately trained. However, the potential for bias and subjectivity may affect the scores, and the thresholds for treatment reported in the literature vary. This scale can also be used to assess the resolution of signs and symptoms after initiating treatment.
To obtain a daily average score, measurements are performed every 4 hours until the patient is stable. If 3 consecutive scores are equal to or greater than 8, treatment for withdrawal is started. The decision to commence treatment can depend on factors other than this score alone, including the reported exposure, the age of the infant, consideration of comorbidities that might influence the score, whether an inpatient or outpatient strategy is used, and the experience of the clinician making treatment decisions.
The infant is best cared for in a unit with experienced personnel who can recognize problems, perform constant evaluations, and institute the necessary interventions.
CAUSES
Current resurgence in heroin use is associated with the introduction of a cheap, smokeable form that is comparable to crack cocaine, only more potent. Cocaine's current popularity is related to increased availability and the presence of newer, cheaper forms.
Depression is common in reproductive age women, and continued pharmacologic treatment of depression during pregnancy may be necessary to prevent relapse. Neonates who are exposed to antidepressant medications during gestation are at increased risk to have neonatal abstinence syndrome.
DIFFERENTIAL DIAGNOSE
- Hyperthyroidism
- Hypocalcemia
- Hypoglycemia
- Sepsis
LABORATORY STUDIES
Health care professionals, hospitals, and clinics have an obligation to assess newborns who exhibit signs and symptoms of drug exposure, whose mothers have been identified as probable substance users, or whose mothers have signs and symptoms of drug use.
Clear evidence suggests that recognizing the substance exposed infant and implementing early intervention services for the child and mother are keys to minimizing the acute and long-term effects of prenatal substance exposure. Thus, even if the infant exhibits no clinically significant difficulties in the neonatal period, identification of the substance exposed infant can improve the long-term outcome.
Specific clinical conditions for which urine or meconium toxicology testing is indicated are noted. Commonly accepted indications for toxicology analysis include no prenatal care, intrauterine growth retardation (IUGR), preterm delivery, abruptio placentae, or cardiovascular accidents in mother or child, especially in those cases in which no other reasons for poor outcome are noted.
[20]The following studies may be necessary to prevent or diagnose cases of neonatal abstinence syndrome (NAS):
Hair analysis- Neonatal hair testing can also identify prenatal drug exposure. Hair begins to form at approximately 6 months' gestation; a positive result indicates use during the last trimester. Hair testing is advantageous because the specimen can be collected at any point during the first 3 months of life, after which time infant hair replaces neonatal hair.[21]
- This method is useful in detecting narcotics, marijuana, cocaine, and cocaine-alcohol metabolites, but the technique is expensive, is not widely available, and is limited by the procedures required to quantify the very small amounts of drug present. Obtaining an adequate sample may be difficult, and recent exposure might not be detected because hair growth is slow.
- Analysis of 1.5 cm of maternal hair reveals the maternal drug use pattern during the previous 3 months. Drug metabolites can be detected in infant hair for 2-3 months after birth
IMAGING STUDIES
Cranial ultrasonography is not routinely recommended, but literature is suggestive of CNS abnormalities, including hemorrhagic ischemic lesions in some drug-exposed infants.
Evidence is insufficient to support a mandate for cranial ultrasonography in all cocaine-exposed infants. Smit et al studied 154 neonates exposed to cocaine in utero and found that none of the infants had severe abnormalities on cranial ultrasonography. Also, the detected abnormalities were not correlated with the duration or maximum amount of cocaine use. Given these findings, they recommended that routine cranial ultrasonography in this population is not warranted.
[22] However, special consideration should be given to specific neuroimaging of cocaine-exposed preterm infants, infants whose head circumference falls below the 10th percentile on standardized fetal growth curves, and infants with abnormal neurologic signs, neurobehavioral dysfunction, or seizure activity.
OTHER TEST
A recent report has suggested that detecting drug exposure from umbilical cord tissue has similar sensitivity and specificity to meconium samples and may have some advantages over collection of meconium.
[23] Testing umbilical cord tissue enables analysis to occur immediately after birth, compared with meconium testing, which is delayed as long as 3 days prior to specimen availability. Umbilical cord is easily and noninvasively collected and may reflect a long window of drug detection; however, because few studies have examined cord tissue analysis to date, interpreting results is difficult.
Drug-exposed infants are at increased risk of acquiring infections transmitted from mothers whose lifestyles include unsafe sexual practices or intravenous drug abuse. Assessment of the mother who abuse drugs and their infants for
hepatitis B and
hepatitis C and sexually transmitted diseases including human immunodeficiency virus (HIV) should be incorporated into the prenatal care setting and delivery hospitalization.
MEDICAL CARE
The large number of infants who suffer from neonatal abstinence syndrome (NAS) and the associated long-term morbidity mandate that affected infants be accurately identified and their treatment and support should be optimized.
The assessment and management of neonatal abstinence syndrome pose difficulties for staff and families and have been hampered by a lack of prospective studies and by few research studies that specifically assess the merits of one management approach over another.
Vomiting and diarrhea leading to dehydration and poor weight gain, in the absence of other diagnoses, are indications for treatment, even in the absence of a high drug-withdrawal score.
In the delivery room, naloxone use is contraindicated in infants whose mothers are known to be dependent on opioids because of the risk of neonatal seizures from abrupt drug withdrawal. However, in the absence of a specific history of opioid abuse in a mother who has recently received narcotics, naloxone treatment remains a reasonable option in the delivery room management of a depressed infant if the infant continues to demonstrate respiratory depression after positive pressure ventilation has restored normal heart rate and color.
Primary treatment of neonatal symptoms related to prenatal substance exposure should be supportive because pharmacologic therapy can prolong hospitalization and exposes the infant to additional agents that are often not necessary. The treatment for morphine administration has been reported to last 8-79 days.
[24] This length of hospitalization interferes with maternal bonding, has potential for nosocomial infection, and is a major use of resources.
[25]Pharmacotherapy for infants with more severe expression of neonatal abstinence syndrome is necessary to allow them to feed, sleep, gain weight, and interact with care givers. Approximately 30-91% of infants who exhibit signs of neonatal abstinence syndrome receive pharmacological treatment.
Nonpharmacologic approaches include the following:
- Assess daily for signs of withdrawal, including sleeping habits, feeding patterns, and weight gain.
- Reduce the degree of ambient light exposure, minimize excessive noise, avoid unnecessary handling, and provide swaddling for settling.
- Provide frequent small feeds of hypercaloric formula
