Approach Considerations
Healthcare 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.
Rapidly detecting fetal exposure to licit and illicit drugs is of considerable medical value. Such information can assist in making diagnosis of neonatal abstinence syndrome (NAS), as well as help clinicians focus the plan for treatment and follow-up for the neonates. 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.
Laboratory Studies
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. [52]
The studies discussed below may be necessary to diagnose neonatal abstinence syndrome (NAS).
Radioimmunoassay and enzyme immunoassay
These are the most commonly used drug screens. Both are semiquantitative and highly sensitive, but enzyme immunoassay takes less time to perform and is less expensive.
These tests inform the clinician about the presence or absence of substance abuse, rather than quantifying the drug level, as in toxicology screens. Perinatal drug testing aims to examine in utero drug exposure over the pregnancy. Each type of specimen has its own advantages and limitations.
Urine toxicology assays
Note the following:
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Urine was traditionally the specimen of choice for neonatal drug testing, although collection is difficult. The adhesive for the collection bag causes skin irritation and frequently fails to adhere. Another disadvantage is the short detection window; urine provides maternal drug use data only for a few days prior to delivery.
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Urine toxicology screening is useful for clinical and research purposes. Urinary excretion of metabolites may be detectable only for a few days (eg, benzoylecgonine) to a few weeks (eg, cannabinoids). One cannot expect to ascertain early pregnancy use or even relatively recent use if the metabolite concentration does not reach the detection threshold.
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Urine is relatively easy to obtain, requires minimal preparation (provided samples are not contaminated by meconium or feces), and can be analyzed using numerous laboratory techniques. Although urine samples generally contain a higher drug concentration than serum samples, the detection of compounds depends on obtaining an appropriate sample as close as possible to birth and also depends on the timing of maternal drug ingestion prior to delivery.
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These tests detect recent use of cocaine and its metabolites, amphetamines, marijuana, barbiturates, and opiates. Cocaine can be detected in urine 6-8 hours after use in the mother and as long as 48-72 hours after use in the newborn. Alcohol is detectable in neonatal urine for 6-16 hours after the last maternal ingestion.
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Detection of drugs depends on many variables, including individual drug metabolism, hydration status of the subject, route of administration, and frequency of ingestion.
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No drugs are known to cross react with the immunoassays for cocaine and marijuana. Several over-the-counter remedies and herbal preparations may contain ephedrine and phenylpropanolamine (recalled from US market), which can produce false-positive enzyme immunoassay test results for amphetamines. Therefore, confirmatory testing is required.
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Immunoassay for opiates does not distinguish between codeine, morphine, or their glucuronide conjugates.
Meconium analysis
Meconium analysis is currently considered the best method for detecting drug exposure in pregnancy. It provides a wider window of detection of gestational exposure, presumably as remote as the second trimester, when drugs begin to accumulate in meconium (by direct deposition from the biliary tree or when the fetus ingests amniotic fluid).
Meconium analysis is reliable for detecting opioid and cocaine exposure after the first trimester and can be used to detect a range of other illicit and prescribed medications.
However, meconium can be contaminated by infant urine, although only cocaine or opiate use within approximately 72 hours of birth is reflected. Thus, false-positive results occur if meconium is contaminated with urine, reflecting antepartum and perinatal exposure. Theoretically, lidocaine can cause a positive result, but a large amount is required.
When a meconium sample is stored at room temperature, it decreases cocaine and cannabinoid levels by 25% per day.
A study comparing umbilical cord tissue and meconium for the confirmation of in utero illicit drug exposure revealed different sensitivities of drug detection in both samples. [53] Meconium provided greater sensitivity over cord tissue, which led the study author to conclude that meconium is likely to remain the specimen of choice when sensitivity is of the greatest importance. [53]
Umbilical cord testing
An option for monitoring in utero drug exposure is the use of umbilical cord tissue testing. [54] A report suggested that detecting drug exposure from umbilical cord tissue has similar sensitivity and specificity to meconium samples and may have some advantages over the collection of meconium. [55] Testing umbilical cord tissue enables analysis to occur immediately after birth, in contrast to meconium testing that is delayed up to 3 days before specimen availability. Moreover, in some cases the meconium is passed in utero, making collection impossible. Umbilical cord tissue is easily and noninvasively collected and may reflect a long window of drug detection. Negative results are usually reported the same day the specimen is received. Presumptive positive results require several days to be reported. [56] Palmer et al showed that umbilical cord tissue toxicology testing yielded a similar detection rate compared to that from meconium testing. [57]
As a result of all these advantages, umbilical cord tissue testing is rapidly replacing meconium studies as the newborn toxicology gold standard because of its universal availability, shortened turnaround time, and improved chain of custody integrity. [56] Although cord tissue offers many advantages from an operational perspective, the yield of testing is lower than that of meconium drug testing, and it may be difficult to draw firm conclusions about timing or duration of exposure. [53]
Blood tests
Blood samples are of limited value, because the window of detection is narrow owing to the rapid effects of metabolism and the low concentrations of drugs present in blood.
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. [58]
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 central nervous system abnormalities, including hemorrhagic ischemic lesions in some drug-exposed infants. [59]
Evidence is insufficient to support a mandate for cranial ultrasonography in all cocaine-exposed infants. van Huis et al studied 154 neonates exposed to cocaine in utero and found that none of the infants had severe abnormalities on cranial ultrasonography. [60] Also, the detected abnormalities were not correlated with the duration or maximum amount of cocaine use. Given these findings, the investigators recommended that routine cranial ultrasonography in infants exposed to cocaine in utero is not warranted. [60] 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. [61]
Other Tests
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.
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Neonatal Abstinence Syndrome. Neonatal abstinence syndrome scoring form.
