Neonatal abstinence syndrome (NAS) is reaching epidemic proportions related to perinatal use of opioids. There are many approaches to assess and manage NAS, including one we have outlined. A standardized approach is likely to reduce length of stay and variability in practice. Circumcision is a frequent, painful procedure performed in the neonatal period. The rationale for providing analgesia is presented as well as a review of methods. Pharmacogenomics and pharmacogenetics have expanded our understanding of diseases and their drug therapy. Some applications of pharmacogenomics to the neonatal period are presented, along with pediatric challenges of developmental expression of drug-metabolizing enzymes.
Key points
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Maternal substance use and abuse during pregnancy is dramatically increasing in North America.
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Despite increasing frequency of neonatal abstinence syndrome (NAS), high-quality evidence and treatment guidelines remain limited and there is wide interinstitution variability in treatment strategies.
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Newborns show physiologic responses to painful stimuli. Untreated or undertreated pain in the newborn period may have effects on future response to pain and anxiety.
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Current available evidence for nonpharmacologic and pharmacologic approaches to pain management for common medical procedures (including circumcision) are described.
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Single nucleotide polymorphisms contribute to diseases and differences in drug metabolism (pharmacogenomics/pharmacogenetics) and must be distinguished from developmental differences in the level of activity of drug-metabolizing enzymes.
Maternal drug abuse and neonatal abstinence syndrome
The American Academy of Pediatrics (AAP) Committee on Drugs and the Committee on Fetus and Newborn recently updated their Clinical Report on Neonatal Withdrawal. This was an extensive review of the topic. In it, they recommended that every nursery have a policy for assessing maternal substance abuse and have a standardized plan for the evaluation and management of infants at risk for or showing withdrawal. In this article, we work through an example of such a standardized plan.
Fig. 1 provides an algorithm that can be used by the nursery team to assess the newborn with in utero drug exposure and to make management decisions regarding neonatal abstinence syndrome (NAS). It represents a starting point for the organization of care and decision making regarding nursery management of in utero drug exposure.
Assessment of the Drug-Exposed Newborn
1. Confirm the maternal history of prenatal drug use
It is important to know all of the drugs taken by the mother, because that will help to determine the risk to the newborn of developing withdrawal symptoms. It is also often the first opportunity for the pediatrician to meet the mother and start forming a positive relationship around the care of her infant.
2. Perform drug testing
Each nursery should have a uniform policy regarding which infants to test for drug exposure. Oral and Strang surveyed drug screening practices in Iowa and compiled a list of maternal and neonatal characteristics that are used to determine which mother–infant dyads should undergo drug testing ( Table 1 ). Other nurseries have a universal screening policy, for example, 7 hospitals in the greater Cincinnati area began universal drug testing on all expectant mothers in 2013.
| Maternal Risk Factors | Infant Risk Factors |
|---|---|
| Report of illicit drug use Maternal or paternal incarceration Prostitution Domestic violence Multiparity (>3) Children removed from home owing to child abuse Poor prenatal care Tobacco/alcohol use during pregnancy Depression Unexplained acute hypertension Unexplained stroke, myocardial infarction Abruptio placenta Precipitous labor (<3 h) Sexually transmitted diseases (human immunodeficiency virus, hepatitis B, hepatitis C, and syphilis) Signs of withdrawal or drug influence, intravenous drug use | Signs of withdrawal Unexplained low birth weight Unexplained small head circumference Unexplained prematurity (<37 wk) Congenital anomalies |
The most common type of drug testing is performed on urine and meconium, but umbilical cord analysis is gaining more acceptance. A drugs of abuse screen for urine reflects only recent exposure (within the last 72 hours). It is best to collect the first void after delivery, which is easily missed. Meconium analysis has become the “gold standard” for detection of in utero drug exposure because a positive test indicates exposure sometime after the 18th week of gestation. The first stool after birth is the best to use because it has been there the longest. Umbilical cord analysis also reflects exposure from 18 weeks gestation onward and has been shown to be similar to meconium in sensitivity. It requires a cord segment, which can be collected at the time of delivery. This assay is commercially available and is gaining favor because the cord can be collected at delivery and there is no need to wait until passage of stool.
3. Start discharge planning and assess the safety of the home environment
The concern that a mother of a newborn has a substance use problem is a red flag that the home environment may not be safe. Many newborns exposed to drugs of abuse in utero are medically stable and may not require a lengthy in-hospital stay. It is imperative to involve the social work team as soon as possible to help assess the mother’s ability to care for her newborn at home. Child protective services may need to be involved, depending on state law. It is equally important to identify the medical home, especially if discharge management involves medications and close follow-up.
4. Is the newborn at risk for developing clinically significant neonatal abstinence syndrome?
After assessing the type of in utero drug exposure, the pediatrician needs to assess whether this infant is at risk to develop clinically significant NAS. This step is important in medical decision making for the newborn.
Withdrawal, neurobehavioral dysregulation, and neonatal abstinence syndrome
There remains a lack of consistency in the literature and in pediatric practice in the use of the term NAS. The term neonatal abstinence syndrome (NAS) has been principally used to describe neonatal symptoms occurring after in utero exposure to opioids. This is because the majority of those newborns exposed to in utero opioids display a consistent neurobehavioral pattern, therefore qualifying as a syndrome. The pattern of neonatal neurobehaviors attributed to other substances such as cocaine or methamphetamine, as discussed herein, is not nearly as consistent and usually decreases progressively after birth. Non-narcotic drugs can cause neonatal psychomotor behavior that are consistent with withdrawal (often referred to as discontinuation signs), but rarely require pharmacotherapy when they are not used in conjunction with other drugs that affect the central nervous system. These include alcohol, barbiturates, caffeine, benzodiazepines, nicotine, selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs) and other antidepressants.
5. Stimulants, selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, and benzodiazepines can cause discontinuation signs of neurologic irritability, but rarely require pharmacotherapy
- •
Methamphetamine
- ○
There are no identifiable patterns of neurobehavior that are consistent with a methamphetamine exposure “syndrome.”
- ○
The Infant Development, Environment, and Lifestyle (IDEAL) Study found that methamphetamine had a small but measurable impact on birth weight and gestational age, and that heavy methamphetamine use was related to lower arousal, more lethargy, and increased physiologic stress in the newborn. This is similar to the effects of cocaine and can be termed “neurobehavioral dysregulation.”
- ○
These subtle neurobehavioral findings are consistent with previous findings in cocaine- and nicotine-exposed children.
- ○
- •
Cocaine
- ○
There is no cocaine withdrawal syndrome because the neonatal presentation is not consistent. Both depressed and excitable profiles have been observed, which may be related to the dose and exposure.
- ○
The Maternal Lifestyle Study (MLS) is a longitudinal cohort study focusing on cocaine-exposed children. It enrolled mother–infant dyads from 1993 to 1995 and has been providing longitudinal developmental follow-up ever since. The MLS found that cocaine-exposed infants showed more “soft signs” and behavioral effects in the newborn period.
- ○
As with methamphetamine exposure, the most pressing management issues are those concerning the safety of the home environment
- ○
- •
Antidepressants: SSRIs and SNRIs
- ○
SSRIs and SNRIs are 2 of the most commonly prescribed classes of drugs in pregnancy, yet not much is known about their potential for adverse effects
- ○
They cross the placenta and accumulate in the fetus to varying degrees, depending on the specific drug and its pharmacologic properties.
- ○
It is uncommon to need pharmacotherapy to treat neonatal symptoms of withdrawal from SSRIs or SNRIs. It is important to be aware that clinical signs like irritability can develop over the first week of life. This is something to communicate with the parents and the medical home provider.
- ○
Given that methamphetamine, cocaine, SSRIs, SNRIs, and benzodiazepines rarely require pharmacotherapy, the algorithm presented herein recommends observation, nonpharmacologic treatment and heightened awareness in the medical home of the infant’s developmental risk.
6. Marijuana, a special case
There are changing attitudes regarding marijuana use in the United States. Twenty states have laws legalizing some form of marijuana use, and 2 states (Colorado and Washington) have legalized its recreational use. This means that the nursery provider will be encountering the marijuana-exposed neonate with increased frequency. The clinician should not anticipate that the marijuana-exposed newborn will develop clinically significant neonatal withdrawal signs requiring pharmacotherapy with exclusively gestational marijuana exposure. The need to report to child protective services for marijuana positivity is state dependent.
7. Provide nonpharmacologic care and developmental follow-up in the medical home
Provision of nonpharmacologic care does not usually require use of a scoring tool. Some clinicians do decide to start using a scoring system (see step 10) to evaluate signs and symptoms of withdrawal in newborns exposed to these nonopioid drugs. This is an area that needs more research to assess the cost–benefit ratio of using a scoring system and requiring a predetermined length of stay.
All infants born to a mother who used drugs that affect the central nervous system should undergo periodic developmental assessment in the medical home. It is not only the direct exposure to these drugs that may place the infant at risk, but the myriad of other environmental factors that may accompany drug use that also may impact early development.
8. Short-acting opioids
If the newborn is exposed to opioids, then she is at risk for developing clinically significant NAS. The significant increases in NAS that we are all seeing in our nurseries is owing, for the most part, to the increase in prescription pain medication misuse and abuse across the country. Most of these are short-acting opioids. There is a difference in the risk to the infant in developing clinically significant NAS when exposed to short-acting opioids compared with those exposed to long-acting opioids, such as methadone and buprenorphine. Kellogg and colleagues in 2011 reported a retrospective review from Mayo Clinic. Out of 26,314 deliveries from 1998 to 2009, they found 167 women who used prescription narcotics during pregnancy and NAS was seen in only 5.6% of the infants. The reasons for the mothers to be on these potent analgesics included headaches, chronic pain, genitourinary pathology (stones), and orthopedic issues. The AAP 2012 Clinical Report states that if it has been longer than 1 week since the mother last took the opioid, then the incidence of neonatal withdrawal is relatively low. This statement is based on an observation made by a pediatrician in a 1957 paper and referred to heroin exposure. Despite the surge of short-acting pain medication use in pregnant women over the past decade, there has been no systematic analysis of the risk of NAS in relationship to the time of the last use of a narcotic analgesic before delivery.
9. Long-acting opioids
It is important to recognize when a newborn has been exposed to long-acting opioids in utero to evaluate the risk of developing NAS and determine the length of observation. Methadone is a long-acting opioid that remains the standard of care for narcotic addiction management in pregnancy in the United States. The elimination half-life in neonates is longer than 24 hours; thus, the exposed newborn may not start manifesting signs of NAS for up to 3 days. Buprenorphine alone (Subutex) or in combination with naloxone (Suboxone) are also long-acting opioids whose use is increasing for opioid dependency in pregnancy. Newborns exposed to these long-acting opiates are very likely to develop clinically significant NAS.
10. Start neonatal abstinence scoring
The standard of care for the in-patient management of NAS begins with the use of an abstinence scoring tool to measure the severity of the withdrawal and help to guide treatment as it increases or decreases. The goal of NAS scoring tools is to quantify the severity of symptoms to determine the need for pharmacotherapeutic intervention. The scoring tools help to provide uniform assessments of newborns at risk for clinically significant NAS. Nurseries should establish a consistent method to train and periodically assess the use of the scoring system by the nursing staff to maximize interrater reliability for the score that physicians use to determine pharmacologic intervention. Several scoring systems are available; the most common are the modified Neonatal Abstinence Scoring System, The Lipsitz tool, and the Neonatal Withdrawal Inventory. Each of these tools uses a different “number” as the threshold for determining the need to initiate pharmacotherapy.
Length of observation
The length of observation for the newborn at risk for developing clinically significant NAS should be standardized in nurseries. Prenatal care providers need to be aware that NAS occurs in 55% to 94% of opioid exposed newborns and that early discharge for the newborn may not be indicated medically. It is generally accepted that an infant born to a mother who took a low dose of a short-acting opioid during pregnancy may be safely discharged if asymptomatic after 3 days of observation. Smirk and colleagues at the University of Melbourne conducted a 10-year retrospective analysis of babies treated pharmacologically for NAS and found that 94% of the 142 infants exposed to long-acting opioids (methadone or buprenorphine) developed NAS symptomatology requiring treatment by day 5 of life.
11. Provide nonpharmacologic care
The goal of NAS treatment is to relieve symptoms that are interfering with physiologic stability, weight gain, the ability to be consoled, and sleep. There is also a paramount need to educate the mother (who in most cases will be involved with the ongoing care of her infant) about her newborn’s neurobehavioral dysfunction and the best ways to interact with her newborn. Box 1 lists common nonpharmacologic techniques. Velez and Jansson wrote an in-depth article for physicians and nurses about the complexity and vulnerability of the opioid-dependent pregnant and post partum woman and her infant that offers practical advice to nursery staff to better understand these dyads.
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Nursing support
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Swaddling with soft blankets
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Quiet, dark environment
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Frequent small feedings of hypercaloric formula
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Try a pacifier with simple syrup
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Skin care
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High degree of suspicion for other disease processes
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Organize care to minimize handling
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Swings; helpful for some
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Determine level of stimulation infant can tolerate
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Breastfeeding issues
It is safe to breastfeed with methadone and other opioids if the mother is negative for the human immunodeficiency virus, and she is not using other substances of abuse, such as cocaine or methamphetamine. Methadone concentrations in breast milk are low and not related to maternal dose of the opioid. A 2010 retrospective study looking for independent predictors of response to treatment for NAS found that infants born to mothers on methadone who were breastfed had a shorter median duration of pharmacotherapy for NAS and that the favorable response correlates with the volume of the breast milk ingested as a proportion of total intake. Sudden cessation of breastfeeding by mothers treated with methadone has been associated with recurrence of NAS. The physician and mother should both be aware of this risk.
Rooming-in
Some nurseries are allowing newborns with NAS to room in with their mothers. Hunseler and colleagues in Germany found that infants with opioid-induced NAS required less pharmacotherapy for NAS and had shorter hospital stays when placed with their mothers in the postnatal unit compared with infants admitted to the neonatal unit.
12. Start pharmacotherapy if scores reach treatment threshold
There are numerous pharmacologic treatment strategies published. Reviews have, in general, concluded that there is a lack of strong evidence on the relative efficacy of the different drug regimens for the treatment of NAS. Morphine remains the most widely used initial medication for treatment of NAS. Nurseries should establish dosing regimens for morphine based on their chosen scoring system to standardize the approach. Treatment algorithms available on-line specify initial dosing, escalation, and weaning parameters. Treating NAS with methadone is also used in some nurseries. The Vermont Children’s Hospital guidelines specify a dosing and weaning schedule. No longer recommended for treatment of NAS are diazepam, paregoric, and diluted tincture of opium.
13. Adjunctive pharmacotherapy—consider with polydrug exposure
When morphine or methadone alone is not controlling symptoms to enable the newborn to sleep and eat adequately, adjunctive treatment may be considered. If the newborn has been exposed to multiple drug classes or has significant neurologic hyperirritability, oral phenobarbital can be considered. It is important to remember that phenobarbital does not control gastrointestinal symptoms. A neonatal loading dose of 16 mg/kg per day is recommended with a maintenance dose between 2 and 8 mg/kg per day, titrated to the symptoms.
Clonidine is also used for adjunctive and, at times, primary treatment for NAS. It reduces the signs and symptoms of NAS while the newborn’s neurons are reversing their tolerance to opioids. Because of its potential to cause hypotension, blood pressures and heart rates should be closely monitored before each dose for 24 hours after initiation or change in dosing.
14. Discharge issues: medication weaning, safety of the home environment, and establishing a medical home
The discharge of newborns treated for NAS depends on a number of factors. Although many treatment algorithms specify that the scores must be below the treatment threshold, it is more important to assess the goals of treatment and determine if the newborn is (1) gaining weight appropriately, (2) getting adequate sleep, and (3) has behavior that a nonprofessional caretaker can manage. Scoring helps to direct the uniform and consistent care given, but these characteristics, not a number on a scoring system, are what determines readiness for discharge.
As stated in step 3 of the algorithm, the safety of the home environment and assessment of support systems for the home care provider need to be determined. In addition, a medical home for the newborn needs to be established, with direct communication to the primary care provider about the out-patient management. One of the most important issues is the out-patient management of the drug(s) used to treat NAS. The decision to send the newborn home on NAS medications with a plan to wean the medication over time varies across the country. Medication options for home weaning include phenobarbital and methadone. There are no published studies on the outpatient weaning of clonidine. As with the in-patient management of NAS, the out-patient management has not been rigorously studied to assess the success of different weaning regimens.
The goal of out-patient pharmacologic management should be to wean the infant off the medications as efficiently as is safely possible while still maintaining adequate weight gain, sleep, and the ability to be consoled. This process can be challenging for both the medical home provider and the caregivers, especially when assessing infant behavior at 4 to 6 weeks of age. This is the age when all term newborns become fussier as a part of normal development. There is a risk that parents and medical care providers will perceive that any discomfort or annoying behavior in the infant needs to be treated with medications. This needs to be taken into consideration when assessing the infant exposed to opioids in utero and it should not be presumed that all irritability is owing to withdrawal. Nonpharmacologic intervention as described herein can be used. The medical home should also provide developmental surveillance of infants with NAS, as with other high-risk newborns.
Summary
The newborn exposed to a drug in utero is best managed with a standard team approach with flexibility to consider each infant individually and utilize outpatient management in the medical home.
Maternal drug abuse and neonatal abstinence syndrome
The American Academy of Pediatrics (AAP) Committee on Drugs and the Committee on Fetus and Newborn recently updated their Clinical Report on Neonatal Withdrawal. This was an extensive review of the topic. In it, they recommended that every nursery have a policy for assessing maternal substance abuse and have a standardized plan for the evaluation and management of infants at risk for or showing withdrawal. In this article, we work through an example of such a standardized plan.
Fig. 1 provides an algorithm that can be used by the nursery team to assess the newborn with in utero drug exposure and to make management decisions regarding neonatal abstinence syndrome (NAS). It represents a starting point for the organization of care and decision making regarding nursery management of in utero drug exposure.
Assessment of the Drug-Exposed Newborn
1. Confirm the maternal history of prenatal drug use
It is important to know all of the drugs taken by the mother, because that will help to determine the risk to the newborn of developing withdrawal symptoms. It is also often the first opportunity for the pediatrician to meet the mother and start forming a positive relationship around the care of her infant.
2. Perform drug testing
Each nursery should have a uniform policy regarding which infants to test for drug exposure. Oral and Strang surveyed drug screening practices in Iowa and compiled a list of maternal and neonatal characteristics that are used to determine which mother–infant dyads should undergo drug testing ( Table 1 ). Other nurseries have a universal screening policy, for example, 7 hospitals in the greater Cincinnati area began universal drug testing on all expectant mothers in 2013.
| Maternal Risk Factors | Infant Risk Factors |
|---|---|
| Report of illicit drug use Maternal or paternal incarceration Prostitution Domestic violence Multiparity (>3) Children removed from home owing to child abuse Poor prenatal care Tobacco/alcohol use during pregnancy Depression Unexplained acute hypertension Unexplained stroke, myocardial infarction Abruptio placenta Precipitous labor (<3 h) Sexually transmitted diseases (human immunodeficiency virus, hepatitis B, hepatitis C, and syphilis) Signs of withdrawal or drug influence, intravenous drug use | Signs of withdrawal Unexplained low birth weight Unexplained small head circumference Unexplained prematurity (<37 wk) Congenital anomalies |
The most common type of drug testing is performed on urine and meconium, but umbilical cord analysis is gaining more acceptance. A drugs of abuse screen for urine reflects only recent exposure (within the last 72 hours). It is best to collect the first void after delivery, which is easily missed. Meconium analysis has become the “gold standard” for detection of in utero drug exposure because a positive test indicates exposure sometime after the 18th week of gestation. The first stool after birth is the best to use because it has been there the longest. Umbilical cord analysis also reflects exposure from 18 weeks gestation onward and has been shown to be similar to meconium in sensitivity. It requires a cord segment, which can be collected at the time of delivery. This assay is commercially available and is gaining favor because the cord can be collected at delivery and there is no need to wait until passage of stool.
3. Start discharge planning and assess the safety of the home environment
The concern that a mother of a newborn has a substance use problem is a red flag that the home environment may not be safe. Many newborns exposed to drugs of abuse in utero are medically stable and may not require a lengthy in-hospital stay. It is imperative to involve the social work team as soon as possible to help assess the mother’s ability to care for her newborn at home. Child protective services may need to be involved, depending on state law. It is equally important to identify the medical home, especially if discharge management involves medications and close follow-up.
4. Is the newborn at risk for developing clinically significant neonatal abstinence syndrome?
After assessing the type of in utero drug exposure, the pediatrician needs to assess whether this infant is at risk to develop clinically significant NAS. This step is important in medical decision making for the newborn.
Withdrawal, neurobehavioral dysregulation, and neonatal abstinence syndrome
There remains a lack of consistency in the literature and in pediatric practice in the use of the term NAS. The term neonatal abstinence syndrome (NAS) has been principally used to describe neonatal symptoms occurring after in utero exposure to opioids. This is because the majority of those newborns exposed to in utero opioids display a consistent neurobehavioral pattern, therefore qualifying as a syndrome. The pattern of neonatal neurobehaviors attributed to other substances such as cocaine or methamphetamine, as discussed herein, is not nearly as consistent and usually decreases progressively after birth. Non-narcotic drugs can cause neonatal psychomotor behavior that are consistent with withdrawal (often referred to as discontinuation signs), but rarely require pharmacotherapy when they are not used in conjunction with other drugs that affect the central nervous system. These include alcohol, barbiturates, caffeine, benzodiazepines, nicotine, selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs) and other antidepressants.
5. Stimulants, selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, and benzodiazepines can cause discontinuation signs of neurologic irritability, but rarely require pharmacotherapy
- •
Methamphetamine
- ○
There are no identifiable patterns of neurobehavior that are consistent with a methamphetamine exposure “syndrome.”
- ○
The Infant Development, Environment, and Lifestyle (IDEAL) Study found that methamphetamine had a small but measurable impact on birth weight and gestational age, and that heavy methamphetamine use was related to lower arousal, more lethargy, and increased physiologic stress in the newborn. This is similar to the effects of cocaine and can be termed “neurobehavioral dysregulation.”
- ○
These subtle neurobehavioral findings are consistent with previous findings in cocaine- and nicotine-exposed children.
- ○
- •
Cocaine
- ○
There is no cocaine withdrawal syndrome because the neonatal presentation is not consistent. Both depressed and excitable profiles have been observed, which may be related to the dose and exposure.
- ○
The Maternal Lifestyle Study (MLS) is a longitudinal cohort study focusing on cocaine-exposed children. It enrolled mother–infant dyads from 1993 to 1995 and has been providing longitudinal developmental follow-up ever since. The MLS found that cocaine-exposed infants showed more “soft signs” and behavioral effects in the newborn period.
- ○
As with methamphetamine exposure, the most pressing management issues are those concerning the safety of the home environment
- ○
- •
Antidepressants: SSRIs and SNRIs
- ○
SSRIs and SNRIs are 2 of the most commonly prescribed classes of drugs in pregnancy, yet not much is known about their potential for adverse effects
- ○
They cross the placenta and accumulate in the fetus to varying degrees, depending on the specific drug and its pharmacologic properties.
- ○
It is uncommon to need pharmacotherapy to treat neonatal symptoms of withdrawal from SSRIs or SNRIs. It is important to be aware that clinical signs like irritability can develop over the first week of life. This is something to communicate with the parents and the medical home provider.
- ○
Given that methamphetamine, cocaine, SSRIs, SNRIs, and benzodiazepines rarely require pharmacotherapy, the algorithm presented herein recommends observation, nonpharmacologic treatment and heightened awareness in the medical home of the infant’s developmental risk.
6. Marijuana, a special case
There are changing attitudes regarding marijuana use in the United States. Twenty states have laws legalizing some form of marijuana use, and 2 states (Colorado and Washington) have legalized its recreational use. This means that the nursery provider will be encountering the marijuana-exposed neonate with increased frequency. The clinician should not anticipate that the marijuana-exposed newborn will develop clinically significant neonatal withdrawal signs requiring pharmacotherapy with exclusively gestational marijuana exposure. The need to report to child protective services for marijuana positivity is state dependent.
7. Provide nonpharmacologic care and developmental follow-up in the medical home
Provision of nonpharmacologic care does not usually require use of a scoring tool. Some clinicians do decide to start using a scoring system (see step 10) to evaluate signs and symptoms of withdrawal in newborns exposed to these nonopioid drugs. This is an area that needs more research to assess the cost–benefit ratio of using a scoring system and requiring a predetermined length of stay.
All infants born to a mother who used drugs that affect the central nervous system should undergo periodic developmental assessment in the medical home. It is not only the direct exposure to these drugs that may place the infant at risk, but the myriad of other environmental factors that may accompany drug use that also may impact early development.
8. Short-acting opioids
If the newborn is exposed to opioids, then she is at risk for developing clinically significant NAS. The significant increases in NAS that we are all seeing in our nurseries is owing, for the most part, to the increase in prescription pain medication misuse and abuse across the country. Most of these are short-acting opioids. There is a difference in the risk to the infant in developing clinically significant NAS when exposed to short-acting opioids compared with those exposed to long-acting opioids, such as methadone and buprenorphine. Kellogg and colleagues in 2011 reported a retrospective review from Mayo Clinic. Out of 26,314 deliveries from 1998 to 2009, they found 167 women who used prescription narcotics during pregnancy and NAS was seen in only 5.6% of the infants. The reasons for the mothers to be on these potent analgesics included headaches, chronic pain, genitourinary pathology (stones), and orthopedic issues. The AAP 2012 Clinical Report states that if it has been longer than 1 week since the mother last took the opioid, then the incidence of neonatal withdrawal is relatively low. This statement is based on an observation made by a pediatrician in a 1957 paper and referred to heroin exposure. Despite the surge of short-acting pain medication use in pregnant women over the past decade, there has been no systematic analysis of the risk of NAS in relationship to the time of the last use of a narcotic analgesic before delivery.
9. Long-acting opioids
It is important to recognize when a newborn has been exposed to long-acting opioids in utero to evaluate the risk of developing NAS and determine the length of observation. Methadone is a long-acting opioid that remains the standard of care for narcotic addiction management in pregnancy in the United States. The elimination half-life in neonates is longer than 24 hours; thus, the exposed newborn may not start manifesting signs of NAS for up to 3 days. Buprenorphine alone (Subutex) or in combination with naloxone (Suboxone) are also long-acting opioids whose use is increasing for opioid dependency in pregnancy. Newborns exposed to these long-acting opiates are very likely to develop clinically significant NAS.
10. Start neonatal abstinence scoring
The standard of care for the in-patient management of NAS begins with the use of an abstinence scoring tool to measure the severity of the withdrawal and help to guide treatment as it increases or decreases. The goal of NAS scoring tools is to quantify the severity of symptoms to determine the need for pharmacotherapeutic intervention. The scoring tools help to provide uniform assessments of newborns at risk for clinically significant NAS. Nurseries should establish a consistent method to train and periodically assess the use of the scoring system by the nursing staff to maximize interrater reliability for the score that physicians use to determine pharmacologic intervention. Several scoring systems are available; the most common are the modified Neonatal Abstinence Scoring System, The Lipsitz tool, and the Neonatal Withdrawal Inventory. Each of these tools uses a different “number” as the threshold for determining the need to initiate pharmacotherapy.
Length of observation
The length of observation for the newborn at risk for developing clinically significant NAS should be standardized in nurseries. Prenatal care providers need to be aware that NAS occurs in 55% to 94% of opioid exposed newborns and that early discharge for the newborn may not be indicated medically. It is generally accepted that an infant born to a mother who took a low dose of a short-acting opioid during pregnancy may be safely discharged if asymptomatic after 3 days of observation. Smirk and colleagues at the University of Melbourne conducted a 10-year retrospective analysis of babies treated pharmacologically for NAS and found that 94% of the 142 infants exposed to long-acting opioids (methadone or buprenorphine) developed NAS symptomatology requiring treatment by day 5 of life.
11. Provide nonpharmacologic care
The goal of NAS treatment is to relieve symptoms that are interfering with physiologic stability, weight gain, the ability to be consoled, and sleep. There is also a paramount need to educate the mother (who in most cases will be involved with the ongoing care of her infant) about her newborn’s neurobehavioral dysfunction and the best ways to interact with her newborn. Box 1 lists common nonpharmacologic techniques. Velez and Jansson wrote an in-depth article for physicians and nurses about the complexity and vulnerability of the opioid-dependent pregnant and post partum woman and her infant that offers practical advice to nursery staff to better understand these dyads.
