Pediatric Annals

Healthy Baby/Healthy Child 

Neonatal Abstinence Syndrome

Leah Khan, MD


Opioid use and abuse have skyrocketed in the United States over the last decade. As a result, we have seen a substantial increase in neonates who are exposed to opioids in-utero. Anywhere from 55% to 94% of infants exposed to opioids will experience withdrawal, known as neonatal abstinence syndrome (NAS), and will require management of their symptoms in the hospital. It is important to know what to look for in an infant who is experiencing NAS, how to determine if treatment is needed and what type of treatment is indicated, and how to prepare the infant for discharge once they are stable. Unfortunately, there are no standardized care plans in place for the management of this population. Although assessment tools such as the Finnegan scoring systems are available, they are not validated and can be cumbersome and difficult to administer. Other methods of assessment are being studied and may prove to be more useful in the clinical setting of neonatal withdrawal. Neither nonpharmacologic nor pharmacologic interventions are standardized, with individual institutions determining their plan of care. Development of more standardized care could significantly improve the management of these patients. [Pediatr Ann. 2020;49(1):e3–e7.]


Opioid use and abuse have skyrocketed in the United States over the last decade. As a result, we have seen a substantial increase in neonates who are exposed to opioids in-utero. Anywhere from 55% to 94% of infants exposed to opioids will experience withdrawal, known as neonatal abstinence syndrome (NAS), and will require management of their symptoms in the hospital. It is important to know what to look for in an infant who is experiencing NAS, how to determine if treatment is needed and what type of treatment is indicated, and how to prepare the infant for discharge once they are stable. Unfortunately, there are no standardized care plans in place for the management of this population. Although assessment tools such as the Finnegan scoring systems are available, they are not validated and can be cumbersome and difficult to administer. Other methods of assessment are being studied and may prove to be more useful in the clinical setting of neonatal withdrawal. Neither nonpharmacologic nor pharmacologic interventions are standardized, with individual institutions determining their plan of care. Development of more standardized care could significantly improve the management of these patients. [Pediatr Ann. 2020;49(1):e3–e7.]

Neonatal abstinence syndrome (NAS), also known as neonatal withdrawal syndrome and neonatal withdrawal, is an increasingly prevalent issue as drug use (whether illicit or prescribed) during pregnancy is increasing.1 NAS is most clinically significant when an infant withdrawal from opioid exposure in-utero.2–4 Anywhere from 55% to 94% of infants with opioid exposure will develop signs of withdrawal.1,2 Symptoms typically manifest within the first 24 to 96 hours after delivery, depending on the particular type of opioid as well as the exposure history.5 NAS consists of a constellation of signs and symptoms resulting from the sudden discontinuation of exposure to a substance that was used (or abused) by the mother during pregnancy.6 Symptoms involve primarily the central and autonomic nervous system as well as the gastrointestinal system.1,7,8 Neonates present with tremors, irritability, excessive crying, diarrhea, agitation, poor sleep, and feeding difficulties as well as temperature instability.3,6 Seizures are also present in about 2% to 11% of babies experiencing withdrawal.6

Withdrawal from different opioids can lead to different symptoms. Methadone withdrawal tends to present with more tremors, exaggerated reflexes, hypertonia, and myoclonic jerks.6 Buprenorphine withdrawal consists of more temperature instability, sweating, sneezing, and mottling.6 Severe diarrhea is most common during heroin withdrawal.6 Knowing what an infant has been exposed to can help providers anticipate what the NAS process may look like and allow better education and anticipatory guidance for families who will be involved in infant care. Infants experiencing opioid withdrawal are most often cared for in a neonatal intensive care setting; however, there are different care models emerging that may change this.

History of Neonatal Abstinence Syndrome

The first reported case of neonatal withdrawal was in 1875.6 At this time, it was called congenital morphinism, as morphine was the most common drug exposure of the time.6 Most infants experiencing withdrawal at this time died due to numerous factors.6 In 1903, there was a report of an infant surviving withdrawal with the use of morphine during the immediate postnatal period.6 In 1964, methadone was introduced as a replacement therapy for people addicted to opioids.6 It was initially thought that methadone did not affect the neonate, but soon withdrawal was noted in this setting as well.6 From 1964 to 2002, methadone remained the treatment of choice for opioid addiction. In 2002, buprenorphine was approved for use in the United States as an alternative to methadone.6 There has also been a significant increase in the prescribing of opioids for pain management during pregnancy, and this has led to a whole new etiology of neonatal withdrawal.6 About 5% to 6% of mothers use opioids for more than 1 month during their pregnancies.6,9 With the increase of opioid prescribing and also illicit drug use, there has been a significant increase in neonatal abstinence syndrome as well, with a 5-fold increase over the last decade.3,4 Recent data from the United States Pediatric Health Information System shows an incidence as high as 20 cases of NAS in 1,000 live births.10

Neonatal Withdrawal

Opioids exist in different categories and can be endogenous to our bodies, such as endorphins, or synthetic, such as morphine, codeine, heroin, hydromorphone, fentanyl, and methadone.2 There is also a semi-synthetic category that includes buprenorphine.2 They activate primarily the mu-opioid receptors causing analgesia, sedation, euphoria, miosis, respiratory depression, and decreased gastrointestinal motility.2 Opioids have a narrow therapeutic index, and with chronic exposure a tolerance develops. They can cross the blood-brain barrier and go through the placenta, exposing the fetus to the drug.2

The withdrawal that a neonate experiences is dependent on several factors. The type of opioid and the extent and timing of exposure, the gestational age of the infant, maternal factors such as nutrition and stress, placental opioid metabolism, maternal metabolism, infant metabolism, genetic variabilities, polysubstance exposure, and comorbidities such as infections can all alter the risk and presentation of NAS.1,2,6,11 Opiates easily transfer across the placenta and this increases with gestational age, resulting in a more significant withdrawal in term infants than preterm infants.2,6 Central nervous system immaturity and lower fat deposits of the drug in the preterm infant may also contribute to a lower risk of withdrawal in infants born earlier.2 Synthetic opioids also cross more easily than semi-synthetic ones do, leading to a less significant withdrawal period from substances such as buprenorphine.6

Heroin withdrawal tends to be earlier in onset and last for a shorter period of time than other opiates.6 Methadone and buprenorphine have longer half-lives and, therefore, tend to present with symptoms of withdrawal later and the withdrawal lasts longer.1,6 Although the withdrawal may be more significant with exposure to these opioids, their use allows for steady opioid levels in the mother and fetus, minimizes cravings and suppresses withdrawal, and prevents fetal stress that can occur both with maternal heroin toxicity and withdrawal.2 Methadone, a synthetic opioid, has become the standard of care for treatment of pregnant women with opioid addiction during their pregnancy.6 By treating these women, the medical community can optimize obstetric care, decrease illicit drug use, and improve fetal outcomes despite increasing the risk of NAS and a more prolonged withdrawal than with heroin exposure.2,6,12 Buprenorphine, a semi-synthetic opioid, is becoming increasingly popular as an alternative to methadone for treatment of opioid addiction.6 Studies have shown that the length of treatment for neonates exposed to buprenorphine may be shorter than those exposed to methadone.11

Withdrawal also tends to be more significant in neonates who were exposed to multiple substances in-utero. These can be either illicit or prescribed, such as antidepressants, benzodiazepines, and gabapentin.8 These co-exposures increased the risk of NAS by 30% to 60%.8 Exposure to cigarette smoke is also linked to longer length of treatment and length of stay in neonates with NAS.9 Because opioid withdrawal can have a range of onset, the American Academy of Pediatrics (AAP) recommends observing at-risk neonates for 3 to 7 days after delivery.1,2,8 A 3-day observation period is appropriate for shorter-acting opioids, and more recent evidence suggests that 5 days is adequate in most other cases.1,2,8

Assessment of the Neonate

Several factors go into identifying and assessing neonates at risk for withdrawal in the postpartum period. One of the first important steps is to collect urine and/or meconium from the infant to test and determine more specifically to what they may have been exposed.1,6 This can aid in the treatment and expectations of withdrawal. Samples from the mother are helpful as well but do require her consent to obtain.1

Infants who are at risk for withdrawal should be monitored for signs and symptoms suggestive of NAS. There are several scoring systems available, but the most commonly used is the modified Finnegan Neonatal Abstinence Syndrome (FNAS) scoring system, which is currently recommended by the AAP.1,2,6,8,13 The Finnegan scoring system was developed in 1975 as a tool to assess and guide treatment for infants in withdrawal. It was developed specifically for opioid withdrawal in term infants.1,6 The original scoring system was long and complex so a modified FNAS was developed. It assesses 21 different symptoms of withdrawal, and the resulting score can be used to initiate, titrate, and terminate therapy.1,6,11 Scoring is performed after the infant feeds (about every 3 to 4 hours).6 A score of 8 or 9 for three consecutive assessments or higher than 12 for two assessments indicates the need for treatment initiation or escalation.7 There are several flaws to the FNAS scoring system. Although popular and widely used, it has never been validated.7 It is a lengthy tool that requires extensive training and experience to use correctly, resulting in a fair amount of variability between administrators, which can significantly affect the treatment of an individual neonate.3,4,11 Also, because of the extensive list of symptoms, about 5% of unexposed infants would qualify for treatment of withdrawal based solely on their normal newborn behavior.4

The Lipsitz tool, also known as the Neonatal Drug Withdrawal Scoring System, is a fairly simple tool with good sensitivity that was approved by the AAP in 1998.2 Another scoring system that is gaining popularity is the Maternal Opioid Treatment: Human Experimental Research NAS score, which is based on the Finnegan scoring system but with considerable changes.13 Isemann et al.14 developed an approach intended to predict the need for pharmacologic treatment within the first 48 hours after birth. He used the Finnegan scoring system but only scored infants after on-demand feeds and during skin-to-skin care.14 He avoided waking infants from sleep or removing them from family members to perform the scoring assessment.14 Scores for crying due to hunger were also reduced.14 Based on the information collected from this approach, Isemann14 developed a tool based on three highly predictive symptoms: increased muscle tone, tremors, and excoriation.

A newer approach to NAS management is becoming more popular as more research emerges. The Eat, Sleep, Console (ESC) method prioritizes withdrawal symptoms that are most relevant to the function of a newborn.4,7 Researchers determined that if an infant is able to eat, sleep, and be consoled within certain parameters, pharmacologic treatment is not necessary. Using this method, an infant is considered stable if they are able to eat more than 1 ounce per feed or breast-feed well, sleep for more than 1 hour, and be consoled within 10 minutes.7,8 This approach significantly decreases the amount of medication required for infants experiencing withdrawal.7 One study showed that only 12% of a group of exposed infants needed pharmacologic treatment with the ESC method, whereas 62% of that same group would have received pharmacologic treatment based on Finnegan scoring.4,7 In this same group, morphine was initiated or increased on 8 patient-days using the ESC method compared to 76 patient-days using the Finnegan scoring method.7 In another study, it reduced the percentage of infants exposed to methadone treated with morphine from 94% to 14%.8 It is important to note that these studies also showed no increase in adverse events or readmissions.7 By shifting the focus to the function of the neonate instead of a score based on a variety of symptoms, the ESC method allows infants to rest undisturbed, provides opportunity for more frequent and timely adjustments to treatment if needed, decreases the overall exposure to opioids, and shortens the length of stay in the hospital.7


Nonpharmacologic Treatment

Nonpharmacologic treatment of NAS is recommended as the first-line approach to management; pharmacologic treatment should be initiated only if the infant is unable to be stabilized.6,7 There are several measures that should be implemented to promote the optimal environment for infants experiencing withdrawal. Measures include a low-light and low-noise environment, music therapy, gentle handling only when awake, pacifiers, “kangaroo” care, waterbeds, massage, non-insertive acupuncture, cuddling, and manual rocking.1,2,6,7 Neonates also benefit from frequent high-calorie feeds as they expend more energy due to increased reflux, vomiting, and diarrhea from the NAS.1,2

Breast-feeding has also been found to decrease the symptoms of withdrawal in neonates. It is important to note that breast-feeding is not contraindicated in neonates experiencing NAS unless the mother is taking illicit drugs or has HIV.1,2,6 It has been found that breast milk contains minimal quantities of methadone and buprenorphine in mothers who are taking these medications for management of opioids addiction.6 The amount present is not enough to treat the NAS, nor is it enough to cause withdrawal upon cessation of breast-feeding.6 Breast-feeding also leads to increased bonding between mother and baby, encourages active involvement of parents, and builds confidence in mothers prior to discharge home with their baby.6

A “rooming-in” care model is also being studied and has been in practice in Vancouver, British Columbia, for some time. This model was first described in 2007 and advocates for strong parent or caregiver involvement and stresses the importance of comprehensive discharge planning.14 Some institutions are transitioning care of NAS babies from the neonatal intensive care unit to rooming-in with parents or appointed caregivers. This has been shown to shorten length of stay and length of treatment for infants experiencing NAS.1,4,5,6,8 Not only does rooming-in allow more parent/caregiver involvement, it is also more conducive to a low-stimulation environment that is ideal for a neonate in withdrawal.5 In one study, maximum parental presence during the newborn hospital stay was associated with a 9-day decrease in length of stay and a 1-point daily decrease in FNAS scores.4 Although rooming-in and parental involvement are ideal, there are challenges to achieving this. Many families struggle with lack of transportation, other child-care responsibilities, the need to leave for off-site methadone or buprenorphine dosing, residential treatment requirements, stigma, and guilt.4 This model of care also requires significant support from patient families, health care providers, volunteers, and the health care system as a whole.15 To appropriately support a rooming-in model of care, the health care system will need a strong infrastructure and financial support to help these families be present in the hospital for 1 to 2 weeks.15 Prenatal planning with the mother to prepare for a prolonged hospital stay improves success with rooming-in.4 It is important to note that in the studies done on rooming-in, no adverse events were recorded associated with the rooming-in.5

Pharmacologic Treatment

Although evidence is emerging that the ESC method may decrease pharmacologic treatment, using the current standard Finnegan scoring, approximately 60% to 80% of infants require pharmacologic intervention for NAS.1,10 The decision to start medication is made based on sustained high withdrawal scores or more serious symptoms such as seizures or severe dehydration from vomiting and diarrhea.6 There are two main medications used in the management of neonatal withdrawal: morphine and methadone.1,6,8,10 Buprenorphine is also now being used at some institutions to treat NAS with promising results.2

Regimens of morphine dosing vary among institutions, with some basing dose on weight and others basing dose on Finnegan scores.9 Morphine is dosed every 3 to 4 hours and has a short half-life.1,6,9 This can be beneficial in some cases as it allows for more frequent titration of medication. The downside to morphine is that it is more likely to cause sedation and respiratory depression than the other medications.1 Studies also show that using morphine for treatment prolongs the hospital stay when compared to other medications.1

Methadone has a longer half-life and a more consistent concentration in the blood, allowing for better control of symptoms and less frequent dosing (every 8–12 hours).1,6,9 Recent studies have shown that methadone decreases the length of treatment compared to morphine, likely due to this improved symptom control.1,4,10

There is also emerging evidence that using buprenorphine to manage NAS may result in a significant reduction in length of treatment and length of stay as compared to morphine and methadone.1,8 Disher et al.16 concluded that buprenorphine was the optimal treatment for NAS, resulting in the largest reduction in length of treatment as compared to other pharmacologic interventions. Currently, buprenorphine is used by only a handful of institutions.10

In some cases, infants will require adjuvant therapy in addition to the primary medication when symptoms are not well controlled or in special circumstances such as seizure activity. Phenobarbital and clonidine are the most commonly used adjunct medications.1,10,11 Although useful for controlling symptoms, prolonged exposure to phenobarbital can have a negative impact on future neurodevelopment and behavior.11 Clonidine appears to be safe, but long-term outcomes have not been well studied.11

Most infants who receive pharmacologic treatment are managed in the hospital for the entire length of treatment and are discharged home without opioid medication. However, in some cases, infants are discharged home to complete the weaning process as an outpatient. Studies have shown that although this does decrease the length of stay, resulting in less use of hospital resources, it significantly increases the length of treatment, exposing the infant to longer courses of opioids.11,17 Infants who were discharged home to complete therapy also had more emergency department visits within the first 6 months after discharge.15 One study found that many families did not even fill the prescriptions to complete the wean at home, abruptly stopping the medical management of withdrawal in these babies.15 Other barriers and challenges to outpatient management include the need for frequent follow-up for dose management and weaning, inability to fill prescriptions easily, and nonadherence to therapy for a variety of reasons.17

It is important to note that we do not have long-term data regarding the effects of withdrawal in infants or the pharmacologic treatment of withdrawal. We know that in the short term, pharmacologic treatment improves clinical signs of withdrawal.2 It is unclear, however, what the long-term morbidity of postnatal drug exposure is, making it difficult to determine whether withdrawal or its treatment puts infants at higher risk of neurobehavioral problems or other morbidities later in life.2

Other Considerations

It has been noted time and again that institutions that have a strong plan of care for infants exposed to opioids improves their management and can decrease morbidity. In 2012, the AAP issued a policy statement that expressed the importance of a comprehensive plan for the management of infants exposed to opioids that included guidelines for screening for maternal substance use, nonpharmacologic treatment of infants with NAS, pharmacologic management if needed, breastfeeding, and duration of observation for infants exposed to opiods.2 The Comprehensive Addiction and Recovery Act of 2016 mandates a specific care plan.4 There also needs to be stronger emphasis on primary prevention of opioid exposure with the aim of reducing prescribing of opioids to women of child-bearing age.3 This can be implemented with programs to monitor opioid prescribing, regulation of pain clinics, and establishment of standard opioid-dosing thresholds with special consideration of women who are pregnant.

Significant planning before the neonate is born can also improve outcomes. Clinicians who are able to provide respectful and nonjudgmental care to pregnant women with opioid use disorder build collaborative relationships that increase engagement and compliance with perinatal services.1,18 This can improve prenatal monitoring, encourage adherence to treatment, and help both care providers and families set expectations for what will happen after delivery. Planning should include discussions about involvement of child protective service, discharge planning, insurance coverage, and family support and involvement.18 Planning ahead also allows for assessment of a mother's ability to provide adequate care and a safe environment for her newborn after discharge, and, if she is unable to do so, to make alternate plans.1

Not only is it important to care for infants as they experience withdrawal in the acute phase, it is equally important to ensure close follow-up after they are discharged. Appointments with the infant's primary provider and a home nurse, as well as referral to early childhood intervention should all be in place prior to discharge.4 Follow-up care for an infant who has been through NAS should include neurodevelopmental assessments to identify any delays, psycho-behavioral assessment to monitor for attention-deficit/hyperactivity disorder and impulsivity, ophthalmologic evaluations, growth and nutritional status, and the family social situation and support.6 A strong discharge plan that includes social support services and case workers is essential as illicit opioid use is often accompanied by a chaotic lifestyle that makes getting to follow-up appointments and adhering to recommendations more difficult.1


The opioid crisis in the United States has grown, and as a result there are significantly more babies being born who were exposed to these substances in-utero. It is increasingly important that we manage these infants appropriately to provide the best possible long-term outcomes. More work is needed to determine the best way to assess these infants and determine their true need for pharmacologic intervention. Enhancing nonpharmacologic interventions and promoting as much family involvement as possible is a good place to start. Determining the safest and most efficacious form of pharmacologic treatment when necessary will also help improve the long-term outcomes for this at-risk population by decreasing their overall opioid exposure. Finally, addressing the core problem of opioid abuse and opioid use disorder and enhancing the social services available for dealing with this issue also help to stabilize and enhance the lives of neonates who experience NAS.


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Leah Khan, MD

Leah Khan, MD, is a Pediatrician, Park Nicollet Clinics.

Address correspondence to Leah Khan, MD, 300 Lake Drive East, Chanhassen, MN 55317; email:

Disclosure: The author has no relevant financial relationships to disclose.


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