Neonatal Abstinence Syndrome (FL INITIAL Autonomous Practice - Differential Diagnosis)

Neonatal abstinence syndrome (NAS) is experienced by newborns exposed to opioids or other substances, such as benzodiazepines and selective serotonin reuptake inhibitors. An infant exposed to such substances in utero is often at risk of developing withdrawal after birth. NAS is a generalized disorder characterized by signs and symptoms of autonomic nervous system dysfunction, respiratory distress, gastrointestinal symptoms, and neurobehavioral dysregulation. NAS describes infants at risk for withdrawal from polysubstance, including opioids. Neonatal opioid withdrawal syndrome (NOWS) describes neonates with opioid-only withdrawal symptoms. The term NAS will be used here to describe both polysubstance and opioid-only exposure and withdrawal.

NAS occurs in 50-95% of infants exposed in utero to substances during pregnancy. These infants often begin to demonstrate signs of withdrawal during the first two to seven days of life. Nurses caring for these infants must have the assessment skills to assist in the timely diagnosis and treatment of these infants. The care of these infants often requires environmental modifications, developmental modifications, feeding plans, and family partnership in care, and between 42-94% of these infants require pharmacotherapy treatment (Patrick et al., 2020).

NAS is defined by signs of postnatal drug withdrawal and can occur from exposure to either licit (oxycodone, fentanyl) or illicit substances (heroin) in utero. It is also associated with antenatal exposure to medication used to treat opioid use disorder, such as methadone or buprenorphine. NAS causes major physiological changes in the infant, including respiratory distress, autonomic nervous system dysfunctions, nervous system irritability, and gastrointestinal disturbances.

The United States is experiencing an opioid use crisis, leading to an increased incidence of NAS. The number of infants covered by Medicaid diagnosed with NAS has increased fivefold from 2004 to 2017. In 2004, four per 1000 births resulted in NAS, compared to seven out of 1000 births in 2017 (Hirai et al., 2021). Newborns with NAS stay nine days longer compared to non-NAS newborns, with an average of $14,600 in additional costs (Bhatt et al., 2021). In 2014, $563 million was spent on costs for the treatment of NAS; 82% of this was covered by state Medicaid programs, reflecting the greater tendency of mothers using opioids during pregnancy to be from lower-income communities (Honein et al., 2019).

The pathophysiology of NAS and the various factors that affect the severity is not completely understood today; however, it is directly related to the agonist effects of opioids. These agonist effects of opioids lead to supraspinal analgesia, sedation, euphoria, respiratory depression, and decreased gastrointestinal motility. Opioids at the cellular level inhibit the release of noradrenaline at synaptic terminals. Chronic exposure to opioids causes tolerance as noradrenaline release from the synapse rate increases towards normal. When the discontinuation of opioids occurs at birth, there is a supranormal release of noradrenaline, which then causes autonomic and behavioral symptoms of withdrawal. The mu receptors are more concentrated in the gastrointestinal tissue and the central nervous system; therefore, withdrawal likely includes the central nervous system, overactive autonomic system, and gastrointestinal disturbances (Hirai et al., 2021).

The onset of NAS symptoms and clinical signs of withdrawal vary depending on the history of the intrauterine exposure and the half-life of the substance used. For neonates exposed to maternal heroin and prescription opioids, withdrawal symptoms commonly present in the first 24 hours of life. Clinical signs and symptoms of withdrawal from methadone or buprenorphine generally start between 48 to 72 hours after birth because those substances are long-acting. However, for all opioids, withdrawal may be delayed for up to 5-7 days after birth.

The classic signs of NAS are related to the dysfunction of state of control and attention, motor and tone control, sensory integration, and autonomic functioning. Symptoms include the following:

• Metabolic, vasomotor, and respiratory system:
  • Temperate instability
  • Frequent yawning
  • Sweating
  • Sneezing
  • Nasal congestion
  • Tachypnea
  • Mottling
• Gastrointestinal system:
  • Projectile vomiting
  • Reflux
  • Loose/watery stools
  • Poor weight gain
  • Poor feeding
  • Excessive sucking
• Central Nervous System:
  • Jitteriness
  • Short sleep cycles
  • Difficulty maintaining an alert state
  • High-pitched cry
  • Irritability
  • Seizures
  • Hyperarousal state
  • Excoriation

Healthcare providers caring for infants at risk for NAS based on maternal history or those newborns with suspected NAS are assessed and scored on a specific NAS scale to monitor the presence and severity of their withdrawal and help manage their care. Several screening tools have been developed over the past several decades; however, the Finnegan Neonatal Abstinence Scoring System is the most widely used. Loretta Finnegan developed this tool in 1975 to provide a standardized method for assessing full-term neonates exposed to narcotics. The tool assesses 21 of the most commonly found clinical symptoms and signs of newborn drug withdrawal, and the total score can range from 0-62. The newer function-based approach and assessment of the Eat, Sleep, Console care is gaining use throughout the United States. In 2014, Grossman and colleagues developed the Eat, Sleep, Console approach for the assessment of infants experiencing opioid withdrawal; this approach focuses on the newborn's ability to eat, sleep, and be consoled using nonpharmacologic interventions and empowerment of families and caregiver teams of the newborns (Young et al., 2023). NAS assessment should begin at birth for all newborns with known opioids and other substance exposure, and the assessment should be performed every 2-4 hours for the length of the newborn's hospital stay.

It should be noted that most of the assessment tools to assess NAS are based on a full-term infant and are not appropriate for use in preterm newborns. Preterm infants less than 35 weeks gestation have lower rates of NAS when compared to full-term newborns. NAS symptoms are noted to be less severe as gestational age decreases. This syndrome is related to the developmental immaturity of the central nervous system and decreased mu receptor development, and a lower amount of fat deposition of substances. Premature infants also have a limited ability to express signs of motor dysfunction and experience reduced total substance exposure during their shortened intrauterine period.

Identification of NAS in neonates is through the reported maternal history of drug use, physical examination, and laboratory tests. The clinical diagnosis of perinatal drug exposure is based on the reported or suspected history of maternal opioid use, positive maternal drug screening, positive newborn drug screen results, or neonates presenting with findings consistent with NAS. Identifying newborns at risk for NAS begins during prenatal care of the mother. Suppose the healthcare team is aware of the maternal use of opioid substances before the newborn's birth. In that case, the team will be able to provide accurate clinical assessments and early interventions and mitigate signs of NAS. However, women are often less likely to self-report illegal drug use with their healthcare providers because of social and legal consequences. Screening for maternal substance use through toxicology requires consent, and currently, there is no consensus on universal screening. In the United States, screening newborns' biological specimens for substance exposure may not require maternal consent based on state laws. Neonatal testing is most commonly performed on urine, although this screening has a low sensitivity. Hair, meconium, and umbilical cord tissue are other specific toxicology tests used to assess newborn intrauterine drug exposure. Although a positive maternal or neonatal toxicology specimen is useful in confirming the diagnosis of NAS, it should always be considered an adjunct to the healthcare providers' clinical assessment.

NAS may also have similar features to other conditions affecting newborns; therefore, clinical signs should not be purely attributed to drug withdrawal without assessment and diagnostic tests to differentiate from other causes. Seizure-like activity may be related to hypocalcemia, hypoglycemia, and hypoxic-ischemic encephalopathy. Newborns presenting with fever, irritability, and poor feeding may be linked to sepsis, hyperthyroidism, and polycythemia.

The care of the newborn at risk for or diagnosed with NAS must be delivered by a nonjudgmental multidisciplinary team trained in the management of maternal substance use disorder and NAS. Social services and healthcare providers must work together to care for the newborn-mother dyad during their hospital stay and outpatient care. The goal of the care is to promote maternal-infant bonding, normal growth and development, and minimize signs of NAS expression. The goal should be accomplished in a safe, compassionate environment designed to be inclusive for the mother and her newborn. The mother's ability to assist in the care of her infant has positive effects on both mother and newborn and leads to enhanced bonding and parenting. If the mother cannot provide care to her newborn, the family should be incorporated into the place of care.

Since the signs of withdrawal can begin almost immediately after birth, all healthcare workers must know how to assess these newborns. Like the Finnegan Neonatal Abstinence Scoring System, a standard assessment tool should be initiated within the first two hours of life and performed every four hours until discharged from the hospital. Nurses caring for mothers and their newborns after birth must be highly trained on these tools. The tool assesses the severity of the withdrawal and the effects of individualized adaptations to care. When postpartum nurses have an increased understanding and knowledge of their institution's chosen assessment tool, they can better determine which symptoms can lead to an earlier diagnosis and treatment plan.

Nursing care for this vulnerable population includes both nonpharmacologic and pharmacologic therapies. The nurse uniquely designed the nursing care based on the infant's behavioral symptoms to minimize withdrawal symptoms. Environmental modifications include dim lighting, quiet, limited handling, stimulation, cotton linens, soft music or white noise, swaddling, and aromatherapy. These modifications address the hypersensitivity NAS infants experience to external stimuli. They assist in reducing hyperactivity and help the infant organize their behaviors. Non-nutritive sucking, frequent smaller feeds, diaper creams, and frequent diaper changes can assist in minimizing the gastrointestinal side effects associated with NAS. Breastfeeding should be encouraged for mothers taking prescribed opioids, methadone, or buprenorphine. Breastfeeding may reduce the severity of the NAS symptoms and the need for pharmacologic treatment. Breastfeeding provides more easily digestible milk in small and more frequent on-demand feeds.

Nurses who assess infants with jitteriness, myoclonic jerks, excessive moro reflexes, and neurologic hypersensitivity can use treatments that may help the newborn relax. These treatments can include Reiki, infant massage, and swaddling. Swaddling also helps skin excoriation due to excessive rubbing, thereby reducing trauma to the skin. Topical barrier creams help treat diaper dermatitis and should be used at the earliest signs of skin irritation. Kangaroo care should be performed when the mother can, which will assist the newborn in regulating their temperature, oxygenation, heart rate, and respiratory rate. Evidence supports the nurse caring for the mother-newborn dyad and encouraging rooming-in. Rooming-in is associated with improved breastfeeding outcomes, increased maternal satisfaction, and greater involvement in the maternal care of the newborn.

In many cases, even with continued thorough nursing assessments and individualized non-pharmacologic care of the NAS newborn, a pharmacologic intervention has to be initiated. Pharmacologic therapy is designed to be a short-term agent used to improve the clinical symptomology of NAS. The goal of the therapy is to mitigate the signs of withdrawal, seizures, fever, weight loss, and dehydration. Although guidelines suggest the preferred treatment method is opioid therapy, there is no universal standard of care, and variations in practice exist. Morphine and methadone are the preferred opioid formulations, morphine being a short-acting opioid and methadone a long-acting opioid.

Each medication has advantages and disadvantages, and recent research suggests that a standardized protocol for the pharmacological treatment of NAS is more important than which drug is used to treat it. Improved standardization of nursing assessment, standards of nursing care, pharmacological treatment plans, and weaning protocols lead to shorter durations of medication use and reduced length of hospitalization. Discharge planning of the NAS infant must involve a multidisciplinary team. The mother's health and her maternal functioning, mental health, substance abuse treatment, the home environment, and support systems must all be assessed. Healthcare providers should educate the mother on sudden infant death syndrome (SIDS), sleeping positions, ongoing substance use disorder treatment, infant signs of infection, and the traditional newborn education received during the postpartum period.

The long-term effects of intrauterine opioid exposure on the child's development are difficult to determine because of the small sample sizes of published studies and other variables. Prenatal variables include polysubstance exposure, low birth weight, intrauterine growth restriction, etc., and postnatal variables range from continued maternal drug abuse, socioeconomic status, maternal educational levels, and other multiple factors. Several observational studies have found associations between NAS and a negative effect on neurodevelopment and psychological outcomes, including lower intelligence scores, educational disabilities, maltreatment, and trauma during childhood. These adverse outcomes suggest a need for early intervention for both the newborn and the mother. After discharge, pediatric and social service follow-up is recommended for child safety and the promotion of healthy development and continued maternal substance use treatment. For mothers and newborns with NAS, the complexity of their care, both while hospitalized and after discharge, requires collaboration between early intervention programs, child protective services, and healthcare team members. This collaboration may lead to a more positive outcome for the dyad and their families.

Newborns with intrauterine exposure to opioids are at risk for developing NAS after birth. Recently, researchers noted that male infants are more likely to be diagnosed with NAS when compared to females. Researchers have also found that maternal polysubstances combined with benzodiazepines, cigarettes, and male-gender newborns have been associated with increased severity of NAS (Anbalagan et al., 2023).

Additionally, there is a greater risk for a newborn to develop NAS when they were exposed for greater than 30 days in utero compared to a shorter duration of exposure, and there was a greater risk when the opioid exposure was during the third versus first or second-trimester intrauterine exposure (Anbalagan et al., 2023).

The primary prevention of NAS includes awareness about the risks associated with the use of opioids and other substances to prevent addiction in all women, especially during the reproductive age. Before pregnancy, healthcare providers need to take opportunities to assess and treat any unhealthy drug use prior to conception. Clinicians should counsel women of reproductive age about the risks associated with opioid therapy, misuse, addiction potential, and the risks to pregnancy. Routine screening for unhealthy substance use at all healthcare visits will help increase primary prevention opportunities. Women should be routinely asked about alcohol and drug use during pregnancy, including opioids and prescriptive medications. Referrals should readily be made when appropriate to substance abuse treatment services for managing opioid dependency during pregnancy. Opioid abuse prevention for women is the gold standard for primary prevention of NAS in newborns.

Identifying infants at risk for NAS and standardized treatment of newborns with NAS are strategies to reduce NAS effects. Nonpharmacological treatment plans should be initiated first, including rooming in, breastfeeding, minimizing stimuli, swaddling, and others discussed in the above sections. Pharmacologic therapies should be coupled with customized nonpharmacologic strategies as recommended by the Academy of Pediatrics.

Baby boy Jack was born at 37 weeks gestation to a mother who received fragmented prenatal care. At 24 hours of age, the postpartum nurse notes that his respiratory rate is 65, and he has nasal congestion, increased moro reflex, mild tremors, and a high-pitched cry. The mother has been exclusively breastfeeding and reports that he cluster-fed most of the night.

Think about:

• Differential diagnoses:
  • Hypoglycemia – glucose 96
  • Hypocalcemia – calcium is 9
  • Hypomagnesemia– magnesium is 1.6
  • Hyponatremia – sodium is 140
  • Birth injury – Apgars 8 & 9
• What additional history is important to gather?
  • The obstetric team could not do a toxicology screen on the mother before delivery because she was in active labor on admission and delivered within ten minutes of arrival.
  • The postpartum nurse reviews the mother's chart from her limited prenatal care and finds a positive urine drug screen for opiates and marijuana from her 20-week maternal-fetal medicine appointment.
• What studies confirm the diagnosis?
  • An infant urine drug screen and meconium drug screen were positive for opioids and marijuana. NAS diagnosis is confirmed.
• What are the next steps?

After talking with the women's health social worker, Jack's mom revealed she had a history of heroin use, and one year ago, she overdosed and started a methadone program. She could not commit to the program and began buying methadone off the street. She also admitted to intermittently smoking marijuana for many years.

Think about:

• What are some of the risk factors in this case?
• What type of continuous assessment needs to be performed on this baby?
• What type of nonpharmacologic interventions can the nurse start?
• What pharmacologic therapies should the nurse anticipate?

The Eat, Sleep, and Console approach was initiated to care for the newborn and mother. The social worker, provider, and nurse worked together to establish a plan with the mother to best care for her infant experiencing withdrawal. The mother was exclusively breastfed in a dimly lit room, external stimuli were kept to a minimum, and soft white noise was played. When the infant was not breastfeeding or skin-to-skin, that infant was swaddled tightly and had frequent diaper changes, and diaper cream was applied with each change. The mother agreed to an outpatient treatment program that included parenting classes and regular visits with support services. Five days after delivery, the newborn and mother were discharged home with a safe newborn and mother plan of care in place and extensive community resources.

• Anbalagan, S., & Mendez, M. D. (2023). Neonatal abstinence syndrome. In StatPearls. StatPearls Publishing. Visit Source.
• Bhatt, P., Umscheid, J., Parmar, N., Vasudeva, R., Patel, K. G., Ameley, A., Donda, K., Policano, B., & Dapaah-Siakwan, F. (2021). Predictors of length of stay and cost of hospitalization of Neonatal Abstinence Syndrome in the United States. Cureus, 13(7), e16248. Visit Source.
• Hirai, A. H., Ko, J. Y., Owens, P. L., Stocks, C., & Patrick, S. W. (2021). Neonatal Abstinence Syndrome and maternal opioid-related diagnoses in the US, 2010-2017. JAMA, 325(2), 146–155. Visit Source.
• Honein, M. A., Boyle, C., & Redfield, R. R. (2019). Public health surveillance of prenatal opioid exposure in mothers and infants. Pediatrics, 143(3), e20183801. Visit Source.
• Patrick, S. W., Barfield, W. D., Poindexter, B. B., & COMMITTEE ON FETUS AND NEWBORN, COMMITTEE ON SUBSTANCE USE AND PREVENTION (2020). Neonatal Opioid Withdrawal Syndrome. Pediatrics, 146(5), e2020029074. Visit Source.
• Young, L. W., Ounpraseuth, S. T., Merhar, S. L., Hu, Z., Simon, A. E., Bremer, A. A., Lee, J. Y., Das, A., Crawford, M. M., Greenberg, R. G., Smith, P. B., Poindexter, B. B., Higgins, R. D., Walsh, M. C., Rice, W., Paul, D. A., Maxwell, J. R., Telang, S., Fung, C. M., Wright, T., … ACT NOW Collaborative (2023). Eat, sleep, console approach or usual care for Neonatal Opioid Withdrawal. The New England Journal of Medicine, 388(25), 2326–2337. Visit Source.

Additional resources:

• Jansson, L.M. (2024). Neonatal Abstinence Syndrome (NAS): Management and outcome. UpToDate. Visit Source.
• Jilani, S. M., Jones, H. E., Grossman, M., Jansson, L. M., Terplan, M., Faherty, L. J., Khodyakov, D., Patrick, S. W., & Davis, J. M. (2022). Standardizing the clinical definition of opioid withdrawal in the neonate. The Journal of Pediatrics, 243, 33–39.e1. Visit Source.
• Velez, M. L., Jordan, C., & Jansson, L. M. (2021). Reconceptualizing non-pharmacologic approaches to Neonatal Abstinence Syndrome (NAS) and Neonatal Opioid Withdrawal Syndrome (NOWS): A theoretical and evidence-based approach. Part II: The clinical application of nonpharmacologic care for NAS/NOWS. Neurotoxicology and Teratology, 88, 107032. Visit Source.