Newest Advances in Care for Neonatal Opioid Withdrawal, Prenatal Opioid Exposure

Over the past 5 years, important advances have occurred in the diagnosis, management, and outcome assessment for infants with prenatal opioid exposure (POE) and neonatal opioid withdrawal syndrome (NOWS). A state-of-the-art review, published in Pediatrics, explores these advances and also highlights the work that is still needed to improve outcomes for affected children and their families.

In the past 2 decades, the prevalence of POE and NOWS has markedly increased in the United States. Particularly, rural areas and pregnant persons with lower income and publicly funded health insurance are most heavily impacted by these conditions. In light of this increased prevalence, this state-of-the-art review provides clinicians with updated evidence on identification, diagnosis, treatment, and postpartum follow-up for POE, and identifies factors that may predict the severity of NOWS.

Identification and Diagnostic Conventions

The authors have outlined guidelines and policies that institutions can adopt for proper screening, assessment, and management of NOWS. Particularly, they detail the best practices for the duration, frequency, and timing of infant withdrawal screening.

For prenatal identification of fetal opioid exposure, validated clinical questionnaire-based assessments should be prioritized over toxicology screenings. Toxicology tests should be limited to contexts in which the results are likely to guide treatment. Furthermore, the authors note that screenings for substance use, and toxicology testing in particular, have frequently occurred in the context of racial and ethnic bias. Clinicians should therefore remain aware of the pervasive racial/ethnic disparities in perinatal toxicology testing and how testing may result in mandated child protective services reporting.

The 2 most commonly used assessment tools for evaluating NOWS are the Finnegan Neonatal Abstinence Scoring Tool (FNAST) and the Eat, Sleep, and Console (ESC) assessment. The ESC approach, in particular, has become widely adopted in the US. It scores infant status in the domains of sufficient feeding ability, capacity for undisturbed sleep, and amount of soothing time needed to be consoled. Recent research indicates its use may shorten hospital stays for newborns with NOWS.

Official standardized diagnostic criteria for NOWS were recently proposed following an expert consensus panel convened by the US Department of Health and Human Services in 2022. For a clinical diagnosis of NOWS, there must be 1) exposure to opioids during pregnancy, as identified via self-report or toxicology testing, and 2) the presence of at least 2 withdrawal symptoms in the newborn. These symptoms can include excessive crying, fragmented sleep, tremors, hypertonia, and gastrointestinal dysfunction. In infants with symptoms recalcitrant to treatment, clinicians should consider alternative diagnoses including infection, respiratory distress, epilepsy, and hyperthyroidism.

Management

During delivery hospitalization, teams should establish a trusting and positive experience with their patients as families affected by POE are often subject to intense stigma and shame. Clinical staff should recognize and reduce bias in care, provide counseling support for family members, and establish preferred, person-first, non-stigmatizing language with patients and their caregivers.

As with any perinatal dyad, rooming-in of the primary caregiver with the infant is advised whenever possible. This has been confirmed to yield shorter periods of treatment with opioids, shorter total hospitalization, and reduced pharmacologic treatment. A potential barrier is cardiorespiratory monitoring of newborns during treatment with opioid medication of a newborn. Outbreaks of infectious diseases, such as COVID-19, may also influence rooming-in protocols.

First-line treatment of NOWS is non-pharmacologic. This includes:

• ensuring caregiver well-being and ability to respond to the infant’s needs,
• physical contact and swaddling practices,
• optimal sound and light environment,
• and alignment of clinical care and infant sleep patterns.

Practices and technologies using special beds, such as vibrating mattresses, and low-stimulation environments have not been sufficiently studied to warrant robust recommendations.

Feeding and necessary weight gain can be challenging in the context of NOWS. Despite the excessive drive to feed, infants with NOWS may gain insufficient weight or even lose weight. Breastfeeding, absent any contraindications, is associated with shorter duration and less severe symptoms of NOWS. To date, different varieties of infant formulas have not yet shown actionably different outcomes for weight loss, duration of care, and need for pharmacologic treatment. Nasogastric feeding may be considered if oral feeding remains insufficient to sustain and gain weight.

For an infant with NOWS who is not sufficiently responsive to nonpharmacologic treatment, opioid medications (ie, morphine, methadone, and buprenorphine) are considered primary drug options. Second-line medications include clonidine and phenobarbital. One of the most notable changes in practice recommendations is the use of symptom-triggered, need-based dosing as opposed to standing, scheduled dosing. However, research into such dosing schedules, particularly comparing morphine and methadone, is ongoing. Additionally, adjuvant therapies, such as ondansetron, have shown promise in reducing opioid pharmacologic therapy, according to a recent multi-site randomized trial.

Regardless of an institution’s choice of primary or secondary agents, standardized protocols are recommended for both dosing and weaning of first- and second-line medications.

Determinants of NOWS Severity

Several recent studies have identified factors that contribute to NOWS severity. In evaluating the effect of medications to treat OUD, research indicates that infants who have been exposed to buprenorphine may be less likely to receive a diagnosis of NOWS. However, exposure to non-prescribed fentanyl, among other factors, may limit the applicability of this research finding. Additionally, the risk for NOWS increases with exposure to higher doses of opioids, exposure to 1 or more of a variety of psychiatric medications, and concurrent exposure to substances such as cannabis and cocaine. In addition to medications and substance use, research indicates that prenatal care and genetic and epigenetic factors are associated with NOWS severity.  

Discharge and Outpatient Follow-Up

The authors recommend the use of a clinical readiness checklist to evaluate whether an infant with NOWS is ready for safe discharge. Readiness factors include symptom readiness and cessation of pharmacologic treatment, infant feeding and weight status, caregiver safety, establishing a care plan, and the placement of necessary outpatient referrals.

Post-discharge care is important for preserving the health of any newborn, but few evidence-based recommendations are available for post-discharge care in the context of POE and NOWS. Likewise, few studies have investigated the risk for motor and cognitive delays in children with histories of NOWS and/or POE. At this time, the authors recommend that infants with a history of POE receive a formal evaluation for developmental delays and receive early intervention services, if possible. Other recommendations include screening for hepatitis C and potential visual dysfunction.

Directions for Future Research and Clinical Care Improvement

The growing prevalence of these conditions emphasizes the need for new treatments and enhanced understanding of POE and NOWS — especially long-term outcomes that are underexplored. To improve outcomes and advance clinical practice, there are a number of areas for future research.

Although clear clinical diagnostic criteria have recently emerged for NOWS, there is still a need for standardized diagnostic terminology across clinical, public health, and diagnostic coding authorities. This standardization would be crucial for researchers to accurately identify and quantify the impact of POE. Accordingly, stigmatizing language in official medical coding should be eliminated. Currently, the International Classification of Diseases, Tenth Revision (ICD-10) codes use the phrase “maternal use of drugs of addiction”, and do not provide alternative, nonstigmatizing options when POE results from medications used to treat opioid use disorder.

Furthermore, there is a critical need for more long-term explorations of the impact of POE and NOWS management approaches. There is currently a lack of data on the potential adverse neurodevelopmental effects of POE and NOWS and how interpersonal and environmental supports could improve outcomes for opioid-exposed children and families.

While there have recently been major advances in the care for POE and NOWS, future studies should incorporate the above recommendations to improve outcomes for opioid-exposed dyads at each step of clinical care.

This article originally appeared on Psychiatry Advisor