Implementation of a Standardized Clinical Definition of Opioid Withdrawal in the Neonate

Challenges and Opportunities

Shahla M. Jilani, MD¹; Hendrée E. Jones, PhD^2,3; Jonathan M. Davis

As a consequence of the US opioid crisis, opioid use disorder (OUD) and correspondingly, neonatal abstinence syndrome (NAS) have significantly affected pregnant people and neonates. The most recent published data show that in 2017, 6065 pregnant individuals had opioid-related diagnoses and 5375 neonates had NAS in the US. This represents an increase of 4.6 per 1000 deliveries and 3.3 per 1000 birth hospitalizations from 2010 to 2017.¹

Despite this increase, a standard clinical definition for NAS has been lacking for more than 45 years. Even though NAS has been described as a constellation of clinical signs of withdrawal that can result from prenatal exposure to opioids and other psychotropic substances,² an agreed-upon definition has not been established. Accordingly, there has not been consensus on the precise signs of withdrawal or how to diagnose NAS at the bedside. This has created a diagnostic gap, introducing broad variability in how NAS has been clinically identified, ranging from a neonate with a history of opioid exposure to one requiring pharmacotherapy. Although specific to the neonate, this diagnostic gap has had considerable influence on care management, administrative coding and data collection, research efforts, and public health policy for the mother-infant dyad.

To address this need, a national collaboration among clinicians, researchers, policy experts, and the US Department of Health and Human Services was recently established. This group published recommendations for a clinical definition of opioid withdrawal in the neonate that is applicable to NAS and neonatal opioid withdrawal syndrome (NOWS), considered a subset of NAS characterized by opioid exposure alone.³ Notably, given an additional consensus gap for the use of these particular terminologies (ie, NAS, NOWS, NAS/NOWS), the recommendations specifically focus on the clinical presentation of clinical opioid withdrawal in the neonate. As diagnostic criteria, they do not address severity, clinical assessment tools, nonpharmacological care, or pharmacotherapy. Nonetheless, the use of a consistent clinical definition is essential in informing these considerations and other related issues such as treatment protocols, administrative coding, surveillance, research criteria, and the spectrum of care for the mother-infant dyad. This ranges from maternal preconception health to family-centered programs and policies.

To navigate limitations in clinical trial and consensus data, recommendations were developed using a modified Delphi method, integrating available evidence with expert input. The new definition of opioid withdrawal in the neonate includes 2 specific elements: in utero exposure to opioids with or without exposure to other psychotropic substances and the presence of 2 of 5 of the most common clinical signs of opioid withdrawal in the neonate (excessive crying, fragmented sleep, tremors, increased muscle tone, and gastrointestinal dysfunction [eg, hyperphagia, poor feeding, feeding intolerance, or loose or watery stools]). These elements were selected to balance specificity with sensitivity for even mild presentations after prenatal opioid exposure, including those requiring only nonpharmacological (supportive) care.

These criteria were introduced at a 2021 US Department of Health and Human Services national convening of clinicians, researchers, and policy experts. Numerous issues were prioritized regarding shared interests of the mother-infant dyad such as identifying and addressing clinical and supportive care, legal considerations of substance exposure, family-centered policy implementation, and limitations of inconsistent inclusion and exclusion criteria in research. The unintended consequences of this definition were also considered including (1) using the diagnosis as evidence of harm, (2) more maternal stigmatization related to an increased number of neonates receiving a diagnosis of NAS/NOWS, and (3) maternal reticence of seeking OUD care and treatment.

This approach is unique in the need to harmonize evidence-based medicine and bioethics with foundational principles created to specify uses (clinical) and misuses (punitive) of the definition. Given the multiple factors involved in the care of mothers and their neonates including familial, social, and environmental, these principles indicate that the definition is intended for clinical purposes only and should not be considered evidence of harm or be used to remove the neonate from parental custody. These principles are consistent with guidance from the National Center on Substance Abuse and Child Welfare for drug testing, which highlights the importance of considering a combination of factors in determining child welfare risk.⁴ However, this definition is specifically designed to identify neonates who may need follow-up and early intervention services, including those offered through local child and family services.

Even though bioethical principles are not routinely linked to diagnostic criteria in the pediatric or adult literature, they are critical for this clinical definition because criminalization of substance use during pregnancy adversely affects both the mother and neonate as well as research on prenatal substance exposure and NAS.⁵ Thus, using the clinical definition for the bedside diagnosis is intended to inform discussions about clinical approaches to better support the mother-infant dyad and not increase punitive approaches toward pregnant people. This is particularly important given that treatment for OUD itself can increase the risk of NAS/NOWS while significantly improving maternal and neonatal outcomes such as decreased maternal overdose deaths and preterm births.⁶

Standardizing the diagnosis of NAS/NOWS also could assist with ongoing needs to harmonize severity assessments, scoring tools, and treatment protocols. Applying this definition to the development of a severity index is a logical next step toward standardizing the clinical approach to prenatally opioid–exposed neonates. Moreover, clinical monitoring approaches (eg, the Finnegan Neonatal Abstinence Scoring System, the Eat, Sleep, Console assessment tool) may benefit from inclusion of standard diagnostic criteria as a common starting point. Development of bedside treatment protocols (pharmacological and nonpharmacological) may likewise benefit from integration of a standard definition for consistent diagnosis of opioid withdrawal in neonates.

Beyond establishing the clinical diagnosis to guide patient care, standardizing the clinical definition may also improve existing administrative practices, including the accuracy and reproducibility of administrative coding, which currently limits the utility of administrative data sets in public health research. Although administrative data have high positive predictive value for properly identifying NAS, they require an accurate clinical diagnosis.⁷ Starting with a common clinical definition will provide the opportunity to refine inconsistent coding practices and documentation of NAS/NOWS. Using this definition to supplement the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification also offers an opportunity to refine coding guidelines to increase accuracy. Even though the clinical definition is distinct (for bedside diagnosis) from the case definition (for public health reporting), it may complement efforts of the Council of State and Territorial Epidemiologists to standardize NAS reporting for state epidemiological surveillance.⁸

A common clinical definition could promote standardization of data collection and enhance research efforts. For example, the lack of consistent inclusion and exclusion criteria leads to significant variability in clinical trial design and enrollment. Pharmacotherapeutic trials, whether evaluating treatments for OUD or NAS, will benefit from the use of consistent and definitive inclusion and exclusion criteria. Likewise, research can explore how inclusion of maternal OUD (treated or untreated) and chronic opioid use (with or without OUD) may inform this recommended clinical definition so clinicians and researchers can better understand any intended or unintended consequences.

Most important, a standardized clinical definition is pertinent to multiple policies and programs resulting from legislation that supports mothers, infants, and families. Accordingly, having a standardized clinical definition could more accurately identify specific communities where these programs will be most beneficial. Moreover, the use of this clinical definition could serve to standardize language used around services for NAS/NOWS at federal, state, and local levels to address long-standing variability. Unquestionably, such potential benefits must be balanced by the real risk that significantly more neonates will receive the diagnosis, including the potential for false-positive cases. Yet, standard criteria to capture and consistently diagnose even mild presentations is necessary to better understand and address the public health consequences of the opioid crisis. A more inclusive diagnosis can facilitate referral to programs that may serve the short- and long-term needs and improve outcomes for the mother-infant dyad and family.

The new clinical definition should be independently validated. However, these recommendations have the potential to provide a significant shift in the way mothers and neonates with prenatal opioid exposure are identified, centering around creation of a common diagnostic language. First, implementation by clinicians could promote standardized practice to inform clinical needs and care delivery for the mother-infant dyad and their families. Second, application of the definition by researchers and public health advocates could help to fill gaps in administrative coding and data collection, research efforts, and public health policy with designated services and funding reaching as many affected mother-infant dyads as possible. This clinical definition with accompanying validation and implementation steps represents a promising path forward to provide the care and services that pregnant people and neonates with prenatal opioid exposure need to improve their health and well-being.