Neonatal opioid withdrawal syndrome (NOWS) follows in utero exposure to opioids. Signs of opioid withdrawal are manifest in autonomic, neurologic, and gastrointestinal domains with a recent expert panel consensus of at least 2 of 5 signs: excessive crying, fragmented sleep, tremors, increased muscle tone, and/or gastrointestinal dysfunction as well as a history of in utero exposure required for a diagnosis of NOWS [1].

A widely used scoring instrument to assess severity of neonatal opioid withdrawal is the Finnegan neonatal abstinence scoring system (FNAS) which includes 21 scored elements [2, 3]. One variant with a high degree of overlap is the MOTHER NAS scale (MNAS) with 19 scored elements [4]. Other short variants of FNAS with a goal of reducing the scoring burden while maintaining diagnostic accuracy have been developed. Maguire developed a seven-element FNAS score [5], Devlin generated an 8-element score [6], and Gomez-Pomar developed a 10-element score [7] with excellent specificity and negative predictive value for identifying infants with FNAS scores ≥8 and ≥12, which are common cutoffs used to guide dosing adjustments in neonates requiring pharmacotherapy. These shortened scores varied in the number of elements and the specific elements chosen. The gestational ages used were ≥36 (Devlin), ≥37 (Gomez-Pomar) and mixed in Maguire (though ~95% were ≥37 weeks).

We previously developed nine-element short scale scoring systems that maintained high sensitivity and specificity for matching the key dichotomized FNAS/MNAS scores of ≥ 8 and ≥ 12. While differences in study populations make direct comparisons difficult, these two nine-element versions, sFNAS-9 and sMNAS-9, had better test characteristics than the seven-element score proposed by Maguire, and were similar in performance to the 10-element score of Gomez-Pomar, except in improved sensitivity for predicting > 12 decision points in the full FNAS score. Furthermore, the 9-element shortened MNAS includes all 5 clinical signs determined characteristic of NOWS by consensus [1]. The MOTHER NAS scale (MNAS) and 9-element MNAS score (sMNAS-9) are shown in Table 1 (reproduced from [8]).

In the present work, we sought to develop new treatment algorithms with clinic decision rules based on cut off values for the short sMNAS-9 instrument while maintaining the integrity of the algorithms currently in use based on the original MNAS scoring. The Thomas Jefferson University Hospital Neonatal Intensive Care Unit (NICU) order set for morphine treatment of NOWS utilizing the original 19-item MNAS scoring tool was created in 2011 and refined into an algorithm in 2017 to reflect clinical practice in place since 2005 (Fig. 1) [4]. A similar algorithm for buprenorphine treatment was developed in 2018 after a successful randomized clinical trial established that treatment with sublingual buprenorphine resulted in a shorter duration of treatment and shorter length of hospital stay than treatment with oral morphine, with similar rates of adverse events [9]. The algorithm for buprenorphine treatment of NOWS based on full MNAS scoring is shown in Fig. 2. Our objective was to maintain the logic and clinical decision rules to increase, maintain, decrease the dose, begin or discontinue morphine or buprenorphine treatment while replacing the decision rules based on original MNAS scoring with decision rules based on cut-offs derived for sMNAS-9 scores. For this purpose, the thresholds based on longitudinal measures of full MNAS scores (single score, sums or averages of the last 3 scores or all scores within past 24 h) were considered “gold standard”, and similarly computed sums or averages of sMNAS-9 scores were used as predictors to optimize the cutoffs for sMNAS-9 that match as best as possible the cutoffs for full MNAS. The optimization of the cutoffs for sMNAS-9 was performed in the designated training set, and an independent test set was used to evaluate the agreement between the cutoffs for sMNAS-9 and the cutoffs for the full MNAS.

Algorithm for morphine treatment of NOWS based on full MNAS scoring and respective sMNAS-9 cutoff scores (purple, bolded).

Algorithm for buprenorphine treatment of NOWS based on full MNAS scoring and respective sMNAS-9 cutoff scores (purple, bolded).