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. 2024 Feb 5;11(2):203.
doi: 10.3390/children11020203.

Neonatal Abstinence Signs during Treatment: Trajectory, Resurgence and Heterogeneity

Jennifer S Miller  1   2 , Henrietta S Bada  2 , Philip M Westgate  3 , Thitinart Sithisarn  2 , Markos Leggas  4
Affiliations

Neonatal Abstinence Signs during Treatment: Trajectory, Resurgence and Heterogeneity

Jennifer S Miller et al. Children (Basel). .

Abstract

Neonatal abstinence syndrome (NAS) presents with a varying severity of withdrawal signs and length of treatment (LOT). We examined the course and relevance of each of the NAS withdrawal signs during treatment in a sample of 182 infants with any prenatal opioid exposure, gestational age ≥ 35 weeks, without other medical conditions, and meeting the criteria for pharmacological treatment. Infants were monitored using the Finnegan Neonatal Abstinence Scoring Tool. Daily mean Finnegan scores were estimated using linear mixed models with random subject effects to account for repeated withdrawal scores from the same subject. Daily item prevalence was estimated using generalized estimating equations with a within-subject exchangeable correlation structure. The median LOT was 12.86 days. The prevalence of withdrawal signs decreased from day one to day three of treatment. However, certain central nervous system (CNS) and gastrointestinal (GI) signs showed sporadic increases in prevalence notable around two weeks of treatment, accounting for increases in Finnegan scores that guided pharmacotherapy. We question whether the resurgence of signs with a prolonged LOT is mainly a consequence of opioid tolerance or withdrawal. Monitoring CNS and GI signs throughout treatment is crucial. Future studies directed to better understand this clinical phenomenon may lead to the refining of NAS pharmacotherapy and perhaps the discovery of treatment alternatives.

Keywords: CNS/GI withdrawal signs trajectory; Finnegan neonatal abstinence scoring tool (FNAST); gut–brain axis; length of treatment (LOT); neonatal abstinence syndrome (NAS); neonatal opioid withdrawal syndrome (NOWS); withdrawal sign resurgence.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
The y-axis represents the proportion of infants plotted against the duration of treatment (x-axis) in days. The vertical line drawn to the left of day 20 indicates the median duration of treatment for all the infants in the study sample.
Figure 2
Figure 2
In panel (A), the decreasing number of infants in the sample as the LOT increased are shown, with separate plots for the group with a LOT ≤ 13 days or >13 days. Panel (B) shows the number of Finnegan Scores of treated infants analyzed per day, with plots separated by LOT ≤ 13 days or >13 days.
Figure 3
Figure 3
(A,B) The means (95% CI) of the Finnegan scores (FNAS Score) are plotted over time (duration or day of treatment) for all infants in the sample in panel A, while in panel B, the means (95% CI) of the Finnegan scores are plotted separately for those with a LOT ≤ 13 and a LOT > 13 days.
Figure 4
Figure 4
(A,B) Daily mean prevalence (95% CI) of excessive or continuous high-pitched crying and/or sleep < 1 h in all infants (A) and when infants were grouped as to length of treatment (B). Note the sporadic increases in prevalence in infants with a LOT > 13 days.
Figure 5
Figure 5
(A,B) Daily prevalence (95% CI) of loose or watery stools and/or regurgitation or projectile vomiting in all infants over the course of treatment (A) and in infants separated by shorter versus longer length of treatment group (B).
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