Early pharmacotherapy versus no pharmacotherapy: difference in skin conductance response to physical stimuli in infants with neonatal opioid withdrawal syndrome.

BACKGROUND

Infants with neonatal opioid withdrawal syndrome often exhibit heightened sympathetic arousal that increases with symptom severity, with more severe clinical signs linked to elevated skin conductance responses. It is hypothesized that early pharmacotherapy may be associated with these physiologic stress responses. The purpose of the study is to examine whether early pharmacotherapy (within 24-48 h of birth) is associated with skin conductance responses in infants at risk for neonatal opioid withdrawal syndrome.

METHODS

This exploratory observational feasibility study recruited 35 infants with neonatal opioid withdrawal syndrome at a single large regional medical center. Of those recruited, 14 were excluded (5 due to ineffective stimulus and 9 due to non-severe withdrawal or parental refusal), leaving 21 infants for analysis. Infants were put into non-randomized groups by neonatal abstinence scores into early methadone pharmacotherapy (n = 12) or no pharmacotherapy (n = 9), with the primary outcome being infant stress measured as skin conductance, obtained near discharge, via the Med-Storm device at three time points relative to a standardized stimulus. Mann-Whitney U-tests and Wilcoxon signed-rank tests were used to assess group differences and between-phase differences, with further comparisons between treated and untreated groups performed using independent samples t-tests, Fisher's exact tests, and descriptive statistics.

RESULTS

Among 21 infants (76% female; 39-week 5-day postconceptional age) studied, 12 (57.1%) received early pharmacotherapy. Baseline skin conductance was higher in non-treated infants, though not statistically significant. Following alcohol swab stimulation, post-stimulus electrodermal response per second was 0.11 (IQR, 0.10-0.15) in non-treated infants and 0.11 (IQR, 0.07-0.13) in treated infants (p = 0.59). Average peak skin conductance was 0.11 (IQR, 0.05-0.19) vs. 0.08 (IQR, 0.05-0.19), respectively (p = 0.97). Within-patient skin conductance measures did not change significantly following physical stimulation in either treated or non-treated infants.

CONCLUSIONS

Skin conductance responses did not differ significantly between infants who received early pharmacotherapy and those who did not; however, directional patterns suggest a possible relationship between early treatment and physiological stress responses in high-risk infants. Maternal medication for opioid use disorder differed between groups, potentially influencing withdrawal severity. These findings support the potential utility of objective measures as adjuncts to traditional clinical scoring and warrant further investigation in larger cohorts.