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J Matern Fetal Neonatal Med. 2019 Apr 9:1-8. doi: 10.1080/14767058.2019.1588876. [Epub ahead of print]

Prenatal opioid exposure heightens sympathetic arousal and facial expressions of pain/distress in term neonates at 24-48 hours post birth.

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a Department of Pediatrics, Division of Neonatal-Perinatal Medicine , Penn State Health Children's Hospital , Hershey , PA , USA.
b Department of Pediatrics , Penn State College of Medicine , Hershey , PA , USA.
c Department of Neural and Behavioral Sciences , Penn State College of Medicine , Hershey , PA , USA.



The rising issue of opioid use during pregnancy poses an increased risk of fetal exposure to opioids in-utero and the development of neonatal abstinence syndrome (NAS). The cessation of exposure to opioids upon birth causes elevated levels of norepinephrine in the circulation enhancing sympathetic arousal. Skin conductance (SC) detects sympathetic-mediated sweating while the Neonatal Facial Coding System (NFCS) depicts facial expressions of stress and pain. We hypothesize that there will be a direct correlation between SC and NFCS scores, such that neonates with prenatal opioid exposure will have higher SC and facial responses to pain/stress as compared with healthy neonates without prenatal opioid exposure.


This study evaluates the utility of SC and the NFCS in the objective assessment of early postnatal pain response in opioid-exposed and non-opioid exposed neonates.


This prospective, single-center, pilot study enrolled opioid-exposed term neonates (>37 weeks) and healthy controls. Subjects were observed within 24-48 hours post-birth (and prior to opioid withdrawal) for pain at baseline, during, and post-heel lance/squeeze (HLS) with simultaneously measured SC and videotaped facial expressions. SC data included electro-dermal responses over time (EDR/second) and the average amplitude of responses (mean of peaks [MP]). Video data were scored using the NFCS by two trained coders with inter-rater agreement >85%.


SC and NFCS scores were significantly associated with both groups. The opioid-exposed neonates had significantly higher skin conductance indices, EDR/sec for the HLS phase, and MP for HLS and post phases as compared with controls (p < .05). Opioid-exposed neonates demonstrated higher NFCS at baseline (p = .003).


Prenatal opioid exposure was associated with heightened sympathetic arousal during both pain and recovery phases and higher facial expressions of pain/distress at baseline only. A multimodal system of assessment may be useful in understanding the complexity and severity of opioid withdrawal associated with NAS.


Neonatal Facial Coding System; Neonatal abstinence syndrome; neonatal opioid withdrawal; neonatal pain; skin conductance

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