The electrophysiology of Neonatal Abstinence Syndrome

Boulton, Richard George (2015) The electrophysiology of Neonatal Abstinence Syndrome. PhD thesis, University of Glasgow.

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Background​: The recommended treatment for pregnant drug misusing women is maintenance methadone. This is of proven benefit in terms of improving maternal well­being, but is commonly associated with neonatal abstinence syndrome (NAS). NAS reflects withdrawal at birth from in utero exposure to licit (including maintenance methadone prescribed to reduce illicit drug use) or illicit opioids (heroin). Symptoms include diarrhoea, extreme irritability, feeding problems, jitteriness and sleep disturbance and in some cases seizures. These signs suggest impaired regulation of homoeostatic processes, postulated to be due to dysfunctional vagal regulation. At present NAS cannot be predicted in individual cases, therefore management must include prolonged hospital stay to monitor for symptoms, and pre­emptive treatment is not feasible. Resting heart rate variability (HRV) is a well ­established measure of the parasympathetic autonomic nervous system, reflective of cardiac vagal tone (CVT). The purpose of this study was to develop a better understanding of the electrophysiology of methadone ­exposed neonates using EEG, ECG and CVT, with the aim of improving short and longer term management of the in utero drug exposed infant.​

Materials and Methods​: Twenty six methadone­ exposed infants and thirty controls matched for gestation, birth weight, and postcode of residence underwent a one hour sleep polysomnogram (PSG) incorporating an electroencephalogram (EEG) and electrocardiogram (ECG), recorded within the first 48 hours of life (preceding onset of any NAS). In utero drug exposure was described by a combination of maternal drug and alcohol history and urinalysis, and infant meconium and urine toxicology. PSGs were scored for sleep state (quiet; intermediate; active), and artefact­ free epochs extracted by an experienced paediatric neurologist. EEG spectral analysis was performed and HRV used to estimate CVT.​

Results: PSGs from 45 infants (80% of those tested), including 20 methadone exposed infants, were deemed suitable for a sleep study analysis. For the 20 methadone­exposed infants, additional drug exposure was as follows: opioids 12/20 (60%): benzodiazepines 11/20 (55%): amphetamines 7/20 (35%): cocaine 4/20 (20%) and cannabis 13/20 (65%). Three of these 20 infants developed significant NAS requiring treatment. The EEG analysis showed cases tended​ to have increased EEG power and lower spectral edge frequencies but no group differences reached significance. The ECG analysis showed higher power amongst cases for many of the HRV parameters, but none reached significance between groups. However, control infants had lower CVT for all sleep states than methadone ­exposed infants: active sleep CVT 1.9 vs 3.5 (p=0.002), indeterminate sleep CVT 2.4 vs 3.7 (p=0.033) and quiet sleep CVT 3.2 vs 4.6​ (p=0.362).​

Conclusion​: Newly born infants of opioid­ dependent mothers prescribed maintenance methadone have increased CVT consistent with impaired homeostatic regulation of the autonomic nervous system. Although CVT did not predict NAS for the small number of infants who required treatment, CVT may have potential as a predictor of NAS in conjunction with other neonatal and maternal parameters.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: R Medicine > R Medicine (General)
R Medicine > RJ Pediatrics
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Bradnam, Dr. Michael and Mactier, Dr. Helen and Hamilton, Dr. Ruth
Date of Award: 2015
Depositing User: Mr Richard Boulton
Unique ID: glathesis:2015-5909
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 30 Jan 2015 08:37
Last Modified: 30 Jan 2015 08:39

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