Hira Shrestha

Date of Award


Level of Access Assigned by Author

Open-Access Thesis

Degree Name

Master of Arts (MA)




Marie J Hayes

Second Committee Member

Alan Rosenwasser

Third Committee Member

Cynthia Erdley


Prenatal substance exposure such as alcohol, nicotine, and opiates is known to modulate autonomic regulatory function during sleep, and to decrease arousability and spontaneous movements (SM). SM during sleep may reflect a protective mechanism for immature patterns of arousals. Neurodevelopmental compromise in sleep and arousal systems may underlie sudden infant death syndrome (SIDS) risk in which infants expire during sleep. Previous studies from our laboratory found abnormal patterns of neonatal arousal, sleep fragmentation, and deficits in sleep-related SM in infants with prenatal alcohol exposure. In this study, prenatal exposure to methadone was hypothesized to disrupt the development of sleep and arousal neural circuitry, which have been found for other high-risk samples. Neonatal Abstinence Syndrome (NAS) is a common consequence of prenatal methadone exposure that may appear within 24 - 72 hours postbirth, and is known to disrupt sleep due to hyperarousability. As a secondary hypothesis, the neonatal age (day 1 or 2 of life) was expected to affect infant sleep and arousal outcomes in methadone-exposed neonates particularly on day 2 when NAS symptoms increase. Additionally, single nucleotide polymorphism (SNP) in the catechol-O-methyltransferase (COMT) gene was found to associate with the severity of NAS in our previous study. NAS severity has been associated with sleep disorders. Therefore, the second hypothesis of this thesis study is that the minor allelic variants (AG/GG) of the COMT gene previously identified as protective of NAS severity may also associate with better sleep organization and more robust SM than the carriers of the AA genotype. Rural, disadvantaged Caucasian mothers and infants (N=58 dyads: methadone=37, comparison=21) were recruited from multiple narcotic treatment sites and prenatal clinic at Eastern Maine Medical Center (EMMC). Mothers were interviewed to determine demographics, psychiatric status, and substance abuse history during the 3rd trimester. Biweekly maternal urinalysis screens and neonatal meconium were applied to verify comorbid alcohol, tobacco, and other drug use. Finnegan scores determined symptoms of withdrawal in opioid exposed newborns. Videosomnographic recordings of behavioral states were collected in the newborn nursery of EMMC overnight, and recordings between 2400-0500h were analyzed for frequency and duration of sleep, wake, arousal, and SM. Saliva samples for genetic study was collected using OrageneTM kits. Results from behavioral state analysis (n=50) showed that methadone-exposed neonates were significantly hyper-aroused and crying more on both day 1 and 2 of life (p<.05); and both the frequency and duration of these parameters increased significantly in the methadoneexposed neonates on day 2 of life, as expected. In the genetic study (n=20), neonates with NAS protective AG/GG genotypes showed better behavioral sleep, fewer arousals, and robust SM than infants with NAS risk AA genotype (p<.05). These findings support evidence of sleep fragmentation in the exposed neonates that is exacerbated by the passage of time since birth when withdrawal symptoms compound the intensity of sleep disturbance and infant distress. Consistent with other findings from other SIDS-risk samples, these findings indicate that arousal and SM regulation may be disrupted in methadone-exposed neonates, suggesting that prenatal methadone may increase risk for SIDS.

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