Poppy McLaughlin1, Helen Mactier2, Cheryl Gillis3, Tamas Hickish4, Anton Parker4, Wei-Jun Liang1, M David Osselton1. 1. Department of Archaeology, Anthropology, and Forensic Science, Bournemouth University, Poole, United Kingdom. 2. Neonatal Unit, Princess Royal Maternity, Glasgow, United Kingdom. Electronic address: helen.mactier@ggc.scot.nhs.uk. 3. Neonatal Unit, Princess Royal Maternity, Glasgow, United Kingdom. 4. Department of Molecular Pathology, Royal Bournemouth Hospital, Bournemouth, United Kingdom.
Abstract
OBJECTIVE: To investigate whether in utero opioid exposure, which has been linked to adverse neurodevelopmental and social outcomes, is associated with altered DNA methylation of opioid-related genes at birth. STUDY DESIGN: Observational cohort study of 21 healthy methadone-maintained opioid-dependent mother-infant dyads consecutively delivered at >36 weeks of gestation, and 2 comparator groups: smoking, "deprived" opioid-naïve mother-infant dyads (n = 17) and nonsmoking, "affluent" opioid-naïve mother-infant dyads (n = 15). DNA methylation of ABCB1, CYP2D6, and OPRM1 genes for mothers and babies was determined from buccal swabs. Plasma methadone concentrations were additionally measured for methadone-maintained opioid-dependent mothers. RESULTS: DNA methylation for ABCB1 and CYP2D6 was similar in opioid-naïve infants compared with their mothers, but was less for OPRM1 (3 ± 1.6% vs 8 ± 1%, P < .0005). Opioid-exposed newborns had similar DNA methylation to their mothers for all genes studied and greater methylation of ABCB1 (18 ± 4.8% vs 3 ± 0.5%), CYP2D6 (92 ± 1.2% vs 89 ± 2.4%), and OPRM1 (8 ± 0.3% vs 3 ± 1.6%) compared with opioid-naïve newborns (P < .0005 for all 3 genes). Infant DNA methylation was not related to birth weight, length of hospital stay, maternal smoking, dose or plasma concentration of methadone at delivery, or postcode of residence. CONCLUSIONS: In utero exposure to opioids is associated with increased methylation of opioid-related genes in the newborn infant. It is not clear whether these findings are due to opioid exposure per se or other associated lifestyle factors.
OBJECTIVE: To investigate whether in utero opioid exposure, which has been linked to adverse neurodevelopmental and social outcomes, is associated with altered DNA methylation of opioid-related genes at birth. STUDY DESIGN: Observational cohort study of 21 healthy methadone-maintained opioid-dependent mother-infant dyads consecutively delivered at >36 weeks of gestation, and 2 comparator groups: smoking, "deprived" opioid-naïve mother-infant dyads (n = 17) and nonsmoking, "affluent" opioid-naïve mother-infant dyads (n = 15). DNA methylation of ABCB1, CYP2D6, and OPRM1 genes for mothers and babies was determined from buccal swabs. Plasma methadone concentrations were additionally measured for methadone-maintained opioid-dependent mothers. RESULTS: DNA methylation for ABCB1 and CYP2D6 was similar in opioid-naïve infants compared with their mothers, but was less for OPRM1 (3 ± 1.6% vs 8 ± 1%, P < .0005). Opioid-exposed newborns had similar DNA methylation to their mothers for all genes studied and greater methylation of ABCB1 (18 ± 4.8% vs 3 ± 0.5%), CYP2D6 (92 ± 1.2% vs 89 ± 2.4%), and OPRM1 (8 ± 0.3% vs 3 ± 1.6%) compared with opioid-naïve newborns (P < .0005 for all 3 genes). Infant DNA methylation was not related to birth weight, length of hospital stay, maternal smoking, dose or plasma concentration of methadone at delivery, or postcode of residence. CONCLUSIONS: In utero exposure to opioids is associated with increased methylation of opioid-related genes in the newborn infant. It is not clear whether these findings are due to opioid exposure per se or other associated lifestyle factors.
Authors: Marie Camerota; Jonathan M Davis; Lynne M Dansereau; Erica L Oliveira; James F Padbury; Barry M Lester Journal: J Pediatr Date: 2021-12-28 Impact factor: 4.406
Authors: Brittany L Smith; Tess A Guzman; Alexander H Brendle; Collin J Laaker; Alexis Ford; Adam R Hiltz; Junfang Zhao; Kenneth D R Setchell; Teresa M Reyes Journal: eNeuro Date: 2022-10-17
Authors: Elisabeth Conradt; Tess Flannery; Judy L Aschner; Robert D Annett; Lisa A Croen; Cristiane S Duarte; Alexander M Friedman; Constance Guille; Monique M Hedderson; Julie A Hofheimer; Miranda R Jones; Christine Ladd-Acosta; Monica McGrath; Angela Moreland; Jenae M Neiderhiser; Ruby H N Nguyen; Jonathan Posner; Judith L Ross; David A Savitz; Steven J Ondersma; Barry M Lester Journal: Pediatrics Date: 2019-09 Impact factor: 9.703
Authors: Madeleine C Allen; Nora K Moog; Claudia Buss; Elizabeth Yen; Hanna C Gustafsson; Elinor L Sullivan; Alice M Graham Journal: Neurotoxicol Teratol Date: 2021-09-30 Impact factor: 4.071
Authors: Ludmila N Bakhireva; Rajesh C Miranda; Amanda H Mahnke; Melissa H Roberts; Lawrence Leeman; Xingya Ma Journal: Sci Rep Date: 2022-04-08 Impact factor: 4.379
Authors: Andrew E Weller; Richard C Crist; Benjamin C Reiner; Glenn A Doyle; Wade H Berrettini Journal: Cold Spring Harb Perspect Med Date: 2021-03-01 Impact factor: 6.915