Association of placental OPRM1 methylation levels with NOWS outcomes
CpG site
Unadjusted results
P-value univariate
Adjusted results
P-value multivariate
NOWS pharmacologic treatment: OR (95% CI)
-60
1.00 (0.95–1.06)
0.92
1.01 (0.95–1.07)
0.83
-50
0.98 (0.89–1.07)
0.62
0.97 (0.87–1.08)
0.52
-32
1.01 (0.92–1.11)
0.86
1.02 (0.90–1.16)
0.75
-25
0.97 (0.87–1.08)
0.53
0.96 (0.84–1.09)
0.50
-18
0.99 (0.88–1.11)
0.84
1.04 (0.90–1.19)
0.62
-14
0.99 (0.93–1.05)
0.67
0.99 (0.93–1.06)
0.76
Average
0.99 (0.89–1.09)
0.78
0.99 (0.89–1.11)
0.90
LOS (days) due to NOWS: beta (95% CI)
-60
–0.001 (–0.19, 0.19)
0.99
–0.02 (–0.20, 0.17)
0.85
-50
0.03 (–0.30, 0.37)
0.84
0.02 (–0.29, 0.34)
0.89
-32
0.007 (–0.33, 0.34)
0.99
–0.06 (–0.39, 0.27)
0.72
-25
–0.04 (–0.41, 0.32)
0.81
–0.08 (–0.43, 0.20)
0.66
-18
–0.16 (–0.58, 0.27)
0.47
–0.05 (–0.47, 0.38)
0.83
-14
0.06 (–0.14, 0.26)
0.55
0.07 (–0.13, 0.27)
0.48
Average
0.01 (–0.33, 0.36)
0.94
0.0009 (–0.33, 0.33)
0.99
Morphine treatment days: beta (95% CI)
-60
1.00 (0.94, 1.07)
0.92
1.00 (0.94, 1.07)
0.97
-50
0.96 (0.86, 1.07)
0.47
0.94 (0.84, 1.06)
0.35
-32
1.07 (0.96, 1.18)
0.22
1.05 (0.95, 1.17)
0.34
-25
1.05 (0.93, 1.19)
0.43
1.03 (0.92, 1.17)
0.59
-18
0.99 (0.87, 1.14)
0.98
0.99 (0.86, 1.14)
0.90
-14
1.01 (0.94, 1.08)
0.83
1.00 (0.94, 1.07)
0.98
Average
1.02 (0.97, 1.13)
0.77
1.01 (0.90, 1.12)
0.92
Two medications to treat NOWS: OR (95% CI)
-60
–0.06 (–0.27, 0.14)
0.54
–0.05 (–0.26, 0.16)
0.62
-50
0.06 (–0.29, 0.42)
0.72
0.07 (–0.29, 0.44)
0.69
-32
–0.13 (–0.48, 0.21)
0.44
–0.14 (–0.51, 0.23)
0.45
-25
–0.06 (–0.42, 0.30)
0.73
–0.06 (–0.44, 0.32)
0.74
-18
–0.16 (–0.64, 0.32)
0.51
–0.17 (–0.69, 0.34)
0.50
-14
0.05 (–0.17, 0.28)
0.63
0.07 (–0.16, 0.29)
0.56
Average
–0.05 (–0.44, 0.33)
0.78
–0.04 (–0.44, 0.36)
0.85
NOWS pharmacologic treatment adjusted for smoking and maternal opioid; LOS and morphine treatment days adjusted for illicit drugs, smoking, and maternal opioid; two medications for NOWS adjusted for smoking. CI: confidence interval; OR: odds ratio
We would like to acknowledge EpigenDx (Ashland, MA; epigendx.com) who performed the DNA methylation studies; the research assistants who assisted with patient enrollment, sample collection, and data collection; and the BMC RESPECT NOWS Research Group.
Author contributions
EMW and AW contributed to the conception and design of the study; HS and JAB organized the database; EMW wrote the first draft of the manuscript; BCI wrote sections of the manuscript; JAB and AH performed the data analysis; HS and BCI performed the subject enrollment, sample and data collection; AW performed the DNA isolation; JAB, CB, and HZ contributed to the analysis and interpretation of the data. All authors contributed to the manuscript revision, read and approved the submitted version.
Conflicts of interest
The authors declare that they have no conflicts of interest.
Ethical approval
The study was approved by the Boston University Medical Campus Institutional Review Board.
Consent to participate
Written consent was obtained from those subjects in the opioid cohort as part of a more extensive study protocol. Informed consent was waived for those subjects in the control cohort due to the collection of discarded placental tissue only for these subjects.
Consent to publication
Not applicable.
Availability of data and materials
All relevant data is contained within the manuscript. The dataset used for this manuscript will not be made publicly available due to the confidentiality issues and the sensitive nature of the data related to maternal substance use disorder.
Funding
This project was supported by the Boston University Genome Science Institute, Boston University Clinical and Translational Science Institute (1UL1TR001430), and a Young Clinical Scientist grant from FAMRI (Flight Attendant Medical Research Institute).
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