scholarly journals Variations in Infant CYP2B6 Genotype Associated with the Need for Pharmacological Treatment for Neonatal Abstinence Syndrome in Infants of Methadone-Maintained Opioid-Dependent Mothers

2017 ◽  
Vol 34 (09) ◽  
pp. 918-921 ◽  
Author(s):  
Poppy McLaughlin ◽  
Cheryl Gillis ◽  
Michael Osselton ◽  
Helen Mactier
Keyword(s):  
Pharmacological Treatment ◽  
Maternal Blood ◽  
Maternal Plasma ◽  
Genomic Variation ◽  
Neonatal Abstinence Syndrome ◽  
Abstinence Syndrome ◽  
Buccal Swabs ◽  
Cyp2b6 Gene ◽  
Observational Cohort

Background Neonatal abstinence syndrome (NAS) in infants of methadone-maintained opioid-dependent (MMOD) mothers cannot be predicted in individual cases. We investigated whether variation in infant genotype is associated with severity of NAS. Methods This is a pilot observational cohort study of 21 MMOD mothers and their newborns. Infant buccal swabs were obtained soon after delivery, together with a maternal blood sample for the determination of maternal plasma methadone concentration. Genomic variation in five opioid-related genes (ABCB1, COMT, CYP2B6, CYP2D6, and OPRM1) was ascertained from infant buccal swabs and related to need for pharmacological treatment of NAS. Results Out of 21 infants, 11 (52%) required treatment for NAS. Mothers of treated infants tended to have been prescribed higher doses of methadone, but plasma methadone concentrations did not differ between mothers of treated or untreated babies. Treated and untreated babies did not differ in terms of method of feeding. Treated infants were more likely to carry the normal (homozygous) allele at 516 and 785 regions of CYP2B6 gene (p = 0.015 and 0.023, respectively). There were no differences in any other genes between infants who did or did not require treatment for NAS. Conclusion Genomic variation in CYP2B6 may explain, at least in part, severity of NAS.

Patterns of conceptus development and of progesterone concentrations in maternal blood preceding spontaneous early pregnancy failure in mares

2018 ◽  
Vol 30 (8) ◽  
pp. 1066 ◽  
Author(s):  
Keith J. Betteridge ◽  
James I. Raeside ◽  
Rudolf O. Waelchli ◽  
Heather L. Christie ◽  
M. Anthony Hayes
Keyword(s):  
Early Pregnancy ◽  
Experimental Studies ◽  
Maternal Blood ◽  
Maternal Plasma ◽  
Plasma Progesterone ◽  
Pregnancy Failure ◽  
Early Pregnancy Failure ◽  
Conceptus Development ◽  
Simultaneous Loss

Sixteen cases of spontaneous pregnancy loss (11 of singletons and five of pairs of twins) are described. The losses occurred between gestation Days 13 and 25 in 12 mares being monitored almost daily by transrectal ultrasonography (for measurement of conceptus growth) and blood sampling (for determination of maternal plasma progesterone concentrations as evidence of luteolysis) in experimental studies of early pregnancy. In 10 of the 16 cases the uterus was flushed and eight conceptuses were recovered for morphological assessment. Five of the 11 losses of singletons occurred before Day 16 and, with one exception, were preceded or accompanied by luteolysis. The remaining six singleton pregnancies failed after Day 16, with two cases evidencing luteolysis beforehand. Thus, overall, 6/11 singleton losses were associated with luteolysis while 5/11 were not. The five cases of simultaneous loss or degeneration of twin conceptuses all occurred on Day 19 or 20, preceded by luteolysis in only one case. These observations suggest that while the causes of spontaneous early pregnancy failure are multifactorial, luteolysis might contribute to the problem more often than has been previously contended.

scholarly journals Neonatal abstinence syndrome: Neurobehavior at 6 weeks of age in infants with or without pharmacological treatment for withdrawal

2017 ◽  
Vol 59 (5) ◽  
pp. 574-582 ◽  
Author(s):  
Nicole A. Heller ◽  
Beth A. Logan ◽  
Deborah G. Morrison ◽  
Jonathan A. Paul ◽  
Mark S. Brown ◽  
...  
Keyword(s):  
Pharmacological Treatment ◽  
Neonatal Abstinence Syndrome ◽  
Abstinence Syndrome

scholarly journals Pharmacological Treatment for Neonatal Abstinence Syndrome is Associated with Altered DNA Methylation and Neurobehavior

2021 ◽  
Author(s):  
Marie Camerota ◽  
Jonathan M Davis ◽  
Lynne M. Dansereau ◽  
Erica L Oliveira ◽  
James F Padbury ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Pharmacological Treatment ◽  
Receptor Gene ◽  
Post Treatment ◽  
Neonatal Abstinence Syndrome ◽  
Abstinence Syndrome ◽  
Oprm1 Gene ◽  
Cpg Sites ◽  
Length Of Treatment ◽  
Before And After

Objective: To determine whether pharmacological treatment for neonatal abstinence syndrome (NAS) is associated with changes in DNA methylation (DNAm) of the mu-opioid receptor gene (OPRM1) and improvements in neonatal neurobehavior.Study Design: Buccal swabs were collected from 37 neonates before and after morphine treatment for NAS. Genomic DNA was extracted and DNAm was examined at four CpG sites within the OPRM1 gene. The NICU Network Neurobehavioral Scales (NNNS) was also performed before and after NAS treatment. Changes in DNAm (DNAmpost-tx – DNAmpre-tx) and NNNS summary scores (NNNSpost-tx – NNNSpre-tx) were then calculated. Path analysis was used to examine associations among pharmacologic treatment (length of treatment and total dose of morphine), changes in DNAm, and changes in NNNS summary scores. Results: DNAm significantly decreased from pre- to post-treatment at 1 of 4 CpG sites within the OPRM1 gene. Neonates also demonstrated decreased excitability, hypertonia, lethargy, signs of stress and abstinence, and increased quality of movement and regulation from pre- to post-treatment. Increased length of treatment and higher morphine doses were associated with greater decreases in DNAm; greater decreases in DNAm were associated with greater decreases in excitability and hypertonia on the NNNS.Conclusions: Pharmacological treatment of NAS is associated with decreased DNAm of the OPRM1 gene and improved neonatal neurobehavior. Epigenetic changes may play a role in these changes in neonatal neurobehavior.

Oral Morphine Weaning for Neonatal Abstinence Syndrome at Home Compared with In-Hospital: An Observational Cohort Study

2014 ◽  
Vol 17 (2) ◽  
pp. 151-157 ◽  
Author(s):  
Lauren E. Kelly ◽  
David Knoppert ◽  
Henry Roukema ◽  
Michael J. Rieder ◽  
Gideon Koren
Keyword(s):  
Cohort Study ◽  
Oral Morphine ◽  
Observational Cohort Study ◽  
Neonatal Abstinence Syndrome ◽  
Abstinence Syndrome ◽  
Observational Cohort ◽  
At Home

scholarly journals Rooming-in for Infants at Risk for Neonatal Abstinence Syndrome: Outcomes 5 Years following Its Introduction as the Standard of Care at One Hospital

2020 ◽  
Author(s):  
Adam Isaiah Newman ◽  
Dane Mauer-Vakil ◽  
Helen Coo ◽  
Lynn Newton ◽  
Emily Wilkerson ◽  
...  
Keyword(s):  
Pilot Study ◽  
Hospital Stay ◽  
Pharmacological Treatment ◽  
Standard Care ◽  
Neonatal Intensive Care ◽  
Length Of Hospital Stay ◽  
Standard Of Care ◽  
Neonatal Abstinence Syndrome ◽  
Abstinence Syndrome ◽  
Lengths Of Stay

Objective The practice of rooming-in for opioid-dependent infants was introduced as the standard of care at our hospital following a pilot study which demonstrated that such infants had shorter lengths of stay and were less likely to require pharmacological treatment. We sought to determine whether these benefits have continued, and whether outcomes support continuing to use rooming-in as standard care. Study Design Opioid-dependent infants delivered at 36 weeks gestation or later between January 1, 2015, and December 31, 2019, were eligible for rooming-in. Charts were reviewed and data were extracted regarding maternal and infant conditions, whether neonatal pharmacological treatment was required, and total length of hospital stay. Outcomes were compared with two historical groups reported in a previous pilot study: 24 healthy near-term opioid-dependent newborns who were admitted directly to the neonatal intensive care unit (NICU) prior to the introduction of rooming-in (May 1, 2012–May 31, 2013), and 20 similar opioid-dependent infants who were the first to room-in at our hospital (September 1, 2013–September 30, 2014). Results Only 3.5% of 57 infants who roomed-in during the 5-year study period required pharmacological treatment, compared with 15% who roomed-in during the first year of the program's introduction and 83.3% who had been admitted directly to the NICU. The median length of stay remained 5 days for infants rooming-in, compared with 24 days for opioid-dependent infants in the cohort admitted to the NICU. Conclusion Early observations of the benefits of rooming-in on neonatal outcomes were sustained. Infants allowed to room-in were significantly less likely to require initiation of pharmacotherapy and a prolonged hospital stay than similar infants prior to the implementation of rooming-in as standard care. A large proportion of the infants who might have benefited from rooming-in required admission to the NICU for reasons other than neonatal abstinence syndrome (NAS). Key Points

scholarly journals ASSESSMENT OF CORRELATION BETWEEN MIRNAS-21-3P AND -210-3P EXPRESSION IN MATERNAL AND UMBILICAL CORD PLASMA AND FETAL WEIGHT AT BIRTH

2021 ◽  
Vol 74 (2) ◽  
pp. 236-240
Author(s):  
Oksana D. Shchurevska ◽  
Svitlana I. Zhuk
Keyword(s):  
Cord Blood ◽  
Pregnant Women ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Maternal Blood ◽  
Maternal Plasma ◽  
High Positive Correlation ◽  
Positive Correlation ◽  
Fetal Plasma

The aim: To determine the degree of correlation of mass of the fetus and the level of mir-21, mir210 in maternal blood and umbilical cord blood of the fetus in uncomplicated gestation. Materials and methods: 60 pregnant women with a single baby pregnancy in the third trimester (37-40 weeks) were examined. They all were given a general clinical, obstetric and the level of miRNA21-3р and miRNA210-3р were determined in the whole blood of pregnant women (before labor) and in fetal blood obtained from the umbilical artery at birth. The level of miRNAs was determined by the TaqMan method. Results: After examining maternal and fetal plasma samples, we were able to determine 49 samples of hsa-miR210-3p and hsa-miR21-3p from maternal plasma, 44 samples of hsa-miR210-3p and 37 samples of hsa-miR21-3p from the cord blood, which is a satisfactory result of more than 50%. Subsequently, between the results obtained and the birth weight of the fetus Pearson’s correlation coefficient was studied. According to the results obtained, we found no correlation between fetal mass and hsa-miR210-3p level in maternal plasma (r-0,068674), low positive correlation of fetal mass with hsa-miR21-3p level in maternal plasma (r-0,212181 ), an average positive correlation with the level of hsa-miR21-3p in umbilical cord blood (r- 0.363374) and a high positive correlation with hsa-miR210-3p in umbilical cord blood (r-0.528616). Conclusions: Determination of the level of hypoxic miRNAs, in particular hsa-miR210-3p in the umbilical cord blood of the newborn may be a marker of the functional status of the placenta, which programs the normal development of the fetus.

scholarly journals 2421 Development and validation of a translational rat model of neonatal abstinence syndrome

2018 ◽  
Vol 2 (S1) ◽  
pp. 9-9
Author(s):  
Lisa Brents ◽  
Bryce A. Griffin ◽  
Caitlin Caperton ◽  
Lauren Russell ◽  
Christian Cabanlong ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Rat Model ◽  
Maternal Blood ◽  
Positive Control ◽  
Neonatal Abstinence Syndrome ◽  
Abstinence Syndrome ◽  
Blood Concentrations ◽  
Pregnant Rat ◽  
Withdrawal Signs ◽  
Buprenorphine Treatment

OBJECTIVES/SPECIFIC AIMS: Rodent models can be used to study neonatal abstinence syndrome (NAS), but the applicability of findings from the models to NAS in humans is not well understood. The objective of this study was to develop a rat model of norbuprenorphine-induced NAS and validate its translational value by comparing blood concentrations in the norbuprenorphine-treated pregnant rat to those previously reported in pregnant women undergoing buprenorphine treatment. METHODS/STUDY POPULATION: Pregnant Long-Evans rats were implanted with 14-day osmotic minipumps containing vehicle, morphine (positive control), or norbuprenorphine (0.3–3 mg/kg/d) on gestation day 9. Within 12 hours of delivery, pups were tested for spontaneous or precipitated opioid withdrawal by injecting them with saline (10 mL/kg, i.p.) or naltrexone (1 or 10 mg/kg, i.p), respectively, and observing them for well-validated neonatal withdrawal signs. Blood was sampled via indwelling jugular catheters from a subset of norbuprenorphine-treated dams on gestation day 8, 10, 13, 17, and 20. Norbuprenorphine concentrations in whole blood samples were quantified using LC/MS/MS. RESULTS/ANTICIPATED RESULTS: Blood concentrations of norbuprenorphine in rats exposed to 1–3 mg/kg/d of norbuprenorphine were similar to levels previously reported in pregnant women undergoing buprenorphine treatment. Pups born to dams treated with these doses exhibited robust withdrawal signs. Blood concentrations of norbuprenorphine decreased across gestation, which is similar to previous reports in humans. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that dosing dams with 1–3 mg/kg/day norbuprenorphine produces maternal blood concentrations and withdrawal severity similar to those previously reported in humans. This provides evidence that, at these doses, this model is useful for testing hypotheses about norbuprenorphine that are applicable to NAS in humans.

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