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Objective To pilot measurement of hair cortisol concentration (HCC) in pregnant women with opioid use disorder and their infants over time and study the potential utility of hair cortisol as a biomarker of chronic stress in this population. Study Design In this pilot prospective cohort study of mother–infant dyads with and without prenatal opioid exposure, we obtained mother–infant HCCs at delivery and again within 1 to 3 months' postpartum. HCCs were compared between the opioid and control groups and between the two time points. Results There were no significant differences between opioid and control group maternal or infant HCCs at either time point. However, within the opioid-exposed group, there was a significant increase in infant HCCs across the two time points. Conclusion This pilot study describes our experience with the measurement of HCCs in opioid-exposed mother–infant dyads. Key Points Maternal stress impacts fetal and child health. Many stressors in pregnant women with opioid use disorder. Hair cortisol may be a useful stress biomarker. [ABSTRACT FROM AUTHOR]

Naltrexone is a medication used to treat both opioid and alcohol use disorder with limited experience in pregnant individuals, particularly in comparison to more commonly utilized treatments such as buprenorphine-naloxone. The long-term outcomes of infants exposed to naltrexone has not been previously examined. To compare the neurobehavioral outcomes of naltrexone versus buprenorphine-naloxone exposed infants. Multi-centered prospective cohort study. Pregnant people on prescribed buprenorphine-naloxone or naltrexone were enrolled during pregnancy and the dyad followed until 12 months after delivery. Infants were evaluated at 4–6 weeks corrected gestational age (CGA) using the NICU Neonatal Neurobehavioral Scale (NNNS) and at the 12-month CGA visit using the Ages and Stages Questionnaire, Third Edition (ASQ-3). There were 7 dyads in the naltrexone group and 34 in the buprenorphine-naloxone group. On the NNNS, infants exposed to naltrexone had higher median scores for arousal and excitability, and lower median scores for attention and regulation at 4–6 weeks CGA compared to the buprenorphine-naloxone group. None of the infants in the naltrexone group were monitored for NOWS and had shorter length of hospital stay compared with the buprenorphine-naloxone group. Although no statistically significant differences were observed, more infants in the buprenorphine-naloxone group were identified as at risk for development delays in the communication, problem solving, and personal social domains of the ASQ-3 at 12 months CGA. Results should be interpreted with caution given this study's small sample size and lack of a prospective comparison cohort. In this small cohort, there are differences noted in infant neurobehavior by NNNS at 4–6 weeks of age when comparing the buprenorphine-naloxone and naltrexone groups. At 12 months, ASQ-3 scores were similar but with percentage differences in potential development delay risk observed between the two groups. Larger cohort studies are needed to determine the long-term child outcomes after naltrexone exposure in pregnancy. • Neurobehavior of infants exposed to naltrexone vs buprenorphine-naloxone were compared. • Infants exposed to naltrexone demonstrated differences in neurobehavior at 4–6 weeks. • Infants in the naltrexone group had shorter hospitalizations with no NOWS diagnoses. [ABSTRACT FROM AUTHOR]

The use of the opioid antagonist naltrexone (NTX) for pregnant women with opioid use disorder (OUD) remains understudied. The purpose of this pilot study was to examine pregnancy and neonatal outcomes in a cohort of NTX-treated women. This single-center, retrospective cohort study included 6 mother–infant dyads taking NTX compared with 13 taking buprenorphine (BUP) between 2017 and 2019. Maternal demographic characteristics, any unprescribed or illicit opioid use per urine toxicology or provider report during the pregnancy or 6 months' postdelivery, delivery outcomes, gestational age, birth weight, Apgar scores, neonatal intensive care unit admission, and neonatal abstinence syndrome (NAS) outcomes (NAS diagnosis, pharmacologic treatment, and total hospital length of stay) were compared. Maternal and infant demographic characteristics were similar between the 2 groups, with the exception of cigarette smoking in the BUP group being more common (92% vs 33%; P = 0.02). None of the women on NTX versus 23% of the women on BUP had documented opioid misuse (P = 0.52). No infants in the NTX group had a NAS diagnosis versus 92% in the BUP group (P < 0.001). Forty-six percent of the BUP-exposed infants were treated for NAS versus 0% in the NTX group (P < 0.001). NTX-exposed infants had a shorter length of stay (mean [SD], 3.2 [1.6] vs 10.9 [8.2] days; P = 0.008). Maintaining women on NTX during pregnancy was associated with favorable outcomes. These results support the need for larger multicenter studies sufficiently powered to detect possible differences between the medications on long-term maternal and child safety and efficacy outcomes. [ABSTRACT FROM AUTHOR]

Highlights • Psychiatric medications are often taken in pregnant women with opioid use disorder. • Psychiatric polypharmacy is common and associated with more severe NAS. • Benzodiazepines and gabapentin are associated with more severe NAS. Abstract Background Among opioid-exposed infants, psychiatric medication co-exposure is common. Our objective was to compare Neonatal Abstinence Syndrome (NAS) outcomes based on individual psychiatric medication co-exposures. Methods A retrospective study of 744 opioid-exposed mother-infant dyads from a single institution was performed. Mothers on pharmacotherapy with methadone or buprenorphine at delivery were included. Data were collected on maternal demographics, psychiatric medication use, and NAS outcomes, including any medication treatment, adjunctive medication treatment, length of hospital stay (LOS), and opioid treatment days. The extent to which individual psychiatric medication and polypharmacy exposure were associated with NAS outcomes was assessed using multivariable regression. Results Fifty-four percent of the mothers were on ≥1 psychiatric medication, with 32% on ≥2 or psychiatric medications (polypharmacy group). In adjusted models, polypharmacy exposure was associated with longer LOS (β = 4.31 days, 95% CI 2.55–6.06) and opioid treatment days (β = 3.98 days, 95% CI 2.24–5.72) and more treatment with adjunctive medication for NAS (aOR = 2.49, 95% CI 1.57–3.95). Benzodiazepines were associated with longer LOS (β = 4.94, 95% CI 2.86–7.03) and opioid treatment days (β = 4.86, 95% CI 2.61–6.75), and more adjunctive medication treatment (aOR = 2.57, 95% CI 1.49–4.42). Gabapentin was associated with longer LOS (β = 2.79, 95% CI 0.54–5.03), more NAS medication treatment (aOR = 2.96, 95% CI 1.18–7.42) including more adjunctive medications (aOR = 1.92, 95% CI 1.05–3.53). Conclusion For infants of mothers with OUD who are also on concurrent psychiatric medications, polypharmacy was associated with worse NAS severity. When medically indicated, limiting use of multiple psychiatric medications, particularly benzodiazepines and gabapentin, during pregnancy should be considered to improve NAS outcomes. [ABSTRACT FROM AUTHOR]

Background: Among opioid-exposed infants, psychiatric medication co-exposure is common. Our objective was to compare Neonatal Abstinence Syndrome (NAS) outcomes based on individual psychiatric medication co-exposures.Methods: A retrospective study of 744 opioid-exposed mother-infant dyads from a single institution was performed. Mothers on pharmacotherapy with methadone or buprenorphine at delivery were included. Data were collected on maternal demographics, psychiatric medication use, and NAS outcomes, including any medication treatment, adjunctive medication treatment, length of hospital stay (LOS), and opioid treatment days. The extent to which individual psychiatric medication and polypharmacy exposure were associated with NAS outcomes was assessed using multivariable regression.Results: Fifty-four percent of the mothers were on ≥1 psychiatric medication, with 32% on ≥2 or psychiatric medications (polypharmacy group). In adjusted models, polypharmacy exposure was associated with longer LOS (β = 4.31 days, 95% CI 2.55-6.06) and opioid treatment days (β = 3.98 days, 95% CI 2.24-5.72) and more treatment with adjunctive medication for NAS (aOR = 2.49, 95% CI 1.57-3.95). Benzodiazepines were associated with longer LOS (β = 4.94, 95% CI 2.86-7.03) and opioid treatment days (β = 4.86, 95% CI 2.61-6.75), and more adjunctive medication treatment (aOR = 2.57, 95% CI 1.49-4.42). Gabapentin was associated with longer LOS (β = 2.79, 95% CI 0.54-5.03), more NAS medication treatment (aOR = 2.96, 95% CI 1.18-7.42) including more adjunctive medications (aOR = 1.92, 95% CI 1.05-3.53).Conclusion: For infants of mothers with OUD who are also on concurrent psychiatric medications, polypharmacy was associated with worse NAS severity. When medically indicated, limiting use of multiple psychiatric medications, particularly benzodiazepines and gabapentin, during pregnancy should be considered to improve NAS outcomes. [ABSTRACT FROM AUTHOR]

Background and Objectives: There is significant variability in severity of neonatal abstinence syndrome (NAS) due to in utero opioid exposure. Our previous study identified single nucleotide polymorphisms (SNPs) in the prepronociceptin (PNOC) and catechol-O-methyltransferase (COMT) genes that were associated with differences in NAS outcomes. This study looks at the same SNPs in PNOC and COMT in an independent cohort in an attempt to replicate previous findings.Methods: For the replication cohort, full-term opioid-exposed newborns and their mothers (n = 113 pairs) were studied. A DNA sample was obtained and genotyped for five SNPs in the PNOC and COMT genes. The association of each SNP with NAS outcomes (length of hospitalization, need for pharmacologic treatment, and total opioid days) was evaluated, with an experiment-wise significance level set at α < .003 and point-wise level of α < .05. SNP associations in a combined cohort of n = 199 pairs (replication cohort plus 86 pairs previously reported), were also examined.Results: In the replication cohort, mothers with the COMT rs4680 G allele had infants with a reduced risk for treatment with two medications for NAS (adjusted OR = .5, p = .04), meeting point-wise significance. In the combined cohort, infants with the PNOC rs4732636 A allele had a reduced need for medication treatment (adjusted OR 2.0, p = .04); mothers with the PNOC rs351776 A allele had infants who were treated more often with two medications (adjusted OR 2.3, p = .004) with longer hospitalization by 3.3 days (p = .01). Mothers with the COMT rs740603 A allele had infants who were less often treated with any medication (adjusted OR .5, p = .02). Though all SNP associations all met point wise and clinical significance, they did not meet the experiment-wise significance threshold.Conclusions and Scientific Significance: We found differences in NAS outcomes depending on PNOC and COMT SNP genotype. This has important implications for identifying infants at risk for severe NAS who could benefit from tailored treatment regimens. Further testing in a larger sample is warranted. This has important implications for prenatal prediction and personalized treatment regimens for infants with NAS. (Am J Addict 2017;26:42-49). [ABSTRACT FROM AUTHOR]