Treatment Of Neonatal Abstinence Syndrome Research Articles

Comparison of the effect of phenobarbital & levetiracetam in the treatment of neonatal abstinence syndrome (NAS) as adjuvant treatment in neonates admitted to the neonatal intensive care unit: a randomized clinical trial

BackgroundInfants who are born from mothers with substance use disorder might suffer from neonatal abstinence syndrome (NAS) and need treatment with medicines. One of these medicines is phenobarbital, which may cause side effects in long-term consumption. Alternative drugs can be used to reduce these side effects. This study seeks the comparison of the effects of phenobarbital & levetiracetam as adjuvant therapy in neonatal abstinence syndrome.MethodsThis randomized clinical trial was performed in one year from May 2021 until May 2022. The neonates who were born from mothers with substance use disorder and had neonatal abstinence syndrome in Afzalipoor Hospital of Kerman were studied. The treatment started with morphine initially and every four hours the infants were checked. The infants who were diagnosed with uncontrolled symptoms After obtaining informed consent from the parents were randomly divided into two groups and treated with secondary drugs, either phenobarbital or levetiracetam.ResultsBased on the obtained results, it was clear that there was no significant difference between the hospitalization time of the two infant groups under therapy (phenobarbital: 18.59 days versus Levetiracetam 18.24 days) (P-value = 0.512). Also, there was no significant difference between both groups in terms of the frequency of re-hospitalization during the first week after discharge, the occurrence of complications, and third treatment line prescription (P-value = 0.644).ConclusionsBased on the obtained results, like hospitalization duration time (P-value = 0.512) it seems that levetiracetam can be used to substitute phenobarbital in treating neonatal abstinence syndrome.Trial registrationThe current study has been registered in the Iran registry of clinical trials website (fa.irct.ir) on the date 25/2/2022 with registration no. IRCT20211218053444N2.

Gut Microbiota and Symptom Expression and Severity in Neonatal Abstinence Syndrome.

Problem: Neonatal abstinence syndrome (NAS) affecting neonates with fetal exposure to opioids, is defined by expression and severity of symptoms. The pathophysiology behind symptoms variability is lacking. The study aims were to examine (a) differences in gut microbiota of neonates with and without NAS, (b) the relationships between gut microbiota and symptom expression and NAS severity, and (c) the changes in the neonate gut microbiota diversity during the course of NAS treatment. Methods: A cross-sectional observational design was used to examine differences in microbiota and a longitudinal, repeated measures approach was used to determine relationships between gut microbiota and NAS symptoms. Symptom data were collected using the Finnegan Neonatal Abstinence Scoring Tool and the Neonatal Pain Agitation and Sedation Scale. Stool samples were collected for microbiome analyses with 16S rRNA microbiome sequencing. Results: Differences in alpha and beta diversity between neonates with and without NAS were seen. Relative abundance results revealed 18 taxa were different in neonates with NAS compared to neonates without NAS. No differences were found in alpha or beta diversity in neonates with NAS between enrollment and hospital discharge. There was increased abundance of Escherichia-Shigella and Bacteriodes genera related to higher symptom scores. Discussion: Differences in alpha and beta diversity between neonates with and without NAS may be due to differences in birth mode and type of feeding. The findings of specific increased bacteria related to increased symptoms in the neonates with NAS may also be influenced by birth mode and type of feeding.

Neonatal Abstinence Syndrome: A Review of Treatment in the Neonatal Intensive Care Unit.

Neonatal abstinence syndrome (NAS) is a collection of symptoms that neonates may experience following antenatal exposure to substances that induce withdrawal. Optimal management remains unknown, and there is variation in management and outcomes. To describe the management, length of hospitalization, and adverse events in near-term and full-term neonates with NAS for whom treatment (pharmacotherapy and/or supportive care) was initiated in the neonatal intensive care unit (NICU). A chart review was conducted of neonates admitted to the NICU of Surrey Memorial Hospital, Surrey, British Columbia, who received treatment for NAS between September 1, 2016, and September 1, 2021. A total of 48 neonates met the inclusion criteria. Opioids represented the most frequent type of antenatal exposure. Polysubstance exposures occurred in 45 (94%) of the neonates. Morphine was given to 29 (60%) of the neonates, and phenobarbital to 6 (13%); 5 of these neonates received both medications. The average duration of morphine treatment was 14 days, and the average length of hospitalization (all patients) was 16 days. All of the neonates experienced adverse events; in particular, 9 (30%) of the 30 who received pharmacotherapy were too sedated to feed, compared with 0% of the 18 with no pharmacotherapy. The common finding of polysubstance antenatal exposure, involving predominantly opioids, was associated with scheduled morphine pharmacotherapy for the majority of patients, prolonged hospitalization, and frequent adverse events. Pharmacotherapy for NAS was associated with levels of sedation that interfered with feeding in neonates.

Neonatal Abstinence Syndrome in Infants with Prenatal Exposure to Methadone versus Buprenorphine.

Neonatal abstinence syndrome (NAS) has been of increasing concern. Studies suggest that prenatal exposure to buprenorphine may be preferred to methadone in regard to neonatal withdrawal. Our aim was to determine whether the incidence and severity of NAS are different between babies prenatally exposed to methadone or buprenorphine in pregnancy. This retrospective analysis of infants ≥ 35-weeks-old exposed to methadone/buprenorphine alone or in conjunction with other substances in utero. They were divided into four groups: 1-methadone alone (Met), 2-buprenorphine alone (Bup), 3 and 4-those exposed to methadone and buprenorphine, respectively, in conjunction with other drugs (Met+ and Bup+). The frequency of NAS treatment, duration of treatment (LOT) and length of stay (LOS) were compared between groups. Of the 290 mothers, 59% were in the Met group, 18% in the Bup group, 14% in the Met or Bup and another opiate group, and 9% took methadone or buprenorphine plus various other substances. Infants born to Met/Met+ mothers had a four-times higher likelihood of developing NAS (p < 0.001). There was no difference in the LOS (p = 0.08) or LOT (p = 0.11) between groups. The buprenorphine treatment in pregnancy decreased the risk of babies developing NAS. However, once the NAS required pharmacological treatment, the type of maternal prenatal exposure did not affect the LOS or LOT.

Effects on Neonatal Abstinence Syndrome of Parental Caregivers' Ability to Leave the Postpartum Unit During the COVID-19 Pandemic

ObjectiveTo determine if a policy change that limited the ability of parental caregivers to leave the postpartum unit during the COVID-19 pandemic influenced neonatal abstinence syndrome (NAS) scores, admissions to the NICU for NAS treatment, and length of stay (LOS) on the nursing unit. DesignRetrospective chart review. Setting/Local ProblemDuring the pandemic, a change in policy limited parental caregivers from leaving the nursing unit. ParticipantsNeonates being screened for NAS during the period before the policy change from April 2, 2019, through April 1, 2020 (n = 44), and the period after the policy change (n = 23) from April 2, 2020, to April 1, 2021. MeasurementsLevene’s test was used to determine homogeneity of variance before independent t tests on mean NAS scores and LOS across groups. A linear mixed-effects model tested differences in NAS scores, accounting for time and group. Chi-square tests determined differences in the number of neonates transferred to the NICU across groups. ResultsNo differences between group variables were found, with the exception of feeding type and cocaine/cannabinoid use (p < .05). No significant differences were found in mean NAS scores (p = .96), LOS (p = .77) or NAS scores accounting for time and between groups (p = .069). Transfers to the NICU in the pre–policy change group were significantly greater (p = .05). ConclusionAlthough no decrease was observed for mean NAS scores and LOS of the neonates, a decrease in transfers to the NICU for pharmacologic treatment for NAS was observed. Further research is required to determine casual relationships for the decrease in NICU transfers.

Effect of Neonatal Abstinence Syndrome Treatment Status and Maternal Depressive Symptomatology on Maternal Reports of Infant Behaviors.

The objective of this study is to investigate the effects of maternal perinatal depression symptoms and infant treatment status for neonatal abstinence syndrome (NAS) on maternal perceptions of infant regulatory behavior at 6 weeks of age. Mothers and their infants (N = 106; 53 dyads) were recruited from a rural, White cohort in Northeast Maine. Mothers in medication-assisted treatment (methadone) and their infants (n = 35 dyads) were divided based on the infant's NAS pharmacological treatment (n = 20, NAS+ group; n = 15, NAS- group) and compared with a demographically similar, nonexposed comparison group (n = 18 dyads; COMP group). At 6 weeks postpartum, mothers reported their depression symptoms Beck Depression Inventory-2nd Edition) and infant regulatory behaviors [Mother and Baby Scales (MABS)]. Infant neurobehavior was assessed during the same visit using the Neonatal Network Neurobehavioral Scale (NNNS). Mothers in the NAS+ group showed significantly higher depression scores than the COMP group (p < .05) while the NAS- group did not. Across the sample, mothers with higher depression scores reported higher infant "unsettled-irregularity" MABS scores, regardless of group status. Agreement between maternal reports of infant regulatory behaviors and observer-assessed NNNS summary scares was poor in both the NAS+ and COMP groups. Postpartum women in opioid recovery with infants requiring pharmacological intervention for NAS are more at risk for depression which may adversely influence their perceptions of their infants' regulatory profiles. Unique, targeted attachment interventions may be needed for this population.

Long-Term Developmental Outcomes of Infants With Neonatal Abstinence Syndrome [ID: 1375900

INTRODUCTION: There is limited information on long-term developmental outcomes in infants with neonatal abstinence syndrome (NAS). We evaluated the infant outcomes of women with opioid use disorder based on newborn pharmacologic treatment of NAS after birth. METHODS: This retrospective cohort study identified opioid-exposed gestations presenting for delivery from January 2017 to July 2022. Infants were included if follow-up data was available and were divided based on pharmacologic treatment of NAS. Pregnancy information, newborn demographics, and infant care up to 4 years of age were collected. Assessments of infant outcomes included standardized developmental milestones along with any developmental delays. Statistical analysis included chi-square and Student t tests with significance levels of P&lt;.05. RESULTS: There were 387 infants with 170 (44%) requiring pharmacologic treatment of NAS and 217 (56%) not requiring treatment. The gestational age at delivery, mode of delivery, birth weight, and rate of Plan of Safe Care (POSC) on discharge were similar between groups. Newborns receiving pharmacologic treatment were more likely to experience preterm birth (PTB) (22.4% versus 12.9%, P=.02), have a positive toxicology (83.4% versus 64.2%, P=.001), and a longer median length of stay with PTB removed (9.0 versus 7.0 days, P=.001). Developmental outcomes related to social-emotional delay, language-communication delay, cognitive delay, and physical-motor delay were similar between groups at 2–6 months (n=177), 9–18 months (n=138), and 2–4 years (n=94). CONCLUSION: Infants from opioid-exposed gestations that experienced NAS have similar long-term outcomes regardless of pharmacologic treatment for NAS after birth.

An innovative approach to NAS: Eat, Sleep, Console

Maternal substance abuse during pregnancy has dramatically increased in prevalence in the United States. Consequently, neonatal abstinence syndrome (NAS) is now a leading cause of developmental and medical problems in newborns (Thigpen and Melton, 2014). Eat, Sleep, Console (ESC) is an innovative approach to the treatment of NAS, which hospitals are implementing to improve outcomes for women and infants with perinatal opioid exposure (Whalen et al., 2018). This educational innovation project incorporates current, evidence-based practice (EBP) guidelines into the associate degree nursing (ADN) program curriculum at a community college to better prepare nurses to provide safe, therapeutic nursing care to infants and their families.

A Prolonged Treatment Associated With Absent Septum Pellucidum in Neonatal Abstinence Syndrome: A Case Report

Neonatal abstinence syndrome (NAS) involves a widely variable treatment course among affected individuals. Prognostic indicators that would help predict length of hospital stay and individualize treatment would be valuable to newborns, parents, and hospital staff, including advanced practice registered nurses. We describe a newborn with a prolonged NAS treatment course necessitating high doses of opioids and phenobarbital, found to have an isolated absent septum pellucidum (ASP). We hypothesize a mechanism for an association between an ASP and a difficult NAS treatment course. Should this be substantiated by other cases, it could provide a valuable prognosticator and indicate alternate treatment pathways.

Drug use in pregnancy in Ireland’s capital city: A decade of trends and outcomes

ObjectiveThe aim of this study was to present contemporary trends in opiate use disorder (OUD) and substance use in pregnancy in Ireland, with associated obstetric outcomes, over the last ten years. Study designThis retrospective observational cohort study was conducted at an Irish tertiary maternity unit. All women with OUD or substance use in pregnancy delivered under this service between 2010 and 2019 were included. Drug-exposure was self-reported. Data was collected by combining electronic and hand-held patient records. Trends and outcomes were analysed by year of delivery. Approval for the study was granted by the institution’s clinical governance committee. ResultsOf the 82,669 women delivered, 525 had OUD or substance use in pregnancy (1 in every 160 women booking). 11.6% were homeless, 20.0% were in full-time employment and 91.0% smoked tobacco in pregnancy. 66.3% had a history of psychiatric disorders.Over the ten years, there was a significant reduction in women delivered with OUD or substance use in pregnancy (0.8 % to 0.4 %, RR 0.55, 95 % CI 0.36–0.85), significant reduction in the proportion of women on Opioid-Substitute-Treatment (OST, RR 0.66 95 % CI 0.51–0.87) and an increase in mean maternal age (30.7to32.0 years). Rates of cocaine and cannabis consumption increased (20.6 %, RR 3.8, 95 % CI 1.57–9.44: 24.0 %, RR 3.7, 95 % CI 1.58–8.86 respectively).The maternal mortality rate was 380.9:100,000 births. The perinatal mortality rate was 15.6:1000 births. The preterm birth rate was 17.9 %, with a mean birth weight of 2832 g. The rate of NICU admission was 52.0 % and the mean length of stay was 22.4 days. Amongst the smaller OUD population, the rate of NICU admission for Neonatal Abstinence Syndrome (NAS) and treatment for NAS increased over the study timeframe (36.0 %, RR 2.97, 95 % CI 1.86–4.75: 28.5 %, RR 2.92, 95 % CI 1.70–5.0 respectively). ConclusionsThe obstetric population attending an Irish antenatal service with opiate use disorder or substance exposure is reducing in size with older patients, less opioid substitute therapy and increasing cocaine and cannabis use. These women have high rates of maternal and perinatal morbidity and mortality. Specialist antenatal addiction services, coordinated by the drug-liaison midwife, are critical in adapting care to respond to this dynamic and vulnerable patient cohort.

Future Newborns with Opioid-Induced Neonatal Abstinence Syndrome (NAS) Could Be Assessed with the Genetic Addiction Risk Severity (GARS) Test and Potentially Treated Using Precision Amino-Acid Enkephalinase Inhibition Therapy (KB220) as a Frontline Modality Instead of Potent Opioids.

In this nonsystematic review and opinion, including articles primarily selected from PubMed, we examine the pharmacological and nonpharmacological treatments of neonatal abstinence syndrome (NAS) in order to craft a reasonable opinion to help forge a paradigm shift in the treatment and prevention of primarily opioid-induced NAS. Newborns of individuals who use illicit and licit substances during pregnancy are at risk for withdrawal, also known as NAS. In the US, the reported prevalence of NAS has increased from 4.0 per 1000 hospital births in 2010 to 7.3 per 1000 hospital births in 2017, which is an 82% increase. The management of NAS is varied and involves a combination of nonpharmacologic and pharmacologic therapy. The preferred first-line pharmacological treatment for NAS is opioid therapy, specifically morphine, and the goal is the short-term improvement in NAS symptomatology. Nonpharmacological therapies are individualized and typically focus on general care measures, the newborn-parent/caregiver relationship, the environment, and feeding. When used appropriately, nonpharmacologic therapies can help newborns with NAS avoid or reduce the amount of pharmacologic therapy required and the length of hospitalization. In addition, genetic polymorphisms of the catechol-o-methyltransferase (COMT) and mu-opioid receptor (OPRM1) genes appear to affect the length of stay and the need for pharmacotherapy in newborns with prenatal opioid exposure. Therefore, based on this extensive literature and additional research, this team of coauthors suggests that, in the future, in addition to the current nonpharmacological therapies, patients with opioid-induced NAS should undergo genetic assessment (i.e., the genetic addiction risk severity (GARS) test), which can subsequently be used to guide DNA-directed precision amino-acid enkephalinase inhibition (KB220) therapy as a frontline modality instead of potent opioids.

Understanding the effects of opioids vs non-opioids in the treatment of neonatal abstinence syndrome, an in vitro model.

Neonatal abstinence syndrome (NAS) refers to cadre of withdrawal manifestations in infants born to mothers who used illicit and licit substances during pregnancy. The increasing prevalence of NAS has been largely due to the maternal use of opioids during pregnancy. NAS contributes to increased morbidity and long-term disability in surviving infants. Clinically, oral opioid therapies for opioid exposure have been a standard treatment with morphine (MO) being the most commonly used medication. Recently, a non-opioid agent, clonidine (CD) has also been used with potentially favorable short- and long-term outcomes in infants. However, data regarding the cellular and molecular effects of these treatments on the developing brain is still lacking due to a lack of a reliable animal model that targets the neonatal brain. To address this gap in knowledge we determined the effects of MO or CD on the cell death of neonatal cortical explant cultures that were exposed to oxycodone (OXY) in utero. Sprague Dawley rats were randomized and implanted with programmable infusion pumps before mating to receive either the OXY (dose increasing from 1.21-1.90 mg/kg/day to a maximum dose of 2.86-3.49 mg/kg/day) or normal saline (NS) throughout pregnancy and until one week after delivery. Male and female rat pups were sacrificed on postnatal day 4, and the prefrontal cortex (PFC) and hippocampus (HC) were dissected and treated with MO (0.10-1.00 µM) or CD (1.20-120.00 µM) in culture media. After 5 days of treatment the explants were labeled with propidium iodide to detect cell death. Dead cells were analyzed and counted under fluorescence microscopy. In explants from the PFC, cell death was greater in those prenatally exposed to OXY and postnatally treated with MO (OXY/MO) (736.8 ± 76.5) compared to OXY/CD (620.9 ± 75.0; p = 0.005). In the HC explants, mean cell death counts were not significantly different between groups regardless of prenatal exposure or postnatal treatment (p = 0.19). The PFC is vital in controlling higher-order executive functions such as behavioral flexibility, learning and working memory. Therefore, our finding is consistent with executive function problems in children with prenatal opioid exposure.

A Preliminary Assessment of the Effects of Pharmacist-Driven Methadone Stewardship for the Treatment of Neonatal Abstinence Syndrome at a Tertiary Children's Hospital.

Lack of a standardized opioid wean guideline for the treatment of neonatal abstinence syndrome (NAS) has the potential to increase the length of the wean and subsequently the length of stay for neonates in the neonatal intensive care unit (NICU). The purpose of this study was to assess the effect of a pharmacist-driven methadone stewardship program for NAS treatment. The NAS stewardship program consisted of provider, pharmacist, and nursing education, a pharmacy surveillance system rule, and an updated clinical practice guideline. The pre- and post-intervention period were defined as patients admitted to the NICU from July 2019-October 2019 and August 2020-November 2020, respectively. The primary objective was to assess the effect of the stewardship program on the duration of opioid treatment in days. Secondary outcomes included number of dose titrations and length of hospital stay. A total of 21 patients were included in this study. Neonates treated following the adoption of the stewardship program (n = 8) experienced a 34% decreased median duration of treatment (29 days vs 19 days; p = 0.84). Secondary endpoints of median number of titrations and length of stay were decreased by 15% (1.5 titrations; p = 0.52) and 24% (8 days; p = 0.85), respectively, leading to an average cost savings of $60,020 per patient. Implementation of a standardized stewardship guideline for treatment of NAS resulted in a favorable decrease in all considered endpoints. Implications of the study further support the need for more evidence-based standardized guidelines for optimal treatment of patients with NAS.

Quality Improvement Targeting Non-pharmacologic Care and As-needed Morphine Improves Outcomes in Neonatal Abstinence Syndrome.

We developed a protocol for NAS treatment emphasizing early transfer to general pediatric units, maximization of non-pharmacologic care, and use of as-needed morphine whenever pharmacologic treatment is required. Outcome metrics were the day of life at discharge and cumulative morphine exposure. As a process measure, we also monitored the day of life at transfer to general pediatric units. In addition, we utilized statistical process control charts to track changes in performance. Twenty-eight patients met the inclusion criteria for analysis over 24 months following project initiation. Day of life at discharge decreased by 61% (20.0 versus 7.89 days, P < 0.001), and cumulative morphine exposure decreased by 81% (13.66 versus 2.57 mg morphine, P ≤ 0.001). Day of life at transfer to general pediatric units decreased by 49% (11.13 versus 5.7 days, P = 0.002). There were no readmissions or other identified adverse events. We achieved significant improvements in NAS outcomes using improved non-pharmacologic care and as-needed morphine. Moreover, the improvement did not require transitioning to a new scoring system. These results support the efficacy and safety of as-needed morphine for NAS management.

Postnatal oxytocin treatment improves survival and neurodevelopmental outcomes in an animal model of neonatal abstinence syndrome

Prenatal exposure to drugs of abuse results in neonatal abstinence syndrome (NAS). NAS causes significant morbidity and is associated with costly and lengthy hospitalization. Current pharmacotherapy is suboptimal with no FDA approved treatments. We examined the effect of postnatal oxytocin treatment on survival and neurodevelopmental outcomes in rats prenatally exposed to opioids or benzodiazepines. Sprague-Dawley rat dams were injected with escalating doses of morphine (10–50 mg/kg/day) or diazepam (2–15 mg/kg/day) throughout gestation. In an initial experiment, exposed rat pups received subcutaneous injections of 2 mg/kg oxytocin or saline for the first 10 postnatal days and survival rates were assessed. In a second experiment, exposed rat pups received subcutaneous injections of 0.3, 1, or 2 mg/kg oxytocin or saline for the first 10 postnatal days and survival and body weight were assessed for 30 days. In animals surviving through adolescence, neurodevelopmental outcomes and biological parameters (blood glucose, corticosterone, aldosterone) were also measured. Postnatal oxytocin treatment improved survival in animals prenatally exposed to morphine or diazepam. Preliminary evidence showed that postnatal oxytocin treatment improves long-term learning and memory processes in animals prenatally exposed to morphine or diazepam. These findings highlight the potential of oxytocin as a novel treatment for NAS resulting from prenatal exposure to opioids or benzodiazepines.

HHS releases standard definition for opioid withdrawal in infants

Also called neonatal abstinence syndrome (NAS) or neonatal opioid withdrawal syndrome (NOWS), opioid withdrawal in infants has been for decades surrounded by inconsistent clinical definitions and, more importantly, treatments. In many cases, the condition, which is usually transient and results from maternal opioid use, including therapeutic opioid use, resolves on its own, especially with breastfeeding and rooming in (see ‘Best – and least costly – treatment for NAS is mother‐infant bond,’ ADAW June 12, 2017; https://onlinelibrary.wiley.com/doi/10.1002/adaw.30979). In other cases, the condition leads to removing the child from the mother and even prosecution of the mother (‘Prosecutions of drug‐using women now targeting miscarriage cases,’ ADAW Oct. 25, 2021; https://onlinelibrary.wiley.com/doi/10.1002/adaw.33235). The prosecutions happened in various states, including Tennessee (see ‘Tenn. bill would criminalize pregnant women who use drugs,’ April 21, 2014; https://onlinelibrary.wiley.com/doi/10.1002/adaw.20422), so it's significant that one of the authors of the new definition, Stephen Patrick, M.D., is a pediatrician at Vanderbilt University in Tennessee.

Use of Phenobarbital to Treat Neonatal Abstinence Syndrome From Exposure to Single vs. Multiple Substances.

Drug use in pregnancy is a major public health issue. Intrauterine exposure to opioids alone or in addition to other substances may lead to neonatal abstinence syndrome (NAS). Little consensus exists on optimal therapy, especially for those exposed to multiple drugs. We aim to determine whether the use of opioids alone vs. in combination with phenobarbital will affect short-term neonatal outcomes. This retrospective review of infants admitted to the neonatal intensive care unit (NICU) included newborns ≥35 weeks of gestation exposed to opioids, or multiple substances including opioids, in utero. Treatment with opioids alone, and addition of phenobarbital as initial therapy vs. rescue, was evaluated. Out of 182 newborns, 54 (30%) were exposed to methadone alone vs. 128 (70%) to multiple drugs. Length of stay (LOS) in the hospital was not significantly affected (p = 0.684) by single vs. multiple drug exposure in utero. Treatment of NAS with opioid alone resulted in significantly shorter LOS (27 days), as compared to those treated with opioid and phenobarbital (45 days, p < 0.001). LOS was further prolonged in those treated with phenobarbital as a “rescue” medication in addition to an opioid (49 days, p < 0.0001). There was a significant increase in LOS and duration of opioid treatment for all infants treated with phenobarbital, both in those exposed to opioids alone, and to multiple substances in utero.

Effects of Pharmacologic Treatment for Neonatal Abstinence Syndrome on DNA Methylation and Neurobehavior: A Prospective Cohort Study

To determine whether pharmacologic 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. Buccal swabs were collected from 37 neonates before and after morphine treatment for NAS. Genomic DNA was extracted, and DNAm was examined at 4 cytosine-phosphate-guanine (CpG) sites within the OPRM1 gene. Assessment with 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 [LOT] and total dose of morphine), changes in DNAm, and changes in NNNS summary scores. DNAm was significantly decreased from pretreatment 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 pretreatment to post-treatment. Longer LOT and higher morphine dose were associated with greater decreases in DNAm; greater decreases in DNAm were associated with greater decreases in excitability and hypertonia on the NNNS. Pharmacologic 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.

Buprenorphine Dosing Frequency is not Associated with Maternal Stability and Neonatal Outcomes

Pregnancy alters pharmacokinetics for buprenorphine with variation in dosing suggested from the common once a day (QD) scheme outside pregnancy. Our objective was to determine the relationship between dosing frequency and maternal stability, as measured by rates of relapse and prenatal compliance, and neonatal abstinence syndrome (NAS) rates. This study was from a longitudinal cohort of women receiving care through the PATHways program between 2015 and 2021. We compared outcomes for enrollees prescribed twice a day (BID) or greater dosing of buprenorphine at delivery versus QD. Maternal compliance with treatment goals included inappropriate maternal UDS results, reported illicit use at prenatal appointments, and no-call, no-show visits. This score was the percentage meeting goals from all prescribed visits. Women not taking buprenorphine at delivery were excluded as well as those with less than 6 weeks duration of antepartum therapy. Fisher’s exact test was used for our statistical analysis. 284 patients were included, with 226 (79.5%) underwent QD dosing versus 58 dosed BID or TID. Demographics were similar between groups. Mean total dose per day was significantly higher in the BID/TID group (14.61 ± 5.3 vs 11.86 ± 5.01, P=0.003), see Table 1. When comparing dosing frequency subgroups, maternal compliance scores were not significantly different (0.54± 0.31 vs 0.55± 0.31, P=0.83). No difference was evident in the total antepartum visits attended per group. When neonatal outcomes were assessed, no differences between birthweight, gestational age at delivery, rates of NAS, NAS treatment duration, or neonatal length of stay, see Table 2. Dosing frequency of buprenorphine was related to total daily dose but was not associated with maternal stability or neonatal outcomes. The presence of equipoise for this clinical finding provides justification for a randomized trial to evaluate differences based on dosing frequency.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Use of Methadone Maintenance Therapy for Opioid Use Disorder in Pregnancy.

Use of Methadone Maintenance Therapy for Opioid Use Disorder in Pregnancy.