Neonatal Abstinence Syndrome Outcomes Research Articles

Otolaryngologic conditions in children with neonatal abstinence syndrome: A descriptive study

PurposeLiterature on otolaryngologic sequelae of children with neonatal abstinence syndrome (NAS) has been scarce to date. Prior reports suggest some otologic conditions associated with long-term NAS outcomes, but no comprehensive exploration of these relationships currently exists. This study aims to characterize the breadth of otolaryngologic conditions diagnosed in children with NAS. MethodsThis is a retrospective descriptive study conducted at a tertiary care hospital. We identified 524 children with NAS born between 1/1/2014 and 12/31/2019 who were evaluated by the otolaryngology department. Diagnoses were categorized as otologic, oropharyngeal, sinonasal, and laryngeal. Additional diagnoses of obstructive sleep apnea (OSA) and congenital abnormalities of head and neck were noted separately. Descriptive statistics were calculated, and ANCOVA testing analyzed for differences in mean number of diagnoses. Results680 total otolaryngologic diagnoses were analyzed across 524 patients. Otologic conditions comprised 39.7 % of total diagnoses, oropharyngeal conditions 26.8 %, sinonasal conditions 18.4 %, laryngeal conditions 5.3 %, OSA 1.5 %, and congenital abnormalities 8.3 %. After adjusting for covariates, there were a significantly higher number of otologic diagnoses compared to the other subcategories with mean (standard deviation) of 0.46 (0.83), followed by oropharyngeal 0.35 (0.55), sinonasal 0.24 (0.49), and laryngeal 0.07 (0.29). Thirty total otolaryngology-related procedures were performed in our sample, with myringotomy with tube insertion as the most common. ConclusionUnderstanding the otolaryngologic sequelae of children with NAS is important as these conditions impact children's early development. Our study also highlights various socioeconomic factors that may impact pediatric ENT care and the follow-up of patients born with NAS.

A review of the genomics of neonatal abstinence syndrome.

Neonatal abstinence syndrome (NAS) is a constellation of signs of withdrawal occurring after birth following in utero exposure to licit or illicit opioids. Despite significant research and public health efforts, NAS remains challenging to diagnose, predict, and manage due to highly variable expression. Biomarker discovery in the field of NAS is crucial for stratifying risk, allocating resources, monitoring longitudinal outcomes, and identifying novel therapeutics. There is considerable interest in identifying important genetic and epigenetic markers of NAS severity and outcome that can guide medical decision making, research efforts, and public policy. A number of recent studies have suggested that genetic and epigenetic changes are associated with NAS severity, including evidence of neurodevelopmental instability. This review will provide an overview of the role of genetics and epigenetics in short and longer-term NAS outcomes. We will also describe novel research efforts using polygenic risk scores for NAS risk stratification and salivary gene expression to understand neurobehavioral modulation. Finally, emerging research focused on neuroinflammation from prenatal opioid exposure may elucidate novel mechanisms that could lead to development of future novel therapeutics.

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.

A population-based descriptive study of neonatal abstinence syndrome using hospital discharge and birth certificate data

ABSTRACT Background Neonatal abstinence syndrome (NAS), largely a consequence of prenatal opioid exposure, results in substantial morbidity. Population-based studies of NAS going beyond Medicaid populations and hospital discharge data (HDD) alone are limited. Using statewide Tennessee (TN) HDD and birth certificate (BC) data, we examined trends and evaluated maternal and infant factors associated with NAS. Methods We conducted a population-based descriptive study during 2013–2017 in TN. NAS infants were identified with International Classification of Diseases (ICD)-9-Clinical Modification (CM) and ICD-10-CM codes in HDD and linked to BC data using iterative deterministic matching algorithms. Descriptive analyses were conducted for infant and maternal factors (exposures) by NAS (outcome). Multivariable logistic regression models were used to estimate adjusted ORs and 95% CIs. Results NAS incidence increased from 13.4 to 15.4 per 1,000 live births between 2013 and 2017 (15% increase; ptrend <0.001), but remained stable in 2017. In adjusted models, maternal factors associated with reduced odds of NAS included breastfeeding (OR:0.55, 95%CI:0.52–0.59) and prenatal care (OR:0.36, 95%CI:0.32–0.41). Smoking, preterm birth, and lower birthweight were associated with increased odds of NAS. Conclusions This study highlights the value of utilizing surveillance data to monitor trends and correlates of NAS to inform prevention efforts and targeting of public health resources.

Outcomes of Neonates Exposed to Buprenorphine versus Methadone in Utero: A Systematic Review and Meta-Analysis of Safety in the Fetus and Neonate

We assessed the prevalence of neonatal abstinence syndrome (NAS) and fetal growth outcomes in neonates exposed to methadone compared to buprenorphine in utero. Three authors assessed the titles and abstracts of all potentially eligible studies. The selection criteria were randomized controlled trials and observational cohort studies from January 2000 to January 2020 which indexed and reported original data for occurrence of NAS and fetal growth outcomes in pregnant people who received methadone vs. buprenorphine treatment. The quality and possible bias of each study was assessed using the Cochrane-risk-of-bias tool. Data were pooled to compare the occurrence of NAS and fetal growth restriction among women who received methadone vs. buprenorphine treatment. Of the 106 articles screened, 1 randomized controlled trial and 5 observational cohort studies including 2041 pregnancies fulfilled the inclusion criteria. Buprenorphine is associated with less NAS and improved growth outcomes compared to methadone. (OR = 0.515; p-value &lt; 0.001). Compared to methadone, buprenorphine is associated with less adverse neonatal outcomes in terms of gestational age at birth, birthweight, and head circumference. With the prevalence of NAS continuing to rise, this study adds to the expanding academic research aimed at creating safer treatment protocols.

The Time is Now: Equity and Inclusion in Newborn Quality Improvement.

As maternal opioid exposure increased fourfold over a recent 15 year span,1 the incidence of neonatal abstinence syndrome (NAS) grew from 1.6 cases per 1000 live births in 2004 to 8.8 in 2016.2 Given this growing number of affected infants, optimization and standardization of care for opioid exposed newborns (OENs) has great potential for impact. The Eat, Sleep, Console (ESC) assessment strategy is a relatively new approach focusing on the infant’s ability to feed, sleep, and be consoled in a timely manner.3 ESC is often used in conjunction with nonpharmacologic methods of management for infants with NAS. Evaluating the implementation and outcomes of the ESC strategy is an important and active area of research.4,5 Although infants with NAS are more likely to be White, NAS affects infants from all demographic groups; in 2016, 5.8% of infants diagnosed with NAS were Hispanic.2 Disparities in quality of care and outcomes have been found in Hispanic populations of newborns treated in the NICU6,7; however, approaches to care that directly seek to address such gaps have been more limited. Therefore, evaluation of how outcomes resulting from interventions like ESC differ by race and ethnicity is a critically important area of inquiry. Before the study by Weikel et al8 in this issue of Hospital Pediatrics , little was known about differences in NAS management and outcomes in Hispanic and non-Hispanic populations. This study describes important factors about the care of patients with NAS and highlights equity factors warranting increased consideration in quality improvement (QI) projects more generally. This includes equity-oriented data collection and clear recognition of and approaches to mitigate ill effects of racism, ethnocentrism, and immigration status. Equity provides a lens through which to view opportunities for improved design and implementation of …

505 Incidence of neonatal abstinence syndrome in term pregnancies complicated by medication assisted treatment

To compare the incidence of neonatal abstinence syndrome (NAS) and related neonatal outcomes in women on medication assisted treatment (MAT, methadone, buprenorphine or buprenorphine/naloxone) across varying gestational ages (GA) at time of delivery. This is a retrospective cohort study of spontaneous singleton deliveries 1/1/2010 through 12/30/2019. Patients were categorized based on maintenance medication at the time of delivery. Incidence of NAS and related outcomes were stratified by GA intervals (in weeks): 36 0/7-36 6/7, 37 0/7-37 6/7, 38 0/7-38 6/7, and > 39 0/7 (reference group). The primary outcome was the incidence of NAS. Related neonatal outcomes of interest were peak Finnegan Score (FS), treatment of NAS, neonatal intensive care unit (NICU) admission and NICU length of stay. Chi-squared test was used for categorical data and Kruskal-Wallis test was used for continuous data to test for associations between gestational age and demographic characteristics. Regression analyses were used to identified that MAT at delivery differed between the GA groups and adjustment was performed accordingly. A p-value < 0.05 was considered significant. A total of 476 patients met inclusion criteria: 67.9% buprenorphine, 28.8% methadone and 3.3% buprenorphine/naloxone. 7.1%, 11.6%, 11.8%, 69.5% delivered at 36, 37, 38, and > 39 completed weeks, respectively. There were no differences in maternal demographic characteristics with the exception of MAT use (Table 1). No significant differences were noted for the incidence of NAS by GA at delivery (Table 2). A higher proportion of babies born > 39 weeks had a peak FS >12 compared to other GA groups (p < 0.01). Babies born at > 39 weeks required more pharmacological treatment for NAS compared to those born between 36 0/7- 36 6/7 weeks. All other secondary outcomes were not statistically significant (Table 2). Our study demonstrates that there is no difference in NAS and related neonatal outcomes across varying gestational ages among women on MAT. As such, modification of the timing of delivery is not warranted in this population.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Neonatal Abstinence Syndrome (NAS) in Appalachia: Changing Trends, Clinical Presentation and Management of NAS

Neonatal abstinence syndrome is a significant and rapidly growing public health concern in Appalachia. In 2017, 1090 cases of NAS were reported to the State of Tennessee surveillance program. The incidence of NAS in Tennessee since early 2000s has increased 10-fold, while the national average over the same time period has only increased 3-fold, with the highest rate of increase between 2000-2012. Currently, buprenorphine is a predominant drug of opioid exposure in our region. In this review article, authors describe the incidence of NAS, changing trends, clinical presentation, management protocols and long-term outcomes of infants exposed to buprenorphine. We reviewed the literature, in terms of clinical presentation, changing trends in drug use in pregnancy and choice of drugs available for the management of NAS.

Prevalence of birth defects among infants with neonatal abstinence syndrome in Illinois, 2015-2016.

Opioid use has reached historically high levels across the United States and infants exposed during pregnancy are at risk of developing a drug withdrawal syndrome called neonatal abstinence syndrome (NAS). The prevalence of birth defects among Illinois infants exhibiting NAS has not been estimated. We linked birth certificate data for Illinois-resident infants born in Illinois in 2015 or 2016 to previously collected NAS and Adverse Pregnancy Outcome Reporting System birth defect data. We examined the prevalence of selected specific birth defects and of newborn infants with one or more of the National Birth Defects Prevention Network's (NBDPN) birth defects, comparing infants with and without NAS. We used logistic regression to estimate the odds ratio for having one or more NBDPN birth defects in infants with and without NAS, after adjusting for other risk factors. Of 302,043 Illinois-resident births, 899 (3.0/1,000 live births) had NAS, and 4,250 (140.7/10,000 live births) had one or more NBDPN birth defect. Infants with an NBDPN birth defect were 1.9 (95% CI [1.3, 2.9]) times more likely to have developed NAS at delivery, and specifically, there was a higher prevalence of ventricular septal defect, club foot, and oral cleft, among infants with NAS when compared to those born without. Elevated prevalence rates and odds ratios add to the growing evidence of an association between NAS and birth defects. Other studies have found similar associations between opioid exposure and the birth defects identified in this analysis.

Buprenorphine-Naloxone Versus Buprenorphine for Treatment of Opioid Use Disorder in Pregnancy [07E

INTRODUCTION: Treatments for opioid use disorder (OUD) in pregnancy remain understudied. The safety and efficacy of buprenorphine (BUP), a partial opioid agonist, and methadone, a full opioid agonist, in pregnancy has been established (1). Outside of pregnancy, the combination of BUP and naloxone (BUP-NX), a partial opioid antagonist, is commonly favored due to the decreased risk of diversion (2). Historically, women on BUP-NX are transitioned to BUP in pregnancy due to concerns for fetal exposure to naloxone (3,4). Recently, several small retrospective studies explored the use of BUP-NX in pregnancy and found no adverse maternal or neonatal outcomes (5,6). This is the first study to directly compare BUP-NX and BUP use in pregnancy. METHODS: This single-center, retrospective cohort study assessed 33 pregnancies managed with BUP-NX and 22 managed with BUP. Maternal outcomes included demographic characteristics, gestational age at treatment initiation, number of prenatal visits, gestational age at delivery, concurrent prescribed psychiatric medications, unprescribed or illicit substance use per urine drug screening, and delivery outcomes. Infant outcomes included birth weight, Apgar scores, and neonatal abstinence syndrome outcomes (diagnosis, treatment, and length of hospital stay). RESULTS: There was no significant difference in prenatal care utilization, maternal substance use, delivery outcomes, or neonatal outcomes. Among a subgroup of women transitioned from BUP to BUP-NX mid-pregnancy, no incidences of treatment destabilization were observed post-transition. CONCLUSION: Our study finds that BUP-NX is non-inferior to BUP in the treatment of OUD in pregnancy and supports the growing body of data indicating the safety of BUP-NX use in pregnancy.

Impact of psychiatric medication co-exposure on Neonatal Abstinence Syndrome severity

BackgroundAmong 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. MethodsA 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. ResultsFifty-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). ConclusionFor 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.

Quality improvement initiative to improve inpatient outcomes for Neonatal Abstinence Syndrome.

To improve Neonatal Abstinence Syndrome (NAS) inpatient outcomes through a comprehensive quality improvement (QI) program. Inclusion criteria were opioid-exposed infants ≥36 weeks. QI methodology including stakeholder interviews and plan-do-study-act (PDSA) cycles were utilized. We compared pre- and post-intervention NAS outcomes after a QI initiative that included: A non-pharmacologic care bundle, function-based assessments consisting of symptom prioritization and then the "Eat, Sleep, Console" (ESC) Tool; and a switch to methadone for pharmacologic treatment. Pharmacologic treatment decreased from 87.1 to 40.0%; adjunctive agent use from 33.6 to 2.4%; hospitalization length from a mean 17.4 to 11.3 days, and opioid treatment days from 16.2 to 12.7 (p < 0.001 for all). Total hospital charges decreased from $31,825 to $20,668 per infant. Parental presence increased from 55.6 to 75.8% (p < 0.0001). No adverse events were noted. A comprehensive QI program focused on non-pharmacologic care, function-based assessments, and methadone resulted in significant sustained improvements in NAS outcomes. These findings have important implications for establishing potentially better practices for opioid-exposed newborns.

Epigenetic variation in OPRM1 gene in opioid-exposed mother-infant dyads.

Neonatal abstinence syndrome (NAS) due to in-utero opioid exposure has significant variability of severity. Preliminary studies have suggested that epigenetic variation within the μ-opioid receptor (OPRM1) gene impacts NAS. We aimed to determine if DNA methylation in OPRM1 within opioid-exposed mother-infant dyads is associated with differences in NAS severity in an independent cohort. Full-term opioid-exposed newborns and their mothers (N = 68 pairs) were studied. A DNA sample was obtained and then assessed for level of DNA methylation at 20 CpG sites within the OPRM1 promoter region by next-generation sequencing. Infants were monitored for NAS and treated with replacement opioids according to institutional protocol. The association between DNA methylation level at each CpG site with NAS outcome measures was evaluated using linear and logistic regression models. Higher methylation levels within the infants at the -18 (11.4% vs 4.4%, P = .0001), -14 (46.1% vs 24.0%, P = .002) and +23 (26.3% vs 12.9%, P = .008) CpG sites were associated with higher rates of infant pharmacologic treatment. Higher levels of methylation within the mothers at the -169 (R = 0.43, P = .008), -152 (R = 0.40, P = .002) and +84 (R = 0.44, P = .006) sites were associated point-wise with longer infant length of stay. Maternal associations remained significant point-wise for -169 (β = 0.07, P = .007) and on an experiment-wise level for +84 (β = -0.10, P = .003) using regression models. These results suggest an association of higher levels of OPRM1 methylation at specific CpG sites and increased NAS severity, replicating prior findings. These findings have important implications for personalized treatment regimens for infants at high risk for severe NAS.

Nonopioid Management of Neonatal Abstinence Syndrome.

Current standard therapy for moderate to severe neonatal abstinence syndrome (NAS) includes opioid administration and often results in separation of mother and infant. Impaired maternal-infant bonding and extended neonatal opiate exposure may be associated with adverse developmental outcomes. Increased use of nonopioid adjunctive NAS therapies may decrease postnatal opioid exposure and length of stay (LOS), thereby promoting positive developmental outcomes for NAS-affected infants. To review the efficacy of rooming-in care and acupuncture as nonpharmacologic adjunctive agents to reduce the magnitude of postnatal opioid exposure and LOS. PubMed, Ovid Medline, Embase, and CINAHL databases were searched for primary studies on rooming-in care and acupuncture as adjunctive treatments for NAS; 8 are included in this review. Rooming-in care may decrease postnatal opioid exposure and LOS in NAS-affected infants. Acupuncture is safe in NAS patients; however, its definitive effect on narcotic use and length of hospitalization are inconclusive. Rooming-in care should be offered to NAS patients. Strong evidence does not exist to recommend acupuncture as a routine NAS treatment. Additional randomized clinical trials are necessary to assess the efficacy of acupuncture and to confirm the effect of rooming-in care on NAS outcomes, and delineate optimal elements of a rooming-in care model.

Impact of Parental Presence at Infants’ Bedside on Neonatal Abstinence Syndrome

Despite increased incidence of neonatal abstinence syndrome (NAS) over the past decade, minimal data exist on benefits of parental presence at the bedside on NAS outcomes. To examine the association between rates of parental presence and NAS outcomes. This was a retrospective, single-center cohort study of infants treated pharmacologically for NAS using a rooming-in model of care. Parental presence was documented every 4 hours with nursing cares. We obtained demographic data for mothers and infants and assessed covariates confounding NAS severity and time spent at the bedside. Outcomes included length of stay (LOS) at the hospital, extent of pharmacotherapy, and mean Finnegan withdrawal score. Multiple linear regression modeling assessed the association of parental presence with outcomes. For the 86 mother-infant dyads, the mean parental presence during scoring was on average 54.4% (95% confidence interval [CI], 48.8%-60.7%) of the infant's hospitalization. Maximum (100%) parental presence was associated with a 9 day shorter LOS (r = -0.31; 95% CI, -0.48 to -0.10; P < .01), 8 fewer days of infant opioid therapy (r = -0.34; 95% CI, -0.52 to -0.15; P < .001), and 1 point lower mean Finnegan score (r = -0.35; 95% CI, -0.52 to -0.15; P < .01). After adjusting for breastfeeding, parental presence remained significantly associated with reduced NAS score and opioid treatment days. More parental time spent at the infant's bedside was associated with decreased NAS severity. This has important implications for clinical practice guidelines for NAS.

Association of maternal and infant variants in PNOC and COMT genes with neonatal abstinence syndrome severity.

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. 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. 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. 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).

Revision of Breastfeeding Guidelines in the Setting of Maternal Opioid Use Disorder: One Institution's Experience.

Breastfeeding is recommended for women with opioid use disorder who are treated with methadone or buprenorphine. Infants with neonatal abstinence syndrome (NAS) secondary to in-utero opioid exposure have unique challenges related to breastfeeding but also have significant benefits including improved NAS symptoms with a decreased need for pharmacotherapy. Poor understanding of substance use disorder and treatment, lack of evidence-based recommendations, and vague guidelines from national academies create controversy about breastfeeding eligibility for these women. Defining breastfeeding guidelines is often difficult, particularly in large institutions with multiple providers caring for the mother-infant dyad. Based on the available evidence and review of our institutional data, we revised our breastfeeding guidelines for mothers with opioid use disorder. The aims of our new guidelines are (a) to safely promote breastfeeding in all mothers with opioid use disorder who are in recovery, (b) to improve NAS outcomes through use of breastfeeding as a key nonpharmacologic treatment modality, and (c) to improve staff communication and consistency on the subject of breastfeeding in this patient population.

Implementation of a Neonatal Abstinence Syndrome Weaning Protocol: A Multicenter Cohort Study.

To evaluate the generalizability of stringent protocol-driven weaning in improving total duration of opioid treatment and length of inpatient hospital stay after treatment of neonatal abstinence syndrome (NAS). We conducted a retrospective cohort analysis of 981 infants who completed pharmacologic treatment of NAS with methadone or morphine from January 2012 through August 2014. Before July 2013, 3 of 6 neonatology provider groups (representing Ohio's 6 children's hospitals) directed NAS nursery care by using group-specific treatment protocols containing explicit weaning guidelines. In July 2013, a standardized weaning protocol was adopted by all 6 groups. Statistical analysis was performed to identify effects of adoption of the multicenter weaning protocol on total duration of opioid treatment and length of hospital stay at the protocol-adopting sites and at the sites with preexisting protocol-driven weaning. After adoption of the multicenter protocol, infants treated by the 3 groups previously without stringent weaning guidelines experienced shorter duration of opioid treatment (23.0 vs 34.0 days, P < .001) and length of inpatient hospital stay (23.7 vs 31.6 days, P < .001). Protocol-adopting sites also experienced a lower rate of adjunctive drug therapy (5% vs 21%, P = .004). Outcomes were sustained by the 3 groups who initially had specific weaning guidelines after multicenter adoption (duration of treatment = 17.0 days and length of hospital stay = 23.3 days). Adoption of a stringent weaning protocol resulted in improved NAS outcomes, demonstrating generalizability of the protocol-driven weaning approach. Opportunity remains for additional protocol refinement.

Variations in opioid receptor genes in neonatal abstinence syndrome

BackgroundThere is significant variability in the severity of neonatal abstinence syndrome (NAS) due to in-utero opioid exposure. We wanted to determine if single nucleotide polymorphisms (SNPs) in key candidate genes contribute to this variability. MethodsFull-term opioid-exposed newborns and their mothers (n=86 pairs) were studied. DNA was genotyped for 80 SNPs from 14 genes utilizing a custom designed microarray. The association of each SNP with NAS outcomes was evaluated. ResultsSNPs in two opioid receptor genes in the infants were associated with worse NAS severity: (1) The PNOC rs732636 A allele (OR=3.8, p=0.004) for treatment with 2 medications and a longer hospital stay (LOS) of 5.8 days (p=0.01), and (2) The OPRK1 rs702764 C allele (OR=4.1, p=0.003) for treatment with 2 medications. The OPRM1 rs1799971 G allele (β=−6.9 days, p=0.02) and COMT rs740603 A allele (β=−5.3 days, p=0.01) were associated with shorter LOS. The OPRD1 rs204076 A allele in the mothers was associated with a longer LOS by 6.6 days (p=0.008). Results were significant point-wise but did not meet the experiment-wide significance level. ConclusionsThese findings suggest that SNPs in opioid receptor and the PNOC genes are associated with NAS severity. However, further testing in a large sample is warranted. This has important implications for prenatal prediction and personalized treatment regimens for infants at highest risk for severe NAS.

9: Comparison of Neonatal Abstinence Syndrome Outcomes Before and After Implementation of Revised Management Guidelines

9: Comparison of Neonatal Abstinence Syndrome Outcomes Before and After Implementation of Revised Management Guidelines