Hospital Variation in Neonatal Abstinence Syndrome Incidence, Treatment Modalities, Resource Use, and Costs Across Pediatric Hospitals in the United States, 2013 to 2016

Milliren, Carly E.; Gupta, Munish; Graham, Dionne A.; Melvin, Patrice; Jorina, Maria; Ozonoff, Al

doi:10.1542/hpeds.2017-0077

Cited by 75 publications

(54 citation statements)

References 18 publications

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“…For pregnant women with opioid use disorder (OUD), medication assisted therapy (MAT) is associated with improved perinatal outcomes, decreased risk of relapse, and lower rates of maternal criminal involvement [3, 4]. While adverse outcomes are lower among women on MAT, many infants with prenatal opioid exposure (POE) − whether illicit, prescription, or MAT – have neonatal opioid withdrawal syndrome (NOWS), which is now estimated to affect as many as 2% of all births [5]. …”

Section: Introductionmentioning

confidence: 99%

Association between prenatal opioid exposure, neonatal opioid withdrawal syndrome, and neurodevelopmental and behavioral outcomes at 5–8 months of age

Bakhireva

Holbrook

Shrestha

et al. 2019

Early Human Development

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Background: While use of prescription opioids and medication assisted therapy (MAT) for opioid use disorder in pregnancy, as well as the prevalence of neonatal opioid withdrawal syndrome (NOWS) continue to rise, little is known about outcomes for children with NOWS beyond the newborn period. Methods: We examined 1) prenatal MAT exposure vs. unexposed healthy controls [HC]; and 2) treatment for NOWS and NOWS severity on infant neurodevelopmental and behavioral outcomes at 5–8 months of age in 78 maternal-infant pairs from the ENRICH prospective cohort study. Data were obtained from 3 study visits: prenatal, delivery, and neurodevelopmental evaluation at 5–8 months of age. Neurodevelopmental outcomes included the Bayley Scales of Infant Development [BSID-III], caregiver questionnaires (Parenting Stress Index [PSI-SF], Infant Behavior Questionnaire [IBQ-R], Sensory Profile), and the experimental Still-Face Paradigm (SFP). Results: No differences in the BSID-III, PSI-SF, or IBQ-R scores were observed between MAT groups and HC; however, MAT-exposed and HC infants differed with respect to SFP self-regulation (β=−18.9; p=0.01) and Sensory Profile sensation seeking (OR=4.87; 95% CI: 1.55; 15.30) after adjusting for covariates. No significant differences between Treated-for-NOWS vs. not-Treated-for-NOWS were observed. Shorter timing to NOWS treatment initiation was associated with higher Total Stress (β=−9.08; p=0.035), while longer hospitalization was associated with higher Parent-child dysfunction (p=0.018) on PSI-SF. Conclusions: Our results provide additional evidence of little-to-no effect of MAT and pharmacological treatment of NOWS on infant neurodevelopmental and behavioral outcomes at 5–8 months of age. However, prolonged hospitalization might increase family psychosocial stress and requires further examination.

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Section: Introductionmentioning

confidence: 99%

Association between prenatal opioid exposure, neonatal opioid withdrawal syndrome, and neurodevelopmental and behavioral outcomes at 5–8 months of age

Bakhireva

Holbrook

Shrestha

et al. 2019

Early Human Development

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“…Neonatal abstinence syndrome (NAS) after in‐utero opioid exposure increased 5‐fold in the United States between 2000 and 2012 . The incidence continues to rise with current estimates of 20 per 1000 live births in the United States with a diagnosis NAS . NAS is an opioid withdrawal syndrome characterized by alterations in the central nervous, gastrointestinal and respiratory systems that often is associated with prolonged hospitalizations and extensive medication treatment for affected infants .…”

Section: Introductionmentioning

confidence: 99%

Epigenetic variation in OPRM1 gene in opioid‐exposed mother‐infant dyads

Wachman

Hayes

Shrestha

et al. 2018

Genes Brain and Behavior

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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.

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“…Some hospitals require the presence of maternal exposure to opioids, whereas some limit NAS diagnosis to patients who were treated in neonatal care or required extensive treatment only. In their study on NAS, Milliren et al 18 highlighted that using diagnosis codes to identify possible cases of NAS can underestimate the actual prevalence of NAS. Major hospital databases, such as the KID, rely heavily on International Classification of Diseases codes.…”

Section: Discussionmentioning

confidence: 99%

An Update on the Burden of Neonatal Abstinence Syndrome in the United States

Ramphul

Mejias

Joynauth

2020

Hospital Pediatrics

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To provide an estimate on the most recent burden of neonatal abstinence syndrome (NAS) in the United States. METHODS: The 2016 Kids' Inpatient Database, provided by the Healthcare Cost and Utilization Project and Agency for Healthcare Research and Quality and its partners, was used to identify patients with NAS in the United States. The data consisted of pediatric admissions from 4200 US hospitals recorded between January 1, 2016, and December 31, 2016. Data were converted to weighted form to project a national estimate on the possible number of neonates affected by NAS. Differences in sex, race, location, household income, primary payer form, length of stay, and total charges were studied. RESULTS: The sample contained 32 128 patients with NAS (0.8%), among whom 17 164 (53.5%) were boys and 14 935 (46.5%) were girls (P , .001); 23 027 (80.4%) were white (P , .001), and 13 583 (42.3%) were from the southern parts of the United States (P , .001). Medicaid covered 83.8% of patients, and 40.2% had an income within the first quartile of national averages (P , .001). The overall mean and median length of stay were 16.45 and 12.00 days, respectively, and the mean and median total charges were calculated as $79 937.

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Hospital Variation in Neonatal Abstinence Syndrome Incidence, Treatment Modalities, Resource Use, and Costs Across Pediatric Hospitals in the United States, 2013 to 2016

Abstract: Neonates with NAS, particularly those treated pharmacologically, have lengthier, more expensive hospital stays. Significant variation in pharmacologic treatment reflects opportunities for practice standardization and substantial reductions in resource use.

Cited by 75 publications

References 18 publications

Association between prenatal opioid exposure, neonatal opioid withdrawal syndrome, and neurodevelopmental and behavioral outcomes at 5–8 months of age

Association between prenatal opioid exposure, neonatal opioid withdrawal syndrome, and neurodevelopmental and behavioral outcomes at 5–8 months of age

Epigenetic variation in OPRM1 gene in opioid‐exposed mother‐infant dyads

An Update on the Burden of Neonatal Abstinence Syndrome in the United States

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