Scott L. Wexelblatt

A multicenter cohort study of treatments and hospital outcomes in neonatal abstinence syndrome.

OBJECTIVES: To compare pharmacologic treatment strategies for neonatal abstinence syndrome (NAS) with respect to total duration of opioid treatment and length of inpatient hospital stay. METHODS: We conducted a cohort analysis of late preterm and term neonates who received inpatient pharmacologic treatment of NAS at one of 20 hospitals throughout 6 Ohio regions from January 2012 through July 2013. Physicians managed NAS using 1 of 6 regionally based strategies. RESULTS: Among 547 pharmacologically treated infants, we documented 417 infants managed using an established NAS weaning protocol and 130 patients managed without protocol-driven weaning. Regardless of the treatment opioid chosen, when we accounted for hospital variation, infants receiving protocol-based weans experienced a significantly shorter duration of opioid treatment (17.7 vs 32.1 days, P < .0001) and shorter hospital stay (22.7 vs 32.1 days, P = .004). Among infants receiving protocol-based weaning, there was no difference in the duration of opioid treatment or length of stay when we compared those treated with morphine with those treated with methadone. Additionally, infants treated with phenobarbital were treated with the drug for a longer duration among those following a morphine-based compared with methadone-based weaning protocol. (P ≤ .002). CONCLUSIONS: Use of a stringent protocol to treat NAS, regardless of the initial opioid chosen, reduces the duration of opioid exposure and length of hospital stay. Because the major driver of cost is length of hospitalization, the implications for a reduction in cost of care for NAS management could be substantial.

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

OBJECTIVES: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Universal maternal drug testing in a high-prevalence region of prescription opiate abuse.

OBJECTIVE To evaluate the efficacy of a universal maternal drug testing protocol for all mothers in a community hospital setting that experienced a 3-fold increase in neonatal abstinence syndrome (NAS) over the previous 5 years. STUDY DESIGN We conducted a retrospective cohort study between May 2012 and November 2013 after the implementation of universal maternal urine drug testing. All subjects with positive urine tests were reviewed to identify a history or suspicion of drug use, insufficient prenatal care, placental abruption, sexually transmitted disease, or admission from a justice center, which would have prompted urine testing using our previous risk-based screening guidelines. We also reviewed the records of infants born to mothers with a positive toxicology for opioids to determine whether admission to the special care nursery was required. RESULTS Out of the 2956 maternal specimens, 159 (5.4%) positive results were recorded. Of these, 96 were positive for opioids, representing 3.2% of all maternity admissions. Nineteen of the 96 (20%) opioid-positive urine tests were recorded in mothers without screening risk factors. Seven of these 19 infants (37%) required admission to the special care nursery for worsening signs of NAS, and 1 of these 7 required pharmacologic treatment. CONCLUSION Universal maternal drug testing improves the identification of infants at risk for the development of NAS. Traditional screening methods underestimate in utero opioid exposure.

Cohort Analysis of a Pharmacokinetic-Modeled Methadone Weaning Optimization for Neonatal Abstinence Syndrome

OBJECTIVE To evaluate neonatal abstinence syndrome (NAS) treatment outcomes achieved using an optimized methadone weaning protocol developed using pharmacokinetic (PK) modeling compared with standard methadone weaning. STUDY DESIGN This pre-post cohort study evaluated 360 infants who completed pharmacologic treatment for NAS with methadone as inpatients at 1 of 6 nurseries in southwest Ohio between January 2012 and March 2015. Infants were initially treated with a standard methadone weaning protocol (n = 267). Beginning in July 2014, infants were treated with a revised methadone weaning protocol developed using PK modeling (n = 93). Linear mixed models were used to calculate adjusted mean primary outcomes, including total duration of methadone treatment, total administered methadone dosage, and length of inpatient hospital stay, which were compared between weaning protocols. The use of adjunctive therapy for NAS treatment was examined as a secondary outcome. RESULTS Infants who received NAS treatment with the revised protocol experienced a shorter duration of methadone treatment (13.1 vs 16.4 days; P < .001) and shorter duration of inpatient treatment (18.3 vs 21.7 days; P < .001) compared with infants receiving standard methadone weaning. No difference was observed in total methadone dosage administered (0.52 vs 0.52 mg/kg; P = .97) or in the use of adjunctive therapy (22.6% vs 25.5%; P = .68) between groups. CONCLUSION Refinement of a standard methadone weaning protocol using PK modeling was associated with reduced duration of opioid weaning and shortened length of stay for pharmacologic treatment of NAS.

Self-reported and laboratory evaluation of late pregnancy nicotine exposure and drugs of abuse.

Objective:The objective of this study was to evaluate the prevalence of late pregnancy nicotine exposures, including secondhand smoke exposures, and to evaluate the associated risk of exposure to drugs of abuse.Study Design:The study was a retrospective single-center cohort analysis of more than 18 months. We compared self-reported smoking status from vital birth records with mass spectrometry laboratory results of maternal urine using a chi-square test. Logistic regression estimated adjusted odds for detection of drugs of abuse based on nicotine detection.Results:Compared with 8.6% self-reporting cigarette use, mass spectrometry detected high-level nicotine exposures for 16.5% of 708 women (P<0.001) and an additional 7.5% with low-level exposures. We identified an increased likelihood of exposure to drugs of abuse, presented as adjusted odds ratios, (95% confidence interval (CI), for both low-level (5.69, CI: 2.09 to 15.46) and high-level (13.93, CI: 7.06 to 27.49) nicotine exposures.Conclusion:Improved measurement tactics are critically needed to capture late pregnancy primary and passive nicotine exposures from all potential sources.

Influence of the WIC Program on Loss to Follow-up for Newborn Hearing Screening

BACKGROUND: Newborn hearing screening has a high participation rate of ∼97% of infants nationally, but a high lost to follow-up of ∼32% limits the effectiveness of the program. This study tested an intervention of targeted outpatient rescreening of infants through collaboration with the Women, Infants, and Children (WIC) program to improve follow-up rates for newborn hearing screen referrals. METHODS: Controlled intervention study of WIC-eligible infants who referred on newborn hearing screens at target hospitals. Hearing rescreens were performed by using screening auditory brainstem response testing by trained research assistants, coordinated with the infant’s WIC appointment. Loss to follow-up rates and age at follow-up were compared with non-WIC infants tracked via the Ohio Department of Health during the same time periods at the same hospitals and at nonintervention hospitals. RESULTS: During a 2-year period, there were 1493 hearing screen referrals at 6 hospitals in the Cincinnati region recorded by the Ohio Department of Health. Of these, 260 WIC-eligible infants were referred to the study. Among WIC-eligible intervention infants, the lost to follow-up rate over 2 years was 9.6%, compared with 28.7% for nonintervention infants in the same hospitals and 18.1% for nonintervention hospitals. The average age of hearing confirmation for the WIC intervention group was 34.8 days, compared with 63.6 days in non-WIC infants. One-third of mothers reported barriers to follow-up. CONCLUSIONS: Collaborating with WIC to provide targeted follow-up for newborn hearing screening improved loss to follow-up rates, decreased the age at hearing confirmation by 1 month, and addressed reported care barriers.

Opioid Neonatal Abstinence Syndrome: An Overview

Opioid neonatal abstinence syndrome (NAS) refers to signs of withdrawal observed in infants experiencing intrauterine opioid exposures. Early identification of at-risk infants allows for the prompt initiation of nonpharmacologic supportive care. When withdrawal symptoms are severe despite these interventions, pharmacologic therapy including opioid weaning is initiated. Consistency with standardized nonpharmacologic approaches as well as stringent weaning protocols are important in minimizing the length of stay and length of pharmacologic treatment for these vulnerable patients.

Comparison of Neonatal Abstinence Syndrome Treatment with Sublingual Buprenorphine versus Conventional Opioids

Objective The objective of this study was to compare duration of opioid treatment and length of stay outcomes for neonatal abstinence syndrome (NAS) using sublingual buprenorphine versus traditional weaning with methadone or morphine. Study Design This retrospective cohort analysis evaluated infants treated for NAS at a single community hospital from July 2013 through June 2017. A standardized weaning protocol was introduced in June 2015, allowing for treatment with sublingual buprenorphine regardless of type of intrauterine opioid exposure. General linear models were used to calculate adjusted mean duration of opioid treatment and length of hospitalization with 95% confidence intervals for infants treated with buprenorphine compared with traditional weaning with either methadone or morphine. Results A total of 360 infants were treated with either buprenorphine (n = 174) or a traditional opioid (n = 186). Infants treated with buprenorphine experienced a 3.0‐day reduction in opioid treatment duration of 7.4 (6.3‐8.5) versus 10.4 (9.3‐11.5) days (p < 0.001) and a 2.8‐day reduction in length of stay of 12.4 (11.3‐13.6) versus 15.2 (14.1‐16.4) days (p < 0.001). Conclusion Our study provides an independent confirmation that among infants experiencing NAS following a wide array of intrauterine opioid exposures, buprenorphine weaning supports a shortened treatment duration compared with conventional weaning agents.

Regional care model enables rapid response to adverse drug events.

The recent shortage of erythromycin ophthalmic ointment has compelled pediatricians to choose alternative therapies for ophthalmia neonatorum prophylaxis. The Cincinnati Children’s Division of Neonatology, which staffs nine regional nurseries, recommended substitution of gentamicin ophthalmic ointment (0.3%) after supplies of erythromycin ointment were exhausted. This decision was based on reports of efficacy, cost analysis and the recommendations of the Centers for Disease Control. Gentamicin ophthalmic ointment was in use for 2 days at two hospitals when several infants showed periorbital skin irritation with erythema and edema of the eye lid (Figure 1). The sclera and cornea appeared unaffected and the dermatitis resolved without any specific intervention. Erythromycin ointment contains only mineral oil and petroleum jelly. Gentamicin ointment contains the preservatives methylparaben and propylparaben, which are esters of parahydroxybenzoic acid. Although there are no published reports of skin reaction to gentamicin ophthalmic ointment, use for ophthalmia neonatorum prophylaxis is presumably novel. Within 48 h of identifying the first adverse reaction, we substituted tobramycin ophthalmic solution, which provides the same bacterial coverage and cost savings. This preparation contains the preservative benzalkonium chloride, a quaternary ammonium cationic surfactant, and has not generated any periorbital skin irritation to date. This change in ophthalmia neonatorum prophylaxis, necessitated by a pharmacological shortage, has the potential to affect a large number of infants. In this case, the dermatitis associated with the use of gentamicin ophthalmic ointment was self-limiting and without apparent sequelae. However, this episode reminds us that apparently benign medications may cause potential harm in the vulnerable neonatal population. Our regionalized clinical model allowed us to quickly identify an adverse drug reaction and facilitated prompt discontinuation of this medication. The collaboration and communication between nine area hospitals also helped us to share our experience and to prevent the exposure of many other infants to this medication, thus preventing unnecessary harm.