Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid Withdrawal.

BACKGROUND: Although clinicians have traditionally used the Finnegan Neonatal Abstinence Scoring Tool to assess the severity of neonatal opioid withdrawal, a newer function-based approach - the Eat, Sleep, Console care approach - is increasing in use. Whether the new approach can safely reduce the time until infants are medically ready for discharge when it is applied broadly across diverse sites is unknown. METHODS: In this cluster-randomized, controlled trial at 26 U.S. hospitals, we enrolled infants with neonatal opioid withdrawal syndrome who had been born at 36 weeks' gestation or more. At a randomly assigned time, hospitals transitioned from usual care that used the Finnegan tool to the Eat, Sleep, Console approach. During a 3-month transition period, staff members at each hospital were trained to use the new approach. The primary outcome was the time from birth until medical readiness for discharge as defined by the trial. Composite safety outcomes that were assessed during the first 3 months of postnatal age included in-hospital safety, unscheduled health care visits, and nonaccidental trauma or death. RESULTS: A total of 1305 infants were enrolled. In an intention-to-treat analysis that included 837 infants who met the trial definition for medical readiness for discharge, the number of days from birth until readiness for hospital discharge was 8.2 in the Eat, Sleep, Console group and 14.9 in the usual-care group (adjusted mean difference, 6.7 days; 95% confidence interval [CI], 4.7 to 8.8), for a rate ratio of 0.55 (95% CI, 0.46 to 0.65; P<0.001). The incidence of adverse outcomes was similar in the two groups. CONCLUSIONS: As compared with usual care, use of the Eat, Sleep, Console care approach significantly decreased the number of days until infants with neonatal opioid withdrawal syndrome were medically ready for discharge, without increasing specified adverse outcomes. (Funded by the Helping End Addiction Long-term (HEAL) Initiative of the National Institutes of Health; ESC-NOW ClinicalTrials.gov number, NCT04057820.).

Subclinical and Overt Newborn Opioid Exposure: Prevalence and First-Year Healthcare Utilization.

OBJECTIVES: To categorize newborn infants in Hamilton County, Ohio by late pregnancy fetal opioid exposure status and to assess their first-year healthcare utilization. STUDY DESIGN: We used a population-based cohort of 41 136 live births from 2014-2017 and analyzed healthcare encounters in the first year of life from electronic health records. We prospectively assessed for the presence of opioids in maternal urine collected at delivery and for a diagnosis of newborn neonatal abstinence syndrome (NAS). At birth, infants were classified as unexposed to opioids, exposed to opioids and diagnosed with NAS, or subclinically exposed to opioids (exposure that did not result in NAS). RESULTS: The prevalence of newborn opioid exposure was 37 per 1000 births. The duration of the hospital birth encounter was significantly longer for infants with subclinical exposure compared with unexposed infants (10% increase; 95% CI, 7%-13%). However, duration for infants with subclinical exposure was shorter compared to those with NAS. Neither subclinical exposure nor NAS was associated with total emergency department visits. Subclinical exposure was associated with increased odds of having at least 1 hospitalization in the first year. However, the total length of stay for hospitalizations was 82% that of the unexposed group (95% CI, 75%-89%). Infants with NAS had a 213% longer total length of stay compared with the unexposed group (95% CI, 191%-237%). CONCLUSIONS: Subclinical and overt opioid exposure among newborn infants was associated with increased first-year healthcare utilization. From 2014 to 2017, this cost the Hamilton County healthcare system an estimated $1 109 452 for longer birth encounters alone.

Torticollis in Infants with a History of Neonatal Abstinence Syndrome.

In this retrospective cohort study, we assessed the incidence of torticollis in infants with a history of neonatal abstinence syndrome. Understanding the elevated risk of torticollis in this population is important for early identification and treatment.

Pediatric Primary Care of Children With Intrauterine Opioid Exposure: Survey of Academic Teaching Practices.

OBJECTIVE: Intrauterine opioid exposure (IOE) has increased over the last 2 decades and is associated with additional needs after birth. To date, no clinical guidelines address the primary care of children with IOE. We aimed to characterize clinician-reported screening and referral practices, barriers to effective primary care for children with IOE, and clinician- and practice-level characteristics associated with perceived barriers. METHODS: We conducted a cross-sectional survey of pediatric residents, pediatricians, and advanced practitioners at 28 primary care clinics affiliated with 7 pediatric residency programs (April-June 2022). We assessed screening and other clinical practices related to IOE and perceived barriers to addressing parental opioid use disorder (OUD). We used descriptive statistics to analyze survey responses, assessed the distribution of reported barriers, and applied a 2-stage cluster analysis to assess response patterns. RESULTS: Of 1004 invited clinicians, 329 (32.8%) responses were returned, and 325 pediatric residents and pediatricians were included in the final analytic sample. Almost all (99.3%) reported parental substance use screening as important, but only 11.6% screened routinely. Half of the respondents routinely refer children with IOE to early intervention services and social work. Lack of standard screening for substance use was the most frequently selected barrier to addressing parental OUD. Participants reporting fewer barriers to addressing parental OUD identified having greater access to OUD treatment programs and home visiting programs. CONCLUSIONS: Pediatricians report variations in primary care screenings and referrals for children with IOE. Access to parental OUD treatment programs may mitigate perceived barriers to addressing parental OUD in the pediatric office.

Influence of Eat, Sleep, and Console on Infants Pharmacologically Treated for Opioid Withdrawal: A Post Hoc Subgroup Analysis of the ESC-NOW Randomized Clinical Trial.

Importance: The function-based eat, sleep, console (ESC) care approach substantially reduces the proportion of infants who receive pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS). This reduction has led to concerns for increased postnatal opioid exposure in infants who receive pharmacologic treatment. However, the effect of the ESC care approach on hospital outcomes for infants pharmacologically treated for NOWS is currently unknown. Objective: To evaluate differences in opioid exposure and total length of hospital stay (LOS) for pharmacologically treated infants managed with the ESC care approach vs usual care with the Finnegan tool. Design, Setting, and Participants: This post hoc subgroup analysis involved infants pharmacologically treated in ESC-NOW, a stepped-wedge cluster randomized clinical trial conducted at 26 US hospitals. Hospitals maintained pretrial practices for pharmacologic treatment, including opioid type, scheduled opioid dosing, and use of adjuvant medications. Infants were born at 36 weeks' gestation or later, had evidence of antenatal opioid exposure, and received opioid treatment for NOWS between September 2020 and March 2022. Data were analyzed from November 2022 to January 2024. Exposure: Opioid treatment for NOWS and the ESC care approach. Main Outcomes and Measures: For each outcome (total opioid exposure, peak opioid dose, time from birth to initiation of first opioid dose, length of opioid treatment, and LOS), we used generalized linear mixed models to adjust for the stepped-wedge design and maternal and infant characteristics. Results: In the ESC-NOW trial, 463 of 1305 infants were pharmacologically treated (143/603 [23.7%] in the ESC care approach group and 320/702 [45.6%] in the usual care group). Mean total opioid exposure was lower in the ESC care approach group with an absolute difference of 4.1 morphine milligram equivalents per kilogram (MME/kg) (95% CI, 1.3-7.0) when compared with usual care (4.8 MME/kg vs 8.9 MME/kg, respectively; P = .001). Mean time from birth to initiation of pharmacologic treatment was 22.4 hours (95% CI, 7.1-37.7) longer with the ESC care approach vs usual care (75.4 vs 53.0 hours, respectively; P = .002). No significant difference in mean peak opioid dose was observed between groups (ESC care approach, 0.147 MME/kg, vs usual care, 0.126 MME/kg). The mean length of treatment was 6.3 days shorter (95% CI, 3.0-9.6) in the ESC care approach group vs usual care group (11.8 vs 18.1 days, respectively; P < .001), and mean LOS was 6.2 days shorter (95% CI, 3.0-9.4) with the ESC care approach than with usual care (16.7 vs 22.9 days, respectively; P < .001). Conclusion and Relevance: When compared with usual care, the ESC care approach was associated with less opioid exposure and shorter LOS for infants pharmacologically treated for NOWS. The ESC care approach was not associated with a higher peak opioid dose, although pharmacologic treatment was typically initiated later. Trial Registration: ClinicalTrials.gov Identifier: NCT04057820.

Neonatal Opioid Withdrawal Syndrome: An Update on Developmental Outcomes.

Infants and children with prenatal opioid exposure generally have development within the normal range; however, they seem to be at risk for behavioral problems and for lower scores on cognitive, language, and motor assessments than children without prenatal opioid exposure. It is as of yet unclear whether prenatal opioid exposure itself causes issues with development and behavior, or whether it is simply correlated, due to other confounding factors.

Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-2009.

CONTEXT: Neonatal abstinence syndrome (NAS) is a postnatal drug withdrawal syndrome primarily caused by maternal opiate use. No national estimates are available for the incidence of maternal opiate use at the time of delivery or NAS. OBJECTIVES: To determine the national incidence of NAS and antepartum maternal opiate use and to characterize trends in national health care expenditures associated with NAS between 2000 and 2009. DESIGN, SETTING, AND PATIENTS: A retrospective, serial, cross-sectional analysis of a nationally representative sample of newborns with NAS. The Kids' Inpatient Database (KID) was used to identify newborns with NAS by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code. The Nationwide Inpatient Sample (NIS) was used to identify mothers using diagnosis related groups for vaginal and cesarean deliveries. Clinical conditions were identified using ICD-9-CM diagnosis codes. NAS and maternal opiate use were described as an annual frequency per 1000 hospital births. Missing hospital charges (<5% of cases) were estimated using multiple imputation. Trends in health care utilization outcomes over time were evaluated using variance-weighted regression. All hospital charges were adjusted for inflation to 2009 US dollars. MAIN OUTCOME MEASURES: Incidence of NAS and maternal opiate use, and related hospital charges. RESULTS: The separate years (2000, 2003, 2006, and 2009) of national discharge data included 2920 to 9674 unweighted discharges with NAS and 987 to 4563 unweighted discharges for mothers diagnosed with antepartum opiate use, within data sets including 784,191 to 1.1 million discharges for children (KID) and 816,554 to 879,910 discharges for all ages of delivering mothers (NIS). Between 2000 and 2009, the incidence of NAS among newborns increased from 1.20 (95% CI, 1.04-1.37) to 3.39 (95% CI, 3.12-3.67) per 1000 hospital births per year (P for trend < .001). Antepartum maternal opiate use also increased from 1.19 (95% CI, 1.01-1.35) to 5.63 (95% CI, 4.40-6.71) per 1000 hospital births per year (P for trend < .001). In 2009, newborns with NAS were more likely than all other hospital births to have low birthweight (19.1%; SE, 0.5%; vs 7.0%; SE, 0.2%), have respiratory complications (30.9%; SE, 0.7%; vs 8.9%; SE, 0.1%), and be covered by Medicaid (78.1%; SE, 0.8%; vs 45.5%; SE, 0.7%; all P < .001). Mean hospital charges for discharges with NAS increased from $39,400 (95% CI, $33,400-$45,400) in 2000 to $53,400 (95% CI, $49,000-$57,700) in 2009 (P for trend < .001). By 2009, 77.6% of charges for NAS were attributed to state Medicaid programs. CONCLUSION: Between 2000 and 2009, a substantial increase in the incidence of NAS and maternal opiate use in the United States was observed, as well as hospital charges related to NAS.

Rates of substance and polysubstance use through universal maternal testing at the time of delivery.

OBJECTIVE: To report substance and polysubstance use at the time of delivery. STUDY DESIGN: A cross-sectional study was performed on mothers consented for universal drug testing (99%) during hospital admission at six delivery hospitals in Cincinnati, Ohio. Mass spectrometry urinalysis detected positivity rates of 46 substances. Rates of positive drug tests for individual and common co-occurring substances measured were reported. RESULTS: 2531 maternal samples were tested (88%) and 33% contained cotinine, 11.3% THC, 7.2% opioids, 3.8% cocaine, and 1.9% methamphetamines. Polysubstance use prevalence was as high as 15%. Among mothers testing positive for methadone or buprenorphine, 93% also tested positive for cotinine and 39% tested positive for a third substance in addition to cotinine. CONCLUSIONS: Substance use at delivery is more prevalent than previously reported. Many mothers testing positive for opioids also test positive for other substances, which may increase overdose risk and exacerbate neonatal opioid withdrawal syndrome (NOWS).

Racial Inequities in Breastfeeding Counseling Among Pregnant People Who Use Cannabis.

We examined how breastfeeding advice in the context of cannabis use differed by race and ethnicity. Data from the 2017-2018 PRAMS (Pregnancy Risk Assessment Monitoring System) survey were used to assess differences in breastfeeding guidance related to cannabis use among 1,213 individuals who self-reported cannabis use 3 months before or during pregnancy. A multivariable logistic regression model was specified to examine the extent to which the odds of receiving prenatal advice against breastfeeding if using cannabis differed by self-reported race and ethnicity. We found that non-Hispanic Black people were four times more likely than non-Hispanic White people to be advised against breastfeeding if using cannabis (adjusted odds ratio 4.1, 95% CI 2.1-8.2). Pregnant non-Hispanic Black people were disproportionately advised not to breastfeed if using cannabis.

Regional comparison of self-reported late pregnancy cigarette smoking to mass spectrometry analysis.

OBJECTIVE: To report a more accurate prevalence estimate of late pregnancy nicotine exposures. STUDY DESIGN: A cross-sectional study during a 2-month period in 2019. Participants were women delivering in any of the six county maternity hospitals who consented to universal drug testing at the time of delivery as part of routine hospital admission. RESULTS: Of 2531 tested samples, 18.7% tested positive for high levels of cotinine indicating primary smoking or other primary use of tobacco products. Together, 33.0% of the study population tested positive for nicotine exposure during late pregnancy compared to vital records which reported 8.2% cigarette smoking during the third trimester of pregnancy and 10.5% cigarette smoking at any time during pregnancy through maternal self-report. CONCLUSION: Captured vital birth smoking measures vastly underreport actual primary exposures to nicotine products. Vital birth data also fail to capture secondhand exposures which constitute a significant proportion of the population.

Reported Prevalence of Maternal Hepatitis C Virus Infection in the United States.

OBJECTIVE: To quantify the reported prevalence and trend of maternal hepatitis C virus (HCV) infection in the United States (2009-2017) and identify maternal characteristics and obstetric outcomes associated with HCV infection during pregnancy. METHODS: We conducted a population-based retrospective cohort study of all live births in the United States for the period 2009 through 2017 using National Center for Health Statistics birth records. We estimated reported prevalence and trends over this time period for the United States. We also evaluated demographic factors and pregnancy outcomes associated with maternal HCV infection for a contemporary U.S. cohort (2014-2017). RESULTS: During the 9-year study period, there were 94,824 reported cases of maternal HCV infection among 31,207,898 (0.30%) live births in the United States. The rate of maternal HCV infection increased from 1.8 cases per 1,000 live births to 4.7 cases per 1,000 live births (relative risk [RR] 2.7, 95% CI 2.6-2.8) in the United States. After adjusting for various confounders in the contemporary U.S. cohort (2014-2017), demographic characteristics associated with HCV infection included non-Hispanic white race (adjusted RR 2.8, 95% CI 2.7-2.8), Medicaid insurance (adjusted RR 3.3, CI 3.2-3.3), and cigarette smoking (adjusted RR 11.1, CI 10.9-11.3). Co-infection during pregnancy with hepatitis B (adjusted RR 19.2, CI 18.1-20.3), gonorrhea, chlamydia, or syphilis were also associated with maternal HCV infection. Obstetric and neonatal outcomes associated with maternal HCV infection included cesarean delivery, preterm birth, maternal intensive care unit admission, blood transfusion, having small-for-gestational-age neonates (less than the 10th percentile) birth weight, neonatal intensive care unit admission, need for assisted neonatal ventilation, and neonatal death. CONCLUSION: The reported prevalence of maternal HCV infection has increased 161% from 2009 to 2017.

Developmental Disorders and Medical Complications Among Infants with Subclinical Intrauterine Opioid Exposures.

The objective was to compare diagnosis rates representing developmental outcomes and medical complications between infants with intrauterine opioid exposures who did not receive pharmacologic treatment for neonatal abstinence syndrome at the time of birth and infants for whom no exposure to substances of abuse were detected. This retrospective, descriptive study included approximately 95% of Hamilton County, Ohio resident births in 2014 and 2015. Universal maternal drug test results, performed at the time of birth, were documented and linked to electronic health records representing pediatric primary and subspecialty follow-up care as well as urgent care, emergency care, and inpatient services provided by Cincinnati Children's Hospital Medical Center through 2017, when all children were at least 24 months old. Diagnosis rates were compared between drug exposure groups using chi-square tests. Among infants born at >34 weeks gestation and without other complex clinical conditions, infants with subclinical opioid exposures (N = 473) were more likely than infants with no drug exposures (N = 14,933) to be diagnosed with behavioral or emotional disorders (3.0% vs 1.1%, P = 0.0008), developmental delay (15.6% vs 7.6%, P < 0.0001), speech disorder (10.1% vs 6.5%, P = 0.001), or strabismus (3.4% vs 1.0%, P < 0.0001), and more likely to be exposed to the hepatitis C virus (6.8% vs 0.1%, P < 0.0001). Increased diagnosis rates among all opioid exposed infants, regardless of withdrawal severity, may warrant the additional allocation of resources for screening and follow-up. Awareness of the increased risk for certain developmental delays and medical conditions is critical to early intervention and treatment supporting improved outcomes.

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.

Retrospective review of neurodevelopmental outcomes in infants treated for neonatal abstinence syndrome.

OBJECTIVE: Little is known about developmental outcomes in neonatal abstinence syndrome (NAS). We hypothesized that children treated for NAS would score lower than the normative sample on the Bayley Scales of Infant Development, 3rd edition. STUDY DESIGN: We performed a retrospective cohort study of 87 infants treated for NAS and evaluated at 2 years of age. RESULTS: Children treated for NAS scored significantly lower than the norm (mean 100) on all 3 subscales (cognitive mean 96.5, language mean 93.8, motor mean 94.0, all p < 0.03). Children who lived with foster/adoptive families at follow up had higher cognitive scores (median 100 vs. 95, p = 0.03) than those who lived with biological relatives, and were less likely to have motor scores <85 (p = 0.02). Eight percent of children required treatment for strabismus. CONCLUSIONS: Children treated for NAS are at risk for lower developmental scores and higher rates of strabismus at age 2 than the general population.