ObjectiveTo evaluate changes in hospital outcomes for infants with neonatal opioid withdrawal syndrome (NOWS) assessed by the Finnegan Tool before (10/1/2019 to 12/31/2019;pre-epoch) and after (7/1/2021 to 3/31/2022;post-epoch) publication of the 2020 AAP NOWS clinical report.Study designThis subgroup analysis included infants with NOWS assessed with the Finnegan Tool and enrolled in the INFORM NOW study (pre- and post-epoch 183 and 267 infants respectively).ResultsNo differences were found between epochs in initiation or length of pharmacologic treatment(LOT), or length of stay(LOS). Outcomes were modified by opioid type: LOT was 20% shorter (aMR=0.80; 95%CI:[0.69,0.93]) and LOS was 16% shorter (aMR=0.84; 95%CI:[0.73,0.96]) for buprenorphine treated infants post- compared to pre-epoch, while LOT and LOS were longer in the post-epoch for those treated with methadone.ConclusionThere was no difference in outcomes before and after publication of the AAP report. However, the type of postnatal opioid did modify study results.

Importance:Infants with neonatal opioid withdrawal syndrome (NOWS) who receive pharmacologic treatment are traditionally treated with a scheduled opioid taper. An alternate approach, symptom-based dosing, may better align treatment with withdrawal severity. Objective:To compare time from birth to medical readiness for discharge for infants with moderate to severe withdrawal treated with either a symptom-based dosing or scheduled opioid taper approach. Design, Setting, and Participants:In this cluster, crossover randomized clinical trial with run-in period, 23 US hospitals cared for infants using the Eat, Sleep, Console approach (ESC) or Finnegan-based care (a comprehensive scoring system to quantify severity of symptoms; 15 ESC and 8 Finnegan hospitals) and their preferred primary opioid. Opioid dosing was guided by study-approved, site-specific algorithms. Infants with NOWS with a gestational age at birth of at least 36 weeks and at risk for pharmacologic treatment were enrolled between March 25, 2024, and April 9, 2025, with the last 3-month assessment on July 15, 2025. Sample size analyses were conducted between August 1, 2024, and September 23, 2024. Intervention:Sites were randomized to 1 of 2 sequences: (1) symptom-based dosing followed by scheduled opioid taper or (2) scheduled opioid taper followed by symptom-based dosing. Main Outcome and Measure:Time from birth to medical readiness for discharge. Results:Of the 626 enrolled infants (mean [SD] gestational age, 38 [1] weeks; 49% male), 383 were cared for with ESC (primary outcome cohort). The mean time to medical readiness for discharge was significantly shorter in the symptom-based dosing group compared with the scheduled opioid taper group (9.18 vs 11.61 days; adjusted mean ratio [aMR], 0.79 [95% CI, 0.65-0.96]). There was no difference in the risk for initiation of pharmacologic treatment (0.4 vs 0.41; adjusted risk ratio, 0.99 [95% CI, 0.77-1.27]) or length of stay (10.91 vs 12.09 days; aMR, 0.9 [95% CI, 0.72-1.13]) between groups. For infants in the symptom-based group, 35% (95% CI, 25%-45%) required scheduled opioid dosing due to withdrawal severity that was not controlled with intermittent dosing. In the Finnegan cohort (n = 243; planned secondary outcome), there were no significant differences in time to medical readiness for discharge (15.99 vs 17.56 days; aMR, 0.91 [95% CI, 0.72-1.15]) or length of stay (17.38 vs 19.39 days; aMR, 0.9 [95% CI, 0.69-1.16]). The inpatient composite safety outcome occurred rarely (in the ESC cohort, 3 of 188 in the symptom-based dosing vs 2 of 195 in the scheduled opioid taper groups). Conclusions and Relevance:Symptom-based dosing decreased time to medical readiness for discharge compared with a scheduled opioid taper approach among infants cared for with ESC. Trial Registration:ClinicalTrials.gov Identifier: NCT05980260.

Importance Infants with neonatal opioid withdrawal syndrome (NOWS) who receive pharmacologic treatment are traditionally treated with a scheduled opioid taper. An alternate approach, symptom-based dosing, may better align treatment with withdrawal severity. Objective To compare time from birth to medical readiness for discharge for infants with moderate to severe withdrawal treated with either a symptom-based dosing or scheduled opioid taper approach. Design, Setting, and Participants In this cluster, crossover randomized clinical trial with run-in period, 23 US hospitals cared for infants using the Eat, Sleep, Console approach (ESC) or Finnegan-based care (a comprehensive scoring system to quantify severity of symptoms; 15 ESC and 8 Finnegan hospitals) and their preferred primary opioid. Opioid dosing was guided by study-approved, site-specific algorithms. Infants with NOWS with a gestational age at birth of at least 36 weeks and at risk for pharmacologic treatment were enrolled between March 25, 2024, and April 9, 2025, with the last 3-month assessment on July 15, 2025. Sample size analyses were conducted between August 1, 2024, and September 23, 2024. Intervention Sites were randomized to 1 of 2 sequences: (1) symptom-based dosing followed by scheduled opioid taper or (2) scheduled opioid taper followed by symptom-based dosing. Main Outcome and Measure Time from birth to medical readiness for discharge. Results Of the 626 enrolled infants (mean [SD] gestational age, 38 [1] weeks; 49% male), 383 were cared for with ESC (primary outcome cohort). The mean time to medical readiness for discharge was significantly shorter in the symptom-based dosing group compared with the scheduled opioid taper group (9.18 vs 11.61 days; adjusted mean ratio [aMR], 0.79 [95% CI, 0.65-0.96]). There was no difference in the risk for initiation of pharmacologic treatment (0.4 vs 0.41; adjusted risk ratio, 0.99 [95% CI, 0.77-1.27]) or length of stay (10.91 vs 12.09 days; aMR, 0.9 [95% CI, 0.72-1.13]) between groups. For infants in the symptom-based group, 35% (95% CI, 25%-45%) required scheduled opioid dosing due to withdrawal severity that was not controlled with intermittent dosing. In the Finnegan cohort (n = 243; planned secondary outcome), there were no significant differences in time to medical readiness for discharge (15.99 vs 17.56 days; aMR, 0.91 [95% CI, 0.72-1.15]) or length of stay (17.38 vs 19.39 days; aMR, 0.9 [95% CI, 0.69-1.16]). The inpatient composite safety outcome occurred rarely (in the ESC cohort, 3 of 188 in the symptom-based dosing vs 2 of 195 in the scheduled opioid taper groups). Conclusions and Relevance Symptom-based dosing decreased time to medical readiness for discharge compared with a scheduled opioid taper approach among infants cared for with ESC. Trial Registration ClinicalTrials.gov Identifier: NCT05980260

Objective Determine the relationship between maternal Social Deprivation Index (SDI), a composite measure of area-level deprivation, and maternal characteristics and infant outcomes for mother-infant dyads with perinatal opioid exposure. Study Design Post hoc secondary analysis of 1,298 mother-infant dyads in the ESC-NOW study, a multicenter, stepped-wedge cluster-randomized controlled trial (2020-2022) conducted at 26 U.S. study hospitals. The 2016 American Community Survey was used to develop SDI scores based on the maternal zip code of residence at the time of delivery. Outcomes evaluated included receipt of pharmacologic treatment for neonatal opioid withdrawal syndrome (PT), receipt of breastmilk during hospital stay, direct breastfeeding at discharge, discharge disposition, and length of stay for infants who received PT (length of hospital stay, LOS). Results The median SDI score was 62 on a scale of 100. The high SDI group, with a score above the SDI median and more social deprivation, was less likely to receive adequate prenatal care or medication for opioid use disorder and more likely to be Black and/or Hispanic. The mean proportion of infants in the high SDI group was 6.2% points (relative risk [RR]: 0.89; 95% confidence interval [CI]: 0.80, 0.98) less likely to receive breastmilk during the newborn hospitalization and 7.3% points (RR: 0.91; 95% CI: 0.87, 0.96) less likely to be discharged home with a biological parent. There was no difference between the high and low SDI groups in receipt of PT, direct breastfeeding at discharge, or LOS. Conclusion Mothers from high SDI communities with opioid exposure during pregnancy were less likely to receive the established standard of care and more likely to be Black and/or Hispanic. Infants born to these mothers were less likely to receive breastmilk and/or to be discharged home with a biological parent. Targeting interventions to mitigate the impact of social deprivation in high SDI communities may improve outcomes for opioid-exposed infants and their mothers.

Assess the feasibility of using a disposable pressure transducer with integrated digital display to differentiate arterial versus venous line placement in neonates. Infants ≥23 weeks’ gestation with appropriately placed umbilical catheters were enrolled. A single baseline pressure reading was obtained, hypothesizing that arterial placement could be differentiated with a pressure ≥12 mmHg. Forty-five infants were enrolled to obtain 62 measurements, 31 from both umbilical artery catheters(UAC) and umbilical venous catheters(UVC). 100

Background: Antenatal substance exposure due to maternal substance use during pregnancy has increased significantly, leading to suboptimal health outcomes for infants. Telomere length (TL) is a biological aging marker that may be affected by antenatal substance exposures. A comprehensive review of relevant studies is crucial for providing insights into the etiology of infant developmental outcomes. Objectives: This scoping review, guided by the PRISMA guideline, aims to identify and summarize the existing research on the relationships between infants’ antenatal substance exposure and TL. Methods: A systematic literature search was conducted using PubMed, Cochrane, Embase, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO. Search terms included antenatal, prenatal, infant, and various psychotropic substances. The review included studies examining the associations between antenatal substance exposure and TL. The last literature search was conducted on April 16, 2023. Results: Seven articles met the inclusion criteria, addressing diverse substances such as alcohol, opioids, and tobacco. Among the seven studies, one evaluated the influence of antenatal alcohol exposure, one assessed antenatal opioid exposure, and five investigated antenatal tobacco exposure. The findings across the articles were varied, with five reporting indirect correlations and two reporting direct correlations between antenatal substance exposure and the TL in exposed infants. Conclusions: This scoping review identified a significant gap in the current literature about the associations between antenatal substance exposure and TL in infants. The diverse findings emphasize the need for further research to explore whether TL could serve as a potential biomarker for predicting the effects of substance exposure on offspring. This study lays the foundation for future investigation and contributes to understanding the complex relationship between antenatal substance exposure and telomere biology in infants.

Opioid use and misuse during pregnancy rose from 1.5 to 6.5 per 1000 deliveries between 1999 and 2014 and continues as a significant public health concern. A fivefold increase in neonatal opioid withdrawal syndrome (NOWS) has accompanied the increase in opioid use. The Eating, Sleeping, Consoling care approach (ESC) has been shown to improve outcomes for infants with NOWS and is quickly becoming the standard of care for infants affected by opioid use disorder. Quality improvement initiatives following the implementation of ESC provide some evidence to suggest that symptom-based (i.e., as needed, PRN, just in time) dosing of opioid medications for infants with significant withdrawal may be an effective alternative to using a traditional scheduled opioid taper approach. These initiatives have shown reduced length of hospital stay and decreased postnatal opioid exposure when compared to scheduled opioid dosing for infants with NOWS who receive pharmacologic treatment. It is unknown if the findings from these quality improvement initiatives are generalizable, and little is known about the safety of this approach in a diverse population. The purpose of this manuscript is to describe the design and rationale for an ongoing study to evaluate the effect of symptom-based opioid dosing compared to traditional scheduled opioid taper on short-term outcomes for infants with NOWS. In this ongoing multi-center two-period cluster crossover randomized controlled trial, 24 sites within the USA were randomized at the site level into one of two sequences. Prior to randomization, sites were stratified by care approach used (ESC vs. usual care) and these strata were independently randomized. All study sites will provide care based on their random allocation. Data will be collected under waiver of consent for in-hospital and short-term outcomes for eligible infants. A minimum of 480 infants will be enrolled. We hypothesize that use of symptom-based dosing will safely reduce the length of time until infants with NOWS and at risk for pharmacological treatment are medically ready for discharge when compared to infants treated with a scheduled opioid taper. This trial is uniquely and efficiently designed to establish the efficacy, safety, and generalizability of the symptom-based dosing approach to opioid treatment for NOWS. NCT05980260 ; registered July 27, 2023.

ObjectiveEvaluate associations between antenatal exposure to medication for opioid use disorder (MOUD), including MOUD type, and neonatal outcomes for infants with neonatal opioid withdrawal syndrome (NOWS).Study designData from 768 neonates with NOWS born between 36-0/7 to 41-6/7 weeks gestation were retrospectively collected from 13 United States hospitals.ResultsCompared to neonates with antenatal exposure to non-MOUD opioids, neonates with antenatal exposure to MOUD opioids had a 51% lower odds of delivery before 39 weeks and 2.72-fold greater odds of breastfeeding. Compared to neonates with antenatal exposure to prescribed methadone, neonates exposed to prescribed buprenorphine or buprenorphine/naloxone had increased mean head circumference z-scores (0.31 and 0.48 units respectively), decreased odds of pharmacologic treatment (49% and 58%, respectively), and a reduced mean length of hospital stay (35% and 39%, respectively).ConclusionAntenatal exposure to MOUD opioids, specifically prescribed buprenorphine, was associated with significantly improved neonatal outcomes.ClinicalTrials.gov IDINFORM NOW: N/A

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.

Infants with neonatal opioid withdrawal syndrome (NOWS) cared for with the Eat, Sleep, Console (ESC) care approach receive less pharmacologic treatment and have shorter hospital stays compared to usual care with the Finnegan Neonatal Abstinence Scoring Tool, but the effects of these approaches on feeding and weight are unknown. To evaluate feeding practices and weight trajectories in infants cared for with ESC vs usual care. ESC-NOW is a cluster randomized trial of infants with NOWS born at 36 weeks’ gestation or later at 26 US hospitals from September 2020 to March 2022. Each site transitioned from usual care to ESC (the study intervention) at a randomized time. Feeding was per site practice and not specified by the intervention. Feeding and weight outcomes were assessed at hospital discharge. ESC vs usual care. Outcomes include prospectively identified secondary end points related to feeding and weight. z Scores were used for growth to account for corrected gestational age at the time of measurement. All analyses were intention to treat and adjusted for study design. Maternal/infant characteristics were included in adjusted models. The analyses included 1305 infants (702 in usual care and 603 in ESC; mean [SD] gestational age, 38.6 [1.3] weeks; 655 [50.2%] male and 650 [49.8%] female). Baseline demographic characteristics were similar between groups. The proportion of breastfed infants was higher in the ESC group (52.7% vs 41.7%; absolute difference, 11%; 95% CI, 1.0-20.9). A higher proportion of infants cared for with ESC received exclusive breast milk (15.1% vs 6.7%; absolute difference, 8.4%; 95% CI, 0.9-5.8) or any breast milk (38.8% vs 27.4%; absolute difference, 11.4%; 95% CI, 0.2-23.1) and were directly breastfeeding at discharge (35.2% vs 19.5%; absolute difference, 15.7%; 95% CI, 4.1-27.3). There was no difference in proportion of infants with weight loss greater than 10% or maximum percentage weight loss, although infants cared for with ESC had a lower weight z score on day of life 3 (−1.08 vs −1.01; absolute difference, 0.07; 95% CI, 0.02-0.12). When pharmacologic treatment was added into the model, no breastfeeding outcomes were statistically significant. In this study, infants cared for with ESC were more likely to initiate and continue breastfeeding and had no difference in percentage weight loss. The improvement in breastfeeding with ESC may be driven by reduction in pharmacologic treatment and provision of effective nonpharmacologic care. ClinicalTrials.gov Identifier: NCT04057820

Background: Medical record abstraction (MRA) is a commonly used method for data collection in clinical research, but is prone to error, and the influence of quality control (QC) measures is seldom and inconsistently assessed during the course of a study. We employed a novel, standardized MRA-QC framework as part of an ongoing observational study in an effort to control MRA error rates. In order to assess the effectiveness of our framework, we compared our error rates against traditional MRA studies that had not reported using formalized MRA-QC methods. Thus, the objective of this study was to compare the MRA error rates derived from the literature with the error rates found in a study using MRA as the sole method of data collection that employed an MRA-QC framework. Methods: Using a moderator meta-analysis employed with Q-test, the MRA error rates from the meta-analysis of the literature were compared with the error rate from a recent study that implemented formalized MRA training and continuous QC processes. Results: The MRA process for data acquisition in clinical research was associated with both high and highly variable error rates (70 – 2,784 errors per 10,000 fields). Error rates for the study using our MRA-QC framework were between 1.04% (optimistic, all-field rate) and 2.57% (conservative, populated-field rate) (or 104 – 257 errors per 10,000 fields), 4.00 – 5.53 percentage points less than the observed rate from the literature (p<0.0001). Conclusions: Review of the literature indicated that the accuracy associated with MRA varied widely across studies. However, our results demonstrate that, with appropriate training and continuous QC, MRA error rates can be significantly controlled during the course of a clinical research study.

ImportanceThe 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.ObjectiveTo 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 ParticipantsThis 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.ExposureOpioid treatment for NOWS and the ESC care approach.Main Outcomes and MeasuresFor 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.ResultsIn 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 RelevanceWhen 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 RegistrationClinicalTrials.gov Identifier: NCT04057820

Background:In clinical research, prevention of systematic and random errors of data collected is paramount to ensuring reproducibility of trial results and the safety and efficacy of the resulting interventions. Over the last 40 years, empirical assessments of data accuracy in clinical research have been reported in the literature. Although there have been reports of data error and discrepancy rates in clinical studies, there has been little systematic synthesis of these results. Further, although notable exceptions exist, little evidence exists regarding the relative accuracy of different data processing methods. We aim to address this gap by evaluating error rates for 4 data processing methods. Methods:A systematic review of the literature identified through PubMed was performed to identify studies that evaluated the quality of data obtained through data processing methods typically used in clinical trials: medical record abstraction (MRA), optical scanning, single-data entry, and double-data entry. Quantitative information on data accuracy was abstracted from the manuscripts and pooled. Meta-analysis of single proportions based on the Freeman-Tukey transformation method and the generalized linear mixed model approach were used to derive an overall estimate of error rates across data processing methods used in each study for comparison. Results:A total of 93 papers (published from 1978 to 2008) meeting our inclusion criteria were categorized according to their data processing methods. The accuracy associated with data processing methods varied widely, with error rates ranging from 2 errors per 10,000 fields to 2,784 errors per 10,000 fields. MRA was associated with both high and highly variable error rates, having a pooled error rate of 6.57% (95% CI: 5.51, 7.72). In comparison, the pooled error rates for optical scanning, single-data entry, and double-data entry methods were 0.74% (0.21, 1.60), 0.29% (0.24, 0.35) and 0.14% (0.08, 0.20), respectively. Conclusions:Data processing and cleaning methods may explain a significant amount of the variability in data accuracy. MRA error rates, for example, were high enough to impact decisions made using the data and could necessitate increases in sample sizes to preserve statistical power. Thus, the choice of data processing methods can likely impact process capability and, ultimately, the validity of trial results.

Importance:Infants with neonatal opioid withdrawal syndrome (NOWS) cared for with the Eat, Sleep, Console (ESC) care approach receive less pharmacologic treatment and have shorter hospital stays compared to usual care with the Finnegan Neonatal Abstinence Scoring Tool, but the effects of these approaches on feeding and weight are unknown. Objective:To evaluate feeding practices and weight trajectories in infants cared for with ESC vs usual care. Design, Setting, and Participants:ESC-NOW is a cluster randomized trial of infants with NOWS born at 36 weeks' gestation or later at 26 US hospitals from September 2020 to March 2022. Each site transitioned from usual care to ESC (the study intervention) at a randomized time. Feeding was per site practice and not specified by the intervention. Feeding and weight outcomes were assessed at hospital discharge. Intervention:ESC vs usual care. Main Outcomes and Measures:Outcomes include prospectively identified secondary end points related to feeding and weight. z Scores were used for growth to account for corrected gestational age at the time of measurement. All analyses were intention to treat and adjusted for study design. Maternal/infant characteristics were included in adjusted models. Results:The analyses included 1305 infants (702 in usual care and 603 in ESC; mean [SD] gestational age, 38.6 [1.3] weeks; 655 [50.2%] male and 650 [49.8%] female). Baseline demographic characteristics were similar between groups. The proportion of breastfed infants was higher in the ESC group (52.7% vs 41.7%; absolute difference, 11%; 95% CI, 1.0-20.9). A higher proportion of infants cared for with ESC received exclusive breast milk (15.1% vs 6.7%; absolute difference, 8.4%; 95% CI, 0.9-5.8) or any breast milk (38.8% vs 27.4%; absolute difference, 11.4%; 95% CI, 0.2-23.1) and were directly breastfeeding at discharge (35.2% vs 19.5%; absolute difference, 15.7%; 95% CI, 4.1-27.3). There was no difference in proportion of infants with weight loss greater than 10% or maximum percentage weight loss, although infants cared for with ESC had a lower weight z score on day of life 3 (-1.08 vs -1.01; absolute difference, 0.07; 95% CI, 0.02-0.12). When pharmacologic treatment was added into the model, no breastfeeding outcomes were statistically significant. Conclusions and Relevance:In this study, infants cared for with ESC were more likely to initiate and continue breastfeeding and had no difference in percentage weight loss. The improvement in breastfeeding with ESC may be driven by reduction in pharmacologic treatment and provision of effective nonpharmacologic care. Trial Registration:ClinicalTrials.gov Identifier: NCT04057820.

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.).

(1) To evaluate the direct (un-mediated) and indirect (mediated) relationship between antenatal exposure to opioid agonist medication as treatment for opioid use disorder (MOUD) and the severity of neonatal opioid withdrawal syndrome (NOWS), and (2) to understand the degree to which mediating factors influence the direct relationship between MOUD exposure and NOWS severity. This cross-sectional study includes data abstracted from the medical records of 1294 opioid-exposed infants (859 MOUD exposed and 435 non-MOUD exposed) born at or admitted to one of 30 US hospitals from July 1, 2016, to June 30, 2017. Regression models and mediation analyses were used to evaluate the relationship between MOUD exposure and NOWS severity (i.e., infant pharmacologic treatment and length of newborn hospital stay (LOS)) to identify potential mediators of this relationship in analyses adjusted for confounding factors. A direct (un-mediated) association was found between antenatal exposure to MOUD and both pharmacologic treatment for NOWS (aOR 2.34; 95

Abstract Background: Over the last 30 years, empirical assessments of data accuracy in clinical research have been reported in the literature. Although there have been articles summarizing results reported in multiple papers, there has been little synthesis of these results. Further, although notable exceptions exist, little evidence has been obtained regarding the relative accuracy of different data processing methods. Methods: A systematic review of the literature was performed to identify clinical research studies that evaluated the quality of data obtained from data processing methods typically used in clinical research (e.g., medical record abstraction, optical scanning, single-data entry, and double-data entry). A total of 93 papers meeting our inclusion criteria were categorized according to their data processing methods. Quantitative information on data accuracy was abstracted from the articles and pooled. Meta-analysis of single proportions based on an inverse variance method and generalized linear mixed model approach of studies from the literature were used to derive an overall estimate of error rates across data processing methods for comparison. Results: Review of the literature indicated that the accuracy associated with data processing methods varies widely, with error rates ranging from 2 errors per 10,000 fields to 2,784errors per 10,000 fields. The medical record abstraction process for data acquisition in clinical research was associated with both high and highly variable error rates, with a variability of 3 orders of magnitude in accuracy (70 – 2,784 errors per 10,000 fields). Error rates for data processed with optical methods were comparable to data processed using single-data entry (2 – 358 vs. 4 – 650 per 10,000 fields, respectively). In comparison, double-data entry was associated with the lowest error rates (4 – 33 per 10,000 fields). Conclusions: Data processing and cleaning methods may explain a significant amount of the variability in data accuracy.

(N Engl J Med. 2023; 388:2326–2337) The diagnosis of neonatal opioid withdrawal syndrome is a frequent occurrence within US hospitals. Most often neonates are evaluated for withdrawal-related symptoms with the Finnegan Neonatal Abstinence Scoring Tool and the associated modifications, however this approach may lead to overuse of pharmacologic agents such as morphine. These authors sought to evaluate whether the Eat, Sleep, Console approach could reduce length of hospital stays experienced by neonates without compromising their safety.

Introduction Management of uncontrolled, moderate-to-severe asthma during pregnancy can be challenging. Despite advances in treatments, a limited evidence base and potential maternal and foetal risks can result in clinician uncertainty and anxiety amongst patients. Our aim was to describe our current practice and compare asthma at baseline and during pregnancy. Methods Retrospective review of patients attending a new dedicated asthma in pregnancy clinic at a large tertiary severe asthma service between December 2020 and March 2023. Standardised questionnaire results, adherence, exacerbation, and medication history was compared before and during pregnancy. A paired t-test was used to investigate differences in asthma control at baseline and during pregnancy. Results 47 women with 48 pregnancies were reviewed. Median age was 28 years (interquartile range, 26–32 years). Pre-pregnancy, most women were on a Global Initiative for Asthma treatment step 3–5 (42/48, 88%) and were considered to have uncontrolled asthma (an asthma control questionnaire (ACQ-6) score of ≥1.5 and/or ≥1 exacerbation requiring high dose steroids in the previous 12 months; 35/48, 73%). 12 women (26%) had documented anxiety about their asthma while pregnant, of which 4 women (4/12, 33%) admitted to stopping some or all their asthma treatments prior to coming to the first clinic appointment. A switch to a more suitable inhaled-device, dose increase, or addition of another controller was attempted in 23/48 (48%) pregnancies to optimise asthma. 6 (6/48,13%) pregnancies were associated with a deterioration of asthma, 9 (9/48, 19%) improved and 32 (32/48, 68%) women's asthma control remained the same. Measures of asthma (ACQ-6, exacerbations, hospitalisations, short-acting bronchodilator collections) did not significantly change during pregnancy except for the mean mini-Asthma Quality of Life Questionnaire score (3.7±1.8 vs. 3.1±1.6, p=0.04) which decreased and mean percentage adherence which improved (65%±27 vs. 77%±22, p=0.03). Conclusions Asthma management during pregnancy is guided by asthma control pre-conception. Attending a dedicated asthma in pregnancy clinic is an opportunity to educate women, improve adherence and manage anxiety. Attempts to optimise treatment were not always successful, which may partly be due to other physiological mechanisms in pregnancy. Further qualitative research and improved education may be a patient-centred solution.