Successful and Rapid Reduction in Neurosedative and Analgesic Medications in Complex Infants with Severe Bronchopulmonary Dysplasia After Tracheostomy Placement: Experience with 24-hour Propofol Infusions.

Infants with severe bronchopulmonary dysplasia may require high doses of neurosedative medications to ensure pain control and stability following tracheostomy placement. Subsequent weaning of these medications safely and rapidly is a challenge. We describe a 24-hour propofol infusion to reduce neurosedative medications in 3 high-risk infants following tracheostomy placement.

Association of an In-Hospital Desirability of Outcomes Ranking Scale With Postdischarge Health-Related Quality of Life: A Secondary Analysis of the Life After Pediatric Sepsis Evaluation.

OBJECTIVES: To develop a desirability of outcome ranking (DOOR) scale for use in children with septic shock and determine its correlation with a decrease in 3-month postadmission health-related quality of life (HRQL) or death. DESIGN: Secondary analysis of the Life After Pediatric Sepsis Evaluation prospective study. SETTING: Twelve U.S. PICUs, 2013-2017. PATIENTS: Children (1 mo-18 yr) with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We applied a 7-point pediatric critical care (PCC) DOOR scale: 7: death; 6: extracorporeal life support; 5: supported by life-sustaining therapies (continuous renal replacement therapy, vasoactive, or invasive ventilation); 4: hospitalized with or 3: without organ dysfunction; 2: discharged with or 1: without new morbidity to patients by assigning the highest applicable score on specific days post-PICU admission. We analyzed Spearman rank-order correlations (95% CIs) between proximal outcomes (PCC-DOOR scale on days 7, 14, and 21, ventilator-free days, cumulative 28-day Pediatric Logistic Organ Dysfunction-2 (PELOD-2) scores, and PICU-free days) and 3-month decrease in HRQL or death. HRQL was measured by Pediatric Quality of Life Inventory 4.0 or Functional Status II-R for patients with developmental delay. Patients who died were assigned the worst possible HRQL score. PCC-DOOR scores were applied to 385 patients, median age 6 years (interquartile range 2, 13) and 177 (46%) with a complex chronic condition(s). Three-month outcomes were available for 245 patients (64%) and 42 patients (17%) died. PCC-DOOR scale on days 7, 14, and 21 demonstrated fair correlation with the primary outcome (-0.42 [-0.52, -0.31], -0.47 [-0.56, -0.36], and -0.52 [-0.61, -0.42]), similar to the correlations for cumulative 28-day PELOD-2 scores (-0.51 [-0.59, -0.41]), ventilator-free days (0.43 [0.32, 0.53]), and PICU-free days (0.46 [0.35, 0.55]). CONCLUSIONS: The PCC-DOOR scale is a feasible, practical outcome for pediatric sepsis trials and demonstrates fair correlation with decrease in HRQL or death at 3 months.

The association of maternal country/region of origin and nativity with infant mortality rate among Hispanic preterm infants.

OBJECTIVES: Among US-born preterm infants of Hispanic mothers, we analyzed the unadjusted and adjusted infant mortality rate (IMR) by country/region of origin and maternal nativity status. STUDY DESIGN: Using linked national US birth and death certificate data (2005-2014), we examined preterm infants of Hispanic mothers by subgroup and nativity. Clinical and sociodemographic covariates were included and the main outcome was death in the first year of life. RESULTS: In our cohort of 891,216 preterm Hispanic infants, we demonstrated different rates of infant mortality by country and region of origin, but no difference between infants of Hispanic mothers who were US vs. foreign-born. CONCLUSION: These findings highlight the need to disaggregate the heterogenous Hispanic birthing population into regional and national origin groups to better understand unique factors associated with adverse perinatal outcomes in order to develop more targeted interventions for these subgroups.

The Role of Distance from Home to Hospital on Parental Experience in the NICU: A Qualitative Study.

Prolonged admission to the neonatal intensive care unit presents challenges for families, especially those displaced far from home. Understanding specific barriers to parental engagement in the NICU is key to addressing these challenges with hospital-based interventions. The objective of this qualitative study was to explore the impact of distance from home to hospital on the engagement of parents of very preterm infants (VPT) in the neonatal intensive care unit (NICU). We used a grounded theory approach and conducted 13 qualitative interviews with parents of VPT who were admitted ≥14 days and resided ≥50 miles away using a semi-structured interview guide informed by the socio-ecological framework. We used constant comparative method with double coders for theme emergence. Our results highlight a multitude of facilitators and barriers to engagement. Facilitators included: (1) individual-delivery preparedness and social support; (2) environmental-medical team relationships; and (3) societal-access to perinatal care. Barriers included: (1) individual-transfer stressors, medical needs, mental health, and dependents; (2) environmental-NICU space, communication, and lack of technology; and (3) societal-lack of paid leave. NICU parents with geographic separation from home experienced a multitude of barriers to engagement, many of which could be addressed by hospital-based interventions.

Prevalence and Predictors of Early Intervention Referral Among Substance-Exposed Newborns.

OBJECTIVES: Substance-exposed newborns (SENs) are at risk for developmental delay(s). Early intervention (EI) access, key to addressing these risks, is inequitable. Objectives were to: 1. determine prevalence of EI referral in the Colorado Hospitals Substance-Exposed Newborn Quality Improvement Collaborative; and 2. evaluate predictors of referral. METHODS: Within participating Colorado Hospitals Substance-Exposed Newborn hospitals, maternal-infant dyads with exposure to medications for opioid use disorder (MOUD), illicit/prescription opioids, and/or nonopioid substances were included on the basis of electronic medical record documentation. χ2, Fisher's exact, and analysis of variance tests evaluated differences in maternal/infant characteristics by referral. Multivariable Poisson regression models assessed the independent association of characteristics with referral. RESULTS: Among 1222 dyads, 504 (41%) SENs received EI referral. Infants born to mothers with non-MOUD (adjusted risk ratio [aRR] 2.15, 95% confidence interval [CI] 1.67-2.76) and polysubstance (aRR 1.58, 95% CI 1.26-1.97) exposure were less likely to receive referral compared with infants born to mothers with MOUD exposure. Those with private (aRR 1.26, 95% CI 1.03-1.55) or self-pay/no insurance (aRR 12.32, 95% CI 10.87-13.96) were less likely to receive referral compared with infants with public insurance. CONCLUSIONS: Less than half of identified SENs received EI referral, with variation by substance exposure and maternal insurance status. Systems to ensure equitable access to services are crucial.

Social Determinants of Health and Parenting Self-Efficacy Among Mothers of Preterm Infants.

Objective: To explore the relationships between social and environmental factors and parenting self-efficacy (PSE) among mothers of preterm infants hospitalized in neonatal intensive care units (NICUs) using a social determinants of health (SDoH) framework. Method: We analyzed data from a prospective cohort study that included 187 mother-infant dyads admitted to four NICUs in the Mountain West region between June 2017 and December 2019. We used multivariable linear regression models to assess the independent associations between maternal and infant characteristics and PSE. Results: Our final multiple linear regression model predicting the efficacy score including maternal race/ethnicity, age, insurance, employment status before giving birth, gestational age, depression, and having other children was significant (F(12,160) = 3.17, p = .0004, adjusted R¬2 = .131). Significant predictors of PSE were race/ethnicity (ß= 3.3, p = .022), having another child/children (ß= 4.2, p = .005), and depression (ß= -4.2, p = .004). Conclusions: Findings suggest that social workers and medical practitioners should consider SDoH, such as insurance type, household income, and employment, along with traditional clinical indicators when assessing families' infant care needs. Social workers, medical practitioners, and researchers should be mindful of how implicit bias may influence the allocation of care and parental supports.

Discharge Best Practices of High-Risk Infants From Regional Children's Hospital NICUs.

OBJECTIVES: Lack of discharge preparedness after NICU hospitalization is associated with risk of readmission and parental stress. Complex infants cared for at regional children's hospital NICUs would benefit from a systematic approach to transition home. Our objective was to identify potential best practices for NICU discharge and examine priorities for incorporating these best practices in regional children's hospital NICUs. METHODS: We used techniques from quality improvement, including fish bone and key driver diagrams, yielding 52 potential best practice statements for discharge preparation. Using the modified Delphi method, we surveyed stakeholders on their level of agreement for the statement to be included in the final guideline regarding discharge processes and parental education. Consensus was defined as 85% agreement among respondents. To identify implementation feasibility and understand unit-level priorities, a prioritization and feasibility assessment survey was used to rank the top best practices and performed gap analyses for the first prioritized intervention. RESULTS: Fifty of the 52 statements met the predefined criteria for consensus. The prioritization survey of potential best practice statements named assessment of families' social determinants of health with a standardized tool as the top priority among respondents. Conducting gap analyses enabled an understanding of current practice, barriers, and affordances, allowing for implementation planning. CONCLUSIONS: This multicenter and interdisciplinary expert panel reached a consensus on multiple potential best practices for complex discharge preparation from regional children's hospital NICUs. Better support for families navigating the complex NICU discharge process has the potential to improve infant health outcomes.

Racial and Ethnic Disparities in Sudden Unexpected Infant Death Among US Infants Born Preterm.

OBJECTIVE: To investigate among US infants born at <37 weeks gestation (a) racial and ethnic disparities in sudden unexpected infant death (SUID) and (b) state variation in SUID rates and non-Hispanic Black (NHB)-non-Hispanic White (NHW) SUID disparity ratio. METHODS: In this retrospective cohort analysis of linked birth and death certificates from 50 states from 2005 to 2014, SUID was defined by the following International Classification of Diseases, 9th or 10th edition, codes listed on death certificates: (7980, R95 or Recode 135; ASSB: E913, W75 or Recode 146; Unknown: 7999 R99 or Recode 134). Multivariable models were used to assess the independent association between maternal race and ethnicity and SUID, adjusting for several maternal and infant characteristics. The NHB-NHW SUID disparity ratios were calculated for each state. RESULTS: Among 4 086 504 preterm infants born during the study period, 8096 infants (0.2% or 2.0 per 1000 live births) experienced SUID. State variation in SUID ranged from the lowest rate of 0.82 per 1000 live births in Vermont to the highest rate of 3.87 per 1000 live births in Mississippi. Unadjusted SUID rates across racial and ethnic groups varied from 0.69 (Asian/Pacific Islander) to 3.51 (NHB) per 1000 live births. In the adjusted analysis, compared with NHW infants, NHB and Alaska Native/American Indian preterm infants had greater odds of SUID (aOR, 1.5;[95% CI, 1.42-1.59] and aOR, 1.44 [95% CI, 1.21-1.72]) with varying magnitude of SUID rates and NHB-NHW disparities across states. CONCLUSIONS: Significant racial and ethnic disparities in SUID among preterm infants exist with variation across US states. Additional research to identify the drivers of these disparities within and across states is needed.

NICU Visitation Time and Adherence to Safe Sleep Practices Among Mothers of Very Preterm Infants.

BACKGROUND: Sleep-associated infant death is the leading cause of postneonatal mortality in the United States. Preterm infants are at higher risk for sleep-associated death, but maternal adherence to safe sleep practices is lower than for mothers of full-term infants. Data are lacking on whether maternal neonatal intensive care unit (NICU) visitation time impacts safe sleep compliance after hospital discharge. PURPOSE: For mothers of preterm infants, to investigate the association of time days per week spent in the NICU and adherence to safe sleep practices after discharge. METHODS: A prospective observational study of 109 mothers with infants born at less than 32 weeks from 4 Colorado NICUs who completed a survey at 6 weeks after discharge about infant sleep practices. Maternal time spent in the NICU was defined as the average number of days spent in the NICU per week of infant hospitalization, as documented in the electronic medical record. Multivariable logistic regression models assessed the relationship between time in the NICU and safe sleep adherence. Covariates included maternal/infant characteristics significant at P < .2 level in bivariate analysis. RESULTS: Predictors of compliance with all safe infant sleep practices included public/no insurance compared with private insurance (adjusted odds ratio [AOR] 0.29; 95% confidence interval [CI] 0.09-0.96), some college/associate-level education versus bachelor's degree (AOR 5.88; 95% CI 1.21-28.67), and depression/anxiety symptoms (AOR 0.37; 95% CI 0.14-0.97). NICU visitation days was not associated with adherence to safe sleep practices. IMPLICATIONS FOR PRACTICE AND RESEARCH: Maternal visitation days was not associated with adherence to safe infant sleep practices after discharge, highlighting the need to identify barriers and facilitators to engaging families about SUID risk-reducing behaviors.

Association of Rural and Frontier Residence with Very Preterm and Very Low Birth Weight Delivery in Nonlevel III NICUs.

OBJECTIVE: Delivery of very preterm and very low birth weight neonates (VPT/VLBW) in a nonlevel III neonatal intensive care unit (NICU) increases risk of morbidity and mortality. Study objectives included the following: (1) Determine incidence of VPT/VLBW delivery (<32 weeks gestational age and/or birth weight <1,500 g), in nonlevel III units in Colorado; (2) Evaluate the independent association between residence and nonlevel III unit delivery; (3) Determine the incidence of and factors associated with postnatal transfer. STUDY DESIGN: This retrospective cohort study used 2007 to 2016 Colorado birth certificate data. Demographic and clinical characteristics by VPT/VLBW delivery in level III NICUs versus nonlevel III units were compared using Chi-square analyses. Multivariable logistic regression was used to estimate the independent association between residence and VPT/VLBW delivery. RESULTS: Among patients, 897 of 10,015 (8.96%) VPT/VLBW births occurred in nonlevel III units. Compared with infants born to pregnant persons in urban counties, infants born to those residing in rural (adjusted odds ratio [AOR] = 1.58, 95% confidence interval [CI]: 1.33, 1.88) or frontier (AOR = 3.19, 95% CI: 2.14, 4.75) counties were more likely to deliver in nonlevel III units and to experience postnatal transfer within 24 hours (rural AOR = 2.24, 95% CI: 1.60, 3.15; frontier AOR = 3.91, 95% CI: 1.76, 8.67). Compared with non-Hispanic Whites, Hispanics were more likely to deliver VPT/VLBW infants in nonlevel III units (AOR = 1.36, 95% CI: 1.15, 1.61). CONCLUSION: A significant number of VPT/VLBW neonates were born in nonlevel III units with associated disparities by race/ethnicity and nonurban residence. KEY POINTS: · Preterm delivery in a nonlevel III NICU increases risk of neonatal morbidity and mortality.. · A significant number of preterm deliveries in Colorado occur in hospitals with nonlevel III NICUs.. · Disparities in preterm delivery by race/ethnicity and nonurban residence exist..

Prevalence and Predictors of Pediatric COVID-19 Vaccine Acceptance.

OBJECTIVE: As pediatric COVID-19 vaccine eligibility expands, understanding predictors of vaccine intent is critical to effectively address parental concerns. Objectives included: (1) Evaluate maternal COVID-19 vaccine intent for child(ren) and associated predictors of stated intent; (2) Describe attitudes related to hypothetical vaccination policies; (3) Summarize themes associated with intention to vaccinate child(ren) for COVID-19. STUDY DESIGN: Mothers enrolled in Heath eMoms, a longitudinal survey project, were recruited for this electronic COVID-19 survey. Chi-square analysis was used to compare proportions of respondent characteristics based on vaccination intent. Population survey logistic regression was used for multivariable modeling to assess the independent association between vaccine intent and demographics. RESULTS: The response rate was 65.3% (n = 1884); 44.2% would choose vaccination, 20.3% would not choose vaccination, and 35.5% are unsure whether to have their child(ren) vaccinated for COVID-19. Black mothers (AOR 0.26, 95% CI 0.13, 0.54), respondents with less than high school education (AOR 0.26, 95% 0.12, 0.56) and those in rural areas (AOR 0.28, 95% CI 0.16, 0.48) were less likely to choose vaccination. Commonly cited reasons for vaccine hesitancy include the belief that the vaccine was not tested enough, is not safe, and there are concerns regarding its side effects. CONCLUSION: Over 50% of respondents do not intend or are unsure about their intent to vaccinate their child(ren) for COVID-19 with variability noted by demographics. Opportunities exist for perinatal and pediatric providers to educate pregnant people, parents, and caregivers with a focus on addressing concerns regarding vaccine safety and efficacy. KEY POINTS: · COVID-19 vaccination rates remain suboptimal, especially in the pediatric population, with variation across states.. · We found that the prevalence of vaccine acceptance for young children is low.. · We highlight opportunities for providers to educate parents, focusing on addressing vaccine safety and efficacy..

Defining an Infant's Race and Ethnicity: A Systematic Review.

CONTEXT: Infant race and ethnicity are used ubiquitously in research and reporting, though inconsistent approaches to data collection and definitions yield variable results. The consistency of these data has an impact on reported findings and outcomes. OBJECTIVE: To systematically review and examine concordance among differing race and ethnicity data collection techniques presented in perinatal health care literature. DATA SOURCES: PubMed, CINAHL, and Ovid were searched on June 17, 2021. STUDY SELECTION: English language articles published between 1980 and 2021 were included if they reported on the United States' infant population and compared 2 or more methods of capturing race and/or ethnicity. DATA EXTRACTION: Two authors independently evaluated articles for inclusion and quality, with disagreements resolved by a third reviewer. RESULTS: Our initial search identified 4329 unique citations. Forty articles passed title/abstract review and were reviewed in full text. Nineteen were considered relevant and assessed for quality and bias, from which 12 studies were ultimately included. Discordance in infant race and ethnicity data were common among multiple data collection methods, including those frequently used in perinatal health outcomes research. Infants of color and those born to racially and/or ethnically discordant parents were the most likely to be misclassified across data sources. LIMITATIONS: Studies were heterogeneous in methodology and populations of study and data could not be compiled for analysis. CONCLUSIONS: Racial and ethnic misclassification of infants leads to inaccurate measurement and reporting of infant morbidity and mortality, often underestimating burden in minoritized populations while overestimating it in the non-Hispanic/Latinx white population.

Comparisons of Three Measures of Maternal Engagement Activities in the Neonatal Intensive Care Unit.

BACKGROUND: Mothers' engagement with their hospitalized preterm infant(s) is recognized as an important aspect of treatment in neonatal intensive care units (NICUs). However, no gold standard exists for measuring maternal engagement, and the various methods used to measure mothers' time have documented limitations. OBJECTIVES: This study sought to compare three measurement methods of maternal engagement (a five-item maternal cross-sectional survey, time use diaries, and electronic health records [EHRs]) to identify whether these methods capture consistent data and patterns in detected differences in measures of engagement. METHODS: Maternal engagement was defined as time spent visiting the infant in the NICU (presence), holding (blanket holding in the mother's arms or by kangaroo care [KC]), and caregiving (e.g., bathing and changing diapers). The survey estimating daily maternal engagement was administered in two Level III NICUs and one Level IV NICU at study enrollment, at least 2 weeks after admission. Mothers then completed the daily time use diaries until infant discharge. Data were also collected from participants' EHRs, charted by nursing staff. Wilcoxon signed-rank tests were used for pairwise analysis of the three measures for maternal engagement activities. RESULTS: A total of 146 participants had data across all three measurement types and were included in the analysis. In the Level III NICUs (n = 101), EHR data showed significantly more time spent with all engagement activities than the diary data. In the Level IV data, only differences in time holding were significant when comparing EHR data with survey data, with mothers reporting more time doing KC and less time blanket holding. Comparison of EHR data with diary data showed more time in all activities except KC. DISCUSSION: In most cases, time spent in engagement activities measured in the EHR was higher than in the surveys or time use diaries. Accuracy of measurements could not be determined because of limitations in data collection, and there is no gold standard for comparison. Nevertheless, findings contribute to ongoing efforts to develop the most valuable and accurate strategies for measuring maternal engagement-a significant predictor of maternal and infant health.

Impact of Coronavirus Disease-19 "Stay-At-Home" Orders on Preterm Birth in Colorado.

In this retrospective cohort analysis of Colorado birth certificate records from April to December 2015-2020, we demonstrate that Colorado birthing individuals experienced lower adjusted odds of preterm birth after issuance of coronavirus-19 "stay-at-home" orders. However, this positive birth outcome was experienced only by non-Hispanic white and Hispanic mothers.

The Association of Social Factors and Time Spent in the NICU for Mothers of Very Preterm Infants.

OBJECTIVES: Evaluate the association between maternal social factors and maternal time spent in the NICU for very preterm infants admitted to 4 level III and IV NICUs. METHODS: In this prospective observational cohort study, we enrolled mother-infant dyads whose infants were born <32 weeks' gestation. Enrollment occurred after 2 weeks of NICU exposure, when maternal social factors and demographic information was collected. Maternal time spent in the NICU was abstracted from the electronic medical record and was dichotomized into 0 to 6 days and ≥6 days per week. Demographic differences between the 2 groups were compared by using χ2 tests. Logistic regression was used to assess the independent association between maternal social factors and the average number of days per week spent in the NICU. RESULTS: A total of 169 mother-infant dyads were analyzed. Maternal social factors associated with more time spent in the NICU included an annual household income of >$100 000, compared with those with an annual household income of <$50 000 (adjusted odds ratio [aOR]: 5.68; 95% confidence interval [CI] 1.77-18.19), a travel time <30 minutes to the NICU (compared with those who traveled >60 minutes [aOR: 7.85; 95% CI 2.81-21.96]), and the lack of other children in the household, compared with women with other children (aOR: 3.15; 95% CI 1.39-7.11). CONCLUSIONS: Maternal time spent in the NICU during a prolonged birth hospitalization of a very preterm infant differed by socioeconomic status, travel time, and presence of other dependents. Strategies to better identify and reduce these disparities to optimize engagement and, subsequently, improve infant health outcomes is needed.

Racial/Ethnic Differences in Prenatal and Postnatal Counseling About Maternal and Infant Health-Promoting Practices Among Teen Mothers.

STUDY OBJECTIVE: Disparities in perinatal counseling among all pregnant women exist, yet teen data are lacking. We evaluated racial/ethnic differences in (1) prenatal and (2) postnatal counseling of teen mothers. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study included Pregnancy Risk Assessment Monitoring System data from 2012-2016 and included mothers 19 years of age and younger. INTERVENTIONS AND MAIN OUTCOME MEASURES: Counseling measures included tobacco, alcohol and illicit drugs, weight gain, HIV testing, influenza vaccination, breastfeeding, infant safe sleep, postpartum depression, and contraception. Bivariate associations of maternal/infant characteristics and counseling were estimated using χ2 tests. Multivariable logistic regression was used to assess the independent relationship between race/ethnicity and counseling. RESULTS: A weighted sample of 544,930 teen mothers was analyzed. Compared with non-Hispanic white (NHW) teens, non-Hispanic black teens were more likely to receive counseling on tobacco (adjusted odds ratio [aOR], 1.4; 95% confidence interval [CI], 1.10-1.77), alcohol (aOR, 1.77; 95% CI, 1.28-2.46), illicit drugs (aOR, 1.79; 95% CI, 1.33-2.41), and HIV testing (aOR, 1.62; 95% CI, 1.26-2.09). Compared with NHW teens, Hispanic teens were less likely to receive tobacco counseling (aOR, 0.78; 95% CI, 0.64-0.97) and more likely to receive influenza vaccine counseling (aOR, 1.44; 95% CI, 1.18-1.76). No difference was found in receipt of postnatal counseling. CONCLUSION: Racial/ethnic differences in receipt of perinatal counseling exist, with non-Hispanic black teens being more likely to receive counseling on substance use and HIV testing and Hispanic teens being more likely to receive influenza vaccine recommendations compared with NHW teens. Ongoing investigation is needed to understand drivers of these differences.

The Colorado Hospitals Substance Exposed Newborn Quality Improvement Collaborative: Standardization of Care for Opioid-Exposed Newborns Shortens Length of Stay and Reduces Number of Infants Requiring Opiate Therapy.

OBJECTIVES: To decrease the average length of stay (LOS) of opioid-exposed newborns (OENs) by 20% from baseline from April 2017 to December 2019. METHODS: The Colorado Hospitals Substance Exposed Newborn Quality Improvement Collaborative is a consortium of neonatal providers, public health experts, and legislative experts that provides infrastructure and resources for Colorado birthing hospitals to undertake initiatives focused on improving the care of OENs. The Colorado Hospitals Substance Exposed Newborn Quality Improvement Collaborative was started in September 2017 and includes 19 birthing hospitals in Colorado, with 12 contributing data to the centralized database. The interventions were focused on (1) hospital engagement and (2) increasing nonpharmacologic care (by using the Eat, Sleep, Console assessment tool; developing guidelines for breastfeeding eligibility; employing comfort measures before pharmacologic therapy; and administering opiate therapy on an as-needed basis). RESULTS: From April 2017 to December 2019, 787 OENs were identified. Among infants ≥35 weeks' gestational age without other medical diagnoses (n = 647), statistical process control charts revealed significant reduction in the primary outcome of interest, average hospital LOS, from 14.8 to 5.9 days. For all OENs, receipt of pharmacologic therapy declined from 61% to 23%. Among OENs who received pharmacologic therapy (and were ≥35 weeks' gestational age without other medical diagnoses), average LOS also declined from 21.9 to 8.0 days. CONCLUSIONS: Through standardization of OEN care focused on family engagement and nonpharmacologic care, this statewide collaborative reduced average LOS, the percentage of OENs requiring opiate therapy, and average LOS for OENs requiring opiate therapy.

Effects of chronic hyperinsulinemia on metabolic pathways and insulin signaling in the fetal liver.

The effect of chronic of hyperinsulinemia in the fetal liver is poorly understood. Here, we produced hyperinsulinemia with euglycemia for ∼8 days in fetal sheep [hyperinsulinemic (INS)] at 0.9 gestation. INS fetuses had increased insulin and decreased oxygen and amino acid (AA) concentrations compared with saline-infused fetuses [control (CON)]. Glucose (whole body) utilization rates were increased, as expected, in INS fetuses. In the liver, however, there were few differences in genes and metabolites related to glucose and lipid metabolism and no activation of insulin signaling proteins (Akt and mTOR). There was increased p-AMPK activation and decreased mitochondrial mass (PGC1A expression, mitochondrial DNA content) in INS livers. Using an unbiased multivariate analysis with 162 metabolites, we identified effects on AA and one-carbon metabolism in the INS liver. Expression of the transaminase BCAT2 and glutaminase genes GLS1 and GLS2 was decreased, supporting decreased AA utilization. We further evaluated the roles of hyperinsulinemia and hypoxemia, both present in INS fetuses, on outcomes in the liver. Expression of PGC1A correlated only with hyperinsulinemia, p-AMPK correlated only with hypoxemia, and other genes and metabolites correlated with both hyperinsulinemia and hypoxemia. In fetal hepatocytes, acute treatment with insulin activated p-Akt and decreased PGC1A, whereas hypoxia activated p-AMPK. Overall, chronic hyperinsulinemia produced greater effects on amino acid metabolism compared with glucose and lipid metabolism and a novel effect on one-carbon metabolism in the fetal liver. These hepatic metabolic responses may result from the downregulation of insulin signaling and antagonistic effects of hypoxemia-induced AMPK activation that develop with chronic hyperinsulinemia.