The impact of exclusive human milk diet on short-term growth of very preterm infants.

OBJECTIVES: The impact of exclusive human milk diet (EHMD) on postnatal growth remains controversial. This study aims to investigate the association between EHMD and short-term growth. METHODS: This multicenter retrospective study aims to compare growth between the EHMD and non-EHMD groups among infants <32 weeks of gestation. Primary outcomes include weight, length, and head circumference growth trajectories between birth and 34 weeks postmenstrual age. Sensitivity and subgroup analyses were performed. RESULTS: An EHMD was independently associated with poorer length growth, especially in infants born at ≥28 weeks' gestation or those exposed to hypertensive disorders of pregnancy. While initiating fortification at <26 kcal/oz on an EHMD showed inferior growth, initiating fortification at ≥26 kcal/oz was associated with improved weight growth, and similar length and head circumference growth when compared to the non-EHMD group. CONCLUSIONS: An EHMD with initial fortification at ≥26 kcal/oz may be implemented to avoid bovine milk exposure while sustaining comparable growth.

Institutional and Regional Variation in Opioid Prescribing for Hospitalized Infants in the US.

Importance: High-risk infants, defined as newborns with substantial neonatal-perinatal morbidities, often undergo multiple procedures and require prolonged intubation, resulting in extended opioid exposure that is associated with poor outcomes. Understanding variation in opioid prescribing can inform quality improvement and best-practice initiatives. Objective: To examine regional and institutional variation in opioid prescribing, including short- and long-acting agents, in high-risk hospitalized infants. Design, Setting, and Participants: This retrospective cohort study assessed high-risk infants younger than 1 year from January 1, 2016, to December 31, 2022, at 47 children's hospitals participating in the Pediatric Health Information System (PHIS). The cohort was stratified by US Census region (Northeast, South, Midwest, and West). Variation in cumulative days of opioid exposure and methadone treatment was examined among institutions using a hierarchical generalized linear model. High-risk infants were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for congenital heart disease surgery, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and other abdominal surgery. Infants with neonatal opioid withdrawal syndrome, in utero substance exposure, or malignant tumors were excluded. Exposure: Any opioid exposure and methadone treatment. Main Outcomes and Measures: Regional and institutional variations in opioid exposure. Results: Overall, 132 658 high-risk infants were identified (median [IQR] gestational age, 34 [28-38] weeks; 54.5% male). Prematurity occurred in 30.3%, and 55.3% underwent surgery. During hospitalization, 76.5% of high-risk infants were exposed to opioids and 7.9% received methadone. Median (IQR) length of any opioid exposure was 5 (2-12) cumulative days, and median (IQR) length of methadone treatment was 19 (7-46) cumulative days. There was significant hospital-level variation in opioid and methadone exposure and cumulative days of exposure within each US region. The computed intraclass correlation coefficient estimated that 16% of the variability in overall opioid prescribing and 20% of the variability in methadone treatment was attributed to the individual hospital. Conclusions and Relevance: In this retrospective cohort study of high-risk hospitalized infants, institution-level variation in overall opioid exposure and methadone treatment persisted across the US. These findings highlight the need for standardization of opioid prescribing in this vulnerable population.

Uncertainty and the NICU Experience: A Qualitative Evaluation of Family and Provider Perspectives.

There is limited information regarding caregiver and provider perspectives on uncertainty across the continuum of the neonatal intensive care unit (NICU) experience. Open-ended semi-structured interviews were conducted with providers and English- and Spanish-speaking caregivers of infants with a history of admission to a quaternary safety-net NICU. Major themes were generated using inductive-deductive thematic analysis. Seventy-six individuals participated in the study: 47 caregivers and 29 providers. The median gestational age of the infants was 29 weeks and 85% were classified as having chronic complex disease per the Pediatric Medical Complexity Algorithm. Most providers were neonatologists (37%) and nurses (27%) and more than half had over ten years of experience. A conceptual model of caregiver uncertainty was developed and key domains included drivers of uncertainty and its impact, and factors influencing coping and adaptation. Our analysis found a positive association between caregiver information gathering, clinical continuity, support systems, maternal mental health supports, and witnessing a child's progress and the development of adjustment to chronic uncertainty. These results suggest key areas for intervention that can promote parental adaptation to the uncertainty inherent in the NICU experience.

Current Trends in Invasive Closure of Patent Ductus Arteriosus in Very Low Birth Weight Infants in United States Children's Hospitals, 2016-2021.

OBJECTIVE: To describe the current practices in invasive patent ductus arteriosus (PDA) closure (surgical ligation or transcatheter occlusion) in very low birth weight (VLBW) infants and changes in patient characteristics and outcomes from 2016 to 2021 among US children's hospitals. STUDY DESIGN: We evaluated a retrospective cohort of VLBW infants (birth weight 400-1499 g and gestational age 22-31 weeks) who had invasive PDA closure within 6 months of age from 2016 to 2021 in children's hospitals in the Pediatric Health Information System. Changes in patient characteristics and outcomes over time were evaluated using generalized linear models and generalized linear mixed models. RESULTS: 2418 VLBW infants (1182 surgical ligation; 1236 transcatheter occlusion) from 42 hospitals were included. The proportion of infants receiving transcatheter occlusion increased from 17.2% in 2016 to 84.4% in 2021 (P < .001). In 2021, 28/42 (67%) hospitals had performed transcatheter occlusion in > 80% of their VLBW infants needing invasive PDA closure, compared with only 2/42 (5%) in 2016. Although median postmenstrual age (PMA) at PDA closure did not change for the overall cohort, PMA at transcatheter occlusion decreased from 38 weeks in 2016 to 31 weeks by 2020, P < .001. Among those infants not intubated prior to PDA closure, extubation within 3 days postprocedure increased over time (yearly adjusted odds ratios of 1.26 [1.08-1.48]). Length of stay and mortality did not change over time. CONCLUSION: We report rapid adoption of transcatheter occlusion for PDA among VLBW infants in US children's hospitals over time. Transcatheter occlusions were performed at younger PMA over time.

Mobile applications to support parents in the transition from neonatal intensive care unit to home: a narrative review.

Background and Objective: Among the unique challenges for parents in the transition of infant care from neonatal intensive care unit (NICU) to home are the medical complexity of their babies and the psychological burden of caring for this special patient population. Despite the increased use and accessibility of smartphones, mobile applications (apps) intended for use by families during this transition remain underdeveloped and understudied. Apps to support parents of infants in the NICU represent an accessible potential solution to mitigate existing disparities in follow up. Through this Narrative Review, we intend to describe the characteristics of and development process for apps intended to address the challenges parents with NICU babies may face, and to provide recommendations for further development of apps for this purpose. Methods: We conducted a review of articles published between November 2012 to November 2022. This search spanned three major databases, PubMed, Embase, and CINAHL, using a controlled vocabulary and keywords for mobile apps and the NICU. These three databases generated 473 articles for review. Utilizing the online primary screening and data extraction tool Covidence, we ultimately included eight articles in this narrative review. Key Content and Findings: There are few existing mobile apps intended to ease the transition home for parents of babies in the NICU. There are even fewer apps that have been critically evaluated using acceptable methods and produced with contribution from healthcare practitioners. Among the existing articles on app solutions to benefit education and socioemotional support for parents, many emphasized the importance of including key stakeholders during the app development process and highlighted both qualitative and quantitative measures for assessing relative success of these apps in a clinical setting. Conclusions: Although the experiences of parents with infants admitted to the NICU have been well-studied, there remain relatively few existing apps to provide educational and socioemotional support to this population. Future studies should focus on an iterative process of app development whereby both parents and providers are closely involved, in combination with critical appraisal of the app to assess for appropriate support and education of caregivers.

Opioid and Methadone Use for Infants With Surgically Treated Necrotizing Enterocolitis.

Importance: Necrotizing enterocolitis (NEC) requiring surgical intervention is the most common reason for surgical procedures in preterm neonates. Opioids are used to manage postoperative pain, with some infants requiring methadone to treat physiologic opioid dependence or wean from nonmethadone opioid treatment during recovery. Objective: To describe postoperative opioid use and methadone treatment for infants with surgically treated NEC and evaluate postoperative outcomes. Design, Setting, and Participants: A cohort study of infants with surgically treated NEC admitted from January 1, 2013, to December 31, 2022, to 48 Children's Hospital Association hospitals contributing data to the Pediatric Health Information System (PHIS) was performed. Infants who received methadone preoperatively, were aged 14 days or less at the time of the operation, had a congenital heart disease-related operation, or died within 90 days of the operation were excluded. Mixed-effects multivariable logistic regression was used to evaluate thresholds for duration of opioid use after the operation associated with methadone treatment and clinical outcomes associated with methadone use were enumerated. Exposure: Postoperative administration of nonmethadone opioids. Main Outcomes and Measures: Methadone use and postoperative length of stay, ventilator days, and total parenteral nutrition (TPN) days. Results: Of the 2037 infants with surgically treated NEC identified, the median birth weight was 920 (IQR, 700.0-1479.5) g; 1204 were male (59.1%), 911 were White (44.7%), and 343 were Hispanic (16.8%). Infants received nonmethadone opioids for a median of 15 (IQR, 6-30) days after the operation and 231 received methadone (11.3%). The median first day of methadone use was postoperative day 18 (IQR, days 9-64) and continued for 28 days (IQR, 14-73). Compared with infants who received nonmethadone opioids for 1 to 5 days, infants receiving 16 to 21 days of opioids were most likely to receive methadone treatment (odds ratio, 11.45; 95% CI, 6.31-20.77). Methadone use was associated with 21.41 (95% CI, 10.81-32.02) more days of postoperative length of stay, 10.80 (95% CI, 3.63-17.98) more ventilator days, and 16.21 (95% CI, 6.34-26.10) more TPN days. Conclusions and Relevance: In this cohort study of infants with surgically treated NEC, prolonged use of nonmethadone opioids after the operation was associated with an increased likelihood of methadone treatment and increased postoperative length of stay, ventilation, and TPN use. Optimizing postoperative pain management for infants requiring an operation may decrease the need for methadone treatment and improve health care use.

Disparities and Early Engagement Associated with the 18- to 36-Month High-Risk Infant Follow-Up Visit among Very Low Birthweight Infants in California.

OBJECTIVE: To determine follow-up rates for the high-risk infant follow-up (HRIF) visit at 18-36 months among infants with very low birthweights and identify factors associated with completion. STUDY DESIGN: We completed a retrospective cohort study using linked California Perinatal Quality of Care Collaborative neonatal intensive care unit, California Perinatal Quality of Care Collaborative California Children's Services HRIF, and Vital Statistics Birth Cohort databases. We identified maternal, sociodemographic, neonatal, clinical, and HRIF program level factors associated with the 18- to 36-month follow-up using multivariable Poisson regression. RESULTS: From 2010 to 2015, among 19 284 infants with very low birthweight expected to attend at least 1 visit at 18-36 months, 10 249 (53%) attended. On multivariable analysis, factors independently associated with attendance at an 18- to 36-month visit included estimated gestational age (relative risk [RR], 1.21; 95% CI, 1.15-1.26; <26 weeks vs ≥31 weeks), maternal education (RR, 1.09; 95% CI, 1.06-1.12; college degree or more vs high school), distance from clinic (RR, 0.92; 95% CI, 0.89-0.97; fourth quartile vs first quartile), and Black non-Hispanic race vs White race (RR, 0.88; 95% CI, 0.84-0.92). However, completion of an initial HRIF visit within the first 12 months was the factor most strongly associated with completion of an 18- to 36-month visit (RR, 6.47; 95% CI, 5.91-7.08). CONCLUSIONS: In a California very low birthweight cohort, maternal education, race, and distance from the clinic were associated with sustained HRIF participation, but attendance at a visit by 12 months was the most significantly associated factor. These findings highlight the importance of early engagement with all families to ensure equitable follow-through for children born preterm.

Variation in Family Involvement on Rounds Between English-Speaking and Spanish-Speaking Families.

BACKGROUND: Family-centered rounds (FCR) is the standard of care in inpatient pediatrics. Results of studies have revealed that Spanish-speaking families can experience communication challenges and decreased empowerment on rounds. In our study, we aim to identify variation in FCR practices for Spanish-speaking compared to English-speaking families and factors contributing to these disparities. METHODS: This is a cross-sectional observational study performed by secondary analysis of a quality improvement initiative conducted at a quaternary children's hospital. Data were collected from June 2019 to March 2020 by using observational audits. Encounters were analyzed to compare key elements of FCR (including rounds location, elicitation of family questions, involvement in discharge planning) for English-speaking and Spanish-speaking families. Multivariable logistic regression was used to compare family involvement in FCR. A sensitivity analysis was conducted to evaluate unmeasured confounding. RESULTS: Rounding encounters included 394 families (261 English-speaking and 133 Spanish-speaking). Fewer Spanish-speaking families were included in the medical team's discussion on rounds (64.7% vs 76.3%, P = .017), were asked about questions at the start of rounds (44.4% vs 56.3%, P = .025), or were involved in discussion of discharge criteria (72.2% vs 82.8%, P = .018) when compared to English-speaking families. These differences were magnified for resident teams rounding with subspecialists. The finding of decreased family involvement in the discussion on rounds persisted after adjusting for patient age and team type. CONCLUSIONS: Spanish-speaking families were less likely to be involved in FCR compared to English-speaking families. Further investigation is needed to explore the root causes of this practice variation and to develop interventions to address disparities.

Designing a Mobile Health Solution to Facilitate the Transition from NICU to Home: A Qualitative Study.

There is limited information about caregiver and provider perspectives regarding the design of a mobile health solution to facilitate the transition from the neonatal intensive care unit (NICU) to home. Focus groups were conducted with English- or Spanish-speaking families enrolled in an urban high-risk infant follow-up clinic and with their care providers. We generated salient themes using an inductive thematic analysis. Twenty-two participants completed the study. Among caregivers, the infant's median gestational age (IQR) was 29 (23, 34) weeks and 63% were Hispanic. Among the providers, 55% had practiced for more than 10 years and 18% were bilingual. Key stakeholder (family and provider) priorities for designing a mobile health solution were organized into eight domains, i.e., implementation ideas around user interface and timing, providing path planning and information, increasing support, improving engagement with providers and services, mitigating barriers to care after discharge and strengthening parenting role and confidence. The results from this study suggest that families and healthcare providers prioritize path planning, information and support as the pillars for designing an effective NICU-to-home transition mobile health application. Implications for product development include family empowerment, being a credible source of information and creating a resource for caregiver support and mental health.

Neonates with mild hypoxic-ischaemic encephalopathy receiving supportive care versus therapeutic hypothermia in California.

OBJECTIVE: The use of therapeutic hypothermia (TH) for mild hypoxic-ischaemic encephalopathy (HIE) remains controversial and inconsistent. We analysed trends in TH and maternal and infant characteristics associated with short-term outcomes of infants with mild HIE. DESIGN: Retrospective cohort analysis of the California Perinatal Quality Care Collaborative database 2010-2018. E-value analysis was conducted to determine the potential impact of unmeasured confounding. SETTING: California neonatal intensive care units. PATIENTS: 1364 neonates with mild HIE. INTERVENTIONS: Supportive care versus TH. MAIN OUTCOME MEASURES: Factors associated with TH and mortality. RESULTS: The proportion of infants receiving TH increased from 46% in 2010 to 79% in 2018. TH was more likely in the setting of singleton birth (OR 2.69, 95% CI 1.21 to 5.39), no major birth defects (OR 2.18, 95% CI 1.42 to 3.30), operative vaginal delivery (OR 3.04, 95% CI 1.80 to 5.10) and 5-minute Apgar score ≤5 (OR 3.17, 95% CI 2.43 to 4.13). Mortality was associated with small for gestational age (OR 5.79, 95% CI 1.90 to 18.48), <38 weeks' gestation (OR 7.31 95% CI 2.39 to 24.93), major birth defects (OR 11.62, 95% CI 3.97 to 38.00), inhaled nitric oxide (OR 12.73, 95% CI 4.00 to 44.53) and nosocomial infection (OR 7.98, 95% CI 1.15 to 47.03). E-value analyses suggest that unmeasured confounding may have contributed to some of the observed effects. CONCLUSIONS: Variation in management of mild HIE persists, but therapeutic drift has become more prevalent over time. Further studies are needed to assess long-term outcomes alongside resource utilisation to inform evidence-based practice.

The financial burden experienced by families of preterm infants after NICU discharge.

BACKGROUND AND OBJECTIVES: Describe the financial burden and worry that families of preterm infants experience after discharge from the neonatal intensive care unit (NICU). METHODS: We surveyed 365 parents of preterm infants in a cross-sectional study regarding socio-demographics, supplemental security income (SSI), and financial worry. We completed a multivariable logistic regression model to examine the adjusted association of financial worry with modifiable factors. RESULTS: We found that 53% of participants worried about healthcare costs after NICU discharge. After adjusting for socio-demographic and infant characteristics, we identified that, aOR (95% CI), out-of-pocket costs from the NICU index hospitalization, 3.51 (1.7, 7.26) and durable medical equipment use, 2.41 (1.11, 5.23) was associated with increased financial worry while enrollment in SSI, 0.38 (0.19, 0.76) was associated with decreased financial worry. CONCLUSIONS: We identified factors that could contribute to financial burden after NICU discharge that may advise future work to target financial support systems.

Predictors of venous thromboembolism among infants in children's hospitals in the United States: a retrospective Pediatric Health Information Study.

OBJECTIVES: Examine: (1) Prevalence of diagnosed venous thromboembolism (VTE) in infants <6 months discharged from U.S. NICUs; (2) Associations between sociodemographic and clinical factors and VTE; (3) Secondary outcomes related to VTE. STUDY DESIGN: Multivariable logistic regressions examined associations between VTE and sociodemographic and clinical factors among infants <6 months discharged from Pediatric Health Information System (PHIS) NICUs between 2016 and 2019. RESULTS: Of 201,033 infants, 2720 (1.35%) had diagnosed VTE. Birthweight 300-1000 g (aOR 3.14, 95% CI 2.54-3.88), 1000-1500 g (aOR 1.77, 95% CI 1.40-2.42) versus 2500-3999 g, and public (aOR 1.18, 95% CI 1.02-1.37) versus private insurance were associated with increased odds of VTE, as were CVC, TPN, mechanical ventilation, infection, ECMO, and surgery. All types of central lines (non-tunneled and tunneled CVCs, PICCs, and umbilical catheters) had higher odds of VTE than not having that type of line. CVCs in upper versus lower extremities had higher odds of VTE. CONCLUSION: Infants with risk factors may require monitoring for VTE. Results may inform VTE prevention.

Connecting to Early Intervention Services After Neonatal Intensive Care Unit Discharge in a Medicaid Sample.

OBJECTIVE: To describe caregiver perspectives regarding connecting to early intervention (EI) services after neonatal intensive care unit discharge in a Medicaid sample. METHODS: Open-ended semistructured interviews and focus groups were conducted with English- or Spanish-speaking families enrolled in Medicaid in an urban high-risk infant follow-up clinic at a safety-net center, which serves preterm and high-risk term infants. We generated salient themes using inductive-deductive thematic analysis. RESULTS: Thirty-two participants completed the study. The infant's median (interquartile range) birth weight was 1365 (969, 2800) grams; 50% were Hispanic; 31% reported living in a neighborhood with fourth quartile economic hardship. Eighty-one percent were classified as having chronic complex disease per the Pediatric Medical Complexity Algorithm and 63% had a diagnosis of developmental delay. A conceptual model was constructed and the analysis revealed major themes describing families' challenges and ideas to facilitate connection to EI. We identified subthemes related to the person in environment: health care environment/support and socio-economic resources, parent perspectives and built environment; provider level factors such as appointment scheduling, staff limitations, and parent suggestions to improve health care and service navigation, which included improved information sharing, the importance of patient advocates, video resources, early referrals to EI facilitated by the discharging hospital and system workarounds. CONCLUSIONS: The results from this study may provide a granular roadmap for providers to help facilitate referrals to EI services. We identified several ideas such as using advocates and providing transitional resources, including online media, that might improve the connection to EI services.

The association of inborn status and resource utilization among neonates who received extracorporeal membrane oxygenation.

BACKGROUND: Many studies have established that extracorporeal membrane oxygenation (ECMO) can be a cost-effective treatment in some populations, but limited data exist on which factors are associated with length of stay (LOS) and total hospital costs. This study aimed to determine if inborn (i.e., cared for in their birth hospitals) neonates who receive ECMO have different resource utilization and outcomes compared to outborn (i.e., not cared for in their birth hospitals) neonates who receive ECMO. METHODS: A retrospective cohort study was conducted using the Healthcare Cost and Utilization Project's Kids' Inpatient Database from 1997-2012. Neonates (infants, <28 days) placed on ECMO were categorized as either inborn or outborn. Salient clinical characteristics were compared between groups. A multivariable analysis was performed to identify the factors associated with length of stay (LOS), total hospital costs, and mortality in these two patient populations. RESULTS: Of 5,152 neonates receiving ECMO, 800 were inborn and 4,352 were outborn. Inborn neonates were more frequently diagnosed with cardiac-related diagnoses (70.5% vs 62.1%, p < 0.001). After adjusting for demographics and hospital-level factors, inborn neonates had longer hospital LOS (13.2 days, 95% CI, 8.7-18.7; p < 0.001), higher total encounter costs ($62,000, 95% CI, 40,000-85,000; p < 0.001) and higher mortality (OR 2.4, 95% CI 1.9-2.9; p < 0.001) compared to outborn neonates. CONCLUSIONS: Inborn neonates placed on ECMO were more frequently diagnosed with cardiac-related diseases or congenital diaphragmatic hernia, had longer LOS, higher total encounter costs, and higher mortality rates relative to their outborn counterparts, and likely represent a higher risk population. These two populations of infants may be inherently different and their differences should be further explored to inform decision making about optimal site of delivery.

Maternal post-traumatic stress and depression symptoms and outcomes after NICU discharge in a low-income sample: a cross-sectional study.

BACKGROUND: Having a preterm newborn and the experience of staying in the neonatal intensive care unit (NICU) has the potential to impact a mother's mental health and overall quality of life. However, currently there are few studies that have examined the association of acute post-traumatic stress (PTS) and depression symptoms and infant and maternal outcomes in low-income populations. DESIGN/ METHODS: In a cross-sectional study, we examined adjusted associations between positive screens for PTS and depression using the Perinatal Post-traumatic stress Questionnaire (PPQ) and the Patient Health-Questionnaire 2 (PHQ-2) with outcomes using unconditional logistic and linear regression models. RESULTS: One hundred sixty-nine parents answered the questionnaire with 150 complete responses. The majority of our sample was Hispanic (68%), non-English speaking (67%) and reported an annual income of <$20,000 (58%). 33% of the participants had a positive PPQ screen and 34% a positive PHQ-2 screen. After adjusting for confounders, we identified that a positive PHQ-2 depression score was associated with a negative unit (95% CI) change on the infant's Vineland Adaptive Behavior Scales, second edition of - 9.08 (- 15.6, - 2.6) (p < 0.01). There were no significant associations between maternal stress and depression scores and infant Bayley Scales of Infant Development III scores or re-hospitalizations or emergency room visits. However, positive PPQ and screening score were associated with a negative unit (95% CI) unit change on the maternal Multicultural Quality of Life Index score of - 8.1 (- 12, - 3.9)(p < 0.01) and - 7.7 (- 12, - 3) (p = 0.01) respectively. CONCLUSIONS: More than one-third of the mothers in this sample screened positively for PTS and depression symptoms. Screening scores positive for stress and depression symptoms were associated with a negative change in some infant development scores and maternal quality of life scores. Thoughtful screening programs for maternal stress and depression symptoms should be instituted.