The Ladder of Inference as a tool to reduce implicit bias in pediatric clinical practice.

Implicit bias in healthcare professionals is a widespread phenomenon that leads to worse healthcare outcomes for marginalized patient populations. One tool that can help providers identify when biases are impacting the clinical care they are providing and enable them to take corrective action in real time is the "Ladder of Inference" (LOI). The LOI is an instrument that elucidates the process by which we take in information about another person, filter that data through our own interests, needs, perspectives and biases, and then use it to draw conclusions about the individual. These conclusions are often profoundly inaccurate, yet we then act upon them. Thus, we propose the LOI as an "implicit bias detection tool" for neonatal intensive care unit (NICU) clinical practice. We demonstrate on two common NICU cases how utilizing the LOI can uncover mechanisms by which positive and negative feedback loops secondary to unregulated implicit bias lead to a stepwise increase or decrease in the quality of care. As the cases demonstrate, the subtle differences in individual steps up the ladder can lead to care differences of a large magnitude in either direction, hugely positive or detrimentally negative. This shift in the quality of care, then, may contribute to the significant neonatal outcome disparities in infants from minoritized groups. Using the LOI as a practical tool, we demonstrate how it becomes possible to detect one's own implicit biases and thus to consciously monitor the inferences we are making about patients and their families in order to counteract them.

Utility of do-not-resuscitate orders for critically ill infants in the NICU.

OBJECTIVE: To better understand the value of DNR orders for critically ill infants in the NICU. METHODS: A prospective mixed-methods approach was utilized including chart review of infants who died in a regional NICU over a twenty-six-month period and surveys of their neonatologists, neonatal fellows, and nurses. RESULTS: 40 infants died during the study period and 120 staff surveys were completed. Infants with DNR orders were of a higher gestational age at birth and a higher chronological age at death. Nurses were more likely to perceive benefit from DNR orders than physicians. Medical staff recollection of the existence of DNR orders was not always accurate. Time and fear of adding unnecessary emotional burden to parents were identified as barriers to DNR order implementation. An advanced care planning model built on open communication instead of DNR order documentation was deemed the best approach. CONCLUSION: Though DNR orders are beneficial for a subset of infants, DNR orders are likely not applicable for all infants who die in the NICU. More important is supportive, individualized communication between families and the medical team to ensure quality end-of-life care. IMPACT: In the adult and pediatric ICU literature, DNR orders are associated with improved qualitative "good death" assessments and decreased familial decision regret. In the NICU, rates of DNR usage aren't well reported and their overall utility is unclear. Though DNR orders can help guide clinical decision making in the NICU and may be associated with higher quality ethical discussion, our data suggest that they are not applicable in all patient cases. We hope that this work will help guide approaches to end-of-life care in the NICU and underscore the importance of frequent, open communication between families and their medical team.

The new normal: parental use of online health communities in the NICU.

BACKGROUND: The aim of this study was to identify if and why NICU families use online health communities (OHCs) and to assess how participation in these virtual spaces impacts relationships between parents and their child's medical team. METHODS: Surveys were administered to eligible persons. Quantitative analysis was conducted using standard statistical methods. Publicly accessible posts from the platform Reddit were aggregated and analyzed for recurring themes. RESULTS: In all, 58.3% (n = 141) of NICU parents surveyed endorsed OHC use, primarily for the purpose of connecting with other NICU families and alleviating distress regarding their child's health. Risks of OHCs as discussed in previous studies including health information privacy and medical misinformation were similarly identified. However, parents did not report a harmful association between OHC use and their relationship with their child's providers, with only 2.8, 4.3, and 2.8% of participants reporting an overall negative effect of OHC use on communication, trust, and confidence, respectively. CONCLUSIONS: OHCs are a commonly used resource that help NICU families build communities and reduce anxiety. These data suggest that OHCs do not inherently pose a threat to the parent-provider relationship and should be validated by the medical team as a valuable potential resource, while acknowledging the legitimate risks that exist. IMPACT: Use of OHCs is increasingly common among NICU parents; however, it has been met with concern by many medical professionals. Existing literature has not yet explored the effect on dynamics in the NICU. Overall, our data show that OHCs have become a vital resource for families looking to build community among NICU parents and reduce anxiety. Though risks do exist around patient privacy and access to medical misinformation, fears regarding the impact of OHC use on parent-provider relationships may be largely unfounded. By using data to demonstrate how OHCs benefit the NICU parent experience, we hope to reframe OHC use and allow physicians to validate engagement and therefore mitigate legitimate concerns.

Providing Support for Neonatal Intensive Care Unit Health Care Professionals: A Bereavement Debriefing Program.

OBJECTIVE: The aim of this study is to evaluate formal bereavement debriefing sessions after infant death on neonatal intensive care unit (NICU) staff. STUDY DESIGN: Prospective mixed methods study. Pre- and postbereavement debriefing intervention surveys were sent to clinical staff. Evaluation surveys were distributed to participants after each debriefing session. Notes on themes were taken during each session. RESULTS: More staff attended sessions (p < 0.0001) and attended more sessions (p < 0.0001) during the postdebriefing intervention epoch compared with the predebriefing epoch. Stress levels associated with the death of a patient whose family the care provider have developed a close relationship with decreased (p = 0.0123). An increased number of debriefing session participants was associated with infant age at the time of death (p = 0.03). Themes were (1) family and provider relationships, (2) evaluation of the death, (3) team cohesion, (4) caring for one another, and (5) emotional impact. CONCLUSION: Bereavement debriefings for NICU staff reduced the stress of caring for dying infants and contributed to staff well-being. KEY POINTS: · Providing end-of-life care in NICU is challenging.. · Debriefings assist staff in coping with grief.. · Staff well-being impacts patient care..

The Mother Baby Comfort Care Pathway: The Development of a Rooming-In-Based Perinatal Palliative Care Program.

BACKGROUND: Traditionally, the provision of comfort care and support during the dying process for infants born with life-limiting diagnoses has occurred in the neonatal intensive care unit (NICU). A major goal for the families of these infants is often the opportunity to spend as much time as possible with their infant in order to make memories and parent their infant. PURPOSE: The objective of the Mother Baby Comfort Care Pathway is to implement a program of family-centered care with logistically flexible care delivery, allowing mothers and their families to share as normal a postpartum care experience as possible with a focus on quality of life, memory making, and time spent together. METHODS: The program was developed with the nucleus of care coordination and provision on the Mother Baby Unit (postpartum unit), with involvement from the labor and delivery room, NICU, and other units as necessary to provide the postpartum mother, her dying infant, as well as possible additional siblings (in the case of multiple gestation), postpartum care while rooming-in. The program was rolled out with training workshops for postpartum nurses. FINDINGS: Nurses who took part in the workshops and the patient care program rated both highly. IMPLICATIONS FOR PRACTICE: The Mother Baby Comfort Care Pathway aims to offer a framework for providing multidisciplinary family-centered comfort care to newborns during the postpartum period in a compassionate, evidence-based, and individualized manner in order to maximize quality time together for families with a dying infant.

Transcriptomic profiling of fetal membranes of mice deficient in biglycan and decorin as a model of preterm birth†.

Approximately, 25% of all preterm births are due to preterm premature rupture of membranes. Mice deficient in proteoglycans biglycan (Bgn) and decorin (Dcn) display abnormal fetal membranes and increased incidence of preterm birth. We conducted RNA-Seq to profile fetal membranes and identify molecular pathways that may lead to preterm birth in double knockout (DKO) mice (Bgn-/-; Dcn-/-) compared to wild-type (WT) at two different gestational stages, E12 and E18 (n = 3 in each group). 3264 transcripts were differentially regulated in E18 DKO vs. WT fetal membranes, and 96 transcripts differentially regulated in E12 DKO vs. WT fetal membranes (FDR < 0.05, log 2 FC ≥ 1). Differentially regulated transcripts in E18 DKO fetal membranes were significantly enriched for genes involved in cell cycle regulation, extracellular matrix-receptor interaction, and the complement cascade. Fifty transcripts involved in the cell cycle were altered in E18 DKO fetal membranes (40↓, 10↑, FDR < 0.05), including p21 and p57 (↑), and Tgfb2, Smad3, CycA, Cdk1, and Cdk2(↓). Thirty-one transcripts involved in the complement cascade were altered (11↓, 20↑, FDR < 0.05) in E18 DKO fetal membranes, including C1q, C2, and C3 (↑). Differentially expressed genes in the top three molecular pathways (1) showed evidence of negative or purifying selection, and (2) were significantly enriched (Z-score > 10) for transcription factor binding sites for Nr2f1 at E18. We propose that in DKO mice, cell cycle arrest results in lack of cell proliferation in fetal membranes, inability to contain the growing fetus, and preterm birth.

A Quality Improvement Initiative to Increase Hand Hygiene Awareness and Compliance in a Neonatal Intensive Care Unit in Haiti.

INTRODUCTION: Healthcare-associated infections (HCAI) are major causes of morbidity, mortality, increased lengths of stay and are an economic burden on healthcare systems in resources-limited settings. This is especially true for neonates, who are more susceptible with underdeveloped immune systems. Hand hygiene (HH) is a key weapon against HCAI, yet globally, HH compliance remains substandard. This study sought to determine the compliance with HH among healthcare workers (HCWs) in a children's hospital neonatal intensive care unit (NICU) in Haiti. METHODS: A HH educational intervention was performed in the NICU, including lectures and posters. Pre- and post-intervention HH data were collected on HCWs and parents using the World Health Organization '5 Moments for HH'. Data were analyzed using standard statistical analysis. RESULTS: HH increased in all HCW roles but not in parents. Correct HH increased in all groups, including parents. HH was more likely to occur prior to patient contact than after patient contact. Correct HH was more likely to occur with alcohol-based hand rub than with soap and water. CONCLUSION: This study demonstrates that an inexpensive and simple intervention can significantly increase HH compliance in a resource-limited NICU, which may lead to decreased rates of hospital-acquired sepsis. Parents, however, due to cultural norms as well as literacy and language barriers, need targeted educational interventions distinct from those that HCW benefit from.

Seeking the best training model for difficult conversations in neonatology.

OBJECTIVES: We hypothesize that a formal simulation curriculum prepares neonatology fellows for difficult conversations better than traditional didactics. METHODS: Single-center neonatology fellowship graduates from 1999 to 2013 were sent a retrospective web-based survey. Some had been exposed to a Difficult Conversations curriculum (simulation group), others had not (no simulation group). The simulation group participated in one workshop annually, consisting of lecture, simulation, and debriefing. Scenarios were customized to year of training. Epoch comparisons were made between the simulation and no simulation groups. RESULTS: Self-rated baseline effectiveness at discussing difficult topics was not different. The simulation group reported more supervised family meetings and feedback after fellow-led meetings. Simulations were rated very positively. The simulation group reported increased comfort levels. Strategic pause and body positioning were specific communication skills more frequently acquired in the simulation group. In both groups, the highest ranked contributors to learning were mentor observation and clinical practice. In the simulation group, simulation and debriefing outranked didactics or other experiences. CONCLUSIONS: Simulation-based workshops improve communication skills in high stakes conversations. However, they do not substitute for mentor observation and experience. Establishing a structured simulation-based difficult conversations curriculum refines vital communication skills necessary for the high stakes conversations neonatologists direct in clinical practice.

Compensatory fetal membrane mechanisms between biglycan and decorin in inflammation.

Preterm premature rupture of fetal membranes (PPROM) is associated with infection, and is one of the most common causes of preterm birth. Abnormal expression of biglycan and decorin, two extracellular matrix proteoglycans, leads to preterm birth and aberrant fetal membrane morphology and signaling in the mouse. In humans and mice, decorin dysregulation is associated with inflammation in PPROM. We therefore investigated the link between biglycan and decorin and inflammation in fetal membranes using mouse models of intraperitoneal Escherichia coli injections superimposed on genetic biglycan and decorin deficiencies. We assessed outcomes in vivo as well as in vitro using quantitative PCR, Western blotting, and enzyme-linked immunosorbent assays. Our results suggest that biglycan and decorin compensate for each other in the fetal membranes, but lose the ability to do so under inflammation, leading to decreased latency to preterm birth. Furthermore, our findings suggest that biglycan and decorin play discrete roles in fetal membrane signaling pathways during inflammation, leading to changes in the abundance of MMP8 and collagen α1VI, two components of the fetal membrane extracellular matrix that influence the pathophysiology of PPROM. In summary, these findings underline the importance of biglycan and decorin as targets for the manipulation of fetal membrane extracellular matrix stability in the context of inflammation.

Counseling for personal care options at neonatal end of life: a quantitative and qualitative parent survey.

BACKGROUND: The death of a newborn is a traumatic life changing event in the lives of parents. We hypothesized that bereaved parents of newborn infants want to have choices in the personal care of their infant at the end of life. METHODS: Parents who had suffered a perinatal or neonatal loss between 1 and 6 years before the survey in a regional level IV neonatal intensive care unit (NICU) and associated labor and delivery room were invited to participate. Parents chose between an online survey, paper survey or telephone interview. The survey included multiple choice and open ended questions. RESULTS: Parents prefer multiple options for the personal care of their infant at the end of life. Emergent themes were need for guidance by the medical team, memory making, feeling cared for and respected by staff, and regrets related to missed opportunities. CONCLUSION: While parents differ in their preferences in utilizing specific personal care options for their infant's end of life, they share a common preference for being presented with multiple options to choose from and in being guided and supported by healthcare providers, while being afforded the opportunity to make memories with their infant by bonding with and parenting them.

Altered decorin and Smad expression in human fetal membranes in PPROM.

Humans with Ehlers-Danlos syndrome, a subtype of which is caused by abnormal decorin expression, are at increased risk of preterm birth due to preterm premature rupture of fetal membranes (PPROM). In the mouse model, the absence of decorin leads to fetal membrane abnormalities, preterm birth, and dysregulation of decorin's downstream pathway components, including the transcription factor p-Smad-2. However, the role of decorin and p-Smad-2 in idiopathic human PPROM is unknown. Fetal membranes from 20-25 pregnancies per group were obtained as a cross-sectional sample of births at one institution between January 2010 and December 2012. The groups were term, preterm without PPROM, and preterm with PPROM. Immunohistochemical analysis of fetal membranes was performed for decorin and p-Smad-2 using localization and quantification assessment. Decorin expression is developmentally regulated in fetal membranes and is decreased in preterm birth with PPROM compared to preterm birth without PPROM. In preterm with PPROM samples, the presence of infection is associated with significant decorin downregulation compared to preterm with PPROM samples without infection. The preterm with PPROM group exhibited decreased p-Smad-2 staining compared to both the term controls and the preterm-without-PPROM group. Our findings suggest that dysregulation of decorin and its downstream pathway component p-Smad-2 occurs in fetal membranes during the second trimester in pathological pregnancies, thus supporting a role for decorin and p-Smad-2 in the pathophysiology of fetal membranes and adverse pregnancy outcomes. These findings may lead to the discovery of new targets for the diagnosis and treatment of PPROM.

Equity, inclusion and cultural humility: contemporizing the neonatal intensive care unit family-centered care model.

Existing NICU family centered care models lack the key elements of equity, inclusion and cultural humility. These models were conceived to support families during the stressful life event of an infant's NICU admission. Their development, however, occurred prior to recognition of the medical field's systematic shortcomings in providing equitable care and their impact on outcome disparities for marginalized communities; thus, they do not include cultural or equitable healthcare considerations. Given the significant neonatal care inequities for marginalized groups, incorporating the experience of these patients in a targeted manner into family centered care frameworks is of critical importance to ensure culturally humble and thus more just and equitable treatment. Here, we review past approaches to NICU family centered care and propose a novel, updated framework which integrates culturally humble care into the NICU family centered care framework.

Biglycan is an extracellular MuSK binding protein important for synapse stability.

The receptor tyrosine kinase MuSK is indispensable for nerve-muscle synapse formation and maintenance. MuSK is necessary for prepatterning of the endplate zone anlage and as a signaling receptor for agrin-mediated postsynaptic differentiation. MuSK-associated proteins such as Dok7, LRP4, and Wnt11r are involved in these early events in neuromuscular junction formation. However, the mechanisms regulating synapse stability are poorly understood. Here we examine a novel role for the extracellular matrix protein biglycan in synapse stability. Synaptic development in fetal and early postnatal biglycan null (bgn(-/o)) muscle is indistinguishable from wild-type controls. However, by 5 weeks after birth, nerve-muscle synapses in bgn(-/o) mice are abnormal as judged by the presence of perijunctional folds, increased segmentation, and focal misalignment of acetylcholinesterase and AChRs. These observations indicate that previously occupied presynaptic and postsynaptic territory has been vacated. Biglycan binds MuSK and the levels of this receptor tyrosine kinase are selectively reduced at bgn(-/o) synapses. In bgn(-/o) myotubes, the initial stages of agrin-induced MuSK phosphorylation and AChR clustering are normal, but the AChR clusters are unstable. This stability defect can be substantially rescued by the addition of purified biglycan. Together, these results indicate that biglycan is an extracellular ligand for MuSK that is important for synapse stability.

Words matter: exploring communication between parents and neonatologists.

OBJECTIVE: To evaluate how neonatologists and NICU parents perceive communication in the NICU. STUDY DESIGN: A mixed-methods approach using an online survey and three focus groups with NICU parents and neonatologists, utilizing videos of simulated conversations between a neonatologist and mother. RESULTS: A total of 72 participants responded to the online survey. Parents ranked the invasiveness of common NICU clinical procedures differently than the neonatologist standard but assessed the quality of the simulated conversation similarly. A total of 13 parents and 6 physicians participated in the focus groups. Major themes from both neonatologist and parent focus groups were the impact of making a connection with the parents, the importance of making decisions yet not making assumptions based on the divergent use of language by neonatologists and parents, and providing hope. CONCLUSIONS: Parents and neonatologists differ in their perception of key aspects of NICU language use and communication but also agree on many aspects.

A mouse model of spontaneous preterm birth based on the genetic ablation of biglycan and decorin.

Preterm premature rupture of membranes is responsible for one-third of preterm births. Ehlers-Danlos syndrome (EDS) is associated with preterm premature rupture of membranes in humans. In particular, an EDS variant is caused by a genetic mutation resulting in abnormal secretion of biglycan and decorin, two small leucine-rich proteoglycans highly expressed in reproductive tissues. Because biglycan/decorin null mutant (Bgn(-/-)Dcn(-/-)) mice demonstrate phenotypic changes similar to EDS, we used this model to test whether either biglycan or decorin or both play a role in the attainment of successful term gestation. Wild-type biglycan null mutant, decorin null mutant, and biglycan/decorin null mutant pregnancies were assessed for the length of gestation, pup and placenta weight, and litter size. Quantitative real-time PCR was performed to measure biglycan and decorin gene expression, and immunohistochemistry was performed to assess protein expression in placenta and fetal membranes at embryonic days E12, E15, and E18. Bgn(-/-)Dcn(-/-) dams displayed preterm birth, whereas the possession of at least two biglycan or decorin wild-type alleles was protective of preterm birth. The number of Bgn(-/-)Dcn(-/-) pups was decreased at postnatal day P1 but not at E18. Biglycan and decorin were upregulated in the placenta in the absence of each other and were developmentally regulated in fetal membranes, suggesting that these two proteoglycans demonstrate genetic complementation and contribute to gestational success in a dose-dependent manner. Thus, the biglycan/decorin null mutant mouse is a model of genetically induced preterm birth and perinatal loss. This model presents novel targets for preventive or therapeutic manipulation of preterm birth.

Perspectives on Race and Medicine in the NICU.

Current data regarding racial and ethnic disparities in health outcomes of newborns requiring care in an NICU reveal significant differences in quality and access to care that disproportionally affects infants of color, particularly African American infants. These inequalities result in an increased infant mortality rate for Black children and higher preterm birth rates, as well as an increase in deaths due to low birth weight and decreased gestational age. Concurrently, there is emerging research exploring the role of diversity and adequate representation among medical providers in patient outcomes in Black communities. In this editorial, we present commentaries from a medical student, a neonatologist, and a parent of former NICU patients to further explore race in the NICU from different perspectives and understand what can be learned from their experiences about these systemic issues and why representation is a critical component of successful change.

Serum Decorin, Biglycan, and Extracellular Matrix Component Expression in Preterm Birth.

Preterm birth is a leading cause of infant morbidity and mortality. Decorin and biglycan are proteoglycans that play key roles in maintaining the connective tissue matrix and tensile strength of human fetal membranes and have been previously linked to PPROM. Extracellular matrix proteins, such as matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), TIMP metallopeptidase inhibitor 1 (TIMP-1), TIMP metallopeptidase inhibitor 2 (TIMP-2), and collagen VI (COL-6), have also been linked to PPROM and may have utility in a serum-based screening model for this condition. To define the natural course of serum decorin and biglycan expression throughout the duration of healthy pregnancy, to explore patterns of serum decorin and biglycan expression in serum of asymptomatic women who go on to develop spontaneous preterm labor, and to investigate the potential role for matrix metalloproteinases, their inhibitors, and collagen VI in a serum-based screening model to predict PPROM. Serum decorin level decreases less than 1% per week, and serum biglycan decreases by 2.9% per week over the duration of healthy pregnancy. Serum decorin and biglycan concentrations do not differ in spontaneous preterm labor cases compared with those in controls. Mean concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, and COL-6 do not differ in PPROM cases compared with those in controls. We have demonstrated that serum decorin and biglycan concentrations remain stable throughout the duration of normal pregnancy and are not early indicators of preterm labor, while common MMPs, TIMPs, and collagen VI are not early indicators of PPROM.

"Quality of life": parent and neonatologist perspectives.

OBJECTIVE: To assess how physicians and families understand quality of life (QOL) for NICU patients, and to explore the feasibility of developing a standardized definition for QOL. STUDY DESIGN: Surveys were developed and administered to neonatologists and eligible families. Quantitative analysis was conducted using standard statistical methods. Qualitative analysis was conducted using NVivo software. Focus groups were conducted with the same groups, and audio recordings were obtained and analyzed for recurring themes. RESULTS: Both parents and physicians value QOL as a metric for guiding care in the NICU. Parents were more likely to accept higher levels of disability, while neonatologists were more likely to accept higher levels of dependence on medical equipment. In relation to infant QOL, predominant themes expressed in the parent focus groups were stress levels in the NICU, advocating as parents, and the way in which long-term outcomes were presented by the medical team; in the physician focus group, the ambiguity of predicting outcomes and thus QOL was the main theme. CONCLUSIONS: Both parents and physicians recognize the importance of QOL in the decision-making process for critically ill infants, but the two groups differ in their assessment of what QOL means in this context. These data suggest that QOL cannot be adequately defined for standardized use in a clinical context, and as such, should be used thoughtfully by neonatologists in discussions of end- of-life care.