Neonatal Sepsis Episodes and Retinopathy of Prematurity in Very Preterm Infants.

Importance: Retinopathy of prematurity (ROP) is a major morbidity of preterm infants causing visual impairment, including blindness, for which timely treatment is vital and prevention is key. Increasing evidence suggests that exposure to neonatal sepsis contributes to ROP development. Objective: To investigate the association between neonatal sepsis and ROP in 2 large-scale cohorts of preterm infants born at less than 29 weeks' gestation. Design, Setting, and Participants: This retrospective cohort study was conducted using data from the German Neonatal Network (GNN) and Norwegian Neonatal Network (NNN). The GNN involves 68 and the NNN includes 21 level III neonatal intensive care units. Participants were infants born at a gestation of 22 weeks and 0 days to 28 weeks and 6 days and enrolled in the GNN between January 1, 2009, and December 31, 2022, and NNN between January 1, 2009, and December 31, 2018. Data were analyzed from February through September 2023. Exposure: Single or multiple episodes of culture-proven sepsis. Main Outcomes and Measures: Any ROP and treatment-warranted ROP. Results: Among 12 794 infants in the GNN (6043 female [47.2%] and 6751 male [52.8%]; mean [SD] gestational age, 26.4 [1.5] weeks) and 1844 infants in the NNN (866 female [47.0%] and 978 male [53.0%]; mean [SD] gestational age, 25.6 [1.5] weeks), the mean (SD) birth weight was 848 (229) g and 807 (215) g, respectively. Any ROP was present in 6370 infants (49.8%) in GNN and 620 infants (33.6%) in NNN, and treatment-warranted ROP was present in 840 infants (6.6%) in GNN and 140 infants (7.6%) in NNN. In both cohorts, there were increasing rates of treatment-warranted ROP with each sepsis episode (no sepsis: 572 of 10 658 infants [5.4%] in GNN and 85 of 1492 infants (5.7%) in NNN; 1 episode: 190 of 1738 infants in GNN [10.9%] and 29 of 293 infants [9.9%] in NNN; 2 episodes: 53 of 314 infants in GNN [16.9%] and 13 of 49 infants [26.5%] in NNN; 3 episodes: 25 of 84 infants [29.8%] in GNN and 3 of 10 infants [30.0%] in NNN). After adjusting for multiple confounders in the GNN dataset, the number of sepsis episodes was associated with ROP and treatment-warranted ROP compared with 0 episodes (1 episode: adjusted odds ratio [aOR], 1.44 [95% CI, 1.27-1.63]; P < .001 and OR, 1.60 [95% CI, 1.31-1.96]; P < .001, respectively; 2 episodes: OR, 1.81 [95% CI, 1.35-2.42]; P < .001 and OR, 2.38 [95% CI, 1.68-3.37]; P < .001, respectively; 3 episodes: OR, 4.39 [95% CI, 2.19-8.78]; P < .001 and OR, 3.88 [95% CI, 2.29-6.55]; P < .001, respectively). These associations were confirmed for any ROP by propensity score matching (for example, the aOR with propensity score matching was 1.76 [95% CI, 1.54-2.02]; P < .001 for 1 episode vs 0 episodes and 1.58 [95% CI, 1.12-2.22]; P = .007 for 3 episodes vs 0 or 1 episode). In the NNN dataset, surgical NEC was associated with treatment-warranted ROP (multivariable analysis: aOR, 3.37 [95% CI, 1.78-6.37]; P < .001). Conclusions and Relevance: This study found that in the large-scale GNN cohort, recurrent culture-proven sepsis was associated with ROP and treatment-warranted ROP in infants born at less than 29 weeks.

Developmental authenticity - underlying dynamics of inner work processes.

An emerging body of research attends to grasp the concept of authenticity. Nonetheless, a view on the developmental part with its underlying facets of Inner Work processes, is rare. In this paper, we aim to take a deeper look into the dynamics of inner work processes, that define certain authenticity developmental stages. Building upon our recently proposed "4C-view" of authenticity, we approach this developmental perspective from two different angles: from a process characteristic angle and a developmental level angle. Using vignettes of authentic client personality coaching processes, we propose that the interwoven dynamic between those two aspects yields several combinations of maturity levels within the individual. Continuity as an overarching concept thus contains various developmental authenticity stages that could be identified through different markers and vary in particular contexts.

Neonatal sepsis as a cause of retinopathy of prematurity: An etiological explanation.

Retinopathy of prematurity (ROP) is a complex neonatal disorder with multiple contributing factors. In this paper we have mounted the evidence in support of the proposal that neonatal sepsis meets all requirements for being a cause of ROP (not a condition, mechanism, or even innocent bystander) by means of initiating the early stages of the pathomechanism of ROP occurrence, systemic inflammation. We use the model of etiological explanation, which distinguishes between two overlapping processes in ROP causation. It can be shown that sepsis can initiate the early stages of the pathomechanism via systemic inflammation (causation process) and that systemic inflammation can contribute to growth factor aberrations and the retinal characteristics of ROP (disease process). The combined contribution of these factors with immaturity at birth (as intrinsic risk modifier) and prenatal inflammation (as extrinsic facilitator) seems to provide a cogent functional framework of ROP occurrence. Finally, we apply the Bradford Hill heuristics to the available evidence. Taken together, the above suggests that neonatal sepsis is a causal inducer of ROP.

Erythrocyte transfusions are associated with retinopathy of prematurity in extremely low gestational age newborns.

AIM: Retinopathy of prematurity (ROP) is a major morbidity in preterm infants causing visual impairment including blindness. Prevention and timely treatment are critical. We investigated the potential role of red blood cell (RBC) transfusions as risk factor for ROP development. METHODS: Retrospective cohort study of data from 68 tertiary level neonatal intensive care units in Germany. Preterm infants born at 22 + 0 to 28 + 6 weeks of gestation between January 2009 and December 2021 were enrolled. RESULTS: We included n = 12 565 infants. Prevalence of any ROP was 49.2% with most infants being diagnosed with stage 1 (21.5%) and 2 disease (17.2%). ROP stage 3 was present in 10.2%, stage 4 in 0.3%, and ROP requiring treatment in 6.6%. Infants with ROP had significantly more frequently a history of RBC transfusions. Adjusting for confounders, RBC transfusions were associated with increased odds of ROP (OR 1.4, p < 0.001), ROP progression (OR 2.1, p < 0.01) and ROP requiring treatment (OR 3.6, p < 0.001). Restrictive transfusion approaches correlated with decreased (OR 0.7, p < 0.001), liberal regimes with increased odds (OR 1.2, p = 0.001). CONCLUSION: The present study confirmed an association of RBC transfusions and ROP. Our findings emphasise the need for anaemia prevention and critical re-evaluation of transfusion practices in preterm infants.

Retinal structure and visual pathway function at school age in children born extremely preterm: a population-based study.

BACKGROUND: Children born extremely preterm (gestational age < 28 weeks) show reduced visual function even without any cerebral or ophthalmological neonatal diagnosis. In this study, we aimed to assess the retinal structure with optical coherence tomography (OCT) and visual function with pattern-reversal visual evoked potentials (PR-VEPs) in a geographically defined population-based cohort of school-aged children born extremely preterm. Moreover, we aimed to explore the association between measures of retinal structure and visual pathway function in this cohort. METHODS: All children born extremely preterm from 2006-2011 (n = 65) in Central Norway were invited to participate. Thirty-six children (55%) with a median age of 13 years (range = 10-16) were examined with OCT, OCT-angiography (OCT-A), and PR-VEPs. The foveal avascular zone (FAZ) and circularity, central macular vascular density, and flow were measured on OCT-A images. Central retinal thickness, circumpapillary retinal nerve fibre layer (RNFL) and inner plexiform ganglion cell layer (IPGCL) thickness were measured on OCT images. The N70-P100 peak-to-peak amplitude and N70 and P100 latencies were assessed from PR-VEPs. RESULTS: Participants displayed abnormal retinal structure and P100 latencies (≥ 2 SD) compared to reference populations. Moreover, there was a negative correlation between P100 latency in large checks and RNFL (r = -.54, p = .003) and IPGCL (r = -.41, p = .003) thickness. The FAZ was smaller (p = .003), macular vascular density (p = .006) and flow were higher (p = .004), and RNFL (p = .006) and IPGCL (p = .014) were thinner in participants with ROP (n = 7). CONCLUSION: Children born extremely preterm without preterm brain injury sequelae have signs of persistent immaturity of retinal vasculature and neuroretinal layers. Thinner neuroretinal layers are associated with delayed P100 latency, prompting further exploration of the visual pathway development in preterms.

Caritas only when.

IMPACT: Finding and respecting the human facets of the patient-parent-physician relationship will enable us to return to where we come from and to offer what is worthy of the appellation "care". The poem adds a piece to the mosaic of humanist pediatrics. Hopefully, the message will add a silver lining to the clouds of professional responsibility and burnout hovering over large parts of the pediatric workforce.

Opioid-related mortality: Dynamic temporal and spatial trends by drug type and demographic subpopulations, Massachusetts, 2005-2021.

BACKGROUND: Fatal opioid-related overdoses (OOD) present significant public health challenges. Intuitive and replicable analytical approaches are needed to inform targeted public health responses. METHODS: We obtained fatal OOD data for 2005-2021 from the Massachusetts Registry of Vital Records and Statistics. We conducted heatmap analyses to assess trends in fatal OOD rates per 100,000 residents, visualizing rates by death year and decedent age at one-year intervals, stratifying by race/ethnicity, sex, rurality, and involved substances. We calculated Getis-Ord Gi* statistics to identify spatial clusters of OOD rates. RESULTS: Among 20,774 fatal OODs, rates were higher among males, and highly variable by race/ethnicity, age group, and rurality. While fatal OOD rates increased in urban before rural communities, rates were higher in rural communities by 2018-2019. Stimulant-related fatal OODs were elevated in 2020 and 2021. Fatal OOD rates involving fentanyl and stimulants increased precipitously and simultaneously in the non-Hispanic Black population in 2020 and 2021, with a bimodal age distribution peaking among those in their 40s and 60s. Elevated rates among 30-to-60 year old Hispanic residents were largely tied to synthetic opioids from 2015 to 2021. Spatial clusters were detected for prescription opioids, heroin, and stimulants in western Massachusetts. For synthetic opioids, hotspots became more ubiquitous across the state from 2016 to 2021, intensifying in southeastern Massachusetts. CONCLUSION: Our novel approach uncovered new time varying and spatial patterns in fatal OOD rates not previously reported. Identified shifts in fatal OOD rates by sex, age, and race/ethnicity can inform location-specific field actions targeting subpopulations at disproportionally high risk.

Small Area Forecasting of Opioid-Related Mortality: Bayesian Spatiotemporal Dynamic Modeling Approach.

BACKGROUND: Opioid-related overdose mortality has remained at crisis levels across the United States, increasing 5-fold and worsened during the COVID-19 pandemic. The ability to provide forecasts of opioid-related mortality at granular geographical and temporal scales may help guide preemptive public health responses. Current forecasting models focus on prediction on a large geographical scale, such as states or counties, lacking the spatial granularity that local public health officials desire to guide policy decisions and resource allocation. OBJECTIVE: The overarching objective of our study was to develop Bayesian spatiotemporal dynamic models to predict opioid-related mortality counts and rates at temporally and geographically granular scales (ie, ZIP Code Tabulation Areas [ZCTAs]) for Massachusetts. METHODS: We obtained decedent data from the Massachusetts Registry of Vital Records and Statistics for 2005 through 2019. We developed Bayesian spatiotemporal dynamic models to predict opioid-related mortality across Massachusetts' 537 ZCTAs. We evaluated the prediction performance of our models using the one-year ahead approach. We investigated the potential improvement of prediction accuracy by incorporating ZCTA-level demographic and socioeconomic determinants. We identified ZCTAs with the highest predicted opioid-related mortality in terms of rates and counts and stratified them by rural and urban areas. RESULTS: Bayesian dynamic models with the full spatial and temporal dependency performed best. Inclusion of the ZCTA-level demographic and socioeconomic variables as predictors improved the prediction accuracy, but only in the model that did not account for the neighborhood-level spatial dependency of the ZCTAs. Predictions were better for urban areas than for rural areas, which were more sparsely populated. Using the best performing model and the Massachusetts opioid-related mortality data from 2005 through 2019, our models suggested a stabilizing pattern in opioid-related overdose mortality in 2020 and 2021 if there were no disruptive changes to the trends observed for 2005-2019. CONCLUSIONS: Our Bayesian spatiotemporal models focused on opioid-related overdose mortality data facilitated prediction approaches that can inform preemptive public health decision-making and resource allocation. While sparse data from rural and less populated locales typically pose special challenges in small area predictions, our dynamic Bayesian models, which maximized information borrowing across geographic areas and time points, were used to provide more accurate predictions for small areas. Such approaches can be replicated in other jurisdictions and at varying temporal and geographical levels. We encourage the formation of a modeling consortium for fatal opioid-related overdose predictions, where different modeling techniques could be ensembled to inform public health policy.

Visual function correlates with neurodevelopment in a population cohort of school-aged children born extremely preterm.

AIM: To investigate visual function and neurodevelopment in a geographically defined population cohort of school-aged children born extremely preterm. METHODS: All children born extremely preterm in Central Norway between 2006 and 2011 (n=65) were identified, and 36 (median age, min/max: 13, 10/16) were included. Best-corrected visual acuity (BCVA), contrast sensitivity (four spatial frequencies), parent-reported challenges and neuropsychological testing in learning, executive functions, motor skills, perception, reaction time, working and visual memory, processing speed, and pattern separation were measured. Brain MRI (3T) was acquired and read by a neuroradiologist. RESULTS: Median (min/max) BCVA letter score was 85 (35/91) in the better and 82 (13/89) in the worse eye. ROP participants (n=7) had lower contrast sensitivity in the two highest spatial frequencies (p = 0.024 and p = 0.004). Parent-reported challenges correlated negatively with BCVA (learning: p = 0.014; executive functions: p = 0.002; motor skills: p = 0.000; and perception: p = 0.001), while motor skills correlated negatively with one (p = 0.010) and perception with two (p = 0.003 and p = 0.009) of four spatial frequencies. Neuropsychological tests were reduced relative to norms. None had MRI-verified preterm brain injury. CONCLUSION: Visual function was subnormal and correlated with parent-reported challenges in a small cohort of extremely preterm school-aged children, indicating that visual function may be a marker of neurodevelopmental outcomes.

PRENATAL MATERNAL CHARACTERISTICS ASSOCIATED WITH RETINOPATHY OF PREMATURITY.

PURPOSE: Determine whether prenatal maternal characteristics such as sociodemographic characteristics, comorbidities, or pregnancy complications affect retinopathy of prematurity (ROP) development. METHODS: Medical records of 236 mother-infant dyads from our institution were reviewed, only including dyads in which infants were born at 30 weeks gestational age or earlier. The primary outcome measure was the risk of ROP (defined Stage 1 or greater in either eye) and its association with prenatal maternal variables. RESULTS: Maternal Medicaid insurance, smoking during pregnancy, and chorioamnionitis were associated with an increased risk of ROP. For Medicaid insurance and chorioamnionitis, these risks were not appreciably altered by adjustment for potential confounders. CONCLUSION: These results suggest that several prenatal maternal factors may independently affect the risk of ROP in preterm infants. Validation of our findings could aid in the identification of infants at high risk for ROP based on prenatal clinical features.

Retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a devastating neurovascular disease of the retina in newborn infants that can lead to vision deficits or even blindness. In this concise review we discuss our current knowledge about diagnosis, etiology, pathogenesis, intervention, and outcomes of the disease. Major advancements have been made both in categorizing the disease in the new International Classification of Retinopathy of Prematurity, Third Edition classification and in treating severe ROP with anti-vascular endothelial growth factor (VEGF) agents. New development always creates new questions and opens up new areas of research. We will discuss in this review both the benefits and downsides of the new anti-VEGF treatment approaches in ROP, especially in light of our improved understanding of the underlying ROP pathophysiology. We also offer pointers to areas where more research is needed. WHAT THIS PAPER ADDS: Concise update on all aspects of retinopathy of prematurity (ROP), including advances in understanding and treatment. Benefits and risks of the new treatment method of anti-vascular endothelial growth factor injections in ROP are discussed. New research areas that deserve attention in the coming years are identified.

Web-Based Health Information-Seeking Methods and Time Since Provider Engagement: Cross-sectional Study.

BACKGROUND: The use of web-based methods to seek health information is increasing in popularity. As web-based health information (WHI)-seeking affects health-related decision support and chronic symptom self-management, WHI-seeking from online sources may impact health care decisions and outcomes, including care-seeking decisions. Patients who are routinely connected to physicians are more likely to receive better and more consistent care. Little is known about whether WHI-seeking impacts the frequency at which patients engage with health care providers. OBJECTIVE: Our primary objective was to describe the associations between the use of web-based methods to seek information about one's own health and the time since last engaging with a health care provider about one's own health. Additionally, we aimed to assess participants' trust in health care organizations to contextualize our findings. METHODS: We analyzed data from US adults participating in the nationally representative Tufts Equity in Health, Wealth, and Civic Engagement Survey (N=1034). Bivariate associations between demographic characteristics and health information-seeking methods were assessed with Pearson chi-squared tests. Bivariate associations of Medical Mistrust Index (MMI) scores with each health information-seeking method and time since provider engagement were assessed with F tests and adjusted Wald tests. We fit a multivariable logistic regression model to assess the association between WHI-seeking within the 12 months prior to survey (alone or in combination with provider-based methods versus provider only) and engagement with a provider more than 1 year prior to the time of survey, adjusting for age, race and ethnicity, sex, education, insurance coverage, and MMI. RESULTS: Age, race and ethnicity, educational attainment, health insurance source, MMI, and time since provider engagement were each significantly associated with the health information-seeking method in bivariate analyses. Compared to using only provider-based health information seeking methods, WHI-based methods alone or in combination with provider-based methods were associated with a 51% lower likelihood (odds ratio 0.49, 95% CI 0.27-0.87) of engaging with a provider within the previous year. Participants who used WHI-seeking methods alone and those who had not engaged with a health care provider within the previous year demonstrated a higher mean MMI score; however, MMI was not a significant predictor of time since engagement with a provider in the multivariable analysis. CONCLUSIONS: Our findings from a nationally representative survey suggest that for those who use WHI-seeking methods (alone or in combination with provider-based information-seeking methods), there is a statistically significant lower likelihood of engaging with a provider in a year compared to those who only use provider-based methods. Future research should consider the intent of a person's visit with a provider, trust in health care systems, methods of provider engagement, and specific web-based platforms for health information.

The Representation of Causality and Causation with Ontologies: A Systematic Literature Review.

Objective: To explore how disease-related causality is formally represented in current ontologies and identify their potential limitations. Methods: We conducted a systematic literature search on eight databases (PubMed, Institute of Electrical and Electronic Engendering (IEEE Xplore), Association for Computing Machinery (ACM), Scopus, Web of Science databases, Ontobee, OBO Foundry, and Bioportal. We included studies published between January 1, 1970, and December 9, 2020, that formally represent the notions of causality and causation in the medical domain using ontology as a representational tool. Further inclusion criteria were publication in English and peer-reviewed journals or conference proceedings. Two authors (SS, RM) independently assessed study quality and performed content analysis using a modified validated extraction grid with pre-established categorization. Results: The search strategy led to a total of 8,501 potentially relevant papers, of which 50 met the inclusion criteria. Only 14 out of 50 (28%) specified the nature of causation, and only 7 (14%) included clear and non-circular natural language definitions. Although several theories of causality were mentioned, none of the articles offers a widely accepted conceptualization of how causation and causality can be formally represented. Conclusion: No current ontology captures the wealth of available concepts of causality. This provides an opportunity for the development of a formal ontology of causation/causality.

Health Humanities in Medicina: The Auxiliary Stance.

At the core of medicine is the idea to help fellow human beings by improving or even restoring their health [...].

Causation and causal inference in obstetrics-gynecology.

Causation and causal inference are of utmost importance in obstetrics and gynecology. In many clinical situations, causal reasoning is involved in etiological explanations, diagnostic considerations, and conversations about prognosis. In this paper, we offer an overview of the philosophical accounts of causation that may not be familiar to, but still be appreciated by, the busy clinician. In our discussion, we do not try to simplify what is a rather complex range of ideas. We begin with an introduction to some important basic ideas, followed by 2 sections on the metaphysical and epistemological aspects of causality, which offer a more detailed discussion of some of its specific philosophical facets, using examples from obstetrical and gynecologic research and practice along the way. We hope our discussion will help deepen the thinking and discourse about causation and causal inference in gynecology and obstetrics.