Social Networks as a Key Health Determinant in Acute Illness Recovery: A Lesson from the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic highlighted the importance of considering social determinants of health in health outcomes. Within this spectrum of determinants, social networks garnered attention as the pandemic highlighted the negative effects of social isolation in the context of social distancing measures. Post-pandemic, examining the role social networks play in COVID-19 recovery can help guide patient care and shape future health policies. This study aimed to investigate the relationship between social networks and self-rated health change, as well as physical function, in patients recovering from COVID-19 pneumonia. METHODS: This was a retrospective cohort study utilizing clinical data from two New York City hospitals and a 9-month follow-up survey of COVID-19 pneumonia survivors. We evaluated a composite Social Network Score from the 6-item Lubben Social Network Scale and its association with two outcomes: 1) self-rated health change and 2) physical function. RESULTS: A total of 208 patients were included in this study. A one-point increase in the Social Network Score was associated with greater odds of both improved or similar self-rated health change (odds ratio [OR] 1.07, 95% CI 1.02 - 1.12, p = 0.01), as well as unimpaired physical function (OR 1.08, 95% CI 1.03 - 1.14, p < 0.01). CONCLUSION: This study emphasized the importance of social networks as a social determinant of health among patients recovering from COVID-19 hospitalization. Targeted interventions to enhance social networks may benefit not only COVID-19 patients but also individuals recovering from other acute illnesses.

Pediatric Mental Health Emergencies During 5 COVID-19 Waves in New York City.

OBJECTIVES: To describe the proportion of pediatric mental health emergency department (MH-ED) visits across 5 COVID-19 waves in New York City (NYC) and to examine the relationship between MH-ED visits, COVID-19 prevalence, and societal restrictions. METHODS: We conducted a time-series analysis of MH-ED visits among patients ages 5 to 17 years using the INSIGHT Clinical Research Network, a database from 5 medical centers in NYC from January 1, 2016, to June 12, 2022. We estimated seasonally adjusted changes in MH-ED visit rates during the COVID-19 pandemic, compared with predicted prepandemic levels, specific to each COVID-19 wave and stratified by mental health diagnoses and sociodemographic characteristics. We estimated associations between MH-ED visit rates, COVID-19 prevalence, and societal restrictions measured by the Stringency Index. RESULTS: Of 686 500 ED visits in the cohort, 27 168 (4.0%) were MH-ED visits. The proportion of MH-ED visits was higher during each COVID-19 wave compared with predicted prepandemic trends. Increased MH-ED visits were seen for eating disorders across all waves; anxiety disorders in all except wave 3; depressive disorders and suicidality/self-harm in wave 2; and substance use disorders in waves 2, 4, and 5. MH-ED visits were increased from expected among female, adolescent, Asian race, high Child Opportunity Index patients. There was no association between MH-ED visits and NYC COVID-19 prevalence or NY State Stringency Index. CONCLUSIONS: The proportion of pediatric MH-ED visits during the COVID-19 pandemic was higher during each wave compared with the predicted prepandemic period, with varied increases among diagnostic and sociodemographic subgroups. Enhanced pediatric mental health resources are essential to address these findings.

Effect of Sepsis on Death as Modified by Solid Organ Transplantation.

Background: Patients who have undergone solid organ transplants (SOT) have an increased risk for sepsis compared with the general population. Paradoxically, studies suggest that SOT patients with sepsis may experience better outcomes compared with those without a SOT. However, these analyses used previous definitions of sepsis. It remains unknown whether the more recent definitions of sepsis and modern analytic approaches demonstrate a similar relationship. Methods: Using the Weill Cornell-Critical Care Database for Advanced Research, we analyzed granular physiologic, microbiologic, comorbidity, and therapeutic data in patients with and without SOT admitted to intensive care units (ICUs). We used a survival analysis with a targeted minimum loss-based estimation, adjusting for within-group (SOT and non-SOT) potential confounders to ascertain whether the effect of sepsis, defined by sepsis-3, on 28-day mortality was modified by SOT status. We performed additional analyses on restricted populations. Results: We analyzed 28 431 patients: 439 with SOT and sepsis, 281 with SOT without sepsis, 6793 with sepsis and without SOT, and 20 918 with neither. The most common SOT types were kidney (475) and liver (163). Despite a higher severity of illness in both sepsis groups, the adjusted sepsis-attributable effect on 28-day mortality for non-SOT patients was 4.1% (95% confidence interval [CI], 3.8-4.5) and -14.4% (95% CI, -16.8 to -12) for SOT patients. The adjusted SOT effect modification was -18.5% (95% CI, -21.2 to -15.9). The adjusted sepsis-attributable effect for immunocompromised controls was -3.5% (95% CI, -4.5 to -2.6). Conclusions: Across a large database of patients admitted to ICUs, the sepsis-associated 28-day mortality effect was significantly lower in SOT patients compared with controls.

COVID-19 is Observed in Older Children During the Omicron Wave in New York City.

BACKGROUND: The Omicron variant of SARS-CoV-2 has a predilection for the upper airways, causing symptoms such as sore throat, hoarse voice, and stridor. OBJECTIVE: We describe a series of children with COVID-19-associated croup in an urban multicenter hospital system. METHODS: We conducted a cross-sectional study of children ≤18 years of age presenting to the emergency department during the COVID-19 pandemic. Data were extracted from an institutional data repository comprised of all patients who were tested for SARS-CoV-2. We included patients with a croup diagnosis by International Classification of Diseases, 10th revision code and a positive SARS-CoV-2 test within 3 days of presentation. We compared demographics, clinical characteristics, and outcomes for patients presenting during a pre-Omicron period (March 1, 2020-December 1, 2021) to the Omicron wave (December 2, 2021-February 15, 2022). RESULTS: We identified 67 children with croup, 10 (15%) pre-Omicron and 57 (85%) during the Omicron wave. The prevalence of croup among SARS-CoV-2-positive children increased by a factor of 5.8 (95% confidence interval 3.0-11.4) during the Omicron wave compared to prior. More patients were ≥6 years of age in the Omicron wave than prior (19% vs. 0%). The majority were not hospitalized (77%). More patients ≥6 years of age received epinephrine therapy for croup during the Omicron wave (73% vs. 35%). Most patients ≥6 years of age had no croup history (64%) and only 45% were vaccinated against SARS-CoV-2. CONCLUSION: Croup was prevalent during the Omicron wave, atypically affecting patients ≥6 years of age. COVID-19-associated croup should be added to the differential diagnosis of children with stridor, regardless of age. © 2022 Elsevier Inc.

Urine-based multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS), a life-threatening condition during critical illness, is a common complication of COVID-19. It can originate from various disease etiologies, including severe infections, major injury, or inhalation of irritants. ARDS poses substantial clinical challenges due to a lack of etiology-specific therapies, multisystem involvement, and heterogeneous, poor patient outcomes. A molecular comparison of ARDS groups holds the potential to reveal common and distinct mechanisms underlying ARDS pathogenesis. METHODS: We performed a comparative analysis of urine-based metabolomics and proteomics profiles from COVID-19 ARDS patients (n = 42) and bacterial sepsis-induced ARDS patients (n = 17). To this end, we used two different approaches, first we compared the molecular omics profiles between ARDS groups, and second, we correlated clinical manifestations within each group with the omics profiles. RESULTS: The comparison of the two ARDS etiologies identified 150 metabolites and 70 proteins that were differentially abundant between the two groups. Based on these findings, we interrogated the interplay of cell adhesion/extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis through a multi-omic network approach. Moreover, we identified a proteomic signature associated with mortality in COVID-19 ARDS patients, which contained several proteins that had previously been implicated in clinical manifestations frequently linked with ARDS pathogenesis. CONCLUSION: In summary, our results provide evidence for significant molecular differences in ARDS patients from different etiologies and a potential synergy of extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis. The proteomic mortality signature should be further investigated in future studies to develop prediction models for COVID-19 patient outcomes.

Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. METHODS AND FINDINGS: In this study, we compared COVID-19 ARDS (n = 43) and bacterial sepsis-induced (non-COVID-19) ARDS (n = 24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. CONCLUSION: We present a first comprehensive molecular characterization of differences between two ARDS etiologies-COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions.

Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS.

Background: Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. Methods and Findings: In this study, we compared COVID-19 ARDS (n=43) and bacterial sepsis-induced (non-COVID-19) ARDS (n=24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within-ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. Conclusion: We present a first comprehensive molecular characterization of differences between two ARDS etiologies - COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions.

Urine-based multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS.

Acute respiratory distress syndrome (ARDS), a life-threatening condition during critical illness, is a common complication of COVID-19. It can originate from various disease etiologies, including severe infections, major injury, or inhalation of irritants. ARDS poses substantial clinical challenges due to a lack of etiology-specific therapies, multisystem involvement, and heterogeneous, poor patient outcomes. A molecular comparison of ARDS groups holds the potential to reveal common and distinct mechanisms underlying ARDS pathogenesis. In this study, we performed a comparative analysis of urine-based metabolomics and proteomics profiles from COVID-19 ARDS patients (n = 42) and bacterial sepsis-induced ARDS patients (n = 17). The comparison of these ARDS etiologies identified 150 metabolites and 70 proteins that were differentially abundant between the two groups. Based on these findings, we interrogated the interplay of cell adhesion/extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis through a multi-omic network approach. Moreover, we identified a proteomic signature associated with mortality in COVID-19 ARDS patients, which contained several proteins that had previously been implicated in clinical manifestations frequently linked with ARDS pathogenesis. In summary, our results provide evidence for significant molecular differences in ARDS patients from different etiologies and a potential synergy of extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis. The proteomic mortality signature should be further investigated in future studies to develop prediction models for COVID-19 patient outcomes.

Indications for Hospitalization in Children with SARS-CoV-2 Infection during the Omicron Wave in New York City.

The emergence of the Omicron variant was accompanied by an acute increase in COVID-19 cases and hospitalizations in New York City. An increased incidence of COVID-19-associated croup in children during the Omicron wave has been recognized, suggesting that there may be other changes in clinical symptoms and severity. To better understand clinical outcomes and health care utilization in children infected with SARS-CoV-2 during the Omicron wave, we performed a cross-sectional study in pediatric patients aged ≤18 years who were tested for SARS-CoV-2 in pediatric emergency departments within a large medical system in New York City from 2 December 2021 to 23 January 2022. We described the clinical characteristics and outcomes of pediatric patients who presented to the pediatric emergency department and were hospitalized with SARS-CoV-2 infection during the Omicron wave in New York City. There were 2515 children tested in the ED for SARS-CoV-2 of whom 794 (31.6%) tested positive. Fifty-eight children were hospitalized for a COVID-19-related indication, representing 7.3% of all COVID-19-positive children and 72% of hospitalized COVID-19-positive children. Most (64%) children hospitalized for a COVID-19-related indication were less than 5 years old. Indications for hospitalization included respiratory symptoms, clinical monitoring of patients with comorbid conditions, and exacerbations of underlying disease. Eleven (19%) hospitalized children were admitted to the ICU and six (10%) required mechanical ventilation. Children infected with COVID-19 during the Omicron wave, particularly those less than 5 years old, were at risk for hospitalization. A majority of hospitalizations were directly related to COVID-19 infection although clinical indications varied with less than a half being admitted for respiratory diseases including croup. Our findings underscore the need for an effective COVID-19 vaccine in those less than 5 years old, continued monitoring for changes in clinical outcomes and health care utilization in children as more SARS-CoV-2 variants emerge, and understanding that children are often admitted for non-respiratory diseases with COVID-19.

Integrative metabolomic and proteomic signatures define clinical outcomes in severe COVID-19.

The coronavirus disease-19 (COVID-19) pandemic has ravaged global healthcare with previously unseen levels of morbidity and mortality. In this study, we performed large-scale integrative multi-omics analyses of serum obtained from COVID-19 patients with the goal of uncovering novel pathogenic complexities of this disease and identifying molecular signatures that predict clinical outcomes. We assembled a network of protein-metabolite interactions through targeted metabolomic and proteomic profiling in 330 COVID-19 patients compared to 97 non-COVID, hospitalized controls. Our network identified distinct protein-metabolite cross talk related to immune modulation, energy and nucleotide metabolism, vascular homeostasis, and collagen catabolism. Additionally, our data linked multiple proteins and metabolites to clinical indices associated with long-term mortality and morbidity. Finally, we developed a novel composite outcome measure for COVID-19 disease severity based on metabolomics data. The model predicts severe disease with a concordance index of around 0.69, and shows high predictive power of 0.83-0.93 in two independent datasets.

Baseline haemoglobin A1c and the risk of COVID-19 hospitalization among patients with diabetes in the INSIGHT Clinical Research Network.

AIMS: To examine the association between baseline glucose control and risk of COVID-19 hospitalization and in-hospital death among patients with diabetes. METHODS: We performed a retrospective cohort study of adult patients in the INSIGHT Clinical Research Network with a diabetes diagnosis and haemoglobin A1c (HbA1c) measurement in the year prior to an index date of March 15, 2020. Patients were divided into four exposure groups based on their most recent HbA1c measurement (in mmol/mol): 39-46 (5.7%-6.4%), 48-57 (6.5%-7.4%), 58-85 (7.5%-9.9%), and ≥86 (10%). Time to COVID-19 hospitalization was compared in the four groups in a propensity score-weighted Cox proportional hazards model adjusting for potential confounders. Patients were followed until June 15, 2020. In-hospital death was examined as a secondary outcome. RESULTS: Of 168,803 patients who met inclusion criteria; 50,016 patients had baseline HbA1c 39-46 (5.7%-6.4%); 54,729 had HbA1c 48-57 (6.5-7.4%); 47,640 had HbA1c 58-85 (7.5^%-9.9%) and 16,418 had HbA1c ≥86 (10%). Compared with patients with HbA1c 48-57 (6.5%-7.4%), the risk of hospitalization was incrementally greater for those with HbA1c 58-85 (7.5%-9.9%) (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI] 1.06-1.34) and HbA1c ≥86 (10%) (aHR 1.40, 95% CI 1.19-1.64). The risk of COVID-19 in-hospital death was increased only in patients with HbA1c 58-85 (7.5%-9.9%) (aHR 1.29, 95% CI 1.06, 1.61). CONCLUSIONS: Diabetes patients with high baseline HbA1c had a greater risk of COVID-19 hospitalization, although association between HbA1c and in-hospital death was less consistent. Preventive efforts for COVID-19 should be focused on diabetes patients with poor glucose control.

Building climate-sensitive nutrition programmes.

The food system and climate are closely interconnected. Although most research has focused on the need to adopt a plant-based diet to help mitigate climate change, there is also an urgent need to examine the effects of climate change on food systems to adapt to climate change. A systems approach can help identify the pathways through which climate influences food systems, thereby ensuring that programmes combating malnutrition take climate into account. Although little is known about how climate considerations are currently incorporated into nutrition programming, climate information services have the potential to help target the delivery of interventions for at-risk populations and reduce climate-related disruption during their implementation. To ensure climate services provide timely information relevant to nutrition programmes, it is important to fill gaps in our knowledge about the influence of climate variability on food supply chains. A proposed roadmap for developing climate-sensitive nutrition programmes recommends: (i) research aimed at achieving a better understanding of the pathways through which climate influences diet and nutrition, including any time lags; (ii) the identification of entry points for climate information into the decision-making process for nutrition programme delivery; and (iii) capacity-building and training programmes to better equip public health practitioners with the knowledge, confidence and motivation to incorporate climate resilience into nutrition programmes. With sustained investment in capacity-building, data collection and analysis, climate information services can be developed to provide the data, analyses and forecasts needed to ensure nutrition programmes target their interventions where and when they are most needed.

Les systèmes alimentaire et climatique sont étroitement liés. Bien que la plupart des recherches se concentrent sur le besoin d'adopter un régime végétarien pour contribuer à atténuer le changement climatique, il est également urgent d'examiner les effets de ce changement climatique sur les systèmes alimentaires afin de les adapter en conséquence. Une approche systémique peut aider à déterminer dans quelle mesure le climat influence les systèmes alimentaires, et dès lors à faire en sorte que les programmes de lutte contre la malnutrition en tiennent compte. On ignore encore sous quelle forme les considérations climatiques sont actuellement intégrées dans les programmes de nutrition. Cependant, les services climatologiques peuvent contribuer à cibler le déploiement d'interventions pour les populations à risque, ainsi qu'à réduire les perturbations causées par le climat au cours de leur mise en œuvre. Pour veiller à ce que ces services fournissent à point nommé des informations utiles aux programmes de nutrition, il faut impérativement combler le manque de connaissances en matière d'impact des variations climatiques sur les chaînes d'approvisionnement alimentaire. La feuille de route proposée pour l'élaboration de programmes de nutrition adaptés au changement climatique recommande: (i) de mener des recherches visant à mieux comprendre dans quelle mesure le climat influence l'alimentation et la nutrition, en tenant compte des éventuels décalages temporelshoraires; (ii) d'identifier les points d'entrée des informations relatives au climat dans le processus décisionnel de déploiement des programmes alimentaires; et enfin, (iii) de développer des plans de formation et de renforcement des capacités afin que les professionnels de la santé publique disposent des connaissances, de la confiance et de la motivation nécessaires pour intégrer l'adaptation au changement climatique dans les programmes de nutrition. En investissant durablement dans le renforcement des capacités ainsi que dans la collecte et l'analyse de données, il est possible d'instaurer des services climatologiques qui communiqueront les informations, analyses et prévisions requises pour que les programmes de nutrition organisent leurs actions à l'endroit et au moment où elles deviennent indispensables.

El sistema alimentario y el clima están muy interconectados. Aunque la mayoría de las investigaciones se han centrado en la necesidad de adoptar una dieta basada en el consumo de plantas para ayudar a mitigar el cambio climático, también es urgente analizar los efectos del cambio climático en los sistemas alimentarios para adaptarse al mismo. Un enfoque sistémico puede ayudar a identificar las vías a través de las que el clima influye en los sistemas alimentarios, garantizando así que los programas de lucha contra la malnutrición tengan en cuenta el clima. Si bien se sabe poco sobre cómo se incorporan en la actualidad los aspectos climáticos a los programas de nutrición, los servicios de información climática tienen el potencial de ayudar a orientar las intervenciones hacia las poblaciones de riesgo y a reducir los trastornos relacionados con el clima durante su aplicación. Para garantizar que los servicios climáticos proporcionen información oportuna y relevante a los programas de nutrición, es importante solucionar las carencias de nuestros conocimientos sobre la influencia de la variabilidad climática en las cadenas de suministro de alimentos. Una hoja de ruta propuesta para desarrollar programas de nutrición sensibles al clima recomienda i) la investigación destinada a lograr una mejor comprensión de las vías a través de las que el clima influye en la dieta y en la nutrición, incluidos los retrasos; ii) la identificación de los puntos de entrada de la información sobre el clima en el proceso de toma de decisiones para la ejecución de los programas de nutrición; y iii) los programas de creación de capacidad y formación para preparar mejor a los profesionales de la salud pública con los conocimientos, la confianza y la motivación que permitan incorporar la adaptación al clima en los programas de nutrición. Si se invierte de manera sostenida en la creación de capacidades, la recopilación y el análisis de datos, se pueden desarrollar servicios de información climática que proporcionen los datos, los análisis y las previsiones necesarios para garantizar que los programas de nutrición orienten sus intervenciones donde y cuando más se necesiten.

Modeling complex effects of exposure to particulate matter and extreme heat during pregnancy on congenital heart defects: A U.S. population-based case-control study in the National Birth Defects Prevention Study.

BACKGROUND/OBJECTIVE: Research suggests gestational exposure to particulate matter ≤2.5 µm (PM2.5) and extreme heat may independently increase risk of birth defects. We investigated whether duration of gestational extreme heat exposure modifies associations between PM2.5 exposure and specific congenital heart defects (CHDs). We also explored nonlinear exposure-outcome relationships. METHODS: We identified CHD case children (n = 2824) and non-malformed live-birth control children (n = 4033) from pregnancies ending between 1999 and 2007 in the National Birth Defects Prevention Study, a U.S. population-based multicenter case-control study. We assigned mothers 6-week averages of PM2.5 exposure during the cardiac critical period (postconceptional weeks 3-8) using the closest monitor within 50 km of maternal residence. We assigned a count of extreme heat days (EHDs, days above the 90th percentile of daily maximum temperature for year, season, and weather station) during this period using the closest weather station. Using generalized additive models, we explored logit-nonlinear exposure-outcome relationships, concluding logistic models were reasonable. We estimated joint effects of PM2.5 and EHDs on six CHDs using logistic regression models adjusted for mean dewpoint and maternal age, education, and race/ethnicity. We assessed multiplicative and additive effect modification. RESULTS: Conditional on the highest observed EHD count (15) and at least one critical period day during spring/summer, each 5 µg/m3 increase in average PM2.5 exposure was significantly associated with perimembranous ventricular septal defects (VSDpm; OR: 1.54 [95% CI: 1.01, 2.41]). High EHD counts (8+) in the same population were positively, but non-significantly, associated with both overall septal defects and VSDpm. Null or inverse associations were observed for lower EHD counts. Multiplicative and additive effect modification estimates were consistently positive in all septal models. CONCLUSIONS: Results provide limited evidence that duration of extreme heat exposure modifies the PM2.5-septal defects relationship. Future research with enhanced exposure assessment and modeling techniques could clarify these relationships.