Social Distancing During the COVID-19 Pandemic and Neonatal Mortality in the US.

Importance: Neonatal mortality is a major public health concern that was potentially impacted by the COVID-19 pandemic. To prepare for future health crises, it is important to investigate whether COVID-19 pandemic-related interventions were associated with changes in neonatal mortality. Objective: To investigate whether social distancing during the pandemic was associated with a higher neonatal mortality rate. Design, Setting, and Participants: This cohort study examined maternal-linked birth and infant death records from the National Center for Health Statistics, a population-level US database, from 2016 through 2020. The mortality rates were correlated using machine learning-based autoregressive integrated moving average (ARIMA) models with the social distancing index (SDI). The reference period was January 2016 through February 2020, and the pandemic period was March through December 2020. Statistical analysis was performed from March 2023 to May 2024. Exposures: SDI, computed from 6 mobility metrics. Main Outcomes and Measures: The primary outcome was neonatal mortality rate, defined as death at age less than 28 days. Results: The study included 18 011 173 births, of which 15 136 596 were from the reference period (7 753 555 [51.22%] male; 11 643 094 [76.92%] with maternal age of 20 to 34 years) and 2 874 577 were from the pandemic period (1 472 539 [51.23%] male; 2 190 158 [76.19%] with maternal age of 20 to 34 years). Through ARIMA-adjusted analyses, accounting for the declining mortality trend in the reference period, the mortality rates during the pandemic period did not significantly differ from the expected rates. SDI did not exhibit significant correlations with neonatal mortality (unadjusted: correlation coefficient [CC], 0.14 [95% CI, -0.53 to 0.70]; ARIMA adjusted: CC, 0.29 [95% CI, -0.41 to 0.77]), early neonatal mortality (unadjusted: CC, 0.33 [95% CI, -0.37 to 0.79]; ARIMA adjusted: CC, 0.45 [95% CI, -0.24 to 0.84]), and infant mortality (unadjusted: CC, -0.09 [95% CI, -0.68 to 0.57]; ARIMA adjusted: CC, 0.35 [95% CI, -0.35 to 0.80]). However, lag analyses found that SDI was associated with higher neonatal and early neonatal mortality rates with a 2-month lag period, but not with infant mortality rate. SDI was also associated with increases in 22-to-27 weeks' and 28-to-32 weeks' preterm delivery with a 1-month lag period. Conclusions and Relevance: In this population-level study of National Center for Health Statistics databases, neonatal, early neonatal, and infant mortality rates did not increase during the initial COVID-19 pandemic period. However, associations were observed between the pandemic period social distancing measures and higher rates of neonatal and early neonatal mortality, as well as preterm birth rate with a lag period, suggesting the importance of monitoring infant health outcomes following pandemic-related population behavior changes.

Neonatal fluid overload-ignorance is no longer bliss.

Excessive accumulation of fluid may result in interstitial edema and multiorgan dysfunction. Over the past few decades, the detrimental impact of fluid overload has been further defined in adult and pediatric populations. Growing evidence highlights the importance of monitoring, preventing, managing, and treating fluid overload appropriately. Translating this knowledge to neonates is difficult as they have different disease pathophysiologies, and because neonatal physiology changes rapidly postnatally in many of the organ systems (i.e., skin, kidneys, and cardiovascular, pulmonary, and gastrointestinal). Thus, evaluations of the optimal targets for fluid balance need to consider the disease state as well as the gestational and postmenstrual age of the infant. Integration of what is known about neonatal fluid overload with individual alterations in physiology is imperative in clinical management. This comprehensive review will address what is known about the epidemiology and pathophysiology of neonatal fluid overload and highlight the known knowledge gaps. Finally, we provide clinical recommendations for monitoring, prevention, and treatment of fluid overload.

Age Related Bioenergetics Profiles in Isolated Rat Cardiomyocytes Using Extracellular Flux Analyses.

Mitochondrial dysfunction is increasingly recognized and studied as a mediator of heart disease. Extracellular flux analysis (XF) has emerged as a powerful tool to investigate cellular bioenergetics in the context of cardiac health and disease, however its use and interpretation requires improved understanding of the normal metabolic differences in cardiomyocytes (CM) at various stages of maturation. This study standardized XF analyses methods (mitochondrial stress test, glycolytic stress test and palmitate oxidation test) and established age related differences in bioenergetics profiles of healthy CMs at newborn (NB1), weaning (3WK), adult (10WK) and aged (12-18MO) time points. Findings show that immature CMs demonstrate a more robust and sustained glycolytic capacity and a relative inability to oxidize fatty acids when compared to older CMs. The study also highlights the need to recognize the contribution of CO2 from the Krebs cycle as well as lactate from anaerobic glycolysis to the proton production rate before interpreting glycolytic capacity in CMs. Overall, this study demonstrates that caution should be taken to assure that translatable developmental time points are used to investigate mitochondrial dysfunction as a cause of cardiac disease. Specifically, XF analysis of newborn CMs should be reserved to study fetal/neonatal disease and older CMs (≥10 weeks) should be used to investigate adult disease pathogenesis. Knowledge gained will aid in improved investigation of developmentally programmed heart disease and stress the importance of discerning maturational differences in bioenergetics when developing mitochondrial targeted preventative and therapeutic strategies for cardiac disease.

Maternal high-fat diet impairs cardiac function in offspring of diabetic pregnancy through metabolic stress and mitochondrial dysfunction.

Offspring of diabetic pregnancies are at risk of cardiovascular disease at birth and throughout life, purportedly through fuel-mediated influences on the developing heart. Preventative measures focus on glycemic control, but the contribution of additional offenders, including lipids, is not understood. Cellular bioenergetics can be influenced by both diabetes and hyperlipidemia and play a pivotal role in the pathophysiology of adult cardiovascular disease. This study investigated whether a maternal high-fat diet, independently or additively with diabetes, could impair fuel metabolism, mitochondrial function, and cardiac physiology in the developing offspring's heart. Sprague-Dawley rats fed a control or high-fat diet were administered placebo or streptozotocin to induce diabetes during pregnancy and then delivered offspring from four groups: control, diabetes exposed, diet exposed, and combination exposed. Cardiac function, cellular bioenergetics (mitochondrial stress test, glycolytic stress test, and palmitate oxidation assay), lipid peroxidation, mitochondrial histology, and copy number were determined. Diabetes-exposed offspring had impaired glycolytic and respiratory capacity and a reduced proton leak. High-fat diet-exposed offspring had increased mitochondrial copy number, increased lipid peroxidation, and evidence of mitochondrial dysfunction. Combination-exposed pups were most severely affected and demonstrated cardiac lipid droplet accumulation and diastolic/systolic cardiac dysfunction that mimics that of adult diabetic cardiomyopathy. This study is the first to demonstrate that a maternal high-fat diet impairs cardiac function in offspring of diabetic pregnancies through metabolic stress and serves as a critical step in understanding the role of cellular bioenergetics in developmentally programmed cardiac disease.

Exogenous modification of platelet membranes with the omega-3 fatty acids EPA and DHA reduces platelet procoagulant activity and thrombus formation.

Several studies have implicated the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in inhibition of normal platelet function, suggesting a role for platelets in EPA- and DHA-mediated cardioprotection. However, it is unclear whether the cardioprotective mechanisms arise from alterations to platelet-platelet, platelet-matrix, or platelet-coagulation factor interactions. Our previous results led us to hypothesize that EPA and DHA alter the ability of platelets to catalyze the generation of thrombin. We tested this hypothesis by exogenously modifying platelet membranes with EPA and DHA, which resulted in compositional changes analogous to increased dietary EPA and DHA intake. Platelets treated with EPA and DHA showed reductions in the rate of thrombin generation and exposure of platelet phosphatidylserine. In addition, treatment of platelets with EPA and DHA decreased thrombus formation and altered the processing of thrombin precursor proteins. Furthermore, treatment of whole blood with EPA and DHA resulted in increased occlusion time and a sharply reduced accumulation of fibrin under flow conditions. These results demonstrate that EPA and DHA inhibit, but do not eliminate, the ability of platelets to catalyze thrombin generation in vitro. The ability of EPA and DHA to reduce the procoagulant function of platelets provides a possible mechanism behind the cardioprotective phenotype in individuals consuming high levels of EPA and DHA.