Assessment of Cardiovascular Health of Children Ages 6 to 10 Years Conceived by Assisted Reproductive Technology.

Importance: Assisted reproductive technology (ART) has been widely used for treatment of infertility and has brought millions of births worldwide. The health of offspring conceived by ART has been of much concern, and adverse cardiovascular health outcomes have been reported by previous studies. Objective: To assess the cardiovascular health of children conceived by ART. Design, Setting, and Participants: This cohort study was conducted among participants recruited from November 2017 to February 2019. Participants were 382 children conceived by ART who were selected from a single reproductive center and 382 children who were naturally conceived, randomly selected from a primary school, and matched by sex, age, and maternal age at the child's birth (2 years older or younger). Data were analyzed from March 2019 through December 2019. Exposures: Conception by ART. Main Outcomes and Measures: Blood pressure was measured, and echocardiography was performed to determine left ventricular structural and functional parameters. Adjusted relative wall thickness (aRWT) was found for age, with high RWT defined as an aRWT of 0.375 or more. Results: Among 764 children aged 6 to 10 years, 382 children were conceived by ART (mean [SD] age, 7.20 [1.21] years; 201 [52.6%] boys) and 382 children were naturally conceived (mean [SD] age, 7.20 [1.21] years; 201 [52.6%] boys). Children conceived by ART had statistically significantly increased mean (SD) height (130.2 [9.5] cm vs 128.5 [8.1] cm; P = .007) and body mass index (17.6 [3.6] vs 17.1 [2.7]; P = .03). Those conceived by ART, compared with children in the matched control group, had statistically significantly increased blood pressure (mean [SD] systolic blood pressure, 105.5 [6.9] mm Hg vs 103.5 [8.4] mm Hg; adjusted P < .001; mean [SD] diastolic blood pressure, 67.2 [5.6] mm Hg vs 62.2 [6.3] mm Hg ; adjusted P < .001), left ventricular systolic dysfunction (mean [SD] left ventricular ejection fraction, 64.61% [3.20%] vs 66.70% [3.89%]; adjusted P < .001), and diastolic dysfunction (mean [SD] early/late mitral/tricuspid diastolic velocities ratio, 1.66 [0.28] vs 2.21 [0.36]; adjusted P < .001). They also had statistically significantly increased parameters of left ventricular structure, including mean (SD) left ventricular mass index (31.97 [5.04] g/m2.7 vs 28.28 [3.54] g/m2.7; adjusted P < .001) and RWT (3.30 [0.41] mm vs 2.98 [0.14] mm; adjusted P < .001). Additionally, children conceived by ART had statistically significantly increased prevalence of left ventricular hypertrophy (9 children [2.4%] vs 2 children [0.5%]; P = .03), high RWT (61 children [16.0%] vs 0 children; P < .001), and left ventricle remodeling patterns, including concentric remodeling (60 children [15.7%] vs 0 children), eccentric hypertrophy (8 children [2.1%] vs 2 children [0.5%]), and concentric hypertrophy (1 child [0.3%] vs 0 children) (P for left ventricle remodeling < .001). Conclusions and Relevance: This study found that children conceived by ART had increased blood pressure and unfavorable changes in left ventricular structure and function compared with children who were naturally conceived. These findings suggest that further studies are needed to investigate the potential mechanisms and long-term outcomes associated with these differences.

Work-life conflict and cardiovascular health: 5-year follow-up of the Gutenberg Health Study.

INTRODUCTION: Work-life conflicts (WLC) may impact health, but few studies prospectively consider the impact of WLC on objective outcomes such as cardiovascular disease. Using data from the Gutenberg Health Study (GHS), we examined if WLC at baseline was associated with an increased five-year incidence of cardiovascular events (myocardial infarct, stroke, atrial fibrillation, peripheral artery disease, coronary artery disease, chronic heart failure, sudden cardiac death). We also considered if WLC was associated with incident hypertension and arterial stiffness and if the effects of WLC on cardiovascular health differ for men and women. METHODS: A working subsample of the 15,010 GHS cohort participants completed the Copenhagen Psychosocial Questionnaire, which included five "work-privacy conflict" questions at baseline and at the five-year follow-up. Relative risks for incident hypertension due to increased WLC at baseline (WLC scores exceeding 60 out of 100) were estimated with Poisson regression in the subgroup of participants without hypertension at baseline (n = 2426). Categories of WLC at baseline and follow-up were also used to examine the risk of hypertension due to chronic/recurrent WLC. In this subgroup, we also examined the association between WLC as a continuous score ranging from 0 to 100 with change to arterial stiffness after five years using linear regression. Hazard ratios were estimated for incident cardiovascular events in a larger subsample of participants without prevalent cardiovascular disease at baseline (n = 3698) using Cox regression. We used various multivariable regression models to adjust for sex, age, socioeconomic status, occupational, household, and cardiovascular risk factors. RESULTS: We found no association between WLC and incident hypertension or increased arterial stiffness. The fully-adjusted relative risk for WLC >60 at baseline and hypertension was 0.93 (95% 0.74-1.17). The risk of hypertension due to chronic/recurrent WLC >60 was increased but not statistically significant (RR = 1.13, 95% CI 0.83-1.54). Overall, hazard ratios for incident cardiovascular events were also not increased. However, stratifying the results by sex resulted in a hazard ratio of 1.47 (95% CI 0.54-3.98) for incident cardiovascular disease among women in the fully adjusted model. CONCLUSIONS: Although our results were not statistically significant, they indicate that WLC is negatively impacting the cardiovascular health of women. While these results need to be confirmed with additional research and a longer follow-up, interventions to prevent WLC will promote health and could be especially beneficial for women.

Assessment of Exercise Intolerance in Patients with Pre-Dialysis CKD with Cardiopulmonary Function Testing: Translation to Everyday Practice.

BACKGROUND: Chronic kidney disease (CKD) is often characterized by increased prevalence of cardiovascular risk factors and increased incidence of cardiovascular events and death. Reduced cardiovascular reserve and exercise intolerance are common in patients with CKD and are associated with adverse outcomes. SUMMARY: The gold standard for identifying exercise limitation is cardiopulmonary exercise testing (CPET). CPET provides an integrative evaluation of cardiovascular, pulmonary, hematopoietic, neuropsychological, and metabolic function during maximal or submaximal exercise. It is useful in clinical setting for differentiation of the causes of exercise intolerance, risk stratification, and assessment of response to relevant treatments. A number of recent studies have used CPET in patients with pre-dialysis CKD, aiming to assess the cardiovascular reserve of these individuals, as well as the effect of interventions such as exercise training programs on their functional capacity. This review provides an in-depth description of CPET methodology and an overview of studies that utilized CPET technology to assess cardiovascular reserve in patients with pre-dialysis CKD. Key Messages: CPET can delineate multisystem changes and offer comprehensive phenotyping of factors determining overall cardiovascular risk. Potential clinical applications of CPET in CKD patients range from objective diagnosis of exercise intolerance to preoperative and long-term risk stratification and providing intermediate endpoints for clinical trials. Future studies should delineate the association of CPET indexes, with cardiovascular and respiratory alterations and hard outcomes in CKD patients, to enhance its diagnostic and prognostic utility in this population.

Assessment and Management of Volume Overload Among Patients on Chronic Dialysis.

Volume overload is the most common complication in end-stage renal disease (ESRD) patients, being directly related to numerous complications including resistant hypertension, cardiac hypertrophy, congestive heart failure or arterial stiffness, among others. Therefore, volume overload is now considered an important risk factor for hard outcomes, like all-cause or cardiovascular mortality. Relying solely on clinical examination for assessing volume overload in ESRD patients lacks sensitivity and specificity. Numerous efforts have been made to identify new methods that could objectively assess volume status; however, each of them has important limitations. This review aims to discuss the most frequently used methods (biomarkers, inferior vena cava assessment, lung ultrasonography, bioimpedance analysis and blood volume monitoring) and to compare the advantage of each method vs. the overall/ clinical strategy.

Examining "race" in physiology.

Racial disparities in cardiovascular and cerebrovascular health outcomes are well described, and recent research has shed light on the mechanistic underpinnings of those disparities. However, "race" is a social construct that is poorly defined and continually evolving and is historically based on faulty premises. The continued categorization by race in physiological research suggests that there are inherent differences between races, rather than addressing the specific underlying factors that result in health disparities between groups. The purpose of this Perspectives article is to provide a brief history of the genesis of categorization by race, why such categorization should be reconsidered in physiology research, and offer recommendations to more directly investigate the underlying factors that result in group disparities in cardiovascular and cerebrovascular health.

Validation of four-dimensional flow cardiovascular magnetic resonance for aortic stenosis assessment.

The management of patients with aortic stenosis (AS) crucially depends on accurate diagnosis. The main aim of this study were to validate the four-dimensional flow (4D flow) cardiovascular magnetic resonance (CMR) methods for AS assessment. Eighteen patients with clinically severe AS were recruited. All patients had pre-valve intervention 6MWT, echocardiography and CMR with 4D flow. Of these, ten patients had a surgical valve replacement, and eight patients had successful transcatheter aortic valve implantation (TAVI). TAVI patients had invasive pressure gradient assessments. A repeat assessment was performed at 3-4 months to assess the remodelling response. The peak pressure gradient by 4D flow was comparable to an invasive pressure gradient (54 ± 26 mmHG vs 50 ± 34 mmHg, P = 0.67). However, Doppler yielded significantly higher pressure gradient compared to invasive assessment (61 ± 32 mmHG vs 50 ± 34 mmHg, P = 0.0002). 6MWT was associated with 4D flow CMR derived pressure gradient (r = -0.45, P = 0.01) and EOA (r = 0.54, P < 0.01) but only with Doppler EOA (r = 0.45, P = 0.01). Left ventricular mass regression was better associated with 4D flow derived pressure gradient change (r = 0.64, P = 0.04). 4D flow CMR offers an alternative method for non-invasive assessment of AS. In addition, 4D flow derived valve metrics have a superior association to prognostically relevant 6MWT and LV mass regression than echocardiography.

Temporal Changes in Hypertensive Disorders of Pregnancy and Impact on Cardiovascular and Obstetric Outcomes.

Hypertensive disorders of pregnancy (HDP) are a major cause of maternal morbidity. However, short-term outcomes of HDP subgroups remain unknown. Using National Inpatient Sample database, all delivery hospitalizations between 2004 and 2014 with or without HDP (preeclampsia/eclampsia, chronic hypertension, superimposed preeclampsia on chronic hypertension, and gestational hypertension) were analyzed to examine the association between HDP and adverse in-hospital outcomes. We identified >44 million delivery hospitalizations, within which the prevalence of HDP increased from 8% to 11% over a decade with increasing comorbidity burden. Women with chronic hypertension have higher risks of myocardial infarction, peripartum cardiomyopathy, arrhythmia, and stillbirth compared to women with preeclampsia. Out of all HDP subgroups, the superimposed preeclampsia population had the highest risk of stroke (odds ratio [OR] 7.83, 95% confidence interval [CI] 6.25 to 9.80), myocardial infarction (OR 5.20, 95% CI 3.11 to 8.69), peripartum cardiomyopathy (OR 4.37, 95% CI 3.64 to 5.26), preterm birth (OR 4.65, 95% CI 4.48 to 4.83), placental abruption (OR 2.22, 95% CI 2.09 to 2.36), and stillbirth (OR 1.78, 95% CI 1.66 to 1.92) compared to women without HDP. In conclusion, we are the first to evaluate chronic systemic hypertension without superimposed preeclampsia as a distinct subgroup in HDP and show that women with chronic systemic hypertension are at even higher risk of some adverse outcomes compared to women with preeclampsia. In conclusion, the chronic hypertension population, with and without superimposed preeclampsia, is a particularly high-risk group and may benefit from increased antenatal surveillance and the use of a prognostic risk assessment model incorporating HDP to stratify intrapartum care.

Neuroendocrine and cardiovascular responses to shifting status.

We review recent work on human neuroendocrine and cardiovascular responses to stable and unstable status. We describe experiments examining inter-personal and inter-group contexts, involving both experimentally created as well as naturalistic (gender, SES) status differences. Across studies the pattern of results is clear: Stable status differences are stressful for those low in status, which is evident from increased cortisol and a cardiovascular response-pattern indicative of threat (low cardiac output, high vascular resistance); however, when status differences are unstable the same effects are found among those high in status, while those low in status show challenge (low vascular resistance, high cardiac output). Potential status-loss also leads to increased testosterone. We discuss implications and suggestions for further research.

Depression and cardiovascular disease: The deep blue sea of women's heart.

Cardiovascular disease (CVD) constitutes a leading worldwide health problem, with increasing evidence of differences between women and men both in epidemiology, pathophysiology, clinical management, and outcomes. Data from the literature suggest that women experience a doubled incidence of CVD related deaths, while angina, heart failure and stroke are increasingly prevalent in females. About 20-25% of women go through depression during their life, and depressive symptoms have been considered a relevant emergent, non-traditional risk factor for CVD in this part of the general population. Underlying mechanisms explaining the link between depression and CVD may range from behavioral to biological risk factors, including sympathetic nervous system hyperactivity and impairment in hypothalamic-pituitary-adrenal function. However, the neuroendocrine-driven background could only partially explain the differences mentioned above for chronic systemic inflammation, altered hemostasis and modulation of cardiac autonomic control. In addition, some evidence also suggests the existence of gender-specific differences in biological responses to mental stress. Given these premises, we here summarize the current knowledge about depression and CVD relationship in women, highlighting the sex differences in physiopathology, clinical presentation and treatments.

The Influence of Sex on Cardiac Physiology and Cardiovascular Diseases.

Cardiovascular disease (CVD) is the leading cause of death world-wide. Most of treatment strategies were based on studies conducted on male patients. Studies have shown that significant differences exist between the two sexes in the development of CVD. There are certain differences between men and women in the structure and physiological functions of the heart such as left ventricular mass index, resting heart rate, and contractile function. Accordingly, the pathological features of the heart such as the extend of hypertrophy, fibrosis, and remodeling are also different. In addition, different genders also affect clinical symptoms, responses to treatment and prognosis in the development of CVD. Therefore, it is important to take these differences into consideration when design treatment options for men and women.

Vascular Pathways of Testosterone: Clinical Implications.

Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. Testosterone (T) is an important sex hormone that triggers several genomic and non-genomic pathways, leading to improvements of several cardiovascular risk factors and quality of life in men. At the vascular level, the key effect of T is the vasorelaxation. This review discusses the molecular pathways and clinical implications of T in the vascular system. Firstly, the mechanisms involved in the T vasodilator effect will be presented. Then, it will be discussed the association of T with the main risks for CVD, namely metabolic syndrome, type 2 diabetes mellitus, obesity, atherosclerosis, dyslipidaemia and hypertension. Several studies have shown a correlation between low T levels and an increased prevalence of several CVD. These observations suggest that T has beneficial effects on the cardiovascular system and that testosterone replacement therapy may become a therapeutic reality for some of these disorders. Graphical abstract .

Sex differences in respiratory and circulatory cost during hypoxic walking: potential impact on oxygen saturation.

Energy expenditure (EE) during treadmill walking under normal conditions (normobaric normoxia, 21% O2) and moderate hypoxia (13% O2) was measured. Ten healthy young men and ten healthy young women walked on a level (0°) gradient a range of speeds (0.67-1.67 m s-1). During walking, there were no significant differences in reductions in arterial oxygen saturation (SpO2) between the sexes. The hypoxia-induced increase in EE, heart rate (HR [bpm]) and ventilation ([Formula: see text] [L min-1]) were calculated. Using a multivariate model that combined EE, [Formula: see text], and HR to predict ΔSpO2 (hypoxia-induced reduction), a very strong fit model both for men (r2 = 0.900, P < 0.001) and for women was obtained (r2 = 0.957, P < 0.001). The contributions of EE, VE, and HR to ΔSpO2 were markedly different between men and women. [Formula: see text] and EE had a stronger effect on ΔSpO2 in women ([Formula: see text]: 4.1% in women vs. 1.7% in men; EE: 28.1% in women vs. 15.8% in men), while HR had a greater effect in men (82.5% in men and 67.9% in women). These findings suggested that high-altitude adaptation in response to hypoxemia has different underlying mechanisms between men and women. These results can help to explain how to adapt high-altitude for men and women, respectively.

Cardiovascular prevention in women: a narrative review from the Italian Society of Cardiology working groups on 'Cardiovascular Prevention, Hypertension and peripheral circulation' and on 'Women Disease'.

: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in women.Some authors highlighted that the female risk profile consists of traditional and emerging risk factors. Despite the lower prevalence of type 2 diabetes, years of life lost owing to the disease for women are substantially higher compared with men. In addition, pregnancy complicated by gestational diabetes represents a risk factor for CVD. Women with gestational diabetes have a higher prevalence of coronary artery disease that occur at a younger age and are independent of T2DM.Hypertension is an important cardiovascular risk factor in women. Estrogens and progesterone, known to have an impact on blood pressure levels, have also been proposed to be protective against sleep-disordered breathing. It is very difficult to understand whereas obstructive sleep apnea in women is independently associated with hypertension or if many confounders acting at different stages of the woman lifespan mediate this relation.The cardioprotective effect of physical activity in women of all ages is well known. Women are generally more physically inactive than men. During and after menopause, most women tend to reduce their physical activity levels and together with the reduction in basal metabolic rate, women experience loss of skeletal muscle mass with a negative change in the ratio of fat-to-lean mass.In conclusion, sex differences in the cardiovascular system are because of dissimilarities in gene expression and sex hormones; these result in variations in prevalence and presentation of CVD and associated conditions, such as diabetes, hypertension and vascular and cardiac remodeling.Changes in lifestyle and increase in physical activity could help in prevention of cardiovascular disease in women.

Rationale, design and study protocol of the randomised controlled trial: Diabetes Interventional Assessment of Slimming or Training tO Lessen Inconspicuous Cardiovascular Dysfunction (the DIASTOLIC study).

INTRODUCTION: Despite their young age and relatively short duration of disease, younger adults with type 2 diabetes (T2D) already have diastolic dysfunction and may be at risk of incipient heart failure. Whether weight loss or exercise training improve cardiac dysfunction in people with T2D remains to be established. METHODS AND ANALYSIS: Prospective, randomised, open-label, blind endpoint trial. The primary aim of the study is to determine if diastolic function can be improved by either a meal replacement plan or a supervised exercise programme, compared with guideline-directed care. A total of 90 obese participants with T2D (aged 18-65 years), diabetes duration <12 years and not on insulin treatment will be randomised to either guideline-directed clinical care with lifestyle coaching, a low-energy meal replacement diet (average ≈810 kcal/day) or a supervised exercise programme for 12 weeks. Participants undergo glycometabolic profiling, cardiopulmonary exercise testing, echocardiography and MRI scanning to assesses cardiac structure and function and dual-energy X-ray absorptiometry scanning for body composition. Key secondary aims are to assess the effects of the interventions on glycaemic control and insulin resistance, exercise capacity, blood pressure, changes in body composition and association of favourable cardiac remodelling with improvements in weight loss, exercise capacity and glycometabolic control. ETHICS AND DISSEMINATION: The study has full ethical approval, and data collection was completed in August 2018. The study results will be submitted for publication within 6 months of completion. TRIAL REGISTRATION NUMBER: NCT02590822; Pre-results.

A Tale of Three Gorges in the Yangtze River: Comparing the Prevalence of Metabolic Syndrome According to ATPIII, WHO, and IDF Criteria and the Association with Vascular Health in Modernizing China.

BACKGROUND: Metabolic syndrome (MS) is associated with atherosclerotic diseases. The prevalence of MS according to the Adult Treatment Panel III (ATPIII), World Health Organization (WHO), and International Diabetes Federation (IDF) criteria are variable but increasing in western countries and modernizing China. This study aimed to evaluate the prevalence of MS according to these three criteria, in farmers or ex-farming residents in three-gorges territories undergoing rapid lifestyle changes. METHODS: We compared 95 residents (ex-farmers) in Wu Shan (WS) (28.4% men, aged 49.7 ± 9 years) resettled uphill for 3-5 years, and 87 age- and gender-matched farmers in Da Chang (DC) (27.6% men, aged 48.8 ± 10 years) before migration. MS and other traditional risk factors were assessed and carotid intima-media thickness (IMT) measured. RESULTS: Ninety-nine percent of WS residents were retired or adopted nonfarming jobs. Compared with DC farmers, WS ex-farmers had higher waist circumference, low density lipoprotein-cholesterol, and triglycerides (P < 0.0001), but their blood pressures, HDL-cholesterol, and fasting glucose were similar. MS were identified in 43.2% (IDF), 36.8% (WHO), and 29.5% (ATPIII) respectively in WS ex-farmers, compared with 17.2%, 13.8%, and 11.5% respectively in DC farmers. Carotid IMT was significantly higher in WS ex-farmers (0.74 ± 0.16 mm) than in DC farmers (0.64 ± 0.11 mm) (P < 0.0001). On multivariate regression analysis, prevalence of MS was correlated with job nature (beta = 0.425, P < 0.0001). Carotid IMT was better correlated with IDF MS criteria (beta = 0.208, P = 0.021), independent of age and WS location (regression adjusted R2 = 0.444, F-value 12.0, P < 0.0001), but not with the ATPIII or WHO criteria. CONCLUSIONS: IDF MS criteria is more sensitive, better correlates with atherosclerosis surrogate, and accordingly is more readily applicable to modernizing China.

Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet.

The burden of diabetic cardiovascular autonomic neuropathy (CAN) is expected to increase due to the diabetes epidemic and its early and widespread appearance. CAN has a definite prognostic role for mortality and cardiovascular morbidity. Putative mechanisms for this are tachycardia, QT interval prolongation, orthostatic hypotension, reverse dipping, and impaired heart rate variability, while emerging mechanisms like inflammation support the pervasiveness of autonomic dysfunction. Efforts to overcome CAN under-diagnosis are on the table: by promoting screening for symptoms and signs; by simplifying cardiovascular reflex tests; and by selecting the candidates for screening. CAN assessment allows for treatment of its manifestations, cardiovascular risk stratification, and tailoring therapeutic targets. Risk factors for CAN are mainly glycaemic control in type 1 diabetes mellitus (T1DM) and, in addition, hypertension, dyslipidaemia, and obesity in type 2 diabetes mellitus (T2DM), while preliminary data regard glycaemic variability, vitamin B12 and D changes, oxidative stress, inflammation, and genetic biomarkers. Glycaemic control prevents CAN in T1DM, whereas multifactorial intervention might be effective in T2DM. Lifestyle intervention improves autonomic function mostly in pre-diabetes. While there is no conclusive evidence for a disease-modifying therapy, treatment of CAN manifestations is available. The modulation of autonomic function by SGLT2i represents a promising research field with possible clinical relevance.

Multi-Modality Imaging in the Assessment of Cardiovascular Toxicity in the Cancer Patient.

Cancer therapy can be associated with both cardiac and vascular toxicity. Advanced multi-modality imaging can be used to stratify patient risk, identify cardiovascular injury during and after therapy, and forecast recovery. Echocardiography continues to be the mainstay in the evaluation of cardiac toxicity. Particularly, echocardiography-based strain imaging is useful for risk stratification of patients at baseline, and detection of subclinical left ventricle (LV) dysfunction during therapy. Cardiac magnetic resonance (CMR) serves a complementary role in the patient with poor echocardiographic or equilibrium radionuclide angiographic image quality or in situations where a more accurate and precise LV ejection fraction measurement is needed to inform decisions regarding discontinuation of chemotherapy. New CMR techniques like T1 and T2 mapping and positron emission tomography (PET) imaging will help us better understand the structural, pathological, and metabolic myocardial changes associated with ventricular dysfunction or release of serum biomarkers. CMR may also be helpful in the evaluation of vascular complications of cancer therapy. Stress echocardiography, stress CMR, computed tomography, and PET are excellent imaging options in the evaluation of ischemia in patients receiving therapies that could potentially cause vasospasm or accelerated atherosclerosis.

Integrated evaluation of hemodynamics: a novel approach for the assessment and management of preterm infants with compromised systemic circulation.

OBJECTIVE: To establish normal reference values for tissue oxygen delivery and consumption in preterm infants and demonstrate the usefulness of the integrated evaluation of hemodynamics (IEH) in preterm infants with compromised systemic circulation (CSC). METHODS: This study included 32 stable preterm infants and 6 infants (selected cases) who underwent IEH. IEH is a multimodal approach which integrates clinical parameters: data obtained from near-infrared spectroscopy (NIRS) and targeted neonatal echocardiography (TNE). RESULTS: Thirty-two hemodynamically stable preterm infants underwent 57 IEH studies. The mean (10th and 90th percentiles) were 0.23 (0.14 and 0.29) for cerebral fractional oxygen extraction (crFOE), 0.2 (0.13 and 0.24) for renal fractional oxygen extraction (rnFOE), and 0.22 (0.19 and 0.27) for mesenteric fractional oxygen extraction (msFOE). The time to full clinical recovery in all sick infants after the change of management was between 4 and 48 h. CONCLUSION: IEH was useful in targeting the management of preterm infants with CSC.