Validation of Indirect Calorimetry in Children Undergoing Single-Limb Non-Invasive Ventilation: A Proof of Concept, Cross-Over Study.

BACKGROUND: The accurate assessment of resting energy expenditure (REE) is essential for personalized nutrition, particularly in critically ill children. Indirect calorimetry (IC) is the gold standard for measuring REE. This methodology is based on the measurement of oxygen consumption (VO2) and carbon dioxide production (VCO2). These parameters are integrated into the Weir equation to calculate REE. Additionally, IC facilitates the determination of the respiratory quotient (RQ), offering valuable insights into a patient's carbohydrate and lipid consumption. IC validation is limited to spontaneously breathing and mechanically ventilated patients, but it is not validated in patients undergoing non-invasive ventilation (NIV). This study investigates the application of IC during NIV-CPAP (continuous positive airway pressure) and NIV-PS (pressure support). METHODS: This study was conducted in the Pediatric Intensive Care Unit of IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, between 2019 and 2021. Children < 6 years weaning from NIV were enrolled. IC was performed during spontaneous breathing (SB), NIV-CPAP, and NIV-PS in each patient. A Bland-Altman analysis was employed to compare REE, VO2, VCO2, and RQ measured by IC. RESULTS: Fourteen patients (median age 7 (4; 18) months, median weight 7.7 (5.5; 9.7) kg) were enrolled. The REE, VO2, VCO2, and RQ did not differ significantly between the groups. The Limits of Agreement (LoA) and bias of REE indicated good agreement between SB and NIV-CPAP (LoA +28.2, -19.4 kcal/kg/day; bias +4.4 kcal/kg/day), and between SB and NIV-PS (LoA -22.2, +23.1 kcal/kg/day; bias 0.4 kcal/kg/day). CONCLUSIONS: These preliminary findings support the accuracy of IC in children undergoing NIV. Further validation in a larger cohort is warranted.

Alpha-Linolenic Acid and Cardiovascular Events: A Narrative Review.

Cardiovascular diseases (CVDs) represent the leading cause of global mortality with 1.7 million deaths a year. One of the alternative systems to drug therapy to minimize the risk of CVDs is represented by alpha-linolenic acid (ALA), an essential fatty acid of the omega-3 series, known for its cholesterol-lowering effect. The main purpose of this review is to analyze the effects of ALA and investigate the relevant omega-6/omega-3 ratio in order to maintain functionally beneficial effects. Concerning the lipid-lowering preventive effects, ALA may favorably affect the values of LDL-C and triglycerides in both adult and pediatric populations. Furthermore, ALA has shown protective effects against hypertension, contributing to balancing blood pressure through customary diet. According to the 2009 EFSA statement, dietary ALA may contribute to reducing the risk of CVDs, thanks to anti-hypertensive, anti-atherosclerotic and cardioprotective effects.

Effects of vitamin D supplementation in obese and overweight children and adolescents: A systematic review and meta-analysis.

Due to the lipophilic nature of vitamin D, overweight and obese patients have an increased risk of inadequate circulating 25-hydroxy-vitamin D (25(OH)D) concentrations. Vitamin D deficiency has in turn several consequences especially among children and adolescents. Therefore, a few supplementation strategies of vitamin D for pediatric subjects with an excessive body weight have been proposed, but their efficacy remains controversial. The aim of this systematic review and meta-analysis was to evaluate the effect of vitamin D supplementation in overweight and obese children and adolescents. Three databases (PubMed, Embase and Web of Science) were searched to collect trials on the effect of vitamin D supplementation in the pediatric overweight or obese population. Twenty-three studies were included in the systematic review. Results on modification of metabolic or cardiovascular outcomes were controversial. On the other hand, the meta-analysis showed a mean difference by 1.6 ng/ml in subjects supplemented with vitamin D as compared to placebo. In conclusion, vitamin D supplementation slightly increases 25(OH)D levels in pediatric subjects with overweight and obesity. However, the effects on metabolic and cardiovascular outcomes remain controversial. New efforts should be devoted to promoting effective interventions to improve the health of children and adolescents with overweight and obesity.

Associations between Dietary Intake, Blood Levels of Omega-3 and Omega-6 Fatty Acids and Reading Abilities in Children.

Lower levels of omega-3 polyunsaturated fatty acids (PUFAs) have been described in individuals with reading difficulties, but the degree and the nature of such deficiencies as well as the role of nutrition are a matter of debate. The aim of the present study was to investigate the associations between PUFA blood levels, nutritional status, and reading/writing/phonological awareness performances in 42 school-age children with varying levels of reading ability. Significant correlations were found between PUFA levels (specific omega-6/omega-3 ratios), the ratio of omega-6-derived calories to the total amount of calories and reading scores. Mediation analysis showed a mediating effect of fatty acids on the association between reading speed scores and nutritional status. Moderation analysis, moreover, showed that the associations of omega-6/omega-3 ratios in the blood and Kcal omega-6/Kcal total in dietary intake were moderated by reading speed performances. Results of the mediation and moderation models confirm that the associations of dietary intake with PUFA levels in the blood vary depending on learning abilities. Reading skills appear to be sensitive to the effects of a complex set of favorable conditions related to the presence of higher omega-3 blood levels. These conditions may reflect the action of dietary as well as genetic and epigenetic mechanisms.

Effect of Vitamin D and Docosahexaenoic Acid Co-Supplementation on Vitamin D Status, Body Composition, and Metabolic Markers in Obese Children: A Randomized, Double Blind, Controlled Study.

Obese children are at high risk of developing vitamin D deficiency. Omega-3 polyunsaturated fatty acids and their derivatives might have a beneficial effect on vitamin D status of obese children, due to their anti-inflammatory action, and increasing its absorption. This multicenter, randomized, double-blind controlled study aims to investigate the effect of vitamin D and docosahexaenoic acid (DHA) co-supplementation for six months on vitamin D status, body composition, and metabolic markers of obese children with vitamin D deficiency. A total of 108 children were enrolled and 73 children completed the study: 33 were supplemented with an oral dose of 500 mg of DHA and 1200 IU/day of vitamin D3 and 41 were supplemented with 1200 IU/day of vitamin D3 + wheat germ oil. At the end of the study, more than 50% of the subjects improved their vitamin D status. However, co-supplementation was not more effective than vitamin D plus wheat germ oil. Fat mass percentage was significantly reduced, and body mass index improved in both groups, even if all the subjects were still obese at the end of the study. Children receiving both vitamin D and DHA presented a higher increase of DHA levels that could be relevant to prevent inflammatory-associated complications of obesity, but they had no effect on vitamin D levels.

Understanding feeding problems in autistic children: Exploring the interplay between internalizing symptoms and sensory features.

LAY ABSTRACT: This study adds to a growing body of research documenting feeding problems in autistic children. Our results indicate that children aged 1.5-5 years with feeding problems may present with elevated internalizing difficulties and alterations in sensory processing when compared to same-age children without feeding problems. Our study also proposes that sensory processing may be an important, mediating factor in the relationship between autism features and feeding problems. The present work suggests, therefore, that implementers should thoroughly consider the sensory profile of autistic children prior to intervening on feeding behaviors. In particular, based on these preliminary findings, feeding interventions could benefit from environments designed to support children who can find them noisy and overwhelming.

Artificial Neural Network Algorithms to Predict Resting Energy Expenditure in Critically Ill Children.

INTRODUCTION: Accurate assessment of resting energy expenditure (REE) can guide optimal nutritional prescription in critically ill children. Indirect calorimetry (IC) is the gold standard for REE measurement, but its use is limited. Alternatively, REE estimates by predictive equations/formulae are often inaccurate. Recently, predicting REE with artificial neural networks (ANN) was found to be accurate in healthy children. We aimed to investigate the role of ANN in predicting REE in critically ill children and to compare the accuracy with common equations/formulae. STUDY METHODS: We enrolled 257 critically ill children. Nutritional status/vital signs/biochemical values were recorded. We used IC to measure REE. Commonly employed equations/formulae and the VCO2-based Mehta equation were estimated. ANN analysis to predict REE was conducted, employing the TWIST system. RESULTS: ANN considered demographic/anthropometric data to model REE. The predictive model was good (accuracy 75.6%; R2 = 0.71) but not better than Talbot tables for weight. After adding vital signs/biochemical values, the model became superior to all equations/formulae (accuracy 82.3%, R2 = 0.80) and comparable to the Mehta equation. Including IC-measured VCO2 increased the accuracy to 89.6%, superior to the Mehta equation. CONCLUSIONS: We described the accuracy of REE prediction using models that include demographic/anthropometric/clinical/metabolic variables. ANN may represent a reliable option for REE estimation, overcoming the inaccuracies of traditional predictive equations/formulae.

Premature Senescence and Increased Oxidative Stress in the Thymus of Down Syndrome Patients.

Down syndrome (DS) patients prematurely show clinical manifestations usually associated with aging. Their immune system declines earlier than healthy individuals, leading to increased susceptibility to infections and higher incidence of autoimmune phenomena. Clinical features of accelerated aging indicate that trisomy 21 increases the biological age of tissues. Based on previous studies suggesting immune senescence in DS, we hypothesized that induction of cellular senescence may contribute to early thymic involution and immune dysregulation. Immunohistochemical analysis of thymic tissue showed signs of accelerated thymic aging in DS patients, normally seen in older healthy subjects. Moreover, our whole transcriptomic analysis on human Epcam-enriched thymic epithelial cells (hTEC), isolated from three DS children, which revealed disease-specific transcriptomic alterations. Gene set enrichment analysis (GSEA) of DS TEC revealed an enrichment in genes involved in cellular response to stress, epigenetic histone DNA modifications and senescence. Analysis of senescent markers and oxidative stress in hTEC and thymocytes confirmed these findings. We detected senescence features in DS TEC, thymocytes and peripheral T cells, such as increased ß-galactosidase activity, increased levels of the cell cycle inhibitor p16, telomere length and integrity markers and increased levels of reactive oxygen species (ROS), all factors contributing to cellular damage. In conclusion, our findings support the key role of cellular senescence in the pathogenesis of immune defect in DS while adding new players, such as epigenetic regulation and increased oxidative stress, to the pathogenesis of immune dysregulation.

Fluid therapy in mechanically ventilated critically ill children: the sodium, chloride and water burden of fluid creep.

BACKGROUND: Fluid therapy is a cornerstone of pediatric intensive care medicine. We aimed at quantifying the load of water, sodium and chloride due to different fluid indications in our pediatric intensive care unit (PICU). We were particularly interested in the role of fluid creep, i.e. fluid administered mainly as the vehicle for drugs, and the association between sodium load and water balance. METHODS: Critically ill children aged ≤3 years and invasively ventilated for ≥48 h between 2016 and 2019 in a single tertiary center PICU were retrospectively enrolled. Need for renal replacement therapy, plasmapheresis or parenteral nutrition constituted exclusion criteria. Quantity, quality and indication of fluids administered intravenously or enterally, urinary output and fluid balance were recorded for the first 48 h following intubation. Concentrations of sodium and chloride provided by the manufacturers were used to compute the electrolyte load. RESULTS: Forty-three patients (median 7 months (IQR 3-15)) were enrolled. Patients received 1004 ± 284 ml of water daily (153 ± 36 ml/kg/day), mainly due to enteral (39%), creep (34%) and maintenance (24%) fluids. Patients received 14.4 ± 4.8 mEq/kg/day of sodium and 13.6 ± 4.7 mEq/kg/day of chloride, respectively. The majority of sodium and chloride derived from fluid creep (56 and 58%). Daily fluid balance was 417 ± 221 ml (64 ± 30 ml/kg/day) and was associated with total sodium intake (r2 = 0.49, p < 0.001). CONCLUSIONS: Critically ill children are exposed, especially in the acute phase, to extremely high loads of water, sodium and chloride, possibly contributing to edema development. Fluid creep is quantitatively the most relevant fluid in the PICU and future research efforts should address this topic in order to reduce the inadvertent water and electrolyte burden and improve the quality of care of critically ill children.

Coronary artery bypass grafting in patients with concomitant solid tumours: early and long-term results.

OBJECTIVES: Our goal was to analyse a consecutive series of patients with solid organ tumours undergoing coronary artery bypass grafting (CABG) by defining the risk factors for early and long-term outcomes. METHODS: Between 2005 and 2016, a consecutive series of 4079 patients underwent isolated CABG at our institution. Of 103 patients (2.5%) with active malignancy, we enrolled 82 patients (mean age 71 ± 7 years) with solid organ tumours, divided into 4 subgroups: lung (9 patients-11%), gastroenteric (16 patients-20%), urinary (48 patients-58%) and other solid tumours (9 patients-11%). A deterministic record linkage between the clinical database and the National Hospital Information System allowed identification of long-term survival rates and freedom from major adverse cardiovascular events (acute myocardial infarction, repeated admissions for percutaneous coronary intervention and heart failure). RESULTS: The most common forms of cancer were prostate, colon and carcinoma of the lung. Compared to patients without cancer, patients with neoplasms were significantly older and had a higher rate of comorbidities, without significant differences among the cancer subgroups. The 30-day mortality rate was significantly higher in patients with cancer compared to those without cancer (4.9% vs 1.8%). However, on logistic regression analysis, cancer was an independent risk factor for postoperative pulmonary dysfunction but not for in-hospital death. The median follow-up time was 58 ± 12 months. The overall 5-year survival rate was 60% [95% confidence interval (CI) 47-71%], with a dismal 32% (95% CI 5-65%) survival rate among patients who had lung tumours only. The 5-year freedom from major adverse cardiovascular events was 64% (95% CI 52-74%), without significant differences among subgroups, and was comparable to that of the non-cancer population. Resolution of coronary heart disease allowed safe cancer surgical resection in 80% of the population. CONCLUSIONS: Based on the results from the present study, CABG should not be denied to patients with solid organ tumours by claiming a worse prognosis or less graft durability. Further studies with larger numbers are warranted.

Prediction of Resting Energy Expenditure in Children: May Artificial Neural Networks Improve Our Accuracy?

The inaccuracy of resting energy expenditure (REE) prediction formulae to calculate energy metabolism in children may lead to either under- or overestimated real caloric needs with clinical consequences. The aim of this paper was to apply artificial neural networks algorithms (ANNs) to REE prediction. We enrolled 561 healthy children (2-17 years). Nutritional status was classified according to World Health Organization (WHO) criteria, and 113 were obese. REE was measured using indirect calorimetry and estimated with WHO, Harris-Benedict, Schofield, and Oxford formulae. The ANNs considered specific anthropometric data to model REE. The mean absolute error (mean ± SD) of the prediction was 95.8 ± 80.8 and was strongly correlated with REE values (R2 = 0.88). The performance of ANNs was higher in the subgroup of obese children (101 ± 91.8) with a lower grade of imprecision (5.4%). ANNs as a novel approach may give valuable information regarding energy requirements and weight management in children.

Thymic Epithelium Abnormalities in DiGeorge and Down Syndrome Patients Contribute to Dysregulation in T Cell Development.

The thymus plays a fundamental role in establishing and maintaining central and peripheral tolerance and defects in thymic architecture or AIRE expression result in the development of autoreactive lymphocytes. Patients with partial DiGeorge Syndrome (pDGS) and Down Syndrome (DS) present alterations in size and architecture of the thymus and higher risk to develop autoimmunity. We sought to evaluate thymic architecture and thymocyte development in DGS and DS patients and to determine the extent to which thymic defects result in immune dysregulation and T cell homeostasis perturbation in these patients. Thymi from pediatric patients and age-matched controls were obtained to evaluate cortex and medullary compartments, AIRE expression and thymocyte development. In the same patients we also characterized immunophenotype of peripheral T cells. Phenotypic and functional characterization of thymic and peripheral regulatory T (Treg) cells was finally assessed. Histologic analysis revealed peculiar alterations in thymic medulla size and maturation in DGS and DS patients. Perturbed distribution of thymocytes and altered thymic output was also observed. DGS patients showed lower mature CD4+ and CD8+ T cell frequency, associated with reduced proportion and function of Tregs both in thymus and peripheral blood. DS patients showed increased frequency of single positive (SP) thymocytes and thymic Treg cells. However, Tregs isolated both from thymus and peripheral blood of DS patients showed reduced suppressive ability. Our results provide novel insights on thymic defects associated with DGS and DS and their impact on peripheral immune dysregulation. Indeed, thymic abnormalities and defect in thymocyte development, in particular in Treg cell number and function could contribute in the pathogenesis of the immunodysregulation present in pDGS and in DS patients.

The Role of Lipids in Human Milk and Infant Formulae.

The quantity and quality of dietary lipids in infant formulae have a significant impact on health outcomes, especially when fat storing and/or absorption are limited (e.g., preterm birth and short bowel disease) or when fat byproducts may help to prevent some pathologies (e.g., atopy). The lipid composition of infant formulae varies according to the different fat sources used, and the potential biological effects are related to the variety of saturated and unsaturated fatty acids. For example, since lipids are the main source of energy when the normal absorptive capacity of the digestive tract is compromised, medium-chain saturated fatty acids might cover this requirement. Instead, ruminant-derived trans fatty acids and metabolites of n-3 long-chain polyunsaturated fatty acids with their anti-inflammatory properties can modulate immune function. Furthermore, dietary fats may influence the nutrient profile of formulae, improving the acceptance of these products and the compliance with dietary schedules.

The Metabolic Response to Stress and Infection in Critically Ill Children: The Opportunity of an Individualized Approach.

The metabolic response to stress and infection is closely related to the corresponding requirements of energy and nutrients. On a general level, the response is driven by a complex endocrine network and related to the nature and severity of the insult. On an individual level, the effects of nutritional interventions are highly variable and a possible source of complications. This narrative review aims to discuss the metabolic changes in critically-ill children and the potential of developing personalized nutritional interventions. Through a literature search strategy, we have investigated the importance of blood glucose levels, the nutritional aspects of the different phases of acute stress response, and the reliability of the available tools to assess the energy expenditure. The dynamics of metabolism during stressful events reveals the difficult balance between risk of hypo- or hyperglycemia and under- or overfeeding. Within this context, individualized and accurate measurement of energy expenditure may help in defining the metabolic needs of patients. Given the variability of the metabolic response in critical conditions, randomized clinical studies in ill children are needed to evaluate the effect of individualized nutritional intervention on health outcomes.

Surgical rescue after transcatheter interventional procedures in congenital heart disease patients: an existing problem.

AIMS: Nowadays, transcatheter approaches are the treatment of choice for several congenital heart defects. However, adverse events may occur during interventional procedures. Even if the complication rate has been reduced remarkably because of learning curve and technological improvements, catastrophic events are still possible. The aim of this study was to review cardiac catheter complications that required surgical treatment during or after a percutaneous procedure. METHODS AND RESULTS: We evaluated retrospectively a thirteen-year experience at our centre. We examined all transcatheter procedures involving device release or implantation needing surgical rescue. We performed 3,205 interventional catheterisation procedures with device release or implantation: ASD device closure (n=2,205), PDA device occlusion (n=355), VSD device closure (n=218), aortic coarctation or recoarctation stenting (n=199), pulmonary artery stenting (n=154) and pulmonary valve implantation (n=74). Complications that required surgical treatment occurred in 1.2% of cases. Early surgery was performed in 22 cases, while in 18 patients a surgical treatment related to late complications was performed in a mean follow-up of 17 months. There were no deaths in either group. CONCLUSIONS: A spectrum of CHD can be treated today by transcatheter interventional procedures with good results and a low, but not negligible, risk of complications that require a surgical operation. The risk of developing late complications makes a long-term follow-up mandatory in such patients.

Comparison of 30-day and 5-year outcomes of percutaneous coronary intervention versus coronary artery bypass grafting in patients aged≤50 years (the Coronary aRtery diseAse in younG adultS Study).

Data on the outcome of young patients after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are scarce. Data on 2,209 consecutive patients aged≤50 years who underwent CABG or PCI were retrospectively collected from 15 European institutions. PCI and CABG had similar 30-day mortality rates (0.8% vs 1.4%, p=0.27), late survival (at 5 years, 97.8% vs 94.9%, p=0.082), and freedom from stroke (at 5 years, 98.0% and 98.0%, p=0.731). PCI was associated with significantly lower freedom from major adverse cardiac and cerebrovascular events (at 5 years, 73.9% vs 85.0%, p<0.0001), repeat revascularization (at 5 years, 77.6% vs 92.5%, p<0.0001), and myocardial infarction (at 5 years, 89.9% vs 96.6%, p<0.0001) compared with CABG. These findings were confirmed in propensity score-adjusted and matched analyses. Freedom from major adverse cardiac and cerebrovascular events after PCI was particularly low in diabetics (at 5 years, 58.0% vs 75.9%, p<0.0001) and in patients with multivessel disease (at 5 years, 63.6% vs 85.1%, p<0.0001). PCI in patients with ST elevation myocardial infarction was associated with significantly better 5-year survival (97.5% vs 88.8%, p=0.001), which was driven by its lower 30-day mortality rate (1.5% vs 6.0%, p=0.017). In conclusion, patients aged≤50 years have an excellent immediate outcome after either PCI or CABG with similar long-term survival when used according to the current clinical practice. PCI was associated with significantly lower freedom from myocardial infarction and repeat revascularization.

Towards an individualized approach to bicuspid aortopathy: different valve types have unique determinants of aortic dilatation.

OBJECTIVES: Bicuspid aortic valve (BAV)-related aortopathy is increasingly recognized to be a heterogeneous disease entity, although the surgical approach, from indications to techniques, is still standard rather than individualized. We aimed to define the determinants of aortic dilatation in BAV patients stratified according to the valve morphotype. METHODS: A consecutive echocardiographic series of 622 BAV patients was analysed. Among demographic (age, sex), anthropometric (height, weight, body surface area, body mass index), clinical (associated diseases) and echocardiographic variables (valve function, ventricular parameters), the determinants of aortic root and ascending tract diameter were assessed by multivariate regression models, as well as the predictors of aortic dilatation (size index >2.1 cm/m(2)) both in the overall population and separately in groups of different valve morphotypes (RL, right-left fusion; RN, right-non-coronary fusion). RESULTS: Independent determinants of aortic root diameter (at sinuses) were age (P < 0.001), significant aortic regurgitation (P < 0.001), sex (female protective, P < 0.001) and valve morphotype (RN protective, P < 0.001). Independent determinants of ascending aortic diameter (tubular tract) were age (P < 0.001), RN morphotype (P < 0.001), body mass index (P = 0.005) and chronic obstructive pulmonary disease (P < 0.001). In univariate analysis, the RL morphotype was associated with dilatation (ASI > 2.1 cm/m(2)) at sinuses in 41% cases vs 22% for RN (P < 0.001), and the RN morphotype was associated with dilatation at the tubular tract in 68 vs 56% for RL (P = 0.007). The presence of root dilatation was predicted by age and absence of significant stenosis in the RL morphotype subgroup, and by severe regurgitation in the RN subgroup. In the RL-type subgroup, non-regurgitant aortic valve and chronic lung disease predicted dilatation at the ascending level; and in the RN-type subgroup, age and obesity. CONCLUSIONS: The two most common BAV morphotypes are associated with aortic dilatation at two different tracts (RL at the root; RN at the tubular ascending tract) independently of valve function. Moreover, the determinants of aortic dilatation were at least in part different between the two morphotypes: this may provide stratification criteria for individualized methods of follow-up and treatment.

Pattern of ascending aortic dimensions predicts the growth rate of the aorta in patients with bicuspid aortic valve.

OBJECTIVES: This study sought to identify risk factors for rapid growth of the ascending aorta in patients with bicuspid aortic valve (BAV) disease, taking into account its phenotypic variability. BACKGROUND: Phenotypic heterogeneity of BAV-related aortopathy has recently been widely recognized. However, few studies have addressed the determinants of aortic growth so far, not distinguishing among morphological phenotypes. METHODS: Serial retrospective data on 133 adult outpatients with BAV undergoing echocardiographic follow-up were analyzed to search for factors associated with aortic diameter growth over time and with rapid aortic growth (fifth quintile of growth rate distribution), focusing on the impact of different valve morphotypes (i.e., cusp fusion pattern: right-left coronary [RL] and right-noncoronary [RN]) and previously defined aortic phenotypes (nondilated aorta, ascending dilation, root dilation). RESULTS: The RL pattern was present in 69% of patients with BAV and RN in 31%. At baseline, an ascending dilation phenotype was observed in 57% of patients and a root phenotype in 13.5%. No patient with RN-BAV had a root dilation phenotype at either baseline or last examination. Follow-up time averaged 4.0 ± 2.7 years (535 patient-years). The mean growth rate was 0.3 mm/year at the sinuses and 0.6 mm/year at the ascending level. Aortic regurgitation predicted an increase in ascending diameter over time (odds ratio [OR]: 2.3; p = 0.03). Root phenotype at presentation, not absolute baseline diameter, was an independent predictor of fast progression (>0.9 mm/year) for the ascending tract (OR: 14; p = 0.001). Fast growth was rarely seen in patients with the RL morphotype and ascending phenotype (6% at the root and 10% at the ascending level). CONCLUSIONS: In patients with BAV, the root phenotype (aortic dilation predominantly at the sinuses, with normal or less dilated ascending tract) may be a marker of more severe aortopathy, warranting closer surveillance and earlier treatment. The more common ascending phenotype proved to be a more stable disease entity, generally with slower progression.

Mechanical aortic valve replacement in young women planning on pregnancy: maternal and fetal outcomes under low oral anticoagulation, a pilot observational study on a comprehensive pre-operative counseling protocol.

OBJECTIVES: This pilot prospective observational study aimed to evaluate the maternal and fetal outcomes of pregnancies under low-dose oral anticoagulation therapy after aortic mechanical replacement. BACKGROUND: Need for valve replacement is still an issue for young women with native valve disease who are planning on future pregnancy. Choice of replacement device is a challenging clinical task. METHODS: A comprehensive pre-operative counseling protocol to guide choice of replacement device was developed. The pre-operative anticoagulation trial to determine the warfarin daily dosage needed to reach target international normalized ratio (INR) represented the main stem of such protocol. Pregnancies on low-dose anticoagulation therapy (target INR: 1.5 to 2.5) were allowed in a highly selected subset of mechanical aortic valve recipients. RESULTS: Twenty-two patients of 40 originally referred for native valve disease surgery requiring valve replacement, safely underwent the pre-operative anticoagulation challenge. No maternal or fetal complications were detected in 16 pregnancies under low oral anticoagulation. Patterns of warfarin daily dosage and induced INRs were characterized during pregnancy. CONCLUSIONS: In this small sample observational study, a pre-operative anticoagulation therapy trial helped young women scheduled for valve replacement to acquire complete information as to the choice of prosthetic device. In selected third-generation mechanical aortic prosthesis recipients, low-dose anticoagulation therapy seems safe and feasible for both mother and fetus. Further studies are needed to validate this approach.