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Fetal exposure to maternal cancer during pregnancy with or without treatment did not have an adverse effect on cognitive, cardiac, or general development in early childhood. Fetal development is a complex process. At different stages of development, different aspects can be influenced by external factors (e.g., teratogenic drugs, alcohol, smoking, maternal stress, and altered nutrition). Among women in whom cancer is diagnosed during pregnancy, factors such as maternal illness, diagnostic tests, cancer treatment, and increased levels of maternal stress can negatively influence fetal development. Cancer treatment during pregnancy exposes the fetus to potentially toxic substances that influence cell division. Chemotherapeutic drugs can cross the placenta in varying amounts. 1 , 2 Data on fetal effects of maternal cancer treatment are based mainly on retrospective cohort studies. 3 – 6 From . . .

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants with high mortality rate, indicating the need for precision treatment. NEC is characterized by intestinal inflammation and ischemia, as well derangements in intestinal microcirculation. Remote ischemic conditioning (RIC) has emerged as a promising tool in protecting distant organs against ischemia-induced damage. However, the effectiveness of RIC against NEC is unknown. To address this gap, we aimed to determine the efficacy and mechanism of action of RIC in experimental NEC. NEC was induced in mouse pups between postnatal day (P) 5 and 9. RIC was applied through intermittent occlusion of hind limb blood flow. RIC, when administered in the early stages of disease progression, decreases intestinal injury and prolongs survival. The mechanism of action of RIC involves increasing intestinal perfusion through vasodilation mediated by nitric oxide and hydrogen sulfide. RIC is a viable and non-invasive treatment strategy for NEC. Necrotizing enterocolitis (NEC) is one of the most lethal gastrointestinal emergencies in neonates needing precision treatment. Here the authors show that remote ischemic conditioning is a non-invasive therapeutic method that enhances blood flow in the intestine, reduces damage, and improves NEC outcome.

The morphology, structure and position of the right ventricle differ substantially from those of the left ventricle and have posed difficulties in the assessment of right ventricular function. Imaging techniques, notably echocardiography and MRI, have enabled a better understanding of right ventricular performance. Mertens and Friedberg discuss the advantages and disadvantages of established and new methods of right ventricular imaging and their potential in the clinical setting. The right ventricle has long been the 'forgotten ventricle', as it is difficult to image owing to its complex morphology, its thin wall with coarse trabeculations, and its anterior position within the chest. Developments in cardiac magnetic resonance imaging (CMR) and echocardiography have provided new insights into right ventricular (RV) structure and function. RV performance seems to be an important determinant of clinical status and long-term outcome in patients with pulmonary hypertension, cardiomyopathies, and, especially, in patients with congenital heart disease. A variety of different parameters can be measured to assess RV function, but a lot of uncertainty remains on how to assess RV performance in daily clinical practice and which measurements to use in clinical decision-making. CMR is currently considered the reference technique for RV volumetry and calculation of ejection fraction. Various echocardiographic techniques can provide reliable information on RV dimensions and RV systolic and diastolic function that can be used in clinical follow-up. The introduction of newer echocardiographic techniques, such as three-dimensional echocardiography, tissue Doppler ultrasonography, and ultrasound strain imaging, challenge the leading role of CMR in RV functional assessment, but further validation and accumulation of data are required before these techniques can play a key part in clinical decision-making. Key Points The determination of right ventricular (RV) function is important in the assessment of the clinical status and outcome of patients with pulmonary hypertension, cardiomyopathies, or congenital heart disease Cardiac magnetic resonance imaging (CMR) is the reference technique for RV volumetric measurements and calculation of ejection fraction, but good standardization of the technique is required Three-dimensional echocardiography is a promising alternative to CMR, but requires further optimization and validation to be useful in clinical practice RV tissue characterization by CMR can be used to identify fibrofatty tissue infiltration and fibrosis in the RV wall, but its role in clinical practice is still uncertain Echocardiographic measurement of tricuspid annular motion, tricuspid annular tissue Doppler velocities, or longitudinal systolic strain in the RV free wall can be performed to monitor RV systolic function in routine clinical practice

To evaluate clinical practice, neonatologists’ attitudes, and the extent of training and accreditation regarding targeted neonatal echocardiography (TnEcho) among Chinese neonatologists. A web-based questionnaire was emailed to 331 neonatologists across China who completed training in subspecialty neonatology. The survey covered various aspects of TnEcho, including the characteristics of clinical practice, attitudes towards its usefulness, and perceived barriers to implementation and training methods. Survey response rate was 68.0% (225/331). Seventy-nine (35.1%) respondents stated that TnEcho was utilized in their NICUs. Most respondents reported the use of echocardiography to evaluate hemodynamic significance of the patent ductus arteriosus (PDA, 94.9%). The eyeballing technique was most used to evaluate left (82.3%) and right (77.2%) ventricular function. Most respondents (87.3–96.2%) positively valued the role of TnEcho in providing timely and longitudinal hemodynamic information to guide cardiovascular care. Access to TnEcho was more likely in centers with on-site pediatric cardiology service ( p  = .003), larger bed capacity ( p  = .004), or level IV status ( p  = .003). Lack of experienced practitioners with echocardiography expertise (88.9%) and accredited training programs (85.8%) was perceived to be the major barrier to implementation. Of concern, most practitioners with TnEcho skills received training in an informal manner through workshops (60.8%) or self-directed learning (54.4%). Conclusions : The use of TnEcho for longitudinal evaluation of infants with hemodynamic instability is growing within Chinese NICUs. There is an urgent need to develop standardized training programs and accreditation for TnEcho which are adapted to the Chinese context. What is Known: • Targeted neonatal echocardiography (TnEcho) is an emerging technique to aid characterization of the hemodynamics of sick neonates in the neonatal intensive care units (NICUs) around the world. • Evidence is accumulating which supports the positive impact of TnEcho service on clinical management and patient outcomes. What is New: • This is the first report to show that the use of TnEcho for longitudinal evaluation of infants with hemodynamic instability is growing within Chinese NICUs. • There is an urgent need to develop standardized training programs and accreditation for TnEcho which are adapted to the Chinese context.

Chemotherapy for the treatment of maternal cancers during pregnancy has become more acceptable in the past decade; however, the effect of prenatal exposure to chemotherapy on cardiac and neurodevelopmental outcomes of the offspring is still uncertain. We aimed to record the general health, cardiac function, and neurodevelopmental outcomes of children who were prenatally exposed to chemotherapy. We did an interim analysis of a multicentre observational cohort study assessing children who were prenatally exposed to maternal cancer staging and treatment, including chemotherapy. We assessed children at birth, at age 18 months, and at age 5–6, 8–9, 11–12, 14–15, or 18 years. We did clinical neurological examinations, tests of the general level of cognitive functioning (Bayley or intelligence quotient [IQ] test), electrocardiography and echocardiography, and administered a questionnaire on general health and development. From age 5 years, we also did audiometry, the Auditory Verbal Learning Test, and subtasks of the Children's Memory Scale, and the Test of Everyday Attention for Children, and we also completed the Child Behavior Checklist. This study is registered with ClinicalTrials.gov, number NCT00330447. 236 cycles of chemotherapy were administered in 68 pregnancies. We assessed 70 children, born at a median gestational age of 35·7 weeks (range 28·3–41·0; IQR 3·3; 47 women at <37 weeks), with a median follow-up period of 22·3 months (range 16·8–211·6; IQR 54·9). Although neurocognitive outcomes were within normal ranges, cognitive development scores were lower for children who were born preterm than for those born at full term. When controlling for age, sex, and country, the score for IQ increased by an average 11·6 points (95% CI 6·0–17·1) for each additional month of gestation (p<0·0001). Our measurements of the children's behaviour, general health, hearing, and growth corresponded with those of the general population. Cardiac dimensions and functions were within normal ranges. We identified a severe neurodevelopmental delay in both members of one twin pregnancy. Fetal exposure to chemotherapy was not associated with increased CNS, cardiac or auditory morbidity, or with impairments to general health and growth compared with the general population. However, subtle changes in cardiac and neurocognitive measurements emphasise the need for longer follow-up. Prematurity was common and was associated with impaired cognitive development. Therefore, iatrogenic preterm delivery should be avoided when possible. Research Foundation-Flanders; Research Fund-K U Leuven; Agency for Innovation by Science and Technology; Stichting tegen Kanker; Clinical Research Fund-University Hospitals Leuven; and Belgian Cancer Plan, Ministery of Health.

Congenital diaphragmatic hernia (CDH) is a birth defect characterized by incomplete closure of the diaphragm, herniation of abdominal organs into the chest, and compression of the lungs and the heart. Besides complications related to pulmonary hypoplasia, 1 in 4 survivors develop neurodevelopmental impairment, whose etiology remains unclear. Using a fetal rat model of CDH, we demonstrated that the compression exerted by herniated organs on the mediastinal structures results in decreased brain perfusion on ultrafast ultrasound, cerebral hypoxia with compensatory angiogenesis, mature neuron and oligodendrocyte loss, and activated microglia. In CDH fetuses, apoptosis was prominent in the subventricular and subgranular zones, areas that are key for neurogenesis. We validated these findings in the autopsy samples of four human fetuses with CDH compared to age- and sex-matched controls. This study reveals the molecular mechanisms and cellular changes that occur in the brain of fetuses with CDH and creates opportunities for therapeutic targets.

RationalePreterm neonates needing rescue treatments with inotropes and/or inhaled nitric oxide (iNO) (acute critical illnesses, ACIs) in neonatal intensive care units (NICUs) are at high risk of mortality. While targeted neonatal echocardiography consultations (TNE) are increasingly used to guide management, its clinical impact need evaluation.ObjectivesTo investigate clinical outcomes in relation to TNE utilisation during episodes of ACIs among preterm neonates.MethodsThis retrospective cohort study, conducted at two tertiary NICUs over 10 years, included neonates<37 weeks gestational age (GA) who developed ACIs. Patients receiving TNE-guided care (TNE within 24 hours of treatment initiation) were compared with non-TNE management. Outcomes included predischarge mortality, episode-related mortality (<7 days) and a new diagnosis of intraventricular haemorrhage≥grade 3 (IVH-3). Inverse probability of treatment weighting (IPTW) using propensity score was used to account for confounders, including site, birth years and baseline illness severity.Measurements and main resultsOf 622 included patients, 297 (48%) had TNE; median (IQR) GA at ACI was 26.4 (25.0–28.4) weeks. TNE group demonstrated higher baseline mean airway pressure, oxygen requirement and heart rate and frequently received both inotrope and iNO during ACI. IPTW analysis revealed TNE was associated with lower mortality (adjusted OR (95% CI) 0.75 (0.59 to 0.95)), episode-related mortality (0.54 (0.40 to 0.72)) and death or IVH-3 (0.78 (0.62 to 0.99)). TNE group received more varied inotropic agents, demonstrated earlier improvements in blood pressures, without increasing overall inotrpoic burden.ConclusionsAmong preterm neonates requiring rescue treatments with inotropes/iNO, TNE utilisation to guide clinical management may be associated with improved survival.

Purpose This study investigated the diagnostic utility of nontargeted genomic testing in patients with pediatric heart disease. Methods We analyzed genome sequencing data of 111 families with cardiac lesions for rare, disease-associated variation. Results In 14 families (12.6%), we identified causative variants: seven were de novo ( ANKRD11 , KMT2D , NR2F2 , POGZ , PTPN11 , PURA , SALL1 ) and six were inherited from parents with no or subclinical heart phenotypes ( FLT4 , DNAH9 , MYH11 , NEXMIF , NIPBL , PTPN11 ). Outcome of the testing was associated with the presence of extracardiac features ( p  = 0.02), but not a positive family history for cardiac lesions ( p  = 0.67). We also report novel plausible gene–disease associations for tetralogy of Fallot/pulmonary stenosis ( CDC42BPA , FGD5 ), hypoplastic left or right heart ( SMARCC1 , TLN2 , TRPM4 , VASP ), congenitally corrected transposition of the great arteries ( UBXN10 ), and early-onset cardiomyopathy ( TPCN1 ). The identified candidate genes have critical functions in heart development, such as angiogenesis, mechanotransduction, regulation of heart size, chromatin remodeling, or ciliogenesis. Conclusion This data set demonstrates the diagnostic and scientific value of genome sequencing in pediatric heart disease, anticipating its role as a first-tier diagnostic test. The genetic heterogeneity will necessitate large-scale genomic initiatives for delineating novel gene–disease associations.

Newborns with congenital heart diseases requiring cardiopulmonary bypass (CPB) are at risk of neurodevelopmental impairment. The impact of deep hypothermia cardiopulmonary bypass (DH-CPB) on cerebrovascular autoregulation (CAR) that controls brain perfusion in the presence of blood pressure variation is not well understood. Recently, ultrafast power Doppler (UPD) showed potential to study CAR in neonates based on cerebral blood volume (CBV). However, since CAR relies mainly on arterial vasoconstriction/vasodilation, monitoring of brain perfusion variation based on CBV requires the discrimination of arterial from venous CBV. This study aims to use UPD combined with an algorithm for the discrimination of arteries and veins to monitor CAR during DH-CPB in neonates. Transfontanellar ultrafast power Doppler was performed in two groups of newborns: those undergoing deep hypothermic cardiopulmonary bypass with circulatory arrest (18–20 °C, n  = 6, “DH group”) and those undergoing full-flow CPB at mild hypothermia (32–34 °C, n  = 6, “non-DH group”). Blood flow directionality was used to differentiate arterial compartments of CBV from venous CBV in specific brain regions where arterial and venous flows exhibit opposite directions. To study CAR, a linear mixed effect model was used to find the association between arterial CBV and mean arterial blood pressure (MAP). In the “non-DH group”, we found a negative association between arterial CBV and MAP, indicating that an increase in MAP is associated with a decrease in arterial CBV (slope = -0.020 , p  = 0.047). Conversely, in the “DH group” no significant association was found such that arterial CBV remained stable as MAP increased ( p  = 0.314). We interpret the reduction in arterial CBV with increasing MAP in the “non-DH group” as an active arterial vasoconstriction triggered by CAR, whereas the lack of variation of arterial CBV in the DH group suggests impaired CAR response. Our findings highlight the potential of ultrafast ultrasound imaging for intra-operative CAR monitoring, paving the way for a better understanding of the impact of different types of CPB on cerebral perfusion.