Flow-resistive loading and diaphragmatic muscle function in term and preterm infants.

PURPOSE: We aimed to assess diaphragmatic function in term and preterm infants with and without history of bronchopulmonary dysplasia (BPD), before and after the application of inspiratory flow resistive loading. METHODS: Forty infants of a median (range) gestational age of 34 (25-40) weeks were studied. BPD was defined as supplemental oxygen requirement for >28 days of life. Seventeen infants were term, 17 preterm without history of BPD, and six preterm with a history of BPD. The diaphragmatic pressure-time index (PTIdi) was calculated as the mean to maximum trans-diaphragmatic pressure ratio times the inspiratory duty cycle. The PTIdi was calculated before and after the application of an inspiratory-flow resistance for 120 s. Airflow was measured by a pneumotachograph and the transdiaphragmatic pressure by a dual pressure catheter. RESULTS: The median (interquartile range [IQR]) pre-resistance PTIdi was higher in preterm infants without BPD (0.064 [0.050-0.077]) compared with term infants (0.052 [0.044-0.062], p = .029) and was higher in preterm infants with BPD (0.119 [0.086-0.132]) compared with a subgroup of preterm infants without BPD (0.062 [0.056-0.072], p = .004). The median (IQR) postresistance PTIdi was higher in preterm infants without BPD (0.101 [0.084-0.132]) compared with term infants (0.067 [0.055-0.083], p < .001) and was higher in preterm infants with BPD [0.201(0.172-0.272)] compared with the preterm subgroup without BPD (0.091 [0.081-0.108],p = .004). The median (IQR) percentage change of the PTIdi after the application of the resistance was higher in preterm infants without BPD (65 [51-92] %) compared with term infants (34 [20-39] %, p < .001). CONCLUSIONS: Preterm infants, especially those recovering from BPD, are at increased risk of diaphragmatic muscle fatigue under conditions of increased inspiratory loading.

Diaphragmatic muscle function in term and preterm infants.

We aimed to assess the determinants of diaphragmatic function in term and preterm infants. 149 infants (56 term; 93 preterm, of whom 14 were diagnosed with bronchopulmonary dysplasia-BPD) were studied before discharge. Diaphragmatic function was assessed by measurement of the maximum transdiaphragmatic pressure (Pdimax)-a measure of diaphragmatic strength, and the pressure-time index of the diaphragm (PTIdi)-a measure of the load-to-capacity ratio of the diaphragm. The Pdimax was higher in term than preterm infants without BPD (90.1 ± 16.3 vs 81.1 ± 11.8 cmH2O; P = 0.001). Term-born infants also had lower PTIdi compared to preterms without BPD (0.052 ± 0.014 vs 0.060 ± 0.017; P = 0.006). In term and preterm infants without BPD, GA was the most significant predictor of Pdimax and PTIdi, independently of the duration of mechanical ventilation and oxygen support. In infants with GA < 32 weeks (n = 30), the Pdimax was higher in infants without BPD compared to those with BPD (76.1 ± 11.1 vs 65.2 ± 11.9 cmH2O; P = 0.015). Preterms without BPD also had lower PTIdi compared to those with BPD (0.069 ± 0.016 vs 0.109 ± 0.017; P < 0.001). In this subgroup, GA was the only significant independent determinant of Pdimax, while BPD and the GA were significant determinants of the PTIdi.  Conclusions: Preterm infants present lower diaphragmatic strength and impaired ability to sustain the generated force over time, which renders them prone to diaphragmatic fatigue. In very preterm infants, BPD may further aggravate diaphragmatic function. What is Known: • The diaphragm of preterm infants has limited capacity to undertake the work of breathing effectively. • The maximum transdiaphragmatic pressure (a measure of diaphragmatic strength) and the pressure-time index of the diaphragm (a measure of the load-to-capacity ratio of the muscle) have not been extensively assessed in small infants. What is New: • Preterm infants have lower diaphragmatic strength and impaired ability to sustain the generated force over time, which renders them prone to diaphragmatic fatigue. • In very preterm infants, bronchopulmonary dysplasia may further impair diaphragmatic function.

Preterm newborns exposed to early-onset preeclampsia have altered postnatal Tumor Necrosis Factor-related apoptosis-inducing ligand trends versus controls.

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a protein with anti-atherogenic and vasoprotective effects that has never been studied in newborns exposed to preeclampsia. Our aim was to examine TRAIL serum concentrations in such neonates after birth and during the transitional period. METHODS: Serum TRAIL levels were measured on the first and fifth day of life (DOL1 and DOL5, respectively) in 38 newborns exposed to early-onset preeclampsia and 38 controls born of normotensive mothers. RESULTS: TRAIL values on DOL1 and DOL5 did not differ between cases and controls. However, from DOL1 to DOL5 TRAIL levels increased in controls (from 20.54 ± 7.35 to 23.93 ± 11.02 pg/ml, p = 0.044) but decreased in those exposed to preeclampsia (from 25.58 ± 15.74 to 20.53 ± 10.72 pg/ml, p = 0.035). Overall, the relative change of TRAIL values from DOL1 to DOL5 was positively related to birth weight (beta coefficient 0.234, p = 0.042) and inversely related to preeclampsia (beta coefficient -0.241, p = 0.036). CONCLUSION: Newborns exposed to early-onset preeclampsia present a decrease in serum TRAIL levels during the transitional period. This pattern is exactly the opposite from what is observed in neonates born to normotensive mothers, and most likely points towards a defective mechanism of extrauterine adaptation related to preeclampsia exposure in utero. IMPACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels during the transitional period do not differ between infants exposed to early-onset preeclampsia and controls The pattern of change of TRAIL levels after birth is different; TRAIL decreases in newborns exposed to preeclampsia but increases in controls The decrease of TRAIL levels during the transitional period points towards a defective mechanism of extrauterine adaptation and an altered cardiometabolic profile in newborns exposed to early-onset preeclampsia.

Nutrition of Infants with Bronchopulmonary Dysplasia before and after Discharge from the Neonatal Intensive Care Unit.

Bronchopulmonary dysplasia (BPD) represents a severe sequela in neonates born very prematurely. The provision of adequate nutritional support in this high-risk population is challenging. The development of the lungs and physical growth are closely linked together in infants with BPD. Growth deficiency has been associated with pulmonary dysfunction, whereas improvement in respiratory status results in growth acceleration. Currently, there is not enough data regarding optimal nutritional strategies in this population. Nutrition in these infants should provide sufficient calories and nutrients to establish growth, avoid growth retardation and assist alveolarization of the lungs. Meticulous follow-up is mandatory during and after discharge from the Neonatal Intensive care Unit (NICU) to minimize growth retardation and improve lung function. Despite the significant literature supporting the contribution of growth and nutrition in the avoidance of BPD, there is limited research regarding interventions and management of infants with established BPD. Our aim was to review clinical strategies applied in everyday clinical practice and identify debates on the nutritional approach of newborns with BPD. Well-organized interventions and clinical trials regarding the somatic development and nutrition of infants with BPD are warranted.

Influenza vaccination among caregivers and household contacts of children with congenital heart disease before and during COVID-19 pandemic.

AIM: We aimed to investigate the influenza immunisation status of caregivers and household contacts of children with congenital heart disease (CHD) and potential barriers to vaccine uptake. METHODS: Prospective questionnaire-based survey over two influenza seasons (2019-2020 and 2020-2021) on 161 children with CHD attending a tertiary paediatric cardiology clinic and their families. Logistic regression and factor analysis were performed to identify factors associated with influenza vaccine uptake. RESULTS: Influenza vaccination coverage of children was 65%, whereas that of their fathers and mothers was 34% and 26%, respectively. Children with unvaccinated siblings represented 43% and those with unvaccinated adults in the household 79% of our study population. No statistically significant differences were found before and during COVID-19 pandemic on vaccine uptake. Logistic regression analysis showed that higher education level, understanding the risk of contracting the disease and vaccination status of the child determined the vaccination status of parents, regardless of their age, age of their child, severity of CHD, beliefs about vaccine safety and efficacy and risk of transmission if not vaccinated. Factor analysis revealed distinct groups among unvaccinated parents (76.3% of the variation in the responses). CONCLUSIONS: Vaccination coverage of caregivers and household contacts of children with CHD is suboptimal. Influenza vaccination campaigns should take into consideration the specific characteristics of parental groups and target interventions accordingly to increase their vaccine uptake and indirectly protect children with CHD.

Anxiety levels in parents of asymptomatic neonates and young infants referred for echocardiography.

INTRODUCTION: Previous studies in children with innocent murmurs have shown that parental concern is common. METHODS: We assessed the anxiety levels among parents of asymptomatic neonates or infants up-to 6 weeks referred for cardiologic consultation because of a heart murmur. A six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI) was completed by the parents before and after consultation. RESULTS: The average STAI score decreased from 14.42 ± 4.54 on arrival to 9.69 ± 4.26 after the consultation (p < 0.001). Overall, the parents felt more calm, less tense, less upset, more relaxed, more content and less worried after the consultation (p < 0.001). Multivariable linear regression analysis showed that the STAI score prior to consultation was related to infants age (coefficient ß = - 0.172; P = 0.046) and STAI score post consultation was related to the final diagnosis (ß = 0.312; P < 0.001). CONCLUSION: In conclusion, parents of asymptomatic neonates and young infants with a murmur exhibit moderate levels of anxiety which can be ameliorated after consultation. Parental education in the field is of paramount importance and the role of both paediatric cardiologists as well as primary care physicians is crucial and decisive.

Parents under siege: the psychological impact of COVID-19 outbreak on children's caregivers.

AIMS OF THE STUDY: It is well known that parenting stress is an important but often underestimated psychosocial variable. Data regarding the impact of the corona virus disease 2019 (COVID-19) outbreak on parental psychology are currently lacking. The aim of the present study was to assess parenting stress during the COVID-19 pandemic in Greece. METHODS: An Internet e-survey was conducted adhering to CHERRIES guidelines of the EQUATOR network and released from 16 March to 22 March 2020, using the Perceived Stress Scale (PSS) and Revised Impact of Event Scale (IES-R). A convenience sample of 1105 Greek parents of children with or without chronic or severe underlying disorders was enrolled, identified by a network of collaborating paediatricians across the country, and invited via personal emails. RESULTS: The participation rate was 91.6% and the completion rate was 100%. A total of 178 (16.1%) of the participants had children with underlying disorders (198 affected children in total). Parents of children with underlying disorders had significantly higher stress levels than those of healthy children (PSS 21.22 ± 5.06 vs 19.02 ± 6.85, p <0.001; IES-R 40.71 ± 11.58 v. 35.86 ± 12.69, p <0.001), particularly those caring for children with cardiovascular or respiratory disorders, or immunodeficiencies. The presence of children with underlying disorders was a strong predictor of PSS and IES-R scores, independently of parental sex, age, education and place of residence. CONCLUSIONS: The impact of COVID-19 outbreak on parental stress is substantial, and those caring for children with underlying disorders are more profoundly affected. Pending the global socioeconomic rebooting after the pandemic, the possible short- and long-term consequences of parental stress should not be ignored. As for other vulnerable groups, accurate health information and resources for psychological support should be provided to parents, especially those caring for children with underlying disorders.

Preeclampsia Emerging as a Risk Factor of Cardiovascular Disease in Women.

The objective of this literature review was to explore the long-term cardiovascular effects of preeclampsia in women. The primary goal was to determine which organs were most commonly affected in this population. Although it was previously believed that preeclampsia is cured after the delivery of the fetus and the placenta current evidence supports an association between preeclampsia and cardiovascular disease later in life, many years after the manifestation of this hypertensive pregnancy related disorder. Therefore preeclampsia may be emerging as a novel cardiovascular risk factor for women, which requires long-term follow up.

Parental anxiety and misperceptions in children with innocent murmurs.

BACKGROUND: Previous studies in children with innocent murmurs have shown that parental concern is common. Our aim was to assess the level of anxiety among parents of children referred for cardiology evaluation because of an innocent heart murmur and investigate their perceptions about innocent murmurs. METHODS: A questionnaire was completed by parents before and after consultation. The questionnaire included a six-item short form of the state scale of the Spielberger State-Trait Anxiety Inventory. After the echocardiogram, a detailed consultation was offered including a thorough explanation that the results were normal, as well as a written report. RESULTS: A total of 417 questionnaires were completed by parents of 340 children. Almost half of the parents believed that a heart murmur signifies heart disease or may interfere with child's ability to exercise; 21% of them stated that the siblings should also be investigated irrespective of the presence of a murmur. The mean Spielberger State-Trait Anxiety Inventory questionnaire score before pediatric cardiology consultation was 17.1 ± 4.3 and increased to 22.6 ± 2.8 after the consultation (Wilcoxon P < 0.001). CONCLUSIONS: Parents of infants and children with innocent murmurs exhibit moderate levels of anxiety and this condition can be ameliorated significantly after pediatric cardiology consultation. Focused parental education is of paramount importance and the role of pediatric cardiologists is crucial and decisive.

Aortic intima-media thickness in neonates exposed to early-onset preeclampsia.

Aortic intima-media thickness (aIMT) and its ratio to aortic diameter (aIMT/AoD) were measured on the second and fifth postnatal day in 39 neonates exposed to early-onset preeclampsia and 39 controls. Both aIMT and aIMT/AoD were higher in neonates exposed to preeclampsia (P < 0.001 for all comparisons).

Work of Breathing in Mechanically Ventilated Preterm Neonates.

OBJECTIVES: To compare the imposed work of breathing by means of pressure-time product of the diaphragm in newborn infants receiving different modes of mechanical ventilation. DESIGN: Prospective observational crossover study. SETTING: Tertiary care neonatal unit. PATIENTS: Forty preterm newborns (gestational age ≤ 37 wk) in the phase of weaning from mechanical ventilation. INTERVENTIONS: Participants were ventilated in assist control, synchronized intermittent mandatory ventilation, and intermittent mandatory ventilation mode, in a crossover manner. The combination synchronized intermittent mandatory ventilation-pressure support (SIMV-PS) at 50% (SIMV-PS50) and 75% (SIMV-PS75) of the difference between peak inflating and positive end-expiratory pressure, was also applied in a subset of infants (n = 11). Each mode was maintained for 30 minutes. Transdiaphragmatic pressure was obtained by digital subtraction of esophageal from gastric pressure (both measured using a dual pressure-tipped catheter), and pressure-time product of the diaphragm was computed by integration of transdiaphragmatic pressure over inspiratory time. MEASUREMENTS AND MAIN RESULTS: The pressure-time product of the diaphragm was 224.2 ± 112.8 in the intermittent mandatory ventilation mode, 165.8 ± 58.8 in the synchronized intermittent mandatory ventilation mode, and 125.5 ± 61.8 cm H2O × s × min in the assist control mode; all values were significantly different to each other (p < 0.0001). The pressure-time product of the diaphragm difference between assist control and intermittent mandatory ventilation, and assist control and synchronized intermittent mandatory ventilation was negatively related to postmenstrual age (regression coefficient, -0.365; p = 0.020 and -0.341; p = 0.031, respectively). In the SIMV-PS subcohort, the pressure-time product of the diaphragm was significantly higher in the intermittent mandatory ventilation mode as compared with assist control (p < 0.0001) or SIMV-PS75 (p = 0.0027), and in the synchronized intermittent mandatory ventilation mode as compared with assist control (p = 0.0301). CONCLUSIONS: In preterm infants, patient-triggered ventilation modalities result in lower work of breathing than intermittent mandatory ventilation, while the assist control mode is also associated with lower pressure-time product of the diaphragm compared with synchronized intermittent mandatory ventilation. The difference in the imposed diaphragmatic workload between these ventilation modalities was inversely related to postmenstrual age, implying that less mature infants benefit more from assist control-based ventilation strategies.

Effect of Early-Onset Preeclampsia on Offspring's Blood Pressure during the First Month of Life.

OBJECTIVE: To explore the effect of early-onset preeclampsia on the blood pressure of offspring during the first month of life. STUDY DESIGN: This prospective case-control study included 106 neonates of mothers with early-onset preeclampsia (developing at <34 weeks of gestation) and 106 infants of normotensive mothers, matched 1-to-1 for sex and gestational age. Serial blood pressure measurements were obtained on admission, daily for the first postnatal week, and then weekly up to the fourth week of life. RESULTS: There were no differences in blood pressure values on admission and the first day of life between cases and controls. Conversely, infants exposed to preeclampsia had significantly higher systolic (SBP), diastolic (DBP), and mean blood pressure (MBP) on the subsequent days up to the fourth postnatal week (P <.001-.033). Multiple regression analyses with adjustment for sex, gestational age, antenatal corticosteroid use, and maternal antihypertensive medication use confirmed the foregoing findings (P <.001-.048). Repeated-measures ANOVA also identified preeclampsia as a significant determinant of trends in SBP, DBP, and MBP during the first month of life (F = 16.2, P < .001; F = 16.4, P < .001; and F = 17.7, P < .001, respectively). CONCLUSIONS: Infants of mothers with early-onset preeclampsia have elevated blood pressure values throughout the neonatal period compared with infants born to normotensive mothers.

Preeclampsia Emerging as a Novel Risk Factor for Cardiovascular Disease in the Offspring.

INTRODUCTION: Preeclampsia is a pregnancy specific disorder which affects 2%-8% of all gestations and is associated with high maternal, fetal and neonatal morbidity and mortality worldwide. There is no "cure" for the disease except for early delivery of the fetus and placenta, however leaving preeclampsia a long term health risk both for mothers and infants. AIM: The aim of the study is to review currently available information linking preclampsia to longterm cardiovascular complications in infants and children. RESULTS: Currently, there is evidence of predisposition to cardiovascular disease, and a higher incidence of cardiovascular risk factors among children born to preeclamptic mothers. Both in experimental models and human epidemiological studies it is now clear that the infants of pregnancies complicated by preeclampsia have an increased risk of developing high blood pressure and double the risk of stroke in later life. Preeclampsia is consistently associated with higher blood pressure and body mass index as early as 4-10 years of age. Also there is some evidence of higher cardiovascular risk in adults exposed to maternal hypertensive disorders of pregnancy. It seems that preeclampsia has an impact on the cardiovascular system independent of preterm birth and is associated with endothelial dysfunction, increased carotid intima media thickness and reductions in cardiac function that cannot be accounted for by prematurity alone. CONCLUSION: Taking into consideration the currently available evidence, it can now be suggested that preeclampsia is linked to adverse effects on the cardiometabolic health of the infant. Understanding the relationship between preeclampsia and cardiovascular disease will allow for implementation of early interventions to prevent or delay the onset of adverse events in this high risk population.

Nutrition of neonates with congenital heart disease: existing evidence, conflicts and concerns.

Introduction: Congenital heart disease is one of the most of the groups of congenital anomalies with an incidence of about 1 per 100 live births. Almost one-third of these infants require some type of intervention, usually in the first year of life and increasingly often in the neonatal period. Innovative reparative and palliative surgical procedures and advanced medical support in the Neonatal Intensive Care Unit have significantly reduced the mortality related to congenital heart disease. Achieving survival is not the only target of clinicians for these patients. Appropriate growth, development, and improved quality of life are also very important. Growth failure is a very common problem of these children and nutritional support and management are a challenge for health care providers. Early intervention and identification of at-risk patients have the potential to decrease morbidity and mortality related to malnutrition.Aim/methods: The purpose of this article is to analyze the existing evidence and common concerns about perioperative and postdischarge nutritional management of neonates with congenital heart disease based on the special issues or complications that may arise. Furthermore, we reviewed the recent literature about current practices and proposed policies that could prevent malnutrition and improve the outcomes of neonates with congenital heart disease.Results/conclusion: A standardized institutional protocol and clear guidelines referring to feeding initiation, prompt estimation of caloric needs and provision of adequate and appropriate nutrient intake is likely to benefit these patients. Clear definitions for the nutritional approach in the setting of medical complications and close assessment of growth by pediatricians and specialized nutritionists are crucial for the long-term outlook and quality of life of these infants.

Osteoprotegerin and RANKL serum concentrations in neonates of mothers with early-onset pre-eclampsia: comparison with neonates of normotensive mothers.

BACKGROUND: Pre-eclampsia is a known risk factor for long-term cardiovascular complications. Osteoprotegerin (OPG) and the receptor activator of nuclear factor κB ligand (RANKL) have been implicated in the pathogenesis of cardiovascular disease. The OPG-RANKL axis function is also altered in pregnant women with pre-eclampsia, but there is lack of data regarding OPG and RANKL concentrations in their neonates. AIMS: To examine the effects of early-onset pre-eclampsia on OPG and RANKL serum concentrations at birth, taking into account the influence of various perinatal factors. STUDY DESIGN: OPG and RANKL serum concentrations were measured in 28 premature newborns of mothers with early onset pre-eclampsia, and in 28 preterm and 28 full-term neonates of normotensive mothers (control groups). RESULTS: Neonates of pre-eclamptic mothers had higher OPG and lower RANKL levels compared to both control groups (Kruskal-Wallis P < 0.0001 and P = 0.014, respectively). Regression analysis showed that pre-eclampsia (P < 0.0001), birth weight z-score (P = 0.048) and antenatal steroid administration (P = 0.034) were significant determinants of OPG levels. Multivariable regression analysis also showed that pre-eclampsia was an independent predictor of increased diastolic and mean blood pressure in these neonates. CONCLUSIONS: Early-onset pre-eclampsia affects OPG concentrations at birth and is an independent predictor of increased blood pressure in the offspring. Our findings suggest that altered OPG-RANKL axis function may be one of the mechanisms of cardiovascular 'programming' in fetuses exposed to pre-eclampsia.