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.

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.

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.

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.

Antenatal vaccination for influenza and pertussis: a call to action.

Pregnant women should receive influenza and pertussis vaccines according to the National Immunisation Schedule in Greece. The purpose of this study was to assess the knowledge, attitudes and factors associated with antenatal vaccination of women in Greece. A cross-sectional prospective survey was conducted involving 432 pregnant women and women who had recently given birth in Western Greece. Although the majority of women were aware of both diseases (289, 66.9%), they admitted lack of knowledge about antenatal vaccination (317, 73.4%). Overall, there was poor awareness that the vaccination is safe during pregnancy (95, 22%). Only 26 (6%) of women have been offered the vaccines during current pregnancy. Prior vaccination and obstetrician`s recommendation were the stronger predictors of antenatal vaccine uptake. There is substantial room for improvement among antenatal care providers in both patient education and the provision of the vaccines.Impact StatementWhat is already known about the topic? Maternal vaccination has been recognised as an important public health intervention to protect both pregnant women and their offspring from various infectious diseases. Pregnant women should receive influenza and pertussis vaccines according to the National Immunisation Schedules in many countries worldwide. However, scepticism still exists upon vaccine uptake during pregnancy.What do the results of this study add? The purpose of the study was to assess the knowledge, attitudes and factors associated with antenatal vaccination of women in Greece. We found that the knowledge and uptake of influenza and pertussis vaccine among pregnant women in Greece is poor.What the implications are of these findings for clinical practice and/or further research? There is substantial room for improvement among antenatal care providers in both patient education and the provision of the vaccines.

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.

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.

Left ventricular non-compaction in a child with bicuspid aortic valve and aortic coarctation.

We present the case of a 3-year-old boy with bicuspid aortic valve, aortic coarctation, and left ventricular non-compaction. The diagnosis was made post-natally with ultrasonography and was verified by cardiac MRI. Aortic coarctation was initially repaired surgically. At age 3 months, recoarctation and heart failure developed. Balloon angioplasty was performed with immediate improvement. At age 3 years, the patient remains asymptomatic and normotensive.

Neonatal cardiac dysfunction in intrauterine growth restriction.

BACKGROUND: The early postnatal cardiovascular consequences of intrauterine growth restriction (IUGR) have not been completely elucidated. This study aimed to evaluate the effect of IUGR on neonatal myocardial function and cardiovascular adaptation to extrauterine life. METHODS: Conventional and tissue Doppler echocardiographic parameters were compared on the second and fifth postnatal day between 30 IUGR and 30 appropriate-for-gestational age (AGA) neonates. RESULTS: IUGR neonates presented relative interventricular septum (IVS) hypertrophy (IVS to left ventricular (LV) posterior wall diastolic ratio: median IUGR-AGA difference of 0.05 (interquartile range: 0.04-0.06); P = 0.020), relative LV dilatation (wall thickness to end-diastolic LV dimension difference of 0.12 (0.06-0.16); P = 0.012), and increased left myocardial performance index (MPI difference of 0.19 (0.05-0.28); P = 0.012). Repeated measurements ANOVA revealed a different pattern of change in LV stroke volume (LVSV; P < 0.001), LV cardiac output (LVCO; P < 0.001), MPI (P < 0.001), and heart rate (HR; P = 0.025) between AGA and IUGR infants. From the second to the fifth postnatal day, AGA neonates presented a decrease in MPI and HR with an increase in LVSV and LVCO. IUGR neonates failed to achieve similar changes in MPI, HR, and LVSV, whereas their LVCO decreased. CONCLUSION: IUGR neonates present changes in cardiac morphology and subclinical myocardial dysfunction, which may result in an altered pattern of cardiovascular adaptation to extrauterine life.

Optimizing Oxygen Delivery by Low-Flow Nasal Cannula to Small Infants: A Bench Study.

BACKGROUND: In infants treated with a low-flow nasal cannula (LFNC), the oxygen concentration delivered to the lungs (i.e., the effective FiO2) is difficult to estimate. The existing mathematical formulas rely on important assumptions regarding the values of respiratory parameters and, thus, may be inaccurate. We aimed to assess oxygen delivery by LFNC to small infants using realistic simulations on a mechanical breathing model. METHODS: A mechanical breathing simulator (infant upper-airway replica, single-space breathing compartment, electric motor, microcontroller) was developed. Breathing simulations (n = 1200) were performed at various tidal volume (VT), inspiratory time (Ti), and respiratory rate (RR) combinations and different cannula flows. RESULTS: Minute ventilation (MV) was the most significant predictor of effective FiO2. FiO2 was higher at lower VT and higher Ti values. Benaron and Benitz's formula underestimated the effective FiO2 at lower MV values, while Finer's formula significantly overestimated it. A set of predictive FiO2 charts was developed based on cannula flow, infant body weight, and RR. CONCLUSIONS: The effective FiO2 delivered by LFNC to small infants critically depends on VT, Ti, and RR. However, since VT and Ti values are not available in clinical practice, the existing mathematical formulas may be inaccurate. Our novel predictive FiO2 charts could assist in optimizing oxygen delivery by LFNC using easy-to-obtain parameters, such as infant body weight and RR.

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.

Cardiopulmonary Exercise Performance of Children Born Non-Extremely Preterm.

Data on exercise tolerance of children born non-extremely preterm are sparse. We aimed to explore the cardiopulmonary exercise testing (CPET) characteristics in this population. We studied 63 children (age 7-12 years) born at 290/7-366/7 weeks of gestation (34 were late preterm, 29 were preterm) and 63 age-matched, term-born controls. All performed spirometry and CPET (cycle ergometry). There were no differences in activity levels and spirometric parameters between the group of preterm-born children and controls. A peak oxygen uptake (VO2peak) of <80% was noted in 25.4% of the term-born and 49.2% of preterm-born children (p = 0.001). Term-born participants presented similar VO2peak to late-preterm children but higher than those born at <340/7 weeks of gestation (p = 0.002). Ventilatory limitation was noted in 4.8% of term and 7.9% of preterm participants, while only one preterm child presented cardiovascular limitation. Children born before 34 weeks of gestation had higher respiratory rates and smaller tidal volumes at maximum exercise, as well as lower oxygen uptake for the level of generated work. We conclude that school-age children born at 29-34 weeks of gestation may present decreased exercise performance attributed to an altered ventilatory response to exercise and impaired O2 utilization by their skeletal muscles rather than other cardiopulmonary limiting factors.

Monocyte Chemoattractant Protein-1 (MCP-1), Activin-A and Clusterin in Children and Adolescents with Obesity or Type-1 Diabetes Mellitus.

Inflammation plays a crucial role in diabetes and obesity through macrophage activation. Macrophage chemoattractant protein-1 (MCP-1), activin-A, and clusterin are chemokines with known roles in diabetes and obesity. The aim of this study is to investigate their possible diagnostic and/or early prognostic values in children and adolescents with obesity and type-1 diabetes mellitus (T1DM). METHODS: We obtained serum samples from children and adolescents with a history of T1DM or obesity, in order to measure and compare MCP-1, activin-A, and clusterin concentrations. RESULTS: Forty-three subjects were included in each of the three groups (controls, T1DM, and obesity). MCP-1 values were positively correlated to BMI z-score. Activin-A was increased in children with obesity compared to the control group. A trend for higher values was detected in children with T1DM. MCP-1 and activin-A levels were positively correlated. Clusterin levels showed a trend towards lower values in children with T1DM or obesity compared to the control group and were negatively correlated to renal function. CONCLUSIONS: The inflammation markers MCP-1, activin-A, and clusterin are not altered in children with T1DM. Conversely, obesity in children is positively correlated to serum MCP-1 values and characterized by higher activin-A levels, which may reflect an already established systematic inflammation with obesity since childhood.