Parents-reported nutrition and feeding difficulties in infants with congenital diaphragmatic hernia after hospital discharge.

PURPOSE: Congenital diaphragmatic hernia (CDH) affects 1 in 3000-5000 newborns. In survivors, long-term complications include gastroesophageal reflux (GER), feeding difficulties, and failure to thrive. Data from the parents' perspective remain scarce. This study aims to report the prevalence and impact of feeding difficulties on CDH families after discharge. METHODS: National web-based survey amongst families with CDH infants in 2021. RESULTS: Caregivers of 112 CDH survivors participated. The baseline characteristics were representative with 54 % male, 83 % left-sided CDH, prenatal diagnosis in 83 %, and 34 % requiring extracorporeal membrane oxygenation. Most infants (81 %) were discharged within three months, with 62 % feeding by mouth, and 30 % requiring a feeding tube. Persisting feeding difficulties were experienced by 73 %, GER being the most common (66 %), followed by insufficient weight gain (64 %). After discharge, 41 % received medical support for failure to thrive. The primary-care pediatrician was consulted most frequently for information (61 %) and treatment of feeding difficulties (74 %). Therapeutic success was reported in 64 %. A cessation of symptoms was achieved in 89 % within three years. CONCLUSION: The majority of CDH infants had persistent feeding difficulties. This survey highlights the impact surrounding feeding problems on CDH families. Further studies and support systems are needed to raise the quality of life in CDH infants and their families.

Vasoactive Management of Pulmonary Hypertension and Ventricular Dysfunction in Neonates Following Complicated Monochorionic Twin Pregnancies: A Single-Center Experience.

OBJECTIVES: Twins resulting from a complicated monochorionic (MC) twin pregnancy are at risk for postnatal evolution of pulmonary hypertension (PH) and cardiac dysfunction (CD). Both pathologies are important contributors to short- and long-term morbidity in these infants. The aim of the present retrospective single-center cohort study was to evaluate the need for vasoactive treatment for PH and CD in these neonates. METHODOLOGY: In-born neonates following a complicated MC twin pregnancy admitted to the department of neonatology of the University Children's Hospital Bonn (UKB) between October 2019 and December 2023 were screened for study inclusion. Finally, 70 neonates were included in the final analysis, with 37 neonates subclassified as recipient twins (group A) and 33 neonates as donor twins (group B). RESULTS: The overall PH incidence at day of life (DOL) 1 was 17% and decreased to 6% at DOL 7 (p = 0.013), with no PH findings at DOL 28. The overall incidence of CD was 56% at DOL 1 and decreased strongly until DOL 7 (10%, p = 0.015), with no diagnosis of CD at DOL 28. The use of dobutamine, norepinephrine, and vasopressin at DOL 1 until DOL 7 did not differ between the subgroups, whereas the dosing of milrinone was significantly higher in Group B at DOL 1 (p = 0.043). Inhaled nitric oxide (iNO) was used in 16% of the cohort, and a levosimendan therapy was administered in 34% of the neonates. One-third of the cohort was treated with oral beta blockers, and in 10%, an intravenous beta blockade (landiolol) was administered. The maximum levosimendan vasoactive-inotropic score (LVISmax) increased from DOL 1 (12.4 [3/27]) to DOL 2 (14.6 [1/68], p = 0.777), with a significant decrease thereafter as measured at DOL 7 (9.5 [2/30], p = 0.011). CONCLUSION: Early PH and CD are frequent diagnoses in neonates following a complicated MC twin pregnancy, and an individualized vasoactive treatment strategy is required in the management of these infants.

Arterial hypertension in infants with congenital diaphragmatic hernia following surgical repair.

Pulmonary hypertension (PH) and cardiac dysfunction are established comorbidities of congenital diaphragmatic hernia (CDH). However, there is very little data focusing on arterial hypertension in CDH. This study aims to investigate the incidence of arterial hypertension in neonates with CDH at hospital discharge. Archived clinical data of 167 CDH infants who received surgical repair of the diaphragmatic defect and survived for > 60 days were retrospectively analyzed. Blood pressure (BP) values were averaged for the last 7 days before discharge and compared to standard BP values for sex, age, and height provided by the AHA in 2004. BP values reaching or extending the 95th percentile were defined as arterial hypertension. The use of antihypertensive medication was analyzed at discharge and during hospitalization. Arterial hypertension at discharge was observed in 19 of 167 infants (11.3%) of which 12 (63%) were not receiving antihypertensive medication. Eighty patients (47.9%) received antihypertensive medication at any point during hospitalization and 28.9% of 152 survivors (n = 44) received antihypertensive medication at discharge, although in 45.5% (n = 20) of patients receiving antihypertensive medication, the indication for antihypertensive medication was myocardial hypertrophy or frequency control. BP was significantly higher in ECMO compared to non-ECMO patients, despite a similar incidence of arterial hypertension in both groups (13.8% vs. 10.1%, p = 0.473). Non-isolated CDH, formula feeding, and minimal creatinine in the first week of life were significantly associated with arterial hypertension on univariate analysis. Following multivariate analysis, only minimal creatinine remained independently associated with arterial hypertension.   Conclusion: This study demonstrates a moderately high incidence of arterial hypertension in CDH infants at discharge and an independent association of creatinine values with arterial hypertension. Physicians should be aware of this risk and include regular BP measurements and test of renal function in CDH care and follow-up. What is Known: • Due to decreasing mortality, morbidity is increasing in surviving CDH patients. • Pulmonary hypertension and cardiac dysfunction are well-known cardiovascular comorbidities of CDH. What is New: • There is a moderately high incidence of arterial hypertension in CDH infants at discharge even in a population with frequent treatment with antihypertensive medication. • A more complicated hospital course (ECMO, higher degree of PH, larger defect size) was associated with a higher risk for arterial hypertension.

Spontaneous breathing in selected neonates with very mild congenital diaphragmatic hernia.

AIMS: Current treatment guidelines recommend immediate postnatal intubation in all neonates with congenital diaphragmatic hernia (CDH). This study aimed to investigate the feasibility and outcomes of a spontaneous breathing approach (SBA) versus immediate intubation in neonates with prenatally diagnosed very mild CDH. METHODS: A retrospective study was conducted comparing neonates with very mild CDH (left-sided, liver-down, observed-to-expected lung-to-head ratio ≥45%) undergoing SBA and matched controls receiving standard treatment. Data on early echocardiographic findings, respiratory support, length of hospital stay, and clinical outcomes were analyzed. RESULTS: Of 151 CDH neonates, eight underwent SBA, while 31 received standard treatment. SBA was successful in six of eight patients. SBA patients had shorter length of stay (14 vs. 30 days, p = .005), mechanical ventilation (3.5 vs. 8.7 days, p = .011), and oxygen supplementation (3.2 vs. 9.3 days, p = .013) compared to matched controls. Echocardiographic evidence of pulmonary hypertension and cardiac dysfunction were significantly lower in SBA neonates after admission but similar before surgical repair. The SBA group tolerated enteral feeding earlier (day of life 7 vs. 16, p = .019). CONCLUSIONS: SBA appears feasible and beneficial for prenatally diagnosed very mild CDH. It was associated with a shortened hospital stay supportive therapies. However, larger trials are needed to confirm these findings and determine optimal respiratory support.

Dynamics of pulmonary hypertension severity in the first 48†h in neonates with prenatally diagnosed congenital diaphragmatic hernia.

Introduction: Pulmonary hypertension (PH) is one of the major contributing factors to the high morbidity and mortality in neonates with congenital diaphragmatic hernia (CDH). The severity and duration of postnatal PH are an established risk factor for patient outcome; however, the early postnatal dynamics of PH have not been investigated. This study aims to describe the early course of PH in CDH infants, and its relation to established prognostic markers and outcome measures. Methods: We performed a monocentric retrospective review of neonates with prenatally diagnosed CDH, who received three standardized echocardiographic examinations at 2-6 h, 24, and 48 h of life. The degree of PH was graded as one of three categories: mild/no, moderate, or severe PH. The characteristics of the three groups and their course of PH over 48 h were compared using univariate and correlational analyses. Results: Of 165 eligible CDH cases, initial PH classification was mild/no in 28%, moderate in 35%, and severe PH in 37%. The course of PH varied markedly based on the initial staging. No patient with initial no/mild PH developed severe PH, required extracorporeal membrane oxygenation (ECMO)-therapy, or died. Of cases with initial severe PH, 63% had persistent PH at 48 h, 69% required ECMO, and 54% died. Risk factors for any PH included younger gestational age, intrathoracic liver herniation, prenatal fetoscopic endoluminal tracheal occlusion (FETO)-intervention, lower lung to head ratio (LHR), and total fetal lung volume (TFLV). Patients with moderate and severe PH showed similar characteristics, except liver position at 24- (p = 0.042) and 48 h (p = 0.001), mortality (p = 0.001), and ECMO-rate (p = 0.035). Discussion: To our knowledge, this is the first study to systematically assess the dynamics of PH in the first postnatal 48 h at three defined time points. CDH infants with initial moderate and severe PH have a high variation in postnatal PH severity over the first 48 h of life. Patients with mild/no PH have less change in PH severity, and an excellent prognosis. Patients with severe PH at any point have a significantly higher risk for ECMO and mortality. Assessing PH within 2-6 h should be a primary goal in the care for CDH neonates.

Evaluation of levosimendan as treatment option in a large case-series of preterm infants with cardiac dysfunction and pulmonary hypertension.

Levosimendan as a calcium-sensitizer is a promising innovative therapeutical option for the treatment of severe cardiac dysfunction (CD) and pulmonary hypertension (PH) in preterm infants, but no data are available analyzing levosimendan in cohorts of preterm infants. The design/setting of the evaluation is in a large case-series of preterm infants with CD and PH. Data of all preterm infants (gestational age (GA) < 37 weeks) with levosimendan treatment and CD and/or PH in the echocardiographic assessment between 01/2018 and 06/2021 were screened for analysis. The primary clinical endpoint was defined as echocardiographic response to levosimendan. Preterm infants (105) were finally enrolled for further analysis. The preterm infants (48%) were classified as extremely low GA newborns (ELGANs, < 28 weeks of GA) and 73% as very low birth weight infants (< 1500 g, VLBW). The primary endpoint was reached in 71%, without difference regarding GA or BW. The incidence of moderate or severe PH decreased from baseline to follow-up (24 h) in about 30%, with a significant decrease in the responder group (p < 0.001). The incidence of left ventricular dysfunction and bi-ventricular dysfunction decreased significantly from baseline to follow-up (24 h) in the responder-group (p = 0.007, and p < 0.001, respectively). The arterial lactate level decreased significantly from baseline (4.7 mmol/l) to 12 h (3.6 mmol/l, p < 0.05), and 24 h (3.1 mmol/l, p < 0.01).  Conclusion: Levosimendan treatment is associated with an improvement of both CD and PH in preterm infants, with a stabilization of the mean arterial pressure during the treatment and a significant decrease of arterial lactate levels. Future prospective trials are highly warranted. What is Known: • Levosimendan as a calcium-sensitizer and inodilator is known to improve the low cardiac output syndrome (LCOS), and improves ventricular dysfunction, and PH, both in pediatric as well as in adult populations. Data related to critically ill neonates without major cardiac surgery and preterm infants are not available. What is New: • This study evaluated the effect of levosimendan on hemodynamics, clinical scores, echocardiographic severity parameters, and arterial lactate levels in a case-series of 105 preterm infants for the first time. Levosimendan treatment in preterm infants is associated with a rapid improvement of CD and PH, an increase of the mean arterial pressure, and a significant decrease in arterial lactate levels, as surrogate marker for a LCOS. • How this study might affect research, practice, or policy. As no data are available regarding the use of levosimendan in this population, our results hopefully animate the research community to conduct future prospective trails analyzing levosimendan in randomized controlled trials (RCT) and observational control studies. Additionally, our results potentially motivate clinicians to introduce levosimendan as second second-line therapy in cases of severe CD and PH in preterm infants without improvement using standard treatment strategies.

Ductus arteriosus flow predicts outcome in neonates with congenital diaphragmatic hernia.

OBJECTIVE: To investigate whether the pattern of flow through the ductus arteriosus (DA) is associated with the need for extracorporeal membrane oxygenation support (ECMO) or death in neonates with congenital diaphragmatic hernia (CDH). DESIGN: Retrospective observational study. SETTING: German level III Neonatal Intensive Care Unit. PARTICIPANTS: 139 CDH neonates were born between March 2009 and May 2021. METHODS: DA flow pattern was assessed in echocardiograms obtained within 24 h of life by measuring flow time and velocity time integral (VTI) for both left-to-right (LR) and right-to-left (RL) components of the ductal shunt. A VTI ratio (VTILR/VTIRL) < 1.0 and an RL relative flow time (Flow timeRL/(Flow timeLR+Flow timeRL)) >33% were defined as markers of abnormal flow patterns. The primary outcome was the need for ECMO. The secondary outcome was death. RESULTS: 72 patients (51.8%) had a VTI ratio <1.0, 73 (52.5%) an RL relative flow time >33%. 59 patients (42.4%) had an alteration of both values. Need for ECMO was present in 37.4% (n = 52), while 19.4% (n = 27) died. A VTI ratio <1.0 had the highest diagnostic accuracy for the need for ECMO, (sensitivity 82.7%, specificity 66.7%, negative predictive value [NPV] 86.6%, and positive predictive value [PPV] 59.7%) as well as for death (sensitivity 77.8%, specificity 54.5%, NPV 91.0%, and PPV 29.2%). Patients with VTI ratio <1.0 were 4.7 times more likely to need ECMO and 3.3 times more likely to die. VTI ratio values correlated significantly with pulmonary hypertension (PH) severity (r = -0.516, p < 0.001). CONCLUSIONS: A VTI ratio <1.0 is a valuable threshold to identify high-risk CDH neonates. For improved risk stratification, other parameters-for example, left ventricular cardiac dysfunction-should be combined with DA flow assessment.

Image quality and radiation dose of dual source high pitch computed tomography in pediatric congenital heart disease.

To explore the image quality and radiation dose of dual source high-pitch cardiac computed tomography with tailored contrast injection protocols for pediatric congenital heart disease patients (CHD). In total, 27 infants with CHD (median age 109 days [IQR 6-199]) were retrospectively analyzed regarding dose length product (DLP) and effective dose (ED) after undergoing cardiothoracic CT imaging. Scan parameters were adjusted on a dual source/detector CT (DSCT) to minimize radiation dose while maintaining adequate quality. Image acquisition was performed at 70% of the R-R interval. Dose reducing measures included prospective electrocardiogram gating, utilizing slow injection velocities and foregoing bolus tracking during contrast injection. Image quality was assessed for artefacts, vessel definition, and noise on a 5-point scale (1 non-diagnostic, 5 excellent). Series were scored on a 0-to-3-point scale regarding answered clinical questions (0 non-diagnostic, 3 all clinical questions could be answered). The median DLP was 5.2 mGy*cm (IQR 3.5-7.8) leading to a median ED of 0.20 mSv (IQR 0.14-0.30). On average the acquired images scored 13.3 ± 2.1 (SD) out of a maximum 15 points with an intraclass correlation coefficient (ICC) of 0.94. All acquired series were able to fully answer all clinical questions scoring maximum points (ICC 1.0). Dual source high pitch CT protocols combined with custom contrast agent injection protocols in pediatric patients with CHD delivered sufficiently high diagnostic imaging quality combined with low submilisievert radiation doses. Prospective high pitch imaging is a reliable method for depiction of cardiac anatomy even in very young pediatric CHD patients with elevated heart rates.

The combined prevalence of classified rare rheumatic diseases is almost double that of ankylosing spondylitis.

BACKGROUND: Rare diseases (RDs) affect less than 5/10,000 people in Europe and fewer than 200,000 individuals in the United States. In rheumatology, RDs are heterogeneous and lack systemic classification. Clinical courses involve a variety of diverse symptoms, and patients may be misdiagnosed and not receive appropriate treatment. The objective of this study was to identify and classify some of the most important RDs in rheumatology. We also attempted to determine their combined prevalence to more precisely define this area of rheumatology and increase awareness of RDs in healthcare systems. We conducted a comprehensive literature search and analyzed each disease for the specified criteria, such as clinical symptoms, treatment regimens, prognoses, and point prevalences. If no epidemiological data were available, we estimated the prevalence as 1/1,000,000. The total point prevalence for all RDs in rheumatology was estimated as the sum of the individually determined prevalences. RESULTS: A total of 76 syndromes and diseases were identified, including vasculitis/vasculopathy (n = 15), arthritis/arthropathy (n = 11), autoinflammatory syndromes (n = 11), myositis (n = 9), bone disorders (n = 11), connective tissue diseases (n = 8), overgrowth syndromes (n = 3), and others (n = 8). Out of the 76 diseases, 61 (80%) are classified as chronic, with a remitting-relapsing course in 27 cases (35%) upon adequate treatment. Another 34 (45%) diseases were predominantly progressive and difficult to control. Corticosteroids are a therapeutic option in 49 (64%) syndromes. Mortality is variable and could not be determined precisely. Epidemiological studies and prevalence data were available for 33 syndromes and diseases. For an additional eight diseases, only incidence data were accessible. The summed prevalence of all RDs was 28.8/10,000. CONCLUSIONS: RDs in rheumatology are frequently chronic, progressive, and present variable symptoms. Treatment options are often restricted to corticosteroids, presumably because of the scarcity of randomized controlled trials. The estimated combined prevalence is significant and almost double that of ankylosing spondylitis (18/10,000). Thus, healthcare systems should assign RDs similar importance as any other common disease in rheumatology.

Therapeutic options for patients with rare rheumatic diseases: a systematic review and meta-analysis.

BACKGROUND: Rare diseases (RDs) in rheumatology as a group have a high prevalence, but randomized controlled trials are hampered by their heterogeneity and low individual prevalence. To survey the current evidence of pharmacotherapies for rare rheumatic diseases, we conducted a systematic review and meta-analysis. Randomized controlled trials (RCTs) of RDs in rheumatology for different pharmaco-interventions were included into this meta-analysis if there were two or more trials investigating the same RD and using the same assessment tools or outcome parameters. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PUBMED were searched up to April 2nd 2020. The overall objective of this study was to identify RCTs of RDs in rheumatology, evaluate the overall quality of these studies, outline the evidence of pharmacotherapy, and summarize recommended therapeutic regimens. RESULTS: We screened 187 publications, and 50 RCTs met our inclusion criteria. In total, we analyzed data of 13 different RDs. We identified several sources of potential bias, such as a lack of description of blinding methods and allocation concealment, as well as small size of the study population. Meta-analysis was possible for 26 studies covering six RDs: Hunter disease, Behçet's disease, giant cell arteritis, ANCA-associated vasculitis, reactive arthritis, and systemic sclerosis. The pharmacotherapies tested in these studies consisted of immunosuppressants, such as corticosteroids, methotrexate and azathioprine, or biologicals. We found solid evidence for idursulfase as a treatment for Hunter syndrome. In Behçet's disease, apremilast and IF-α showed promising results with regard to total and partial remission, and Tocilizumab with regard to relapse-free remission in giant cell arteritis. Rituximab, cyclophosphamide, and azathioprine were equally effective in ANCA-associated vasculitis, while mepolizumab improved the efficacy of glucocorticoids. The combination of rifampicin and azithromycin showed promising results in reactive arthritis, while there was no convincing evidence for the efficacy of pharmacotherapy in systemic sclerosis. CONCLUSION: For some diseases such as systemic sclerosis, ANCA-associated vasculitis, or Behcet's disease, higher quality trials were available. These RCTs showed satisfactory efficacies for immunosuppressants or biological drugs, except for systemic sclerosis. More high quality RCTs are urgently warranted for a wide spectrum of RDs in rheumatology.