Advancing the Clinical and Molecular Understanding of Cornelia de Lange Syndrome: A Multidisciplinary Pediatric Case Series and Review of the Literature.

Cornelia de Lange syndrome (CdLS) is a complex genetic disorder with distinct facial features, growth limitations, and limb anomalies. Its broad clinical spectrum presents significant challenges in pediatric diagnosis and management. Due to cohesin complex mutations, the disorder's variable presentation requires extensive research to refine care and improve outcomes. This article provides a case series review of pediatric CdLS patients alongside a comprehensive literature review, exploring clinical variability and the relationship between genotypic changes and phenotypic outcomes. It also discusses the evolution of diagnostic and therapeutic techniques, emphasizing innovations in genetic testing, including detecting mosaicism and novel genetic variations. The aim is to synthesize case studies with current research to advance our understanding of CdLS and the effectiveness of management strategies in pediatric healthcare. This work highlights the need for an integrated, evidence-based approach to diagnosis and treatment. It aims to fill existing research gaps and advocate for holistic care protocols and tailored treatment plans for CdLS patients, ultimately improving their quality of life.

Cerebral oxygenation and bioelectrical activity in preterm infants during surfactant replacement therapy with porcine and bovine preparations.

Introduction: Surfactant replacement therapy (SRT) might cause acute changes in cerebral oxygenation and alteration of brain bioelectrical activity. Varying physiologic responses and clinical outcomes were observed when different surfactant preparations were instilled to treat neonatal respiratory distress syndrome (RDS). Material and methods: Neonates born at 26-30 weeks of gestation with RDS requiring intubation and mechanical ventilation were randomized to SRT either with poractant alfa (A) or beractant (B). Saturation (SpO2), heart rate (HR), cerebral tissue oxygenation (StO2) and amplitude-integrated electroencephalography (aEEG) were simultaneously recorded prior to and up to 4 h after SRT. Results: Mean SpO2, HR and StO2 values were comparable between groups at baseline and after SRT. There were differences in mean aEEG voltage before SRT, but amplitudes were within a range considered as normal in both groups. Immediately after SRT and at a few single post-intervention time points mean aEEG voltage was higher in the beractant group. There was a significant difference in the percentage of time with the aEEG signal < 5 µV after SRT between groups (mean 25.7% (A) vs. 16.5% (B), p < 0.05). Quantity of bursts per minute and mean length of inter-burst intervals (IBI) in the aEEG recording varied insignificantly but there was a significant difference in the percentage of IBI > 30 s between groups (52.5% (A) vs. 36.6% (B), p <0.05). Conclusions: This is the first study assessing brain bioelectrical function and oxygenation while using two different surfactant preparations in a neonate. Cerebral effects of SRT are observed regardless of the type of surfactant, but their magnitude may depend on the preparation and/or dosing used.

Polymorphisms of fibronectin-1 (rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655) are not associated with bronchopulmonary dysplasia in preterm infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects premature newborns. Many different factors, increasingly genetic, are involved in the pathogenesis of BPD. The aim of the study is to investigate the possible influence of fibronectin SNP on the occurrence of BPD. The study included 108 infants born between 24 and 32 weeks of gestation. BPD was diagnosed based on the National Institutes of Health Consensus definition. The 5 FN1 gene polymorphisms assessed in the study were the following: rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655. BPD developed in 30 (27.8%) out of the 108 preterm infants. Incidence of BPD was higher in infants with lower APGAR scores and low birthweight. Investigation did not confirm any significant prevalence for BPD development in any genotypes and alleles of FN1. Further studies should be performed to confirm the role of genetic factors in etiology and pathogenesis of BPD.

Spontaneous Resolution of Congenital Dural Venous Sinus Ectasia Associated With Polymicrogyria-Case Report.

Dural venous sinus ectasia belongs to a rare group of venous sinus malformations of unknown origin and uncertain prognosis. We report the first patient with idiopathic congenital ectasia of the confluence of sinuses with thrombosis associated with bilateral polymicrogyria. It may highlight the causative relation between ischemia within the central nervous system due to torcular herophili ectasia with thrombosis in early pregnancy and the development of cortical malformations in neonates. We also highlight the role of MR neuroimaging in the diagnosis of these entities.

Effects of heliox and non-invasive neurally adjusted ventilatory assist (NIV-NAVA) in preterm infants.

Due to its unique properties, helium-oxygen (heliox) mixtures may provide benefits during non-invasive ventilation, however, knowledge regarding the effects of such therapy in premature infants is limited. This is the first report of heliox non-invasive neurally adjusted ventilatory assist (NIV-NAVA) ventilation applied in neonates born ≤ 32 weeks gestational age. After baseline NIV-NAVA ventilation with a standard mixture of air and oxygen, heliox was introduced for 3 h, followed by 3 h of air-oxygen. Heart rate, peripheral capillary oxygen saturation, cerebral oxygenation, electrical activity of the diaphragm (Edi) and selected ventilatory parameters (e.g., respiratory rate, peak inspiratory pressure) were continuously monitored. We found that application of heliox NIV-NAVA in preterm infants was feasible and associated with a prompt and significant decrease of Edi suggesting reduced respiratory effort, while all other parameters were stable throughout the study, and had similar values during heliox and air-oxygen ventilation. This therapy may potentially enhance the efficacy of non-invasive respiratory support in preterm neonates and reduce the number of infants progressing to ventilatory failure.

Management of retinopathy of prematurity (ROP) in a Polish cohort of infants.

Retinopathy of prematurity (ROP) is potentially blinding, but screening and timely treatment can stop its progression. The data on treatment outcomes of ROP from Central and Eastern Europe are scarce. Therefore, we aimed to analyze the latest results of ROP management in Poznan medical center to update the data from this world region. In the years 2016-2019, 178 patients (350 eyes) received treatment for ROP (6.1% of the screened population). The mean gestational age was 26 weeks (range 22-31 weeks), the mean birth weight was 868 g (range 410-1890 g). The most frequent ROP stage at treatment was zone II, stage 3 + (34.9%). As the first line of treatment, 115 infants (226 eyes, 64.6%) underwent laser photocoagulation (LP); 61 infants (120 eyes, 34.3%) received intravitreal ranibizumab injections (IVR); and 2 infants (4 eyes, 0.6%) were treated simultaneously with LP and IVR. One hundred twenty-six eyes (36%) of 63 patients required retreatment: 20.4% treated with LP and 66.7% treated with IVR. Retinal detachment occurred in 14 eyes (4%). The incidence of ROP, ROP requiring treatment, and reoccurrence rates are higher in the Polish population than in Western Europe and the USA. The identified treatment patterns find increasing use of anti-VEGF agents.

Impact of Computer Calculation Program on Quality of Individualized Parenteral Nutrition and Selected Clinical Parameters of Extremely Low-Birth-Weight Infants.

BACKGROUND: The aim of the study was to assess the effects of computerized provider order entry (CPOE) for parenteral nutrition (PN) on selected clinical parameters of extremely low-birth-weight (ELBW) neonates in a tertiary neonatal intensive care unit. METHODS: This study was a retrospective data analysis of preterm infants born over a 1-year period before and after introduction of CPOE. PN composition during the first 2 weeks of life, change in weight, head circumference and body length z-scores were assessed. Duration of PN and selected neonatal complications were compared. Logistic regression was used to adjust for confounding variables (sex, birth weight, and birth-gestational age). RESULTS: Ninety-four patients in 2 equal groups were analyzed. Birth weight (median 810 vs 825 g) and gestational age (27 vs 27 weeks) were comparable. After adjustment for confounding variables, on the first and seventh day of life, significantly more energy (P < .001), protein (P < .001), lipid (P < .03), and carbohydrate (P < .02) were administered in the CPOE group than in the manually calculated (MC) prescriptions group. The CPOE group had lower weight loss (P < .001), a significant improvement in linear growth, and faster regain of birth weight (P < .01) compared with the MC group. CONCLUSION: The CPOE positively influences the quality of PN in ELBW infants. It also significantly reduced initial weight loss, time to regain birth weight, and linear growth. It may also have beneficial effects on selected clinical outcomes, which requires further study.

Cerebral oxygenation and circulatory parameters during pressure-controlled vs volume-targeted mechanical ventilation in extremely preterm infants.

BACKGROUND: Respiratory distress syndrome (RDS) is the most common cause of respiratory failure of infants born prematurely with very low birth weight (VLBW). Essential elements of RDS management include ventilatory support and endotracheal administration of a surfactant. OBJECTIVES: To assess the effect of volume-targeted compared to pressure-controlled mechanical ventilation (MV) on circulatory parameters and cerebral oxygenation StO2 in extremely preterm infants. MATERIAL AND METHODS: This prospective, cross-over trial enrolled neonates born before 28 weeks of gestation. The patients were ventilated for 3 h in pressure-controlled assist-control (PC-AC) mode, followed by 3 h of volume-guarantee assist-control ventilation (VG-AC). Pulse oximetry (saturation (SpO2) and heart rate (HR)), near-infrared spectroscopy (NIRS), StO2, and electrical cardiometry (EC) were used in monitoring of the patients. RESULTS: Twenty preterm infants with a mean gestational age of 26 weeks were studied. The patients' mean postnatal age was 7.7 days. The SpO2 values and HR were comparable during PC-AC and VG-AC. The mean values of peak inspiratory pressure (PIP), mean airway pressure (MAP) and expiratory tidal volume (VTE) were lower, while the respiratory rate (RR) was higher during PC-VG. There were no significant differences in the mean values of StO2, but based on a comparison of the standard deviations (SD) the StO2 variability was significantly lower during VG-AC. The circulatory parameters were comparable. CONCLUSIONS: The StO2 is more stable during VG than PC ventilation. These findings support the use of VG mode in premature infants.

Cerebral tissue oxygenation during cranial osteopathic CV4 procedure in newborns.

BACKGROUND: The cranial osteopathic manipulative medicine has been shown to alter regional cerebral tissue oxygenation (cStO2) in adult patients; however, there are no reports regarding the neonatal population. OBJECTIVES: To assess the influence of compression of the 4th ventricle (CV4) osteopathic procedure on cStO2 in neonates. MATERIAL AND METHODS: Thirty-one patients born between 25 and 39 weeks of gestation were screened for inclusion in the neonatal unit. Twenty-two infants presenting with hyperstimulation of autonomous nervous system (ANS) according to the Neonatal Behavioral Assessment Scale were enrolled in the study. Near-infrared spectroscopy was used for continuous cStO2 monitoring; pulse oximeter oxygen saturation (SpO2) and heart rate (HR) measured with pulse oximetry were simultaneously monitored 10 min before CV4, during the therapy and 10 min after it was stopped. RESULTS: Patients' condition remained stable throughout the study. There were no significant differences in the mean cStO2 values recorded before (69 ±8%), during (69 ±8%) and after CV4 (70 ±8%; p > 0.05). Mean SpO2 was almost constant during the study (96 ±4% before, 95 ±3% during and 95 ±4% after the intervention). Heart rate was also stable pre-, during and post-therapy (153 ±21 min, 151 ±18 min and 151 ±20/min, respectively). CONCLUSIONS: Compression of the 4th ventricle osteopathic procedure does not influence the cStO2 in newborns. This method seems to be well-tolerated but its clinical efficacy needs to be further investigated in this group of patients.

Genotype-phenotype correlation in two Polish neonates with alveolar capillary dysplasia.

BACKGROUND: Alveolar capillary dysplasia (ACD) is a rare cause of severe pulmonary hypertension and respiratory failure in neonates. The onset of ACD is usually preceded by a short asymptomatic period. The condition is refractory to all available therapies as it irreversibly affects development of the capillary bed in the lungs. The diagnosis of ACD is based on histopathological evaluation of lung biopsy or autopsy tissue or genetic testing of FOXF1 on chromosome 16q24.1. Here, we describe the first two Polish patients with ACD confirmed by histopathological and genetic examination. CASE PRESENTATION: The patients were term neonates with high Apgar scores in the first minutes of life. They both were diagnosed prenatally with heart defects. Additionally, the first patient presented with omphalocele. The neonate slightly deteriorated around 12th hour of life, but underwent surgical repair of omphalocele followed by mechanical ventilation. Due to further deterioration, therapy included inhaled nitric oxide (iNO), inotropes and surfactant administration. The second patient was treated with prostaglandin E1 since birth due to suspicion of aortic coarctation (CoA). After ruling out CoA in the 3rd day of life, infusion of prostaglandin E1 was discountinued and immediately patient's condition worsened. Subsequent treatment included re-administration of prostaglandin E1, iNO and mechanical ventilation. Both patients presented with transient improvement after application of iNO, but died despite maximized therapy. They were histopathologically diagnosed post-mortem with ACD. Array comparative genomic hybridization in patient one and patient two revealed copy-number variant (CNV) deletions, respectively, ~ 1.45 Mb in size involving FOXF1 and an ~ 0.7 Mb in size involving FOXF1 enhancer and leaving FOXF1 intact. CONCLUSIONS: Both patients presented with a distinct course of ACD, extra-pulmonary manifestations and response to medications. Surgery and ceasing of prostaglandin E1 infusion should be considered as potential causes of this variability. We further highlight the necessity of thorough genetic testing and histopathological examination and propose immunostaining for CD31 and CD34 to facilitate the diagnostic process for better management of infants with ACD.

Perinatal Ureaplasma Exposure Is Associated With Increased Risk of Late Onset Sepsis and Imbalanced Inflammation in Preterm Infants and May Add to Lung Injury.

Background: Controversy remains concerning the impact of Ureaplasma on preterm neonatal morbidity. Methods: Prospective single-center study in very low birth weight infants <30 weeks' gestation. Cord blood and initial nasopharyngeal swabs were screened for Ureaplasma parvum and U. urealyticum using culture technique and polymerase chain reaction. Neonatal outcomes were followed until death or discharge. Multi-analyte immunoassay provided cord blood levels of inflammatory markers. Using multivariate regression analyses, perinatal Ureaplasma exposure was evaluated as risk factor for the development of bronchopulmonary dysplasia (BPD), other neonatal morbidities until discharge and systemic inflammation at admission. Results: 40/103 (39%) infants were positive for Ureaplasma in one or both specimens, with U. parvum being the predominant species. While exposure to Ureaplasma alone was not associated with BPD, we found an increased risk of BPD in Ureaplasma-positive infants ventilated ≥5 days (OR 1.64; 95% CI 0.12-22.98; p = 0.009). Presence of Ureaplasma was associated with a 7-fold risk of late onset sepsis (LOS) (95% CI 1.80-27.39; p = 0.014). Moreover, Ureaplasma-positive infants had higher I/T ratios (b 0.39; 95% CI 0.08-0.71; p = 0.014), increased levels of interleukin (IL)-17 (b 0.16; 95% CI 0.02-0.30; p = 0.025) and matrix metalloproteinase 8 (b 0.77; 95% CI 0.10-1.44; p = 0.020), decreased levels of IL-10 (b -0.77; 95% CI -1.58 to -0.01; p = 0.043) and increased ratios of Tumor necrosis factor-α, IL-8, and IL-17 to anti-inflammatory IL-10 (p = 0.003, p = 0.012, p < 0.001). Conclusions: Positive Ureaplasma screening was not associated with BPD. However, exposure contributed to BPD in infants ventilated ≥5 days and conferred an increased risk of LOS and imbalanced inflammatory cytokine responses.

Conservative management of placenta previa complicated by abnormal placentation.

OBJECTIVE: Abnormal implantation of placenta previa is life-threatening condition. The purpose of this study was to evaluate the impact of the conservative management of pregnancies with such complication on maternal morbidity rate and the chance for uterine preservation (fertility). METHODS: Eleven patients with abnormal implantation of placenta previa were analyzed prospectively. This complication was diagnosed antenatally by two-dimensional ultrasound and color flow Doppler. The following outcomes were analyzed: need for blood transfusion, admission and duration of stay in intensive care unit, infections, coagulopathies, time between cesarean section and delivery of placenta, hysterectomy and preservation of uterus. RESULTS: Among the 20 085 women who had a singleton gestation, 11 (0.054%) were identified with placenta previa with abnormal placentation. In five patients (group A), hysterectomy was performed because of hemorrhage or placenta ablation. In six patients (group B), conservative management succeeded and placenta were preserved. In group A, placenta were delivered earlier (2 d-8 weeks) in comparison with group B (6-15 weeks). Estimated blood loss during the delayed delivery of placenta was higher in the group with hysterectomy (respectively, 450-1600 and 300-500 ml). CONCLUSIONS: Conservative management of placenta previa with abnormal implantation decreases the risk of severe hemorrhage at the time of delivery and can preserve fertility.