Neonatal diagnosis of ACTA2-related disease: A case report and review of literature.

Multisystemic smooth muscle dysfunction syndrome (MSMDS, OMIM # 613834) is a rare autosomal dominant condition caused by pathogenetic variants of ACTA2 gene that result in impaired muscle contraction. MSMDS is characterized by an increased susceptibility to aneurismal dilatations and dissections, patent ductus arteriosus, early onset coronary artery disease, congenital mydriasis, chronic interstitial lung disease, hypoperistalsis, hydrops of gall bladder, and hypotonic bladder. Here, we report an early diagnosis of a MSMDS related to ACTA2 p.Arg179His (R179H) mutation in a newborn and performed a review of the literature. An early diagnosis of MSMDS is extremely important, because of the severe involvement of cardiovascular system in the MSMDS. Multidisciplinary care and surveillance and timely management of symptoms are important to reduce the risk of complications.

Phenotype characterisation of TBX4 mutation and deletion carriers with neonatal and paediatric pulmonary hypertension.

Rare variants in the T-box transcription factor 4 gene (TBX4) have recently been recognised as an emerging cause of paediatric pulmonary hypertension (PH). Their pathophysiology and contribution to persistent pulmonary hypertension in neonates (PPHN) are unknown. We sought to define the spectrum of clinical manifestations and histopathology associated with TBX4 variants in neonates and children with PH.We assessed clinical data and lung tissue in 19 children with PH, including PPHN, carrying TBX4 rare variants identified by next-generation sequencing and copy number variation arrays.Variants included six 17q23 deletions encompassing the entire TBX4 locus and neighbouring genes, and 12 likely damaging mutations. 10 infants presented with neonatal hypoxic respiratory failure and PPHN, and were subsequently discharged home. PH was diagnosed later in infancy or childhood. Three children died and two required lung transplantation. Associated anomalies included patent ductus arteriosus, septal defects, foot anomalies and developmental disability, the latter with a higher prevalence in deletion carriers. Histology in seven infants showed abnormal distal lung development and pulmonary hypertensive remodelling.TBX4 mutations and 17q23 deletions underlie a new form of developmental lung disease manifesting with severe, often biphasic PH at birth and/or later in infancy and childhood, often associated with skeletal anomalies, cardiac defects, neurodevelopmental disability and other anomalies.

Ultrastructural characterization of genetic diffuse lung diseases in infants and children: a cohort study and review.

Pediatric diffuse lung diseases are rare disorders with an onset in the neonatal period or in infancy, characterized by chronic respiratory symptoms and diffuse interstitial changes on imaging studies. Genetic disorders of surfactant homeostasis represent the main etiology. Surfactant protein B and ABCA3 deficiencies typically cause neonatal respiratory failure, which is often lethal within a few weeks or months. Although heterozygous ABCA3 mutation carriers are mostly asymptomatic, there is growing evidence that monoallelic mutations may affect surfactant homeostasis. Surfactant protein C mutations are dominant or sporadic disorders leading to a broad spectrum of manifestations from neonatal respiratory distress syndrome to adult pulmonary fibrosis. The authors performed pathology and ultrastructural studies in 12 infants who underwent clinical lung biopsy. One carried a heterozygous SP-B mutation, 3 carried SP-C mutations, and 7 carried ABCA3 mutations (5 biallelic and 2 monoallelic). Optical microscopy made it possible to distinguish between surfactant-related disorders and other forms. One of the ABCA3 monoallelic carriers had morphological features of alveolar capillary dysplasia, a genetic disorder of lung alveolar, and vascular development. One patient showed no surfactant-related anomalies but had pulmonary interstitial glycogenosis, a developmental disorder of unknown origin. Electron microscopy revealed specific lamellar bodies anomalies in all SP-B, SP-C, and ABCA3 deficiency cases. In addition, the authors showed that heterozygous ABCA3 mutation carriers have an intermediate ultrastructural phenotype between homozygous carriers and normal subjects. Lung biopsy is an essential diagnostic procedure in unexplained diffuse lung disorders, and electron microscopy should be performed systematically, since it may reveal specific alterations in genetic disorders of surfactant homeostasis.

Lumbar Puncture and Meningitis in Infants with Proven Early- or Late-Onset Sepsis: An Italian Prospective Multicenter Observational Study.

Background: To evaluate the rates of lumbar puncture (LP) in infants with culture-proven sepsis. Study design: We prospectively enrolled 400 infants with early- or late-onset sepsis due to Group B streptococcus (GBS) or Eschericha coli, diagnosed within 90 days of life. Rates of LP and potential variables associated with LP performance were evaluated. Moreover, cerebrospinal fluid (CSF) characteristics and results of the molecular analysis were investigated. Results: LP was performed in 228/400 (57.0%) infants; 123/228 LPs (53.9%) were performed after antibiotic initiation, hampering the ability to identify the pathogen in the CSF culture. However, polymerase chain reaction increased the probability of positive results of CSF analysis compared to microbiological culture (28/79, 35.4% vs. 14/79, 17.7%, p = 0.001). Severe clinical presentation and GBS infection were associated with higher LP rates. The rate of meningitis was 28.5% (65/228). Conclusions: Rates of LP are low in culture-proven neonatal sepsis and antibiotics are frequently given before LP is carried out. Thus meningitis may be underestimated, and the chances of giving an effective therapy to the newborn are reduced. LP should be performed before the start of antibiotics when there is a clinical suspicion of infection.

Timing of Symptoms of Early-Onset Sepsis after Intrapartum Antibiotic Prophylaxis: Can It Inform the Neonatal Management?

The effectiveness of "inadequate" intrapartum antibiotic prophylaxis (IAP administered < 4 h prior to delivery) in preventing early-onset sepsis (EOS) is debated. Italian prospective surveillance cohort data (2003-2022) were used to study the type and duration of IAP according to the timing of symptoms onset of group B streptococcus (GBS) and E. coli culture-confirmed EOS cases. IAP was defined "active" when the pathogen yielded in cultures was susceptible. We identified 263 EOS cases (GBS = 191; E. coli = 72). Among GBS EOS, 25% had received IAP (always active when beta-lactams were administered). Most IAP-exposed neonates with GBS were symptomatic at birth (67%) or remained asymptomatic (25%), regardless of IAP duration. Among E. coli EOS, 60% were IAP-exposed. However, IAP was active in only 8% of cases, and these newborns remained asymptomatic or presented with symptoms prior to 6 h of life. In contrast, most newborns exposed to an "inactive" IAP (52%) developed symptoms from 1 to >48 h of life. The key element to define IAP "adequate" seems the pathogen's antimicrobial susceptibility rather than its duration. Newborns exposed to an active antimicrobial (as frequently occurs with GBS infections), who remain asymptomatic in the first 6 h of life, are likely uninfected. Because E. coli isolates are often unsusceptible to beta-lactam antibiotics, IAP-exposed neonates frequently develop symptoms of EOS after birth, up to 48 h of life and beyond.

Neonatal Cerebral Venous Thrombosis following Maternal SARS-CoV-2 Infection in Pregnancy.

A possible consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the development of an exacerbated thrombophilic status, and cerebral venous thrombosis (CVT) is a rare but possible complication of SARS-CoV-2 infection reported both in adults and in children. The present case report describes the clinical course of a term neonate showing extended CVT of unclear origin, whose mother had developed SARS-CoV-2 infection during the third trimester of pregnancy. We speculate that the prothrombotic status induced by maternal SARS-CoV-2 infection may have played a pathophysiological role in the development of such severe neonatal complication. Further investigations are required to confirm such hypothesis.

A previously undescribed de novo 4p15 deletion in a patient with apparently isolated metopic craniosynostosis.

Interstitial deletion of the short arm of chromosome 4, excluding cytoband p16, has been described as a distinct phenotype from the Wolf-Hirschhorn syndrome, characterized by a deletion encompassing cytoband p16. We report on the case of a 14-month-old boy with an apparently isolated craniosynostosis and harboring a de novo microdeletion in band 4p15. The imbalance, about 4 Mb in size is, to date, the smallest deletion ever described in this region, encompassing 12 genes. A comparison with other previously described cases of 4p15 deletion is made, and the possible roles of some genes involved in the deletion are discussed.

Effects of osteopathic approach in infants with deformational plagiocephaly: an outcome research study.

BACKGROUND: The aim of the present study is to investigate the effects of the osteopathic approach in infants with deformational plagiocephaly at 12-month follow up and to evaluate parental satisfaction and safety of the treatments. METHODS: The authors reviewed charts of infants with a medical diagnosis of deformational plagiocephaly consecutively seen in a private paediatric outpatient in Rome, Italy, between December 2016 and February 2018. After applying the exclusion criteria, infants under 6 months of corrected age, with diagnosis of deformational plagiocephaly and assessed with a plagiocephalometry were included. RESULTS: 37 infants (mean age 16,6±5,7 weeks; 19 females) were eligible for this study, generating 35 unilateral deformational plagiocephaly (21 right-sided) and 18 brachycephaly (16 infants had both). After an average of 6.5±2.8 osteopathic manipulative treatments plus postural advice, a significant reduction of all indices of the plagiocephalometry assessments was reported at 12-month follow up. Oblique Diameter Difference Index decreased from 109 ± 4.5 to 103.7 ± 1.9 (Mean diff - 5.3 CI 95% {-5.83; -3.41}, p<0.001); Cranial Proportional Index decreased from 94.9 ± 3.8 to 85.6 ± 2.4 (mean diff -9.3 CI 95% {-11.39; -7.37}, p<0.001); Ear Deviation Index decreased from 7.7 ± 3.3 to 3 ± 1.6 (mean diff -4.7 CI 95% {-6.1; -2.84}, p <0.001). CONCLUSIONS: Osteopathic approach could be considered an interesting option in the treatment of infants with deformational plagiocephaly. Parents were overall satisfied with this approach. No adverse events or reactions were reported in this study. Multicentre randomized controlled trials are recommended.

Congenital self-healing reticulohistiocytosis in a newborn: unusual oral and cutaneous manifestations.

BACKGROUND: Congenital self-healing reticulohistiocytosis (CSHRH), also called Hashimoto-Pritzker disease, is a rare and benign variant of Langerhans cell histiocytosis, characterized by cutaneous lesions without extracutaneous involvement. CASE PRESENTATION: We present a case of CSHRH with diffuse skin lesions and erosions in the oral mucosa, present since birth and lasting for 2 months, and we perform a review of the literature on Pubmed in the last 10 years. CONCLUSIONS: Our case confirm that lesions on oral mucosa, actually underestimated, may be present in patients with CSHRH. Patients affected by CSHRH require a close follow-up until the first years of life, due to the unpredictable course of Langerhans cell histiocytosis, in order to avoid missing diagnosis of more aggressive types of this disorder.

[Parenteral nutrition with preconceived bag in a preterm newborn ELBW.] / Nutrizione parenterale con sacca precostituita in un neonato pretermine di peso estremamente basso.

INTRODUCTION: The administration of adequate nutritional intake, from the first days of life, is of fundamental importance in the management of the newborn extremely low birth weight (ELBW): parenteral nutrition (PN), as a support for early enteral feeding, plays a central role in the attempt to guarantee a quantitative and qualitative growth similar to that of the fetus in utero, allowing an adequate caloric, macro and micronutrient intake. The standardized PN, carried out through pre-established bags, allows in the case in which is not possible a personalized preparation, balanced nutritional contributions, reducing the risk of microbiological contamination and errors in preparation. CLINICAL CASE: We describe the case of an extremely preterm infant with various co-morbid conditions (severe respiratory syndrome, cerebral hemorrhage, anemia, sepsis and patency of the arterial duct) in which PN was used in a pre-established bag, as a support to enteral feeding in the first weeks of life, characterized by extreme clinical instability. CONCLUSIONS: PN is essential for some types of newborns and in particular for the ELBW preterms in which enteral feeding, although undertaken early, does not guarantee the necessary contributions to promote adequate growth. The use of NP in a pre-made bag can be a valid alternative to individualized formulations, where not available.

Nasal high-frequency oscillatory ventilation and CO2 removal: A randomized controlled crossover trial.

OBJECTIVE: To compare short-term application of nasal high-frequency oscillatory ventilation (nHFOV) with nasal continuous positive airway pressure (nCPAP). WORKING HYPOTHESIS: nHFOV improves CO2 removal with respect to nCPAP in preterm infants needing noninvasive respiratory support and persistent oxygen supply after the first 72 h of life. STUDY DESIGN: Multicenter non-blinded prospective randomized crossover study. PATIENT SELECTION: Thirty premature infants from eight tertiary neonatal intensive care units, of mean ± SD 26.4 ± 1.8 weeks of gestational age and 921 ± 177 g of birth weight. METHODOLOGY: Infants were randomly allocated in a 1:1 ratio to receive a starting treatment mode of either nCPAP or nHFOV delivered by the ventilator CNO (Medin, Germany), using short binasal prongs of appropriate size. A crossover design with four 1-h treatment periods was used, such that each infant received both treatments twice. The primary outcome was the mean transcutaneous partial pressure of CO2 (TcCO2 ) value during the 2-h cumulative period of nHFOV compared with the 2-h cumulative period of nCPAP. RESULTS: Significantly lower TcCO2 values were observed during nHFOV compared with nCPAP: 47.5 ± 7.6 versus 49.9 ± 7.2 mmHg, respectively, P = 0.0007. A different TcCO2 behavior was found according to the random sequence: in patients starting on nCPAP, TcCO2 significantly decreased from 50.0 ± 8.0 to 46.6 ± 7.5 mmHg during nHFOV (P = 0.001). In patients starting on nHFOV, TcCO2 slightly increased from 48.5 ± 7.8 to 49.9 ± 6.7 mmHg during nCPAP (P = 0.13). CONCLUSIONS: nHFOV delivered through nasal prongs is more effective than nCPAP in improving the elimination of CO2 .

Cardiac tamponade and bilateral pleural effusion in a very low birth weight infant.

A very low birth weight premature newborn developed a sudden cardiac tamponade due to parenteral fluid extravasation 1 month after central line insertion. Besides tensive pericardial effusion a bilateral pleural effusion also developed. An emergency pericardiocentesis was really life-saving and after pleural fluid removal a complete cardiorespiratory recovery was obtained. Pericardial and bilateral pleural effusions very rarely coexist as a complication of central line extravasation.

Ghrelin, leptin, IGF-1, IGFBP-3, and insulin concentrations at birth: is there a relationship with fetal growth and neonatal anthropometry?

BACKGROUND: Insulin, growth hormone (GH), and growth factors (insulin-like growth factors [IGFs] and their binding proteins [IGFBPs]) are known to influence fetal growth and also the synthesis/secretion of the recently discovered hormones leptin and ghrelin. METHODS: In 153 delivering mothers and their offspring at birth, we prospectively investigated the association between mothers' and babies' serum concentrations of ghrelin, leptin, insulin, IGF-1, and IGFBP-3 and neonatal anthropometric characteristics and the growth of the fetus. We also tried to put babies' serum glucose and GH measurements in this context. RESULTS: Birth weight (BW), birth length, head circumference, and ponderal index (PI) were positively associated with cord IGF-1, IGFBP-3, and leptin and negatively associated with GH. BW was independently associated with maternal stature and prepartum weight, birth length with maternal stature, PI with maternal insulin and prepartum weight, and head circumference with maternal ghrelin. Compared with preterm infants whose development was appropriate for gestational age (AGA), preterm growth-restricted babies displayed alteration in GH-IGF axis (increased GH and low IGF-1 and IGFBP-3 concentrations), low leptin and glucose concentrations, and increased ghrelin concentrations. In large-for-gestational-age (LGA) babies, leptin, IGFBP-3, insulin, and glucose concentrations were significantly higher in asymmetric LGA newborns than in symmetric LGA and AGA newborns. CONCLUSIONS: We found relationships between metabolic factors, fetal growth, and anthropometry. Intrauterine growth restriction involved alteration in the fetal GH-IGF axis, with relatively low leptin and glucose concentrations and increased ghrelin concentrations. Leptin, insulin, and IGFBP-3 delineated subtypes of fetal overgrowth.