Andrea Dotta

Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe

Congenital diaphragmatic hernia (CDH) is associated with high mortality and morbidity. To date, there are no standardized protocols for the treatment of infants with this anomaly. However, protocols based on the literature and expert opinion might improve outcome. This paper is a consensus statement from the CDH EURO Consortium prepared with the aim of achieving standardized postnatal treatment in European countries. During a consensus meeting between high-volume centers with expertise in the treatment of CDH in Europe (CDH EURO Consortium), the most recent literature on CDH was discussed. Thereafter, 5 experts graded the studies according to the Scottish Intercollegiate Guidelines Network (SIGN) Criteria. Differences in opinion were discussed until full consensus was reached. The final consensus statement, therefore, represents the opinion of all consortium members. Multicenter randomized controlled trials on CDH are lacking. Use of a standardized protocol, however, may contribute to more valid comparisons of patient data in multicenter studies and identification of areas for further research.

Breastfeeding promotion in neonatal intensive care unit: impact of a new program toward a BFHI for high‐risk infants

Aim: The study evaluates a breastfeeding promotion program in an Italian neonatal intensive care unit (NICU) over a period of time.

Conventional Mechanical Ventilation Versus High-frequency Oscillatory Ventilation for Congenital Diaphragmatic Hernia: A Randomized Clinical Trial (The VICI-trial).

Objectives:To determine the optimal initial ventilation mode in congenital diaphragmatic hernia. Background:Congenital diaphragmatic hernia is a life-threatening anomaly with significant mortality and morbidity. The maldeveloped lungs have a high susceptibility for oxygen and ventilation damage resulting in a high incidence of bronchopulmonary dysplasia (BPD) and chronic respiratory morbidity. Methods:An international, multicenter study (NTR 1310), the VICI-trial was performed in prenatally diagnosed congenital diaphragmatic hernia infants (n = 171) born between November 2008 and December 2013, who were randomized for initial ventilation strategy. Results:Ninety-one (53.2%) patients initially received conventional mechanical ventilation and 80 (46.8%) high-frequency oscillation. Forty-one patients (45.1%) randomized to conventional mechanical ventilation died/ had BPD compared with 43 patients (53.8%) in the high-frequency oscillation group. An odds ratio of 0.62 [95% confidence interval (95% CI) 0.25–1.55] (P = 0.31) for death/BPD for conventional mechanical ventilation vs high-frequency oscillation was demonstrated, after adjustment for center, head-lung ratio, side of the defect, and liver position. Patients initially ventilated by conventional mechanical ventilation were ventilated for fewer days (P = 0.03), less often needed extracorporeal membrane oxygenation support (P = 0.007), inhaled nitric oxide (P = 0.045), sildenafil (P = 0.004), had a shorter duration of vasoactive drugs (P = 0.02), and less often failed treatment (P = 0.01) as compared with infants initially ventilated by high-frequency oscillation. Conclusions:Our results show no statistically significant difference in the combined outcome of mortality or BPD between the 2 ventilation groups in prenatally diagnosed congenital diaphragmatic hernia infants. Other outcomes, including shorter ventilation time and lesser need of extracorporeal membrane oxygenation, favored conventional ventilation.

Long term follow-up in high-risk congenital diaphragmatic hernia survivors: patching the diaphragm affects the outcome

BACKGROUND/PURPOSE The increased survival rate reached in infants with congenital diaphragmatic hernia (CDH) has shown a concomitant increase in late morbidity. A recent report from CDH Study Group showed that dimension of diaphragmatic defect is the only independent risk factor of mortality. However, the influence of defect size on late morbidity is still controversial. The aim of the study was to evaluate the influence of patch repair (proxy of diaphragmatic defects size) on midterm morbidity. METHODS All high-risk (prenatal diagnosis and/or respiratory symptoms within 6 hours of life) CDH survivors treated at our institution from 2004 to 2008 were followed up in a multidisciplinary outpatient clinic as part of a longitudinal prospective study. Auxological, gastroesophageal, pulmonary, and orthopedic evaluations were performed at 6, 12, and 24 months of age. Patient outcomes were compared with respect to +/- patch repair. RESULTS Of 70 survivors, 61 (87%) were enrolled and prospectively evaluated in follow-up. Poorer auxological outcome, increased rate of gastroesophageal reflux, and altered pulmonary function test were observed during follow-up. CONCLUSIONS Patch repair correlates with higher pulmonary, auxological, and gastroesophageal morbidity without increasing chest wall deformities at long-term follow-up.

Phylogenetic and Metabolic Tracking of Gut Microbiota during Perinatal Development

The colonization and development of gut microbiota immediately after birth is highly variable and depends on several factors, such as delivery mode and modality of feeding during the first months of life. A cohort of 31 mother and neonate pairs, including 25 at-term caesarean (CS) and 6 vaginally (V) delivered neonates (DNs), were included in this study and 121 meconium/faecal samples were collected at days 1 through 30 following birth. Operational taxonomic units (OTUs) were assessed in 69 stool samples by phylogenetic microarray HITChip and inter- and intra-individual distributions were established by inter-OTUs correlation matrices and OTUs co-occurrence or co-exclusion networks. 1H-NMR metabolites were determined in 70 stool samples, PCA analysis was performed on 55 CS DNs samples, and metabolome/OTUs co-correlations were assessed in 45 CS samples, providing an integrated map of the early microbiota OTUs-metabolome. A microbiota “core” of OTUs was identified that was independent of delivery mode and lactation stage, suggesting highly specialized communities that act as seminal colonizers of microbial networks. Correlations among OTUs, metabolites, and OTUs-metabolites revealed metabolic profiles associated with early microbial ecological dynamics, maturation of milk components, and host physiology.

Kabuki syndrome: clinical and molecular diagnosis in the first year of life

Objective To review the clinical and molecular genetic characteristics of 16 patients presenting a suspected diagnosis of Kabuki syndrome (KS) in the first year of life, to evaluate the clinical handles leading to a prompt diagnosis of KS in newborns. Clinical diagnosis of KS can be challenging during the first year of life, as many diagnostic features become evident only in subsequent years. Methods All patients were clinically investigated by trained clinical geneticists. A literature review was performed using the Pubmed online database and diagnostic criteria suggested by DYSCERNE–Kabuki Syndrome Guidelines (2010) were used (a European Network of Centres of Expertise for Dysmorphology, funded by the European Commission Executive Agency for Health and Consumers (DG Sanco), Project 2006122). Molecular analysis of the known causative genes of KS, KMT2D/MLL2 and KDM6A, was performed through MiSeq-targeted sequencing platform. All mutations identified were validated by Sanger sequencing protocols. Results Mutations in KMT2D gene were identified in 10/16 (62%) of the patients, whereas none of the patients had KDM6A mutations. Facial dysmorphisms (94%), feeding difficulties (100%) and hypotonia (100%) suggested the clinical diagnosis of KS. No significative differences in terms of facial features were noticed between mutation positive and negative patients of the cohort. Brachydactyly, joint laxity and nail dysplasia were present in about 80% of the patients. Other congenital anomalies were most commonly present in the mutated group of patients, including left-sided cardiac abnormalities, skeletal, renal and anorectal malformations and hypertricosis. Conclusions We present an overview of patients with KS diagnosed during the first year of life. Early diagnosis is serviceable in terms of clinical management and for targeted genetic counselling.

Revised recommendations concerning palivizumab prophylaxis for respiratory syncytial virus (RSV)

Respiratory Syncytial Virus infections are one of the leading causes of severe respiratory diseases that require hospitalization and, in some cases, intensive care. Once resolved, there may be respiratory sequelae of varying severity. The lack of effective treatments for bronchiolitis and the lack of vaccines for RSV accentuate the role of prevention in decreasing the impact of this disease.Prevention of bronchiolitis strongly relies on the adoption of environment and the hygienic behavior measures; an additional prophylactic effect may be offered, in selected cases, by Palivizumab, a humanized monoclonal antibody produced by recombinant DNA technology, able to prevent RSV infection by blocking viral replication.After many years the Italian Society of Neonatology, on the basis of the most recent scientific knowledge, has decided to revise recommendations for the use of palivizumab in the prevention of RSV infection.

Birth of a child with congenital heart disease: emotional reactions of mothers and fathers according to time of diagnosis

Abstract Objective: To evaluate emotional distress, depression and quality of life in parents of infants with severe congenital heart disease (CHD) during their first hospitalization. Methods: A pilot study for 38 parental couples of infants with CHD hospitalized within the 3 months of life. Parents filled up three self-administered questionnaires. We compared differences in the variables measuring emotional distress, depression and quality of life between mothers and fathers, and between prenatal and postnatal diagnosis. Results: Stress and depression levels were significantly higher in mothers than in fathers (stress: 81.8% mothers versus 60.6% fathers; depression: 45.7% mothers versus 20.0% fathers). No difference were found between prenatal and postnatal groups in any field tested but, in percentage, mothers receiving prenatal diagnosis were more depressed, whereas those receiving postnatal diagnosis were more stressed. Fathers showed same tendency. Conclusions: Parents of newborns with severe CHD, especially mothers, need psychological support during their child’s hospitalization. Parents of children diagnosed prenatally may need counseling throughout pregnancy to help them recover from the loss of the imagined healthy child.

Near infrared spectroscopy in newborns with surgical disease

NIRS has been used as a key device with the aim to evaluate the impact of surgery and anesthesia on cerebral and splanchnic oxygenation in neonatal population. The main applications has been in cardiac surgery, congenital diaphragmatic hernia and esophageal atresia. In this report we summarized the results published on the application of NIRS in neonatal surgery with particular respect to cerebral and splanchnic oxygenation, presenting also some future prospective.

Pharmacological research in neonatology

In neonatalogy unit 40 to 80% of the drugs are used as off-label or unlicensed, particularly in Neonatal Intensive Care Unit (NICU), where it has been described that in a single patient up to 60 parenteral drugs can be administered. The course of a drug inside the organism can be defined in 4 different phases: absorption, distribution, metabolism, elimination; for each of these phases the newborn infant has different characteristics than child and adult. In the last years much more attention has been put in pharmacological research specific for the neonatal age and a good trial design should take into account the following points: (1) to define the pediatric disease in terms of natural history, prevalence, severity, treatment and impact of the new drug; (2) to avoid the “try and error” method based on the adult dose corrected for weight or age; (3) to use adapted methodologies (pharmacokinetics); (4) to avoid small clinical trials (limited number of patients), the use of Randomized Controlled Trials rather than observational studies; (5) to consider ethics providing clear information and reducing pain and stress to the baby and its family.