Implementing intact cord resuscitation in very preterm infants: feasibility and pitfalls.

The purpose of this study is to evaluate the feasibility of intact cord resuscitation (ICR) in very preterm infants using a custom-equipped mobile resuscitation trolley (LifeStart®). We collected maternal and neonatal data of all inborn infants < 32 weeks eligible for ICR per our protocol over 9 months from ICR implementation. We compared rates of ICR between the beginning and the end of the study period. We reviewed maternal and neonatal adverse events related to the procedure and direct outcomes. In order to assess potential quality improvements related to the procedure, we collected the same data in the infants born in the 9-month period preceding ICR implementation. Out of 44 infants born < 32 weeks during the period, 27 were eligible for ICR. Failure to initiate ICR occurred in 9/27, exclusively in the first 5.5 months of the study. In one infant, ICR was interrupted prior to 2 min due to placental abruption. No ICR procedure had to be interrupted due to insufficient cord length. Among the 18 infants who completed ICR, cord clamping timing increased significantly over the study period, from 3.0 [2.5-3.5] to 4.2 min [3.1-8.3] (p = 0.02). No significant maternal blood loss or wound complications were noted. No infant deaths were attributable to failure or direct consequence of ICR, and no infant experienced hypoxic respiratory failure (intubation, FiO2 ≥ 0.4), asphyxia (pH < 7.2), or blood pressure instability (< 2 SD) following stabilization. Hemoglobin level after cord clamping was higher in the ICR cohort than in the pre-implementation group. Seven out of 18 infants exposed to ICR had a temperature < 36.5 °C on admission.   Conclusion: ICR is feasible in very preterm infants. Temperature management requires special attention. Multidisciplinary simulation training before implementation and systematic post-implementation quality improvement meetings may significantly increase ICR program success. What is Known: • Because infants born < 32 weeks often require cardiorespiratory resuscitation at birth, they are not offered delayed cord clamping in the majority of neonatal intensive care units. • Recently, fully equipped mobile trolleys have been developed in order to allow bedside resuscitation with an intact cord. What is New: • Variable timing of cord clamping based on the infant's transition and respiratory stability, i.e., "physiology-based cord clamping," is safely achievable in very preterm infants. • Intact cord resuscitation requires specific equipment, operational protocols, and a high level of preparation from both obstetrical and neonatal teams, with a learning curve that can be streamlined by multidisciplinary simulation training.

Torsade de pointe due to QT prolongation following erythromycin administration in a preterm infant.

BACKGROUND: Neonatal sepsis is a major cause of morbidity and mortality in preterm infants. Chorioamnionitis is an important risk factor for the development of sepsis, therefore neonates born to mothers developing signs of amnionitis need to be treated with antibiotics immediately after birth. Ureaplasma spp can be a causative agent of vaginal or intra amniotic infection needing antibiotic treatment. Macrolides are frequently used to treat maternal intrauterine infection, but antibiotic treatment of the neonate should be consciously chosen with consideration of potential side effects. Indeed, macrolides are great purveyors of heart rhythm disorders. CASE PRESENTATION: We describe the case of a 29 weeks preterm infant born to a mother with Ureaplasma spp infection. The baby was treated with erythromycin immediately after birth. During the second day of life, the baby presented some episodes of tachyarrhythmia with premature ventricular beats (PVBs) that were followed by a non-sustained ventricular tachycardia as high as 270 bpm leading to a cardiac arrest. After resuscitation, tachycardia resolved but the rhythm was characterised by numerous PVBs and an electrocardiogram (ECG) diagnosed a Long QT Syndrome (LQTS). Erythromycin was discontinued, and the rhythm normalised a few days after withdrawal. CONCLUSIONS: Erythromycin should be administered in neonates only if no other choice is available, as although generally well tolerated, its administration can be associated with QTc interval prolongation. When no other option is available, paediatricians should be aware to perform cardiac monitoring or at least serial ECGs before and during erythromycin administration.

Early diagnosis and targeted approaches to pulmonary vascular disease in bronchopulmonary dysplasia.

Pulmonary hypertension has emerged as a life-threatening disease in preterm infants suffering from bronchopulmonary dysplasia (BPD). Its development is closely linked to respiratory disease, as vasculogenesis and alveologenesis are closely interconnected. Once clinically significant, BPD-associated pulmonary hypertension (BPD-PH) can be challenging to manage, due to poor reversibility and multiple comorbidities frequently associated. The pulmonary vascular disease process underlying BPD-PH is the result of multiple innate and acquired factors, and emerging evidence suggests that it progressively develops since birth and, in certain instances, may begin as early as fetal life. Therefore, early recognition and intervention are of great importance in order to improve long-term outcomes. Based on the most recent knowledge of BPD-PH pathophysiology, we review state-of-the-art screening and diagnostic imaging techniques currently available, their utility for clinicians, and their applicability and limitations in this specific population. We also discuss some biochemical markers studied in humans as a possible complement to imaging for the detection of pulmonary vascular disease at its early stages and the monitoring of its progression. In the second part, we review pharmacological agents currently available for BPD-PH treatment or under preclinical investigation, and discuss their applicability, as well as possible approaches for early-stage interventions in fetuses and neonates. IMPACT: BPD-associated PH is a complex disease involving genetic and epigenetic factors, as well as environmental exposures starting from fetal life. The value of combining multiple imaging and biochemical biomarkers is emerging, but requires larger, multicenter studies for validation and diffusion. Since "single-bullet" approaches have proven elusive so far, combined pharmacological regimen and cell-based therapies may represent important avenues for research leading to future cure and prevention.

Antenatal diagnosis of CHARGE syndrome: Prenatal ultrasound findings and crucial role of fetal dysmorphic signs. About a series of 10 cases and review of literature.

Although the prognosis of CHARGE syndrome can be highly variable from mild until severe, final diagnosis is difficult to establish in utero. The aim of our study is to compare antenatal and postnatal findings in a retrospective cohort of 10 successive patients with a positive CHD7 gene variant in order to identify the specific prenatal features for CHARGE syndrome diagnosis. Fetal ultrasound, follow-up and supplementary investigations are collected and compared to postnatal findings. Congenital heart defect (7/10), choanal atresia (7/10) and tracheoesophageal atresia (4/10) are the most frequent fetal anomalies found. Inner and external ear anomalies appear as the keystone (constant features) for prenatal diagnosis of CHARGE syndrome in fetuses with multiple anomalies and normal microarray karyotype. External ear malformations are identified in all cases by 3D ultrasound when carefully evaluated. MRI and temporal bone CT-Scan are second line useful tools to assess the diagnosis when looking for semicircular canal agenesis, arhinencephaly and/or choanal atresia. Before availability of prenatal exome sequencing in clinical routine, present findings lead to the recommendation that fetuses, with congenital heart defect (mainly septal and conotruncal), cleft lip/palate or unexplained polyhydramnios should carefully be screened for clues suggesting CHARGE syndrome using 2D and 3D ultrasound, MRI and temporal bone CT-Scan. When CHARGE syndrome is suspected with normal molecular karyotype, CHD7 gene sequencing must be offered.

Nutrients and Microbiota in Lung Diseases of Prematurity: The Placenta-Gut-Lung Triangle.

Cardiorespiratory function is not only the foremost determinant of life after premature birth, but also a major factor of long-term outcomes. However, the path from placental disconnection to nutritional autonomy is enduring and challenging for the preterm infant and, at each step, will have profound influences on respiratory physiology and disease. Fluid and energy intake, specific nutrients such as amino-acids, lipids and vitamins, and their ways of administration -parenteral or enteral-have direct implications on lung tissue composition and cellular functions, thus affect lung development and homeostasis and contributing to acute and chronic respiratory disorders. In addition, metabolomic signatures have recently emerged as biomarkers of bronchopulmonary dysplasia and other neonatal diseases, suggesting a profound implication of specific metabolites such as amino-acids, acylcarnitine and fatty acids in lung injury and repair, inflammation and immune modulation. Recent advances have highlighted the profound influence of the microbiome on many short- and long-term outcomes in the preterm infant. Lung and intestinal microbiomes are deeply intricated, and nutrition plays a prominent role in their establishment and regulation. There is an emerging evidence that human milk prevents bronchopulmonary dysplasia in premature infants, potentially through microbiome composition and/or inflammation modulation. Restoring antibiotic therapy-mediated microbiome disruption is another potentially beneficial action of human milk, which can be in part emulated by pre- and probiotics and supplements. This review will explore the many facets of the gut-lung axis and its pathophysiology in acute and chronic respiratory disorders of the prematurely born infant, and explore established and innovative nutritional approaches for prevention and treatment.