Postnatal cytomegalovirus infection and pulmonary vascular disease in extremely premature infants: A case series.

BACKGROUND: Pulmonary vascular disease (PVD) is a major determinant of both morbidity and mortality in extremely low birth weight infants. It is biologically plausible that postnatal cytomegalovirus (pCMV) infection may lead to PVD in premature infants secondary to pneumonitis or via derangement of pulmonary vascular development directly through endothelial dysfunction. Uncertainty remains, however, regarding thresholds for intervention in premature infants with cardiorespiratory instability and presumed CMV infection likely secondary to the limited understanding of the natural history of the disease. METHODS/RESULTS: We describe four cases of premature infants with clinical and echocardiography features of PVD, in the setting of postnatally acquired CMV. All patients had atypical PVD trajectories, refractory to vasodilator treatment, which improved after initiation of CMV treatment. CONCLUSION: We highlight the need to consider postnatally acquired CMV infection in patients with PVD non-responsive to standard pulmonary vasodilator therapies or disease severity which is out of proportion of the usual clinical trajectory. Treatment of extremely premature infants with CMV-associated PVD may have positive impact on cardiorespiratory health, although duration of therapy remains uncertain.

Arterial pressure is not reflective of right ventricular function in neonates with hypoxic ischemic encephalopathy treated with therapeutic hypothermia.

AIM: to evaluate the correlation of recovery of arterial pressure with physiological recovery among patients with hypoxic ischemic encephalopathy undergoing therapeutic hypothermia. METHODS: At 24 h postnatal age, we compared 53 neonates of whom 22 (41%) were inotrope-treated to those untreated with cardiovascular medications. RESULTS: Inotrope-treated patients had persistent severe right ventricular (RV) dysfunction and evidence of abnormal brain tissue oxygen delivery, despite recovered arterial pressure. CONCLUSION: Arterial pressure is not reflective of RV function and the need for inotropic agents may be reflective of abnormal brain tissue oxygen delivery.

Impact of early screening echocardiography and targeted PDA treatment on neonatal outcomes in "22-23" week and "24-26" infants.

The hemodynamically significant patent ductus arteriosus (hsPDA) is a controversial topic in neonatology, particularly among neonates at the earliest gestational ages of 22+0-23+6 weeks. There is little, to no data on the natural history or impact of the PDA in extremely preterm babies. In addition, these high-risk patients have typically been excluded from randomized clinical trials of PDA treatment. In this work, we present the impact of early hemodynamic screening (HS) of a cohort of patients born 22+0-23+6 weeks gestation who either were diagnosed with hsPDA or died in the first postnatal week as compared to a historical control (HC) cohort. We also report a comparator population of 24+0-26+6 weeks gestation. All patients in the HS epoch were evaluated between 12-18h postnatal age and treated based on disease physiology whereas the HC patients underwent echocardiography at the discretion of the clinical team. We demonstrate a two-fold reduction in the composite primary outcome of death prior to 36 weeks or severe BPD and report a lower incidence of severe intraventricular hemorrhage (n=5, 7% vs n=27, 27%), necrotizing enterocolitis (n=1, 1% vs n=11, 11%) and first-week vasopressor use (n=7, 11% vs n=40, 39%) in the HS cohort. HS was also associated with an increase in survival free of severe morbidity from the already high rate of 50% to 73% among neonates <24 weeks gestation. We present a biophysiological rationale behind the potential modulator role of hsPDA on these outcomes and review the physiology relevant to neonates born at these extremely preterm gestations. These data highlight the need for further interrogation of the biological impact of hsPDA and impact of early echocardiography directed therapy in infants born less than 24 weeks gestation.

Management of cardiac dysfunction in neonates with pulmonary hypertension and the role of the ductus arteriosus.

Pulmonary hypertension in the neonate is associated with cardiopulmonary disturbances and neurodevelopment morbidity. The patent ductus arteriosus is a persistent fetal shunt that can be pathologic vs supportive in the setting of neonatal pulmonary hypertension. Understanding the underlying pathophysiology of pulmonary hypertension and the cardiopulmonary effects of various phenotypes can guide management in this vulnerable population. In this narrative, we will summarize the physiologic principles of pulmonary hypertension, the impact of the patent ductus arteriosus on various phenotypes, and the utility of serial targeted neonatal echocardiography to individualize clinical assessment and management.

Association of hemoglobin and spontaneous closure of the ductus arteriosus during the transitional period in very low birth weight infants.

OBJECTIVES: To determine the association between plasma hemoglobin (HB) at three time-points (birth, postnatal days 0-3 and 0-10) and spontaneous closure of the ductus arteriosus (sDAC). STUDY DESIGN: A retrospective case-control study of preterm infants born (2013-2016) between 24 and 29 weeks of gestational age (GA) was conducted in a level three perinatal center in Switzerland. We collected hemoglobin at birth, between days 0-3 and 0-10 in two distinct groups: (i) patients treated for a PDA and (ii) patients with spontaneous closure of the ductus arteriosus (sDAC). Antenatal and postnatal demographic data and neonatal morbidity were collected. Bivariate analysis was performed and a stepwise logistic regression was done to investigate factors associated with sDAC. RESULTS: We reviewed the medical chart of 184 premature infants of whom 146 (79.3%) satisfied eligibility criteria. Of these, 74 (51%) were classified as sDAC. Patients with sDAC were older (GA: 28 vs 27, p < 0.001), more stable (clinical risk index for babies score (CRIB score): 2 vs 5, p < 0.001) and had better clinical outcomes than patients who received treatment for a PDA. Infants in the sDAC group had a higher level of hemoglobin during the first ten postnatal days. Multiple logistic regression analysis revealed that lower HB level (day 0-10) were associated with failure of sDAC (p < 0.05). CONCLUSIONS: This is one of the first studies to highlight a potential association between hemoglobin during the transitional period and sDAC. The biological nature of this observation requires prospective clarification.

Patent ductus arteriosus and cerebral, cardiac, and gut hemodynamics in premature neonates.

Patent ductus arteriosus is associated with multiple comorbidities in premature infants, however a causal link or strategy to decrease these morbidities has not been found. The association between the patent ductus arteriosus and morbidities has biologic plausibility as, like any cardiac mixing lesion, a significant systemic to pulmonic shunt may lead to pulmonary over-circulation and systemic hypoperfusion. Understanding the underlying pathophysiology of associated morbidities in the setting of a patent ductus arteriosus may aid in risk stratifying infants and offer a patient targeted approach to infants with a pathological ductal shunt. While the deleterious impact of increased pulmonary blood flow maybe easier to identify, the impact on end-organ perfusion is more challenging. In this review, we will discuss the pathophysiology of a hemodynamically significant patent ductus arteriosus in premature infants, impact on end-organ perfusion and associated morbidities, and novel modalities to assess shunt volume and effect on end-organ perfusion.

Targeted Neonatal Echocardiography-Guided Therapy in Vein of Galen Aneurysmal Malformation: A Report of Two Cases with a Review of Physiology and Approach to Management.

Vein of Galen malformation results in predictable changes in physiology which exist on a continuum. Severe pulmonary hypertension may present as hypoxemia; however, excessive reduction in pulmonary vascular resistance may precipitate progressive pulmonary overcirculation and impaired systemic blood flow. Right ventricular performance and the patency and direction of the ductus arteriosus may play a crucial role in postductal organ perfusion. Physiological stabilization may be complex and variable over time. The utilization of targeted neonatal echocardiography to guide treatment decisions may improve the ability to provide therapy tailored to the specific disease pathophysiology and monitor serially as conditions change. An enhanced approach to physiological stabilization may reduce the risk of unexpected decompensation and allow for thoughtful, controlled endovascular embolization in appropriate candidates.