A Review of Serotonin in the Developing Lung and Neonatal Pulmonary Hypertension.

Serotonin (5-HT) is a bioamine that has been implicated in the pathogenesis of pulmonary hypertension (PH). The lung serves as an important site of 5-HT synthesis, uptake, and metabolism with signaling primarily regulated by tryptophan hydroxylase (TPH), the 5-HT transporter (SERT), and numerous unique 5-HT receptors. The 5-HT hypothesis of PH was first proposed in the 1960s and, since that time, preclinical and clinical studies have worked to elucidate the role of 5-HT in adult PH. Over the past several decades, accumulating evidence from both clinical and preclinical studies has suggested that the 5-HT signaling pathway may play an important role in neonatal cardiopulmonary transition and the development of PH in newborns. The expression of TPH, SERT, and the 5-HT receptors is developmentally regulated, with alterations resulting in pulmonary vasoconstriction and pulmonary vascular remodeling. However, much remains unknown about the role of 5-HT in the developing and newborn lung. The purpose of this review is to discuss the implications of 5-HT on fetal and neonatal pulmonary circulation and summarize the existing preclinical and clinical literature on 5-HT in neonatal PH.

Platelets and ductus arteriosus closure in neonates.

Platelet plug formation is critically involved in murine ductus arteriosus closure and thrombocytopenia in preterm infants seems to negatively affect spontaneous and pharmacologically induced ductal closure. Furthermore, platelet dysfunction may contribute to ductal patency, especially in extremely immature infants. Neonatal platelets likely have multifaceted roles during ductal closure, such as secretion of several signaling molecules and facilitation of specific cell-cell interactions. The only available randomized-controlled trial on platelet transfusions in preterm infants with patent ductus arteriosus demonstrated that a liberal transfusion regimen did not promote ductal closure, but was associated with an increased rate of intraventricular hemorrhage. Herein, we discuss the available mechanistic evidence on the role of platelets in ductus arteriosus closure and their potential clinical implications in preterm infants. We further briefly outline future research directions aimed at a better understanding of platelet-endothelial interactions in neonatal health and disease.

Serotonin-deficient neonatal mice are not protected against the development of experimental bronchopulmonary dysplasia or pulmonary hypertension.

Serotonin (5-hydroxytryptamine, 5-HT) is a potent pulmonary vasoconstrictor and contributes to high pulmonary vascular resistance in the developing ovine lung. In experimental pulmonary hypertension (PH), pulmonary expression of tryptophan hydroxylase-1 (TPH1), the rate limiting enzyme in 5-HT synthesis, and plasma 5-HT are increased. 5-HT blockade increases pulmonary blood flow and prevents pulmonary vascular remodeling and PH in neonatal models of PH with bronchopulmonary dysplasia (BPD). We hypothesized that neonatal tph1 knock-out (KO) mice would be protected from hypoxia-induced alveolar simplification, decreased vessel density, and PH. Newborn wild-type (WT) and tph1 KO mice were exposed to normoxia or hypoxia for 2 weeks. Normoxic WT and KO mice exhibited similar alveolar development, pulmonary vascular density, right ventricular systolic pressures (RVSPs), and right heart size. Circulating (plasma and platelet) 5-HT decreased in both hypoxia-exposed WT and KO mice. Tph1 KO mice were not protected from hypoxia-induced alveolar simplification, decreased pulmonary vascular density, or right ventricular hypertrophy, but displayed attenuation to hypoxia-induced RVSP elevation compared with WT mice. Tph1 KO neonatal mice are not protected against hypoxia-induced alveolar simplification, reduction in pulmonary vessel density, or RVH. While genetic and pharmacologic inhibition of tph1 has protective effects in adult models of PH, our results suggest that tph1 inhibition would not be beneficial in neonates with PH associated with BPD.

A Quality Initiative for Optimal Therapeutic Hypothermia during Transport for Neonates with Neonatal Encephalopathy.

INTRODUCTION: Neuroprotection with therapeutic hypothermia (TH) is standard of care for neonatal encephalopathy (NE) and decreases death and neurodevelopmental disability. TH initiated shortly after birth insult results in greater neuroprotection compared with delayed initiation. METHODS: Quality improvement methodology was used to improve temperature control during transport to a level IV neonatal intensive care unit. We included neonates with NE transported to a single institution for TH from 2010 to 2016. The quality improvement interventions were 2-fold. Review of the Transport Body Cooling Protocol revealed a suboptimal temperature goal of 34-35°C; this protocol was revised to 33-34°C. The second intervention was the implementation of an active cooling protocol. Clinical characteristics were compared using 2-sample t tests for continuous variables and Fisher's exact tests for categorical variables; statistical process control chart was used to monitor admission temperatures. RESULTS: We obtained baseline data for 78 neonates admitted from 2010 to 2014. These data were compared with postintervention data for 26 patients admitted between 2015 and 2016. Distance transported, NE severity, and seizures were similar between the 2 groups. The use of active cooling increased from 8% preimplementation to 31% postimplementation (P < 0.01). After implementation of the 2 interventions, more infants were admitted within the goal temperature of 33-34°C, 58% versus 22% (P < 0.01), and the average neonatal intensive care unit admission temperature improved from 34.4 ± 0.8°C to 33.8 ± 0.8°C (P < 0.01). CONCLUSION: Increased utilization of active cooling during transport for TH improves the percentage of neonates admitted within the target temperature range. However, 42% of neonates remained outside the target temperature range, supporting the need for additional tools to improve admission temperatures.

Late onset diaphragmatic hernia complicated by intestinal strangulation.

We present a case of a 7-week-old infant who presented with nonspecific respiratory symptoms that quickly progressed to sudden cardiac arrest as a consequence of late-onset diaphragmatic hernia and intestinal strangulation. Unless discovered as an incidental finding, late-onset diaphragmatic hernia should be considered a surgical emergency.