Association of the EPAS1 rs7557402 Polymorphism with Hemodynamically Significant Patent Ductus Arteriosus Closure Failure in Premature Newborns under Pharmacological Treatment with Ibuprofen.

Patent ductus arteriosus (PDA) is frequent in preterm newborns, and its incidence is inversely associated with the degree of prematurity. The first choice of pharmacological treatment is ibuprofen. Several genes, including EPAS1, have been proposed as probable markers associated with a genetic predisposition for the development of PDA in preterm infants. EPAS 1 NG_016000.1:g.84131C>G or rs7557402 has been reported to be probably benign and associated with familial erythrocytosis by the Illumina Clinical Services Laboratory. Other variants of EPAS1 have been previously reported to be benign for familial erythrocytosis because they decrease gene function and are positive for familial erythrocytosis because the overexpression of EPAS1 is a key factor in uncontrolled erythrocyte proliferation. However, this could be inconvenient for ductal closure, since for this process to occur, cell proliferation, migration, and differentiation should take place, and a decrease in EPAS1 gene activity would negatively affect these processes. Single-nucleotide polymorphisms (SNPs) in EPAS1 and TFAP2B genes were searched with high-resolution melting and Sanger sequencing in blood samples of preterm infants with hemodynamically significant PDA treated with ibuprofen at the National Institute of Perinatology. The variant rs7557402, present in the EPAS1 gene eighth intron, was associated with a decreased response to treatment (p = 0.007, OR = 3.53). The SNP rs7557402 was associated with an increased risk of pharmacological treatment failure. A probable mechanism involved could be the decreased activity of the product of the EPAS1 gene.

Findings From Somatic and Cerebral Near-Infrared Spectroscopy and Echocardiographic Monitoring During Ductus Arteriosus Ligation: Description of Two Cases and Review of Literature.

Background: Preterm infants with hemodynamically significant patent ductus arteriosus (HsPDA) are exposed to low cerebral tissue oxygen saturation (rScO2) values. Additionally, infants requiring surgical ligation are at risk of further changes in cerebral oxygenation and postligation cardiac syndrome (PLCS). Previous studies have assessed the effect of PDA ligation on rScO2 with variable results. Cases description: In this report we analyse near-infrared spectroscopy (NIRS) and echocardiographic findings of two patients who underwent ligation of PDA and presented low cardiac output. Literature on regional tissue oxygenation saturation (rSO2) before and after PDA ligation was briefly reviewed. Discussion: Cerebral oxygenation values before and after PDA ligation may be influenced by gestational age, vasopressor use, ductal shunt volume, time of exposure HsPDA, chronological age and the presence of cerebral autoregulation. PLCS complicates 28-45% of all PDA ligations and is associated with higher mortality. Cerebral and somatic NIRS monitoring in the postoperative period may enhance the identification of PLCS at early stages. Conclusion: Cerebral oxygenation in the perioperative period of PDA ligation may be influenced by numerous clinical factors. Early detection of PLCS using multisite NIRS after ligation could prevent further alterations in cerebral hemodynamics and improve outcomes. A decrease in somatic-cerebral difference and/or a significant drop in somatic NIRS values may precede clinical signs of hypoperfusion. NIRS values should be interpreted as trends along with echocardiographic findings to guide goal directed interventions.

Inflammatory Response in Preterm and Very Preterm Newborns with Sepsis.

The response of the adaptive immune system is usually less intense in premature neonates than term neonates. The primary objective of this study was to determine whether immunological parameters vary between preterm (PT) neonates (≥32 weeks of gestational age) and very preterm (VPT) neonates (<32 weeks of gestational age). A cross-sectional study was designed to prospectively follow PT and VPT neonates at risk of developing sepsis. Plasma concentrations of IFN-γ, TNF-α, IL-6, IL-4, and IL-10 were detected using flow cytometry. C-reactive protein (C-RP) and the complex SC5b-9 were detected in the plasma using commercial kits. A total of 83 patients were included. The laboratory results and clinical histories showed that 26 patients had sepsis; 14 were VPT, and 12 were PT. The levels of C-RP, SC5b-9 (innate immune response mediators), and IL-10 or IL-4 (anti-inflammatory cytokines) were elevated during sepsis in both groups. IFN-γ, TNF-α, and IL-6 (proinflammatory cytokines) were differentially elevated only in PT neonates. The VPT neonates with sepsis presented increases in C-RP, SC5b-9, and anti-inflammatory cytokines but not in proinflammatory cytokines, whereas PT neonates showed increases in all studied mediators of inflammation.

Epidemiología del embarazo gemelar doble en el Instituto Nacional de Perinatología Isidro Espinosa de los Reyes / Epidemiology of twin pregnancy at the Instituto Nacional de Perinatología Isidro Espinosa de los Reyes

Introducción: El embarazo gemelar se considera una entidad con alto riesgo de salud perinatal. En nuestra institución, el porcentaje de recién nacidos vivos, producto de embarazos gemelares dobles, varía entre 4.8 y 6.5%. Los embarazos múltiples tienen un impacto mayor en los sistemas de salud, debido a mayor frecuencia de complicaciones. Objetivo: Describir las características maternas y neonatales asociadas al embarazo gemelar doble de la población atendida en el Instituto Nacional de Perinatología Isidro Espinosa de los Reyes y determinar las diferencias de morbilidad entre el primero y el segundo gemelo. Material y métodos: El estudio se llevó a cabo del 1 de enero de 2007 al 31 de diciembre del 2008. Se incluyeron todos los recién nacidos vivos, producto de embarazos gemelares dobles. Se realizó estadística descriptiva mediante tablas de frecuencia y estadística analítica, para el contraste entre gemelos. Resultados: Se incluyeron 654 casos de recién nacidos producto de embarazos gemelares dobles. El embarazo fue espontáneo en el 92%. La preeclampsia fue la morbilidad materna más frecuente y se presentó en el 14.8% de los casos. La principal morbilidad encontrada en los recién nacidos fue restricción de crecimiento intrauterino (55.2%) y prematurez en el 54.9%. No hubo diferencias significativas en la morbilidad entre el gemelo uno y el gemelo dos. Conclusiones: Debido a una mayor morbilidad materna y neonatal en el embarazo gemelar doble es necesario realizar medidas preventivas en el periodo perinatal, para disminuir complicaciones.

Introduction: The twin pregnancy is considered a high risk entity. In our institution, the percentage of live newborns due to double pregnancies varies between 4.8 and 6.5%. Multiple pregnancies have a greater impact on health systems due to high rate of complications. Objective: To describe the maternal and neonatal characteristics of twin pregnancies at the Instituto Nacional de Perinatología, and determine differences in morbidity between the first and second twin. Material and Methods: The study was conducted in the all newborns products of twin pregnancies from January 1st 2007 to December 31st 2008 were included. Descriptive statistics by means of tables and analytical statistics was used to compare the twins. Results: A total of 654 newborn cases from 327 twin pregnancies were included. Spontaneous pregnancy was found in 92%. Preeclampsia was the most common cause of maternal mortality presented in 14.2% of the pregnancies. Intrauterine growth restriction was found in 55.2% and prematurity in 54.9%. No statistical differences were observed in the morbidity between the first and the second twin. Conclusions: Due to an increased maternal and fetal morbidity and mortality observed in twin pregnancies, measures to prevent complications most be applied during the perinatal period.