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.

Double-blind, randomised clinical assay to evaluate the efficacy of probiotics in preterm newborns weighing less than 1500 g in the prevention of necrotising enterocolitis.

BACKGROUND: A randomised, double-blind clinical trial was undertaken in order to assess the effectiveness of probiotics in the prevention of necrotising enterocolitis (NEC) in newborns weighing <1500 g. METHODS: We studied a group of 150 patients who were randomised in two groups after parental consent was obtained, to receive either a daily feeding supplementation with a multispecies probiotic (Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus casei, Lactobacillus plantarum, Bifidobacteruim infantis, Streptococcus thermophillus) 1 g per day plus their regular feedings or to receive their regular feedings with nothing added (control group), over the period of January 2007 through June 2010. Clinicians in care of the infants were blinded to the group assignment. RESULTS: The primary outcome was the development of NEC. Both groups were comparable, with no differences during hospitalisation, including the type of nutrition received. Blood cultures obtained from cases that developed sepsis did not reveal lactobacillus or Bifidobacteria growth. No differences were detected in terms of NEC risk reduction (RR: 0.54, 95% CI 0.21 to 1.39) although we did observe a clear trend in the reduction of NEC frequency in the studied cases: 6 (8%) versus 12 (16%) in the control group. When the combined risk of NEC or death was calculated as a post hoc analysis, we found a significantly lower risk (RR: 0.39, 95% CI 0.17 to 0.87) for the study group. CONCLUSIONS: Probiotics may offer potential benefits for premature infants and are a promising strategy in the reduction of the risk of NEC in preterm newborns.

Efectividad del ácido ursodesoxicólico versus fenobarbital para el tratamiento de la colestasis en prematuros. Ensayo clínico cruzado / Efectiveness of ursodeoxycholic acid versus phenobarbital for the treatment of neonatal cholestasis: a cross-randomizad clinical trial

Introducción. La prevalencia de colestasis neonatal varía del 7-57%. Parte del manejo incluye al ácido ursodesoxicólico (UDCA) y al fenobarbital, ambos con débil sustento en la literatura. El objetivo de este trabajo es comparar la efectividad del UDCA vs fenobarbital en la reducción de las cifras de bilirrubina directa, en recién nacidos prematuros con colestasis, con peso entre 1 000-2 000 g. Métodos. Se realizó un ensayo clínico aleatorizado cruzado en 18 pacientes. Cada individuo recibió al azar una de las dos intervenciones: UDCA (10 mg/kg/día c/12 h) o fenobarbital (a 3 mg/kg/día c/24 h) durante un período inicial de 7 días. Después de 7 días de lavado, se les asignó el tratamiento contrario. En total se realizaron 36 tratamientos. Se midieron bilirrubinas y pruebas de función hepática al inicio y final de cada tratamiento. El análisis se realizó por medio de medidas de tendencia central y de dispersión, de acuerdo al tipo de variable. Para la comprobación de hipótesis se realizó t pareada. Resultados. En el grupo que recibió UDCA a 10 mg/kg/día c/12 h por 7 días, disminuyeron las cifras de bilirrubina directa en 2.7 mg/dL (P<0.01). Conclusiones. Se recomienda el uso de UDCA a dosis de 10 mg/kg/día c/12 h por vía enteral como coadyuvante para el tratamiento de colestasis neonatal.

Background. The prevalence of neonatal cholestasis varies from 7-57%. Part of the treatment includes ursodeoxycholic acid (UDCA) and phenobarbital, both with little supporting evidence in the literature. We undertook this study to compare the effectiveness of phenobarbital vs. UDCA in reducing the direct serum bilirubin levels in patients with cholestasis and weighing from 1 000 to 2 000 g. Methods. Using a cross-randomized clinical trial, 18 patients were included with 36 treatments. Each subject randomly received one of the two interventions: UDCA (10 mg/kg/day) every 12 h or phenobarbital (3 mg/kg/day, every 24 h for 7 days) continuing with 7 days of wash-out to return to their initial state, and to subsequently receive the other treatment. At the beginning and at the end of the administration of each medication, bilirubin concentrations and hepatic test functions were measured. Central tendency and dispersion measurements were applied according to the type of variable. For hypothesis confirmation, paired t-test was carried out. Results. The obtained results indicate that with UDCA at a dose of 10 mg/kg/day every 12 h for 7 days, serum bilirubin levels decreased to 2.7 mg/dL (p <0.01). Phenobarbital had no effect in reducing bilirubin concentration. Conclusion. Use of UDCA is recommended at a dose of 10 mg/kg/dose every 12 h (PO) as a coadjuvant in the treatment of neonatal cholestasis.