Prostaglandin E2 and patent ductus arteriosus in premature infants

Abstract

Background Patent ductus arteriosus (PDA) is a congenital heart disease most commonly occurring in premature infants. Spontaneous ductus arteriosus (DA) closure in premature infants has been suggested to be associated with duct lumen maturity and the DA sensitivity to prostaglandin E2 (PGE2).Objective To assess for a possible correlation between serum PGE2 levels and PDA size in premature infants.Methods This observational study using repeated measurements on premature infants with PDA detected at days 2-3 of life was undertaken in Cipto Mangunkusumo Hospital and Fatmawati Hospital, Jakarta, from April to May 2014. The PDA was diagnosed using 2-D echocardiography and PGE2 levels were measured by immunoassay. Pearson’s correlation test was used to evaluate a possible correlation between PGE2 level and DA diameter.Results Thirty-three premature infants of median gestational age 31 (range 28-32) weeks and median birth weight 1,360 (range 1,000-1,500) grams were enrolled. Almost two-thirds of the subjects were male. Almost all (30/33) subjects had spontaneous DA closure before the age of 10 days. Subjects’ mean DA diameter was 2.9 (SD 0.5) mm with maximum flow velocity of 0.2 (SD 0.06) cm/sec, and left atrial-to-aortic root ratio (LA/Ao) of 1.5 (SD 0.2). Their mean PGE2 levels at the ages of 2-3, 5-7, and after 10 days were 5,238.6 (SD 1,225.2), 4,178.2 (SD 1,534.5), and 915.2 (SD 151.6) pg/mL, respectively. The PGE2 level at days 2-3 was significantly correlated with DA diameter (r = 0.667; P < 0.001), but not at days 5-7 (r = 0.292; P = 0.105) or at day 10 (r = 0.041; P = 0.941).Conclusion There is a strong, positive correlation between the PGE2 level and DA diameter in preterm infants at 2-3 days of age. However, there is no significant correlation between PGE2 level and persistence of PDA.

Genetic Foundation of Prostaglandin Metabolism Influences Patent Ductus Arteriosus Closure in Extremely Low Birth Weight Infants

“…Ductal remodeling and closure were studied in wild-type and PGDH-knockout mice. 9 These knockout mice all had significantly higher PGE 2 levels, had patent ductus arteriosus (PDA) without remodeling, and died within 12 to 48 hours. 13 In extremely preterm infants, persistent PDA has been associated with an increased risk of neonatal morbidities including bronchopulmonary dysplasia, 14,15 necrotizing enterocolitis, 16 mortality, 17 retinopathy of prematurity, 18 intraventricular hemorrhage, 19 periventricular leukomalacia, 20 and poor neurodevelopmental outcomes.…”

“…Prostaglandin E2 (PGE 2 ) is a derivative of arachidonic acid with strong biological effects on smooth muscle stimulation and vasodilation. 9 PGE 2 is produced in both the placenta and the DA in fetal life, exerting its effect via various seven-transmembrane G protein-coupled PGE receptors (EP 2 , EP 3 , and EP 4 ). EP 2 and EP 4 receptors activate adenylyl cyclase via G s , increasing intracellular cyclic adenosine monophosphate (cAMP) which leads to inhibition of myosin light chain kinase and thereby vasodilation.…”

“…11 PGE 2 is degraded in the lungs by 15-hydroxyprostaglandin dehydrogenase (PGDH) to metabolites which are excreted in the urine (90%) and feces (10%). 9 Expression of PGDH increases dramatically late in gestation, particularly in the fetal lung. In utero, blood is shunted away from the lung, protecting the circulating PGE 2 from catabolism.…”

“…Ductal remodeling and closure were studied in wild-type and PGDH-knockout mice. 9 These knockout mice all had significantly higher PGE 2 levels, had patent ductus arteriosus (PDA) without remodeling, and died within 12 to 48 hours. 13…”