Association between oxidative stress in pregnancy and preterm premature rupture of membranes Mariangela Longini, Serafina Perrone, Piero Vezzosi, Barbara Marzocchi, Antonio Kenanidis, Giovanni Centini, Lucia Rosignoli, Giuseppe Buonocore ⁎ Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Policlinico “Le Scotte”, V.le Bracci 36, 53100 Siena, Italy Received 4 January 2007; received in revised form 27 February 2007; accepted 12 March 2007 Available online 20 March 2007 Abstract Background: Premature rupture of membranes (PROM) is caused by collagen damage in the chorioamniotic sac leading to tearing. Reactive oxygen species (ROS) may be the cause of collagen damage. Isoprostanes (F 2 -IP) are produced by ROS attack on polyunsaturated fatty acids and are sensitive and specific biomarkers of lipid-peroxidation in vivo. Aim: To verify whether oxidative stress occurs in pregnancies associated with preterm PROM. Methods: F 2 -IPs were measured in amniotic fluid of 16 pregnancies with preterm PROM (Group II) and 97 without PROM (Group I). Results: F 2 -IP concentrations (pg/mL) were significantly higher in group II than group I (p < 0.0001). The ROC curve showed a sensitivity of 100% and a specificity of 84.5% at a cut-off of 124.4 pg/mL. Conclusions: An association exists between oxidative stress in pregnancy and preterm PROM. The detection of amniotic fluid F 2 -IP concentrations seems to be a reliable predictive index of risk of preterm PROM. © 2007 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Keywords: Oxidative stress; Lipid peroxidation; Reactive oxygen species; Amniotic fluid; Chorioamniotic sac; High risk pregnancies Introduction Premature rupture of the membrane (PROM) prior to onset of labour complicates approximately 10% of all pregnancies; about a third of which before term. Preterm premature rupture of the membranes (P-PROM) is defined as a spontaneously rupture in the chorioamnion, before the 37 weeks' gestation. Preterm premature rupture of the membranes occurs in approximately 1% of all pregnancies and is associated with 30% to 40% of preterm deliveries [1,2]. Membrane rupture is related to biochemical processes in- volving collagen synthesized by fibroblasts in the foetal mem- branes. Since the strength and the elasticity of the foetal membranes is primarily due to collagen, reduced concentrations and/or an altered collagen cross-link profile can induced PROM [3]. Known clinical risk factors for PROM include low socio- economic status, low body mass index, prior preterm birth, cigarette smoking, urinary tract infection, sexually transmitted diseases, cervical conization or cerclage, overdistended uterus, amniocentesis in the current pregnancy, prior preterm labour and symptomatic contractions in the current pregnancy [4–7]. Neonatal complications are related to the gestational age at which membrane rupture and delivery occur. Respiratory distress syndrome is the most common serious complication after PROM at any gestational age. Other serious morbidities, including necrotizing enterocolitis, intraventricular haemorrhage, sepsis, bronchopulmonary dysplasia and retinopathy of prematurity, decrease with advancing gestational age at delivery [8–11]. Maintenance of the chorioamniotic sac throughout normal pregnancy requires a balance between collagen synthesis by fibroblasts and collagenolytic activity by controlled responses of enzymes expressed in the foetal membrane. The membranes are reported to be stronger before term than at term, which suggests that preterm rupture may be related to loss of strength and elasticity [3]. Reactive oxygen species (ROS), unstable molecules gener- ated continuously in the body, could be responsible for collagen Clinical Biochemistry 40 (2007) 793 – 797 ⁎ Corresponding author. Fax: +39 577 586182. E-mail address: buonocore@unisi.it (G. Buonocore). 0009-9120/$ - see front matter © 2007 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.clinbiochem.2007.03.004