Late pregnancy associated plasma protein A levels decrease in preterm labor ALEV ATIS 1 , TURKAN TANDOGAN 1 , YAVUZ AYDIN 2 , CIHAT SEN 2 , FATMA TURGAY 3 , NEZAKET EREN 3 ,& NIMET GOKER 1 1 Department of Obstetrics and Gynecology, Sisli Etfal Training and Research Hospital, Istanbul, Turkey, 2 Department of Obstetrics and Gynecology, Cerrahpasa Medical Faculty of Istanbul University, Istanbul, Turkey, and 3 Department of Biochemistry, Sisli Etfal Training and Research Hospital, Istanbul, Turkey (Received 12 July 2010; revised 30 July 2010; accepted 7 October 2010) Abstract Objective. The purpose of the present study is to evaluate late, ‘at admission’, Pregnancy-associated plasma protein-A (PAPP-A) levels as a predictor of preterm birth in women with complaints of preterm labor or preterm painful contractions. Methods. Prospective cohort study of singleton gestations, 23–37 weeks, and symptoms of preterm labor. Primary end point was delivery 5 37 weeks. Predictive PAPP-A values were calculated both for preterm delivery and threatened preterm delivery on receiver operator curve. Results. In all, 41 women (38.3%) delivered before 37 weeks (Group 1); 32 women (30.7%) had symptoms of preterm labor but did not deliver preterm (Group 2); 31 women (29.7%) delivered term (Group 3, control). Mean PAPP-A levels in preterm-labor and its matched control were 33.4 + 19.9 and 52.5 + 25.4 mIU/ml, respectively, and difference was statistically significant (p ¼ 0.003). Mean PAPP-A level in threatened preterm labor group was 47.6 + 25.3 mIU/ml and difference was significant compared to preterm-labor, but not significant compared to control group (p ¼ 0.028 and p ¼ 0.74, respectively). Conclusion. Late PAPP-A levels decreased in preterm labor, levels 5 29.8 mIU/ml was associated with increased risk for preterm birth, supporting active management whereas cutoff value of 33.6 mIU/ml is useful for discrimination of preterm birth from threatened preterm birth reaching to term. Keywords: PAPP-A, preterm birth, threatened preterm labor, late pregnancy Introduction Preterm birth, defined as birth occurring before 37 gestational weeks, complicates 12.5% of all deliveries in the USA and accounts for approximately 75% of all neonatal deaths and 50% of childhood neurological morbidities [1,2]. Moreover, it is associated with high immediate and long-term costs after discharge from the hospital and remains the leading cause of perinatal mortality and morbidity [1–3]. The etiology of preterm delivery is unclear, but is likely to be complex and influenced by genetics and enviromental factors. Two- thirds of preterm deliveries are spontaneous, and in nearly all these cases, threatened preterm labor (TPL) precedes delivery [4–6]. Pregnancy-associated plasma protein-A (PAPP-A) is a product of the placenta and decidua and is secreted into the maternal circulation during human pregnancy [7,8]. It has been recently identified as an IGF binding protein (IGFBP)- 4 protease. Presumed functions at the mater- nal–fetal interface are to proteolyze IGFBP-4 and thus increase IGF bioavailability locally in the placenta, to promote IGF-II-mediated trophoblast invasion into the maternal decidua, and to modulate IGF regulation of steroidogenesis and glucose and amino acid transport in the villi [9]. Throughout the pregnancy, PAPP-A concentration in serum correlated to gestational age significantly increases with pregnancy until term [10–13]. Maternal serum concentrations of PAPP-A ( pappalysin-1, EC 3.4.24.79) are used to predict the occurrence of Down syndrome in the first trimester [14,15]. From previous reports, PAPP-A levels in the first trimester have been found also predictive in adverse pregnancy outcomes like fetal growth restriction, premature delivery, and preeclampsia [16,17]. IGFs are believed to play an important role in the regulation of trophoblast invasion of the decidua. Impaired release of free IGFs may be a cause for poor placental perfusion, thereby affecting the fetal growth and the onset of other adverse pregnancy conditions [9,18]. PAPP-A expression has been shown to be regulated by inflammatory cytokines such as TNF-a, IL-1b [19]. These data provide a mechanism for the regulation of PAPP-A in response to injury and further implicate PAPP-A as an acute reactant in inflammatory processes, one of which may be preterm labor. The pathological processes implicated in the preterm birth syndrome include inflammatory intrauterine infection and non-inflammatory group, uterine ischaemia (maternal–placental vasculopathy, uterine overdistension, abnormal allogenic recognition, allergic-like reaction, Correspondence: Alev Atis, Halkalı, Atakent mah.Soyak Olimpiakent sitesi.D:12 blok D:53, 34303,Ku ¨c ¸u ¨ kc ¸ekmece/Istanbul,Turkey. Tel: þ905323851290. E-mail: alevatis@mynet.com The Journal of Maternal-Fetal and Neonatal Medicine, 2011; Early Online, 1–5 ISSN 1476-7058 print/ISSN 1476-4954 online Ó 2011 Informa UK, Ltd. DOI: 10.3109/14767058.2010.531320 J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by 178.243.161.44 on 05/11/11 For personal use only.