OBSTETRICS Clinical and inflammatory markers in amniotic fluid as predictors of adverse outcomes in preterm premature rupture of membranes Teresa Cobo, MD; Montse Palacio, MD; Mónica Martínez-Terrón, MD; Aleix Navarro-Sastre, MD; Jordi Bosch, MD; Xavier Filella, MD; Eduard Gratacós, MD OBJECTIVE: We sought to evaluate gestational age, cervical length, amniotic fluid interleukin (IL)-6, and selected proteomic biomarkers as independent predictors of adverse outcome in preterm premature rup- ture of membranes (PPROM). STUDY DESIGN: This was a prospective cohort study of 65 consecutive women with PPROM (20.0-34.6 weeks). Gestational age, cervical length, amniotic fluid IL-6, and proteomic biomarkers (calgranulins A and C, and neutrophil defensins 1 and 2) were evaluated at diagnosis. The predictive value for intraamniotic infection and neonatal composite morbidity was calculated by logistic regression. RESULTS: Proteomic biomarkers were independent predictors of in- traamniotic infection (odds ratio, 22.1; P = .011) and neonatal composite morbidity (odds ratio, 17.6; P = .02). With the exception of a trend between gestational age and neonatal morbidity (P = .054), none of the other parameters were independent predictors of outcome measures. CONCLUSION: Selected proteomic biomarkers were the only indepen- dent predictors of adverse outcomes in PPROM. Contrary to what is re- ported in preterm labor with intact membranes, gestational age, cervi- cal length, and IL-6 were not. Key words: cervical length, gestational age at membrane rupture, interleukin-6, intraamniotic infection, selected proteomic biomarkers Cite this article as: Cobo T, Palacio M, Martínez-Terrón M, et al. Clinical and inflammatory markers in amniotic fluid as predictors of adverse outcomes in preterm premature rupture of membranes. Am J Obstet Gynecol 2011;205:126.e1-8. P reterm premature rupture of mem- branes (PPROM) is responsible for approximately one-third of preterm births 1 and a substantial proportion of neonatal mortality and serious morbid- ity. Neonatal outcome depends on the occurrence of complications in relation with prematurity or infection. 2 Predict- ing the risk of neonatal adverse outcomes is a critical need and consti- tutes the basis for improving pregnancy management and parental counseling. Subclinical intraamniotic inflammation (IAI), which is present in a substantial proportion of patients with either preterm labor (PTL) or PPROM, 3 is proposed as the strongest predictor of adverse outcome in these patients, even in the absence of de- monstrable positive cultures. 3 Identification of the risk of adverse out- come in patients with PPROM remains challenging. The role of clinical features with an independent prognostic value among pregnancies with PTL and intact membranes, such as gestational age and short cervical length, 3,4 has so far not been investigated in women with PPROM. Concerning biochemical markers, the per- formance of amniotic fluid interleukin (IL)-6 to predict IAI and adverse perinatal outcome is poorer in pregnancies present- ing with PPROM with respect to that de- scribed for women with PTL and intact membranes. 5,6 Recently, new biomarkers of inflammation in amniotic fluid, inte- grated in a mass restricted score, such as calgranulins A and C, and neutrophil de- fensins have shown promising results as predictors of intraamniotic infection and neonatal sepsis in patients at risk. 7-9 In co- horts containing only women with PTL and intact membranes, these inflamma- tory proteins predict IAI with a similar ac- curacy to IL-6, 10 and their combination with IL-6 seems to further increase the pre- dictive value of each biomarker alone. 10 However, the value of calgranulins and neutrophil defensins in cases with only PPROM remains to be investigated. The purpose of this study was to eval- uate the independent and combined value of clinical parameters, including gestational age and cervical length at di- agnosis, and amniotic fluid IL-6 and proteomic biomarkers (calgranulins A From the Department of Maternal-Fetal Medicine, Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Clínic (Drs Cobo, Palacio, Martínez-Terrón, and Gratacós); the Department of Biochemistry and Molecular Genetics, Centre de Diagnòstic Biomèdic, Hospital Clínic (Drs Navarro-Sastre and Filella); the Department of Microbiology (Dr Bosch), Centre de Diagnòstic Biomèdic, Hospital Clínic; the Centro de Investigación Biomédica en Red de Enfermedades Raras (Drs Palacio, Navarro-Sastre, and Gratacós), Barcelona, Spain; and the Institut de Investigacions Biomèdiques August Pi-Sunyer, University of Barcelona, Barcelona, Spain (Drs Palacio, Navarro-Sastre, and Gratacós). Received Nov. 22, 2010; revised Feb. 8, 2011; accepted March 29, 2011. Reprints: Montse Palacio, MD, Prematurity Unit, Department of Maternal-Fetal Medicine, Hospital Clinic, Sabino de Arana 1, Barcelona 08028, Catalonia, Spain. mpalacio@clinic.ub.es. 0002-9378/$36.00 • © 2011 Mosby, Inc. All rights reserved. • doi: 10.1016/j.ajog.2011.03.050 Research www. AJOG.org 126.e1 American Journal of Obstetrics & Gynecology AUGUST 2011