Vaginal Fluid Inflammatory Biomarkers and the Risk of Adverse Neonatal Outcomes in Women with PPROM

Abstract

Objective The purpose of this study was to evaluate the predictive value of vaginal fluid biomarkers for chorioamnionitis and adverse perinatal outcomes in women with preterm premature rupture of membranes (PPROM).

Methods We recruited women with PPROM, without clinical chorioamnionitis, between 22 and 36 weeks' gestation. Vaginal fluid was collected on admission for the measurement of metalloproteinase-8 (MMP-8), interleukin-6 (IL-6), lactate, and glucose concentration. Placental pathology and neonatal charts were reviewed. Primary outcomes were histological chorioamnionitis and adverse neonatal neurological outcomes (intraventricular hemorrhage grade 2 or 3, periventricular leukomalacia, or hypoxic/ischemic encephalopathy). Linear regression analyses were used to adjust for gestational age at PPROM.

Results Twenty-seven women were recruited at a mean gestational age of 31.6 ± 3.1 weeks, including 25 (93%) with successful collection of vaginal fluid sample. Histological chorioamnionitis and adverse neonatal neurological outcomes were observed in nine (33%) and four (15%) cases, respectively. In univariate analysis, MMP-8, IL-6, glucose, and lactate concentrations in vaginal fluid were associated with the risk of chorioamnionitis but not anymore after adjustment for gestational age at PPROM. MMP-8 concentration was the only biomarker associated with adverse neurological outcome, and it remained significant after adjustment for gestational age at PPROM (p = 0.02).

Conclusion Vaginal fluid inflammatory biomarkers at admission for PPROM could predict adverse perinatal outcomes.

Keywords

pregnancy - prematurity - preterm premature rupture of membranes - chorioamnionitis - amniotic fluid - biomarkers

• References

• 1 Mercer BM. Preterm premature rupture of the membranes. Obstet Gynecol 2003; 101 (1) 178-193
• 2 Soraisham AS, Singhal N, McMillan DD, Sauve RS, Lee SK. Canadian Neonatal Network A multicenter study on the clinical outcome of chorioamnionitis in preterm infants. Am J Obstet Gynecol 2009; 200 (4) 372.e1-372.e6
• 3 Peaceman AM, Lai Y, Rouse DJ , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Length of latency with preterm premature rupture of membranes before 32 weeks' gestation. Am J Perinatol 2015; 32 (1) 57-62
• 4 Al-Mandeel H, Alhindi MY, Sauve R. Effects of intentional delivery on maternal and neonatal outcomes in pregnancies with preterm prelabour rupture of membranes between 28 and 34 weeks of gestation: a systematic review and meta-analysis. J Matern Fetal Neonatal Med 2013; 26 (1) 83-89
• 5 Ofman G, Vasco N, Cantey JB. Risk of Early-Onset Sepsis following Preterm, Prolonged Rupture of Membranes with or without Chorioamnionitis. Am J Perinatol 2015;
• 6 Bracci R, Buonocore G. Chorioamnionitis: a risk factor for fetal and neonatal morbidity. Biol Neonate 2003; 83 (2) 85-96
• 7 Murphy DJ, Sellers S, MacKenzie IZ, Yudkin PL, Johnson AM. Case-control study of antenatal and intrapartum risk factors for cerebral palsy in very preterm singleton babies. Lancet 1995; 346 (8988) 1449-1454
• 8 Lee J, Romero R, Dong Z , et al. Unexplained fetal death has a biological signature of maternal anti-fetal rejection: chronic chorioamnionitis and alloimmune anti-human leucocyte antigen antibodies. Histopathology 2011; 59 (5) 928-938
• 9 Park CW, Yoon BH, Park JS, Jun JK. A fetal and an intra-amniotic inflammatory response is more severe in preterm labor than in preterm PROM in the context of funisitis: unexpected observation in human gestations. PLoS ONE 2013; 8 (5) e62521
• 10 Avila C, Willins JL, Jackson M , et al. Usefulness of two clinical chorioamnionitis definitions in predicting neonatal infectious outcomes: a systematic review. Am J Perinatol 2015; 32 (11) 1001-1009
• 11 van der Ham DP, van der Heyden JL, Opmeer BC , et al. Management of late-preterm premature rupture of membranes: the PPROMEXIL-2 trial. Am J Obstet Gynecol 2012; 207 (4) 276.e1-276.e10
• 12 van der Ham DP, Vijgen SM, Nijhuis JG , et al; PPROMEXIL trial group. Induction of labor versus expectant management in women with preterm prelabor rupture of membranes between 34 and 37 weeks: a randomized controlled trial. PLoS Med 2012; 9 (4) e1001208
• 13 Morris JM, Roberts CL, Bowen JR , et al. Immediate delivery compared with expectant management after preterm pre-labour rupture of the membranes close to term (PPROMT trial): a randomised controlled trial. Lancet 2016; 387 (10017) 444-452
• 14 Simhan HN, Canavan TP. Preterm premature rupture of membranes: diagnosis, evaluation and management strategies. BJOG 2005; 112 (Suppl. 01) 32-37
• 15 Lacerte M, Bujold E, Audibert F, Mayrand MH. Amniocentesis for PPROM management: a feasibility study. J Obstet Gynaecol Can 2008; 30 (8) 659-664
• 16 Ramsey PS, Nuthalapaty FS, Lu G, Ramin S, Nuthalapaty ES, Ramin KD. Contemporary management of preterm premature rupture of membranes (PPROM): a survey of maternal-fetal medicine providers. Am J Obstet Gynecol 2004; 191 (4) 1497-1502
• 17 Gonik B, Cotton DB. The use of amniocentesis in preterm premature rupture of membranes. Am J Perinatol 1985; 2 (1) 21-24
• 18 Cotton DB, Gonik B, Bottoms SF. Conservative versus aggressive management of preterm rupture of membranes. A randomized trial of amniocentesis. Am J Perinatol 1984; 1 (4) 322-324
• 19 Cotton DB, Hill LM, Strassner HT, Platt LD, Ledger WJ. Use of amniocentesis in preterm gestation with ruptured membranes. Obstet Gynecol 1984; 63 (1) 38-43
• 20 Yoon BH, Romero R, Kim CJ , et al. Amniotic fluid interleukin-6: a sensitive test for antenatal diagnosis of acute inflammatory lesions of preterm placenta and prediction of perinatal morbidity. Am J Obstet Gynecol 1995; 172 (3) 960-970
• 21 Santhanam U, Avila C, Romero R , et al. Cytokines in normal and abnormal parturition: elevated amniotic fluid interleukin-6 levels in women with premature rupture of membranes associated with intrauterine infection. Cytokine 1991; 3 (2) 155-163
• 22 Romero R, Yoon BH, Mazor M , et al. A comparative study of the diagnostic performance of amniotic fluid glucose, white blood cell count, interleukin-6, and gram stain in the detection of microbial invasion in patients with preterm premature rupture of membranes. Am J Obstet Gynecol 1993; 169 (4) 839-851
• 23 Bujold E, Morency AM, Rallu F , et al. Bacteriology of amniotic fluid in women with suspected cervical insufficiency. J Obstet Gynaecol Can 2008; 30 (10) 882-887
• 24 Kim KW, Romero R, Park HS , et al. A rapid matrix metalloproteinase-8 bedside test for the detection of intraamniotic inflammation in women with preterm premature rupture of membranes. Am J Obstet Gynecol 2007; 197 (3) 292.e1-292.e5
• 25 American College of Obstetricians and Gynecologists Committee on Obstetric Practice. ACOG Committee Opinion No. 485: prevention of early-onset group B streptococcal disease in newborns. Obstet Gynecol 2011; 117 (4) 1019-1027
• 26 Papile LA, Munsick-Bruno G, Schaefer A. Relationship of cerebral intraventricular hemorrhage and early childhood neurologic handicaps. J Pediatr 1983; 103 (2) 273-277
• 27 American Collge of Obstetricians and Gynecologists (ACOG). Neonatal encephalopathy and cerebral palsy: executive summary. Obstet Gynecol 2004; 103 (4) 780-781
• 28 Chaemsaithong P, Romero R, Korzeniewski SJ , et al. A point of care test for interleukin-6 in amniotic fluid in preterm prelabor rupture of membranes: a step toward the early treatment of acute intra-amniotic inflammation/infection. J Matern Fetal Neonatal Med 2016; 29 (3) 360-367
• 29 Torbé A, Czajka R, Kordek A, Rzepka R, Kwiatkowski S, Rudnicki J. Value of vaginal fluid proinflammatory cytokines for the prediction of early-onset neonatal infection in preterm premature rupture of the membranes. J Interferon Cytokine Res 2007; 27 (5) 393-398
• 30 Ryu A, Park KH, Oh KJ, Lee SY, Jeong EH, Park JW. Predictive value of combined cervicovaginal cytokines and gestational age at sampling for intra-amniotic infection in preterm premature rupture of membranes. Acta Obstet Gynecol Scand 2013; 92 (5) 517-524
• 31 Rizzo G, Capponi A, Vlachopoulou A, Angelini E, Grassi C, Romanini C. Interleukin-6 concentrations in cervical secretions in the prediction of intrauterine infection in preterm premature rupture of the membranes. Gynecol Obstet Invest 1998; 46 (2) 91-95
• 32 Jun JK, Yoon BH, Romero R , et al. Interleukin 6 determinations in cervical fluid have diagnostic and prognostic value in preterm premature rupture of membranes. Am J Obstet Gynecol 2000; 183 (4) 868-873