Abstract

Objective: Our objective was to determine the relative importance of demographic characteristics, clinical risk factors, and ancillary screening tests in the prediction of preterm birth as a result of premature rupture of membranes. Study Design: A total of 2929 women were evaluated in 10 centers at 23 to 24 weeks gestation. Demographic and clinical characteristics were ascertained. Cervicovaginal fetal fibronectin and bacterial vaginosis were evaluated. Cervical length was measured by vaginal ultrasonography. Patients were evaluated for spontaneous preterm birth caused by preterm premature rupture of membranes at <37 and <35 weeks gestation. Multivariate analyses were performed separately for nulliparous women and multiparous women. Results: Premature rupture of membranes at <37 weeks gestation complicated 4.5% of pregnancies, accounting for 32.6% of preterm births. Univariate analysis revealed low body mass index, pulmonary disease, contractions within 2 weeks, short cervix ( 25 mm), positive results of fetal fibronectin screening, bacterial vaginosis, and a previous preterm birth caused by premature rupture of membranes (in multiparous women) to be significantly associated with preterm birth caused by premature rupture of membranes in the current gestation. Short cervix, previous preterm birth caused by premature rupture of membranes in multiparous women, and presence of fetal fibronectin were the strongest predictors for both preterm birth caused by premature rupture of membranes at <37 and <35 weeks gestation. Women with positive fetal fibronectin screening results and a short cervix had greater risks both of preterm birth caused by premature rupture of membranes at <37 weeks gestation (relative risk, 4.9) and of preterm birth caused by premature rupture of membranes at <35 weeks gestation (relative risk, 13.5) than did those without these risk factors. Multiparous women with all three risk factors had a 31.3-fold increased risk of preterm birth caused by premature rupture of membranes at <35 weeks gestation. Conclusion: The combination of short cervical length, previous preterm birth caused by preterm premature rupture of membranes, and positive fetal fibronectin screening results was highly associated with preterm delivery caused by preterm premature rupture of membranes in the current gestation. (Am J Obstet Gynecol 2000;183:738-45.)

Romero R, Yoon BH, Mazor M, Gomez R, Gonzalez R, Diamond MP, Baumann P, Araneda H, Kenney JS, Cotton DB Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Hutzel Hospital, Detroit, MI 48201. American Journal of Obstetrics and Gynecology [1993, 169(4):839-51]

Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Comparative Study Abstract Highlight Terms Gene Ontology(1) Genes/Proteins(1) Species(2) Chemicals(1) OBJECTIVE: Our aim was to compare the value of amniotic fluid tests for the detection of microbial invasion of the amniotic cavity and in the prediction of the amniocentesis-to-delivery interval and neonatal complications in patients with preterm premature rupture of membranes.

STUDY DESIGN: Amniotic fluid was obtained by transabdominal amniocentesis from 110 consecutive patients with preterm premature rupture of membranes. Fluid was cultured for aerobic and anaerobic bacteria, as well as mycoplasmas. Amniotic fluid analysis included a Gram stain examination, white blood cell count, and glucose and interleukin-6 determinations. Logistic regression and survival techniques (proportional hazards model) were used for statistical analysis. RESULTS: (1) The prevalence of positive amniotic fluid cultures in patients with preterm premature rupture of membranes was 38% (42/110); (2) patients with microbial invasion had a shorter amniocentesis-to-delivery interval and a higher neonatal complication rate than patients with negative cultures; (3) the most sensitive test for the detection of microbial invasion of the amniotic cavity was amniotic fluid interleukin-6 determinations (cutoff 7.9 ng/ml) (sensitivity: for IL-6 80.9%; for white blood cell count 57.1%; for glucose 57.1%; for Gram stain 23.8%; p < 0.05 for all comparisons); (4) the most specific test for the detection of microbial invasion was the Gram stain of amniotic fluid (specificity: for Gram stain 98.5%; for white blood cell count 77.9%; for interleukin-6 75%; for glucose 73.5%; p < 0.01 for all); (5) of all amniotic fluid tests, interleukin-6 determination was the only test that had significant clinical value in the prediction of the amniocentesis-to-delivery interval and neonatal complications. CONCLUSION: Interleukin-6 concentrations in amniotic fluid are a better predictor of microbial invasion of the amniotic cavity, amniocentesis-to-delivery interval and neonatal complications than the amniotic fluid Gram stain, glucose, or white blood cell count in patients with preterm premature rupture of membranes.

The Lancet, Volume 346, Issue 8985, Pages 1271 - 1279, 11 November 1995 <Previous Article|Next Article> doi:10.1016/S0140-6736(95)91868-XCite or Link Using DOI Antimicrobial therapy in expectant management of preterm premature rupture of the membranes B.M Mercer MD * a, K.L Arheart EdD b Abstract Summary We review the impact of antimicrobial treatment on maternal and fetal outcome during expectant management of preterm premature rupture of the membranes. Relevant studies were retrieved from Medline (1966 to August, 1994) with the search term fetal-membrane-premature-rupture and antibiotics or antimicrobial, Excerpta Medica (1972 to August, 1994) with the search term premature fetus, membrane rupture, and antibiotic or antimicrobial therapy, and the Cochrane database of systemic reviews with the criterion antibiotics and prelabour rupture of membranes. We also obtained unpublished data from a randomised clinical trial of ceftizoxime versus placebo. The selected studies were randomised controlled trials of systemic antimicrobial therapy for prolongation of gestation in non-labouring women after preterm premature rupture of the membranes. Data extraction was done by a single reviewer. Studies were evaluated for post-randomisation exclusion and other confounding variables that might introduce analytical bias. Analysis was done with SAS statistical software by a blinded investigator. Antimicrobial therapy after preterm premature rupture of the membranes is associated with a reduced number of women delivering within 1 week (62 vs 76%; OR 051, 95% Cl 041068), and reduced diagnosis of maternal morbidity including chorioamnionitis (12 vs 23%; 045, 033060) and postpartum infection (8 vs 12%; 063, 041-097). Fetal morbidity, including confirmed sepsis (5 vs 9%; 057, 036-088), pneumonia (1 vs 3%; 032, 011-096), and intraventricular haemorrhage (9 vs 14%; 065, 045-092) were less often diagnosed after antimicrobial therapy. Separate analysis of the six placebo-controlled trials revealed similar or improved odds of pregnancy prolongation, chorioamnionitis, neonatal sepsis, postpartum infection, positive infant blood cultures, and pneumonia. Antimicrobial therapy, when used in the expectant management of preterm premature rupture of the membranes is associated with prolongation of pregnancy and a reduction in the diagnosis of maternal and infant morbidity. Further study should be directed towards determination of optimal antimicrobial therapy, increasing pregnancy prolongation, and enhancement of corticosteroid therapy for induction of pulmonary maturity after preterm premature rupture of the membranes. Evidence for the participation of interstitial collagenase (matrix metalloproteinase 1) in preterm premature rupture of membranes Eli Maymon, MDa, Roberto Romero, MDa, b, Percy Pacora, MDa, Maria-Teresa Gervasi, MDa, Katherine Bianco, MDa, Fabio Ghezzi, MDa, Bo Hyun Yoon, MD, PhDc

Abstract

Objective: Rupture of membranes is thought to result from the effects of physical forces in localized areas of the membranes weakened by the degradation of structural collagens. Matrix metalloproteinases are enzymes that degrade extracellular matrix components and have been implicated in membrane rupture. The objective of this study was to determine whether spontaneous rupture of membranes is associated with a change in the amniotic fluid concentration of interstitial collagenase (matrix metalloproteinase 1 [MMP-1]), a major collagenase. Study Design: A cross-sectional study was conducted to determine MMP-1 concentrations in amniotic fluid from 353 women in the following categories: (1) term with intact membranes not in labor and in labor, (2) preterm labor who delivered at term, (3) preterm labor who delivered preterm without microbial invasion of the amniotic cavity, (4) preterm labor who delivered preterm with microbial invasion of the amniotic cavity, (5) preterm premature rupture of membranes with and without microbial invasion of the amniotic cavity, (6) term premature rupture of membranes not in labor and in labor, and (7) mid trimester of pregnancy. Microbial invasion of the amniotic cavity was determined by an amniotic fluid culture positive for microorganisms. MMP-1 concentrations in amniotic fluid were determined by means of sensitive and specific immunoassays. Results: (1) MMP-1 was detectable in 81.3% of amniotic fluid samples (287/353), and its concentrations increased with advancing gestational age (r = 0.4; P < .001). (2) Preterm premature rupture of membranes was associated with a significant increase in the median amniotic fluid concentration of MMP-1 (P = .02). (3) Women with term premature rupture of membranes had a significantly lower amniotic fluid MMP-1 concentration than those with intact membranes at term not in labor (P < .001). (4) Microbial invasion of the amniotic cavity in patients in preterm labor with intact membranes and in patients with preterm premature rupture of membranes was also associated with significant increases in the median amniotic fluid MMP-1 concentrations (P < .05 and P < .01, respectively). (5) Patients with preterm premature rupture of membranes and microbial invasion of the amniotic cavity had a significantly higher median amniotic fluid MMP-1 concentration than those with intact membranes and microbial invasion of the amniotic cavity (P = .01). (6) Neither term nor preterm parturition was associated with changes in amniotic fluid MMP-1 concentrations (P = .6 and P = .3, respectively). Conclusion: (1) Collagenase 1 (MMP-1) is a physiologic constituent of amniotic fluid. (2) Preterm premature rupture of membranes (in both the presence and absence of infection) was associated with an increase in the amniotic fluid MMP-1 concentrations. (3) Neither term nor preterm parturition was associated with a significant increase in the amniotic fluid concentration of MMP-1. (Am J Obstet Gynecol 2000;183:914-20.)

Vitamins C and E: Missing links in preventing preterm premature rupture of membranes? James R. Woods Jr, MD, Mark A. Plessinger, PhD, Richard K. Miller, PhD

Abstract

We propose that generation of reactive oxygen species may be a potentially reversible pathophysiologic pathway leading to preterm premature rupture of the membranes. Reactive oxygen species generated by the body s response to diverse insults such as infection, cigarette smoking, bleeding, or cocaine use can activate collagenolytic enzymes and impair fetal membrane integrity. Vitamin E, a lipid-soluble antioxidant, inhibits membrane-damaging effects of reactive oxygen species induced lipid peroxidation. Vitamin C, a water-soluble antioxidant in plasma, stimulates and protects collagen synthesis while recycling vitamin E. Prior evidence shows that (1) damage by reactive oxygen species can impair fetal membrane integrity, (2) reduced midgestation levels of vitamin C are associated with preterm premature rupture of membranes, and (3) these vitamins can be safely and effectively absorbed and delivered to gestational tissues. Current prenatal vitamin preparations contain vitamins C and E in concentrations that are less than 1/3 and 1/10, respectively; these levels have been suggested for effective antioxidant protection. We hypothesize that increased dietary consumption or supplementation of vitamins C and E during pregnancy may reduce physiologically the risks of that portion of preterm premature rupture of membranes that is mediated by excessive or undamped peroxidation of fetal membranes. This hypothesis, if confirmed, should stimulate initiation of therapeutic trials to test the efficacy of enhanced supplementation with vitamins C and E during pregnancy to prevent preterm premature rupture of membranes. (Am J Obstet Gynecol 2001;185:5-10.)

Volume 22, Supplement A, Pages S38-S44 (April 2001)

ABSTRACT

Reactive Oxygen Species and Preterm Premature Rupture of Membranes A Review J.R. Woods Jraf1 Accepted 19 January 2001. Abstract

Preterm premature rupture of membranes (PPROM) results initially from damage to collagen in the chorioamnion leading to a tear in the membrane. Tissue-damaging molecules called reactive oxygen species (ROS) are capable of damaging collagen in the chorioamnion that could lead to PPROM. This hypothesis is supported by epidemiological studies linking clinical conditions known to produce ROS or reduce antioxidant protection to PPROM, by in-vitro studies in which membrane segments exposed to ROS exhibited tissue alterations consistent with PPROM, and by clinical studies showing that chorioamnion and amniotic fluid samples obtained from PPROM patients exhibit excessive collagen degradation. The role of antioxidants to protect the chorioamnion from ROS damage has been demonstrated in one in-vitro study. A prospective, randomized blinded trial of antioxidant therapy during pregnancy is needed to evaluate this approach for the prevention of PPROM.

Failure of physiologic transformation of the spiral arteries in the placental bed in preterm premature rupture of membranes

Presented at the Twenty-second Annual Meeting of the Society for Maternal-Fetal Medicine, New Orleans, La, January 14-19, 2002. Yeon Mee Kim, MDa, Tinnakorn Chaiworapongsa, MDa, Ricardo Gomez, MDa, Emmanuel Bujold, MDb, Bo Hyun Yoon, MD, PhDc, Siegfried Rotmensch, d, Howard T. Thaler, PhDe, Roberto Romero, MDa

Abstract

Objective: The purpose of this study was to determine whether failure of physiologic transformation of the spiral arteries occurs in patients with preterm premature rupture of membranes (PROM). Study Design: A cross-sectional study was designed to examine the histopathologic findings in the placental bed and placenta of patients with preterm PROM, preeclampsia, and normal women at term. Immunohistochemistry with cytokeratin 7 and periodic acid-Schiff (PAS) were used to detect trophoblast and fibrinoid and to diagnose failure of physiologic transformation of the spiral arteries. Results: One hundred thirteen cases met the inclusion criteria, 59 from patients with normal pregnancies, 31 with preterm PROM, and 23 with preeclampsia. The mean number of the spiral arteries with failure of physiologic transformation of the myometrial segment was significantly higher in patients with preterm PROM and preeclampsia than in normal pregnant women at term (P = .006 and P < .0001, respectively). In contrast, the mean number of the spiral arteries with failure of physiologic transformation of the decidual segment of the spiral arteries in the basal plate of the placenta was not significantly different in patients with preterm PROM from that in normal pregnant women (P > .05). Placentas from patients with preterm PROM had a higher frequency of vascular lesions than those from normal pregnant women (P = .02). Conclusion: Defective placentation, defined as failure of physiologic transformation of the myometrial segment of the spiral artery, is frequently present in preterm PROM. (Am J Obstet Gynecol 2002;187:1137-42.)

Human neutrophil collagenase (matrix metalloproteinase 8) in parturition, premature rupture of the membranes, and intrauterine infection

Eli Maymon, MDa, Roberto Romero, MDa, b, Percy Pacora, MDa, Ricardo Gomez, MDa, Neil Athayde, MDa, Sam Edwin, BSa, Bo H. Yoon, MD, PhDc Received 2 June 1999; received in revised form 8 November 1999; accepted 19 December 1999. Abstract

Objectives: The mechanisms by which microbial invasion of the amniotic cavity leads to membrane weakening and rupture are poorly understood. Recently, endogenous host enzymes have been implicated in this process. Matrix metalloproteinases are a family of potent enzymes that degrade components of the extracellular matrix. Collagen type I provides the main tensile strength of the fetal membranes. Matrix metalloproteinase 8 (MMP-8), or neutrophil collagenase, degrades interstitial collagens, acting preferentially on collagen type I. This study was undertaken (1) to determine whether MMP-8 is present in amniotic fluid and whether its concentrations are changed in preterm and term labor and membrane rupture with and without intra-amniotic infection and (2) to determine whether the amniotic fluid concentrations of MMP-8 in labor at term are different in the lower and upper uterine compartments. Study Design: A cross-sectional study was conducted and transabdominal amniocentesis was performed in women in the following categories: (1) midtrimester (n = 25), (2) preterm labor in the presence and absence of microbial invasion of the amniotic cavity (n = 86), (3) preterm premature rupture of the membranes in the presence and absence of microbial invasion of the amniotic cavity (n = 51), (4) term patients in labor and not in labor (n = 51), and (5) term premature rupture of membranes (n = 20). Additional paired samples of amniotic fluid were retrieved by transabdominal amniocentesis (upper compartment) and transvaginal amniocentesis (lower or forebag compartment) from 14 term patients (28 samples) in spontaneous labor with intact membranes. Amniotic fluid MMP-8 concentrations were determined with a sensitive and specific immunoassay. Results: MMP-8 was detected in 95.4% (249/261) of all samples. (1) Spontaneous human parturition was associated with a significant increase in amniotic fluid concentrations of MMP-8 in both term and preterm gestation. Term (no labor median, 3.3 ng/mL; range, <0.06-38.6 ng/mL; vs labor median, 16.6 ng/mL; range, 0.33-1650 ng/mL; P < .05). Patients with preterm labor who delivered preterm (in the absence of microbial invasion of the amniotic cavity) had a significantly higher median amniotic fluid MMP-8 concentration than those with preterm labor who delivered at term (preterm labor, term delivery median, 3.1 ng/mL; range, <0.06-415.1 ng/mL; vs preterm labor, preterm delivery median, 32.5 ng/mL; range, <0.06-6006.6 ng/mL;P < .003). (2) Spontaneous rupture of membranes in preterm gestation but not in term gestation was associated with elevated amniotic fluid concentrations of MMP-8. Preterm gestation (preterm labor, intact membranes median, 3.1 ng/mL; range, <0.06-415.1 ng/mL; vs preterm premature rupture of membranes median, 35.1 ng/mL; range, 0.71-1184.1 ng/mL; P < .05). Term gestation (intact membranes median, 3.3 ng/mL; range, 0.24-38.6 ng/mL; vs rupture of membranes median, 5.6 ng/mL; range, 0.22-19.8 ng/mL; P = .9). (3) Microbial invasion of the amniotic cavity was associated with a significant increase in amniotic fluid MMP-8 concentration in patients with preterm labor and intact membranes, as well as in patients with preterm premature rupture of membranes. Preterm labor (no microbial invasion of the amniotic cavity, preterm delivery median, 32.5 ng/mL; range, <0.06-6006.6

ng/mL; vs microbial invasion of the amniotic cavity median, 208.1 ng/mL; range, 4.2-14,600 ng/mL; P < .001). Preterm premature rupture of membranes (no microbial invasion of the amniotic cavity median, 35.1 ng/mL; range, 0.71-1184.1 ng/mL; vs microbial invasion of the amniotic cavity median, 317.9 ng/mL; range, 2.16-14,500 ng/mL; P < .01). (4) The median amniotic fluid MMP-8 concentrations were significantly higher in fluid obtained from the forebag compartment than in that obtained from the upper compartment (median, 66.2 ng/mL; range, 7.4-170 ng/mL; vs median, 13.3 ng/mL; range, 2-170 ng/mL; respectively; P < .01). Conclusions: These data suggest a role for a specific interstitial collagenase (MMP-8) in microbial invasion of the amniotic cavity, preterm membrane rupture, and term and preterm labor. The higher concentration of MMP-8 in fluid bathing the cervical region may explain the predilection for membrane rupture to occur close to the lower pole of the uterus. (Am J Obstet Gynecol 2000;183:94-9.)

Medline Abstract for Reference 50 of 'Preterm premature rupture of membranes'50 PubMed A randomized clinical trial of daily nonstress testing versus biophysical profile in the management of preterm premature rupture of membranes. Lewis DF, Adair CD, Weeks JW, Barrilleaux PS, Edwards MS, Garite TJ Am J Obstet Gynecol. 1999;181(6):1495.

OBJECTIVE: Our purpose was to evaluate the ability of 2 different antepartum testing modalities to predict infectious morbidity in patients with preterm premature rupture of membranes.STUDY DESIGN: During a 36-month period, patients with preterm premature rupture of membranes (at 23 to 34 weeks of gestation) were randomly assigned to either a daily nonstress test or a biophysical profile, after a 24hour observational period. We used the original scoring system of Manning et al for the biophysical profile, with a score of</=6 considered abnormal. Nonstress test results were considered abnormal if the test was nonreactive or if the patient had late decelerations or significant variable decelerations; abnormal results led to further evaluation with a biophysical profile. Results of the last test before delivery were evaluated to determine whether infectious complications had been predicted.RESULTS: One hundred thirty-five patients were enrolled in the study. Demographics, pregnancy characteristics, and neonatal outcomes were similar. Neither the daily nonstress test nor the daily biophysical profile had good sensitivity for predicting infectious complications (39.1% and 25.0%, respectively). However, both had good specificity (84.6% and 92.6%, respectively). Positive and negative predictive values were 52.9% and 75.9%, respectively, for the daily nonstress test and 66.7% and 68.4%, respectively, for the daily biophysical profile. Cost was significantly higher in the daily biophysical profile group. Nonstress testing of patients at<28 weeks' gestation generally required a backup biophysical profile.CONCLUSION: Neither the daily nonstress test nor the daily biophysical profile had good sensitivity for predicting infectious complications after preterm premature rupture of membranes.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Louisiana State University Medical Center, Shreveport, USA. PMID Arch Dis Child Fetal Neonatal Ed 2010;95:Fa105 doi:10.1136/adc.2010.189761.56 Poster presentations Pregnancy outcome Outcome of expectant management of extreme preterm premature rupture of membranes S Lahiri, S Houghton Author Affiliations Good Hope Hospital, Sutton Coldfield, U Abstract

Introduction Extreme preterm premature rupture of membranes is a rare condition. Although significant pregnancy prolongation occurs in many cases with expectant management, neonatal outcomes remain poor.

Material and Methods 23 patients were studied over a 3 year period. Patients were hospitalised on confirmation of extreme preterm premature ( 24 weeks) spontaneous rupture of membranes. They were counselled regarding the poor outcome of both the pregnancy and also the baby if it were to reach viable gestation. They all declined termination of pregnancy. They all had speculum examinations to confirm loss of liquor and/or scan confirmation of oligohydramnious. They were monitored with weekly full blood count, C-reactive protein and given oral antibiotic prophylaxis. Those patients who reached 24 weeks gestation were given antenatal steroids.

Results Median gestational age at rupture of membranes was 20.0 weeks (range 16.9 23 weeks); One patient reached term and her data were excluded from analysis due to extreme skewing of results. Of the remaining, median latency period to delivery was 13 days (range 7 96 days), with mean gestational age at delivery of 23.83.4 weeks. Overall survival was <10%. Placental pathology and in some cases limited postmortem indicated chorioamnionitis.

Conclusion This study shows that although significant pregnancy prolongation after previable rupture of membranes occurs in some cases pregnancy outcomes in the majority remain very poor.