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CHIEF EDITORS NOTE: This article is part of a series of continuing education activities in this Journal through which a totalof 36 AMA/PRA category 1 credit hours can be earned in 0. Instructions for how CME credits can be earned appear on the

last page of the Table of Contents.

An Evidence-Based Approach to theEvaluation and Treatment of Premature

Rupture of Membranes: Part ITimothy P. Canavan, MD, FACOG,* Hyagriv N. Simhan MD, MSCR, and

Steve Caritis, MD*Fellow, MaternalFetal Medicine, Assistant Professor, and Director of MaternalFetal Medicine, Magee

Womens Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania

Preterm premature rupture of membranes (PPROM) occurs in 3% of pregnancies and is respon-

sible for one third of all preterm births. PPROM will affect 120,000 women in the United States each

year. It is associated with significant maternal, fetal, and neonatal morbidity and mortality resulting

from infection, umbilical cord compression, abruptio placentae, and prematurity. The etiology is

multifactorial, but the most significant risk factors are previous preterm birth and previous preterm

premature rupture of membranes. Accurate diagnosis is extremely important to assure proper

treatment. Evaluation is based on patient history and clinical examination. This review presents the

available evidence and grades it according to the U.S. Preventative Task Force recommendations.

In part I of this review, the definition, pathophysiology, and methods of PPROM diagnosis are

presented. In part II, the management, treatment, neonatal outcome, and the maternal and fetalevaluation of women with PPROM in the presence of cerclage and medical complications is

reviewed.

Target Audience: Obstetricians & Gynecologists, Family Physicians

Learning Objectives: After completion of this article, the reader should be able to define the term:

preterm premature rupture of membranes, to list the factors associated with premature rupture of

membranes, and to outline the tests available for the diagnosis of intra-amniotic infection.

Premature rupture of the fetal membranes(PPROM) is defined as the rupture of the amnioticmembranes with release of the amniotic fluid more

than 1 hour before the onset of labor. There are 2general categories:

1. Term PROM (TPROM)PROM after 37weeks gestation (not discussed in this review).

2. Preterm PROM (PPROM)PROM before 37weeks gestation.

PATHOPHYSIOLOGY

The etiology of PPROM is multifactorial, and manywomen will have multiple etiologic and associated fac-

tors. Many of these factors are suspected to increase therisk for PPROM as a result of membrane stretch ordegradation, local inflammation, or increased suscepti-

bility to ascending infection (1). In the majority ofcases, the exact etiology of the PPROM is unknown.

The most significant risk factors are a previous preg-nancy complicated by PPROM or preterm labor (PTL).For more details, the reader is referred to Tables 1 and

2 and the references listed (15).A recent study by Sadler and associates (6) evalu-

ated the association of laser conization and loop

Reprint requests to: Timothy P. Canavan, MD, FACOG, Magee

Womens Hospital, Department of Obstetrics, Gynecology & Re-

productive Sciences, 300 Halket Street, Pittsburgh, PA 15213.

E-mail: [email protected]

The authors have disclosed no significant financial or other

relationship with any commercial entity.

CME REVIEWARTICLEVolume 59, Number 9

OBSTETRICAL AND GYNECOLOGICAL SURVEY

Copyright 2004

by Lippincott Williams & Wilkins 26

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electrosurgical excision procedure (LEEP) withPPROM. They found an adjusted relative risk (aRR)of 2.7 (95% confidence interval [CI], 1.35.6) forlaser conization and an aRR of 1.9 (95% CI, 1.03.8)for LEEP. The risk of PPROM increased with theincreased depth of the conization. They found thatwomen in the highest tertile of resection depth(greater than 1.6 cm) had a greater than 3-fold in-creased risk of PPROM compared with untreated

women (aRR 3.6; 95% CI, 1.87.5). Laser abla-tion of the cervix was not associated with PPROM(aRR 1.1; 95% CI, 0.52.4).

PREDICTION OF PREMATURE RUPTUREOF THE FETAL MEMBRANES

Women with a history of PPROM have a 13.5%risk of recurrent preterm birth from PPROM com-pared with 4.1% (relative risk 3.3) for womenwithout that risk (2). The risk of recurrent PPROM isaffected by the gestational age of PPROM in theprevious pregnancy. The risk of recurrent PPROM is13.5 times greater when the previous episode ofPPROM occurred before 28 weeks rather than after28 weeks (1.8% vs. 0.13%) (2). The National Insti-

tute of Child Health & Human Development spon-sored MaternalFetal Medicine Units Network(MFMU) prospectively evaluated factors in a currentpregnancy that might predict PPROM (see Table 3)(7). Women have an increased risk of PPROM in thepresence of a short cervical length, medical compli-cations, working during pregnancy, and in the case ofmultiparous women, a prior episode of PPROM thatcaused a preterm birth. Fetal fibronectin (fFN) aloneis a risk factor for multiparous women. Women with2 or 3 risk factors had a dramatic increased risk forPTB from PPROM compared with women withoutthese factors as presented in Table 4. A combinationof a short cervix and an elevated fFN had a dramaticeffect on a nulliparous womens risk for PPROM,whereas the addition of a prior PTB from PPROMincreased a multiparous womens risk by an oddsratio of 25. In this same study, previously implicatedrisk factors such as black race, vaginal bleeding, and

TABLE 114

Possible Mechanisms for PPROM

Choriodecidual infection

Collagen degradation

Decreased membrane collagen content

Localized membrane defectsMembrane stretch (uterine overdistension)

Programmed amniotic cell death

TABLE 2

Conditions Associated with PPROM

Amniocentesis1

Cervical cerclage1

Cervical insufficiency7

Chronic abruptio placentae5

Cigarette smoking1,4

Laser conization6

Loop electrosurgical excision procedure6

Low socioeconomic status1,4

Prior cervical conization1,4

Prior preterm delivery1,2,4

Prior preterm labor1,2,4

Prior PPROM1,2,4

Sexually transmitted infection1,3,4

Uterine / amnion distension1,3,4

Vaginal bleeding in pregnancy1,4

Working during pregnancy1,7

TABLE 3 Predictors of preterm birth from preterm premature rupture of membranes 7

Prediction Factor Odds Ratio (95% confidence interval)

Nullipara 37 weeks 35 weeks

Bacterial vaginosis 2.1 (1.1 4.1) NS

Cervical length

25 mm 3.7 (1.8 7.7) 9.9 (3.8 25.9)Low body mass index (19.8 kg/m2) 2.0 (1.0 4.0) NS

Medical complications 3.7 (1.59.0) 4.2 (1.116.0)

Positive fetal fibronectin ( 50 ng/ml) NS NS

Symptomatic contractions 2.2 (1.27.5) NS

Working during pregnancy 3.0 (1.5 6.1) 5.3 (1.518.7)

Multipara

Cervical length 25 mm 2.5 (1.4 4.5) 4.2 (2.0 8.9)

Low body mass index (19.8 kg/m2) 1.8 (1.13.0) NS

Positive fetal fibronectin 2.1 (1.1 4.0) 9.0 (3.6 22.5)

Prior preterm birth from PTL 1.8 (1.13.1) 2.6 (1.25.3)

Prior PPROM causing PTB 3.1 (1.8 5.4) 4.1 (2.0 8.7)

NS not significant; PTL preterm labor. Medical complications included diabetes, hypertension, cardiac disease, and endocrine

disorders requiring medication and hemoglobinopathy.

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cigarette smoking were not statistically associatedwith PTB from PPROM (7).

Nutritional status was not evaluated as a risk factorfor PPROM by the MFMU study, but Ferguson andassociates evaluated both the effects of nutrition andsocioeconomic factors on the risk of PPROM (8).These investigators found no nutritional links toPPROM; however, there was a statistically signifi-cant association between PPROM and a maternalhemoglobin less than 11.1 gm/dL (odds ratio [OR],4.33; 95% CI, 1.3814.17) or a low socioeconomicstatus with a total family income less than $25,000Canadian (OR, 3.1; 95% CI, 1.66.0) (8).

Early studies evaluating bacterial vaginosis (BV)and PPROM showed some association, but thesestudies were underpowered and of weak study de-

sign. More recent investigations with better studydesigns have disputed these earlier findings. Gravettand associates (9) evaluated genital pathogens in 534consecutive women in the second and third trimesterof pregnancy and found that BV was associated withPPROM by an OR of 2.4 (95% CI, 1.44.3). Themean gestational age at enrollment was 32.6 weeksand the gestational age at delivery in all patients withBV was 37.8 4.1 weeks. Kurki and associates (10)evaluated BV in early pregnancy and found BVpredicted PPROM with a sensitivity (SEN) of 41% to67%, specificity (SPE) of 79%, negative predictive

value (NPV) of 96% to 99% and a positive predictivevalue (PPV) of 4% to 11%. However, this studyincluded only 9 patients with PPROM. McGregor

and associates (11) performed a double-blind, place-bo-controlled treatment trial of BV in 229 womenand found no association of BV to PPROM. Mercerand the MaternalFetal Medicine Network found thatBV is not an independent risk factor for PPROM atless than 35 weeks (7). The strength of the evidencewould support that BV is not associated withPPROM. Evaluation for asymptomatic BV as ameans to provide treatment and prevent PPROM hasnot been shown to be effective. Evaluation and treat-ment of symptomatic BV can be done to alleviate apatients symptoms like in nonpregnant patients.

DIAGNOSISMETHODS

Physical ExaminationDiagnosis of PPROM is made by a combination of

clinical suspicion, patient history, and some simpletesting. Patient history has an accuracy of 90% forthe diagnosis of PPROM and should not be ignored(12). Numerous tests have been recommended for theevaluation of PPROM, but 2 tests have withstood thetest of time: Nitrazine (Bristol-Myers Squibb, Prince-ton, NJ) paper testing and ferning (also referred to asamniotic fluid crystallization testing) of vaginal poolfluid. Freidman and McElin found that if a combi-nation of patient history, Nitrazine testing, and fern-

ing was used to evaluate a patient for PPROM, theaccuracy was 93.1% when 2 or more tests werepositive (see Table 5) (12).

TABLE 4 Risk of PTB from PPROM among women with multiple risk factors 7

Risk Factor 37 weeks (%) 35 weeks (%)

Nulliparous

All nulliparous women 3.7 1.6

No risk factors present 3.0 0.9

Positive fFN & short cervix (25 mm) 16.7 11.1Multiparous

All multiparous women 5.0 2.3

No risk factors present 3.2 0.8

Previous PTB from PPROM &fFN 15.4 15.4

Previous PTB from PPROM & short cx 23.1 15.4

All 3 risk factors 25.0 25.0

fFN fetal fibronectin; cx cervix; PTB preterm birth; PPROM preterm premature rupture of membranes.

TABLE 5 Methods of diagnosis for PPROM (%)1214

Method Sensitivity Specificity PPV NPV Accuracy

Ferning Friedman12 88 94 94 87 91

Tricomi13 96 96 98 90 96

Kovacs14 96 97 99 91 96

Nitrazine12 89 84 83 90 87

Patient history12 90 89 88 90 89

PPV positive predictive value; NPV negative predictive value.

Evaluation and Treatment of Premature Rupture of Membranes Y CME Review Article 671


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The ferning test should be performed on midvagi-nal or posterior fornix fluid. Contamination withcervical mucous can cause a false-positive result.The slide should be allowed to air dry for a minimumof 10 minutes. The false-negative rate increases withless drying time or with flame-drying (1315). Fern-ing is unaffected by meconium at any concentrationor by changes in pH. Small amounts of blood do notaffect ferning; however, blood and amniotic fluidmixed in equal amounts results in no ferning (15).Amniotic fluid specimens are fern- and Nitrazine-positive up to 2 weeks after amniocentesis (15). TheNitrazine test could be more susceptible to alterationby contamination. The presence of bacterial vagino-sis, cervicitis, semen, alkaline urine, blood, soap, andantiseptic solutions could cause a false-positive Ni-trazine test (1215).

During diagnosis and evaluation of PPROM, digi-tal cervical examination should be avoided. Lewisand associates compared digital cervical examinationwith sterile speculum examination and found thatlatency was shortened significantly by cervical ex-amination at any gestational age (2.1 4.0 vs.11.3 13.4 days, P 0.0001) (16). Alexander andassociates evaluated data from the NICHD MFMUrandomized, controlled trial on antibiotics afterPPROM and found that 1 or 2 cervical examinationsin patients with PPROM between 24 and 32 weekswas associated with a shorter latency (3 vs. 5 days, P

0.009) but did not worsen either maternal or neo-natal outcome (17).

Biochemical Testing

Several chemical markers of PPROM have beensuggested, but there are few data that thoroughlyevaluate their usefulness. These tests can add signif-icant cost and should be used only when the diagno-sis of PPROM is highly suspicious but unable to beverified by the simple bedside testing discussed here.Fetal fibronectin (fFN), alpha-fetoprotein (AFP), and

diamino-oxydase (DAO) have been used to confirmPPROM when other methods have been equivocal.

Fetal Fibronectin, Alpha-fetoprotein andDiamino-oxydase

Although there is little literature to collaborate thissuggestion, fFN has the potential to be a diagnostictest with high NPV for determining PPROM. Theamniotic fluid contains high levels of fFN (approxi-mately 50,000 ng/mL). The presently available fFNassay is considered positive when concentrations ex-

ceed 50 ng/mL. In a patient with a history suspiciousfor PPROM, a negative fFN test would be inconsis-tent with PPROM and could be used to eliminate thatdiagnosis. A positive result would not be helpful inthe evaluation. Eriksen and associates (18) comparedfFN against pooling, ferning, and Nitrazine testing todetermine rupture of membranes (ROM) in termpatients and found fFN has a SEN of 98.2% with aSPE of 26.8%, PPV of 87.5% and a NPV of 75%.Gaucherand and associates (19) compared 131women between 23 and 40 weeks gestation with andwithout gross evidence of ROM and found that fFNwas the best marker for ROM with a SEN of 94%,SPE of 97%, PPV of 97%, and a NPV of 94%. AFPhas a SEN of 88%, a SPE of 84%, PPV of 86%, anda NPV of 87%, whereas DAO has a SEN of 83%, aSPE of 95%, a PPV of 95%, and a NPV of 84.5%.

Ultrasound Testing

Ultrasound can be used to evaluate patients forPPROM. There are few data evaluating ultrasound asa modality to diagnose PPROM. Theoretically, ab-sent or markedly reduced amniotic fluid index (AFI)in a patient with a suspicious history for PPROMcould be used as evidence of ROM. The results ofultrasound testing should be used in conjunction withother testing.

During amniocentesis, dye (indigo carmine) can be

infused into the amniotic fluid. Using a vaginal tam-pon, ROM can be confirmed in those cases with ahigh suspicion of PPROM but equivocal testing. Thepresence of dye on the tampon would confirm con-clusively that rupture of membranes has occurred.

Initial Assessment of Fetal Status With Prema-ture Rupture of the Fetal Membranes

Kundavi and associates (20) compared the distri-bution of amniotic fluid, by ultrasound, between theupper and lower quadrants in patients with premature

ROM at term. They found that if the sum of thevolumes of the 2 upper quadrants was greater thanthe sum of the 2 lower quadrants, there was a statis-tically significant increased risk of meconium stain-ing (P 0.003), abnormal fetal heart rate patterns(P 0.005), operative delivery (cesarean section[P 0.0008] or forceps delivery [P 0.002]) andneonatal intensive-care unit admission (P 0.003).Vermillion and associates (21) evaluated 225 single-ton pregnancies with PPROM between 24 and 32weeks by ultrasound and found that an AFI less than5 cm was associated with an increased risk of cho-



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rioamnionitis (OR, 5.5; P 0.001), endometritis(OR, 6.4; P 0.01), early-onset neonatal sepsis (OR,8.5; P0.034), and a shorter latency to delivery (5.5vs. 14.1 days, P 0.02). These findings could behelpful in counseling patients with PPROM and pre-dicting complications.

Amniocentesis

Infection

Subclinical intrauterine infection has been impli-cated as a major etiologic factor in the pathogenesisand subsequent maternal and neonatal morbidity inPPROM (2226). The rate of positive culture ob-tained by transabdominal amniocentesis at the timeof presentation with PPROM in the absence of labor

is 25% to 40% (22,2733). Amniotic fluid infectionis intimately linked with in utero fetal inflammation(34). Serious newborn and infant adverse outcomes(such as cerebral palsy and chronic lung disease) areclosely tied with this fetal inflammatory process (3538). Reliance on clinical criteria to diagnose amnioticfluid infection, although common practice, might notbe particularly useful. Clinical chorioamnionitis ispresent on admission in only 1% to 2% of womenwho present with PPROM and subsequently devel-ops clinically in 3% to 8% of women (30,39). Themajority of amniotic fluid infection in the setting of

PPROM does not produce the signs and symptomstraditionally used as diagnostic criteria for clinicalchorioamnionitis.

The diagnostic and therapeutic goals of manage-ment of the patient with PPROM focus on a reduc-tion of neonatal morbidity. To that end, presentlyaccepted strategy includes the use of hospitalizedbedrest/expectant management, broad-spectrum anti-biotics, antenatal corticosteroids, and serial maternal/fetal surveillance. These therapies are designed toprolong pregnancy and reduce neonatal morbidity.

The current understanding of the contribution of

infection and inflammation to preterm birth and itsmorbidity supports the notion that intrauterine infec-

tion (clinical or subclinical) is an indication for de-livery (and, by extension, a contraindication to ex-pectant management or pregnancy prolongation).Documentation of amniotic fluid infection in thepatient who presents with PPROM thus enables us totriage our therapeutic decision-making rationally.

It is conceptually important to define subclinicalamniotic fluid infection as a positive amniotic fluidculture. A culture result could take as long as 48hours to return as definitively positive or negative. Inan effort to provide more rapid information regardingamniotic fluid infection status, several short-termtests have been evaluated. The tests that are currentlyavailable for clinical use are Gram stain, white bloodcell count, leukocyte esterase, and glucose concen-tration. Romero and colleagues initially evaluatedleukocyte esterase assay (LEA) and Gram stain

(prevalence of positive cultures was 33.9%). Whenboth tests were combined, a significant increase insensitivity to 50% was observed. This was associatedwith a drop in specificity to 81.4% (40). In a subse-quent study, Romero and coworkers evaluated amni-otic fluid glucose, white blood cell count, interleu-kin-6, and Gram stain. The combination of theclinically available tests, glucose less than 10 mg/dL,WBC 30 cells/mm3, and Gram stain (whereby ifany 1 of the 3 tests is positive, the combination testis considered positive), provides a sensitivity of76.2%, specificity of 60.3%, PPV of 61.0%, and

NPV of 80.4% (33). Table 6 compares these tests.Interleukin (IL)-6 appears to be the best biomarkerfor intraamniotic infection (IAI) but is unavailable inmost hospitals. The evidence suggests that in addi-tion to amniotic fluid culture, the best, practical rapidtests to obtain on amniotic fluid are glucose, WBC,and Gram stain.

Lung Maturity

There is controversy regarding the optimal gesta-

tional age at which expectant management is discon-tinued and delivery is performed. The optimal inter-

TABLE 6 Predicting a positive amniotic fluid culture22,24,27,28,31,33

TEST Sensitivity (%) Specificity (%) PPV (%) NPV (%)

Gram stain 24 99 91 68

AF-WBC (30/mm3) 57 78 - -

LEA 19 87 42 68

Glu (10md/dl) 57 74 57 74

IL-6 81 75 67 86

Glu, AF-WBC & Gram Stain 76 60 61 80

AF-WBC amniotic fluid white blood cell count; Glu glucose; IL-6 interleukin-6; LEA leukocyte esterase.



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val for delivery occurs when the risks of prematurityare outweighed by the risks of pregnancy prolonga-tion in the setting of PPROM (infection, abruption,cord accident). As addressed in this article (and partII of this series), lung maturity assessment could beuseful to guide delivery planning in the 32- to 34-week interval. An amniocentesis performed at 32weeks is helpful with respect to diagnosis of infec-tion (as noted previously) and confirmation of fetal

lung maturity. Both a retrospective cohort study anda randomized trial support the use of amniocentesisamong women with PPROM to aid in delivery plan-ning (30,32). Cotton et al. (30) performed a random-ized, controlled trial (RCT) comparing the use ofamniocentesis for lung maturity testing (lecithin tosphingomyelin ratio and phosphatidylglycerol) andamniotic fluid culture with observation to determinedelivery timing in patients with PPROM between 26and 34 weeks gestation. The amniocentesis was re-peated weekly until pulmonary maturity was reachedor bacteria were identified in the amniotic fluid. They

found that fetal distress, as judged by the fetal mon-itor tracing, was more frequent in the no amniocen-tesis group (P 0.05), and the number of days theinfant remained in the hospital was significantly lessin the amniocentesis group (median, 8.5 days; range,288 days) than in the no amniocentesis group (me-dian, 22 days; range, 2110 days; P 0.01). Thisdifference in neonatal hospital days appears to be theresult of a slower resolution of the multiple problemsof prematurity. This would suggest that when amnio-centesis is used aggressively to determine delivery,neonatal length of stay and morbidity are decreased.

The predictive values of the various lung maturitytests are not changed by the presence of PPROM.The clinical test to be used to determine lung matu-rity is dependent on provider preference and avail-ability and experience of the providers institution.

Likelihood of Success of Amniocentesis and Riskof Complications

There are 9 English-language trials in the literaturethat report the likelihood of success for transabdom-inal amniocentesis in the setting of PPROM. The

success rates range from 49% to 98% with an aver-age of 72% (686 of 950) (29). These studies werepublished between 1979 and 1996. There is a cleartrend toward increased success of amniocentesis withdate of publication of study. Intuitively, as ultrasoundtechnology has developed and training in invasiveprocedures has improved, the likelihood of success islikely to improve. Seven of these 9 studies werepublished before 1990. Thus, one would anticipatethat the likelihood of success today might be some-what better than 72%.

There is only 1 English-language trial in the liter-ature that specifically addresses the frequency ofcomplications of amniocenteses performed in the set-ting of PPROM (41). Yeast et al. found no cases (0 of91) of fetal injury after amniocentesis. They alsonoted that these 91 women did not have a shorter

latency interval than a matched group of women whodid not have amniocentesis.

Noninvasive Testing to Predict IntraamnioticInfection

In the hopes of predicting intraamniotic infection(IAI) noninvasively, nonstress testing, biophysicalprofile (BPP), and umbilical artery Doppler werestudied in patients with PPROM. Vintzileos and as-sociates (42) performed an observational cohortstudy in 73 singleton pregnancies with PPROM at 25

weeks or later and found a BPP score of less than orequal to 7 (performed within 24 hours of delivery)was associated with an infection rate of 93.7% (in-fection was defined as clinical amnionitis, possibleneonatal sepsis, or neonatal sepsis). In a secondstudy, Vintzileos and associates (43) evaluated 3groups of 73 singleton pregnancies greater than 25weeks gestation with PPROM. They compared BPPtesting, observation, and amniocentesis and foundthat a BPP score of 7 or less when used to mandatedelivery, decreased the overall infectious outcome(10.9% vs. 30.1%, P 0.005), amnionitis (5.4 vs.

20.5%, P 0.01), and 5-minute Apgar scores lessthan 7 (0% vs. 12.3%, P 0.005).

Vintzileos and associates (44) performed a retro-spective review of nonstress testing (NST) in 127patients with PPROM at greater than 25 weeks andfound the sensitivity and specificity of the NST(when done within 24 to 48 hours of delivery) topredict infectious outcome (clinical amnionitis, pos-sible neonatal sepsis, or confirmed neonatal sepsis)was 78.1% and 86.3%, respectively, with a NPV of65.7% and a PPV of 92.1%. Several recent studieshave been unable to reproduce these findings. Carroll

TABLE 7 Predicting neonatal morbidity22,33

TEST Odds Ratio

AF-WBC (30 cells/mm3) 4.3 (P .05)

IL-6 (790 pg/ml) 3.32 ( P .05)

AF-WBC

amniotic fluid white blood cell count; IL-6

inter-leukin-6.



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and associates (45) performed a BPP (by the criteriadescribed by Vintzileos (43) in the studies citedpreviously) in 89 women with PPROM ranging from20 to 36 weeks gestation and compared these find-ings with cordocentesis and amniotic fluid cultureresults. They found no association of BPP score withfetal or amniotic infection. In a randomized trial byLewis and associates (46), 135 patients with PPROMbetween 23 and 34 weeks gestation were randomizedto either daily BPP or NST and this was comparedwith amniotic fluid culture or Gram stain, evidenceof clinical amnionitis, or culture evidence of neonatalsepsis. They found that neither the NST (sensitiv-ity 39.1%) nor the BPP (sensitivity 25%) hadsignificant sensitivity to predict IAI. This is consis-tent with the findings of Ghidini and associates (47)who studied 166 singleton pregnancies with PPROM

delivered before 32 weeks gestation and comparedthem with histopathologic placental examination.They found no association between an abnormal BPPscore and severe acute placental inflammation.

These findings differ from a small study by Yuceland associates (48) who compared umbilical arteryDoppler and BPP with histopathology of placentalinflammation in 24 patients with PPROM between25.6 and 36.4 weeks gestation. They found an asso-ciation between abnormal BPP scores and increasedarterial systolic/diastolic (S/D) ratios with histologicevidence of placental inflammation. However, Leo

and associates (49) did not find an association be-tween umbilical artery Doppler S/D ratios and IAI intheir study of 51 patients with PPROM.

There is a discrepancy between the earlier studiesand the more recent studies in regard to whether BPPor NST can predict IAI. Possible neonatal sepsis is avery nonspecific outcome variable and could haveconfounded the results. Most newborns tend to beobserved for possible neonatal sepsis after deliverywhen the pregnancy had been complicated byPPROM. Amniotic fluid culture and histopathologyrepresent more specific end points to assess IAI.

Umbilical artery Doppler S/D ratios are less clear.

SUMMARY

Preterm premature rupture of membranes affectsover 120,000 pregnancies in the United States annu-ally and is associated with significant maternal mor-bidity and neonatal morbidity and mortality. Health-care costs are significantly influenced by theprolonged maternal hospital stay, need for frequenttesting, and the resulting neonatal costs as a result ofprolonged neonatal intensive-care unit care for the

newborn. Management requires an accurate diagno-sis and determination of gestational age. A gesta-tional age approach to therapy is important andshould be adjusted for each hospitals neonatal in-tensive-care unit outcomes. These patients are at highrisk for infection and amniocentesis can be used toevaluate early markers for infection and provide asample of amniotic fluid for culture. Any evidence ofinfection by amniocentesis should be consideredcarefully as an indication for delivery.

We reviewed and evaluated published reports forquality according to the method outlined by the U.S.Preventative Services Task Force:

I. Evidence obtained from at least 1 properly de-signed randomized, controlled trial.

II-1. Evidence obtained from well-designed con-trolled trials without randomization.

II-2. Evidence obtained from well-designed co-hort or case-control analytic studies, prefer-ably from more than 1 center or researchgroup.

II-3. Evidence obtained from multiple time-serieswith or without the intervention. Dramaticresults in uncontrolled experiments alsocould be regarded as this type of evidence.

III. Opinions of respected authorities based onclinical experience, descriptive studies, orreports of expert committees.

Based on the highest level of evidence found in thedata, our recommendations are provided and gradedaccording to the following categories:

Level ARecommendations are based on goodand consistent scientific evidence.

Level BRecommendations are based on limitedor inconsistent scientific evidence.

Level CRecommendations are based primarilyon consensus and expert opinion.

SUMMARY TABLE OFRECOMMENDATIONS

Category A (recommendations are based ongood and consistent scientific evidence):

1. Digital cervical examination should not be per-formed on any patient with PPROM who is notfor immediate delivery.

2. Amniocentesis for lung maturity testing andamniotic fluid culture to determine deliverytiming decreases neonatal length of stay andmorbidity.

3. Amniotic fluid culture is the best predictor ofIAI.



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Category B (recommendations are based on lim-ited or inconsistent scientific evidence):

1. A combination of patient history, Nitrazinetesting, and ferning should be used to evaluate

a patient for PROM. A positive finding in any2 has an accuracy of 93%.2. Evaluation and treatment of BV is not effective

at preventing PPROM.3. Fetal fibronectin can be used to diagnose

PPROM in patients with a suspicious historyfor PPROM but with equivocal pooling, fern-ing, and Nitrazine testing.

4. Amniocentesis is recommended for patientswith PPROM to obtain amniotic fluid for cul-ture and to evaluate the early markers of infec-tion.

5. Amniotic fluid Gram stain, glucose, and leuko-cyte esterase can be used as rapid tests to pre-dict IAI.

6. Amniocentesis should be repeated if the patientdevelops a recurrent episode of preterm labor atless than 28 weeks.

7. Amniocentesis in the setting of PPROM is notassociated with fetal injury or a shorter latency.

8. The present evidence does not support using aBPP score less than 7 to predict IAI.

9. Present evidence does not support the use ofumbilical artery Doppler systolic/diastolic ratioto determine IAI.

Category C (recommendations are based pri-marily on consensus and expert opinion):

1. Cigarette smoking and vaginal bleeding are as-sociated with an increased risk of PPROM.

REFERENCES

1. Mercer BM. Preterm premature rupture of membranes. ObstetGynecol 2003;101:178193. (Level III)

2. Mercer BM, Goldenberg RL, Moawad RL, et al. The preterm

prediction study: effect of gestational age and cause of pre-term birth on subsequent obstetrical outcome. Am J ObstetGynecol 1999;181:12161221. (Level II-2)

3. Parry S, Strauss JF. Premature rupture of membranes. N EnglJ Med 1998;38:663670. (Level III)

4. Premature rupture of membranes. ACOG Practice Bulletin no.1. Washington, DC: American College Obstetricians and Gy-necologists; 1998. (Level III)

5. Elliott JP, Gilpin B, Strong TH Jr, et al. Chronic abruption-oligohydramnios sequence. J Reprod Med 1998;43:418422.(Level II-2)

6. Sadler L, Saftlas A, Wang W, et al. Treatment for cervicalintraepithelial neoplasia and risk of preterm delivery. JAMA2004;291:21002106. (Level II-2)

7. Mercer BM, Goldenberg RL, Meis PJ, et al. The pretermprediction study: prediction of preterm premature rupture of

membranes through clinical findings and ancillary testing.Am J Obstet Gynecol 2000;183:738745. (Level II-1)

8. Ferguson SE, Smith GN, Salenieks ME, et al. Preterm prema-ture rupture of membranes: nutritional and socioeconomicfactors. Obstet Gynecol 2002;100:12501256. (Level II-2)

9. Gravett MG, Nelson HP, DeRouen T, et al. Independent as-

sociations of bacterial vaginosis and Chlamydia trachomatisinfection with adverse pregnancy outcome. JAMA 1986;256:18991903. (Level II-2)

10. Kurki T, Sivonen A, Renkonen OV, et al. Bacterial vaginosis inearly pregnancy and pregnancy outcome. Obstet Gynecol1992;80:173177. (Level II-3)

11. McGregor JA, French JI, Richter R, et al. Cervicovaginal mi-croflora and pregnancy outcome: results of a double-blind,placebo-controlled trial of erythromycin treatment. Am J Ob-stet Gynecol 1990;163:15801591. (Level I)

12. Freidman ML, McElin TW. Diagnosis of ruptured membranes.Am J Obstet Gynecol 1969;104:544550. (Level II-3)

13. Tricomi V, Hall JE, Bittar A, et al. Arborization test for thedetection of ruptured fetal membranes. Obstet Gynecol 1966;27:275279. (Level II-3)

14. Kovacs D. Cystallization test for the diagnosis of ruptured

membranes. Am J Obstet Gynecol 1962;83:12571260. (LevelII-3)

15. Bennett JL, Cullen JB, Sherer DM, et al. The ferning andNitrazine tests of amniotic fluid between 12 & 41 weeks ges-tation. Am J Perinatol 1993;10:101104. (Level II-3)

16. Lewis DF, Major CA, Towers CV, et al Effects of digital vaginalexaminations on latency period in preterm premature ruptureof membranes. Obstet Gynecol 1992;80:630634. (Level II-1)

17. Alexander JM, Mercer BM, Miodovnik M, et al. The impact ofdigital cervical examination on expectantly managed pretermrupture of membranes. Am J Obstet Gynecol 2000;183:10031007. (Level II-2)

18. Eriksen NL, Parisi VM, Daoust S, et al. Fetal fibronectin: amethod for detecting the presence of amniotic fluid. ObstetGynecol 1992;80:451454. (Level II-1)

19. Gaucherand P, Guibaud S, Awada A, et al. Comparative study

of three amniotic fluid markers in premature rupture of mem-branes: fetal fibronectin, alpha-fetoprotein, diamino-oxydase.

Acta Obstet Gynecol Scand 1995;74:118121. (Level II-2)20. Kundavi KM, Kekre AN, Seshadri L. Amniotic fluid distribution

for the predicting perinatal outcome in prelabor rupture ofmembranes at term. Int J Gynecol Onstet 2003;81:4950.(Level II-2)

21. Vermillion ST, Kooba AM, Soper DE. Amniotic fluid indexvalues after preterm premature rupture of the membranes andsubsequent perinatal infection. Am J Obstet Gynecol 2000;183:271276. (Level II-2)

22. Romero R, Quintero R, Oyarzun E, et al. Intraamniotic infec-tion and the onset of labor in preterm premature rupture of themembranes. Am J Obstet Gynecol 1988;159:661666. (LevelII-2)

23. Mercer BM, Miodovnik M, Thurnau GR, et al. Antibiotic ther-

apy for reduction of infant morbidity after preterm prematurerupture of the membranes. A randomized controlled trial. Na-tional Institute of Child Health and Human Development Ma-ternalFetal Medicine Units Network. JAMA 1997;278:989995. (Level I)

24. Romero R, Mazor M. Infection and preterm labor. Clin ObstetGynecol 1988;31:553584. (Level III)

25. McGregor JA, French JI, Lawellin D, et al. Preterm birth andinfection: pathogenic possibilities. Am J Reprod Immunol Mi-crobiol 1988;16:123132. (Level III)

26. Goldenberg RL, Hauth JC, Andrews WW. Mechanisms ofdisease: intrauterine infection and preterm delivery. N EnglJ Med 2000;342:15001507. (Level III)

27. Asrat T, Nageotte MP, Garite TJ, et al. Gram stain results fromamniocentesis in patients with preterm premature rupture of



9/9

membranescomparison of maternal and fetal characteris-tics. Am J Obstet Gynecol 1990;163:887889. (Level II-2)

28. Bashiri A, Horowitz S, Huleihel M, et al. Elevated concentra-tions of interleukin-6 in intra-amniotic infection with Urea-

plasma urealyticum in asymptomatic women during geneticamniocentesis. Acta Obstet Gynecol Scand 1999;78:379

382. (Level II-2)29. Blackwell SC, Berry SM. Role of amniocentesis for the diag-nosis of subclinical intra-amniotic infection in preterm prema-ture rupture of the membranes. Curr Opin Obstet Gynecol1999;11:541547. (Level III)

30. Cotton DB, Gonik B, Bottoms SF. Conservative versus ag-gressive management of preterm rupture of membranes. Arandomized trial of amniocentesis. Am J Perinatol 1984;1:322324. (Level I)

31. Cotton DB, Hill LM, Strassner HT, et al. Use of amniocentesisin preterm gestation with ruptured membranes. Obstet Gy-necol 1984;63:3843. (Level II-3)

32. Dudley J, Malcolm G, Ellwood D. Amniocentesis in the man-agement of preterm premature rupture of the membranes.

Aust N Z J Obstet Gynaecol 1991;31:331336. (Level II-2)33. Romero R, Yoon BH, Mazor M, et al. A comparative study of

the diagnostic performance of amniotic fluid glucose, whiteblood cell count, interleukin-6, and Gram stain in the detectionof microbial invasion in patients with preterm premature rup-ture of membranes. Am J Obstet Gynecol 1993;169:839851.(Level II-1)

34. Gomez R, Romero R, Ghezzi F, et al. The fetal inflammatoryresponse syndrome. Am J Obstet Gynecol 1998;179:194202. (Level II-1)

35. Yoon BH, Romero R, Kim KS, et al. A systemic fetal inflam-matory response and the development of bronchopulmonarydysplasia. Am J Obstet Gynecol 1999;181:773779. (LevelII-1)

36. Yoon BH, Kim CJ, Romero R, et al. Experimentally inducedintrauterine infection causes fetal brain white matter lesions inrabbits. Am J Obstet Gynecol 1997;177:797802. (Level II-1)

37. Maymon E, Romero R, Pacora P, et al. Human neutrophilcollagenase (matrix metalloproteinase 8) in parturition, prema-

ture rupture of the membranes, and intrauterine infection.Am J Obstet Gynecol 2000;183:9499. (Level II-1)

38. Dammann O, Leviton A. Maternal intrauterine infection, cyto-kines, and brain damage in the preterm newborn. Pediatr Res1997;42:18. (Level II-2)

39. Yoon BH, Jun JK, Park KH, et al. Serum C-reactive protein,white blood cell count, and amniotic fluid white blood cellcount in women with preterm premature rupture of mem-branes. Obstet Gynecol 1996;88:10341040. (Level II-2)

40. Romero R, Emamian M, Wan M, et al. The value of theleukocyte esterase test in diagnosing intra-amniotic infection.

Am J Perinatol 1988;5:6469. (Level II-2)41. Yeast JD, Garite TJ, Dorchester W. The risks of amniocentesis

in the management of premature rupture of the membranes.Am J Obstet Gynecol 1984;149:505508. (Level II-2)

42. Vintzileos AM, Campbell WA, Nochimson DJ, et al. The fetalbiophysical profile in patients with premature rupture of themembranesan early predictor of fetal infection. Am J ObstetGynecol 1985;152:510516. (Level II-3)

43. Vintzileos AM, Bors-Koefoed R, Pelegano JF, et al. The use offetal biophysical profile improves pregnancy outcome in pre-mature rupture of the membranes. Am J Obstet Gynecol1987;157:236240. (Level II-2)

44. Vintzileos AM, Campbell WA, Nochimson DJ, et al. The use ofthe nonstress test in patients with premature rupture of themembranes. Am J Obstet Gynecol 1986;155:149153. (LevelII-3)

45. Carroll SG, Papaioannou S, Nicolaides KH. Assessment offetal activity and amniotic fluid volume in the prediction ofintrauterine infection in preterm prelabor amniorrhexis. Am JObstet Gynecol 1995;172:14271435. (Level II-2)

46. Lewis DF, Adair CD, Weeks JW, et al. A randomized clinicaltrial of daily nonstress testing versus biophysical profile in themanagement of preterm premature rupture of membranes.

Am J Obstet Gynecol 1999;181:14951499. (Level I)47. Ghidini A, Salafia CM, Kirn V, et al. Biophysical profile in

predicting acute ascending infection in preterm rupture ofmembranes before 32 weeks. Obstet Gynecol 2000;96:201206. (Level II-3)

48. Yucel N, Yucel O, Yekeler H. The relationship between umbil-ical artery Doppler findings, fetal biophysical score and pla-cental inflammation in cases of premature rupture of mem-branes. Acta Obstet Gynecol Scand 1997;76:532535. (Level

II-3)49. Leo MV, Skurnick JH, Ganesh VV, et al. Clinical chorioamnio-

nitis is not predicted by umbilical artery Doppler velocimetry inpatients with premature rupture of membranes. Obstet Gy-necol 1992;79:916918. (Level II-3)


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