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et

Research www.AJOG.org

OBSTETRICS

Transabdominal amnioinfusion for preterm premature ruptureof membranes: a systematic review and metaanalysisof randomized and observational studiesShay Porat, MD; Hagai Amsalem, MD, MSc; Prakesh S. Shah, MD, MSc; Kellie E. Murphy, MD, MSc

(Tsgdr

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OBJECTIVE: The purpose of this study was to review systematically thefficacy of transabdominal amnioinfusion (TA) in early preterm prema-ure rupture of membranes (PPROM).

STUDY DESIGN: We conducted a literature search of EMBASE,MEDLINE, and ClinicalTrials.gov databases and identified studies inwhich TA was used in cases of proven PPROM and oligohydramnios.Risk of bias was assessed for observational studies and randomizedcontrolled trials. Primary outcomes were latency period and perina-tal mortality rates.

RESULTS: Four observational studies (n � 147) and 3 randomized
controlled trials (n � 165) were eligible. Pooled latency period was 14.4 p
metaanalysis of randomized and observational studies. Am J Obstet Gynecol 2012;2

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most centers.Contents

range, 8.2–20.6) and 11.41 (range �3.4 to 26.2) days longer in theA group in the observational and the randomized controlled trials, re-pectively. Perinatal mortality rates were reduced among the treatmentroups in both the observational studies (odds ratio, 0.12; 95% confi-ence interval, 0.02–0.61) and the randomized controlled trials (oddsatio, 0.33; 95% confidence interval, 0.10–1.12).

CONCLUSION: Serial TA for early PPROM may improve early PPROM-ssociated morbidity and mortality rates. Additional adequately pow-red randomized control trials are needed.

ey words: amnioinfusion, latency period, oligohydramnios, PPROM,
ulmonary hypoplasia
Cite this article as: Porat S, Amsalem H, Shah PS, et al. Transabdominal amnioinfusion for premature preterm rupture of membranes: a systematic review and
07:●●●●.
Preterm premature rupture of mem-branes (PPROM) complicates ap-

proximately 3% of all pregnancies.1 It is amajor cause of neonatal death and mor-bidity, primarily because of pretermbirth. Lack of amniotic fluid may lead topulmonary hypoplasia, infection, and

From the Division of Maternal-Fetal Medicine,Departments of Obstetrics and Gynecology(Drs Porat and Murphy) and Pediatrics (DrShah), Mt Sinai Hospital, Faculty of Medicine,University of Toronto, Toronto, Ontario,Canada; and the Department of Obstetrics andGynecology (Dr Amsalem), Hadassah MtScopus, Hebrew University–Hadassah MedicalCenter, Jerusalem, Israel.

Received April 20, 2012; revised June 12,2012; accepted Aug. 2, 2012.

The authors report no conflict of interest.

Presented as a poster at the 32nd annualmeeting of the Society for Maternal-FetalMedicine, Dallas, TX, Feb. 6-11, 2012.

Reprints not available from the authors.

0002-9378/free© 2012 Mosby, Inc. All rights reserved.http://dx.doi.org/10.1016/j.ajog.2012.08.003

For Editors’ Commentary, see

restrictive joint deformities. Chorioam-nionitis negatively affects neonatal prog-nosis at all gestational ages and warrantsprompt delivery. The standard manage-ment approach to mid-trimester PPROMincludes antibiotic treatment2 and cortico-steroids3 to accelerate fetal lung maturitybetween 24 and 32 weeks of gestation.4

Delivery is warranted if there is clinicalevidence of chorioamnionitis or fetal dis-tress. Termination of pregnancy may beoffered for previable PPROM (�22-23

eeks of gestation) because of the poorrognosis. Despite the relatively high fre-uency of this condition, controversy re-arding the optimal management persists.

In recent years, attempts to decreaseeonatal mortality and morbidity ratesere undertaken with different strategies

hat included intracervical fibrin appli-ation,5 amniopatch,6 fetal endoscopicracheal occlusion,7,8 antioxidant treat-

ent,9 gelatin sponge,10 and progester-one treatment.11 None of these strategieshave proved to be consistently effec-tive, reproducible, or applicable for

d

MONTH 2012 Ame

Amnioinfusion or instillation of phys-iologic solution into the amniotic cavitywas attempted initially to reduce intra-partum variable decelerations.12 Later, itwas suggested as a treatment modality toprolong the latency period and preventthe oligohydramnios-related sequelae incases of early PPROM.13,14 Both transcer-vical15,16 and transabdominal14 routeshave been attempted. One of the hypo-thetic disadvantages of the transcervicalroute is the nonsterile environmentthrough which the infusion catheterpasses, therefore increasing the risk of theintroduction of infectious organisms fromthe vaginal flora into the amniotic sac.Transabdominal amnioinfusion (TA) the-oretically surmounts this pitfall. Several ar-ticleshavedescribedserialTAasaplausibletreatment modality to prolong the latencyperiod between rupture of membranesand birth.17 Recently, a Cochrane reviewassessed the efficacy of TA for PPROMwith the use of data from 2 randomizedtrials and concluded that the small num-ber of subjects in those studies precludeda definitive answer in regards to the effi-cacy of the intervention.18 However, ad-

itional data are available from observa-

rican Journal of Obstetrics & Gynecology 1.e1

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edvds

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Research Obstetrics www.AJOG.org

tional studies of TA that can shed furtherlight on this topic.

Our objective was to review systemat-ically and metaanalyze studies that haveassessed efficacy and safety of TA inwomen with PPROM. This systematicreview provides results of separate qual-itative and quantitative analyses of ran-domized controlled trials (RCTs) andobservational studies.

METHODSSearch strategyWe performed a comprehensive literaturesearch, assisted by an experienced librar-ian, using the MEDLINE from 1950 to De-cember 2011 and EMBASE from 1980 toDecember 2011. We also searched theClinicalTrials.gov database for studiesthat finished recruitment. We used theterms fetal membranes, premature rup-ture, rupture, membrane*, pregnancy,amnioinfus*, premature fetus membranerupture, and amnioinfusion. There were

FIGURE 1Study selection process

Porat. Transabdominal amnioinfusion for PPROM. Am J Ob

no language or geographic restrictions.

1.e2 American Journal of Obstetrics & Gynecology

Bibliography of identified articles wasused to screen for additional relatedarticles.

Study selectionWe included both comparative observa-tional and RCTs in which TA and conven-tional treatment were compared with con-ventional treatment alone. Case reports,case series, and abstract publications wereexcluded. Studies that included patientswith a confirmed diagnosis of PPROM-as-sociated oligohydramnios were included.Studies that included oligohydramniosfrom other causes (eg, intrauterinegrowth restriction, renal anomalies)were excluded. Two reviewers (S.P. andH.A.) independently evaluated studies forinclusion; disagreements were resolvedthrough consensus among the authors.

Outcome measuresThe primary outcomes of interest werelatency period (interval from PPROM to

Gynecol 2012.

birth) and perinatal death. Secondary

MONTH 2012

outcomes of interest were pulmonaryhypoplasia, neonatal death, gestationalage at birth, birthweight, chorioamnio-nitis, early onset (�72 hours from deliv-ry) neonatal sepsis, bronchopulmonaryysplasia, and cesarean delivery. Two in-estigators (S.P. and H.A.) indepen-ently abstracted the relevant data fromelected articles.

Assessment of risk of biasRisk of bias in observational studieswas assessed with the Newcastle-Ot-tawa scale19 and in RCTs with the Co-chrane collaboration’s tool.20 For ob-ervational studies, the domains ofssessment included selection, compara-ility, and outcome assessment biases.or RCTs, the domains included selec-ion, performance, detection, attrition,eporting, and other biases. Two investi-ators (S.P. and H.A.) independentlyssessed risk of bias; discrepancies were re-olved through discussion and involve-

ent of third author.

Data extractionData were extracted in duplicate frompublished reports by 2 authors who useda standardized data collection form. Athird reviewer was consulted in case ofdisagreement between the 2 data extrac-tors; discrepancy was resolved by con-sensus. We did not contact authors formissing information. For continuousoutcomes, means and standard devia-tions were obtained from studies. Whenthey were not reported, they were calcu-lated from range, median, and samplesize according to the method describedby Hozo et al.21 For categoric outcomes,vent rates were obtained.

Statistical analysisStatistical analyses were performed withthe Review Manager (RevMan) software(version 5.1.4; The Nordic CochraneCentre, København, Denmark). Meta-analyses were performed separately forcohort studies and the RCTs. Where datawere sufficiently homogenous, meta-analysis was conducted with the use of arandom effects model, with weighting ofstudies according to the DerSimonian-Laird method. Random-effect modelwas used to account for between and

stet

within study heterogeneity. Cochran’s Q

http://www.clinicaltrials.gov

www.AJOG.org Obstetrics Research

TABLE 1Characteristics of included studies

Study Characteristics

De Santis et al, 200317

.......................................................................................................................................................................................................................................................................................................................................................................

Type of study Quasi-randomized; patients admitted by chance to 1 of 2 divisions of the same department; both divisionsoffered expectant treatment; only 1 division offered TA

.......................................................................................................................................................................................................................................................................................................................................................................

Participants 37 patients in intervention group; 34 patients in control group..............................................................................................................................................................................................................................................................................................................................................................

Inclusion criteria Singleton; PPROM at �26 weeks of gestation; severe and persistent oligohydramnios (AFI �30 mm, lasting �7 d)..............................................................................................................................................................................................................................................................................................................................................................

Exclusion criteria Clinical chorioamnionitis; active labor; autoimmune or metabolic disease; history of multiple invasive procedures;declining treatment after informed consent; delivery in the interim 7-day waiting period from admission; transferfrom other hospitals after a period of treatment

.......................................................................................................................................................................................................................................................................................................................................................................

Diagnosis of PPROM History; sterile speculum examination; vaginal pH �5; AFI measurement by ultrasound scanning.......................................................................................................................................................................................................................................................................................................................................................................

Interventions..............................................................................................................................................................................................................................................................................................................................................................

All Hospital bed rest; antibiotic prophylaxis (mezlocillin, 2 g intravenously twice daily for at least 7 days) or targetedtreatment based on cultures; tocolytic treatment (isoxsuprine, either intravenously or orally) for contractions;betamethasone after 25 weeks; fetal monitoring by daily heart check or cardiocotography after 26 weeks andmodified BPP every 3 days; cesarean delivery performed in the presence of chorioamnionitis, abruptio placentae,and/or fetal distress (abnormal fetal monitoring) or at 30 weeks of gestation

..............................................................................................................................................................................................................................................................................................................................................................

Intervention Weekly saline amnioinfusion in a sufficient amount to increase AFI to 10 cm starting 7 days at least afterPPROM; antibiotics and tocolysis on the day of amnioinfusion

.......................................................................................................................................................................................................................................................................................................................................................................

Outcomes Latency period; gestational age at delivery; cesarean delivery; genitourinary infection, amnionitis/endometritis;neonatal weight; orotracheal intubation; survival; deformities; pulmonary hypoplasia; bronchopulmonarydysplasia; early-onset sepsis; early-onset pneumonitis; abnormal neurologic outcome (includes cerebral palsy,spastic diplegia or tetraplegia, deafness, or blindness)

.......................................................................................................................................................................................................................................................................................................................................................................

Notes Also included were women who underwent PROM after amniocentesis for prenatal diagnosis: 10 patients(27.0%) in the amnioinfusion group and 8 patients (23.5%) in the control group

................................................................................................................................................................................................................................................................................................................................................................................

Tranquilli et al 200535

.......................................................................................................................................................................................................................................................................................................................................................................

Type of study Randomized controlled trial.......................................................................................................................................................................................................................................................................................................................................................................

Participants 17 patients in each arm..............................................................................................................................................................................................................................................................................................................................................................

Inclusion criteria Singleton pregnancy with a certain gestational age confirmed by an early second-trimester ultrasonographicexamination; gestational age 24-33 weeks; evidence of PPROM within 24 hours of admission; oligohydramnios(amniotic fluid index, �10th percentile); absence of uterine contractions at the time of hospitalization; noevidence of clinical chorioamnionitis at admission; no evidence of placental anomalies or major structural fetalanomalies, and normal cardiotocography at the time of admission

.......................................................................................................................................................................................................................................................................................................................................................................

Diagnosis of PPROM PPROM diagnosed on examination by a sterile speculum when obvious leakage of amniotic fluid from thecervical os was confirmed by a positive fibronectin test

.......................................................................................................................................................................................................................................................................................................................................................................

Interventions..............................................................................................................................................................................................................................................................................................................................................................

All Hospital bed rest; antibiotic prophylaxis (sulbactam-ampicillin 3 g, intravenously every 8 hours for 7 days);betamethasone therapy; prophylactic tocolytic (intravenous ritodrine) in the absence of clinical signs ofchorioamnionitis or placental abruption; daily fetal heart rate monitoring

..............................................................................................................................................................................................................................................................................................................................................................

Intervention Weekly serial amnioinfusion if the AFI fell �5th percentile and/or a median pocket of amniotic fluid was �2 cm,with a target AFI of �10th percentile; if repeated AFI was �5, amnioinfusion repeated weekly until 27 weeks ofgestation; a nonstress test performed daily

.......................................................................................................................................................................................................................................................................................................................................................................

Outcomes Latency period; gestational age at delivery; birthweight; admission to neonatal intensive care unit; pulmonaryhypoplasia; abnormal neurologic outcome

................................................................................................................................................................................................................................................................................................................................................................................

Singla et al, 201034

.......................................................................................................................................................................................................................................................................................................................................................................

Type of study Randomized controlled trial.......................................................................................................................................................................................................................................................................................................................................................................

Participants 30 patients in each arm..............................................................................................................................................................................................................................................................................................................................................................

Inclusion criteria Singleton pregnancy; PPROM between 26 and 33 � 6 week gestations; AFI �5th percentile for gestational age..............................................................................................................................................................................................................................................................................................................................................................

Exclusion criteria Women with evidence of clinical chorioamnionitis, placental or fetal anomalies; active labor or AFI �5th percentile................................................................................................................................................................................................................................................................................................................................................................................

Porat. Transabdominal amnioinfusion for PPROM. Am J Obstet Gynecol 2012. (continued )

MONTH 2012 American Journal of Obstetrics & Gynecology 1.e3


TABLE 1Characteristics of included studies (continued)

Study Characteristics

Diagnosis of PPROM Sterile speculum examination or nitrazine/litmus paper test; confirmation by ultrasound scanning.......................................................................................................................................................................................................................................................................................................................................................................

Interventions..............................................................................................................................................................................................................................................................................................................................................................

All 24 hours of observation after admission before randomization; hospital bed rest; antibiotic prophylaxis(erythromycin: 250-mg tablet 4 times per day for 10 days); betamethasone prophylaxis; daily obstetricexamination; weekly BPP, complete blood cell count, and cervical/vaginal cultures

..............................................................................................................................................................................................................................................................................................................................................................

Intervention Amnioinfusion of warmed saline solution in a sufficient amount to maintain the AFI at �5th percentile forgestational age; weekly AFI measurement and repeated amnioinfusion if the AFI fell �5th percentile; laborinduction when there was fetal distress or chorioamnionitis

.......................................................................................................................................................................................................................................................................................................................................................................

Outcomes Latency period; gestational age at delivery; birthweight; intrapartum fetal distress; early neonatal sepsis; rateand causes of neonatal mortality; type and mode of delivery; postpartum sepsis

................................................................................................................................................................................................................................................................................................................................................................................

Vergani et al, 199733

.......................................................................................................................................................................................................................................................................................................................................................................

Type of study Observational.......................................................................................................................................................................................................................................................................................................................................................................

Participants 18 patients in intervention group and 16 patients in historic cohort group who did not undergo the procedure..............................................................................................................................................................................................................................................................................................................................................................

Inclusion criteria Singleton pregnancy; PPROM at �25 completed weeks of gestation; no labor; persistent oligohydramnios(maximum pool depth �2 cm of cord-free pocket of fluid) at �4 days

..............................................................................................................................................................................................................................................................................................................................................................

Exclusion criteria Amniotic fluid leakage after second-trimester amniocentesis; clinical chorioamnionitis; presence of uterinecontractions �4/hour; sonographic diagnosis of structural fetal abnormalities; maternal immunologic diseases;multiple gestations

.......................................................................................................................................................................................................................................................................................................................................................................

Diagnosis of PPROM Observation of vaginal pooling and a positive nitrazine test on sterile speculum examination.......................................................................................................................................................................................................................................................................................................................................................................

Interventions..............................................................................................................................................................................................................................................................................................................................................................

All Hospital bed rest during the first week, then home bed rest until 25 weeks, after which all patients wereadmitted until delivery; tocolytic treatment (intravenous ritodrine) given at �25 weeks for uterine contractions inthe absence of clinical signs of chorioamnionitis or abruption placentae; betamethasone course at least oncebetween 25 and 32 weeks of gestation; 1-week course of prophylactic antibiotic therapy with sulbactam-ampicillin 3 g intravenously every 8 hours and targeted treatment based on cervical and vaginal cultures;sonographic determination of amniotic fluid volume twice a week for outpatients and daily for inpatients; BPPtwice a week at �25 weeks of gestation

..............................................................................................................................................................................................................................................................................................................................................................

Intervention 1-2 TA/wk to aim to restore AFI �5 cm; delivery in the presence of clinical chorioamnionitis, fetal distress,abruption placentae, or documented fetal lung maturity on amniocentesis after 28 weeks of gestation

.......................................................................................................................................................................................................................................................................................................................................................................

Outcomes Gestational age at delivery; latency period; survival rate; pulmonary hypoplasia; chorioamnionitis; fetal distress;placental abruption; preterm labor; in utero death; umbilical cord prolapse

................................................................................................................................................................................................................................................................................................................................................................................

Garzetti et al, 199730

.......................................................................................................................................................................................................................................................................................................................................................................

Type of study Observational.......................................................................................................................................................................................................................................................................................................................................................................

Participants 18 women in each arm; control group recruited from historic data..............................................................................................................................................................................................................................................................................................................................................................

Inclusion criteria Singleton; PPROM between 25 and 32 weeks of gestation; oligohydramnios (AFI, �5th percentile)..............................................................................................................................................................................................................................................................................................................................................................

Exclusion criteria Presence of uncontrolled labor; presence of obstetric complications; maternal immunocompromise; uterinefibroid tumors; lack of written consent

.......................................................................................................................................................................................................................................................................................................................................................................

Diagnosis of PPROM Observation of gross vaginal pooling of amniotic fluid and a positive nitrazine test on speculum examination.......................................................................................................................................................................................................................................................................................................................................................................

Interventions..............................................................................................................................................................................................................................................................................................................................................................

All Hospital bed rest until delivery with minimal activity limited to bathroom necessities; weekly complete blood cellcount and semiquantitative C-reactive protein measurement; weekly ultrasound scanning and cardiocotography;daily nonstress test; prophylactic tocolytic treatment (intravenous ritodrine) in the absence of chorioamnionitis orabruption placentae; prophylactic antibiotic treatment (ceftazidime 2 g/d intramuscularly) and targeted therapybased on cultures; delivery in the presence of clinical chorioamnionitis, positive amniotic fluid culture, fetaldistress, and documented fetal lung maturity

..............................................................................................................................................................................................................................................................................................................................................................

Intervention If AFI �10th percentile for gestational age and deepest pocket of cord-free fluid �10 mm, weekly TA of 150-350 mL warmed saline solution; weekly AFI assessment before and after each procedure; biweekly fetal growthassessment

................................................................................................................................................................................................................................................................................................................................................................................

Porat. Transabdominal amnioinfusion for PPROM. Am J Obstet Gynecol 2012. (continued )

1.e4 American Journal of Obstetrics & Gynecology MONTH 2012

to

vu

iT

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test was used to test for heterogeneity be-tween studies at the .10 level of signifi-cance. The I-squared statistic was used toquantify the degree of heterogeneity.

ReportResults of the metaanalysis of RCTs andthe observational studies were reportedaccording to the Preferred ReportingItems for Systematic Reviews and Meta-

TABLE 1Characteristics of included studies

Study Characteristi

Outcomes Latency periofluid volume a

...................................................................................................................

Ogunyemi and Thompson,200232

..........................................................................................................

Type of study Observational..........................................................................................................

Participants 12 patients in.................................................................................................

Inclusion criteria PPROM at geof gross infec

.................................................................................................

Exclusion criteria Presence of a..........................................................................................................

Diagnosis of PPROM Observation o..........................................................................................................

Interventions.................................................................................................

All Initial hospitaweeks of gessuspected in

.................................................................................................

Intervention Before the prodiscontinuednormal saline

..........................................................................................................

Outcomes Chorioamnionneonatal deat

...................................................................................................................

Gramellini et al, 200331

..........................................................................................................

Type of study Observational..........................................................................................................

Participants 24 patients in.................................................................................................

Inclusion criteria Singleton; �3.................................................................................................

Exclusion criteria Active labor; c..........................................................................................................

Diagnosis of PPROM Observation o..........................................................................................................

Interventions.................................................................................................

All Tocolytic treaprophylactic a

.................................................................................................

Intervention TA of 0.9% nmL/gestationa

..........................................................................................................

Outcomes Gestational agdelivery, and

..........................................................................................................

Notes Refers to a grrefer only to p

...................................................................................................................

AFI, amniotic fluid index; BPP, biophysical profile; CBC, comp

Porat. Transabdominal amnioinfusion for PPROM. Am

analyses statement22 and Metaanalysis of

he Observational Studies in Epidemiol-gy guidelines,23 respectively.

RESULTSOur initial search yielded 141 citations.After review of titles and abstracts, 126citations were excluded (Figure 1). Afterfull text review of the remaining 15articles, 8 articles were excluded (3 be-cause inclusion criteria were not ful-

ntinued)

ration; median amniotic fluid volume and shortfetal short-term variability in the amnioinfusion.........................................................................................................................

.........................................................................................................................

.........................................................................................................................

ch group.........................................................................................................................

ional age �27 weeks; oligohydramnios with AFI; stable mother and fetus.........................................................................................................................

e labor; clinical chorioamnionitis.........................................................................................................................

ginal pooling, a positive nitrazine test or ferning.........................................................................................................................

.........................................................................................................................

d rest, followed by outpatient follow-up evaluatin; magnesium sulfate and terbutaline were useabsence of clinical chorioamnionitis; prophylact.........................................................................................................................

ure, intravenous magnesium sulfate 4 g loadingours after the procedure if preterm labor did no

ution with ampicillin 1 g/L until 27 weeks of ges.........................................................................................................................

latency period; cesarean delivery rate; gestatioerinatal death; total death

.........................................................................................................................

.........................................................................................................................

.........................................................................................................................

ervention group and 29 patients in historic contr.........................................................................................................................

eeks gestational age; PPROM; oligohydramnios.........................................................................................................................

cal evidence of placental abruption or chorioam.........................................................................................................................

rsistent vaginal pooling and a positive nitrazine.........................................................................................................................

.........................................................................................................................

nt (ritodrine) for �4 uterine contractions/20 miniotic therapy (erythromycin 2 g/d) given to 90%

.........................................................................................................................

al saline solution or lactated Ringer’s solution aceek; repeated if AFI measurement �12 hours a.........................................................................................................................

t delivery; latency period; birthweight; rate of intpartum endometritis.........................................................................................................................

of patients in whom the oligohydramnios was nnts affected by PPROM

.........................................................................................................................

lood cell count; PPROM, preterm premature rupture of membran

stet Gynecol 2012.

filled13,14,24; 4 because of it was not w

MONTH 2012 Ame

clear whether reported patients inthese studies were included in otherstudies,25-28 and 1 because the inter-

ention group and control group werenmatched29). The remaining 7 stud-

ies met inclusion criteria and were in-cluded in this review.17,30-35 Character-stics of these studies are summarized inable 1.Of the 7 included studies, 2 studies

m variability; relationship between amnioticup..................................................................................................................

..................................................................................................................

..................................................................................................................

..................................................................................................................

cm; normal fetal anatomic scan; absence

..................................................................................................................

..................................................................................................................

speculum evaluation..................................................................................................................

..................................................................................................................

or stable patients; corticosteroids after 24r tocolysis as needed if preterm labortravenous antibiotics

..................................................................................................................

se followed by 1 g/hr was initiated andsue; weekly amnioinfusion of warm 0.9%

on if AFI �5..................................................................................................................

age at delivery; birthweight; neonatal sepsis;

..................................................................................................................

..................................................................................................................

..................................................................................................................

roup..................................................................................................................

I, �5 cm)..................................................................................................................

itis..................................................................................................................

er test..................................................................................................................

..................................................................................................................

tamethasone after 24 weeks of gestation;patients..................................................................................................................

ding to a volume criterion of 10the procedure was �5 cm

..................................................................................................................

terine death, vaginal bleeding, cesarean

..................................................................................................................

attributed to PPROM; however, all data cited

..................................................................................................................

A, transabdominal amnioinfusion.

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1 study was quasirandomized (34 pa-tients in the control group and 37 in theintervention group), and 4 studies wereobservational studies (75 patients in thecontrol group and 72 in the interventiongroup). In the quasirandomized study,patients were admitted by chance to oneof 2 departments that differed in theirmanagement approach toward PPROM:one department provided standard care;the other department provided standardcare in addition to serial amnioinfusionto consented patients. We decided to in-clude the quasirandomized study withthe other 2 randomized studies becausewe believed that the risk of bias in thatstudy was not high. The gestational age atinclusion varied from 16-33 weeks. In-formation on individual patients wasprovided only in 1 study32; therefore,ubgroup analysis by gestational age was

TABLE 2Quality assessment of observation

Study

Selection

Representativenessof the exposedcohort

Selection of thnonexposedcohort

Ogunyemi andThompson(2002)32

* *

...................................................................................................................

Vergani et al(1997)33

* *

...................................................................................................................

Garzetti et al(1997)30

* *

...................................................................................................................

Gramellini et al(2003)31

* *

...................................................................................................................

Each asterisk represents 1 star in the Newcastle-Ottawa Scal


TABLE 3Quality assessment of randomized

Study

Bias

Selection

Random sequencegeneration

Allocationconcealment

Singla et al(2010)34

Low risk Unclear risk

...................................................................................................................

Tranquilli et al(2005)35

Low risk Low risk

...................................................................................................................

De Santis et al(2003)17

High risk High risk

...................................................................................................................



ot possible. Ascertainment of rupturef membranes was performed in all stud-

es by speculum examination to confirmooling of amniotic fluid in the posterior

ornix. In addition, 6 studies used nitra-ine, and 1 study used fetal fibronectin asconfirmatory test.35 Conventional care

for patients with PPROM included bedrest in the hospital and prophylactic an-tibiotic therapy in all studies. Five studiesused tocolysis only when uterine con-tractions appeared without clinical cho-rioamnionitis or abruptio placenta17,31-34;however, 2 studies used tocolysis as a pro-phylactic measure for all patients, regard-less of the presence of uterine contrac-tions.30,35 Targeted antibiotic therapy

ased on cervical and vaginal culturesas used in 3 studies.17,30,33 Corticoste-

roids for fetal lung maturation was usedafter viability in all but 1 study.30 The

ohort studies by the Newcastle-Otta

Comparability

Ascertainmentof exposure

Demonstrationthat outcome ofinterest was notpresent at startof study

Comparability ofcohorts on thebasis of thedesign oranalysis

* * **

.........................................................................................................................

* *

.........................................................................................................................

* * **

.........................................................................................................................

* *

.........................................................................................................................

tem. The maximum number of stars is 2 for comparability and 1

stet Gynecol 2012.

ntrolled trials

erformance: blindingf participantsnd personnel

Detection: blindingof outcomeassessment

Attritionoutcome

nclear Unclear Low risk

.........................................................................................................................

nclear Unclear Low risk

.........................................................................................................................

nclear High risk Low risk

.........................................................................................................................

stet Gynecol 2012.

MONTH 2012

umber of procedures per patient, suc-ess rate, and volumes infused variedmong different studies and among dif-erent subjects in the same study. The av-rage number of infusions per patientanged from 1.23 in Singla et al34 to 4.0 in

De Santis et al.17 Vergani et al33 reporteda median number of 3 infusions per pa-tient with a range of 1–9. Most of thestudies did not report success rate;however, Garzetti et al30 reported asuccess in 18 of 19 patients, and DeSantis et al17 reported successful am-nioinfusion in 143 of 147 procedures.The infused volumes range from 140-350 mL per infusion.17,30,34,35

De Santis et al17 reported on 5 compli-cations that occurred within 24 hours af-ter infusion: 2 cord prolapses (1 cephalicand 1 transverse lie); 2 abruptio placen-tae, and 1 onset of labor. Gramellini et

Scale system

tcome

Totalstars,n

sessmentoutcome

Was follow-uplong enoughfor outcomesto occur?

Adequacy offollow up ofcohorts

* * 9

..................................................................................................................

* * 7

..................................................................................................................

* * 9

..................................................................................................................

* * 7

..................................................................................................................

ach of the other categories.

ompletea

Reporting:selectivereporting

Othersources Overall

Low risk Low risk Moderate risk

..................................................................................................................

Low risk Low risk Moderate risk

..................................................................................................................

Low risk Low risk High risk

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al31 reported on a higher rate of vaginalleeding in the intervention group (21%)ompared with the nonamnioinfusedroup (7%), although this difference didot reach statistical significance. Ogun-emi and Thompson32 reported on 2 neo-atal complications that can be regarded asirect injuries from the procedure: 1 babyad a 2-cm leg laceration that was sutured,nd 1 baby had a 0.5 � 0.5– cm superficialhest scar that needed no treatment.

Assessment of the risk of bias in in-luded observational cohort studies and

FIGURE 2Effect of serial TA on neonatal outc

Forest plot of the results of the metaanalysis oflengths between the TA and control groups; B, pTA, transabdominal amnioinfusion.


CTs are shown in Tables 2 and 3, re-

pectively. The observational studies hadinimal risk of bias, whereas 2 of 3 RCTs

ad moderate risk of bias, and 1 RCT hadigh risk of bias.

Metaanalyses of observationalstudiesPrimary outcomesThere was prolongation of the latencyperiod (4 studies, 147 participants; meandifference, 14.4 days; 95% confidence in-terval [CI], 8.2–20.6 days; heterogeneity:I2 � 17%; Figure 2) and reduction in

es

ervational studies for A, latency period length, watal mortality rates refer to the odds ratio; and

Gynecol 2012.

perinatal mortality rate (2 studies, 60 h

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participants; pooled odds ratio [OR],0.12; 95% CI, 0.02– 0.61; heterogeneity:I2 � 0%; Figure 2). A subgroup analysis

f periviable vs potentially viable babiesould not be performed because of a lackf reporting data.

econdary outcomesesults of metaanalyses of secondaryutcomes are given in Table 4. Thereere a decreased rate of pulmonary hy-oplasia (2 studies, 45 participants;ooled OR, 0.17; 95% CI, 0.04 – 0.78;

h demonstrates the difference in latency periodulmonary hypoplasia refers to the odds ratio.

om

obs hicerin C, p

stet

eterogeneity: I2 � 0%; Figure 2) and a


esnt0

5

oosCNr

onmn

gsAorttPpd

twogttnittts6atsbp

J Ob


reduced risk for neonatal death (1 study,18 participants; OR, 0.09; 95% CI, 0.01–0.84; heterogeneity: not applicable). Theother tested secondary outcomes did notreach statistical significance.

Metaanalyses of RCTsPrimary outcomesThere was no statistically significant dif-ference in the latency period (3 studies,165 participants; mean difference, 11.4days increase in latency in TA group;however, 95% CI �3.4 to 26.2 days; het-rogeneity: I2 � 89%; Figure 3) and notatistically significant difference in peri-atal mortality rate (2 studies, 131 par-

icipants; pooled OR, 0.33; 95% CI,.10 –1.12; heterogeneity: I2 � 45%; Fig-

ure 3). A subgroup analysis of periviablevs potentially viable babies could not beperformed because of a lack of reportingdata.

Secondary outcomesResults of metaanalyses of secondaryoutcomes are given in Table 4. There wasno statistically significant difference inthe rate of pulmonary hypoplasia (2studies, 69 participants; pooled OR, 0.3;95% CI, 0.05–1.7; heterogeneity: I2 �

TABLE 4Effect of transabdominal amnioinfu

Studied outcome

Met

Stud

Difference in mean gestational age at pretermpremature rupture of membranes, db

4/14

...................................................................................................................

Difference in mean gestational age atdelivery, db

3/11

...................................................................................................................

Difference in mean latency period length, db 4/14...................................................................................................................

Difference in mean birthweight, gb 2/77...................................................................................................................

Perinatal mortality rate 2/60...................................................................................................................

Pulmonary hypoplasia 2/45...................................................................................................................

Amnionitis/endometritis 3/11...................................................................................................................

Early onset sepsis 1/18...................................................................................................................

Neonatal mortality rate 1/18...................................................................................................................

Bronchopulmonary dysplasia 1/18...................................................................................................................

Genitourinary infection N/A...................................................................................................................

Cesarean delivery 2/54...................................................................................................................

N/A, not applicable.a Data are given as odds ratio (95% confidence interval); b The

interval.


2%; Figure 3). f


Interestingly, there was a decreased ratef infectious complications of amnionitisr chorioamnionitis in the TA group (2tudies, 131 participants; OR, 0.28; 95%I, 0.11–0.69; heterogeneity: I2 � 0%).one of the other secondary outcomes

eached statistical significance.

COMMENTMid-trimester PPROM poses a challeng-ing clinical problem. Poor prognosisusually results from the combination ofprematurity, pulmonary hypoplasia, andinfection. The prognosis of mid-trimes-ter PPROM at �21 weeks of gestation isgrave because most fetuses experiencepulmonary hypoplasia.36 Pregnancy out-comes are correlated directly with thegestational age at which the mem-branes are ruptured and the amountof residual fluid after the rupture ofmembranes. Low residual volume ofamniotic fluid has been shown to beassociated with a shorter latency pe-riod37,38 and increased risk for early

nset neonatal sepsis and chorioam-ionitis.37 Lack of an effective treat-ent or intervention to prolong preg-

ancy complicates this situation even

n on the tested outcomes

lysis of observational studies

participants, n Effect estimatea

�12.30 (�18.56 to �6.03)

.........................................................................................................................

�4.11 (�22.23 to 14.00)

.........................................................................................................................

14.40 (8.24–20.56).........................................................................................................................

�129.52 (�691.09 to 432.06).........................................................................................................................

0.12 (0.02–0.61).........................................................................................................................

0.17 (0.04–0.78).........................................................................................................................

0.94 (0.33–2.68).........................................................................................................................

0.10 (0.00–2.35).........................................................................................................................

0.09 (0.01–0.84).........................................................................................................................

2.14 (0.08–60.17).........................................................................................................................

N/A.........................................................................................................................

4.16 (0.96–17.95).........................................................................................................................

rows of data represent mean difference with 95% confidence inte

stet Gynecol 2012.

urther. Despite the seriousness and p

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ravity of this condition, current ob-tetrics management has little to offer.side from close monitoring for signsf infection or early labor, no obstet-ics interventions have demonstratedhe ability to reduce morbidity or mor-ality rate that is the result of earlyPROM or specifically to address theathophysiologic processes that un-erlie the cause of this condition.In this metaanalysis, a better short-

erm prognosis in women with PPROMho underwent serial TA was seen in thebservational studies. The interventionroup had significant latency prolonga-ion and improved perinatal and neona-al survival and experienced less pulmo-ary hypoplasia. These results intensify

n the face of significantly lower gesta-ional age at rupture of membranes inhe intervention group, compared withhe control group in the observationaltudies (12.3 days of difference; 95% CI,.03–18.56). The results from the meta-nalysis of RCTs demonstrated a trendoward benefit, but the results were nottatistically significant. This is possiblyecause of the small number of partici-ants in the studies and the lack of

aanalysis of randomized controlled trials

dies/participants, n Effect estimatea

5 �1.58 (�8.09 to 4.52)

..................................................................................................................

5 3.86 (�16.49 to 24.21)

..................................................................................................................

5 11.41 (�3.36 to 26.18)..................................................................................................................

5 125.00 (�105.68 to 355.68)..................................................................................................................

1 0.33 (0.10–1.12)..................................................................................................................

0.30 (0.05–1.70)..................................................................................................................

1 0.28 (0.11–0.69)..................................................................................................................

0.38 (0.02–6.07)..................................................................................................................

9 0.52 (0.07–3.76)..................................................................................................................

7.67 (0.32–183.01)..................................................................................................................

1.29 (0.49–3.42)..................................................................................................................

2.35 (0.81–6.81)..................................................................................................................

the rest of the rows represent odds ratio with 95% confidence

sio

aana Met

ies/ Stu

7 3/16

......... .........

1 3/16

......... .........

7 3/16......... .........

3/16......... .........

2/13......... .........

2/69......... .........

1 2/13......... .........

2/83......... .........

3/12......... .........

1/20......... .........

1/71......... .........

1/71......... .........

first 4 rval,

ower.

patarecdc


The hypothesis is that infectious/in-flammatory processes are responsiblefor the activation of the laboring pro-cess. Thus, the theoretic benefit of am-nioinfusion or the introduction ofphysiologic solution into the amnioticcavity includes (1) washout/dilutionof preexisting intraamniotic bacteria,(2) washout/dilution of inflammatorycells and mediators (prostaglandins,leukotrienes, cytokines, interleukinsamong others), and (3) increase in in-

FIGURE 3Effect of serial TA on neonatal outc

Forest plot of the results of the metaanalysis of ranlengths between the TA and control groups; B, pTA, transabdominal amnioinfusion.


traamniotic fluid volume and pressure.

Theoretically, washing out or dilutingthe preexisting intraamniotic bacteriaand inflammatory cells may be benefi-cial to prolong the latent period, andthe presence of fluid may promote lungdevelopment and prevent positionalcontractures. There are also potentialsecondary benefits from this interven-tion that include the ability to test fetalgenetics (when indicated), an im-provement in ultrasound imaging ofthe baby, and a decreased risk for cord

es for randomized controlled trials

ized controlled trials for A, latency period length,atal mortality rates refer to the odds ratio; and

Gynecol 2012.

compression. l

MONTH 2012 Ame

The strengths of this metaanalysis,compared with the recently publishedCochrane review,18 include a larger sam-

le size, the inclusion of observationalnd RCT data that give the full picture ofhis intervention, and the assessment ofll clinically important outcomes. Theesults indicate a potentially beneficialffect for the intervention. However, be-ause of the small sizes of included ran-omized studies and our inability toonclude with confidence because of

ich demonstrates the difference in latency periodulmonary hypoplasia refers to odds ratio.

om

dom wherin C, p

stet

ack of power, we suggest large ade-



quately powered studies are needed forthis intervention. Because of the rarity ofthe condition, we suggest that a multi-center collaboration with standardiza-tion of treatment for such women willallow adequate power and generalizabil-ity of findings. Limitations of this reviewinclude the low numbers of participantsboth in the observational studies and theRCTs. In addition, in regards to the pro-tocol and assessment of outcomes, therewas heterogeneity in the reporting of theincluded studies. Finally, there was het-erogeneity in the quality of the studies interms of risk of bias.

If the superiority of serial TA over con-servative management is confirmed byfurther studies, this directly would im-pact both the management and researchof early PPROM. First, this interventioncould be offered to couples who face thegrim situation in which no other inter-ventions are available. Second, it will en-able further research into the contribu-tion of the amount and the constitutionof amniotic fluid for lung developmentat different fetal developmental stages. Itwill raise questions in regards to thelower threshold of amniotic fluid vol-ume or pressure that supports lung de-velopment, which is the role of amnioticfluid turnover and the role of amnioticfluid.

This metaanalysis suggests that se-rial TA improved pregnancy outcomeswhen tested in observational studies,but not in RCTs; however, for bothtypes of studies, the number of patientsthat were included remains very small.These results warrant a large, multi-center RCT to investigate the useful-ness of such an intervention in a hos-pital-based setting. f

ACKNOWLEDGMENTWe thank Ms Elizabeth Uleryk, Chief Librarian atthe Hospital for Sick Children, Toronto, Canada,for her contribution in developing the searchstrategies and for running the search on a peri-odic basis.

REFERENCES1. Mercer BM. Preterm premature rupture ofthe membranes: current approaches to evalu-ation and management. Obstet Gynecol Clin
North Am 2005;32:411-28.
1.e10 American Journal of Obstetrics & Gynecolog

2. Yudin MH, van Schalkwyk J, Van Eyk N, et al.Antibiotic therapy in preterm premature ruptureof the membranes. J Obstet Gynaecol Can2009;31:863-74.3. Harding JE, Pang J, Knight DB, Liggins GC.Do antenatal corticosteroids help in the settingof preterm rupture of membranes? Am J ObstetGynecol 2001;184:131-9.4. Miracle X, Di Renzo GC, Stark A, Fanaroff A,Carbonell-Estrany X, Saling E. Guideline for theuse of antenatal corticosteroids for fetal matu-ration. J Perinat Med 2008;36:191-6.5. Sciscione AC, Manley JS, Pollock M, et al. In-tracervical fibrin sealants: a potential treatment forearly preterm premature rupture of the mem-branes. Am J Obstet Gynecol 2001;184:368-73.6. Deprest J, Emonds MP, Richter J, et al. Am-niopatch for iatrogenic rupture of the fetal mem-branes. Prenat Diagn 2011;31:661-6.7. Kohl T, Geipel A, Tchatcheva K, et al. Life-saving effects of fetal tracheal occlusion on pul-monary hypoplasia from preterm prematurerupture of membranes. Obstet Gynecol 2009;113:480-3.8. Kohl T, Muller A, Franz A, et al. Temporaryfetoscopic tracheal balloon occlusion en-hanced by hyperoncotic lung distension: isthere a role in the treatment of fetal pulmonaryhypoplasia from early preterm premature rup-ture of membranes? Fetal Diagn Ther 2007;22:462-5.9. Borna S, Borna H, Daneshbodie B. VitaminsC and E in the latency period in women withpreterm premature rupture of membranes. Int JGynaecol Obstet 2005;90:16-20.10. O’Brien JM, Milligan DA, Barton JR. Gelatinsponge embolization. a method for the man-agement of iatrogenic preterm premature rup-ture of the membranes. Fetal Diagn Ther2002;17:8-10.11. Briery CM, Veillon EW, Klauser CK, et al.Women with preterm premature rupture of themembranes do not benefit from weekly proges-terone. Am J Obstet Gynecol 2011;204:54.e1-5.12. Nageotte MP, Freeman RK, Garite TJ,Dorchester W. Prophylactic intrapartum am-nioinfusion in patients with preterm prematurerupture of membranes. Am J Obstet Gynecol1985;153:557-62.13. Szabo I, Szilagyi A, Gacs E, Szekely J. Am-nioinfusion for management of preterm prelabourrupture of membranes. Lancet 1993;341:443-4.14. Fisk NM, Ronderos-Dumit D, Soliani A, Nico-lini U, Vaughan J, Rodeck CH. Diagnostic andtherapeutic transabdominal amnioinfusion in oli-gohydramnios. Obstet Gynecol 1991;78:270-8.15. Ogita S, Imanaka M, Matsumoto M, Oka T,Sugawa T. Transcervical amnioinfusion of anti-biotics: a basic study for managing prematurerupture of membranes. Am J Obstet Gynecol1988;158:23-7.16. Sadovsky Y, Amon E, Bade ME, Petrie RH.Prophylactic amnioinfusion during labor compli-cated by meconium: a preliminary report. Am JObstet Gynecol 1989;161:613-7.17. De Santis M, Scavo M, Noia G, et al. Trans-
abdominal amnioinfusion treatment of severe
y MONTH 2012

oligohydramnios in preterm premature ruptureof membranes at less than 26 gestationalweeks. Fetal Diagn Ther 2003;18:412-7.18. Hofmeyr GJ, Essilfie-Appiah G, Lawrie TA.Amnioinfusion for preterm premature rupture ofmembranes. Cochrane Database Syst Rev2011;12:CD000942.19. Wells GA, Shea B, O’Connell D, Peterson J,Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the qualityof nonrandomised studies in meta-analyses.Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm. AccessedSept. 13, 2012.20. Higgins JPT, Green S, eds. CochraneHandbook for Systematic Reviews of Interven-tions, version 5.1.0 [updated March 2011]. TheCochrane Collaboration 2011. Available at:www.cochrane-handbook.org. Accessed Sept.13, 2012.21. Hozo SP, Djulbegovic B, Hozo I. Estimatingthe mean and variance from the median, range,and the size of a sample. BMC Med Res Meth-odol 2005;5:13.22. Moher D, Liberati A, Tetzlaff J, Altman DG.Preferred reporting items for systematic reviewsand meta-analyses: the PRISMA statement.PLoS Med 2009;6:e1000097.23. Stroup DF, Berlin JA, Morton SC, et al.Meta-analysis of observational studies in epidemi-ology: a proposal for reporting: Meta-analysis ofObservational Studies in Epidemiology (MOOSE)group. JAMA 2000;283:2008-12.24. Chhabra S, Dargan R, Nasare M. Antepartumtransabdominal amnioinfusion. Int J GynaecolObstet 2007;97:95-9.25. Locatelli A, Ghidini A, Verderio M, et al. Pre-dictors of perinatal survival in a cohort of pregnan-cies with severe oligohydramnios due to prema-ture rupture of membranes at �26 weeksmanaged with serial amnioinfusions. Eur J ObstetGynecol Reprod Biol 2006;128:97-102.26. Locatelli A, Vergani P, Di Pirro G, Doria V,Biffi A, Ghidini A. Role of amnioinfusion in themanagement of premature rupture of the mem-branes at �26 weeks’ gestation. Am J ObstetGynecol 2000;183:878-82.27. Vergani P, Locatelli A, Verderio M, Assi F.Premature rupture of the membranes at �26weeks’ gestation: role of amnioinfusion in themanagement of oligohydramnios. Acta Biomed2004;75(suppl):62-6.28. De Carolis MP, Romagnoli C, De Santis M,Piersigilli F, Vento G, Caruso A. Is there signifi-cant improvement in neonatal outcome aftertreating pPROM mothers with amnio-infusion?Biol Neonate 2004;86:222-9.29. Turhan NO, Atacan N. Antepartum prophy-lactic transabdominal amnioinfusion in pretermpregnancies complicated by oligohydramnios.Int J Gynaecol Obstet 2002;76:15-21.30. Garzetti GG, Ciavattini A, De Cristofaro F,La Marca N, Arduini D. Prophylactic transab-dominal amnioinfusion in oligohydramnios forpreterm premature rupture of membranes: in-crease of amniotic fluid index during latency pe-
riod. Gynecol Obstet Invest 1997;44:249-54.
http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm

http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm

http://www.cochrane-handbook.org


31. Gramellini D, Fieni S, Kaihura C, Faiola S,Vadora E. Transabdominal antepartum am-nioinfusion. Int J Gynaecol Obstet 2003;83:171-8.32. Ogunyemi D, Thompson W. A case con-trolled study of serial transabdominal amnioin-fusions in the management of second trimesteroligohydramnios due to premature rupture ofmembranes. Eur J Obstet Gynecol Reprod Biol2002;102:167-72.33. Vergani P, Locatelli A, Strobelt N, et al.Amnioinfusion for prevention of pulmonary
hypoplasia in second-trimester rupture of
membranes. Am J Per inatol 1997;14:325-9.34. Singla A, Yadav P, Vaid NB, Suneja A, FaridiMM. Transabdominal amnioinfusion in pretermpremature rupture of membranes. Int J Gynae-col Obstet 2010;108:199-202.35. Tranquilli AL,GiannubiloSR,BezzeccheriV,Sc-agnoli C. Transabdominal amnioinfusion in pretermpremature rupture of membranes: a randomisedcontrolled trial. BJOG 2005;112:759-63.36. Deutsch A, Deutsch E, Totten C, DownesK, Haubner L, Belogolovkin V. Maternal and
neonatal outcomes based on the gestational
MONTH 2012 Ameri

age of midtrimester preterm premature ruptureof membranes. J Matern Fetal Neonatal Med2010;23:1429-34.37. Vermillion ST, Kooba AM, Soper DE. Amni-otic fluid index values after preterm prematurerupture of the membranes and subsequentperinatal infection. Am J Obstet Gynecol2000;183:271-6.38. Coolen J, Kabayashi K, Wong K, MayesDC, Bott N, Demianczuk N. Influence of oligo-hydramnios on preterm premature rupture ofthe membranes at 30 to 36 weeks’ gestation. J
Obstet Gynaecol Can 2010;32:1030-4.
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