Preterm premature rupture of Preterm premature rupture of

membranes Evidence membranes Evidence

Based ViewBased View

Dr.Ruby SehraMD Obstetrics & Gynaecology

Senior Consultant PROGENY AN IVF-ICSI CENTRE

DEFINITIONDEFINITION

Rupture of fetal membranes one hour prior Rupture of fetal membranes one hour prior to the onset of labor at less than 37 weeks of to the onset of labor at less than 37 weeks of pregnancy is called pPROM.pregnancy is called pPROM.

It complicates 2% of all pregnancies.It complicates 2% of all pregnancies. Precedes 1/3Precedes 1/3rdrd of all preterm births of all preterm births

EPIDEMIOLOGY OF PRETERM EPIDEMIOLOGY OF PRETERM BIRTHBIRTH

Incidence - 6% to 10%Incidence - 6% to 10% Spontaneous - 40% to 50%Spontaneous - 40% to 50% Ruptured membrane - 25% to 40%Ruptured membrane - 25% to 40% Obstetrical indications - 20% to 25%Obstetrical indications - 20% to 25%

Incidence of preterm birth in USA, 1981-1999.

National Center for Health Statistics. Goldenberg.. Obstet Gynecol 2002

Functions of membranesFunctions of membranes Fetal membranes Fetal membranes insulateinsulate the fetus against the fetus against

microbial infectionsmicrobial infections Protect the fetus against blunt Protect the fetus against blunt traumatrauma Protect umbilical Protect umbilical cord against compressioncord against compression Have a role in Have a role in enzymaticenzymatic degredation of degredation of

utrotonic substancesutrotonic substances produced in the chorionic produced in the chorionic decidual interfacedecidual interface

STRUCTURE OF MEMBRANESSTRUCTURE OF MEMBRANES

AmnionAmnion made up of epithelium and collagen made up of epithelium and collagen rich connective tissue – gives the maximum rich connective tissue – gives the maximum tensile strength to the membranes.tensile strength to the membranes.

Chorion Chorion consists of multi-layered consists of multi-layered cytotrophoblasts and collagen rich connective cytotrophoblasts and collagen rich connective tissue and is more extensible.tissue and is more extensible.

They fuse at 12 weeks with intermediate They fuse at 12 weeks with intermediate spongy layer.spongy layer.

MECHANISM OF RUPTRE OF MECHANISM OF RUPTRE OF MEMBRANESMEMBRANES

Initiation and control of the labor at molecular level is due Initiation and control of the labor at molecular level is due to interaction between the regulation of to interaction between the regulation of prostaglandinprostaglandin production, proinflammatory production, proinflammatory cytokinescytokines and tissue and tissue remodelling by matrix remodelling by matrix metalloproteinasesmetalloproteinases (MMP’s). All (MMP’s). All these lead to:these lead to:

1.1. Softening and Softening and dilatation of the cervixdilatation of the cervix by re- by re-modeling of connective tissue.modeling of connective tissue.

2.2. Initiation of Initiation of uterine contractionsuterine contractions. . 3.3. Disruption of membrane integrity leading to Disruption of membrane integrity leading to

weakening and rupture of membranes.weakening and rupture of membranes.

CAUSES OF pPROMCAUSES OF pPROM Bacterial invasion of membranes--production Bacterial invasion of membranes--production

of proteases and phospholipases causing of proteases and phospholipases causing leukocyte activation followed by cytokine leukocyte activation followed by cytokine release. release.

Weakness from over distentionWeakness from over distention Strain from uterine activityStrain from uterine activity Direct membrane trauma Direct membrane trauma Developmental (weak spot).Developmental (weak spot).

PATHOGENESIS of PPROMPATHOGENESIS of PPROM

While the exact cause of pprom is While the exact cause of pprom is often unknown, there is strong often unknown, there is strong evidence that intrauterine evidence that intrauterine infection plays a significant role infection plays a significant role in very early rupture of in very early rupture of membranes. membranes.

ACOG NEWS RELEASE November 2002

Bacterial invasion of the chorioamniotic membranesBacterial invasion of the chorioamniotic membranes Recruitment of the leucocytes Recruitment of the leucocytes release of the proinflammatory cytokines e,g.IL-release of the proinflammatory cytokines e,g.IL-

1,IL-6,IL-8 .LPSand TNF-1,IL-6,IL-8 .LPSand TNF-αα which increases which increases PGHS& .thus PGE2.PGHS& .thus PGE2.

Increases in the conc.of MMP9 directly by Increases in the conc.of MMP9 directly by cytokines,by prostaglandins or by inhibiting TIMP.cytokines,by prostaglandins or by inhibiting TIMP.

These MMPs contribute to the weakning of the These MMPs contribute to the weakning of the membranes.Weakning is followed loss of integrity by membranes.Weakning is followed loss of integrity by apoptosis by TNF- apoptosis by TNF- αα &PGE which leads to ruptureof &PGE which leads to ruptureof membranes.membranes.

Bacterial Products

Leukocyte Activation

Cytokine Release

PGE 2

PGF2α

Myometrial contractions

IL- 1, IL-6, TNF - α

Neutrophil Degranulation

Degradation of cervical fibres

IL-8

Degradation of collagen

Cervical Ripening

ILF-1, TNFα,LPS

MMP’s

Rupture Membranes

Digest extracellular

matrix

TNF- α, IFN- γ

Cellular Apoptosis

Weakened Membranes

LPS TNS - α

MMP Tissue Inhibitor

RISK RISK FACTORSFACTORS

Bacterial VaginosisBacterial Vaginosis

Bacterial vaginosis increased the risk of Bacterial vaginosis increased the risk of preterm delivery >2-fold .preterm delivery >2-fold .

Risks were higher for those screened at Risks were higher for those screened at <16 weeks (odds ratio, 7.55; 95% CI, <16 weeks (odds ratio, 7.55; 95% CI, 1.80-31.65) than those at <20 weeks of 1.80-31.65) than those at <20 weeks of gestation (odds ratio, 4.20; 95% CI, 2.11-gestation (odds ratio, 4.20; 95% CI, 2.11-8.39). 8.39).

Leitich et al Am J Obstet Gynecol. 2003 Jul;189(1):139 ( Meta-Analysis)

BACTERIAL VAGINOSISBACTERIAL VAGINOSIS Lactic acid producing lactobacillus predominating vaginal Lactic acid producing lactobacillus predominating vaginal

flora are increased by 10 fold during pregnancy to protect the flora are increased by 10 fold during pregnancy to protect the fetus by inhibiting the growth of pathogenic bacteria. IN fetus by inhibiting the growth of pathogenic bacteria. IN BV,they are replaced by anaerobic bacteria eg:BV,they are replaced by anaerobic bacteria eg:

gardinella vaginalisgardinella vaginalis Mobilincus spp.Mobilincus spp. Ureaplasma urolyticum. Ureaplasma urolyticum. Mycoplasma hominis. Mycoplasma hominis. Bacteriods bivius. Bacteriods bivius. Group Group ββ streptococci. streptococci. Enterococci Enterococci E. Coli.E. Coli.

ANAEROBES PRODUCE KETOACID-- ANAEROBES PRODUCE KETOACID-- ,SUCCINATE ,WHICH PROMOTES THE ,SUCCINATE ,WHICH PROMOTES THE GROWTH OF LARGE NO. OF GROWTH OF LARGE NO. OF POTENTIALLY PATHOGENIC ORGANISMSPOTENTIALLY PATHOGENIC ORGANISMS WITH LITTLE HOST DEFENCE RESPONSEWITH LITTLE HOST DEFENCE RESPONSE

CERVICAL FACTORSCERVICAL FACTORS Shortening of cervical length < 2.5 cm and Shortening of cervical length < 2.5 cm and

dilatation of os > 1 cm is associated 6 times dilatation of os > 1 cm is associated 6 times risk.risk.

LEEP operation (RR 1.9).LEEP operation (RR 1.9). Cold knife conization (RR 1.6)Cold knife conization (RR 1.6) Altered immune response of cervix e.g. IgA Altered immune response of cervix e.g. IgA

secretory leukoproteinase inhibitor, lysozyme, secretory leukoproteinase inhibitor, lysozyme, lactoferrins, the B-defensins and sialidase .lactoferrins, the B-defensins and sialidase .

PREVIOUS PRETERM BIRTHPREVIOUS PRETERM BIRTH 25% recurrence rate.25% recurrence rate. Risk is transmitted to the children also Risk is transmitted to the children also

probably by cervical and genetic factors.probably by cervical and genetic factors.

LIFESTYLE FACTORSLIFESTYLE FACTORS Smoking.Smoking. Alcohol abuse.Alcohol abuse. Young maternal age.Young maternal age. Occupational factors.Occupational factors. Psychological stress.Psychological stress.

NUTRTIONAL FACTORSNUTRTIONAL FACTORS Deficiency of Vitamin C & E leads to decreased Deficiency of Vitamin C & E leads to decreased

ascorbate levels, which acts as a co-enzyme for ascorbate levels, which acts as a co-enzyme for collagen cross-linking for extra cellular matrix in collagen cross-linking for extra cellular matrix in the formation of fetal membranes.the formation of fetal membranes.

OTHER FACTORSOTHER FACTORS VAGINAL BLEEDING:VAGINAL BLEEDING:

37% of pPROM’s are preceded by history of sub-37% of pPROM’s are preceded by history of sub-clinical hemorrhage which acts by coagulation clinical hemorrhage which acts by coagulation cascade system. Thrombin acts on the decidual cascade system. Thrombin acts on the decidual cells and activates MMP’s and PGE which lead to cells and activates MMP’s and PGE which lead to degredation of the membranes.degredation of the membranes.

UTERINE ANOMALIES:UTERINE ANOMALIES: Bicornuate uterusBicornuate uterus Uterus diadelphous.Uterus diadelphous. Uterine septum Uterine septum

CONSEQUENCES OF pPROMSCONSEQUENCES OF pPROMS Microbial invasion leads to shorter rupture to delivery time.Microbial invasion leads to shorter rupture to delivery time.

More chances of cord prolapse, cord compression, More chances of cord prolapse, cord compression, malpresentation, abruptio placenta, prematuritymalpresentation, abruptio placenta, prematurity

Lesser the AFI Greater are the chances of neonatal sepsis Lesser the AFI Greater are the chances of neonatal sepsis &limb deformiies .&limb deformiies .

Increased incidence of adverse neonatal outcome.Increased incidence of adverse neonatal outcome. Lung hypoplasia and chronic lung disease.Lung hypoplasia and chronic lung disease. Intraventricular hemorrhageIntraventricular hemorrhage Cerebral palsyCerebral palsy

MATERNAL MATERNAL COMPLICATIONSCOMPLICATIONS

Chorioamnionitis and EndometritisChorioamnionitis and Endometritis Occurs in 5-15%Occurs in 5-15% Maternal wound infections.Maternal wound infections.

Placental Abruption occurs in 8%Placental Abruption occurs in 8% PPHPPH Retained PlacentaRetained Placenta

NEONATAL NEONATAL COMPLICATIONSCOMPLICATIONS

Respiratory distress syndromeRespiratory distress syndrome Neonatal sepsisNeonatal sepsis HypoglycemiaHypoglycemia hypothermiahypothermia Necrotising enteocolitisNecrotising enteocolitis JaundiceJaundice retinopathyretinopathy Orthopaedic compresionon deformitiesOrthopaedic compresionon deformities Traumatic deliveryTraumatic delivery deathdeath Intraventricular haemmrhageIntraventricular haemmrhage Cerebral palsyCerebral palsy Lung hypoplasiaLung hypoplasia Chronic lung diseaseChronic lung disease

LONG TERM NEONATALLONG TERM NEONATALEFFECTS/MORBIDITIESEFFECTS/MORBIDITIES

SEVERAL STUDIES showSEVERAL STUDIES show

Only 20% preterm children are free of impairments Only 20% preterm children are free of impairments

25% had IQ less than 4025% had IQ less than 40

Children below 750 gm who survived were at serious disadvantages in Children below 750 gm who survived were at serious disadvantages in every skill required for adequate performance every skill required for adequate performance

It is advised that full resuscitation and intensive care should be given at 26It is advised that full resuscitation and intensive care should be given at 26 thth week, probably at 25week, probably at 25thth, possibly at 24, possibly at 24thth but not at 23 weeks. but not at 23 weeks.

Complications in pregnancy after 34 weeks of gestation and babies weighing Complications in pregnancy after 34 weeks of gestation and babies weighing more than 1900 gm are same as that of term pregnancy.more than 1900 gm are same as that of term pregnancy.

Role of cytokines in preterm Role of cytokines in preterm morbidity morbiditymorbidity morbidity

ChorioamnionitisChorioamnionitis accounts for 50% of the long accounts for 50% of the long term sequelae in preterm babies term sequelae in preterm babies

Increased levels of IL-1,IL-6,IL-8&TNF-Increased levels of IL-1,IL-6,IL-8&TNF-αα mediate mediate lung hypoplasia & chronic lung disease.lung hypoplasia & chronic lung disease.

Elevated levels of IL-1, IL-8 & MMPS are Elevated levels of IL-1, IL-8 & MMPS are associated with associated with intraventricular intraventricular haemmrhage ,ischaemic encephalopathy & haemmrhage ,ischaemic encephalopathy & cerebral palsy.cerebral palsy.

Can preterm Can preterm labor be labor be

predicted?predicted?

PREDICTION OF pPROMPREDICTION OF pPROM SYMPTOMS:SYMPTOMS:

i.i. Heaviness in lower abdomenHeaviness in lower abdomenii.ii. Menstruation like cramps.Menstruation like cramps.iii.iii. Low back ache.Low back ache.

PREVIOUS HISTORY OF PRETERM BIRTH.PREVIOUS HISTORY OF PRETERM BIRTH.

SHORT CERVIX OF < 2.5 cm AND OS > 1 cm DILATED.SHORT CERVIX OF < 2.5 cm AND OS > 1 cm DILATED.

PRESENCE OF BACTERIAL VAGINOSIS DIAGNOSED PRESENCE OF BACTERIAL VAGINOSIS DIAGNOSED BY -BY -

i.i. Vaginal pH > 5Vaginal pH > 5ii.ii. An amino odor when vaginal secretions are mixed with KOH.An amino odor when vaginal secretions are mixed with KOH.iii.iii. A homogeneous vaginal dischargeA homogeneous vaginal dischargeiv.iv. Gram stain shows > 5 neutrophils.Gram stain shows > 5 neutrophils.v.v. Clue Cells, e.g. epithelial cells coated with bacilliClue Cells, e.g. epithelial cells coated with bacilli

PRESENCE OF FETAL FIBRONECTIN > 50 ng/ml FROM CERVICO-PRESENCE OF FETAL FIBRONECTIN > 50 ng/ml FROM CERVICO-VAGINAL SECRETIONS.VAGINAL SECRETIONS.

AMNIOTIC FLUID INDICES AMNIOTIC FLUID INDICES i.i. Increased white cell countIncreased white cell countii.ii. Low glucoseLow glucoseiii.iii. High IL-6,TNF-High IL-6,TNF-αα levels levelsiv.iv. Positive Gram staining.Positive Gram staining.

ULTRASOUND FINDINGS:ULTRASOUND FINDINGS: Dilatation of the osDilatation of the osi.i. Funneling of cervical canal with prolapse of the membranesFunneling of cervical canal with prolapse of the membranesii.ii. Shortning of cervical lengthShortning of cervical lengthiii.iii. Absent fetal breathing movementsAbsent fetal breathing movements..

INCREASED SERUM FERRITIN LEVELS >INCREASED SERUM FERRITIN LEVELS > 64.5 ng/ml64.5 ng/ml

Serum testsSerum tests Serum alkaline phosphotaseSerum alkaline phosphotase αα-fetoproteins -fetoproteins 25% had IQ less than 40 25% had IQ less than 40 Granulocyte colony stimulating factorGranulocyte colony stimulating factor

Serum testsSerum tests Serum alkaline phosphotaseSerum alkaline phosphotase αα-fetoproteins -fetoproteins 25% had IQ less than 40 25% had IQ less than 40 Granulocyte colony stimulating factorGranulocyte colony stimulating factor

OutcomeOutcome Sensitivity specificity

Delivery <37

Delivery <34

52%

53%

85%

89%

Delivery within 1 Week

Delivery within 2 Week

Delivery within 3 Week

Leitich & Kaider ,BJOG. 2003 Apr;110 , 20:66-70. Meta-Analysis 40 studies

71%

67%

59% 92%

89%

89%

4-Fibronectin Test4-Fibronectin Test

Vaginal U/S+ Fibronectin Test Vaginal U/S+ Fibronectin Test Suspected preterm labor with no Suspected preterm labor with no

cervical changes :cervical changes :Negative fetal fibronectin + Negative fetal fibronectin + Cervical length > 30 mmCervical length > 30 mm the likelihood of delivering in the next week is the likelihood of delivering in the next week is

less than 1%.less than 1%. Thus most women with a negative test can safely Thus most women with a negative test can safely

be sent home without treatment.be sent home without treatment.

Goldenberg , Obstetrics &Gynecology 11-2002

SOME STUDIES SHOW HIGH SERUM FERRITIN SOME STUDIES SHOW HIGH SERUM FERRITIN LEVELS OF >64.5 ng/ml WITH SHORT CERVIX OF LEVELS OF >64.5 ng/ml WITH SHORT CERVIX OF <10mm ARE ASSOCIATED WITH pPROM <10mm ARE ASSOCIATED WITH pPROM

PRESENCE OF FIBRINOCTIN LEVEL OF >50 NG/ML PRESENCE OF FIBRINOCTIN LEVEL OF >50 NG/ML WITH CERVICAL LENGTH < 2.5CM ARE STRONGEST WITH CERVICAL LENGTH < 2.5CM ARE STRONGEST PREDICTORS OF PRETERM LABOR. PREDICTORS OF PRETERM LABOR.

(YEAR BOOK 2003)(YEAR BOOK 2003)

NONE OF THE TEST ALONE CAN NONE OF THE TEST ALONE CAN PREDICT THE PRETERM LABOUR BUT PREDICT THE PRETERM LABOUR BUT IT IS THE IT IS THE MULTIPLE MARKER TEST MULTIPLE MARKER TEST WHICH IS MOST RELIABLE WHICH IS MOST RELIABLE

ACOG Advises ACOG Advises Screening All Screening All

Pregnant Women for Pregnant Women for Group B Strep.Group B Strep.

ACOG NEWS RELEASE November 2002

PREVENTIONPREVENTION

PREVENTIONPREVENTION Treatment of bacterial vaginosis by as early as Treatment of bacterial vaginosis by as early as

possible in the pregnancypossible in the pregnancy Oral erythromycin 250 mg q.i.d. for 7 daysOral erythromycin 250 mg q.i.d. for 7 days Metrogyl 500 mg t.d.s. for 7 days.Metrogyl 500 mg t.d.s. for 7 days. Clindamycin Clindamycin

Local antibiotics shold be combined with systmic Local antibiotics shold be combined with systmic A/B to cover the organismms in the decidua A/B to cover the organismms in the decidua

Cervical circlageCervical circlage McDonald McDonald PrimaryPrimary ShirodkarShirodkar SecondarySecondary Trans-abdominalTrans-abdominal TertiaryTertiary

Treatment Of Vaginosis Treatment Of Vaginosis

Treatment of asymptomatic abnormal Treatment of asymptomatic abnormal vaginal flora and bacterial vaginosis vaginal flora and bacterial vaginosis with oralwith oral clindamycinclindamycin early in the 2early in the 2ndnd trimester significantly reduces the rate of trimester significantly reduces the rate of late miscarriage and spontaneous late miscarriage and spontaneous preterm birth.preterm birth.

Ugwumadu et al. Lancet. 2003 Mar 22;361:983-8. ) RCT

17 Hydroxy -Progesterone Caproate17 Hydroxy -Progesterone Caproate

Prophylactic use of Prophylactic use of 17 hydroxy progesterone 17 hydroxy progesterone caproatecaproate to prevent preterm labor revealed to prevent preterm labor revealed a significant a significant decrease in preterm birth .decrease in preterm birth .

However, it However, it has nothas not successfully inhibited successfully inhibited active pretermactive preterm labor. labor.

Meis et al. N Engl J Med. 2003 Jun 12;348(24):2379-85.RCT (19 centers )

Keirse. Br J Obstet Gynaecol 1990;97:149-54. Meta-anlysis of 6RCTs.

DIAGNOSIS AND TREATMENT DIAGNOSIS AND TREATMENT OF SYMPTOMATIC pPROMOF SYMPTOMATIC pPROM

PROM: Rupture of membrane prior to onset PROM: Rupture of membrane prior to onset of laborof labor

TermTerm

PretermPreterm ViableViable PreviablePreviable

Diagnosis Diagnosis Clear history of leaking large amounts of fluid Clear history of leaking large amounts of fluid Sterlie speculam for examination Sterlie speculam for examination Nitrazine test (ferning) is 93% accurateNitrazine test (ferning) is 93% accurate wherever possible digital examination should be wherever possible digital examination should be

avoided (lantecy period 2.1 day (no p/v) 11.3 days avoided (lantecy period 2.1 day (no p/v) 11.3 days p/v done)p/v done)

Fetal fibronectin detection (90% senitive , 59% Fetal fibronectin detection (90% senitive , 59% sppecific)from cervicovaginal secretions.sppecific)from cervicovaginal secretions.

Indigo carmine is introduced indoutful cases gives Indigo carmine is introduced indoutful cases gives leaking of bluecolor leaking of bluecolor

Management Of Pre Viable FetusManagement Of Pre Viable Fetus

pprom at 24wks or less pprom at 24wks or less poor prognosispoor prognosis Median Letency periods 6 to 9days,max 90daysMedian Letency periods 6 to 9days,max 90daysChorio amnionitis occurs in 30 to 60%Chorio amnionitis occurs in 30 to 60% Major fetal risks-lung hypoplasia, intraventricular Major fetal risks-lung hypoplasia, intraventricular

haemmrhage and cord compresion leading to severe haemmrhage and cord compresion leading to severe fetal hypoxemiafetal hypoxemia

AFI<2 and ROM more than 14d has been associated AFI<2 and ROM more than 14d has been associated with a neonatal mortality rate >90%. with a neonatal mortality rate >90%.

Algorithm for previable pprom Algorithm for previable pprom

Induction if < 24wks.Induction if < 24wks. Hospitalization >24wks.Hospitalization >24wks. Conservetive management modified bed rest pelvic Conservetive management modified bed rest pelvic

raising,iv antibiotics and corticosteroidsraising,iv antibiotics and corticosteroids Serial ulrasounds for evaluation of oligoamnios and Serial ulrasounds for evaluation of oligoamnios and

pulmanary hypoplasia,fetal wellbeing and growth.pulmanary hypoplasia,fetal wellbeing and growth. Serial clinical and lab invatigations for evaluation Serial clinical and lab invatigations for evaluation

amnionitis,placenta abruptio.amnionitis,placenta abruptio. Continue iv antibiotics for 5days ,switch over to oral Continue iv antibiotics for 5days ,switch over to oral

antibiotics. antibiotics.

Algorithm for previable promAlgorithm for previable prom

Intrapartum GBS prophylaxis by broadspectrum A/B Intrapartum GBS prophylaxis by broadspectrum A/B

Broad spectrum antibiotics(ampi+genta+metrogyl) if amnionitis.Broad spectrum antibiotics(ampi+genta+metrogyl) if amnionitis.

Deliver for amnionitis, nonreassuring fetal hypoxia , placental Deliver for amnionitis, nonreassuring fetal hypoxia , placental abruption,Advance laborabruption,Advance labor

consider delivery at 34weeks gestation consider delivery at 34weeks gestation

Mid Trimester Prom-Novel T/tMid Trimester Prom-Novel T/t Number of novel treatment such as Number of novel treatment such as Transabdominal amnioinfusion of salineTransabdominal amnioinfusion of saline Intraamniotic injection of platelets&cryoprecipitatehave been Intraamniotic injection of platelets&cryoprecipitatehave been

tried foriatrogenic pprom (after amniocentesis,fetoscopy,fetal tried foriatrogenic pprom (after amniocentesis,fetoscopy,fetal shunts)shunts)

transcervical fibrin glue, gel foam after spontaneous pprom transcervical fibrin glue, gel foam after spontaneous pprom have been investigated but without much success .have been investigated but without much success .

Prognosis is dismal.Prognosis is dismal. Thorough counseling and documentation are required.Thorough counseling and documentation are required.

Management of viable fetusManagement of viable fetus Once pprom has set in delievery is iminent Once pprom has set in delievery is iminent

within 24hrs-15 dayswithin 24hrs-15 days The latent period goes on shortning as The latent period goes on shortning as

gestational period increasesgestational period increases

Management beyond 37 weeksManagement beyond 37 weeks Baby should be considered as Baby should be considered as

term&delievered withi 24 hrs of rupture of term&delievered withi 24 hrs of rupture of membranesmembranes

Management of pprom beween 34 -Management of pprom beween 34 -37 weeks37 weeks

Some studies advocate prompt induction and Some studies advocate prompt induction and delievery while othersfavour expectant t/t.delievery while othersfavour expectant t/t.

Expectant t/t causesExpectant t/t causes more incidence of chorioamnionitis(16%vs2)more incidence of chorioamnionitis(16%vs2) More ceasarean delieveries(7%vs5%)More ceasarean delieveries(7%vs5%) More hospital days(5.2vs2.6)More hospital days(5.2vs2.6) More neonatal sepsisMore neonatal sepsis

Management of pprom between 32-Management of pprom between 32-34 weeks34 weeks

Delievery within 1 week after rupture is more Delievery within 1 week after rupture is more cost effective & associated with less neonatal cost effective & associated with less neonatal morbiditiesmorbidities

MANAGEMENT BETWEEN 26-34 MANAGEMENT BETWEEN 26-34 weeksweeks

On expectant management On expectant management

Antibiotic coverageAntibiotic coverage CorticosteroidsCorticosteroids tocolysistocolysis

HydrationHydration Intravenous hydration does not seem to Intravenous hydration does not seem to

be beneficial, even during the period of be beneficial, even during the period of evaluation soon after admission, evaluation soon after admission,

Women with evidence of dehydration Women with evidence of dehydration may, however, benefit from the may, however, benefit from the intervention.intervention.

Stan et al (Cochrane Review 2000). In: The Cochrane Library, Issue 1 2003. Oxford

Group B Streptococci (Group B Streptococci (GBS)GBS) Prophylaxis Prophylaxis

All patients in PROM are All patients in PROM are considered at high risk for considered at high risk for chorioamnionitis &neonatal GBS chorioamnionitis &neonatal GBS sepsis and should receive sepsis and should receive prophylactic antibiotics regardless prophylactic antibiotics regardless of culture status. of culture status.

Goldenberg , Obstetrics &Gynecology 11-2002

AntibioticsAntibiotics Ampicillin IV 2gm every 6 hrlyis recommended for 2days followed by oral Ampicillin IV 2gm every 6 hrlyis recommended for 2days followed by oral

amoxycillin 250 mg 8hrly for 5 days.amoxycillin 250 mg 8hrly for 5 days.

Erythromycin 1 g 8hrly for 2 days followed by333 mg 8hrly oraly for5 daysErythromycin 1 g 8hrly for 2 days followed by333 mg 8hrly oraly for5 days

PURPOSE OF A/B PURPOSE OF A/B Reduce chorioamnionitisReduce chorioamnionitis

Less RDSLess RDS

Less necrotising enterocolitisLess necrotising enterocolitis

Less positive culturesLess positive cultures

Less abnormal cerebral U/S findingsLess abnormal cerebral U/S findings

Increased medintime to delieveryIncreased medintime to delievery

Increased birth weight Increased birth weight

Co-amoxiclav outcomesCo-amoxiclav outcomes More necrotising enterocolitis p=0.04 More necrotising enterocolitis p=0.04

less NICU admission p=0.005less NICU admission p=0.005

Less O2 req p=0.05 Less O2 req p=0.05

ANTIBIOTIC CONCLUSIONSANTIBIOTIC CONCLUSIONS

prolonged use of A/B can lead to growth of prolonged use of A/B can lead to growth of more resistant bacteria e.g pseudomonas more resistant bacteria e.g pseudomonas aeruginosaaeruginosa

Coamoxiclav was more effective in prolonging Coamoxiclav was more effective in prolonging pregnancy than erythropregnancy than erythro

Co- amoxyclav is more associated withmore Co- amoxyclav is more associated withmore risk of necrotising enterocolitisrisk of necrotising enterocolitis

Erythro is associated with less neonatal Erythro is associated with less neonatal morbidity morbidity

Group B Streptococci (Group B Streptococci (GBS)GBS) Prophylaxis Prophylaxis

The goal of this strategy is to The goal of this strategy is to prevent neonatal sepsis, prevent neonatal sepsis, morbidity&mortality, and not morbidity&mortality, and not to prevent preterm birth. to prevent preterm birth.

Goldenberg , Obstetrics &Gynecology 11-2002

CorticosteroidsCorticosteroidsAntenatal corticosteroids are associated with Antenatal corticosteroids are associated with

a significant reduction in rates of RDS, a significant reduction in rates of RDS,

neonatal death and intraventricular neonatal death and intraventricular

haemorrhage, although the numbers needed haemorrhage, although the numbers needed

to treat increase significantly after 34 to treat increase significantly after 34

weeks' gestation.weeks' gestation.

RCOG Guidelines : Grade A Recommendation

CorticosteroidsCorticosteroidsThe optimal treatment-delivery The optimal treatment-delivery

interval for administration of interval for administration of

antenatal corticosteroids is after 24 antenatal corticosteroids is after 24

hours but < 7 days after the start of hours but < 7 days after the start of

treatment. treatment.

RCOG Guidelines : Grade A Recommendation

CorticosteroidsCorticosteroidsTwo 12 mg doses of betamethasone given IM 24 Two 12 mg doses of betamethasone given IM 24

hours apart, Orhours apart, Or

Four 6 mg doses of dexamethasone given IM 12 Four 6 mg doses of dexamethasone given IM 12

hours apart (I-A).hours apart (I-A).

Four doses 500 mg hydrocortisoneFour doses 500 mg hydrocortisone

There is no proof of efficacy for any other regimen.There is no proof of efficacy for any other regimen.

SOGC Recommendation Jan. 2003

Prophylactic Vitamin K Or Phenobarbital Prophylactic Vitamin K Or Phenobarbital

Have not been shown to Have not been shown to significantly prevent significantly prevent periventricular haemorrhages in periventricular haemorrhages in preterm infants. preterm infants.

Goldenberg , May 2003

Crowther & Henderson-Smart (Cochrane Review May 2003 ) In:The Cochrane Library, Issue 1 2003. Oxford: Update Software

Crowther & Henderson-Smart (Cochrane Review Novemb. 2000 ) In:The Cochrane Library, Issue 1 2003. Oxford: Update Software

Is Tocolysis Better Than No Tocolysis Is Tocolysis Better Than No Tocolysis For Preterm rupture?For Preterm rupture?

It is reasonable not to use tocolytic drugs, as It is reasonable not to use tocolytic drugs, as there is no clear evidence that they improve there is no clear evidence that they improve outcome. However, tocolysis should be outcome. However, tocolysis should be considered if the few days gained would be considered if the few days gained would be put to good use, such as completing a course put to good use, such as completing a course of corticosteroids, or of corticosteroids, or in utero in utero transfertransfer

RCOG Guideline Grade A recommendation 2002 (Valid:2005)

Choice Of Tocolytic DrugChoice Of Tocolytic Drug

Nifedipine = EpilateNifedipine = EpilateAtosiban= TractocileAtosiban= Tractocile

B –Sympathomimetic B –Sympathomimetic (Ritodrine)(Ritodrine)Magnesium sulphateMagnesium sulphateIndomethacin Indomethacin

B B -Sympathomimetic Agents.-Sympathomimetic Agents. Maternal Maternal pulmonary edema, myocardial pulmonary edema, myocardial

ischemia :, arrhythmia, and even maternal ischemia :, arrhythmia, and even maternal death. death.

Fetal : Fetal : arrhythmia, cardiac septal hypertrophy , arrhythmia, cardiac septal hypertrophy , hydrops, pulmonary edema, and cardiac hydrops, pulmonary edema, and cardiac failure. hypoglycemia, periventricular-failure. hypoglycemia, periventricular-intraventricular hemorrhage, and fetal and intraventricular hemorrhage, and fetal and neonatal death.neonatal death. . .

Magnesium sulphate is ineffective at Magnesium sulphate is ineffective at delaying birth or preventing delaying birth or preventing preterm birth, and its use is preterm birth, and its use is associated with an increased associated with an increased mortality for the infant.mortality for the infant.

Crowther et al, (Cochrane Review) August 2002. In: The Cochrane Library, Issue 1 2003. Oxford: Update Software.

Magnesium SulfateMagnesium Sulfate

Nitric Oxide DonorsNitric Oxide DonorsThere is insufficient evidence to There is insufficient evidence to

support the routine administration of support the routine administration of nitric oxide donors (nitroglycerinnitric oxide donors (nitroglycerin ) )in in the treatment of preterm labor.the treatment of preterm labor.

Duckitt& Thornton , (Cochrane Review) March 2002. In: The Cochrane Library, Issue 1 2003. Oxford: Update Software.

IndomethacinIndomethacin Compared with ritodrine there is Compared with ritodrine there is

insufficient evidence for any insufficient evidence for any differential effect on delay in delivery, differential effect on delay in delivery, but indomethacin does seem to have but indomethacin does seem to have fewer maternal adverse effects than the fewer maternal adverse effects than the beta-agonists beta-agonists

RCOG Guideline Grade B Recommendation 2002 (Valid:2005)

IndomethacinIndomethacin Fetal risk:Fetal risk: Premature closure of the ductus.Premature closure of the ductus. Renal and cerebral vasoconstriction.Renal and cerebral vasoconstriction. Necrotising enterocolitisNecrotising enterocolitis Common with high dose and prolonged Common with high dose and prolonged

exposure.exposure.

RCOG Guideline Grade B Recommendation 2002 (Valid:2005)

IndomethacinIndomethacin Indomethacin therapy for Indomethacin therapy for < 48 hours < 48 hours < 30-32 weeks' gestation)< 30-32 weeks' gestation) Not > 200mg/day.Not > 200mg/day.appears to be a relatively safe and effective appears to be a relatively safe and effective

tocolytic agent tocolytic agent Goldenberg , Obstetrics &Gynecology 11-2002

IndomethacinIndomethacin Indomethacin can be used as Indomethacin can be used as a second-line tocolytic agent a second-line tocolytic agent in early gestational age in early gestational age preterm labors. preterm labors.

Goldenberg , Obstetrics &Gynecology 11-2002

IndomethacinIndomethacin Indomethacin may be a first-line Indomethacin may be a first-line

tocolytic in:tocolytic in: Associated polyhydramnios :Associated polyhydramnios : ( to have renal effects of ( to have renal effects of

indomethacin)indomethacin)

Newton eMedicine 2002

IndomethacinIndomethacin Capsule 25mg oral Capsule 25mg oral Amp 50mgAmp 50mg Rectal Supp 100 mg Rectal Supp 100 mg

Newton eMedicine 2002

50 mg Loading dose

Then 25-50mg /6hs

Atosiban: TractocilAtosiban: TractocilAtosiban, a synthetic Atosiban, a synthetic

peptide, is a competitive peptide, is a competitive antagonist of oxytocin at antagonist of oxytocin at

uterine oxytocin receptorsuterine oxytocin receptors..

Atosiban: TractocilAtosiban: TractocilAtosibanAtosiban - - compared with beta-agonists-compared with beta-agonists- has:has:Little difference in the effect of these agents on delayed Little difference in the effect of these agents on delayed

deliverydelivery

Fewer maternal adverse effects than beta-agonists, such as Fewer maternal adverse effects than beta-agonists, such as chest pain, palpitations , tachycardia , hypotension , chest pain, palpitations , tachycardia , hypotension , dyspnoea ,vomiting , and headache.dyspnoea ,vomiting , and headache.

Worldwide Atosiban Vs Beta-agonists Study Group. BJOG 2001;108:133–42( RCT)

NifedipineNifedipineNifedipineNifedipine- - compared withcompared with ritodrineritodrine - has:- has:

Higher delaying of delivery for >48 H.Higher delaying of delivery for >48 H.

Lower risk of RDS &Neonatal jundice.Lower risk of RDS &Neonatal jundice.

Lower admission to NN ICU Lower admission to NN ICU

Fewer maternal adverse effectsFewer maternal adverse effects

Tsatsaris et al, . Obstet Gynecol 2001;97:840–7. (Meta-analysis)

NifedipineNifedipineWhen tocolysis is indicated for women in When tocolysis is indicated for women in

preterm labor, calcium channel blockers are preterm labor, calcium channel blockers are preferable to other tocolytic agents preferable to other tocolytic agents compared, mainly betamimetics.compared, mainly betamimetics.

Further research should address the effects of Further research should address the effects of different dosage regimens and formulationsdifferent dosage regimens and formulations

King et al, (Cochrane Review) 9-2002. In: The Cochrane Library, Issue 1 2003. Oxford: Update Software.

NifedipineNifedipine20mg initial 20mg initial

10-20 mg /4-6 h10-20 mg /4-6 h

depin capsule :10mg depin capsule :10mg depin retard Tablet: 20 mg depin retard Tablet: 20 mg

Tsatsaris et al, . Obstet Gynecol 2001;97:840–7. (Meta-analysis)

ConclusionsConclusions

Tocolysis should be considered only for 2 Tocolysis should be considered only for 2 days- if needed - for corticosteroids thereby days- if needed - for corticosteroids thereby , or , or in utero in utero transfer to a tertiary center .transfer to a tertiary center .

Management 0f labourManagement 0f labour Once 34 weeks have reached,no benefit is gained Once 34 weeks have reached,no benefit is gained

interms fetal morbidity &mortality-no point in interms fetal morbidity &mortality-no point in prolonging the pregnancyprolonging the pregnancy

Deleivery to be conducted in tertiary care centre in Deleivery to be conducted in tertiary care centre in the presence of expert neonatologist.the presence of expert neonatologist.

Continuous F.H.S. monitoring in labour room to Continuous F.H.S. monitoring in labour room to predict any s/s of chorioamnionitis or fetal acidosis.predict any s/s of chorioamnionitis or fetal acidosis.

DELEIVERY OF PRETERM BABYDELEIVERY OF PRETERM BABY

Thorogh asepsisThorogh asepsis

All possible efforts should be made to obviate All possible efforts should be made to obviate any trauma to the head during labourany trauma to the head during labour

Forceps assistance is indicated only if Forceps assistance is indicated only if epidural analgesia is given epidural analgesia is given

Indication of LSCSIndication of LSCS Non progress of labourNon progress of labour S/s of corioamnionitisS/s of corioamnionitis

Best incision for lscs is—LOW VERTICAL to Best incision for lscs is—LOW VERTICAL to avoid trauma to preterm fetal headavoid trauma to preterm fetal head

A lot more needs to be done to predict , A lot more needs to be done to predict , prevent & manage pprom to reduce the prevent & manage pprom to reduce the neonatal morbidity &mortality due to this neonatal morbidity &mortality due to this dreadful cause of prematuritydreadful cause of prematurity