Modern Management of Prolonged Rupture of

Membranes

Joseph R. Biggio Jr., M.D.Department of Obstetrics &

GynecologyDivision of Maternal-Fetal Medicine

University of Alabama at Birmingham

PROM

Amniorrhexis prior to onset of active labor regardless of gestational age

Premature Rupture of Membranes

PPROM

Amniorrhexis < 37 weeks’ gestational age

prior to onset of active labor

Preterm Premature Rupture of Membranes

Latency

Interval from Rupture of Membranes

to Onset of Active Labor

Diagnosis History Avoid digital exam Vaginal Pool Nitrazine Paper Ferning Ultrasound Amniocentesis/Dye Study

PROM near Term

Management gestational age dependent

Induction vs. awaiting spontaneous labor

Antibiotic prophylaxis per ACOG/CDC recommendations

Induction vs. Expectant Management

>5,000 women randomized Oxytocin, PGE2 or expectant

management up to 4 days No difference in cesarean section

or neonatal infection Less chorioamnionitis in induction

with oxytocin groupHannah, NEJM, 1996

Epidemiology of Preterm Birth

PPROM

Spontaneous Preterm Delivery

Indicated Preterm Delivery

28 %

46 %26 %

Andrews, 1995

PPROMRisk Factors

Lower/Upper Genital Tract Infection Proteases Prostaglandins

History of PPROM Incompetent Cervix Abruption Polyhydramnios Multiple Gestation Smoking

PPROMComplications

Maternal/Fetal Infection Premature Labor and Delivery Umbilical Cord Prolapse Fetal Hypoxia 2º Cord Compression Increased Rate of Cesarean Section Intrauterine Growth Restriction Abruption Stillbirth

PPROMStandard Management

Confirmation of Diagnosis Verification of Gestational Age R/O Labor/Infection/Fetal

Compromise Avoid Digital Vaginal Examinations In Hospital Observation Bedrest

PPROMLatency

Gestational Age (Weeks)

% P

ati

en

ts w

ith

La

ten

cy

>

1 W

ee

k

25

50

75

25 25-28 29-32 33-360

Wilson, Obstetrics & Gynecology, 1982

PPROMVaginal Examination

24-26 26-28 28-30 30-32 32-34 34-35

Gestational Age (Weeks)

20

15

10

5Lat

ency

Day

s No Exam

Exam

Lewis, Obstetrics & Gynecology, 1992

Previable PPROM

< 24 weeks

Poor prognosis for successful outcome

Outcome may be different for spontaneous vs. iatrogenic

Previable PPROMComplications

Uterine Infection

Pulmonary Hypoplasia

Limb Compression Deformities

Intrauterine Growth Restriction

Previable PPROMOutcomes

Study# of

Infants Chorio. Survival

NormalNeurologicalDevelopment

Taylor 60 25% 22% 38%

Major 71 43% 65% 31%

Moretti 124 39% 32% 33%

Bengston 63 46% 51% 16%

Overall 318 39% 41% 30%

PPROMManagement Issues

Timing of Delivery Tocolysis Antibiotics Steroids Amniocentesis Observation vs. Induction Fetal Lung Maturity Testing Fetal Surveillance

Timing of Delivery

Neonatal Morbidity/MortalityUAB (1995-1996)

%

23 25 27 29 31 33 35 >37

Survival100

25

50

75

Gestational Age (Weeks)

RDS IVH NEC Sepsis

0

RNICU Survival and Morbidity Data (1995-

1996)

23 25 27 29 31 33 35 >37

Survival100

25

50

75

Weeks

RDS

IVH

NEC

Sepsis% N

eon

ates

Tocolysis

Tocolysis(n=33)

Bedrest(n=42)

Gestational age 30.0 29.4Days gained 6.7 5.2> 48 hr 87.9% 76.2%RDS 45.4% 52.4%Sepsis 9.1% 7.1%NEC 18.2% 23.8%Neonatal death 9.1% 11.9%

PPROMTocolysis

Weiner, AJOG, 1988

Tocolysis(n=39)

Expectant(n=40)

Gestational age 27.9 27.3Days gained 11.5 12.0> 48 hr 77% 75%RDS 51% 58%Sepsis 3% 5%IVH 8% 5%Hospital stay 47.5 57.0

PPROMTocolysis

Garite, AJOG, 1987

Antibiotics

Preterm LaborChorioamnion Colonization

0 30 weeks

31- 34 weeks

34- 36weeks

37 weeks

25

50

75

% P

atie

nts

Co

lon

ized

SpontaneousPreterm Labor

Indicated

Cassell, 1993

PPROMAntibiotic Therapy

Reduction Maternal/Perinatal

Infection

Prolong Latency Period

Improve Neonatal Outcome

Antibiotic: PPROMNIH-MFM Network Study

PPROM between 24 and 32 weeks IV ampicillin and erythromycin for 48 h Oral amoxicillin/erythromycin for 5 days Identification and Rx of GBS carriers Tocolysis and corticosteroids prohibited

Mercer, JAMA, 1997

Antibiotics(n=299)

Placebo(n=312) RR

RDS 40.5% 48.7% 0.83IVH 6.4% 7.7% 0.82Sepsis <72 hr 5.4% 6.4% 0.83NEC 2.3% 5.8% 0.40Death 6.4% 5.8% 1.10Composite 44.1% 52.9% 0.84

Antibiotic: NIH-MFM Network Study

Neonatal Morbidity

*

*

*

Antibiotic: Latency PeriodNIH-MFM Network StudyDuration of Latency Antibiotics Control

48 hrs 27.3 % 36.6 %

7 days 55.5 % 73.5 %

14 days 75.6 % 87.9 %

21 days 85.7 % 93.0 %

Median 6.1 days 2.9 days

PPROMAntibiotic Therapy

Optimal Antibiotic Regimen

Route/Duration of Administration

Antibiotics & PPROM: Summary

Reduction in maternal infectious morbidity

Reduction in births <48 h and <7 d Reduction in neonatal infectious

morbidity Reduction in neonates requiring

NICU and ventilation >28 d

Kenyon, Cochrane Library, 1999

Antibiotics & PPROM: Summary

No clear reduction in perinatal death

No clear reduction in cerebral abnormalities

Kenyon, Cochrane Library, 1999

Amniocentesis

PPROMAmniotic Fluid Culture

Group B Streptococcus 20 % Gardnerella vaginalis 17 % Peptostreptococcus 11 % Fusobacteria 10 % Bacteroides fragilis 9 % Other Streptococci 9 % Bacteroides sp. 5 %

Utility of Amniocentesis

Confirm/Refute diagnosis of chorioamnionitis Glucose <15 mg/dL Culture Gram stain

Lung maturity testing

Corticosteroids

Corticosteroids for FLM

Betamethasone

Dexamethasone

PPROMCorticosteroids

BlockTaeuschPapageorgiouYoungGariteCollaborativeIamsNelsonSimpsonMorales

4317173880

1533822

112121

2624193780

1353546

105124

Author Steroids ControlEffect on

RDSNumber of Patients

Treatment Control OR

RDS 83 / 456 149 / 421 0.44

NeonatalInfection

18 / 200 20 / 188 0.82

PPROMCorticosteroids

Crowley, Ob/Gyn Clinics, 1992

*

Steroids(n=38)

No Steroids(n=39)

Gestation at ROM 29.3 29.7EGA at delivery 31.4 32.0RDS 18% 44%IVH ----- 8%NEC ----- 8%Sepsis 3% 5%Death 3% 3%Hospital days 24.8 29.2

PPROMCorticosteroids +

Antibiotics

*

Lewis, Obstetrics & Gynecology, 1996

1994 NIH Consensus Conference:

Corticosteroids in PPROM

Corticosteroids reduce incidence/severity of RDS, IVH

Benefits in PPROM up to 30-32 weeks

No significant adverse outcomes for corticosteroid use in PPROM

Impact less than with intact membranes

Observation vs. Induction

Neonatal Morbidity/MortalityUAB (1995-1996)

%

30 32 34 36

Survival100

25

50

75

Weeks

RDS

IVH NEC Sepsis

Induction(n=46)

Expectant(n=47)

Cesarean delivery 8.7% 6.4%Chorioamnionitis 10.9% 27.7%Survival 100% 100%Oxygen >24 hr 4.4% 2.1%IVH ----- -----NEC ----- -----Sepsis - W/U 28.3% 59.6%Sepsis - Confirmed 6.8% 4.3%

PPROMObservation vs. Induction

Mercer, AJOG, 1993

*

*

PPROMObservation vs Induction

Delivery(n=61)

Expectant(n=68)

Cesarean delivery 23% 12%Chorioamnionitis 2% 15%Stillbirth 0 1.4%Neonatal Death 5% 0RDS 37% 33%IVH 6% 4.3%NEC 1.6% 1.4%Sepsis 3% 7%

Cox, Obstetrics & Gynecology, 1995

Fetal Lung Maturity Testing

Fetal Lung MaturationBiologic Markers

8

6

4

2

0 0

4

2

6

8

20 24 28 32 36 40Gestational Age (weeks)

L:S

Rat

io

% P

ho

sph

olip

id

L:S

PI

PG

10

Fetal Lung Maturity Evaluation in Vaginal Pool

Specimen

L:S Ratio Not Reliable

TDX:FLM Assay Not Validated

PG Useful

Fetal Surveillance

PPROMFetal Surveillance

Daily Non-Stress Test (NST) Variables Tachycardia Loss of reactivity

Biophysical Profile (BPP) Contraction Stress Test (CST)

Summary

UAB Management of PPROM

•PPROM 34 weeks•Deliver

•Previable PROM•Outpatient observation•Antibiotic prophylaxis•Option of termination <22wk•Admission at viability

•PPROM 23 weeks, <34 weeks•Antibiotic prophylaxis: Amoxicillin 500 tid x 10d, Azithromycin 1gm d1 & d5•1 course Betamethasone if <32weeks•Test for pool PG weekly beginning at 32 weeks•Deliver at 34-35 weeks

UAB Management of PPROM