3 centres collaboration

Preterm, pre-labour rupture of membranes (PPROM)

Table of contents

 

Aim

This guideline aims to provide consistent evidence-based advice on the management of preterm pre-labour labour rupture of membranes (PPROM) at the three level six (tertiary) maternity services in Victoria. Namely, Mercy Hospital for Women, Monash Medical Centre and The Royal Women’s Hospital.

This will be of significant benefit to the women being treated and for the service providers, who receive advice and support from these level six maternity hospitals.

It is anticipated that this guideline will be used as a basis for the development of guidelines at other hospitals; which will take into account local service provision and the needs of the local population.

Search and appraisal

The following methods of search and appraisal were used: An Ovid platform database selection was made using Medline, Embase and Cochrane databases for evidence published in English, mostly from the year 2000 onwards.

Professional body websites were also searched and used, namely: American College of Obstetricians and Gynecologists (ACOG), Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), Royal College of Obstetricians and Gynaecologists (RCOG), Society of Obstetricians and Gynaecologists of Canada (SOGC).

Other websites accessed were: National Health and Medical Research Council (NHMRC), National Institute for Health and Clinical Excellence (NICE) and BMJ Best practice.

Where international guideline groups have cited levels of evidence, these have been referred to in the summary boxes at the conclusion of each section. Also see Appendix 2. Evidence tables.

Search terms used singularly and in combinations were: “prolonged”, “premature”, “pre-labour”, “preterm”, “ruptured membranes”, “PPROM”, “corticosteroids”, “tocolytics”, “antibiotics”, “magnesium sulphate (sulfate)”, “randomised controlled trials”, “systematic reviews”.

In the compilation of these recommendations, international guidelines and the results of systematic reviews were used to compare facets of care. Contemporary reviews and recommendations from professional bodies were also used. Individual randomized controlled trials were used if they were a high level of evidence using NHMRC evidence level grading criteria.

Published guidelines from each of the three level six (tertiary) maternity hospitals were gathered, then compared and contrasted against the international reviews and guidelines.

Following an iterative consultation process among key stakeholders from the three level six hospitals, a consensus of opinion was gained in most instances. In cases of conflicting points of view, a variance process was initiated whereby the Co-Chairs of the 3centres Collaboration made the final decision.

Definition of preterm pre-labour rupture of membranes

Preterm pre-labour rupture of membranes (PPROM) is defined as spontaneous rupture of the membranes before the onset of labour and prior to 37 weeks gestation.1

Incidence of preterm pre-labour rupture of membranes

PPROM complicates around 2% of pregnancies but is significantly associated (40%) with preterm birth, which may then lead to substantial neonatal morbidity and mortality.

Causes of neonatal death associated with PPROM include prematurity, sepsis and pulmonary hypoplasia. Women with intrauterine infection (chorioamnionitis) give birth earlier than women without infection and infants born with sepsis have a mortality rate four times higher than those without sepsis.2

Risk factors

Risk for PPROM increases if a woman has a history of previous preterm labour and birth and/or previous PPROM. Uterine infection or inflammation, especially in early gestation is also associated with PPROM. Increased membrane collagen has also been found in women with increasing gestation and PPROM.3

Other factors associated with PPROM include lower socioeconomic groups, smoking, sexually transmitted infections, previous cervical cone biopsy, uterine distension as in the case of twins or hydramnios, cervical cerclage, amniocentesis, and vaginal bleeding.

History

An accurate assessment of maternal and fetal well-being and gestational age are essential to the appropriate evaluation, counseling, and care of women with PPROM.

Ascertain whether there are any predisposing risk factors for PPROM such as a previous preterm labour or birth, recent coitus or trauma.

Gestational age should be confirmed by any available previous ultrasound scan reports or menstrual history.

To exclude the presence of chorioamnionitis, check for a history ruptured membranes, fever, offensive discharge, any lower back pain, cramping or contractions, their length, strength and regularity. Check any history or evidence of antepartum haemorrhage or history of a show.

Examination and investigations

  • Digital examination must be avoided, as this increases the risk of ascending infection and thus, provoking the onset of premature labour.
  • Examination to ascertain any evidence of chorioamnionitis should include:
  • Temperature, pulse and blood pressure.
  • Palpation to assess fetal size and presentation, uterine tone, any tenderness or contractions.
  • A mid stream urine for laboratory culture and sensitivity.
  • Vaginal speculum examination should be performed with full aseptic technique and not touching the cervix with the speculum. Note any evidence of offensive discharge or pooling of amniotic fluid in the posterior vaginal fornix.
  • High and low vaginal swabs should be taken be taken for microscopy and assessment of the presence of group B streptococcus.
  • Ascertaining the presence of amniotic fluid may be assisted by using an Amnisureâ test.
  • Ultrasound - An ultrasound scan may help confirm the diagnosis and assist in the plan for on-going management. It is appropriate to perform this transvaginally.
  • A cardiotocograph (CTG) should be performed to assess fetal wellbeing, providing the fetus is of a viable gestation.
  • Amniocentesis may be appropriate to assess the presence or absence of intra-amniotic sepsis, or to assess fetal lung maturity. Only a consultant obstetrician should make the decision for the use of this investigation.

Initial management

Tocolysis

Aim

The use of tocolysis to prolong pregnancy has not shown to improve perinatal morbidity or mortality. The primary indication of tocolytic treatment for women who are in preterm labour is to postpone birth for 48 hours in order to allow the optimal effect of maternal corticosteroid treatment. If required, it will also facilitate in the transfer of a woman to a hospital with neonatal facilities appropriate for her gestation.

There is currently no evidence to support the role of maintenance therapy beyond the initial 48 hours.

There is no high quality evidence to show that tocolysis improves perinatal outcomes. By suppressing labour in a potentially adverse fetal environment or with an unknown cause for the preterm labour, it could be harmful. For this reason some clinicians may choose not to use tocolysis.

Nifedipine

If tocolysis is used, the tocolytic agent of choice unless contraindicated, is the calcium channel blocker nifedipine. While nifedipine is not approved for use in pregnancy and is classified as a risk category C drug by the Australian Drug Evaluation Committee, it is the most commonly used first line tocolytic therapy.4

The onset of action is usually 30 – 60minutes. It is not recommended that a second line tocolytic drug be considered in the first two hours after giving nifedipine.

Dosage 

Give an initial dose of 20mg of nifedipine tablet orally (not slow or controlled release nifedipine).

After 30 minutes, if contractions persist, give another 20mg nifedipine oral dose.

After a further 30 minutes, if still contracting, follow up with a further 20mg orally.

If the woman’s blood pressure is stable, a maintenance dose of 20mg nifedipine orally, eight hourly for 48 hours may be given where indicated. The maximum dose of nifedipine is 160mg/day.

Nifedipine

Observations

Half hourly maternal pulse and blood pressure until the contractions cease. Maternal hypotension should be treated with IV fluids in the first instance.

Continuous electronic fetal heart rate monitoring should be carried out until contractions have settled.

Contraindications

Suppression of labour in cases where there is an antepartum haemorrhage (APH), preeclampsia, abnormal fetal CTG recording, maternal cardiac disease including cardiac conduction defects, left ventricular failure and hypotension, tocolysis should be used with extreme caution and in consultation with experienced advice.

Clinicians must weigh the possibility of a preterm birth and the sequelae of a preterm infant against the risk of suppressing labour in order to gain time for fetal lung maturation, but with the possibility of a precarious maternal or fetal situation evolving.

While seldom reported in clinical practice, there is a potential interaction between magnesium sulphate (MgSO4) and nifedipine, resulting in hypotension and neuromuscular blockade effects. If severe hypotension occurs, nifedipine and MgSO4 administration should be ceased.

Side effects

Numerous side effects to nifedipine use have been reported. These include:

  • hypotension that may affect blood supply to the uteroplacental bed and cause an alteration in fetal heart rate. Maternal hypotension should be treated promptly and CTG monitoring used to observe the fetal effect.
  • also, maternal facial flushing, headache, nausea, tachycardia, dizziness, and hypotension.

The clinician, in consultation with the woman must decide whether the benefits outweigh these unpleasant side-effects.

Corticosteroids

Corticosteriods are now widely administered for prophylaxis against neonatal respiratory distress syndrome, a single course of betamethasone is given to women with a gestation of between 23 to 34 weeks. The course is administered as two intramuscular (I.M.) injections of 11.4 mg of betamethasone given 24 hours apart.5

While there is compelling evidence that antenatal corticosteroids improve neonatal outcomes when used before 34 weeks gestation, to date the evidence for the optimal drug, dose, route and timing remain unclear.

Antenatal corticosteroid use reduces neonatal death even when infants are born less than 24 hours after the first dose has been given.

The results from one small trial suggest that dexamethasone is more effective in reducing the rate of neonatal intraventricular hemorrhage when compared with betamethasone.

Therefore, should betamethasone be unavailable, clinicians may choose to use dexamethasone as an alternative. It is administered as 6mg I.M. every 12 hours for 4 doses.6

There is currently insufficient evidence regarding the potential risks and long-term effects to recommend the use of repeated doses of corticosteroids in clinical practice, and results from trials with long-term follow-up are required. If a repeat dose of antenatal corticosteroid is contemplated, then caution is advised and senior obstetric opinion should be sought.

If the original indication for the risk of a premature birth is resolved, or 34 weeks gestation is reached, then no further doses are required.

The results from the Australasian Collaborative Trial of Repeat Doses of Corticosteroids for the Prevention of Neonatal Respiratory Disease (ACTORDS) trial will further assist in guiding practice.7

Progesterone

There is currently insufficient evidence to recommend the use of progesterone in cases of preterm pre-labour ruptured membranes. The results of on-going clinical trials will assist in guiding practice.

Antibiotics for systemic infection

If there are signs of systemic infection or chorioamnionitis, the antibiotic treatment should be broad and given according to local protocols. There is no definitive drug or duration of treatment however, an example of a common treatment regimen is: amoxicillin or ampicillin 2 grams intravenously i.v. every 6 hours; plus

Gentamicin 4 to 6mg/kg I.V. for one dose then a maximum of one or two further doses, based on renal function; Plus Metronidazole 500 mg I.V. every 12 hours to provide additional anaerobic coverage.

In women allergic to penicillin, give: Clindamycin or Lincomycin 600mg I.V. every 8 hours.8

Co-amoxiclav should be avoided in women at risk of preterm delivery due to increased risk of neonatal necrotising enterocolitis.9

Prophylactic antibiotics for group b streptococcus (GBS)

If the woman is being treated for a systemic infection, the antibiotics prescribed should replace GBS-specific antibiotic prophylaxis.

If a woman’s GBS status is unknown the following risk factors for GBS infection should guide treatment with appropriate antibiotics.

  • previous infant with early-onset GBS disease
  • GBS bacteriuria in current pregnancy
  • prolonged rupture of membranes (an interval of 18 hours or more between rupture and birth)
  • preterm labour at less than 37 weeks of gestation
  • maternal temperature higher than 38 ̊C.

Antibiotics are not indicated in the following circumstances:

  • regardless of GBS status- antibiotics are unnecessary if the membranes are intact and providing there is no systemic infection or if labour is not established.
  • antibiotic prophylaxis for GBS is also unnecessary for women with preterm rupture of membranes unless she is in established labour.                                                                         

In the following circumstances, the woman should be offered prophylactic GBS antibiotic therapy:

  • when a women is known to have GBS on a mid stream urine test result or low vaginal anorectal swab, or had a previous baby with GBS disease, treatment should be commenced to avoid infection of the fetus, 
  • in established preterm labour with intact or ruptured membranes, in the presence of a positive GBS result.
  • in established preterm labour with intact or ruptured membranes, with a previous baby who had neonatal GBS disease.
  • in established preterm labour, with intact or ruptured membranes, if GBS has been present in the vagina or urine in the current pregnancy.
  • Penicillin 1.2g I.V. bolus followed by 600mg I.V. every 4 hours. If the woman is allergic to penicillin, give Clindamycin or Lincomycin 600mg  I.V. every 8 hours.

Magnesium sulphate for fetal neuroprotection

Although high-level evidence is limited regarding the use of magnesium sulphate as a neuroprotectant, recent meta-analyses have suggested that magnesium sulphate given before preterm birth may be neuroprotective for the fetus.10,11

Accordingly, irrespective of the number of babies in utero, the reason the woman is considered to be at risk of preterm birth, parity, the anticipated mode of birth and whether or not corticosteroids have been given, antenatal magnesium sulphate may be considered for use in women who are already in a hospital where neonatal facilities are appropriate for her gestation, who are at high risk of birth before 30 weeks gestation, or whose birth is planned or anticipated within 24 hours. It is not recommended that magnesium sulphate for neuroprotection is used for those women who are awaiting transfer or who are in transit to an appropriate hospital.

If it has been decided to give MgSo4 then the recommended dosing regimen is:

  • a 4g loading dose given intravenously, slowly over 20-30 minutes with 1 g/hour maintenance dose. This should be continued up until birth or for 24 hours, whichever comes first. If birth no longer appears to be imminent the infusion is stopped, but can be restarted as indicated.

While seldom reported in clinical practice, there is a potential interaction between magnesium sulphate (MgSO4) and nifedipine, resulting in hypotension and neuromuscular blockade effects. If severe hypotension occurs, nifedipine and MgSO4 administration should be ceased.

On-going management

Notify the neonatal team of the woman’s situation. If the woman is not already in a hospital that can provide neonatal services appropriate for her gestation, advice should be sought from the victorian perinatal emergency referral service on 1300137650

Contemporaneous documentation should be kept

Adequate communication with the woman and her family in a manner that they will understand.

Cerclage removal

The optimum time for cerclage removal is unclear and no controlled study has found that by retaining it after PPROM improves neonatal outcome. Early cerclage removal after PPROM may avoid risk for infection.1 However, it may be reasonable to leave a cerclage in situ until corticosteroids and antibiotics have been received and then remove it.

When the immediate assessment and management is complete, consider a transvaginal ultrasound examination for cervical length and assessment of fetal wellbeing, including biometry. If the fetus is found to be growth restricted, umbilical artery dopplers to assess fetal well-being can also be performed.

Expectant management

The woman and her family should be counseled regarding the risks and benefits of expectant versus active management.

A woman may be considered suitable for outpatient management by the by the obstetric team in limited situations, dependant upon her gestation and the fetal and maternal condition.

Following a 24-48 hour inpatient hospital stay, the decision is based on:

  • gestation of fetus and presentation
  • close accessibility to the hospital
  • no evidence of premature labour
  • no evidence or symptoms of infection
  • no maternal or fetal risk factors

On discharge from hospital, the woman should receive the following advice:

  • attend weekly outpatient assessment clinics
  • instructed to check her temperature 4 hourly. a demonstration should be provided prior to discharge including advice to notify the hospital if she notes any signs of infection, or her temperature is above 37 degrees celsius
  • wear sanitary pads not tampons and return to the hospital if she has ‘offensive smelling’ vaginal discharge, or abnormal appearance of vaginal discharge
  • avoid vaginal intercourse
  • encourage showers rather than baths and avoid swimming
  • monitor fetal movements and notify hospital if fetal movements are decreased
  • notify and return to the hospital if any signs of threatened premature labour, vaginal bleeding, or abdominal pain, tenderness occurs

There is no place for expectant management after 36 weeks gestation. 

Footnotes

1. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin Number 80 2007 Premature Rupture of Membranes. Obstetrics & Gynecology. 2007; 109(4):1007-19.

2. RCOG Guideline No. 44. Available from: www.rcog.org.uk/files/rcog-corp/uploaded-files/GT44PretermPrelabourRupture2006.pdf

3. Canavan TP, Simhan HN, Caritis S. An Evidence-Based Approach to the Evaluation and Treatment of Premature Rupture of Membranes: Part 1. Obstetric and Gynecological Survey. 2004;59(9):669-77.

4. King JF, Flenady V, Papatsonis D, Dekker G, Carbonne B. Calcium channel blockers for inhibiting preterm labour. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD002255. DOI: 10.1002/14651858.CD002255.

5. Brownfoot FC, Crowther CA, Middleton P. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD006764. DOI: 10.1002/14651858.CD006764.pub2

6. Elimian A, Antenatal betamethasone compared with dexamethasone (betacode trial): a randomized controlled trial. Obstet Gynecol. 2007 Jul;110(1):26-30.

7. Crowther CA, Doyle LW, Haslam RH, Hiller JE, Harding JE, Robinson JS for the Australasian Collaborative Trial of Repeat Doses of Steroids (ACTORDS) Study Group  Outcomes at Age 2 Years following a Randomized Trial of Repeat Doses of Antenatal Corticosteroids, N Engl J Med 2007;357:1179-89

8. Pelvic inflammatory disease: Severe infection [revised June 2010]. In: eTG complete [Internet]. Melbourne: Therapeutic Guidelines Limited; Accessed Feb. 2010 www.tg.org.au

9. Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochrane Database of Systematic Reviews 2010, Issue 8. Art. No.: CD001058. DOI: 10.1002/14651858.CD001058.pub2.

10. Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD004661. DOI: 10.1002/14651858.CD004661.pub3

11. The Antenatal Magnesium Sulphate for Neuroprotection Guideline Development Panel. Antenatal Magnesium Sulphate Prior to Preterm Birth for Neuroprotection of the Fetus, Infant and Child: National Clinical Practice Guidelines 2010 Feb. Available at: www.adelaide. edu.au/arch/antenatalMagnesium_SulphateGuidelines.pdf.

Appendix 1. Levels of evidence

ACOG

Studies were reviewed and evaluated for quality according to the method outlined by the U.S. Preventive Services Task Force:

I   Evidence obtained from at least one properly designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled trials without randomization.
II-2 Evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group.
II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments also could be regarded as this type of evidence.
III Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
Based on the highest level of evidence found in the data, recommendations are provided and graded according to the following categories:

Level A—Recommendations are based on good and consistent scientific evidence.
Level B—Recommendations are based on limited or inconsistent scientific evidence.
Level C—Recommendations are based primarily on consensus and expert opinion.

RCOG

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