(Preterm contractions without rupture of membranes)
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Objective
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The evidence available shows that, when faced with possible pre-term labour, the aims of treatment should be to establish effective suppression of labour with tocolytic therapy (unless contra-indicated) prior to 34 weeks gestation without undue delay in order to postpone delivery of the fetus for at least 48 hours whilst steroids are given to accelerate fetal lung maturation and consideration is given to transport to a hospital with appropriate neonatal care facilities. There is no evidence-base for tocolytic therapy being employed for longer than 48 hours or at a gestation greater than 34 weeks.
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Principles of management
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Diagnosis:
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- Labour is diagnosed on the basis of regular contractions (at least one per ten minutes) which are associated with effacement and/or dilatation of the cervix.
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- Maternal anxiety often causes difficulty with the diagnosis.
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- The absence of fetal fibronectin (fFN) in the cervical secretions is a very useful negative predictor of imminent birth (negative predictive value for delivery within 7 days 97-98%)[level I and III evidence].1,2
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- The absence of cervical changes does not mean that the patient's complaints of pain or the possibility that she is in early labour may be ignored.
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Selection of women for tocolytic therapy:
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The best results in postponing delivery are obtained in patients who have intact membranes and who are less than 5 cm dilated. However, ruptured membranes or excess dilatation are not absolute contraindications to treatment. Fetal factors such as chorioamnionitis, known group B Streptococcus carrier status, antepartum haemorrhage and intrauterine growth restriction may make delay unwise.
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The decision will fall into one of four categories:
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- Delivery is required immediately or soon because of maternal or fetal condition.
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- Labour is too far advanced to attempt suppression.
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- The fetus is sufficiently mature that the risks of suppression therapy outweighs benefits to the fetus (>34 weeks gestation).
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- Efforts should be made to defer delivery to improve the outcome for the fetus.
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Women who fall into category 2 or 3 should be managed as per the local guidelines for the management of normal labour, and those in category 1 should be managed according to the needs of the clinical condition requiring urgent delivery. These clinical guidelines apply to women in category 4
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Management details
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Admission and investigation:
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On admission , thorough assessment of the patient should include:
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History: particularly relating to rupture of the membranes and antepartum haemorrhage. Gestational age must be confirmed by the best available information regarding menstrual history and any available previous ultrasound data.
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Examination: noting particularly temperature, uterine tone and tenderness, liquor volume and fetal size and presentation.
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Vaginal examination: a speculum examination should be performed with full aseptic technique, not touching the cervix with the speculum, and cervical swabs taken for bacteriological assessment. If the cervix is closed and there is no blood or amniotic fluid to be seen in the vagina, and intercourse has not occurred within the previous 24 hours, a fetal fibronection (fFN) test should be performed. Digital examination should be avoided unless there is a significant possibility of a cord presentation or prolapse, or the cervix cannot be adequately visualised.
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Urine microbiology: if a mid-stream urine is unsatisfactory a catheter specimen of urine should be obtained for microscopy and culture.
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Ultrasound: (if available) - this may assist with assessment of presentation, gestation, fetal weight, and fetal normality.
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Cardiotocography (CTG): should be performed to assess fetal wellbeing.
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Amniocentesis: this investigation may be appropriate to assess the presence or absence of intra-amniotic sepsis, or (rarely) to assess fetal lung maturity. The use of this investigation should only be undertaken by individuals highly experienced in the invasive ultrasound procedures undertaken in level III units.
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In-utero fetal transfer:
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If the patient is admitted to a hospital that does not have a level III neonatal intensive care unit and the gestation is less than 34 weeks, consideration should be given to her transfer to a tertiary obstetric/neonatal hospital. There is clear evidence that neonatal outcomes are best if a significantly preterm infant is born in the hospital which provides the appropriate level of neonatal care, when compared with infants requiring transfer after birth.
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In-utero transfer should not, however, be undertaken if there is significant risk of birth occurring during transfer. Decisions regarding transfer need to be made with an awareness of the risks of neonatal morbidity and mortality at the gestation involved both at the initial admission hospital and at the proposed receiving hospital.
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Ruptured membranes:
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If there is evidence of ruptured membranes, continue as per the guidelines for premature rupture of membranes. If the gestation is greater than 34 weeks labour should be managed as per local guidelines for management of non-preterm labour.
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Maternal fever:
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Any maternal temperature of 37.20C or more MUST lead to formal review of the patient and of the treatment plan.
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No cervical change:
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If the cervix appears closed and uneffaced, there is no evidence of ruptured membranes, and the fetal fibronectin test (fFN) is negative, administer 100 mg to 150 mg Pethidine intramuscularly and reassess the patient within two hours. If contractions persist, then consider treating as below.
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Cervical change:
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If cervical changes are obvious tocolysis should be commenced, unless contraindicated because of abnormalities in maternal or fetal condition (eg. antepartum haemorrhage, pre-eclampsia, choroamnionitis, fetal distress) or because of imminent birth (see below). Cortico-steroids should be given to accelerate lung maturation and to decrease the risk of neonatal intracerebral haemorrhage and necrotising enterocolitis (see below). Antibiotics should also be considered (see below). There is no indication to continue tocolysis of any type after 48 hours.
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After cessation of contractions the patient should continue to be observed in a high dependency situation for 6 - 12 hours. If not already performed, an ultrasound (as mentioned above) should be obtained within 24 hours.
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Administration of Corticosteroids
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Two doses of Betamethasone 11.4 mg are given intramuscularly 24 hours apart, for prophylaxis against neonatal respiratory distress syndrome. Rarely, this may be contraindicated by the suspicion of sepsis or by the presence of unstable maternal Diabetes mellitus.
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Antibiotic therapy
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If progressive labour occurs Group B Streptococcus antibiotic prophylaxis should be prescribed (IVI Penicillin or, if a Penicillin sensitivity is known to exist, Cephazolin (women not at high-risk of anaphylaxis) or Vancomycin (women with a definite history of immediate hypersensitivity reactions).
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If evidence of urinary tract sepsis is seen on urine microscopy Cephalexin 250mg 6 hourly or Nitrofurantoin (Macrodantin) 50mg 6 hourly should be prescribed. If the patient is "toxic" Gentamycin 5mg/kg/day as a daily dose or Ceftriaxone 1g should be administered IV.
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Administration of Tocolytic Therapy
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Nifedipine:
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Unless contra-indicated, the first line tocolytic to be used should be Nifedipine [level I evidence].3 Nifedipine is a calcium channel blocker that inhibits both prostaglandin - and oxytocin-induced contractions. It has similar tocolytic activity to beta-mimetic drugs such as salbutamol but a lower incidence of maternal side effects. Fetal and neonatal outcomes are significantly improved when nifedipine is compared with salbutamol, with lower rates of respiratory distress syndrome, intracranial haemorrhage and perinatal mortality. Contraindications to the use of nifedipine include:
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1. Cardiac disease including cardiac conduction defects and left ventricular failure.
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2. Hypotension.
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3. Nifedipine should not be used concomitantly with beta-mimetic drugs such as salbutamol
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4. Concomitant us of magnesium sulphate - this is not an absolute contraindication but care must be taken since hypotension may result. A patient being treated with nifedipine should not be given a bolus of magnesium sulphate.
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Salbutamol:
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Salbutamol may be used as a second line tocolytic, in the absence of contraindications. It must not be used in addition to Nifedipine, as the two drugs have potentially synergistic actions. Salbutamol should be used with care as it is associated with maternal tachycardia, hypotension, tremor, pulmonary oedema, hyperglycaemia and hypokalaemia. Salbutamol is contra-indicated in the presence of:
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- Maternal or fetal cardiac disease
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- Insulin dependent diabetes
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Glyceryl Trinitrate (GTN):
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Glyceryl Trinitrate (GTN) is a nitric oxide donor and causes smooth muscle relaxation via the metabolite nitric oxide (NO) which acts as a second messenger to increase Calcium ion uptake. Nitric oxide promotes uterine quiescence in pregnancy; current evidence does not support the routine administration of nitric oxide donors in the treatment of threatened preterm labour [level III evidence]4. Peak action occurs 1-2 hours after application. It acts as a vasodilator. GTN patches provide continuous plasma nitrate concentration up to 24 hours.
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Tocolytic drug administration details
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Administration of Nifedipine:
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Dosage
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Nifedipine 20mg orally statum, followed by 20mg orally after 30 minutes if contractions persist, followed by a further 20mg orally after 30 minutes if contractions persist (not slow release nifedipine). The first tablet should be chewed and taken with orange juice to aid rapid absorption. If blood pressure is stable a maintenance dose of 20mg three times daily is continued for 48 hours. Note: Maximum dose is 120mg per day
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Precautions
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1. IV is inserted and baseline electrolytes, urea and creatine and LFT levels measured
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2. Half hourly maternal pulse, BP, respiratory rate. Maternal hypotension should be treated with IV fluids in the first instance.
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3. Continuous electronic fetal heart rate monitoring until contractions have settled.
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4. Cardiovascular examination including auscultation of lung bases every 8 hours for first 24 hour of therapy.
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Action
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Onset of tocolysis is at 30-60 minutes and institution of second line tocolysis should not be considered in the first 2 hours. If contractions do not abate after this time a second line tocolytic may be considered.
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Side effects of Nifedipine
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- Hypotension - this is unusual in normotensive patients
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- Increase in liver enzymes
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Contraindications to Nifedipine
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- Cardiac disease including cardiac conduction defects and left ventricular failure.
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Administration of Salbutamol:
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Dosage
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If salbutamol is to be used for tocolysis, one 5mg (5ml ampoule) is added to 100ml of normal saline to produce a 50 mcg/ml solution. An IV infusion pump must be used for administration.
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Following the establishment of intravenous access, the salbutamol infusion is commenced at 12 mls/hour (10 mcg/minute) and increased by 4 mls/hour (3.3 mcg/minute) every 30 minutes until the contractions cease, or the maternal pulse rate reaches 120 beats/minute or the infusion rate reaches 36 mls/hour (30 mcg/minute) maximum.
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Precautions
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- Baseline electrolytes, urea and creatinine before commencement of infusion; repeat as necessary if abnormal.
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- Baseline maternal blood sugar level; repeat 4 hourly if abnormal
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- Cardiovascular examination including auscultation of lung bases every 8 hours
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- No additional intravenous fluids to avoid fluid overload
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- Half hourly maternal pulse, BP and respiratory rate
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 | - Reduce infusion if maternal pulse >120bpm
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- Baseline electronic fetal heart rate monitoring
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- Do not exceed 48 hours of salbutamol therapy. Only in exceptional circumstances should treatment be continued for more than 24 hours.
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Side effects of Salbutamol
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- Pulmonary oedema and cardiac failure
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Contraindications to Salbutamol
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- Maternal or fetal cardiac disease
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- Insulin dependent diabetes
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Administration of Glyceryl Trinitrate (GTN):
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Dosage
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Apply 5-10mg transdermal GTN patch to abdominal skin, and repeat dose in 1 hour if contractions persist (maximum dose 20mg in 24 hours)
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Side effects
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- ? alteration in uterine blood flow.
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References
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- Honest H, Bachmann LM, Gupta JK, Kleijnen J, Khan KS. Accuracy of cervicovaginal fetal fibronectin test in predicting risk of spontaneous preterm birth: systematic review. BMJ. 2002; 325(7359): 289-290.
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- Watson DL, Kim SJ, Humphrey MD. Study of cervicovaginal fetal fibronectin status to guide treatment of threatened preterm labour. Aust N Z J Obstet Gynaecol. 1998; 38: 185-187
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- King JF, Flenady VJ, Papatsonis DNM, Dekker GA, Carbonne B. Calcium channel blockers for inhibiting preterm labour (Cochrane Review). In: The Cochrane Library, Issue 1 2003. Oxford: Update Software.
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- K Duckitt, S Thornton. Nitric oxide donors for the treatment of preterm labour (Cochrane Review). In: The Cochrane Library, Issue 1, 2003. Oxford: Update Software.
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