In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice in the original guideline document.
Classification of evidence levels (1++ to 4) and grades of recommendations (A–D) are defined at the end of the "Major Recommendations" field.
Uses of Tocolysis for Women in Preterm Labour
Does Tocolysis Prevent Preterm Birth?
A - There is no clear evidence that tocolytic drugs improve outcome and therefore it is reasonable not to use them. However, tocolysis should be considered if the few days gained would be put to good use, such as completing a course of corticosteroids or in utero transfer.
Does the Use of Any Tocolytic Drug Prevent Perinatal or Neonatal Death and Neonatal Morbidity?
A - Use of a tocolytic drug is not associated with a clear reduction in perinatal or neonatal mortality, or neonatal morbidity.
When Should Tocolytic Drugs Be Used?
B - Tocolysis may be considered for women with suspected preterm labour who have had an otherwise uncomplicated pregnancy. It is reasonable not to use any tocolytic drug.
Is One Tocolytic Drug More Effective in Preventing Preterm Birth Than Another?
A - Nifedipine and atosiban have comparable effectiveness in delaying birth for up to seven days.
A - Compared with beta-agonists, nifedipine is associated with improvement in neonatal outcome, although there are no long-term data.
What Are the Comparative Adverse Effects for the Woman of Alternative Tocolytic Drugs for Preterm Labour?
A - Beta-agonists have a high frequency of adverse effects. Nifedipine, atosiban and the cyclo-oxygenase (COX) inhibitors have fewer types of adverse effects, and they occur less frequently than for beta-agonists but how they compare with each other is unclear.
B - Using multiple tocolytic drugs appears to be associated with a higher risk of adverse effects and so should be avoided.
What Are the Comparative Effects for the Baby of Alternative Tocolytic Drugs for Preterm Labour?
B - The comparative effects for the baby of alternative drugs are unclear. Most drugs have been compared with beta-agonists. There are insufficient data on long-term follow-up for reliable conclusions about the effects on the baby for any of these tocolytic drugs.
Is Maintenance Tocolytic Therapy Worthwhile?
A - There is insufficient evidence for any firm conclusions about whether or not maintenance tocolytic therapy following threatened preterm labour is worthwhile. Thus, maintenance therapy is not recommended.
Use of a tocolytic drug is not associated with a clear reduction in perinatal or neonatal mortality or neonatal morbidity. The main effect of tocolytic drugs when used for women in preterm labour is to reduce the numbers who deliver within 48 hours or within 7 days of commencing the drug. Data on long-term outcome are sparse. It remains plausible that, for selected women, such as those who require transfer for neonatal care or time to complete a course of corticosteroids, there may be benefit associated with tocolysis. However, this benefit has not been formally evaluated in randomised trials.
If reliable prediction of which women in suspected preterm labour are likely to have a preterm birth were possible, the use of tocolysis could be reserved for these women. Unfortunately, few tests offer useful predictive value. Fetal fibronectin has been advocated as a promising predictive test but it may have limited accuracy in predicting preterm birth within 7 days for women with symptoms of preterm labour. Ultrasound assessment of cervical length is also a promising predictive test for symptomatic women. It remains unclear whether any predictive test, or combination of tests, is sufficiently accurate to be cost effective.
If the decision is made to use a tocolytic drug, nifedipine and atosiban appear to have comparable effectiveness in delaying delivery, with fewer maternal adverse effects and less risk of rare serious adverse events than alternatives such as ritodrine or indomethacin. There is limited evidence that use of nifedipine, rather than a beta-agonist, is associated with improved short-term neonatal outcome. There is little information about the long-term growth and development of the child for any of the drugs.
Ritodrine and atosiban are licensed in the UK for the treatment of threatened preterm labour. Although the use of nifedipine for preterm labour is an unlicensed indication, it has the advantages of oral administration and a low purchase price.
The available evidence should be discussed with the woman and her partner and their preferences taken into account in determining her care.
Grades of Recommendation
A - At least one meta-analysis, systematic review or randomised controlled trial rated as 1++ and directly applicable to the target population; or
A systematic review of randomised controlled trials or a body of evidence consisting principally of studies rated as 1+ directly applicable to the target population and demonstrating overall consistency of results
B - A body of evidence including studies rated as 2++ directly applicable to the target population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
C - A body of evidence including studies rated as 2+ directly applicable to the target population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
D - Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
Classification of Evidence Levels
1++ High-quality meta-analyses, systematic review of randomised controlled trials or randomised controlled trials with a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a low risk of bias
1- Meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a high risk of bias
2++ High-quality systematic reviews of case–control or cohort studies or high quality case–control or cohort studies with a very low risk of confounding, bias or chance and a high probability that the relationship is causal
2+ Well-conducted case–control or cohort studies with a low risk of confounding, bias or chance and a moderate probability that the relationship is causal
2- Case–control or cohort studies with a high risk of confounding, bias or chance and a significant risk that the relationship is not causal
3 Non-analytical studies, e.g., case reports, case series
4 Expert opinion
Good Practice Point - Recommended best practice based on the clinical experience of the guideline development group