Preterm labour and birth

Single and repeat use of corticosteroids

One updated Cochrane review concluded that repeat courses of maternal corticosteroids were safe and effective for women in suspected preterm labour. The original review had already been considered during guideline development and a recommendation of "do not routinely offer repeat courses of maternal corticosteroids" was created. No topic experts had mentioned this area and NICE did not identify any further evidence during the surveillance review. Therefore, stakeholders were asked at consultation to specifically comment on the implementation of this recommendation in practice. Seven stakeholders confirmed that they believed the recommendation around repeat courses should remain because of the potential risk of harm to the fetus and mother. NICE did not find any evidence of harm during the surveillance review.

The Royal College of Obstetricians and Gynaecologists highlighted further evidence in the form of an individual participant data meta-analysis, which stated that prenatal corticosteroids given to women at ongoing risk of preterm birth after an initial course reduced the likelihood of their baby needing respiratory support after birth and led to neonatal benefits. Additionally, the World Health Organization now recommends repeat courses of maternal corticosteroids for women in suspected preterm labour based on the updated Cochrane review within this area. Therefore, in light of this new evidence, alongside the updated Cochrane review, we propose the guideline is updated to consider the safety and effectiveness of repeat courses of maternal corticosteroids.

Place of birth and transfer to centre with neonatal intensive care

During consultation, NICE asked stakeholders for a view on important gaps in the guideline. The main gap that 3 stakeholders raised was that it fails to highlight the recommended place of birth as an intervention to improve the outcome of preterm birth and the importance of in utero transfer during labour. The British Association of Perinatal Medicine (BAPM) guideline on perinatal management of extreme preterm birth before 27 weeks of gestation gives specific advice in this area. It is also stated in the UK Preterm Clinical Network guidelines for commissioners and providers on reducing preterm birth that it is now a priority NHS England recommendation for local maternity systems to take action to ensure that all women less than 27 weeks pregnant have their babies delivered in centres with a neonatal intensive care unit, and that local maternity systems and corresponding operational delivery networks have clear guidelines for antenatal transfer in the event of impending delivery at less than 27 weeks. NICE's guideline already mentions that clinicians should make an assessment on the need to transfer to another unit in recommendation 1.8.1. However, it is proposed that the recommendation should be refreshed to ensure that clinicians consider the NHS England guidance on saving babies' lives (version two): a care bundle for reducing perinatal mortality.

The use of antibiotics in preterm labour

Two stakeholders raised concerns around the 'treat all' approach with the use of antibiotics in preterm labour and noted that the guideline is not in line with current recommendations from the Royal College of Obstetricians and Gynaecologists Greentop guideline on prevention of early onset neonatal group B streptococcal disease. Recommendation 1.4.4 in NICE's guideline on preterm labour and birth refers to NICE's guideline on neonatal infection (early onset), which is currently being updated. The update is considering intrapartum antibiotics and maternal group B streptococcus status to guide the decision on timing of delivery in women with preterm prelabour rupture of membranes (P‑PROM). Therefore, when this guideline publishes (expected March 2021), we will consider any amendments that could affect NICE's guideline on preterm labour and birth and will update it accordingly.

The efficacy of progesterone

The guideline recommendations on the clinical effectiveness of prophylactic progesterone on the prevention of preterm labour were updated in 2019. The review considered all current evidence and concluded that progesterone is safe and effective to use to prevent preterm labour. Three randomised controlled trials (RCTs) were considered during the surveillance review. One of these did not fully complete. One RCT suggested that there was no difference between the 2 groups when using progesterone, and the results of 1 RCT indicated that progesterone could decrease preterm birth when combined with other treatments such as indomethacin and treatment of bacterial vaginosis. No evidence was found through the surveillance review to contradict current recommendations. Therefore, this area of the guideline will not be updated at this time.

Identifying women at high risk for premature labour (including the use of transvaginal ultrasound scans)

Two topic experts and 2 stakeholders suggested that more information should be given regarding screening for women at high risk of premature labour to align with other guidelines in this area, such as the NHS England guidance on saving babies' lives (version two): a care bundle for reducing perinatal mortality. Identifying women at high risk of premature labour is outside the scope of this guideline and is also considered further by the UK National Screening Committee. Recommendation 1.9.3.1 in the NICE guideline on antenatal care for uncomplicated pregnancies states that routine screening for preterm labour should not be offered. Therefore, the guideline will not be updated to include this area.

Diagnostic testing for women under 30 weeks' pregnancy

One topic expert and 4 stakeholders believed that diagnostic testing should be considered for women under 30 weeks' pregnancy and the UK Preterm Clinical Network guidelines for commissioners and providers on reducing preterm birth suggest that fetal fibronectin testing should be used from 18 weeks' pregnancy. However, NICE's diagnostics guidance on biomarker tests to help diagnose preterm labour in women with intact membranes and 1 Cochrane review found insufficient evidence to support the use of fetal fibronectin for diagnosing preterm labour. During development of the NICE guideline, it was noted that a 'treat all' approach for women under 30 weeks' pregnancy was more cost effective than diagnostic testing. Four stakeholders queried the 'treat all' approach for women under 30 weeks' pregnancy. No evidence was found through surveillance that showed that diagnostic testing would be more effective than a treat all approach in this population and therefore this area of the guideline will not be updated at this time.

Delivery (including mode of delivery, timing of delivery for women with P-PROM and delayed cord clamping)

No evidence was found through the surveillance review regarding mode of birth for women in preterm labour. A stakeholder suggested that caesarean section should not be considered first before vaginal breech delivery; however, the reasons for this were not given. NICE's guideline only recommends considering caesarean section for women presenting in suspected, diagnosed or established preterm labour between 26 weeks and 36 weeks of pregnancy with breech presentation and therefore no amendment to this area of the guideline is needed.

One topic expert requested further information around when women with P‑PROM should deliver. Limited evidence was found through the surveillance review regarding the impact on neonatal outcomes of immediate or expectant management of delivery for this population and therefore no change will be made to this area of the guideline at this time.

One stakeholder suggested that cord milking was not beneficial, and that cord clamping should only occur after the baby cries. One topic expert suggested that delayed cord clamping should have a firmer recommendation in the guideline. There is now a much larger amount of evidence to support the current recommendations that delayed cord clamping is more beneficial to the preterm baby than immediate clamping. The current recommendation is for at least 30 seconds but no longer than 3 minutes, within which time it is presumed a stable baby will cry. No studies were found through the surveillance review to indicate that delayed cord clamping was not beneficial and no studies compared delayed clamping of 30 seconds with delayed clamping of 3 minutes or under, and therefore it is suggested that the current recommendations do not need amending at this time. No evidence was found through the surveillance review to contradict NICE's current recommendations around cord milking and the study provided by the stakeholder to suggest cord milking was not beneficial was never completed. Therefore, this recommendation will not be amended at this time.

The effectiveness of tocolysis and nifedipine

Two stakeholders did not consider tocolysis, specifically the drug nifedipine, to be effective at improving neonatal outcomes in women in preterm labour. The UK Preterm Clinical Network guidelines for commissioners and providers on reducing preterm birth also do not consider tocolysis to be effective. Seven RCTs were found through the surveillance review, which considered the use of nifedipine. No studies were found that concluded that nifedipine was ineffective. In 2 RCTs, nifedipine was considered the safest drug when compared with ritodrine and magnesium sulfate.

Because of the lack of evidence to contradict the current recommendations and new evidence found that supports the current recommendation that tocolytics and nifedipine should be considered in women with suspected preterm labour, there will be no impact to this area of the guideline at this time.

For further details and a summary of all evidence identified in surveillance, see appendix A.