Biomarker tests to help diagnose preterm labour in women with intact membranes

Preterm labour is defined as regular contractions of the uterus resulting in changes in the cervix that start before 37 weeks of pregnancy. Preterm labour and birth is fairly common in the UK, with 8% of babies born before 37 weeks of pregnancy. However, less than 1% of babies are born between 22 and 28 weeks of pregnancy (Royal College of Obstetricians and Gynaecologists 2014).

The World Health Organization defines preterm birth as:

• extremely preterm (less than 28 weeks of pregnancy)

• very preterm (28 to less than 32 weeks of pregnancy)

• moderate to late preterm (32 to less than 37 weeks of pregnancy).

Around 25% of preterm births are planned because of maternal factors such as pre‑eclampsia, or fetal factors such as extreme growth restriction. But most preterm births occur because labour starts early naturally. Known risk factors for preterm labour include:

• previous preterm delivery

• twins or other multiple pregnancies

• genital tract infections

• preterm premature rupture of membranes

• problems with the uterus, cervix or placenta

• some chronic conditions, such as high blood pressure and diabetes

• smoking or drug use

• being underweight or overweight before pregnancy and

• stressful life events.

The Department of Health and Social Care's toolkit for high-quality neonatal services (2009) describes 3 types of hospital units providing neonatal care for preterm babies:

• Special care units (level 1) provide special care for their local population, and may also provide some high dependency services.

• Local neonatal units (level 2) provide neonatal care for their local population, except for the sickest babies. Most babies born after 27 weeks of pregnancy will usually have full care, including short periods of intensive care, in their local neonatal unit.

• Neonatal intensive care units (level 3) are sited alongside specialist obstetric and fetomaternal medicine services. They provide the whole range of medical neonatal care for their local population, along with additional care for babies and their families referred from the neonatal network.

Clinical experts have noted that most babies born after 35 weeks of pregnancy will be looked after on postnatal wards with their mothers.

Preterm birth can potentially lead to short-term health problems in a newborn baby; for example, problems breathing and feeding, and higher risk of infection. The main concerns include:

• chronic lung disease at 36 weeks (corrected age)

• intraventricular haemorrhage

• necrotising enterocolitis

• retinopathy of prematurity.

Babies who are born early, particularly those born before 28 weeks of pregnancy, may have lifelong disabilities. These include physical disabilities, learning disabilities, behavioural problems, and visual and hearing problems.

NICE's guideline on preterm labour and birth states that women reporting symptoms of preterm labour who have intact membranes should have a clinical assessment.

If the clinical assessment suggests that the woman is in suspected preterm labour and she is 29 weeks plus 6 days pregnant or less, treatment for preterm labour is recommended.

Clinical experts have noted that, in practice, not all women in suspected preterm labour who are 29 weeks plus 6 days pregnant or less have treatment. They have stated that these women often have diagnostic testing because there are insufficient resources available to admit or transfer all women, there is concern about the effect of unnecessary treatment and women may prefer to avoid hospital admission and transfer when possible.

If the clinical assessment suggests that the woman is in suspected preterm labour and she is 30 weeks plus 0 days pregnant or more, transvaginal ultrasound measurement of cervical length should be considered to determine the likelihood of birth within 48 hours. If cervical length is more than 15 mm, it is unlikely that the woman is in preterm labour. If cervical length is 15 mm or less, preterm labour should be diagnosed and treatment offered.

NICE's guideline on preterm labour and birth notes that ultrasound scans should be done by healthcare professionals with training in, and experience of, transvaginal ultrasound measurement of cervical length. The guideline committee also noted that transvaginal ultrasound scanning is not routinely available across the NHS because equipment or expertise is limited, and that investment in technology and training may be needed for its universal implementation in the NHS. These limitations also increase the likelihood that biomarker testing will be carried out.

If transvaginal ultrasound measurement of cervical length is indicated but is not available or not acceptable, fetal fibronectin testing should be considered to determine the likelihood of birth within 48 hours for women who are 30 weeks plus 0 days pregnant or more. If the fetal fibronectin test result is negative (concentration 50 ng/ml or less), it is unlikely that the woman is in preterm labour. If the fetal fibronectin test result is positive (concentration more than 50 ng/ml), preterm labour should be diagnosed and treatment offered. NICE's guideline on preterm labour and birth notes that if fetal fibronectin testing is anticipated, the swab should be taken before any digital vaginal examination.

If a woman in suspected preterm labour who is 30 weeks plus 0 days pregnant or more does not have transvaginal ultrasound measurement of cervical length or fetal fibronectin testing to exclude preterm labour, treatment should be offered consistent with her being in diagnosed preterm labour.

A women in suspected preterm labour, but with a negative diagnostic test result suggesting that preterm labour is unlikely, may go home or may continue to be monitored and have treatment in hospital. If the woman goes home, she is advised to return to hospital if symptoms suggesting preterm labour persist or recur.

NICE's guideline on preterm labour and birth notes that transvaginal ultrasound measurement of cervical length and fetal fibronectin testing should not be used in combination to diagnose preterm labour.

The European Association of Perinatal Medicine's recommendations on preterm labour and birth management state that 2 methods can be used to improve the accuracy of the diagnosis of preterm labour in women with symptoms:

• transvaginal ultrasound cervical length measurement

• measurement of biochemical markers in cervical-vaginal secretions (fetal fibronectin or placental alpha macroglobulin‑1 [PAMG‑1] or insulin-like growth factor binding protein‑1 [IGFBP‑1]).