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Preterm labour is defined as regular uterine contractions occurring before 37 completed weeks of gestation, with or without cervical change. Preterm birth (PTB) — delivery before 37 weeks — is the leading cause of neonatal morbidity and mortality worldwide, responsible for approximately 70% of neonatal deaths and significant long-term neurodevelopmental disability including cerebral palsy, chronic lung disease, and cognitive impairment. Rates of preterm birth range from 5-7% in high-income countries to 15-18% in parts of sub-Saharan Africa and South Asia. Risk stratification tools identify women at highest risk who may benefit from preventive interventions. The most clinically validated predictors are: transvaginal ultrasound cervical length measurement — a cervical length below 25 mm at 16-24 weeks is associated with significantly elevated preterm birth risk, with women with a cervical length below 15 mm at 24 weeks having an approximately 80% rate of delivery before 32 weeks; and fetal fibronectin (fFN) assay — a protein found in the extracellular matrix at the choriodecidual interface, present in cervicovaginal secretions when the fetal membranes are beginning to detach. A positive fFN (>50 ng/mL or ≥200 ng/mL using quantitative assays) in women with symptoms of preterm labour predicts imminent preterm delivery with a positive likelihood ratio of approximately 5. The primary preventive intervention for identified high-risk women is vaginal progesterone (200 mg nightly) from 16-22 weeks, which reduces preterm birth risk by approximately 35% in women with a short cervix. Cervical cerclage is an option for women with cervical length below 25 mm in the context of a history of preterm birth or mid-trimester loss.
High risk: Cervical length ≤25 mm at 16-24 weeks; Very high risk: Cervical length ≤15 mm at 24 weeks (≈80% PTB <32 weeks); Positive fFN: >200 ng/mL (quantitative); fFN >50 ng/mL standard threshold; Prevention: vaginal progesterone 200 mg nightly from 16-22 weeks if CL ≤25 mm; Cerclage if CL <25 mm + history of PTB
- 1Assess clinical risk factors at booking: prior preterm birth (strongest predictor — 15-30% recurrence risk), prior second trimester loss, cervical surgery (LLETZ, cone biopsy), multiple pregnancy, uterine anomaly (bicornuate, septate), smoking, substance misuse, short interpregnancy interval, and low socioeconomic status.
- 2Offer transvaginal ultrasound (TVS) cervical length measurement at the anomaly scan (18-22 weeks) for all women with risk factors, or as part of universal screening programmes where adopted. Measure internal os to external os in the sagittal plane with the bladder empty, taking the shortest of three measurements.
- 3Classify cervical length risk: normal ≥25 mm; intermediate 20-24 mm (monitoring and progesterone consideration); short <25 mm (progesterone); very short <15 mm (progesterone + consider cerclage if risk factors).
- 4Perform fetal fibronectin (fFN) swab in women with symptoms of preterm labour (regular contractions, pelvic pressure) at 22-34 weeks with intact membranes and cervical dilation <3 cm. Collect from the posterior fornix before any digital examination. Result available in <30 minutes.
- 5Interpret fFN: negative (<50 ng/mL) = high negative predictive value for delivery within 7 days (>99% negative predictive value); positive (≥50 ng/mL or ≥200 ng/mL quantitative) = positive prediction of preterm delivery within 7-14 days is moderate.
- 6Initiate prevention for high-risk women: vaginal progesterone 200 mg (Cyclogest or equivalent) nightly from 16-22 weeks, continued to 34-36 weeks; cervical cerclage for women with cervical length <25 mm and a history of prior preterm birth or loss; and consider cervical pessary as an alternative to cerclage in some settings.
- 7When preterm labour is established or imminent: administer antenatal corticosteroids (betamethasone 12 mg IM × 2 doses 24 hours apart, or dexamethasone equivalent) before 34+6 weeks for fetal lung maturity; magnesium sulfate before 32 weeks for fetal neuroprotection; and consider tocolysis for 48 hours to complete the corticosteroid course.
Progesterone started immediately; serial CL monitoring every 2-4 weeks; fetal medicine review
Cervical length below 25 mm at 24 weeks in a low-risk patient is an indication for vaginal progesterone, which reduces preterm birth risk by approximately 35%. There is no additional benefit of cerclage in the absence of a prior preterm birth history.
Admit; corticosteroids; magnesium for neuroprotection; NICU alert; consider tocolysis for 48h
A quantitative fFN above 200 ng/mL combined with cervical change and regular contractions represents a true preterm labour. Corticosteroids and MgSO4 have the highest evidence base for improving neonatal outcomes at 29 weeks.
Safe to discharge; reassure; no tocolysis or corticosteroids needed; return if symptoms worsen
A negative fFN has excellent negative predictive value. Unnecessary hospitalisation, tocolysis, and steroid administration are avoided. The quantitative value of 14 ng/mL provides additional reassurance.
Progesterone concurrently; USS surveillance every 2 weeks; tocolysis not routinely given with cerclage
In a woman with a history of preterm birth or mid-trimester loss and a current short cervix (<25 mm), cerclage combined with progesterone reduces preterm birth risk more than progesterone alone. This combination represents evidence-based care for recurrent preterm risk.
Antenatal clinic: TVS cervical length at the anomaly scan (18-22 weeks) in women with prior preterm birth, enabling early progesterone or cerclage., where accurate preterm labour risk analysis through the Preterm Labour Risk supports evidence-based decision-making and quantitative rigor in professional workflows
Labour ward: fFN testing in women with threatened preterm labour to safely discharge those at low risk and target intensive care to those at genuine risk., where accurate preterm labour risk analysis through the Preterm Labour Risk supports evidence-based decision-making and quantitative rigor in professional workflows
Neonatology planning: predicting imminent preterm delivery allows NICU team preparation, parent counselling, and in-utero transfer to a centre with appropriate neonatal capability., where accurate preterm labour risk analysis through the Preterm Labour Risk supports evidence-based decision-making and quantitative rigor in professional workflows
Research: cervical length and fFN are primary surrogate endpoints in trials of new preterm birth prevention interventions including progesterone formulations, pessaries, and antibiotics., where accurate preterm labour risk analysis through the Preterm Labour Risk supports evidence-based decision-making and quantitative rigor in professional workflows
Global health: preterm birth prevention strategies in low-resource settings focus on identifying and treating infection (including bacterial vaginosis), providing tocolysis, and deploying corticosteroids when affordable.
Multiple Pregnancy
Preterm birth is much more common in twin and higher-order pregnancies (approximately 50% of twins deliver before 37 weeks). Progesterone does not reduce preterm birth in unselected multiple pregnancies without a short cervix. Cervical cerclage may increase PTB risk in multiples. Management focuses on antenatal surveillance and corticosteroids when delivery is imminent. NICE does not recommend routine progesterone for twins.
PPROM (Preterm Premature Rupture of Membranes)
PPROM (rupture of membranes before 37 weeks without labour) is a distinct condition from preterm labour. Management includes: expectant management below 34 weeks with antibiotic prophylaxis (erythromycin for 10 days, ORACLE trial); antenatal corticosteroids; magnesium for neuroprotection below 32 weeks; and delivery at 34-37 weeks depending on gestational age and clinical status. fFN is not diagnostic after rupture of membranes.
Previous Preterm Birth
A single prior preterm birth carries a 15-30% recurrence risk in the next pregnancy. These women should be offered proactive cerclage (history-indicated cerclage) from 12-14 weeks if they have had ≥3 prior mid-trimester losses or preterm births, or ultrasound-indicated cerclage and progesterone if cervical length falls below 25 mm at surveillance scans. Pre-conception planning with a specialist obstetric team is strongly recommended.
Tocolysis Controversies
Tocolysis (uterine relaxation drugs: nifedipine, atosiban, terbutaline, indomethacin) is used to delay delivery by 48 hours to administer corticosteroids, not to prevent preterm birth long-term. Long-term tocolysis does not improve outcomes and carries maternal and fetal risks. NICE recommends nifedipine or atosiban as first-line tocolytic agents. Beta-agonists (ritodrine, terbutaline) are no longer recommended due to maternal cardiovascular side effects.
| Cervical Length (mm) | Risk | Action |
|---|---|---|
| ≥30 mm | Low risk | Routine monitoring; reassure |
| 25-29 mm | Borderline — watch | Consider progesterone; repeat CL in 2 weeks |
| 20-24 mm | Elevated risk | Progesterone 200 mg nightly; serial CL; fetal medicine review |
| 15-19 mm | High risk | Progesterone + consider cerclage if prior PTB; close monitoring |
| <15 mm | Very high risk | Progesterone + cerclage if prior PTB/loss; NICU alert; corticosteroids if delivery imminent |
What cervical length is considered high risk for preterm birth?
A cervical length below 25 mm at 16-24 weeks is the commonly used high-risk threshold. Risk increases progressively as cervical length decreases: below 20 mm indicates very high risk, and below 15 mm at 24 weeks is associated with approximately 80% delivery before 32 weeks in symptomatic women. This is particularly important in the context of preterm labour risk calculations, where accuracy directly impacts decision-making. Professionals across multiple industries rely on precise preterm labour risk computations to validate assumptions, optimize processes, and ensure compliance with applicable standards. Understanding the underlying methodology helps users interpret results correctly and identify when additional analysis may be warranted.
How does vaginal progesterone prevent preterm birth?
Vaginal progesterone (200 mg nightly, or 90 mg gel) maintains cervical integrity and reduces inflammatory and contractile signals at the choriodecidual interface. Pooled meta-analyses show it reduces preterm birth before 33 weeks by approximately 35% in women with singleton pregnancies and a short cervix. It is ineffective in multiple pregnancy without a short cervix.
What is fetal fibronectin and how does it work as a test?
Fetal fibronectin (fFN) is a protein found in the extracellular matrix at the junction between the fetal membranes and the decidua. Normally, this matrix is intact and fFN is absent from cervicovaginal secretions between 22 and 34 weeks. Its presence indicates disruption of the choriodecidual interface — an early sign of membrane detachment and preterm labour. Negative fFN has excellent NPV (>99%) for ruling out delivery within 7 days.
What is the difference between preterm labour and threatened preterm labour?
Threatened preterm labour is the clinical presentation of contractions before 37 weeks without confirmed cervical dilation or effacement. Many women presenting with this diagnosis do not deliver preterm — the false positive rate is high. Confirmed preterm labour involves regular contractions with documented cervical change (effacement or dilation ≥2 cm). fFN and cervical length help distinguish the two.
When are antenatal corticosteroids given?
Antenatal corticosteroids (betamethasone 12 mg IM, two doses 24 hours apart) are indicated at 23+0 to 34+6 weeks when preterm delivery is anticipated within 7 days. They mature the fetal lung surfactant system, reducing respiratory distress syndrome, intraventricular haemorrhage, and neonatal death. A single rescue course can be considered after 7 days if the original course was given before 28 weeks and delivery risk persists.
Can cerclage prevent preterm birth in all women?
No. Cerclage is effective for women with a short cervix (CL <25 mm) in the context of a prior preterm birth or mid-trimester loss. It is not effective in unselected populations without prior risk, in multiple pregnancy without prior preterm birth, or for preterm premature rupture of membranes (PPROM). Inappropriate cerclage in low-risk women may increase infection risk without benefit.
What is the cervical pessary?
The Arabin pessary is a silicone ring inserted vaginally to encircle and support the cervix, changing the cervicovaginal angle to reduce amniotic fluid pressure on the cervix. It is a non-surgical alternative to cerclage for women with a short cervix. Evidence from large trials is mixed — some show benefit in selected populations (singleton, short cervix without prior PTB), while others show no effect. Research is ongoing.
What is magnesium sulfate used for in threatened preterm birth?
Magnesium sulfate is given for fetal neuroprotection before 32 weeks (some guidelines extend to 33+6 weeks) when preterm delivery is expected within 24 hours. It reduces the risk of cerebral palsy in surviving preterm infants by approximately 30%. The loading dose (4g IV) and maintenance (1g/hour) are the same as for pre-eclampsia, but the indication differs.
Pro Tips
For women presenting with threatened preterm labour at 22-34 weeks, a negative quantitative fFN (below 10 ng/mL) is more reassuring than a standard negative threshold (below 50 ng/mL), with a negative predictive value approaching 99.5% for delivery within 7 days. Use the quantitative result where available to confidently discharge low-risk women and avoid unnecessary admissions.
Visste du?
The observation that a short cervix predicts preterm birth was first systematically described by Joann Sonek and colleagues in the early 1990s, followed by the landmark study by Ian Crane and colleagues and the large prospective study by Jay Iams in the NICHD Network published in NEJM in 1996. Iams's study of over 2,900 women at 24 weeks showed a clear inverse relationship between cervical length and preterm birth risk, establishing the 25 mm threshold that remains in clinical use today — a founding study in the modern era of preterm birth risk prediction.
Referanser
- ›Iams JD et al. The length of the cervix and the risk of spontaneous premature delivery. NEJM 1996.
- ›Romero R et al. Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix. Am J Obstet Gynecol 2018.
- ›NICE Guideline NG25 — Preterm labour and birth. 2015 (updated 2022).
- ›Feinberg RF et al. Evaluation of oncofetal fibronectin as a marker of preterm delivery. Obstet Gynecol 1992.
- ›Berghella V et al. Cervical length screening for prevention of preterm birth. Obstet Gynecol 2007.