Approach
Labour is diagnosed by regular cervical contractions resulting in cervical change or dilation. However, in premature labour, once these have occurred the opportunity to intervene is limited. Management may therefore be instigated before confirmation of labour. Threatened premature labour (TPTL) refers to those women who present with preterm uterine contractions but without cervical effacement or dilation.
Diagnosis of premature labour involves establishing the likelihood of delivery, determining fetal well-being with a non-stress cardiotocogram (CTG), and looking for an underlying cause such as placental abruption or infection. One third of women who deliver preterm will present with preterm prelabour rupture of membranes (PPROM). Making a diagnosis of labour on a single examination is unreliable. However, frequent uterine contraction, a positive fetal fibronectin test, cervical dilation to >3 cm, and ruptured membranes all increase the likelihood that labour has started.
A number of biochemical tests are available to predict the likelihood of premature labour, including insulin-like growth factor binding protein-1 (IGFBP-1) and fetal fibronectin. A positive fetal fibronectin test result will increase risk of preterm birth about four-fold, while a negative test result will reduce the risk by 70%.[89] Combining cervical ultrasound and fetal fibronectin gives the best prediction of preterm birth.[28]
A calculator for preterm risk incorporating quantitative fetal fibronectin and cervical length, along with clinical history, is available as an app.[90][91]
History and systemic examination
There are no specific thresholds at which the frequency of contractions becomes significant; even regular contractions are not associated with labour in most cases. Uterine tightening is a normal physiological finding, and perception is highly variable. However, the more symptomatic and more frequent the contractions, the more likely they will lead to delivery. Although they cannot be relied upon to positively predict labour, contraction frequencies of >1 in 10 minutes are less likely to be physiological Braxton-Hicks contractions.
Atypical presentations may include non-specific abdominal or back pain. Vaginal bleeding may indicate antepartum haemorrhage due to a placental abruption. It is usually associated with pain and uterine contractions. Systemic fever of any cause, including malaria and listeriosis, can cause premature labour. Maternal or fetal heart rate may increase in response to infection.
History of a previous preterm birth may be present, and this increases the risk of subsequent preterm births even if the first was medically induced. Women who have had induced abortions have an increased risk of premature labour even after a single procedure, and risks increase with subsequent and later procedures.[27] However, the majority of women will not have a history of preterm birth.[17][41]
There may be a history of previous surgery for cervical intra-epithelial neoplasia. Minor ablative procedures such as cryotherapy or laser may not be significant, but most other procedures, including large loop excisions, and particularly cold knife conisation, are associated with increased risk.[23]
About 60% of twins are born preterm, and 19.5% are born before 34 weeks’ gestation.[34] Nearly all triplet and higher-order multiple pregnancies are preterm. Women with a history of recurrent or concurrent urinary tract infections, including asymptomatic bacteriuria, may have an increased risk of premature labour. If treated, the risk of pyelonephritis, preterm birth, and low birth weight is reduced.[13]
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Bacterial vaginosis, particularly in early pregnancy, is associated with higher rates of spontaneous premature labour; however, treatment does not alter this risk.[14][15][16]
A complete family and social history will help identify other risk factors such as poor nutrition, cigarette smoking, single marital status, coffee consumption, use of recreational drugs and alcohol, and poor dental hygiene.[18][19][30] Domestic violence is associated with premature labour, and this is prevalent across all social groups.[22] A higher proportion of premature deliveries occur in women of black ethnicity.[6]
Initial assessment
An initial step to establish well-being of the fetus is a non-stress CTG, and tocography can be used to document the frequency of contractions on a trace. Contraction frequency of >1 every 10 minutes is significant, and premature labour may be more likely.
Serial digital vaginal examination/transvaginal ultrasound of the cervix will confirm whether there is progressive change in association with uterine contractions. In women with PPROM, a digital examination should be avoided unless the likelihood of labour is high, as this has been linked to a reduced latency period from PPROM to delivery.[92] Advanced cervical dilation (>3 cm) or PPROM in association with contractions makes premature labour highly likely. A closed cervix and contractions prior to 37 weeks' gestation is consistent with TPTL.
Absence of fetal breathing movements can indicate an increased risk of delivery. This diagnostic indicator compares favourably to biochemical tests.[93] However, it requires skilled clinicians and takes time, and therefore has not been widely adopted.
Preterm prelabour rupture of membranes (PPROM)
PPROM is a clinical diagnosis, made on a history suggestive of leaking liquor, and confirmed by a sterile speculum examination revealing a pool of fluid in the posterior fornix. If amniotic fluid is not observed, an IGFBP-1 or a placental alpha microglobulin-1 (PAMG-1) test can be used to guide management.[73][94] In women with PPROM, a digital examination should be avoided unless the likelihood of labour is high, as this has been linked to a reduced latency period from PPROM to delivery.[92] Confirmatory tests, such as a nitrazine test, are not routinely necessary. The National Institute for Health and Care Excellence (NICE) recommends against using nitrazine to diagnose PPROM.[73]
Microscopy of vaginal fluid may reveal amniotic fluid that crystallises and may leave a fern-leaf pattern. False negatives are common. Ultrasound examination is useful in confirming the diagnosis, and the amount of liquor found negatively correlates with infectious morbidity. The more liquor left, the lower the likelihood of infection, as the liquor has bacteriostatic properties.
Investigations to predict premature labour
Cervical length
Cervical length measured by transvaginal ultrasound can indicate the likelihood of imminent delivery, as cervical lengths <2 cm are associated with much higher risks of delivery (>60%).[55] However, routine assessment of cervical length is not common practice and has not demonstrated improved outcomes, although research is limited.[95]
Fetal fibronectin
This is detected in cervico-vaginal secretions and can be used to predict spontaneous birth after 24 weeks' gestation in women with and without symptoms. All women presenting with preterm contractions between 24 and 35 weeks' gestation, who are not in advanced labour (cervical dilation <3 cm), should have a cervico-vaginal swab for fetal fibronectin. Positive prediction is not high (<50%), but the negative prediction of the test is good. False positives can occur in the presence of vaginal bleeding, cervical cerclage, and cervical manipulation.
In women presenting with symptoms of premature labour, about 5% delivered within 1 week of presentation; however, 20% of those with a positive fibronectin test delivered within 1 week compared with only 1% with a negative test.[96] In utero transfer to appropriate neonatal facilities and antenatal corticosteroids can be considered on the basis of this test.[97] Some studies have suggested that knowledge of fetal fibronectin may even reduce the incidence of preterm birth through targeting interventions more appropriately.[98]
Although fetal fibronectin is often used as a binary test, a quantitative approach may improve diagnostic accuracy.[50]
The predictive ability of these tests can be enhanced in combination, although they are not valid with advanced dilation of the cervix (>3 cm) or if membranes have ruptured. By combining quantitative fetal fibronectin with cervical length in women who present with threatened premature labour, the likelihood of delivery in 7 days can be more accurately discriminated.[99][100] An app is available for predicting individualised risk of spontaneous preterm delivery using maternal history and quantitative fetal fibronectin or ultrasound-derived transvaginal cervical length.[101] BAPM: QUiPP app toolkit Opens in new window
Insulin-like growth factor binding protein-1 (IGFBP-1) test
The IGFBP-1 test is a bedside immunochromatographical dipstick test that detects the presence of the phosphorylated form of IGFBP-1 in cervical secretions. A positive test result is shown as two blue lines - a control line and a test line in the result area. If only the control line has appeared after 5 minutes, the test result is negative. It has also been used to confirm PPROM with sensitivities of over 90% and specificities over 98%.[102] This test is unavailable in the US.
Placental alpha microglobulin-1 (PAMG-1) test
The PAMG-1 test may be used to determine the risk of delivery in women with threatened preterm labour who have intact membranes.[103] The test is performed by taking a low vaginal swab and inserting the test strip into a small tube that indicates a positive or negative result.
However, the UK National Institute for Health and Care Excellence recommends that there is insufficient evidence for routine use of IGFBP-1 or PAMG-1 to diagnose premature labour in women with intact membranes.[104] Guidance from NHS England recommends fetal fibronectin as it can be used in asymptomatic women and has better sensitivity than alternatives.[105]
Identifying a cause of premature labour
It is important to identify infection as a possible cause of premature labour, but also as a consequence with important management implications. Women who present with TPTL should have a urinalysis for proteinuria, leukocytes, and nitrites and, if positive, a midstream urine for microscopy, culture, and sensitivities. A high vaginal and rectal swab can be taken to screen for group B streptococcus.[106] Signs of chorio-amnionitis should be judiciously sought, including maternal temperature, maternal and fetal heart rate, and any elevation in inflammatory markers (white blood cell count and C-reactive protein).
A positive Kleihauer test, a blood test evaluated in the laboratory for the presence of fetal cells, may indicate retro-placental bleeding as a cause of the preterm contractions, although the clinical utility of this test is uncertain and it is not used in all centres. If placental abruption is suspected, a full blood count to assess the haemoglobin level is recommended.
Use of recreational drugs, particularly cocaine, can precipitate preterm labour, and a urine toxicology screen should be considered if this is thought to be a possibility. It should be noted that such a screen is not definitive for the detection of recreational drugs.
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