In one line
Preterm labour and PPROM are two faces of the same final common pathway, and almost nothing we do stops the birth — so the craft is not tocolysis but buying the ~48 hours of pregnancy in which antenatal corticosteroids and magnesium neuroprotection actually change the baby's outcome, while deciding, condition by condition, when prolonging the pregnancy stops helping and starts harming.
This chapter assumes the diagnostic and screening groundwork in preterm birth & PPROM basics and cervical cerclage; it spends its words on the appraisal, the thresholds and the judgement calls. The prophylaxis story (progesterone, cerclage, cervical-length surveillance) is the prevention arm; this objective is about the woman who is already contracting or has already ruptured.
Why this matters in South Africa
Prematurity is the leading direct cause of neonatal death in the SA Perinatal Problem Identification Programme data, and the modifiable deaths cluster in two places that have nothing to do with heroic neonatal care: steroids not given (or given too late to act) and the very-preterm baby born in a facility with no ventilator or no retrieval pathway. The management of this disease is almost entirely logistical and protocol-driven — getting the steroid in, getting the magnesium running, and getting mother-and-fetus to the right level of care before birth — because the things that move the outcome are cheap, EML-listed and time-critical, while tocolysis, which feels like "doing something", changes no perinatal outcome at all. Early-onset and very-preterm presentations additionally collide with the SA reality that neonatal ICU is scarce and tiered, so the "prolong the pregnancy" calculus a high-income unit takes for granted is, in a district hospital, usually a stabilise-and-transfer-in-utero decision instead. The two competencies that matter are running the time-critical protocol and making the right system-level call about where the woman should deliver.
Pathophysiology — why the subtypes behave differently
Preterm birth is a syndrome, not a diagnosis: a single clinical endpoint reached by several distinct mechanisms, and recognising which pathway is operating changes the management. The basic two-stage "decidual activation → uterotonin release → cervical ripening + membrane weakening" sequence is assumed from Intermediate; classifying the subtypes builds on it.
- Infection/inflammation-driven (intra-amniotic infection or sterile inflammation). Ascending microbial invasion of the amniotic cavity (or a sterile "danger-signal" inflammatory response) activates Toll-like receptors, drives IL-6/IL-8 and prostaglandin release, and matrix metalloproteinases degrade the chorioamniotic membranes. This is the dominant mechanism at the earliest gestations — the more preterm the birth, the more likely infection is driving it. The clinical consequence is decisive: this subtype carries the fetal inflammatory response syndrome (FIRS), which is independently linked to cerebral palsy and bronchopulmonary dysplasia, and it is the subtype where prolonging the pregnancy can harm the fetus even before overt chorioamnionitis appears. Mechanism → action: a raised amniotic IL-6 or a positive Gram stain on amniocentesis predicts imminent delivery and poor neonatal outcome regardless of tocolysis — which is exactly why tocolysis is futile here and why occult intra-amniotic infection is the thing you are always trying to exclude.
- Vascular / ischaemic (decidual haemorrhage, abruption). Thrombin generated at the decidual–placental interface is a powerful uterotonic and also degrades membranes (thrombin → protease-activated receptor signalling). This is the mechanism behind preterm labour or PPROM that follows an abruption or presents with antepartum bleeding. The consequence: bleeding-associated preterm labour is tocolysis-resistant and often progresses fast, and a concealed abruption is a contraindication to prolonging the pregnancy — the bleeding subtype is the one most likely to deteriorate to a fetal-distress or DIC emergency.
- Mechanical / cervical (uterine overdistension and cervical insufficiency). Multiple pregnancy and polyhydramnios stretch the myometrium (stretch → gap-junction and oxytocin-receptor upregulation); a structurally or functionally cervical insufficiency shortens and funnels. This is the subtype the prevention arm (progesterone, cerclage, cervical-length surveillance) actually targets, and the one where a short cervix on this admission predicts recurrence and shapes the next-pregnancy plan.
- Idiopathic / physiological-pathway activation. A proportion have premature activation of the normal labour cascade with no identifiable trigger — the subtype most likely to be over-diagnosed as "threatened preterm labour" and over-treated.
Two mechanism→consequence links anchor the rest of the chapter. First, PPROM and intact-membrane preterm labour are the same syndrome stratified by membrane integrity, and membrane status flips the antibiotic decision completely (the macrolide helps once membranes are ruptured and harms when they are intact — see the evidence section). Second, the gestational gradient of aetiology explains the management philosophy: because infection dominates at the earliest gestations, the very-preterm presentation is the one where (a) you most need to exclude occult chorioamnionitis, (b) tocolysis is most futile, and (c) the neuroprotective interventions (steroids, magnesium) have the largest absolute benefit — so the earlier the gestation, the more the plan is "give the proven interventions and get to neonatal ICU", not "stop the labour".
Assessment
The first job is to confirm you are dealing with what you think you are — over-diagnosis of "threatened preterm labour" fills antenatal wards and exposes women to tocolytics they never needed. The basic clinical picture (contractions, speculum findings) is assumed from Intermediate; the discrimination is what matters — separating true imminent labour from threatened labour, and detecting the occult infection that overrides everything.
- Is this really labour? Regular contractions plus cervical change (SASOG: dilatation >2 cm at the internal os, cervix <1 cm). Contractions without cervical change are threatened labour — observe, do not commit to tocolysis or steroids on contractions alone. The positive predictive value of symptoms alone is poor: most women admitted with "threatened preterm labour" are not delivering within a week, so the next two tests are there to avoid intervening in the majority who will not deliver.
- Transvaginal cervical length is the discriminator. A TVS cervical length ≥30 mm is a strong negative predictor — most such women are not in labour and can be considered for discharge. Combining a short cervix with fetal fibronectin sharpens triage further: a negative fFN has a high negative predictive value for delivery within 7–14 days, so its value is ruling out imminent birth and avoiding unnecessary transfer/steroids, not ruling it in. These tests mislead in defined situations: fFN is invalidated by recent intercourse, a digital examination, vaginal bleeding or lubricant in the preceding 24–48 h (false positives), so it must be taken before you touch the cervix and is uninterpretable if the woman is already frankly bleeding. A positive fFN is not a reason to act — its PPV is modest; the test earns its keep as a rule-out.
- Is the membrane ruptured? Sterile speculum first: pooling is the gold standard. If equivocal, an amniotic protein test (IGFBP-1/PAMG-1) helps, but interpret it against pre-test probability — a positive biomarker with no clinical pooling in a woman with no history of fluid loss is more likely a false positive than true PPROM, and a negative result with a convincing history of a gush does not exclude rupture (intermittent leak, hindwater rupture). Never do a digital examination in suspected PPROM (it shortens latency and seeds infection). The reflex "nitrazine/ferning" tests are too unreliable to hang a diagnosis on and are not the SA standard.
- Is there occult infection driving it? This is the single most important judgement here because it flips the plan from prolong to deliver. Overt chorioamnionitis (the Gibbs criteria — maternal pyrexia ≥38 °C plus two of: maternal tachycardia, fetal tachycardia, uterine tenderness, offensive liquor, maternal leucocytosis) is easy; the danger is subclinical intra-amniotic infection, which presents only as unexplained persistent fetal or maternal tachycardia, a creeping CRP/WCC trend, or labour that simply will not be tocolysed. A single normal CRP does not exclude it — the trend matters. In refractory cases at a tertiary unit, amniocentesis for amniotic glucose (low), Gram stain, culture and IL-6 is the definitive way to confirm occult infection, and a positive result mandates delivery.
- Stage and stratify the fetus. Anchor the gestation precisely (best estimate from the earliest scan; never re-date in the third trimester). Establish EFW, presentation (preterm breech and transverse lie are common and change the delivery plan), liquor volume (oligohydramnios in PPROM predicts shorter latency, cord accidents and pulmonary hypoplasia at early gestations), and CTG from viability. In PPROM the liquor volume and the gestation at rupture together drive the prognosis: rupture before ~22–24 weeks carries a real risk of lethal pulmonary hypoplasia and limb contractures, and that prognosis must be in the counselling.