Why Does Premature Labor Occur?
Intrauterine infection is the single most important cause of spontaneous preterm labor in otherwise healthy women, accounting for at least 40% of all preterm births, particularly those occurring before 30 weeks of gestation. 1, 2, 3
Primary Mechanisms of Spontaneous Preterm Labor
Infection-Mediated Pathway (Most Common)
- Subclinical intrauterine infection triggers preterm labor through activation of Toll-like receptors (TLRs), which initiate a proinflammatory cascade involving cytokines, chemokines, and prostaglandins that directly stimulate uterine contractions and membrane rupture. 1
- Bacterial products from lower genital tract organisms ascend into the uterus, causing histological chorioamnionitis even without clinical symptoms. 3
- This pathway is particularly dominant in early preterm births (before 30 weeks), where infection plays the most significant causative role. 3, 4
Non-Infectious Inflammatory Pathways
- Decidual senescence and breakdown of maternal-fetal immune tolerance can activate the same inflammatory cascades as infection, leading to preterm labor through overlapping molecular mechanisms. 2
- Placental abruption triggers inflammatory responses that mimic infection-related pathways. 5
- The fetal hypothalamic-pituitary-adrenal axis and corticotropin-releasing hormone may prematurely activate prostaglandin production, though evidence for this mechanism remains incomplete. 5
Structural and Anatomical Factors
- Cervical insufficiency causes premature, painless cervical dilation in mid-second trimester without evidence of infection or labor, representing a structural rather than inflammatory cause. 6
- Uterine anomalies (congenital or acquired) mechanically predispose to preterm contractions. 5
Critical Risk Factors in Healthy Women
Strongest Predictors
- Previous preterm delivery is the single most powerful predictor of recurrent preterm labor. 5
- Young maternal age (particularly adolescence) increases risk through multiple mechanisms including cervical immaturity and socioeconomic factors. 5
- Low socioeconomic status correlates with increased infection exposure, nutritional deficiencies, and inadequate prenatal care. 5
Modifiable Risk Factors
- Subclinical lower genital tract infections (bacterial vaginosis, asymptomatic bacteriuria) provide a reservoir for ascending infection. 3, 4
- Smoking increases risk through vascular effects and inflammatory responses. 6
Important Clinical Caveats
The majority of women who experience preterm labor have no identifiable risk factors at the time of presentation, making prediction and prevention extremely challenging. 2 This explains why 50% of pregnant women may be diagnosed with threatened preterm labor during pregnancy, yet only 7% actually deliver prematurely. 5
Preterm labor is a syndrome with multiple distinct pathways, not a single disease entity—this is why tocolytic therapy often fails and why no single intervention prevents all preterm births. 2, 4 The 40% of cases linked to infection represent the most mechanistically understood subset, but the remaining 60% involve complex interactions between genetic susceptibility, environmental exposures, and inflammatory responses that remain incompletely characterized. 2, 4
Distinguishing true preterm labor from Braxton-Hicks contractions is critical: preterm labor involves regular, painful contractions with documented cervical change, whereas Braxton-Hicks contractions are irregular, subside with rest, and cause no cervical dilation. 6, 7