Preterm birth and cytokine gene polymorphisms: what is known

Preterm birth means birth before 37 completed weeks of pregnancy. Illness and death related to prematurity remain major concerns in obstetrics and perinatal medicine. Preterm birth has many causes; relevant factors include previous preterm birth, cervical length, multiple pregnancy, certain maternal diseases and pregnancy complications.

Infection, inflammation and cytokines

Infectious and inflammatory processes can contribute to spontaneous preterm birth, particularly at earlier viable gestational ages. Infection may occur without prominent symptoms; severe conditions, including intra-amniotic infection, are also possible. However, not all preterm births are infection-related, and the proportion varies with gestational age and the population studied.

The inflammatory response involves cytokines and other signaling molecules. They interact with innate immune cells, placental tissue and fetal membranes and may promote cervical ripening, membrane weakening and uterine contractions. The roles of macrophages and natural killer (NK) cells are under investigation; attributing every case to placental damage caused by these cells is incorrect.

Studies have reported associations between preterm birth and altered levels of proinflammatory cytokines—interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α)—and anti-inflammatory interleukin-10 (IL-10) in amniotic fluid, cervical secretions or blood. These observations depend on specimen type, timing and clinical circumstances. Association does not establish causation or universal diagnostic thresholds.

Genetic research: potential and limitations

Cytokine gene expression is regulated in part by the transcription factor NF-κB. Single-nucleotide polymorphisms (SNPs) in regulatory regions may affect expression. Such variants are therefore being investigated as possible susceptibility factors for infectious and inflammatory complications and preterm birth.

However, cytokine gene polymorphism panels are not an established method for predicting an individual’s risk of preterm birth. Carrying a variant does not make a complication inevitable, and its absence does not guarantee a favorable outcome. A result should not independently determine the use of antibiotics, anti-inflammatory medicines, progesterone or other interventions.

Clinical assessment is based on obstetric history, symptoms and examination. Transvaginal cervical length measurement and specific tests to assess the likelihood of imminent birth or membrane rupture are used when indicated. The choice depends on gestational age and the clinical situation. Regular contractions, fluid leakage, vaginal bleeding or increasing pelvic pressure before 37 weeks require urgent obstetric assessment.