What are the possible causes of preterm labor in a completely healthy woman of childbearing age with no prior medical conditions or complications during pregnancy?

Causes of Preterm Labor in Otherwise Healthy Women

Even in completely healthy women with no identifiable risk factors, preterm labor occurs because it is a syndrome with multiple distinct pathophysiological mechanisms—not a single disease—and many of these mechanisms can activate spontaneously without obvious maternal pathology.

Primary Mechanisms in "Healthy" Women

Subclinical Intrauterine Infection

• Intrauterine infection is the most common identifiable cause of spontaneous preterm labor, even when the mother appears clinically healthy 1
• Bacterial colonization of the amniotic cavity can trigger cytokine release and prostaglandin cascades that initiate labor without causing obvious maternal symptoms 2
• The infection may be limited to the decidua or membranes and not produce systemic signs like fever or elevated white blood cell count 1

Decidual Senescence and Cellular Aging

• Premature aging of decidual cells (the uterine lining during pregnancy) can occur spontaneously and trigger inflammatory pathways that lead to labor 1
• This process involves cellular stress responses that activate labor-initiating mechanisms independent of infection or other pathology 1

Breakdown of Maternal-Fetal Immune Tolerance

• Pregnancy requires active immune suppression to prevent rejection of the semi-allogeneic fetus 1
• Spontaneous breakdown of this tolerance can trigger inflammatory responses that initiate preterm labor, even in women without autoimmune disease 1

Activation of the Fetal Hypothalamic-Pituitary-Adrenal Axis

• Premature activation of fetal stress responses can trigger corticotropin-releasing hormone (CRH) production 2
• Elevated CRH stimulates prostaglandin synthesis, which directly causes uterine contractions and cervical ripening 2
• This can occur without identifiable maternal stressors in apparently healthy pregnancies 2

Structural and Mechanical Factors

Cervical Insufficiency (Often Undiagnosed)

• Some women have subtle cervical weakness that only becomes apparent during pregnancy 3
• This may not be detected on routine examination until cervical shortening or dilation begins 3
• The cervix may appear normal early in pregnancy but fail to maintain structural integrity as pregnancy progresses 4

Uterine Overdistension

• Even singleton pregnancies can experience relative uterine overdistension if the fetus is large or amniotic fluid volume is at the upper end of normal 4
• Mechanical stretch of uterine muscle activates contraction-associated proteins and gap junctions 1

Occult Risk Factors Often Missed

Unrecognized Placental Dysfunction

• Subclinical placental abruption or areas of placental infarction may not cause visible bleeding 2
• These processes release inflammatory mediators that can trigger labor 2

Bacterial Vaginosis (Asymptomatic)

• Many women have altered vaginal flora without symptoms 5
• Ascending bacteria can reach the decidua and trigger inflammatory cascades even without frank infection 5

Important Clinical Caveats

The absence of traditional risk factors does not predict who will develop preterm labor—less than 50% of women who experience preterm labor have identifiable risk factors 3, 5. This explains why:

• Approximately 50% of pregnant women are diagnosed with preterm labor symptoms during pregnancy, but less than 10% actually deliver preterm within 7 days 3, 2
• The diagnosis is often made retrospectively when labor progresses despite appearing "low-risk" 4
• Current screening tools cannot reliably predict which healthy women will develop preterm labor 4

The multifactorial nature means multiple mechanisms may operate simultaneously in the same patient, making it impossible to identify a single cause even after delivery 1. This is why preterm labor remains "one syndrome, many causes" 1 and why prevention strategies have had limited success in unselected populations 3.