What causes premature birth?

What Causes Premature Birth

Premature birth is a multifactorial syndrome with multiple distinct pathways leading to delivery before 37 weeks of gestation, including spontaneous preterm labor, preterm premature rupture of membranes (PPROM), and medically indicated preterm delivery due to maternal or fetal complications. 1, 2

Spontaneous Preterm Birth Mechanisms

The majority of preterm births occur spontaneously through several pathophysiologic mechanisms:

Infection and Inflammation

• Intra-amniotic infection triggers inflammatory cascades involving cytokines, chemokines, and prostaglandins that activate the normal labor pathway prematurely, though recent evidence suggests infection may be less common than previously thought, particularly after 32 weeks' gestation 3, 2
• Maternal infections including periodontal disease and reproductive tract infections increase preterm birth risk 4, 2

Cervical Insufficiency

• Cervical incompetency is an independent risk factor for extremely preterm birth (delivery before 28 weeks), with structural weakness of the cervix leading to painless dilation 4
• A short cervical length (≤25 mm) detected before 24 weeks' gestation significantly increases spontaneous preterm delivery risk 1, 5

Placental Dysfunction

• Placental insufficiency appears to cause many cases of spontaneous preterm labor, similar to mechanisms seen in preeclampsia and fetal growth restriction 3
• Impaired uteroplacental blood flow and placental malperfusion disrupt normal pregnancy maintenance 3

Uterine Overdistension

• Multiple pregnancy (twins or higher-order multiples) is an independent risk factor for extremely preterm birth through mechanical overdistension of the uterus 4, 2
• Polyhydramnios can similarly trigger preterm labor 2

Medically Indicated Preterm Birth

Approximately one-quarter of preterm births are iatrogenic, initiated by providers due to maternal or fetal complications:

Maternal Hypertensive Disorders

• Hypertensive disorders complicating pregnancy (including preeclampsia) are independent risk factors for very preterm birth (28-31 weeks) 4
• Pregnancy-induced hypertension can necessitate early delivery to prevent maternal complications including HELLP syndrome 1

Maternal Medical Conditions

• Gestational diabetes mellitus is an independent risk factor for very preterm birth 4
• Chronic maternal medical disorders including chronic hypertension, diabetes, kidney disease, and autoimmune disorders increase preterm birth risk 1

Fetal Compromise

• Fetal intrauterine distress is an independent risk factor for very preterm birth, requiring delivery to prevent fetal demise 4
• Intrauterine growth restriction related to placental insufficiency often necessitates preterm delivery 1, 3

Preterm Premature Rupture of Membranes (PPROM)

• PPROM is the most common risk factor for both extremely preterm and very preterm birth, occurring when membranes rupture before labor onset 4
• PPROM increases risk of ascending infection, cord prolapse, and placental abruption, often necessitating delivery 1

Maternal Risk Factors

Obstetric History

• Prior spontaneous preterm birth is the single strongest predictor of recurrent preterm birth 6, 2
• Primiparity (first pregnancy) is an independent risk factor for extremely preterm birth 4
• Short interpregnancy interval (less than 18 months) increases risk 6
• History of pregnancy loss (miscarriage or stillbirth) confers approximately 2-fold increased risk 1

Demographic and Social Factors

• African-American race carries significantly elevated risk, with preterm birth rates of 14.4% compared to 9.3% in White populations, persisting even after controlling for socioeconomic factors 1, 6
• Low maternal body mass index increases risk 2
• Maternal age extremes (very young or advanced maternal age >35 years) elevate risk 1
• Absence of prenatal care is associated with increased preterm birth 1

Behavioral Factors

• Maternal smoking during pregnancy increases preterm birth risk 1, 6
• Maternal substance abuse contributes to prematurity 1

Stress and Psychological Factors

• High maternal stress and pregnancy-related anxiety are associated with preterm birth, with pregnancy-specific anxiety showing particularly strong associations 1
• Major life events (job loss, death of family member) occurring before or during pregnancy increase risk 1
• Traumatic events (natural disasters, violence) during pregnancy elevate preterm birth risk 1

Systemic and Biological Mechanisms

Progesterone Deficiency

• Inadequate progesterone production or signaling may fail to maintain uterine quiescence, allowing premature labor initiation 2

Immune and Allergic Phenomena

• Allograft reaction between maternal and fetal tissues may trigger preterm labor in susceptible individuals 2
• Allergic phenomena and inflammatory responses can activate labor pathways 2

Vascular Disease

• Maternal vascular disease compromises placental perfusion and can necessitate early delivery 2

Critical Clinical Considerations

The causes of prematurity directly impact fetal brain development and long-term outcomes, as maternal conditions like infection, substance abuse, and hypertension can impair fetal neurologic development independent of prematurity itself 1

Systemic racism and its effects on healthcare access, patient management, stress exposure, and lived experience contribute substantially to persistent racial disparities in preterm birth rates, beyond what can be explained by socioeconomic factors alone 1

The periviable period (20-25 weeks) represents the highest-risk gestational ages, with survival rates ranging from 5-6% at 22 weeks to 67-76% at 25 weeks 1, 7