What is preterm birth syndrome?

Preterm Birth Syndrome: A Complex Clinical Entity

Preterm birth syndrome is not a single disease but rather a complex clinical syndrome arising from multiple distinct pathological processes that prematurely activate one or more components of the normal parturition mechanisms, ultimately resulting in delivery before 37 weeks' gestation. 1, 2

Core Definition and Conceptual Framework

Preterm birth syndrome represents a heterogeneous collection of conditions rather than a unified diagnosis. The syndrome encompasses:

• Delivery occurring before 37 completed weeks of gestation (the traditional threshold), though severity and outcomes vary dramatically based on gestational age at birth 1, 3, 4
• Multiple etiologic pathways including maternal conditions (hypertensive disorders, diabetes, infections), placental dysfunction (abruption, insufficiency), and fetal factors (growth restriction, anomalies) that converge on the final common pathway of premature labor 2
• A functional taxonomy that moves beyond simple gestational age cutoffs to incorporate specific obstetric phenotypes, neonatal clinical presentations, and developmental outcomes up to 2 years of age 2

Pathophysiologic Mechanisms

The syndrome arises through several key mechanisms that prematurely trigger labor:

• Immune dysregulation and inflammatory cascade activation represent the central common pathway, with derangements in IL-22, IL-6, and other inflammatory mediators driving premature parturition 1, 5
• Infection and inflammation in the fetoplacental unit serve as major risk factors, though antibiotic treatment has proven largely ineffective as a cure 5
• Premature activation of normal labor components including cervical ripening, membrane rupture, and myometrial contractions through pathologic rather than physiologic triggers 1

Clinical Spectrum and Risk Stratification

The syndrome manifests across a spectrum of severity:

• Late preterm births (34-36 weeks) account for over two-thirds of cases and carry increased risks of feeding problems, hyperbilirubinemia, and respiratory complications compared to term infants 6, 3
• Early preterm births (<34 weeks) represent nearly one-third of cases with dramatically higher mortality and morbidity, including respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, and long-term developmental delays 3, 4
• Extremely preterm births (<32 weeks) face the highest mortality rates, with 36% of infant deaths attributed to preterm birth despite representing only a fraction of deliveries 3

Key Risk Factors and Predictive Elements

Several factors identify high-risk populations:

• Prior spontaneous preterm birth remains the single strongest predictor of recurrence 6
• Short cervical length (<25 mm before 24 weeks) detected by transvaginal ultrasound identifies increased risk even in nulliparous women without prior preterm birth 6
• Adverse pregnancy outcomes including preeclampsia (3.7-fold increased hypertension risk, 2.2-fold ischemic heart disease risk), gestational diabetes, and intrauterine growth restriction signal underlying pathology 6
• Social, behavioral, clinical, and biologic characteristics contribute to persistent racial and ethnic disparities, with non-Hispanic Black pregnant individuals experiencing 14.4% preterm birth rates versus 9.3% in White individuals 6, 3

Clinical Implications for Management

Understanding preterm birth as a syndrome rather than a single entity has critical management implications:

• Antenatal corticosteroids (betamethasone 12 mg IM × 2 doses, 24 hours apart) reduce respiratory distress syndrome by 29%, decrease respiratory support needs by 20%, and lower severe respiratory complications by 33% when administered between 24-36 weeks to high-risk patients 7, 8
• Vaginal progesterone is recommended for singleton gestations with cervical length 20-25 mm diagnosed before 24 weeks to reduce preterm birth risk 6
• Contraindications to corticosteroids include pregestational diabetes (due to severe neonatal hypoglycemia risk) and low probability of delivery before 37 weeks 7, 9, 8

Post-Prematurity Respiratory Disease

Infants surviving preterm birth often develop post-prematurity respiratory disease (PPRD), a distinct entity:

• PPRD encompasses respiratory disease directly associated with premature birth (<37 weeks' postmenstrual age), including but not limited to bronchopulmonary dysplasia 6
• Lifelong respiratory sequelae include chronic cough, recurrent wheezing, exercise intolerance, hypoxemia, reduced pulmonary function, and increased risk of chronic obstructive pulmonary disease 6
• Increased healthcare utilization with frequent clinic visits, increased respiratory medication use, and higher hospitalization rates characterizes the long-term burden 6

Critical Discharge Considerations

For preterm infants, three physiologic competencies must be achieved before safe discharge:

• Oral feeding sufficient to support appropriate growth, typically achieved between 36-37 weeks' postmenstrual age 6
• Ability to maintain normal body temperature in a home environment without supplemental warming 6
• Sufficiently mature respiratory control, which may require hospitalization up to 44 weeks' postmenstrual age in some cases, with supine sleeping position established from 32 weeks onward to prevent SIDS 6