How Social Factors Get Under Our Skin
The fusion of social science and biology is revealing why where you live and what you experience can determine when your baby arrives.
Imagine a medical mystery that affects 15 million newborns worldwide each year, a puzzle where the usual clues—genetics, infections, and prenatal care—only tell part of the story. This is the enigma of preterm birth (PTB), defined as delivery before 37 weeks of gestation. For decades, researchers have documented a troubling consistency: in the United States, Black women have a 50% higher rate of preterm birth compared to white women 1 . This disparity persists even when accounting for income and education, pointing to factors more complex than simple economics.
The emerging answer may lie in how social determinants of health—the conditions in which people are born, grow, live, work, and age—become biologically embedded through molecular mechanisms. By integrating multi-omics technologies (which analyze the complete set of biological molecules in an organism) with social science, researchers are beginning to decipher how experiences like stress and discrimination can physically manifest to influence pregnancy outcomes.
"Multi-omics" refers to technologies that analyze multiple molecular layers simultaneously—including genomics (DNA sequences), transcriptomics (RNA expression), epigenomics (molecular modifications that regulate gene activity), proteomics (proteins), and metabolomics (metabolites). Together, they provide a comprehensive picture of biological activity.
These approaches have revolutionized our understanding of PTB pathogenesis:
Stress, discrimination, socioeconomic status
Epigenetic changes, HPA axis activation
Inflammation, immune response alterations
Preterm birth risk and timing
Recent research has identified inflammation as a critical biological pathway linking social stressors to preterm birth. A 2025 study examining placental samples from multiple countries found "a surprisingly high rate of inflammation" in preterm births, with leukocyte infiltration correlating with premature delivery 4 .
Gene ontology analyses highlighted "the presence of leukocyte infiltration or activation and inflammatory responses in both the fetal and maternal compartments" 4 . This suggests that social stressors may trigger inflammatory responses that directly contribute to the initiation of labor.
Stressors
HPA Activation
Inflammation
Preterm Birth
A landmark 2025 study published in npj Digital Medicine introduced an innovative approach to PTB prediction by deeply integrating multi-omics data with artificial intelligence 3 6 8 . The research team:
Enrolled 682 pregnant women across two independent hospitals in China in a nested case-control study 6
Collected plasma samples for cell-free DNA (cfDNA) and cell-free RNA (cfRNA) sequencing 6
Developed GeneLLM, a gene-focused large language model designed to interpret complex biological data 3
Built three predictive models using different input data: cfDNA-only, cfRNA-only, and integrated cfDNA+cfRNA 6
The team used a transformer-based architecture—similar to those powering advanced AI systems—to process the genetic information. The quantized DNA or RNA representations were processed individually or combined before being input into the GeneLLM disease tuning module 6 .
cfDNA Data
cfRNA Data
GeneLLM AI Model
PTB Risk Prediction
The findings demonstrated the power of data integration:
AUC: 0.822
Captures genetic variation information
AUC: 0.851
Reflects gene expression activity
AUC: 0.890
Combines complementary biological information
For context, an AUC of 1.0 represents perfect prediction, while 0.5 represents random guessing. The nearly 90% accuracy represented a significant improvement over single-modality models 6 .
| Model Type | AUC (Area Under Curve) | Key Strengths |
|---|---|---|
| cfDNA-only | 0.822 | Captures genetic variation information |
| cfRNA-only | 0.851 | Reflects gene expression activity |
| Integrated cfDNA+cfRNA | 0.890 | Combines complementary biological information |
The research also uncovered a novel molecular insight: RNA editing levels were markedly higher in preterm cases. Models based on RNA editing features alone achieved an AUC of 0.82, outperforming single-omics models and suggesting "a potential mechanistic role of RNA editing in PTB" 3 .
| Research Tool | Function in Preterm Birth Research |
|---|---|
| Cell-free DNA (cfDNA) sequencing | Analyzes genetic material circulating in mother's blood for genetic variations associated with PTB risk 6 |
| Cell-free RNA (cfRNA) sequencing | Captures gene expression patterns using PALM-Seq method, providing dynamic insight into pregnancy health 6 |
| Transformer-based AI models | Integrates multi-omics data through advanced pattern recognition, similar to large language models 6 |
| Placental histopathology | Examines tissue morphology and inflammation rates in placental samples 4 |
The integration of social determinants with multi-omics data offers more than just improved prediction—it opens avenues for personalized prevention. As Dr. Zhou Si, Chief Scientist at BGI Genomics and first author of the AI multi-omics study, explained: "Beyond prediction, our findings also reveal RNA editing as a promising new target for understanding and regulating PTB" 3 .
This research direction aligns with the growing recognition that effective intervention must address both biological and social factors. As one review noted: "Translating multi-omics insights into clinical practice necessitates collaborative efforts to develop cost-effective, accessible biomarker panels and establish standardized guidelines for implementation" 5 .
Most genomic studies to date have focused on white populations, limiting their applicability 1 .
Capturing dynamic biological changes throughout pregnancy requires repeated measurements 5 .
Bridging social epidemiology, molecular biology, and clinical obstetrics is essential but challenging.
Developing cost-effective, accessible biomarker panels for diverse populations.
The fusion of social and biological sciences is transforming our understanding of pregnancy, revealing how our lived experiences become biologically embedded, and offering new hope for addressing one of the most persistent challenges in maternal and child health.
For further reading on this topic, see the recent comprehensive review "Decoding preterm birth: Non-Invasive biomarkers and personalized multi-omics strategies" in Developmental Biology 5 and the groundbreaking study "A novel sequence-based transformer model architecture for integrating multi-omics data in preterm birth risk prediction" in npj Digital Medicine 6 .
The Social Divide: More Than Just Medicine
14%
Preterm birth rate among Black women in the US
50% Higher
PTB risk for Black women compared to white women
30% Higher
PTB rates in most deprived vs. least deprived areas
Profound Disparities in Preterm Birth
Preterm birth is not just a medical issue—it's a social one. The statistics reveal troubling patterns:
Preterm Birth Rates by Ethnicity and Deprivation
The Central Role of Stress and Racism
Research increasingly points to maternal stress as a key pathway through which social factors influence pregnancy outcomes. The connection isn't merely psychological—it's physiological.
Chronic Stress Activation
When environmental demands exceed a person's adaptive capacity, it triggers a cascade of biochemical changes 1 .
The Discrimination Connection
Black populations consistently experience higher levels of psychosocial stressors, particularly discrimination and racism 1 .
Beyond Income
Racial disparities in psychosocial burden persist across income levels, mirroring disparities in birth outcomes 1 .
Biological Mechanism
The biological mechanism is precise: maternal stress activates the hypothalamic-pituitary-adrenal (HPA) axis, the body's central stress response system. This triggers norepinephrine and cortisol release, activating placental corticotropin-releasing hormone (CRH) gene expression, and potentially initiating a cascade of events ending in preterm birth 1 .
Table 1: Social Determinants Influencing Preterm Birth Risk