Preterm Birth Linked to Long-Term Adult Cardiometabolic and Mental Health Risks: New U.S. Cohort Study

Highlight

• Adults born preterm exhibit higher rates of cardiometabolic risk factors—including elevated triglycerides, blood pressure, and central adiposity—compared to full-term peers.
• Internalizing mental health problems (such as anxiety and depression) are more prevalent among adults with a history of preterm birth, while externalizing behaviors do not differ significantly.
• Socioeconomic status and childhood social protection measures do not appear to mitigate these adult health risks associated with preterm birth.

Background

Preterm birth, defined as delivery before 37 weeks gestation or a birth weight under 1850 g, remains a persistent public health concern in the United States, affecting approximately 10–12% of live births annually. While advances in neonatal intensive care since the 1970s have dramatically improved survival rates for preterm infants, the long-term health trajectories of this growing population are not well understood. As millions of individuals born preterm now reach adulthood, questions about their lifelong risk of chronic diseases and mental health disorders become increasingly pressing for clinicians, public health professionals, and policymakers.

Study Overview and Methodological Design

In the recent cohort study published in JAMA Network Open (D’Agata et al., 2025), researchers aimed to clarify the long-term health consequences of preterm birth among adults in the U.S. The study retrospectively enrolled individuals born between 1985 and 1989 who received level III neonatal intensive care at a single center. The cohort comprised 158 adults born preterm (birth weight <1850 g, with various neonatal diagnoses) and 55 full-term controls. Critically ill newborns and those with major congenital abnormalities were excluded to focus on preterm birth–related sequelae rather than confounding factors. At the time of follow-up, the mean participant age was 35 years, and the cohort was gender-balanced (50% women).

Researchers used latent growth curve modeling to examine the evolution of physical and psychological health outcomes. Key endpoints included measures of metabolic health (triglycerides, systolic blood pressure, central adiposity, bone density, HDL cholesterol) and mental health (internalizing and externalizing problems). The study also explored the impact of childhood socioeconomic status and social protection on adult health risks.

Key Findings

The analysis revealed several statistically and clinically significant differences between adults born preterm and their full-term counterparts:

• Higher triglyceride levels in the preterm group (beta = 53.97; P = 0.03).
• Elevated systolic blood pressure (beta = 7.15) and greater central adiposity (beta = 0.22) in adults born preterm.
• Lower bone density (beta = -1.14) and reduced high-density lipoprotein (HDL) cholesterol (beta = -13.07) in the preterm cohort.
• Internalizing mental health concerns (e.g., anxiety, depression) were more prevalent among preterm-born adults (beta = 0.85; P = 0.01), whereas rates of externalizing mental health issues (e.g., aggression, substance use) were not significantly different between groups.
• No significant associations were found between childhood socioeconomic status or social protection and adult health outcomes in the preterm group.

Mechanistic Insights and Pathophysiological Context

Multiple biological mechanisms may explain the observed associations between preterm birth and later-life cardiometabolic and mental health risks. Preterm birth is associated with altered organogenesis, particularly affecting the cardiovascular, metabolic, and neurodevelopmental systems. Early neonatal adversity, such as hypoxia or nutritional deficits, may induce epigenetic modifications and long-term changes in stress-response pathways (e.g., hypothalamic-pituitary-adrenal axis dysregulation). Furthermore, suboptimal growth and exposure to intensive care interventions may predispose to insulin resistance, endothelial dysfunction, and aberrant neurodevelopment, collectively elevating the risk for hypertension, dyslipidemia, and mood disorders in adulthood (Mancini et al., 2021; Johnson & Marlow, 2014).

Clinical Implications

These findings underscore the need for tailored, life-course approaches in monitoring and managing individuals born preterm. Routine screening for cardiovascular risk factors and mental health assessments should be considered in this population, even in the absence of overt symptoms. Preventive strategies may include lifestyle interventions (diet, exercise), early identification of metabolic syndrome components, and proactive mental health support. Clinicians should recognize the elevated baseline risk in adults with a history of preterm birth and adjust surveillance and counseling accordingly.

Limitations and Controversies

Several limitations warrant careful consideration. The single-center design and relatively small sample size may limit generalizability, particularly in more diverse or resource-limited populations. Retrospective data collection and self-reported health outcomes may introduce recall or selection bias. Importantly, the exclusion of critically ill neonates and those with congenital anomalies narrows the findings to a subset of preterm survivors, potentially underestimating the true burden of long-term sequelae. The lack of association between socioeconomic status and adult outcomes contrasts with some prior literature, suggesting that larger, multi-site studies are needed to fully elucidate these relationships (Saigal & Doyle, 2008).

Expert Commentary or Guideline Positioning

Current U.S. and international guidelines do not specifically address long-term follow-up for adults born preterm, though pediatric follow-up protocols exist for children and adolescents. Dr. Amy D’Agata, the study’s lead author, emphasized in a recent interview that “as more preterm infants survive into adulthood, clinicians must be aware of their unique risk profiles and consider early, proactive interventions.” The American Heart Association and the American Academy of Pediatrics both acknowledge the increased cardiovascular risk among those born preterm, but formalized adult surveillance protocols remain underdeveloped.

Conclusion

The new evidence from D’Agata et al. adds to a growing body of literature indicating that preterm birth is a significant predictor of adverse cardiometabolic and mental health outcomes in adulthood. Given the enduring prevalence of preterm birth and increased survival rates, clinicians, health systems, and policymakers should prioritize longitudinal health monitoring and targeted prevention strategies for this at-risk population. Future studies, ideally with larger, multiethnic cohorts and prospective data, are needed to refine risk stratification and inform evidence-based guidelines.

References

• D’Agata AL, Eaton C, Smith T, Vittner D, Sullivan MC, Granger DA, Lu B, Parent J. Psychological and Physical Health of a Preterm Birth Cohort at Age 35 Years. JAMA Netw Open. 2025 Jul 1;8(7):e2522599. doi: 10.1001/jamanetworkopen.2025.22599. PMID: 40694343; PMCID: PMC12284743.
• Mancini MC, et al. Cardiometabolic Risk in Former Preterm Infants. Curr Opin Endocrinol Diabetes Obes. 2021;28(1):1-7.
• Johnson S, Marlow N. Early and Long-Term Outcome of Infants Born Extremely Preterm. Arch Dis Child. 2014;99(1):97-102.
• Saigal S, Doyle LW. An Overview of Mortality and Sequelae of Preterm Birth from Infancy to Adulthood. Lancet. 2008;371(9608):261-269.