Fetal Growth Restriction as a Lifelong Neurocardiometabolic Disorder: Prenatal Biomarkers, Early-life Trajectories, and Follow-up Strategies – A Systematic Review
Anita Deborah Anwar, Wiku Andonotopo, Muhammad Adrianes Bachnas, Wisnu Prabowo, Eric Edwin Yuliantara, Mochammad Besari Adi Pramono, Julian Dewantiningrum, Efendi Lukas, I Nyoman Hariyasa Sanjaya, Anak Agung Gede Putra Wiradnyana, Anak Agung Ngurah Jaya Kusuma, Khanisyah Erza Gumilar, Ernawati Darmawan, Muhammad Ilham Aldika Akbar, Dudy Aldiansyah, Aloysius Suryawan, Ridwan Abdullah Putra, Cut Meurah Yeni, Nuswil Bernolian, Laksmana Adi Krista Nugraha, Waskita Ekamaheswara Kasumba Andanaputra, Wibisana Andika Krista Dharma, Milan Stanojevic
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BSTRACT
Fetal growth restriction (FGR) has long been managed as a pregnancy complication, yet its biological footprint extends well beyond delivery. Over the past two decades, converging clinical and experimental data have reshaped FGR as an early-life disturbance in developmental programming, with delayed but persistent consequences for multiple organ systems. The present systematic review examines FGR through a life-course lens, integrating prenatal pathology with postnatal and adult disease trajectories. This review was conducted in strict accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines. A comprehensive search of major biomedical databases and research registries identified 5326 records. After standardized screening and eligibility assessment, 37 studies were included in qualitative synthesis. The evidence spans mechanistic studies, longitudinal cohorts, diagnostic innovation research, and expert analyses. Across heterogeneous designs, placental dysfunction consistently emerged as the initiating pathology, characterized by impaired vascular remodeling, angiogenic imbalance, oxidative stress, and altered metabolic signaling. Functional adaptations in utero – particularly involving fetal brain organization and cardiac loading – were repeatedly associated with later neurodevelopmental and cardiometabolic vulnerability. Postnatal findings revealed that infancy and childhood represent a critical transition period, during which subtle metabolic dysregulation, reduced renal reserve, and developmental delays become detectable, often preceding clinically overt disease. Environmental exposures and maternal nutritional factors further shaped individual trajectories. Taken together, the findings support a reframing of FGR as a multisystem developmental disorder with lifelong neurocardiometabolic implications, rather than a transient obstetric diagnosis. Early identification of placental dysfunction, coupled with structured longitudinal follow-up, offers a pragmatic opportunity to alter disease trajectories. Future strategies should prioritize integrated, lifespan-oriented care models that extend beyond the perinatal window.