Costanza Sortino

Background: The first 1000 days of life, from conception to 2 years of age, represent a critical window during which nutrition can exert long-lasting effects on neurodevelopment, immune maturation, and susceptibility to prematurity-related morbidity. Docosahexaenoic acid (DHA) is a key structural n-3 long-chain polyunsaturated fatty acid of the brain and retina, characterized by rapid fetal accretion during the third trimester. Methods: We conducted a narrative review of studies published from March 2015 up to December 2025, including randomized controlled trials, follow-up studies, and systematic reviews/meta-analyses about DHA supplementation during pregnancy, lactation, infancy and early childhood, and its role on development. Results: Across the first 1000 days, DHA supplementation improves biochemical DHA status, particularly in populations with low baseline levels (moderate to high level of evidence), while clinical outcomes remain heterogeneous. During pregnancy, some benefits in specific cognitive and behavioral domains have been demonstrated, whereas effects on global cognition and long-term behavior are frequently null (moderate evidence). Visual outcomes appear favorable, with improvements in visual acuity (moderate evidence). In preterm infants, enteral DHA—often combined with arachidonic acid (ARA)—is feasible and well tolerated. DHA may reduce inflammatory markers and necrotizing enterocolitis risk when in equilibrium with ARA (low to moderate evidence), while no evidence supports the link between DHA and reduced risk of bronchopulmonary dysplasia and retinopathy of prematurity (moderate evidence). Neurodevelopmental outcomes are mixed: neuroimaging studies suggest enhanced white matter maturation with DHA + ARA, whereas most trials show no clear benefit regarding standardized developmental scores (moderate evidence). Conclusions: DHA is biologically essential during the first 1000 days, but its clinical impact depends on timing, dose, baseline status, and prematurity-related context. The balance between DHA and ARA, rather than DHA supplementation alone, emerges as a key determinant of clinical efficacy, supporting a shift toward precision-based nutritional strategies in early life.

Background: The first 1000 days of life represent a critical window for developmental programming, during which specific nutritional exposures, such as vitamin D levels, may influence long-term health trajectories. Vitamin D plays a central role in skeletal development, but increasing evidence also supports its possible involvement in immune, metabolic, and neurodevelopmental processes during early life. In this narrative review, we summarize current evidence on the biological functions of vitamin D across the first 1000 days, focusing on its roles in skeletal, immune, metabolic, and neurodevelopmental processes, and its potential role as a programming factor. Methods: We conducted our research using the PubMed, Scopus, and Cochrane databases. We included systematic reviews, randomized controlled trials, and high-quality observational studies published from 2015 onward, focusing on pregnancy, neonatal life, and early childhood. Results: Vitamin D acts through placental, epigenetic, skeletal, immune, metabolic, and neurodevelopmental pathways that are particularly active during early development. Low maternal or early-life vitamin D status has been associated with adverse birth outcomes and impaired bone health. It has also been linked to increased susceptibility to infections and allergic diseases, altered metabolic trajectories, and mild neurodevelopmental differences. Evidence from supplementation trials remains heterogeneous, with benefits appearing more consistent in populations with baseline deficiency. Conclusions: Vitamin D fulfills several biological plausibility criteria for a potential early-life programming factor, although current human evidence remains heterogeneous.