The Early Nutrition Paradox in Preterm and Intrauterine Growth Restricted (IUGR) Infants: A Critical Review of the Developmental Programming Hypothesis and the Limits of Its Evidence

Nutrition during early life may be an important determinant of long-term health. Preterm birth, affecting approximately 10% of deliveries worldwide, and intrauterine growth restriction (IUGR) are major perinatal conditions. The Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that early nutritional and environmental exposures shape adult disease risk. This narrative review synthesizes epidemiological, cohort, animal, and interventional evidence on early nutrition and long-term outcomes in these infants. Rapid weight gain has been associated with later obesity and cardio-metabolic risk; however, this does not show that the tempo of gain, rather than attained size, carries the risk, and catch-up growth after preterm birth or growth restriction supports neurodevelopment. Preterm birth has been associated with a 53% higher risk of ischemic heart disease, whereas IUGR confers overlapping but distinct risks. Hypothesized mechanisms include epigenetic modification, structural organ deficits, hormonal reprogramming, gut-microbiome dysbiosis, and oxidative stress. Because the human evidence is almost entirely observational and vulnerable to confounding and to over-adjustment for attained body size, these associations should be read as hypotheses rather than established causal effects. Individualized, guideline-based and responsive feeding strategies, with support for mothers to provide their own milk, are needed to optimize immediate outcomes while limiting lifelong disease susceptibility.