The Importance of Nutrition in the Neurodevelopment of Preterm Newborns

10 min read /


Key messages:

  • Being born at a time of rapid brain growth makes the brain vulnerable to damage and deficits.
  • High-quality protein is critical for brain development.
  • Neurodevelopment depends on adequate nutrition and intact brain growth factors

Preterm babies are born at a time when rapid brain growth happens in utero, and their premature birth causes them to miss out on this developmental phase and become more vulnerable to deficits. With the catchup required after birth, nutrition becomes an important factor. Studies have shown that neurodevelopment depends on adequate nutrition, such as the impact of high-quality protein, and intact brain growth factors.


Key Messages:

  • Being born at a time of rapid brain growth makes the brain vulnerable to damage and deficits.
  • High-quality protein is critical for brain development.
  • Neurodevelopment depends on adequate nutrition and intact brain growth factors


Several perinatal care strategies have been shown to improve the survival and growth of preterm newborns. Nutrition is particularly important not only for growth, but for neurodevelopment related to better cognitive and motor performance.1 

Being born at a time of accelerated brain growth makes newborns vulnerable to issues like sensory processing disorders, inflammation, bleeding, white matter damage, intestinal microbiota alterations and extrauterine nutrition limitation, increasing the chance of neurocognitive, behavioral, and motor disorders. Preventing injury and improving brain plasticity is therefore crucial for supporting neurodevelopment.2 

Nutritional deficits affect the proliferation and differentiation of neurons, and are both determinants of ultimate neural function. Glia, including oligodendrocytes, astrocytes, and microglia, are particularly nutritionally sensitive and their respective functions of myelination, nutrient delivery and neuronal traffic can be affected by nutritional deficiency. Deficits in protein, energy, iron, zinc, and long chain polyunsaturated fatty acids (LC-PUFAs) can significantly affect brain anatomy.3,4

Glucose is the main source of energy and must be normal at all stages. Fats, including cholesterol, are necessary for myelin synthesis, synaptosome formation, and cell membrane fluidity, crucial in neural processing. Preterm infants have limited ability to synthesize LC-PUFAs, including docosahexaenoic acid (DHA; 22:6 omega-3) and arachidonic acid (AA; 20:4 omega-6) for at least 48 weeks. Deficiencies can therefore result in impaired visual and behavioral processing.4 

Protein plays a fundamental role in brain structural growth and in the formation of growth factors and neurotransmitters, and its deficit is associated with a decrease in the number of synapses and myelination. Therefore, it is necessary to use high quality proteins that will lead to adequate brain growth and better cognitive development.5

Normal brain development
Figure 1. Normal brain development


Micronutrients are deficient in many pregnant women, meaning supplementation is an important part of hospital treatment for premature newborns. Adequate iron levels are related to behavioural improvement such as learning and memory, processing speed and socioemotional regulation.6 

Nutrients needed for normal brain development (Adapted from Comark BE et al​​​​​​​, 2019)
Figure 2. Nutrients needed for normal brain development (Adapted from Comark BE et al, 2019)


Zinc regulates neurotransmission in the hippocampus, rates of DNA, RNA and protein synthesis throughout the brain, and IGF-1 gene expression by acting on metabolic activity. Zinc sufficiency between 24 and 40 weeks of gestational age is important in the development and proper function of the hippocampus, cerebellum, and autonomic nervous system.

Copper regulates iron transport across the blood-brain barrier. Low levels are associated with iron deficiency by altering brain dopamine regulation and cytochrome C status, related to behavioral effects on learning/memory and balance. Iodine deficiency alters thyroid function, resulting in lower brain weight, reduction in dendritic arborization and myelination, causing global cognitive deficits.7

Folate is a cofactor of several neuronal enzymatic pathways and its deficiency in prenatal care is related to neural tube closure defects and with motor deficits in early childhood. Choline participates in the synthesis of neurotransmitters and myelin with implications for the development of the hippocampus. Brain growth factors, IGF1, and neurotrophic factor are nutrition dependent.​​​​​​​

Nutritional management to prevent deficiencies is important for the neurodevelopment of preterm infants and their ability to reach their full potential.



  1. Ramel SE, Georgieff MK. Preterm Nutrition and the Brain. In Koletzko B, Poindexter B, Uauy R (eds): Nutritional Care of Preterm Infants: Scientific Basis and Practical Guidelines. World Rev Nutr Diet. Basel, Karger, 2014, vol 110, pp 190–200 (DOI: 10.1159/000358467.
  2. Ruys CA, Hollanders JJ, Broring T, van Schie PEM, van der Pal SM, van de Lagemaat M, et al. Early-life growth of preterm infants and its impact on neurodevelopment. Pediatr Res 2018 Aug 16. 018-0139-0. 
  3. Embleton ND, Moltu SJ, Lapillonne A, Van Den Akker CHP, et. al Enteral Nutrition in Preterm Infants (2022): A Position Paper From the ESPGHAN Committee on Nutrition and Invited Experts, JPGN 2022;76: 248–268. 
  4. Ottolini KM, Andescavage N, Keller S, Limperopoulos C. Nutrition and the developing brain: the road to optimizing early neurodevelopment: a systematic review. Pediatr Res. 2020 January ; 87(2): 194–201. 
  5. Biasini A, Monti F, Laguardia MC, Stella M, Marvulli M, Neri E. High protein intake in human/maternal milk fortification for 1250g infants: intrahospital growth and neurodevelopmental outcome at two Years. Acta Biomed. 2018;88:470-476. 
  6. Skinner AM, Narchi H. Preterm nutrition and neurodevelopmental outcomes. World J Methodol. 2021 Nov 20; 11(6): 278-293. 
  7. Comark BE, Harding JE, Miller SP, Bloomfiled FH. The Influence of Early Nutrition on Brain Growth and Neurodevelopment in Extremely Preterm Babies: A Narrative Review. Nutrients 2019, 11, 2029; doi:10.3390/nu11092029.