Nutrition and the First 1,000 Days: How Nutrition Affects Preterm Infants

By: Gina Signorelli, MS, RDN, CNSC, IBCLC


The first 1000 days of life, from conception through 2 years of age, is a crucial time to shape a child’s entire life.  The best opportunity to maximize nutrition to support development and long-term health occurs during this phase, influencing the brain, metabolism, immune system, and more. Nutrition will have positive effects not only on physical growth but also on neurodevelopment and the microbiome.  It is a critical window of opportunity where early intervention can have implications that will last a lifetime.

Proper nutrition management can have lifelong effects that have economic and financial implications as well. School achievement differences and increased healthcare costs can be consequential for a child’s entire life. Improving nutrition during the first 1000 days, especially in preterm infants, will directly impact the child and society.

Preterm infants are at high risk given their limited nutrient reserves, growth failure, and medical complications after birth. When development is altered so early in life, malnutrition will impact long-term health consequences, including brain growth delays and neurodevelopmental deficits, impacting these infants throughout the lifespan.

Brain Development

The brain develops more during the first 1000 days than at any other time in life. To keep up with rapid brain growth, it is essential to support sufficient calorie consumption and adequate amounts of key nutrients such as iron, zinc, and iodine.

A baby’s brain already contains billions of cells by the 24th week of gestation. During pregnancy, these cells thrive on nutrition from the mother.

If the pregnant mother is not eating enough or consuming the proper nutrients, the baby’s brain won’t form properly, leading to developmental delays. If the baby is born prematurely, meeting the macronutrient and micronutrient requirements pose a challenge.  Consider this: the brain consumes 60% of a neonate’s total caloric intake.

Although all nutrients are necessary for brain growth, macronutrient (protein, fat, glucose) sufficiency is essential for normal brain development. Early undernutrition of macronutrients is often associated with reduced school success, lower IQ scores, and increased behavioral issues.

In addition, essential micronutrients that support brain development include zinc, folate, iodine, iron, vitamins A, D, B6, and B12, and long-chain polyunsaturated fatty acids. Of these, iron may be the most essential at specific times of brain growth to ensure full developmental potential. Not providing these and other important nutrients during the first 1000 days when brain development is critical may result in reduced long-term brain function even after components are repleted.

Another point to note about proper brain development during the first 1000 days is keeping the various areas of the brain on a proper developmental trajectory.   The brain consists of multiple separate regions (e.g., the hippocampus, striatum, cortex) that ultimately interconnect to make up the complex organ.

Each of these regions has a unique growth trajectory that spans and peaks at different times and requires varying nutrition needs during the first 1000 days. A vital nutrient during one time period may have limited or no effect during another.  Therefore, it is important to ensure time-coordinated development of brain areas designed to work together through proper nutrition support and adequate caloric intake.


The gut microbiome directly affects growth and development of preterm infants.  The first 1,000 days of life is a unique window of opportunity to develop a healthy microbiome for several reasons.

First, substantial growth and development occurs at this time, which also applies to the microbiome.  By age three the microbiome is like that of an adult, so ensuring proper development during this time is critical. Second, the establishment of the microbiome has a strong influence on long-term health outcomes.  And thirdly, there is a lower level of microbial diversity relative to other life stages, which makes interventions more impactful.

The first 1000 days provides a window of opportunity for modulating the microbiota through interventions such as diet, antibiotics, probiotics, prebiotics, or fecal microbiota transplantation to promote healthy growth and development.

Importance of Early Nutrition and Preterm Infants

Without a doubt, nutrition plays an important role in physical growth, brain development, and the establishment of the gut microbiome during the first 1000 days. This is particularly important for preterm infants, who are born during the third trimester. The third trimester, beginning at 27 weeks until 40 weeks, is one of the most critical periods for nutrition.

Although medical science has improved the survival rate of preterm infants, focus has now shifted to the quality of survival.  It is essential to intervene early and provide optimal nutrition. Postnatal growth restriction due to inadequate nutrition is associated with poor cognitive development that can impact the child for many years to come.

How to Feed Preterm Infants

Preterm infants can be fed in a variety of ways, but frequently oral or full enteral feeding are not possible early on. Because of the immature gastrointestinal tract, the inability to provide large volumes of enteral feeds and difficulty delivering adequate nutrients frequently requires the addition of parenteral nutrition for premature infants.

Trophic feeds, or minimal enteral nutrition, are generally considered to be feeds at 10-15 ml/kg/day and preferably within 24 hours of birth. Although there is still uncertainty on the ideal time of initiation, trophic feedings can be beneficial for premature infants.  While nutrients are delivered parenterally, priming the gut with trophic feedings helps to prevent gut atrophy and bacterial translocation.

Early enteral feedings also support gastrointestinal disaccharidase activity, blood flow, gut motility, and microbial flora.  This can help decrease cholestasis, length of time to reach full feedings, and feeding intolerance, while also improving weight gain. In addition, clinical benefits include earlier attainment of full enteral feeds, improved bone mineralization, improved feeding tolerance, reduced systemic sepsis and decreased length of NICU stay.

Early enteral feeding also allows for an easier transition to oral feeding, once the infant is able to breast or bottle feed.

Introducing Human Milk

Gut dysbiosis is common in premature infants. Breast milk has unique properties that are important for neurodevelopment and can benefit preterm infants. The nutrients like enzymes, growth factors, and hormones stimulate the developing gastrointestinal system. Increasing evidence supports a role for the infant microbiome in neurodevelopment and growth. Human milk and breastfeeding contribute to the developing microbiome by colonizing the infant’s gut and enriching it with beneficial types of microbes.

Role of Fortifier

Common practice is to supplement breast milk with a fortifier to better meet a preterm infant’s increased requirements and address the inability to provide a high volume of feeds. Specifically, fortification helps by increasing protein, calcium, and phosphorus amounts in breast milk. There are 2 types of fortifiers available: Cow’s milk and human milk derived fortifiers.

Standards of Care

Preterm infants have higher nutritional needs compared to their full-term counterparts. Optimizing nutrition and growth in an extrauterine environment with enteral and parenteral nutrition is a challenge in the neonatal intensive care unit (NICU).

Not only are there difficulties in providing adequate calories due to gut immaturity and tolerance concerns, but lack of standardization between practitioners and institutions makes it challenging to determine the best standard of care.

For example, there is no consensus on fortification of enteral feeds. Institutions still vary on the ideal time of fortification. Early fortification(<60 ml/kg) can affect growth velocity and clinical outcomes, which can impact the infant significantly during the first 1000 days of life and beyond.

Depending on an institution’s feeding protocols, outcomes such as reaching full enteral feeds and discontinuing parenteral nutrition will also vary. Clinicians may have differing opinions on when to feed, when to fortify, and how fast to advance feeds, which can all alter the amount of nutrients a baby can receive.

In addition, manipulations to nutrients and electrolytes in parenteral nutrition can substantially influence intake. In particular, the amount of protein infused during parenteral nutrition can add to preventable deficits. Due to the high level of inconsistency amongst nutrition approaches, standard of care is difficult to establish in the NICU.


The first 1000 days of life are critical in the development of an infant’s brain, gut, and so many other areas. Improving nutrition during the first 1000 days will optimize a child’s trajectory for long-term health and development. Early initiation of trophic feeds, introducing human milk, and establishing a standard of care can improve outcomes for preterm infants. What occurs during these first 1000 days can affect the rest of a child’s life. Therefore, providing adequate nutrition in the NICU is imperative.