Preterm infants—those born before 37 weeks of gestation—enter the world with bodies that have not yet completed the rapid growth and organ development that normally occurs during the final weeks of pregnancy. This abrupt transition from the intra‑uterine to the extra‑uterine environment creates a unique set of nutritional challenges. Their metabolic pathways are immature, nutrient stores are limited, and the demands for building tissue, supporting brain development, and maintaining vital organ function are markedly higher than those of term newborns. Understanding the specific macro‑ and micronutrient requirements, the physiological reasons behind them, and how to translate that knowledge into an individualized nutrition plan is essential for clinicians, dietitians, and caregivers who support these vulnerable infants.
Physiological Basis for Elevated Nutrient Demands
- Incomplete Organ Maturation
- Gastrointestinal tract: Reduced gastric acidity, immature brush‑border enzymes, and limited intestinal motility impair digestion and absorption, especially of proteins and fats.
- Renal function: Glomerular filtration rate (GFR) is low, affecting fluid and electrolyte handling and the excretion of metabolic waste.
- Accelerated Growth Velocity
- Preterm infants can grow at rates of 15–20 g kg⁻¹ day⁻¹, far exceeding the 10–12 g kg⁻¹ day⁻¹ typical of term infants. This rapid tissue accretion requires proportionally more calories, protein, and minerals.
- Limited In‑Utero Nutrient Stores
- Iron, calcium, phosphorus, and vitamin D stores are primarily accumulated during the third trimester. Infants born before this period start life with markedly reduced reserves, necessitating early external provision.
- Higher Metabolic Turnover
- Basal metabolic rate per kilogram is greater in preterm infants, driven by the need to maintain body temperature, support organ maturation, and sustain high rates of protein synthesis.
Energy Requirements and Caloric Density
- Baseline needs: 110–130 kcal kg⁻¹ day⁻¹ for stable, non‑ventilated preterm infants; up to 150 kcal kg⁻¹ day⁻¹ for those with increased work of breathing or infection.
- Caloric density: Standard term formulas provide ~20 kcal dL⁻¹. For preterm infants, feeds are often concentrated to 22–24 kcal dL⁻¹ (or higher) to meet needs without excessive fluid volumes.
- Fluid restriction: Because of immature renal handling, fluid intake is typically limited to 120–150 mL kg⁻¹ day⁻¹ in the first weeks, making higher caloric density essential.
Protein Needs and Amino Acid Profile
- Quantity: 3.5–4.5 g kg⁻¹ day⁻¹ of high‑quality protein is recommended for very low birth‑weight (VLBW) infants (<1500 g). This translates to 1.5–2.0 g kg⁻¹ day⁻¹ of essential amino acids.
- Quality: A whey‑dominant protein source (≈70 % whey, 30 % casein) mirrors the composition of human milk and improves digestibility. Essential amino acids such as leucine, lysine, and threonine are critical for muscle and brain protein synthesis.
- Timing: Early provision (within the first 24–48 h) of adequate protein is associated with improved linear growth and reduced risk of extra‑uterine growth restriction (EUGR).
Fats: Essential Fatty Acids and Energy Source
- Energy contribution: Fats supply ~50 % of total calories in fortified human milk or preterm formulas, providing a dense energy source without increasing fluid load.
- Long‑chain polyunsaturated fatty acids (LCPUFAs): Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are vital for retinal and cerebral development. Preterm infants miss the third‑trimester surge in placental transfer, making dietary provision essential.
- Fat composition: A balanced ratio of saturated, monounsaturated, and polyunsaturated fats, with a DHA:ARA ratio of roughly 1:1 to 1:2, supports membrane fluidity and neurodevelopment.
Carbohydrates and Osmolality Considerations
- Primary carbohydrate: Lactose is the preferred carbohydrate in human milk, but preterm formulas may incorporate glucose polymers (e.g., maltodextrin) to reduce osmolality while delivering adequate calories.
- Osmolality limits: Feeds should remain ≤450 mOsm kg⁻¹ to avoid gastrointestinal irritation and potential necrotizing enterocolitis (NEC). Careful calculation of added fortifiers and supplements is required to stay within this range.
Micronutrient Requirements
| Micronutrient | Primary Role | Typical Preterm Dose* |
|---|---|---|
| Calcium | Bone mineralization, neuromuscular function | 120–200 mg kg⁻¹ day⁻¹ |
| Phosphorus | Bone matrix, energy metabolism (ATP) | 60–140 mg kg⁻¹ day⁻¹ |
| Vitamin D | Calcium absorption, bone health | 400–800 IU day⁻¹ |
| Iron | Hemoglobin synthesis, neurodevelopment | 2–4 mg kg⁻¹ day⁻¹ (starting at 2 weeks) |
| Zinc | Enzyme function, DNA synthesis | 2–3 mg kg⁻¹ day⁻¹ |
| Selenium | Antioxidant defense, thyroid hormone metabolism | 2–3 µg kg⁻¹ day⁻¹ |
| Vitamin A | Vision, immune function | 500–800 IU day⁻¹ |
| Vitamin E | Membrane protection, antioxidant | 5–10 IU day⁻¹ |
| Folate | DNA synthesis, red blood cell formation | 0.5–1 mg day⁻¹ |
| Vitamin K | Coagulation factor synthesis | 0.5 µg kg⁻¹ day⁻¹ (often given as a single prophylactic dose) |
\*Doses are expressed per kilogram of body weight and may be adjusted based on laboratory values and clinical status.
- Calcium‑Phosphorus Ratio: An optimal Ca:P ratio of 1.5–2:1 (by weight) promotes efficient bone mineralization and reduces the risk of metabolic bone disease.
- Trace Elements: Because preterm infants have limited hepatic storage, regular monitoring of serum copper, zinc, and selenium is advisable, especially in infants receiving prolonged parenteral nutrition.
Fluid and Electrolyte Management
- Initial fluid allowance: 60–80 mL kg⁻¹ day⁻¹ in the first 24 h, advancing to 120–150 mL kg⁻¹ day⁻¹ by day 3–5, depending on insensible losses and clinical stability.
- Sodium: Minimal sodium (≤2 mmol kg⁻¹ day⁻¹) is provided in the first week to avoid fluid overload and hypertension; gradual increase is permitted after day 7 as renal function matures.
- Potassium and Chloride: Introduced after the first 48 h, with typical targets of 2–3 mmol kg⁻¹ day⁻¹ for potassium and 2–4 mmol kg⁻¹ day⁻¹ for chloride.
- Glucose: Maintain serum glucose 45–150 mg/dL; dextrose infusion rates of 4–6 mg kg⁻¹ min⁻¹ are common in the early postnatal period.
Role of Human Milk and Donor Milk in Meeting Nutritional Needs
- Advantages: Human milk provides bioactive factors (immunoglobulins, lactoferrin, oligosaccharides) that reduce infection risk and support gut maturation. Its protein composition (high whey) is more digestible for preterm infants.
- Nutrient gaps: While human milk is the gold standard, it often falls short of the protein, calcium, phosphorus, and caloric density required for very preterm infants. This is why fortification (discussed below) is routinely employed.
- Donor milk: When maternal milk is unavailable, pasteurized donor milk is the preferred alternative to formula, offering similar protective bioactive components, albeit with slightly lower protein content.
Use of Fortifiers and Supplements: Principles and Safety
- Why fortify?
- To bridge the gap between the nutrient composition of human milk and the elevated needs of preterm infants, especially for protein, minerals, and calories.
- Types of fortifiers
- Powdered bovine‑based fortifiers (most common) provide additional protein, calcium, phosphorus, and vitamins.
- Human‑milk‑based fortifiers (derived from donor milk) reduce exposure to bovine proteins and may be advantageous for infants with severe intolerance or allergy risk.
- Dosing strategy
- Start with a “starter” fortification (≈1 packet per 100 mL) and titrate to a “full” fortification (≈2–3 packets per 100 mL) based on growth trends and laboratory markers (e.g., serum phosphorus, alkaline phosphatase).
- Safety considerations
- Osmolality monitoring: Ensure the final feed osmolality remains ≤450 mOsm kg⁻¹.
- Electrolyte balance: Adjust calcium and phosphorus additions to maintain the optimal Ca:P ratio.
- Allergy surveillance: Observe for signs of cow‑milk protein allergy, especially when using bovine‑based products.
Individualizing Nutrition: Gestational Age, Birth Weight, and Clinical Status
- Gestational age categories
- Extremely preterm (<28 weeks): Highest protein (4.0–4.5 g kg⁻¹ day⁻¹) and energy (150 kcal kg⁻¹ day⁻¹) targets; aggressive fortification often required.
- Very preterm (28–32 weeks): Slightly lower protein (3.5–4.0 g kg⁻¹ day⁻¹) and energy (130–140 kcal kg⁻¹ day⁻¹).
- Moderately preterm (32–36 weeks): May approach term infant requirements but still benefit from modest protein enrichment (3.0–3.5 g kg⁻¹ day⁻¹).
- Birth‑weight considerations
- VLBW (<1500 g): Prioritize high‑protein, high‑calorie feeds to prevent EUGR.
- Small for gestational age (SGA): May require tailored protein‑to‑energy ratios to support catch‑up growth while avoiding excessive adiposity.
- Medical comorbidities
- Chronic lung disease (CLD): Increased caloric needs (up to 160 kcal kg⁻¹ day⁻¹) due to higher work of breathing.
- Intraventricular hemorrhage (IVH): Adequate protein and iron are crucial for neurorepair, but fluid restriction must be respected.
- Renal impairment: Adjust electrolyte provision and monitor fluid balance closely.
Monitoring and Adjusting Nutritional Plans
- Growth metrics
- Weight: Daily weight checks; aim for a weight gain of 15–20 g kg⁻¹ day⁻¹.
- Length and head circumference: Measured weekly; head growth is a sensitive indicator of brain development.
- Laboratory surveillance
- Serum electrolytes (Na⁺, K⁺, Cl⁻, Ca²⁺, PO₄³⁻): Twice weekly in the first month, then weekly.
- Alkaline phosphatase and phosphate: Markers of bone mineralization; rising alkaline phosphatase with low phosphate may signal osteopenia.
- Hemoglobin/hematocrit and ferritin: Guide iron supplementation.
- Vitamin D levels: Check at 4–6 weeks; supplement accordingly.
- Adjustments
- Protein: Increase fortifier concentration or add modular protein powders if weight gain stalls.
- Minerals: Add calcium‑phosphate supplements when serum levels fall below target ranges.
- Energy density: Raise caloric concentration (e.g., from 22 to 24 kcal dL⁻¹) if fluid restriction limits total volume.
Impact of Adequate Nutrition on Neurodevelopment and Organ Maturation
- Brain growth: The third trimester is a period of exponential cerebral cortical expansion. Sufficient protein, DHA, and energy are directly linked to improved neurocognitive scores at 2 years corrected age.
- Retinal development: Adequate DHA and vitamin A support visual acuity and reduce the incidence of retinopathy of prematurity (ROP) when provided within safe limits.
- Bone health: Proper calcium, phosphorus, and vitamin D intake prevent metabolic bone disease, which can otherwise lead to fractures and long‑term skeletal deficits.
- Immune competence: Human milk‑derived immunoglobulins and lactoferrin, combined with adequate zinc and selenium, lower infection rates, thereby reducing catabolic stress and supporting growth.
Emerging Research and Future Directions
- Personalized nutrition genomics: Early studies suggest that genetic polymorphisms (e.g., in the FADS1/2 genes affecting DHA synthesis) may influence individual responses to fatty‑acid supplementation, opening the door to genotype‑guided fortification.
- Prebiotic and probiotic adjuncts: While not a primary focus of nutrient provision, ongoing trials are evaluating specific oligosaccharide blends that may enhance gut barrier function and nutrient absorption in preterm infants.
- Micro‑nutrient delivery systems: Nano‑encapsulated iron and vitamin D formulations are being investigated to improve bioavailability while minimizing oxidative stress.
- Longitudinal outcome registries: Large‑scale databases tracking nutrition, growth, and neurodevelopmental outcomes are helping refine target ranges and identify optimal feeding windows for different sub‑populations of preterm infants.
In summary, the nutritional landscape for preterm infants is a delicate balance of meeting heightened macro‑ and micronutrient demands while respecting the physiological limitations of an immature organ system. By grounding feeding practices in a solid understanding of energy, protein, fat, carbohydrate, and micronutrient needs—and by continuously monitoring growth, laboratory parameters, and clinical status—care teams can provide the foundation for optimal growth, neurodevelopment, and long‑term health in these fragile newborns.
