5.1 Preterm Nutrition in the NICU

Preterm Classification and Growth Goals

Nutrition care for the preterm infant begins with precise classification, because exam questions in this domain key off weight and gestational-age categories. Preterm is any birth before 37 completed weeks of gestation. Subcategories matter clinically: late preterm (34 0/7 to 36 6/7 weeks), moderate preterm (32 0/7 to 33 6/7 weeks), very preterm (<32 weeks), and extremely preterm (<28 weeks). By weight, low birth weight (LBW) is <2,500 g, very low birth weight (VLBW) is <1,500 g, and extremely low birth weight (ELBW) is <1,000 g. Size for gestational age is assigned from a reference curve (Fenton 2013 is standard in US NICUs): small for gestational age (SGA) is <10th percentile, appropriate for gestational age (AGA) is 10th-90th percentile, and large for gestational age (LGA) is >90th percentile. An infant can be preterm and SGA at once; the combination, especially with abnormal umbilical artery Dopplers, flags the highest nutritional risk.

The goal: replicate intrauterine accretion

The benchmark for postnatal growth is the rate the fetus would have achieved in utero during the third trimester. In practice that means:

Extrauterine growth restriction (EUGR), also called postnatal growth failure, is classically defined as weight below the 10th percentile at 36 weeks postmenstrual age or at discharge; many clinicians also track a z-score decline of more than 1-2 standard deviations from birth. Despite modern aggressive nutrition, EUGR remains common in VLBW cohorts, and poor head growth is the growth failure most strongly tied to adverse neurodevelopmental outcomes. Preterm infants typically lose 10-15% of birth weight (ELBW infants up to ~20%) through diuresis of extracellular fluid in the first week and should regain birth weight by roughly 2-3 weeks of age; the 15-20 g/kg/day target applies after that point.

Parenteral Nutrition in the First Days

The ELBW infant has essentially no nutritional reserve: without intake, it catabolizes roughly 1 g/kg/day of endogenous protein — about 1-2% of total body protein each day. That is the rationale for early aggressive parenteral nutrition (PN): supply amino acids from day 1 to prevent catabolism, achieve positive nitrogen balance, and avoid the early protein deficit that predicts later growth failure. Randomized trials show early amino acids improve nitrogen retention and growth without increasing metabolic acidosis or intolerance when dosed appropriately.

Current ASPEN and ESPGHAN-aligned practice:

• Amino acids: start on day 1 at 2-3 g/kg/day and advance to 3.5-4.0 g/kg/day for ELBW infants (slightly lower maximums for larger preterm infants).
• Lipids: start on day 1 at ~1 g/kg/day and advance by 0.5-1 g/kg/day to about 3 g/kg/day (usual maximum 3.5-4 g/kg/day with normal triglycerides). Composite/mixed-oil emulsions (soy, MCT, olive, and fish oil) are increasingly preferred over pure soybean emulsion because of a lower association with intestinal failure-associated cholestasis; fish-oil emulsion is the rescue therapy for established PN-associated cholestasis. Monitor triglycerides, especially with corticosteroids, sepsis, or rapid advancement.
• Glucose: begin at a glucose infusion rate (GIR) of about 5-8 mg/kg/min for VLBW infants and advance by 1-2 mg/kg/min/day to roughly 11-12 mg/kg/min. Hyperglycemia is common in ELBW infants; first responses are reducing the GIR and confirming adequate amino acid intake rather than routine insulin, which carries hypoglycemia risk.

Calcium-phosphorus solubility

Mineral precipitation is the classic PN safety issue. Calcium and phosphate can precipitate (with risk of fatal pulmonary emboli), and solubility falls with temperature, high final concentrations, and high pH. Practical safeguards: add calcium early and phosphate last in compounding, prefer organic phosphate salts (sodium glycerophosphate), acidify with cysteine hydrochloride to improve solubility, never co-infuse with bicarbonate, and respect the lower mineral ceiling of peripheral lines (also limited to roughly 900 mOsm/L osmolarity). PN should contain calcium and phosphorus from day 1 to prevent early hypophosphatemia and the refeeding-like syndrome seen when aggressive amino acids are given without minerals.

Enteral Feeding: Trophic Feeds, Advancement, and Intolerance

Trophic feeding (minimal enteral nutrition) means small volumes of human milk — typically 10-20 mL/kg/day — given for the first several days of life. The purpose is explicitly not nutrition: these volumes prime the gut by stimulating villus growth, digestive enzyme and motilin secretion, and mucosal barrier maturation. Meta-analyses show trophic feeding shortens time to full feeds without increasing necrotizing enterocolitis (NEC). Colostrum oral care (buccal administration of mother's colostrum to ventilated or NPO infants) delivers secretory IgA, lactoferrin, and cytokines to the oropharyngeal mucosa and is practiced for immune benefit, not calories.

Advancing feeds

Once trophic feeds are tolerated, advance by roughly 15-30 mL/kg/day. The SIFT trial found advancement at 30 mL/kg/day was as safe as 18 mL/kg/day in stable preterm infants — no increase in NEC or death and faster achievement of full feeds — so prolonged slow advancement in stable infants is no longer defensible. Slower trajectories are still chosen individually for high-risk infants (severe intrauterine growth restriction with absent or reversed end-diastolic flow, hemodynamically significant patent ductus arteriosus, recent indomethacin, or an umbilical arterial catheter in place), though trial data suggest even many growth-restricted infants tolerate standard rates.

Assessing feeding intolerance

Modern practice has abandoned routine gastric residual checks: residual volume and color correlate poorly with NEC, and routine checking delays full feeds and prolongs PN exposure. Residuals are evaluated only when clinical signs appear. Concerning findings are bilious (green) aspirates, new abdominal distension, bloody stools, vomiting, apnea or bradycardia around feeds, and temperature instability. Suspected NEC is described with Bell staging: Stage I (suspected) — mild systemic signs plus feeding intolerance and guaiac-positive stools; Stage II (definite) — pneumatosis intestinalis or portal venous gas on radiograph with moderate systemic illness; Stage III (advanced) — pneumoperitoneum, shock, and likely surgical disease. Distension plus bloody stool plus pneumatosis is the triad to recognize instantly.

NEC Prevention and Human Milk Fortification

NEC affects roughly 5-10% of VLBW infants, with mortality around 20-30% in surgical cases, so prevention dominates NICU nutrition policy. The highest-evidence strategies:

1. Exclusive human milk diet. Mother's own milk is first choice; pasteurized donor human milk is the standard backup for VLBW infants. Human milk reduces NEC risk by roughly half or more versus preterm formula, and dose matters.
2. Standardized feeding protocols. Unit-wide protocols for initiation, advancement, and holding criteria consistently reduce NEC rates.
3. Probiotics. Strain-specific products (certain Lactobacillus and Bifidobacterium combinations) reduce NEC in meta-analyses, and ESPGHAN conditionally recommends select strains. However, no probiotic is FDA-approved as a drug for preterm infants, a 2023 FDA safety communication followed an infant death linked to a contaminated product, and the AAP does not endorse universal use — know both the evidence and the regulatory caution.
4. Cautious advancement in compromised infants, as described above.

Fortifying human milk

Unfortified human milk cannot meet preterm requirements for protein, calcium, phosphorus, and sodium at realistic volumes. Multinutrient human milk fortifier (HMF) is started when enteral intake reaches about 50-100 mL/kg/day, targeting 24 kcal/oz (roughly 80 kcal/dL) as feeds advance toward full volume of about 120-140 mL/kg/day (occasionally up to 150-200 mL/kg/day for growth). Options are bovine milk-derived HMF (standard; liquid formulations avoid the contamination risk of powder) and human milk-derived fortifier (enables an exclusive human milk diet; may further reduce NEC but is expensive and can become protein-limiting with prolonged use). Individualized strategies address the known variability of expressed milk protein, which falls as lactation continues: adjustable fortification titrates protein to blood urea nitrogen and growth, while targeted fortification doses from milk analyzer results.

Minerals, Iron, Vitamin A, and LCPUFAs

Metabolic bone disease of prematurity

About 80% of fetal calcium and phosphorus accretion occurs in the third trimester, so preterm infants are born mineral-depleted. Enteral targets for stable growing preterm infants are calcium 120-200 mg/kg/day and phosphorus 70-115 mg/kg/day (ESPGHAN), with a Ca:P ratio near 1.5-2:1; unfortified human milk supplies only a fraction of this. Metabolic bone disease (osteopenia) of prematurity presents weeks after birth, with fractures or rickets in severe cases. Risk factors: ELBW/VLBW status, prolonged PN, delayed fortification, chronic diuretics (furosemide causes calciuria), corticosteroids, and cholestasis. Monitoring relies on alkaline phosphatase (ALP) and serum phosphorus: an ALP rising above ~500 IU/L with a low phosphorus (below ~4.5-5.5 mg/dL) signals high risk, while serum calcium stays deceptively normal because it is scavenged from bone.

Iron, vitamin A, vitamin D, and LCPUFAs

• Iron: preterm infants are born before the third-trimester iron transfer and face rapid erythropoiesis plus frequent phlebotomy losses. Begin enteral iron at 2-4 mg/kg/day starting at 4-6 weeks of age, once tolerating full feeds, and continue through 12 months; frequently transfused infants may have iron stores reassessed before supplementing.
• Vitamin A: in ELBW infants, intramuscular vitamin A 5,000 IU three times weekly for 4 weeks modestly reduces bronchopulmonary dysplasia (BPD); the number needed to treat is roughly 11-14, and adoption is limited by injection burden and drug shortages. Enteral dosing is far less effective.
• Vitamin D: 400-1,000 IU/day enterally for preterm infants in the NICU per ESPGHAN guidance.
• Long-chain polyunsaturated fatty acids (LCPUFAs): ESPGHAN recommends DHA 55-60 mg/kg/day and arachidonic acid (ARA) 35-45 mg/kg/day, supplied via human milk, preterm formula, or mixed-oil lipid emulsions; accretion supports retinal and brain development.

PN is weaned as enteral feeds climb; full enteral feeding is generally declared around 120-140 mL/kg/day of fortified human milk or preterm formula.