Topic 2: Enteral Nutrition

Subgroup Considerations

Extremely preterm infants may require lower initial rates and more gradual escalation due to an immature gastrointestinal tract.

Implementation

Protocols for standardised initiation and feed advancement are needed.

Monitoring and Evaluation

Monitor compliance with feeding protocols and time to full enteral feeds.

Research Priorities

• High-quality trials comparing different feeding initiation strategies in the first 48 hours after birth in preterm infants.

(NB these two questions have been combined into one recommendation)

Justification

Evidence for the use of infant formula or donor milk is low to very low certainty, based on a single study with no clear benefit for critical outcomes (e.g., mortality, NEC, breastfeeding at discharge). There was no clear gain in growth or earlier discharge and potential delay in establishing breastfeeds. Risks of early formula feeding were not fully captured in the evidence review: May interfere with breastfeeding establishment and lactogenesis, possible impacts on gut microbiota and immune programming, may undermine maternal confidence and motivation to express milk. A recommendation to wait for mother’s milk helps protect equity and breastfeeding.

Subgroup considerations

Whānau Māori experience inequities in early milk provision and breastfeeding outcomes.

Implementation considerations

Clear policy is needed: Units should define when and for whom supplemental milk would be justified and clinically appropriate. For parents, communicate risks/benefits clearly and promote informed choice. Prioritise lactation support and timely milk expression to reduce the need for supplementation with formula or donor milk.

Monitoring and evaluation

Track the following by ethnicity and gestational age: Use of donor milk and formula, time to initiation of mother’s milk and breastfeeding rates at discharge, lactation support provision

Research priorities

• Strategies to optimise lactation and reduce early formula use.
• Research needed on whether donor milk is appropriate in this group.
   

Justification

Strong recommendation for donor milk is based on the critical outcome of reducing NEC, given the negative impact of NEC on the infant, whānau and hospital resources. Recommendation is based on moderate certainty of evidence of large and consistent NEC reduction (33 fewer per 1,000) across studies.

Subgroup considerations

Very preterm / very low birthweight infants benefit most from donor milk as NEC reduction is most relevant in this group. Infant formula may be considered for preterm infants born after 32 weeks’ gestation who are at low clinical risk of NEC, provided sufficient time and support has been given for the mother to establish her lactation. There is no evidence relating specifically to pēpi Māori and their whānau; however, Māori are a priority group because studies suggest they are less likely to receive breastmilk and more likely to receive infant formula.

Implementation considerations

All neonatal units should have equitable access to donor milk. The donor breastmilk must either be pasteurised or screened (both the donor and the breastmilk are screened). Consider equitable access to donor milk, especially for rural hospitals and Māori and Pacific whānau. This may involve establishing a national guideline on peer-to-peer donation to support safer, more consistent practices. Consider fortification and supplementation of donor milk to optimise nutritional intake and growth, especially if pasteurised. Support Māori and Pacific-led breastfeeding promotion and milk donation initiatives.

Monitoring and evaluation

Audit NEC, growth and breastfeeding outcomes across units nationally. Monitor access to donor milk by ethnicity, region and gestational age. Evaluate all of the safety and outcomes above based on peer-to-peer vs unpasteurised screened donor milk use.

Research priorities

• Effects of donor breastmilk on health outcomes to identify potential benefits (e.g., nutrition/NEC) and risks (e.g., pathogens) for the infant.
• The nutritional composition of donor breastmilk compared with preterm mother's own breastmilk is unknown in Aotearoa New Zealand.
• Outcomes in moderate to late preterm infants.
• Cost-effectiveness of donor milk vs formula in the Aotearoa New Zealand context and by gestational age group.
• Safety and effectiveness of double-screened peer-to-peer unpasteurised milk
• Access to donor breastmilk cultural acceptability and preferences of Māori and Pacific families around donor breastmilk.

Justification

The evidence shows little or no difference between slower and faster feed advancement for key outcomes such as NEC, mortality and survival free from neurodisability. Faster feed advancement shortens the time to full enteral feeds and time to regain birthweight but does not appear to affect growth at discharge. Slower advancement may reduce the risk of cerebral palsy, though this is based on low-certainty evidence and hard to interpret given that no other measures of neurodevelopment were different. This conditional recommendation reflects the balance of benefits and risks across outcomes and the low to moderate certainty of evidence.

Subgroup considerations

There is no strong evidence of differential effects for extremely preterm or very low birthweight infants and few data are available for moderate to late preterm infants. No evidence is available specifically for pēpi Māori or Pacific infants.

Implementation considerations

Standardised feeding protocols should include feed advancement rates to ensure consistency in clinical decision-making, particularly across neonatal units, which is important to reduce variation. Supporting maternal milk supply is essential, especially when feed volumes increase quickly, and it may be necessary to hold feed volumes and wait for sufficient breastmilk supply. Clear explanations in a culturally appropriate manner can support parent confidence and engagement.

Monitoring and evaluation

Monitor time to full enteral feeds, incidence of NEC, growth at discharge and length of hospital stay. Ethnicity-specific monitoring will help identify and address any inequities in care or outcomes.

Research priorities

• Further enteral feeding rate trials are needed in moderate and late preterm infants.
• Longer-term outcomes such as growth quality and neurodevelopment need investigation.
• Culturally grounded research exploring whānau Māori and Pacific families’ experiences with feeding decisions and breastfeeding rates at discharge.

Justification

This is a conditional recommendation due to very low to moderate certainty evidence; that suggests routine aspiration may delay full enteral feeding and increase days to regain birthweight without improving clinical outcomes. There is no evidence of benefit from routine gastric aspiration volume monitoring in reducing mortality, NEC or length of hospital stay. Some data suggest it may delay the time to full feeds (MD ~4 days longer) and prolong the time to regain birthweight.

Subgroup considerations

Most evidence is from infants <1500 g, but data on moderate-late preterm or low birthweight infants is limited.

Implementation considerations

Develop and disseminate clear unit protocols recommending: No routine aspiration of gastric residual volumes. Ongoing clinical monitoring of feed tolerance (e.g., abdominal signs, vomiting, distension).

Monitoring and evaluation

Monitor time to full enteral feeds, NEC rates and length of stay. Monitor staff adherence and confidence in revised unit protocols.

Research priorities

• Further RCTs across birthweight and gestational age groups with long-term outcomes such as growth and neurodevelopment.

Justification

The evidence is mixed and generally of low to moderate certainty, with most studies underpowered to detect meaningful differences in critical outcomes like NEC or mortality. There is insufficient evidence to make a recommendation on the use of intermittent bolus feeding via a pump.

Subgroup considerations

Continuous or intermittent pump feeds may be preferable in very immature or haemodynamically unstable infants who are at risk of intolerance or delayed gastric emptying. Bolus feeding may be more appropriate once the infant is clinically stable to support usual feeding rhythms.

Implementation considerations

Units should be supported in making decisions based on clinical context rather than enforcing one method. The goal should be to transition the infant to bolus feeds as the standard of care, establish "normal" feeding rhythms and decrease costs associated with extra tubing and plastic waste.

Monitoring and evaluation

Monitor feeding intolerance, NEC, time to full feeds and weight gain across feeding methods.

Research priorities

• Adequately powered trials comparing continuous vs bolus feeding vs intermittent bolus via pump stratified by gestational age and birthweight.
• Evaluation of nutrient losses in continuous and intermittent feeds, particularly fat and energy.
• Pēpi Māori, Pacific peoples and underrepresented groups -specific outcome data to address equity and inform culturally responsive care.

Justification

Fortification improves early growth outcomes (weight gain, length, head circumference) and supports bone health. These benefits are more pronounced in very preterm or VLBW infants, who are at the highest nutritional risk. No significant increase in NEC or milk curd obstruction was observed, though the certainty of evidence is low to very low. No significant difference in neurodevelopmental outcomes was shown at 18 months. Fortification may support health equity by addressing higher micronutrient deficiency risk in Māori, Pacific and infants from underrepresented groups due to social determinants of health.

Subgroup considerations

Very preterm or VLBW infants: Most evidence applies to this group.
MLPT infants: Fewer data
Māori: Higher baseline risk of deficiency and adverse outcomes suggests they may benefit more from consistent use of fortifiers.

Implementation considerations

Use standardised feeding guidelines for when to initiate and cease adding commercial breastmilk fortifier. Consider standardised protocols on mixing and preparation to reduce infection risk, ensure consistency and decrease osmolality. Provide information to parents on fortifier (e.g., use of videos or apps) to increase acceptability and knowledge.

Monitoring and evaluation

Audit use of fortifier by gestational age and ethnicity. Monitor serum alkaline phosphatase and markers of growth (weekly z-scores). Collect data on NEC, feeding intolerance and milk curd obstruction.

Research priorities

• RCTs on different formulations of fortifier, including both short and long-term outcomes beyond 18 months (growth, neurodevelopment, metabolic and bone health) in an Aotearoa New Zealand context to allow for ethnicity data, particularly in those populations at higher risk of deficiencies. 
• Alternatives to bovine-based fortifiers (e.g., human milk-derived fortifier)
• Strategies for culturally appropriate communication with families.

Justification

There is no direct evidence comparing less than full-strength vs. full-strength breastmilk fortifier in preterm infants. However, theoretical benefits of full-strength fortification include higher nutrient intake, especially protein (and phosphate, potentially reducing the risk of refeeding syndrome) and promoting better growth. In contrast, starting at less than full strength may lead to faltering growth, inaccurate dosing and microbiological risk, with no proven benefit in reducing NEC or improving feed tolerance. Given the lack of evidence and the practical risks associated with altering fortifier doses, commencing breastmilk fortifier at less than full strength is not recommended.

Subgroup considerations

Pēpi Māori are disproportionately affected by preterm birth and may be more vulnerable to inconsistent care practices. Lack of standardisation and culturally safe communication could exacerbate existing health inequities if half-strength fortifier is used without explanation or shared decision-making. Infants at higher risk of NEC (e.g., <28 weeks or growth-restricted) may still require individualised feeding decisions but should be based on clinical indications and evidence-based practice rather than routine half-strength protocols.

Implementation considerations

Full-strength fortifier is easier to administer accurately and safely (1 sachet per 25 ml). Starting at half strength requires dose modification, powder division or a larger volume of breastmilk which increases the risk of contamination or error. Clear protocols and staff education should support consistent fortifier use.

Monitoring and evaluation

Monitor fortifier use, growth, NEC and refeeding outcomes in infants receiving different fortifier strategies.

Research priorities

None

Justification

While individualised fortification shows some potential benefits in intermediate growth outcomes, these gains are small, based on low to moderate certainty evidence and not consistently sustained at discharge. It is not clear whether increased fat mass is positive or negative. Importantly, there is no clear evidence of benefit for critical clinical outcomes such as mortality, NEC, sepsis or neurodevelopment, and the undesirable effects (e.g., increased complexity, resource demands) are notable. Individualised fortification requires significant investment in equipment, training, infrastructure and specialist staff. The resources required are substantial, and feasibility across all neonatal units, particularly those caring for pēpi Māori and Pacific infants may be limited. Without national-level investment, there is a significant risk of widening existing health inequities. Given these considerations, standardised fortification remains the more feasible, equitable and pragmatic option.

Subgroup considerations

Most evidence comes from studies involving very preterm and very low birthweight infants; effects for moderate-late preterm infants remain unclear. No data specific to pēpi Māori or Pacific infants were identified, limiting generalisability to priority populations in Aotearoa New Zealand. Infants with specific growth or biochemical concerns may still benefit from targeted, dietitian-led nutritional interventions.

Implementation considerations

If individualised fortification is used in specific clinical scenarios, it should only occur under the direction of a specialist neonatal dietitian with a clear clinical indication (e.g. documented faltering growth on standard fortification) in the context of local multidisciplinary team consensus with robust protocols and access to essential equipment, with a commitment to equity of access and outcome monitoring.

Monitoring and evaluation

If used in select cases, individualised fortification must be accompanied by robust monitoring. Track short-term outcomes (weight gain, growth velocity, feeding tolerance) and long-term developmental follow-up. Document adverse events (e.g., electrolyte disturbances, feeding intolerance, excessive weight gain). Monitor inequities in access and outcomes, particularly across hospital sites and among pēpi Māori and Pacific families.

Evaluate cost and resource use to ensure sustainability and value.

Research priorities

• High-quality trials comparing individualised vs standard fortification in the Aotearoa New Zealand setting and including pēpi Māori, Pacific infants and underrepresented groups.
• Studies assessing neurodevelopmental outcomes and long-term body composition.
• Cost-effectiveness analyses in Aotearoa, including pēpi Māori-specific outcomes.
• Implementation research on models of fortification that are equitable and sustainable, especially in smaller or under-resourced units.
  

Justification

There is no compelling evidence to demonstrate the benefit of very early fortification. No evidence of benefit or harm, but very small numbers in trials, meaning we do not know if there is an effect or not. The consensus decision was based on this and the lack of feasibility of early fortification.

Subgroup considerations

Most infants were <2,000 g, with some studies including infants <1,500 g. There is no specific data for extremely preterm (<28 weeks) or pēpi Māori, Pacific peoples and underrepresented groups. Fortifier studies included human milk-based and bovine-based.

Implementation considerations

Most NICUs already have fortification protocols that vary by volume thresholds (e.g. at 80 ml/Kg/day feed volume or when 5 ml every 2 hours is reached). Fortification at these thresholds is feasible with current feed preparation processes. This also allows time to seek parental consent for fortification.

Monitoring and evaluation

Key metrics to monitor and assess by ethnicity to monitor inequities are:

• Timing of fortification
• Growth z-scores (especially weight and head circumference)
• Time to reach full enteral feeds
• Rates of NEC and feeding
  

Research priorities

• Trials assessing individualised vs. volume-based timing of fortification.
• Impact on bone health, metabolic markers and neurodevelopment.
• Inclusion of pēpi Māori, Pacific peoples and underrepresented groups.

Justification

No significant effect on critical outcomes (NEC, mortality, neurodevelopment, adverse effects). High-cost differential: $37,000–$56,000 more per infant per admission. Evidence is imprecise, with wide confidence intervals crossing the line of no effect for most outcomes.

In the context of publicly funded neonatal care in Aotearoa New Zealand, the lack of demonstrated clinical benefit does not justify the cost.

Subgroup considerations

No evidence of differential effect by gestational age, birthweight, or ethnicity. Infants <1000 g or <28 weeks may be considered at higher risk of NEC, but current data do not support a tailored recommendation. Equity must be prioritised, restricting access to expensive interventions to only some populations risks widening disparities. Whānau Māori, Pacific families and underrepresented groups, who have higher rates of preterm birth and NEC, must not be disadvantaged by selective use.

Implementation considerations

No implementation considerations are required, given that bovine fortifier is widely used. A human milk-based fortifier is not currently available in New Zealand and would require regulatory approval, procurement contracts, ethical frameworks for its use and equity considerations. Clinical training and new protocols would also be necessary. The cost is prohibitive and would likely not be justifiable under existing neonatal health budgets. Cultural considerations around the use and commercialisation of human breastmilk must be respected.

Monitoring and evaluation

Nil

Research priorities

• Large, contemporary RCTs comparing human- vs. bovine-based fortifiers with adequate power for NEC and long-term outcomes in Aotearoa New Zealand, allowing for the recruitment of pēpi Māori, Pacific infants and underrepresented groups.
• Subgroup analyses by gestational age, birthweight and ethnicity.
• Cost-effectiveness modelling tailored to publicly funded health systems.
  
• Qualitative research on whānau Māori and Pacific families and underrepresented groups views on the commercialisation and use of human breastmilk.

Justification

This recommendation is based on low to very low certainty evidence and moderate anticipated benefits, weighed against higher cost and analysis of outdated studies. Preterm formula is associated with modestly higher weight gain and head circumference growth in the short term. However, long-term growth outcomes (weight, length, HC at 18 months and 7.5–8 years) show no significant difference. There is a moderate improvement in psychomotor development at 18 months (MD ~6.5 points) and a possible small benefit for mental development with preterm formula. No clear effect on intelligence scores in later childhood. Preterm formula does not appear to significantly increase NEC or mortality risk, but confidence intervals are wide. No significant adverse effects were reported; however, metabolic bone disease and cardiometabolic outcomes were not measured. Term formula does not meet the nutrient requirements of preterm infants. Potential benefit for neurodevelopment and growth. No evidence for adverse effects over term formula. The composition of preterm formulas has changed substantially since older trials, therefore, there is no evidence on which to recommend a change of practice to use term formula.

Subgroup considerations

In the absence of evidence to guide this subgroup recommendation, it is pragmatic to align the recommendation for which preterm infants should have preterm formula with the recommendation for breastmilk fortifier, i.e. Infants born at <32 weeks or birthweight <2,000 g.

Implementation considerations

Preterm formula is already in widespread use but consistency and availability is important. Ensure consistent protocols and avoid changing to term formula solely for cost reasons. Consider clear documentation and rationale when selecting a term formula, especially for stable late preterm infants.

Monitoring and evaluation

Growth velocity and z-scores (weight, length, HC), NEC, sepsis and duration of NICU stay. Neurodevelopmental follow-up, where possible.

Research priorities

• Studies including moderate/late preterm, growth-restricted and Māori/Pacific/Indian infants.
• Composition and benefit/harm of preterm formula requires further research for our population using modern formulations of preterm and term formulas.
• Long-term follow-up of neurodevelopment, bone health, and metabolic outcomes.

Justification

Moderate-to-low-certainty evidence suggests that unpasteurised donor milk may shorten the time to achieve full enteral feeds compared with pasteurised donor milk, although effects on mortality and major morbidities remain uncertain. Given the potential benefits of unpasteurised donor milk and the established safety of pasteurised donor milk, either option may be appropriate when mother’s own milk is unavailable, provided robust donor screening and safe handling practices are in place. Unpasteurised donor milk has a lower cost per infant compared to pasteurised milk and is more accessible, improving equity, especially for Māori, Pacific peoples and rural communities where pasteurised donor milk is inaccessible.

Subgroup considerations

Access to donor breastmilk in areas without a breastmilk bank would improve if unpasteurised, screened donor milk was used.

Implementation considerations

All neonatal units should have equitable access to donor milk. For unpasteurised breastmilk to be acceptable for use in neonatal care, the donor must be screened and tested for cytomegalovirus (CMV), human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-lymphotropic virus type 1 (HTLV-1), human T-lymphotropic virus type 2 (HTLV-2).

Monitoring and evaluation

Monitoring for infection rates, growth outcomes, breastfeeding rates at discharge and parental satisfaction should be incorporated. Special attention should be given to monitoring equity of access across regions and populations.

Research priorities

• Well-conducted RCTs comparing unpasteurised vs pasteurised donor milk in diverse preterm populations.
• Research on neurodevelopmental outcomes and long-term safety.
• Studies on culturally appropriate models for donor milk banking and informal donation screening practices.
• Research into pēpi Māori, Pacific peoples and underrepresented groups experiences and preferences regarding donor milk access.

Justification

No evidence that feed osmolality ≤450 mOsm/kg reduces feed intolerance or NEC. The overall certainty of the evidence is very low, with minimal research on which to base a recommendation. While no consistent harms were identified, the biological plausibility of increased risk for NEC and feeding intolerance when osmolality exceeds 600 mOsm/kg warrants caution. No study demonstrated clear benefit from lower osmolality feeds on gastric emptying, feed tolerance, or NEC reduction. A precautionary approach is warranted due to the lack of proven benefit and theoretical risks, supporting a conditional recommendation to avoid routinely exceeding 600 mOsm/kg.

Subgroup considerations

Extremely preterm or low birthweight infants may be more susceptible to the effects of high osmolality feeds, though subgroup-specific evidence is lacking. Māori and Pacific pēpi, who are at greater risk for NEC, may face additional harm of higher osmolality feeds.

Implementation considerations

Consider total feed osmolality when combining fortifiers, supplements and medications. Ensure medications (e.g., multivitamins, iron) are diluted in adequate volumes of breastmilk or given in divided doses or separately from feeds if they are hyperosmolar. Avoid exceeding 600 mOsm/Kg.

Monitoring and evaluation

None

Research priorities

• Studies comparing feed tolerance and NEC rates across defined osmolality ranges (<450 vs. 450–600 vs. >600 mOsm/Kg).
• Develop osmolality resources to include common feed mixtures, including additive interactions and preparation timing.
• Define minimum dilution volumes for common hyperosmolar medications to ensure safe administration.
  

Justification

Studies have suggested potential benefits, but also risks associated with withholding feeds, such as sepsis, feed intolerance and delays in reaching full enteral feeding. No high-quality evidence was found that withholding feeds for transfusion, extubation or eye examinations is beneficial.

Subgroup considerations

None.

Implementation considerations

None.

Monitoring and evaluation

None.

Research priorities

• Large RCTs comparing withholding vs. continuing feeds during transfusion, especially in extremely preterm and very low birthweight infants, including specific reporting of ethnicity and outcomes.
• The WHEAT RCT may provide this evidence.
• Studies are needed to assess outcomes around withholding feeds for extubation and eye examination.

Justification

This recommendation is based on expert opinion. Current evidence shows enhanced short-term weight gain with higher volumes but no demonstrated long-term clinical benefit or harm. However, the sample size is small and the proxy outcome is weight, not growth. The certainty of evidence ranges from high for weight gain to very low for long-term outcomes such as growth <10th centile at 12 months’ corrected age. Given this uncertainty, a flexible approach—either higher or lower volumes—is appropriate, allowing clinicians to tailor fluid management to individual infant needs while recognising both strategies are reasonable.

Subgroup considerations

Infants who are not receiving breastmilk fortifier will likely require >180 ml/Kg/day to grow well. For infants receiving <180 ml/Kg/day with faltering growth, the first step is to increase enteral feed volume.

Implementation considerations

Maintain flexibility in clinical practice to use either approach. Local protocols should define the rationale for selecting higher or lower volumes based on clinical and nutritional needs. Ensure that neonatal staff are trained to monitor growth trends and adjust fluid plans as needed.

Monitoring and evaluation

Track fluid intake practices across units and compare growth outcomes, feeding tolerance, and incidence of complications. Include equity audits to ensure fluid targets are being applied consistently across diverse populations and settings.

Research priorities

• RCTs comparing fluid strategies with longer-term follow-up, particularly neurodevelopment and body composition.
• Investigate optimal fluid targets in specific subgroups (e.g. ELBW, growth-restricted infants), including in pēpi Māori, Pacific peoples and underrepresented groups and rural populations.

Subgroup considerations

Infants <28 weeks or with comorbidities may need higher nutrition intakes.

Implementation considerations

Availability of specific micronutrients and trained staff to support implementation may vary.

Monitoring and evaluation

Audit nutritional intakes, biochemical and anthropometric outcomes regularly.

Research priorities

• More data needed on long-term outcomes of specific micronutrient intakes and optimal timing, specifically for iodine, selenium and zinc.

Justification

Routine additional protein supplementation over baseline is not justified on the evidence. High-certainty evidence supports improved weight gain with additional protein. Gains in length and head circumference are more modest and less certain but directionally favourable. No high-quality evidence of benefit or harm on neurodevelopment, mortality, or NEC. Requires additional dietetic resources, which may limit its acceptability in some neonatal units.

Subgroup considerations

Enteral protein supplementation may be beneficial when growth is faltering or recommended enteral protein intakes are not met.

Implementation considerations

Use should be guided by growth and intake targets, especially where breastmilk fortifier is unavailable or insufficient. Protein powders used must be appropriate for neonatal use and balanced with overall energy intake. Oversight by a neonatal dietitian is needed to ensure individualisation and nutritional adequacy.

Monitoring and evaluation

Track protein intake (g/Kg/day), weekly weight, length and head circumference growth outcomes (z-scores) and any adverse effects.

Research priorities

• RCTs with long-term neurodevelopmental outcomes of different protein doses and timing, including for pēpi Māori, Pacific peoples and underrepresented groups.

Justification

One small study shows very low‐quality evidence of the effects of carbohydrate supplementation of breastmilk in preterm infants. There was a significant effect on weight gain but not on length or head circumference and no data on the short‐ and long‐term health benefits and harms in this population.

Subgroup considerations

Even for groups at risk of growth faltering, evidence is required for an important outcome before this can be recommended.

Implementation considerations

None.

Monitoring and evaluation

None.

Research priorities

• We do not envisage that further trials of glucose polymers will be conducted, except as a component of multi‐nutrient breastmilk fortification.

Justification

Very low‐quality evidence means that there is uncertainty about the effect of fat supplementation on all outcomes.

Subgroup considerations

There may be a subgroup of infants who might benefit (e.g. infants with congenital heart disease) who have restricted fluid intake and high energy needs.

Implementation considerations

Fat supplementation should only be prescribed on specialist advice in consultation with a neonatal dietitian.

Monitoring and evaluation

Growth monitoring (weight, length, head circumference) post commencement of fat supplementation, feed tolerance and gastrointestinal symptoms, nutritional intake (protein, energy balance) and clinical and breastfeeding at discharge outcomes.

Research priorities

• Well-powered RCTs comparing fat supplementation with standard care in different gestational age and weight groups, focusing on body composition, neurodevelopment and long-term cardiometabolic outcomes.
• Equity-focused implementation studies to ensure appropriate use across ethnic and regional groups.

Justification

There is evidence of better outcomes with Vitamin A and D supplementation without harm at low overall cost. However, intramuscular vitamin A injections may not be feasible or acceptable in the NZ setting. There is moderate to very low certainty of evidence overall. A few outcomes—such as reduction in retinopathy of prematurity (Vitamin A) and bronchopulmonary dysplasia (Vitamin C and D)—suggest potential benefits with higher vitamin intake. However, most outcomes show no statistically significant difference between higher and lower doses, and the precision is low across many estimates, with wide confidence intervals and small sample sizes. Despite the limited evidence, the anticipated desirable effects on important outcomes and the very low risk of harm (with no significant increase in adverse outcomes) support a cautious, conditional recommendation in favour of higher vitamin intake. Cost is trivial, and feasibility and acceptability are high, particularly given this practice is already part of standard care in Aotearoa New Zealand.

Subgroup considerations

Supplementation may be needed for preterm infants receiving unfortified breastmilk or term infant formula and may offer increased benefit to populations at high risk of deficiency.

Implementation considerations

Vitamin D supplementation can begin as soon as parenteral vitamins cease or sooner. Close monitoring of individual vitamin intakes is warranted due to wide recommended ranges and the potential risk of providing excessive supplementation e.g. vitamin E, which is provided in very high doses in SMOFLipid emulsion. Infants on long term parenteral nutrition (>3-4 weeks) are most at risk of high serum vitamin E concentrations. Where available, aiming for ESPGHAN dosing may assist standardisation. Family education and culturally safe communication should be prioritised, especially when engaging with whānau Māori, Pacific peoples and underrepresented groups.

Monitoring and evaluation

Monitor for signs of both deficiency and toxicity, with appropriate lab tests where indicated (will need to give guidance on the timing of testing and what to do with results e.g. increase/decrease supplementation and when to recheck) Consider including vitamin supplementation data in national neonatal audits to inform future quality improvement and research.

Research priorities

• RCTs of individual and combined vitamins in preterm infants (stratified by gestational age), with appropriate pēpi Māori, Pacific peoples and underrepresented groups representation.
• Pharmacokinetic studies to determine vitamin stability and optimal dosing in diverse preterm populations. 
• Research to clarify the role of maternal vitamin status, particularly vitamin D, on neonatal outcomes and maternal supplementation as an option to increase vitamin intakes from breastmilk if feasible. Economic evaluations of vitamin supplementation strategies. 
• Evaluation of long-term outcomes, including school-age development.

Justification

Moderate-certainty evidence shows zinc supplementation reduces mortality and improves linear growth and weight gain and is associated with improved neurodevelopmental outcomes. Supplemented infants demonstrated significantly increased serum zinc levels. While effects on head circumference and sepsis were uncertain, supplementation reduced the risk of diarrhoea and showed no harm. Given the known low zinc levels in Aotearoa New Zealand soil and the low cost of supplementation, the balance of effects favours the intervention, even with variable evidence quality across outcomes.

Subgroup considerations

Extremely preterm infants (<28 weeks) and VLBW infants (<1500 g) have higher zinc requirements and greater risk of deficiency. Infants with gastrointestinal losses may require individualised higher doses and monitoring. Infants of vegan or vegetarian mothers or from population groups with low zinc intakes (including some Māori, Pacific and refugee/migrant families), may benefit more from supplementation. No subgroup data are available for pēpi Māori or Pacific infants, but these groups face disproportionate health and nutrition inequities, supporting a universal rather than selective approach to supplementation.

Implementation considerations

Zinc should be routinely supplemented, ideally starting when enteral feeds are established. This zinc supplementation is in addition to that received from fortified breastmilk or preterm formula.

Continue zinc supplementation until full oral feeds (no tube feeds), term or discharge from neonatal care.

Monitoring and evaluation

Growth monitoring (weight, length, head circumference) is the primary indicator of effectiveness.

Monitoring serum zinc concentrations may be considered in infants with faltering growth, especially for infants with a stoma.

Audit zinc prescribing, administration and growth outcomes, disaggregated by ethnicity and gestational age.

Research priorities

• High-quality trials assessing the long-term neurodevelopmental impact of zinc supplementation
• Dose-response studies to refine optimal dosing strategies across different gestational and birthweight strata.
• Cost-effectiveness analyses in the Aotearoa New Zealand context.
• Evaluation of combined micronutrient strategies including zinc and their synergistic effects on growth and infection outcomes including for pēpi Māori, Pacific families and underrepresented groups.

Justification

No eligible studies were identified for this specific question. This is a time when infants transition to oral feeding and is high risk for reduced nutrient intake. Accurate assessment of oral feeding competency and adequate supplementation with NGT top ups of fortified feeds is required to maintain growth especially before term age. Therefore, the recommendation is based on expert opinion of the theoretical benefits and harms. Continuing fortified EBM or preterm formula until term-equivalent age provides substantially more energy and protein, reducing the risk of faltering growth and nutrient deficiencies. Switching to unfortified EBM or term formula may be appropriate in selected infants who are clinically well, growing appropriately and preparing for exclusive breastfeeding or discharge. An abrupt switch at 36 weeks or 2500 g is physiologically arbitrary and may not meet the ongoing nutrient needs of some preterm infants.

Subgroup considerations

All regional centres have access to breastmilk fortifier and preterm formula, and these should be available at all times.

Implementation considerations

Educate staff on the risks of growth inadequacy and nutrient deficiencies that occur after stopping fortifier or preterm formula too early.

Monitoring and evaluation

Monitor:

• Growth parameters (weight, length, head circumference)
• Micronutrient supplementation needs after discontinuing fortifier (e.g. iron, vitamins)
• Time to discharge and post-discharge feeding and growth
  Research priorities
• RCTs or high-quality observational studies comparing:
• Timing of fortifier or preterm formula discontinuation (e.g. at 36 weeks vs. term)
• Outcomes such as growth, neurodevelopment, breastfeeding duration and discharge timing
• Evaluation of gradual weaning strategies (e.g. reducing feed volumes while maintaining fortification)
  

Research priorities

RCTs or high-quality observational studies comparing:

• Timing of fortifier or preterm formula discontinuation (e.g. at 36 weeks vs. term).
• Outcomes such as growth, neurodevelopment, breastfeeding duration and discharge timing.
• Evaluation of gradual weaning strategies (e.g. reducing feed volumes while maintaining fortification).
  

Justification

Recommendation is based on very low certainty evidence suggesting potential benefits, including a reduction in neurodevelopmental impairment at 2 years with no evidence of harm. While there is no consistent improvement in feeding progression, growth or enteral tolerance, the intervention is low-cost, non-invasive, and feasible in many NICU settings.

Subgroup considerations

We are unsure if smell and taste of the feed should be used in infants <32 weeks’ gestation, as there is minimal research in this group. No significant subgroup analyses have been published, but pēpi Māori were included in the DIAMOND trial (15.8%). No differential effects have been shown by gestational age or birthweight.

Implementation considerations

Given the limited evidence and potential for benefit, implementation should be cautious and prioritise equity and cultural safety. Ensuring equitable implementation requires consistent protocols, staff training and meaningful engagement with families to make this practice part of respectful and inclusive neonatal care. Implementation is feasible in most neonatal units with minor workflow adjustments; requires minimal additional resources (e.g., small volumes of milk, swabs/syringes). Staff education and written protocols are needed to ensure consistent delivery and documentation. Must be culturally appropriate, incorporating whānau involvement and sensitivity to parental consent and communication needs. Consider alignment with other feeding protocols and guidelines to promote acceptance by nursing staff.

Monitoring and evaluation

Track implementation among staff and monitor the following outcomes: Time to full enteral feeds and sucking feeds, duration of hospital stay and parent and staff acceptability. Include ethnicity data. Where possible, align with neurodevelopmental follow-up to assess long-term impact.

Research priorities

Larger multicentre RCTs to assess the impact on:

• Neurodevelopment, especially for extremely and very preterm infants.
• Feeding outcomes, body composition, and clinical complications.
• Health economic evaluations in Aotearoa New Zealand settings.
• Qualitative studies exploring parent and staff perspectives, including whānau Māori, Pacific families and underrepresented groups on acceptability.
• Equity-focused implementation research, especially in under-resourced neonatal units.