Unit 1: The Importance of Optimal Nutrition for Preterm Infants

Pre- and post-natal nutrient supply influences the pulmonary health of preterm infants who are at risk of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD) and chronic lung disease (CLD). The general finding that optimal pre- and post-natal nutrition and growth leads to better overall outcomes in preterm infants also applies to their pulmonary development and function. In animal models, the effects of intrauterine growth restriction (IUGR) on the developing lung include impaired development of the pulmonary vasculature, decreased alveolarization, decreased lung weight and diminished surfactant production. In humans, IUGR also appears to increase the preterm infant's risk of RDS and BPD (Moya 2014). Slower postnatal growth in VLBW infants seems to put them at higher risk of BPD (Ehrenkranz et al. 2006).

Fluid management, an integral part of the nutritional care of preterm infants, clearly affects pulmonary function. Fluid overload can cause pulmonary edema, which can, in turn, lead to decreased lung compliance and increased airway resistance. Preterm infants in whom fluids are restricted in the days following birth show a trend towards less BPD (Moya 2014).

Several studies on protein intake, critical for lean body mass accretion and growth, have shown mixed results with respect to pulmonary outcomes (Moya 2014). Overall optimization of nutritional support in the first three weeks of life of ELBW infants was demonstrated in one trial to be associated with less moderate and severe BPD (Ehrenkranz et al. 2011).

Infants with respiratory distress have greater effort in breathing and thereby higher resting energy expenditure (REE). Though it is important to provide sufficient energy to cover this REE and allow for growth, an overreliance on glucose infusions to provide the majority of calories for energy can result in higher CO2 production than if lipids are supplied for energy. Breathing off CO2 can present an extra challenge to preterm infants with lung disease. Caution must be used, therefore, with high rates of glucose infusion in these patients (Moya 2014).

Lipid emulsions through parenteral nutrition provide an important energy source for preterm infants. Long-chain polyunsaturated fatty acids (LC-PUFA) seem to be critical for brain and retina development. Their role in lung growth and function is less established though. However, animal studies have shown some promising results. DHA, an omega-3 LC-PUFA, is believed to be involved in surfactant synthesis. Maternal DHA supplementation appears to increase surfactant in amniotic fluid and the fetal lung of mice (Blanco et al. 2004). Supplementation of lactating women with high-dose DHA decreased the risk of BPD in male infants with GA <33 weeks and all infants with birthweight <1250g (Manley et al. 2011). A retrospective study of preterm infants who had BPD showed that they had had larger postnatal drops in DHA levels than infants who did not develop BPD (Martin et al. 2011).

Soybean oil- based lipid emulsions do not provide any considerable amount of DHA. The use of such intravenous lipid sources has been linked to impaired pulmonary function and increased pulmonary resistance (Vlaardingerbroek & van Goudoever 2015).  Its use also leads to adverse immunological effects, such as the increase of pro-inflammatory mediators contributing to inflammation, infection, and even sepsis (Moya 2014). Newer available lipid emulsions, have partially replaced soybean oil with medium-chain triacylglycerols (MCT's), olive oil, and/or fish oil.  A meta-analysis in VLBW infants revealed that the use of soybean oil based lipid emulsions was linked to higher rates of sepsis as compared to non-purely soybean-based lipid emulsions (Vlaardingerbroek et al. 2012). Therefore the use of pure soybean oil emulsions in VLBW infants should be discouraged (Vlaardingerbroek & van Goudoever 2015). 

Based on the results of  two meta-analyses (Vlaardingerbroek et al. 2012, Simmer & Rao 2005) and a randomized clinical trial (Vlaardingerbroek et al. 2012), it seems that the concern of many neonatologists that the early use of lipid parenteral emulsion in preterm infants may have adverse effects on pulmonary function is not justified. Early lipid administration appears to be well tolerated and be advantageous towards protein synthesis, anabolism, as well as neurodevelopment (dit Trolli et al. 2012). Further long-term follow-up studies are necessary to assess long lasting effects on preterm growth, neurodevelopment and pulmonary outcomes (Vlaardingerbroek & van Goudoever 2015, Moya 2014).

Specific nutrients that are considered to have a role in the pulmonary health of preterm infants include the sugar alcohol inositol, calcium, phosphorus, vitamin A and vitamin E.

Inositol is important for the synthesis of lung surfactant and is found in high amounts in human milk. The course of RDS is worse in infants who have a pronounced drop in serum inositol after birth, but studies in which preterm infants were supplemented with inositol did not show reductions in BPD. However, inositol has been found to bring about significant reductions in non-respiratory outcomes including death and intraventricular hemorrhage as well as lowered rates of retinopathy of prematurity (Howlett et al. 2012).

Phosphorus is important both for surfactant synthesis (phospholipids) and energy storage (ATP). Hypophosphatemia has been associated with an increased risk of BPD, longer ventilator dependence and increased risk of sepsis. Monitoring preterm infants, especially those with IUGR, for phosphorus deficiency is therefore appropriate (Moya 2014).

Calcium has a key role in cardiovascular physiology and, by extension, in the functioning of the respiratory system. Hypocalcemia is associated with apneic episodes in preterm infants. Abnormal bone mineralization due to inadequate calcium (or phosphorus or vitamin D) might affect thoracic stability and thus respiration (Moya 2014).

Low plasma levels of vitamin A are associated with poorer lung growth and repair in preterm infants and can increase their risk of developing chronic lung disease. Giving vitamin A 5000IU intramuscularly three times a week for 4 weeks to preterm infants can reduce the incidence of BPD by 7% (Tyson et al. 1999).

Vitamin E deficiency appears to be associated with increased oxygen toxicity in animals. In humans, low plasma vitamin E levels at birth and on day 3 of life are significantly associated with BPD. Evidence for the benefit of supplementing vitamin E-deficient human infants is lacking, however, an oversupplementation of vitamin E increases the risk of sepsis (Brion et al. 2003).

The current recommended intake of these nutrients for preterm infants is covered in unit 2 of this module.