What is the evidence on how to feed preterm infants?

Providing preterm and, in particular, extremely preterm infants with nourishment is challenging, and many of our daily decisions may have a substantial impact on the shortterm and long-term health of each individual. Over the past few decades, a huge body of evidence has emerged about the nutritional needs of preterm infants. These have resulted in published guidelines (1) that theoretically help clinicians to provide the optimal amounts of macronutrients and micronutrients that extremely preterm infants need, based on a relatively high degree of evidence. However, only a fewguidelines are availablewhen it comes to the practical issue of enteral feeding (2), underlining the controversy about most aspects of feeding such infants and the fact that very few of the methods are based on high-grade evidence. As inmany areas ofmedicine, it is hard to find high degrees of evidence for our everyday problems, such as guidelines that provide limits for treating jaundice or blood glucose issues in preterm infants. This absence of good evidence invokes local strategies that are often based on traditions and the experiences of local centres. A large variety of strategies havebeendeveloped toachieve adequate growth by enteral nutrition, especially in terms of feeding the tiniest babies on our wards. But not even the most important question, aboutwhat optimal growth should look like, can be answered with absolute certainty. Despite increased postnatal energy expenditure, a level of postnatal growth that is similar to intrauterine growth is often proposed. It is well known, from an increasing number of studies, that extrauterine growth restriction is deleterious for outcomes in preterm infants. On the other hand, doing too much also carries a risk for future health problems (3,4). The debate on what optimal postnatal growth should look like is ongoing and new aspects have been proposed, for example individual growth targets using individualised growth trajectories (5). What is the optimal feeding strategy to achieve optimal growth in extremely preterm infants? Multiple strategies have been developed during the past few decades to establish enteral feeding, but there is mostly only low-grade evidence promoting the respective methods. This leaves the most important questions unanswered. When should we start enteral nutritional feeds for extremely preterm infants? What is the optimal rate for increasing feeding volumes? What are the target volumes for enteral feeds? Should we provide feeds continuously or every second or every third hour? Should gastric residuals guide our feeding strategy? Is it safe and beneficial to provide fresh unpasteurised breastmilk orally to preterm infants to induce taste sensations and gustatory stimuli? What is the preferable nutrient and what are second-line and third-line nutrients? Should we add prebiotics or probiotics? What is the optimal way of fortifying human breastmilk? All feeding strategies aim to establish enteral feeding that are optimally adapted to the needs of preterm infants, but do not increase the risk of necrotising enterocolitis (NEC), one of the most serious complications during the neonatal period. NEC is by far one of the greatest problems in neonatal care and is, together with sepsis, an increasing cause of neonatal morbidity and mortality (6). There is a growing body of evidence that NEC is associated with enteral nutrition and the risk of increasing NEC influences all feeding regimes. In the current issue of Acta Paediatrica, Meyer et al. (7) present their local feeding strategy as a different view. Their aim was to stimulate the discussion about feeding regimes in preterm infants, focusing on the interplay between optimal growth and development and the severe complications of NEC that result in short-term and long-term sequelae in these infants. In contrast to the current evidence that suggests that rapidly increasing feeding volumes does not seem to alter the risk for developing NEC (8), Meyer et al. propose a more careful feeding strategy based on a slow increment. But it is not only Meyer et al.’s conservative approach to how to increase feeding volumes that makes their nutritional regime noteworthy. Their feeding regime includes a set of ‘substrategies’ to successfully transfer extremely low-birthweight infants from total parenteral nutrition to total enteral feeding. Thus, it is hard to determine whether the slower increment rate of feeding volumes was the main reason for the remarkably low incidence of NEC reported in their paper (7). For example, the feeding regime that the authors described included an active approach to inducing the passage of meconium by regularly using rectal enemas and orally administered Gastrografin. Furthermore, they used the passage of meconium to determine when to start enteral feeding. This resulted in a variable start in enteral feeding, up to as late as one week of life. Using probiotics to prevent NEC, especially in the tiniest infants, has been intensely debated (9). According to the 2014 Cochrane meta-analysis, no beneficial effects have been shown on the incidence of NEC for infants weighing