Brenda Poindexter, MD, MS

Josef Neu, MD

In this third edition of Gastroenterology and Nutrition: Neonatology Questions and Controversies , a number of emerging controversies have been identified by esteemed leaders in the field of neonatal nutrition. Gastroesophageal reflux (GER) and intestinal motility remain extremely important issues in the care of preterm infants. GER, in itself, is a benign physiologic process that only becomes a disease, that is, gastroesophageal reflux disease (GERD), if it causes clinical symptoms or complications. These include worsening of lung disease, irritability, feeding intolerance, failure to thrive, and stridor. Considerable attention has also been paid to respiratory instabilities, such as apnea and bradycardia, but most recent studies have suggested that the relationship among GER, apnea, and bradycardia is weak and that in most cases, GER is not a cause of apnea and/or bradycardia. Therapeutic interventions used routinely in the past for the prevention of apnea and bradycardia, such as histamine 2 blockers, are not warranted, and nonpharmacologic expectant management should be the mainstay of treatment for most infants with suspected apnea and bradycardia. The exact nature of these treatments and strategies requires further study.

Feeding intolerance is a major problem in many preterm infants and has a multifactorial etiology that is primarily rooted in various immaturities of the developing intestinal tract. Gastrointestinal motility, in many cases, may not be of sufficient maturity to allow rapid advancement to full feedings in preterm infants. This is often complicated by comorbidities, such as hypoxia, sepsis, and inflammation. Management of these motility issues should be tailored to the functional maturity level in an individual infant, rather than based on birth, gestation, or postmenstrual age. A combination of systemic signs and symptoms needs to be considered when interpreting feeding readiness in a preterm infant. Of crucial importance is that enteral feedings accelerate gut motility patterns and that even small quantities may be capable of inducing maturation. Thus prolonged periods of nulla per os (NPO) should be unacceptable in these infants. Gastric capacity is small in most of these infants and emptying delayed because of immaturity. Smaller more frequent feedings may be very helpful in such infants. Drug therapy with erythromycin as a prokinetic agent that induces migrating motor complexes may be beneficial, but its safety and efficacy remain inadequately defined. Its use should be limited to rescue treatment of severe persistent feeding intolerance. New technologies that may provide the clinician with tools beyond clinical examination are being developed to aid in deciding how to best proceed with feeding advancement in these infants.

The composition of nutrients provided to preterm infants remains of major importance. For preterm infants, the quantity, timing, and composition of lipids, provided both parenterally and enterally, have been subject to controversy. Too much lipid, especially when provided intravenously in a preparation that may not be physiologic for the preterm infant, can result in liver damage, cholestasis, and lung disease. Newer preparations with different blends of lipids have been developed and are under scrutiny in their effectiveness and safety for the preterm infant. Although human milk lipids are thought to provide the greatest benefit for preterm infants, their delivery in donor human milk that does not contain active lipases may be limiting.

Infants undergoing surgical procedures, especially those related to the intestinal tract for congenital disorders, such as gastroschisis, or acquired disorders, such as necrotizing enterocolitis (NEC), go through prolonged periods of not being able to feed using the gastrointestinal tract. These infants represent a group that is in high need for specialized formulations of parenteral nutritional products, especially essential lipids that provide for optimal growth and neurodevelopment and that do not cause harm. We have the capability to evaluate and develop such products, and it will take a concerted effort by the scientific community, industry, and the regulatory agencies to move forward in this very critical field.

Human milk provides the best form of enteral nutrition for both term and preterm neonates. However, the rapid growth of extremely low–birth weight infants as well as mitigating factors related to intestinal immaturities often necessitates addition of proteins, minerals, and other fortifiers that will help meet their needs for growth and development. Human milk lipids, microbes, and oligosaccharides are difficult to duplicate in commercial preparations, but studies are suggesting that these are valuable components that may be personalized for each infant. The American Academy of Pediatrics and Canadian Pediatric Society have recommended that all babies of a very low gestational age in neonatal intensive care units (NICUs) be provided with either their own mothers’ milk or banked donor milk. Donor milk is pasteurized, and thus microbial components as well as enzymes, cells and other bioactive molecules lose activity and do not provide the same potential value as the baby’s own mother’s milk. There is a need for studies that will enhance provision of the baby’s own mother’s milk and/or provide a human milk substitute that is as effective nutritionally and immunologically as the baby’s own mother’s milk.

NEC is a devastating disease that represents one of the major causes of mortality and morbidity in NICUs. Despite this, even the definition of this disease remains poorly defined and there are multiple pathways to reach intestinal necrosis. Thus what is being termed “NEC” likely represents several different diseases. The prevalence of NEC increases with decreasing gestational age and appears to peak between 29 and 32 weeks’ corrected gestational age. Several developmental components relate to the development of the classic forms of this disease. These include the innate immune system (e.g., Toll-like receptors), development of the microvasculature (with the developing vascular endothelial growth factor pathways) and the developing microbial ecology of the intestine, which interacts with the developing intestinal immune system, as well as formation of interepithelial tight junctions and inflammatory responses. The microbial ecology of babies who develop NEC differs from those who do not develop this disease, and this fact is leading to intense investigation for microbial therapies that may be utilized to prevent this disease.

Infants with surgical conditions continue to present a major challenge for neonatologists, pediatric surgeons, nutritionists, and others caring for these infants. Surgical infants represent a special population at risk for nutrient deficiencies and growth failure. At this time, the appropriate amino acid and lipid composition for these infants is not defined. Long-term outcomes, such as linear growth, body composition, and neurodevelopment, need to be investigated to help guide the nutritional management of these infants.