enteral milk feeds in infants born with very low birth weight may lead to better short-term weight gain and growth but the evidence is uncertain for longer term outcomes and for the risk of serious illness and death. this includes targeted fortification (adjusting the level of nutrients in response to the results of a test on the breast milk) and adjustable fortification (adding nutrients based on testing the infant). multi-nutrient fortifier used to fortify human milk and formula has traditionally been derived from bovine milk. fortifier derived from humans is available, however, the evidence from clinical trials is uncertain and it is not clear if there are any differences between human-derived fortifier and bovine-derived fortifier in terms of neonatal weight gain, feeding intolerance, infections, or the risk of death. timing of feeds for very preterm infants, most neonatal care centres start milk feeds gradually, rather than starting with a full enteral feeding right away, however, is not clear if starting full enteral feeding early effects the risk of necrotising enterocolitis. in these cases, the preterm infant would be receiving the majority of their nutrition and fluids intravenously. the milk volume is usually gradually increased over the following weeks. research into the ideal timing of enteral feeding and whether delaying enteral feeding or gradually introducing enteral feeds is beneficial at improving growth for preterm infants or low birth weight infants is needed. in addition, the ideal timing of enteral feeds to prevent side effects such as necrotising enterocolitis or mortality in preterm infants who require a packed red blood cell transfusion is not clear. potential disadvantages of a more gradual approach to feeding preterm infants associated with less milk in the gut and include slower gi tract secretion of hormones and gut motility and slower microbial colonization of the gut. regarding the timing of starting fortified milk, preterm infants are often started on fortified milk/formula once they are fed 100 ml/kg of their body weight. other some neonatal specialists feel that starting to feed a preterm infant fortified milk earlier is beneficial to improve intake of nutrients. the risks of feeding intolerance and necrotising enterocolitis related to early versus later fortification of human milk are not clear. once the infant is able to go home from the hospital there is limited evidence to support prescribing a preterm (fortified) formula. intermittent feeding versus continuous feeding for infants who weigh less than 1500 grams, tube feeding is usually necessary. most often, neonatal specialists feed preterm babies intermittently with a prescribed amount of milk over a short period of time. for example, a feed could last 10–20 minutes and be given every 3 hours. this intermittent approach is meant to mimic conditions of normal bodily functions involved with feeding and allow for a cyclic pattern in the release of gastrointestinal tract hormones to promote development of the gastrointestinal system. in certain cases, continuous nasogastric feeding is sometimes preferred. there is low to very low certainty evidence to suggest that low birth weight babies who receive continuous nasogastic feeding may reach the benchmark of tolerating full enteral feeding later than babies fed intermittently and it is not clear if continuous feeding has any effect on weight gain or the number of interruptions in feedings. continuous feeding may have little to no effect on length of body growth or head circumference and the effects of continuous feeding on the risk of developing necrotising enterocolitis is not clear. since preterm infants with gastro-oesophageal reflux disease do not have a fully developed antireflux mechanism, deciding on the most effective approach for nutrition is important. it is not clear if continuous bolus intragastric tube feeding is more effective compared to intermittent bolus intragastric tube feeding for feeding preterm infants with gastroesophageal reflux disease. for infants who would benefit from intermittent bolus feeding, some infants may be fed using the "push feed" method using a syringe to gently push the milk or formula into the stomach of the infant. others may be fed using a gravity feeding system where the syringe is attached directly to a tube and the milk or formula drips into the infant's stomach. it is not clear from medical studies which approach to intermittent bolus feeding is more effective or reduces adverse effects such as apnea, bradycardia, or oxygen desaturation episodes. high volume feeds high-volume (more than 180 ml per kilogram per day) enteral feeds of fortified or non-fortified human breast milk or formula may improve weight gain while the pre-term infant is hospitalized, however, there is insufficient evidence to determine if this approach improves growth of the neonate and other clinical outcomes including length of hospital stay. the risks or adverse effects associated with high-volume enteral feeding of preterm infants including aspiration pneumonia, reflux, apnea, and sudden oxygen desaturation episodes have not been reported in the trials considered in a 2021 systematic review. parenteral (intraveneous) nutrition for preterm infants who are born after 34 weeks of gestation ("late preterm infants") who are critically ill and cannot tolerate milk, there is some weak evidence that the infant may benefit from including amino acids and fats in the intravenous nutrition at a later time point (72 hours or longer from hospital admission) versus early (less than 72 hours from admission to hospital), however further research is required to understand the ideal timing of starting intravenous nutrition. gastric residuals for preterm infants in neonatal intensive care on gavage feeds, monitoring the volume and colour of gastric residuals, the milk and gastrointestinal secretions that remain in the stomach after a set amount of time, is common standard of care practice. gastric residual often contains gastric acid, hormones, enzymes, and other substances that may help improve digestion and mobility of the gastrointestinal tract. analysis of gastric residuals may help guide timing of feeds. increased gastric residual may indicate feeding intolerance or it may be an early sign of necrotizing enterocolitis. increased gastric residual may be caused by an underdeveloped gastrointestinal system that leads to slower gastric emptying or movement of the milk in the intestinal tract, reduced hormone or enzyme secretions from the gastrointestinal tract, duodenogastric reflux, formula, medications, and/or illness. the clinical decision to discard the gastric residuals (versus re-feeding) is often individualized based on the quantity and quality of the residual. some experts also suggest replacing the fresh milk or curded milk and bile-stained aspirates, but not replacing haemorrhagic residual. evidence to support or refute the practice of re-feeding preterm infants with gastric residuals is lacking. hearing assessment the joint committee on infant hearing (jcih) state that for preterm infants who are in the neonatal intensive care unit (nicu) for a prolonged time should have a diagnostic audiologic evaluation before they are discharged from the hospital. well babies follow a 1-2-3-month benchmark timeline where they are screened, diagnosed, and receiving intervention for a hearing loss. however, very premature babies it might not be possible to complete a hearing screen at one month of age due to several factors. once the baby is stable an audiologic evaluation should be performed. for premature babies in the nicu, auditory brainstem response (abr) testing is recommended. if the infant does not pass the screen, they should be referred for an audiologic evaluation by an audiologist. if the infant is on aminoglycosides such as gentamicin for less than five days they should be monitored and have a follow up 6–7 months of being discharged from the hospital to ensure there is no late onset hearing loss due to the medication. outcomes and prognosis preterm infants survival rates preterm births can result in a range of problems including mortality and physical and mental delays. mortality and morbidity in the u.s. where many neonatal infections and other causes of neonatal death have been markedly reduced, prematurity is the leading cause of neonatal mortality at 25%. prematurely born infants are also at greater risk for having subsequent serious chronic health problems as discussed below. the earliest gestational age at which the infant has at least a 50% chance of survival is referred to as the limit of viability. as nicu care has improved over the last 40 years, the limit of viability has reduced to approximately 24 weeks. most newborns who die, and 40% of older infants who die, were born between 20 and 25.9 weeks (gestational age), during the second trimester. as risk of brain damage and developmental delay is significant at that threshold even if the infant survives, there are ethical controversies over the aggressiveness of the care rendered to such infants. the limit of viability has also become a factor in the abortion debate. specific risks for the preterm neonate preterm infants usually show physical signs of prematurity in reverse proportion to the gestational age. as a result, they are at risk for numerous medical problems affecting different organ systems. neurological problems can include apnea of prematurity, hypoxic-ischemic encephalopathy (hie), retinopathy of prematurity (rop), developmental disability, transient hyperammonemia, cerebral palsy, and intraventricular hemorrhage, the latter affecting 25% of babies born preterm, usually before 32 weeks of pregnancy. mild brain bleeds usually leave no or few lasting complications, but severe bleeds often result in brain damage or even death. neurodevelopmental problems have been linked to lack of maternal thyroid hormones, at a time when their own thyroid is unable to meet postnatal needs. cardiovascular complications may arise from the failure of the ductus arteriosus to close after birth: patent ductus arteriosus (pda). respiratory problems are common, specifically the respiratory distress syndrome (rds or irds) (previously called hyaline membrane disease). another problem can be chronic lung disease (previously called bronchopulmonary dysplasia or bpd). gastrointestinal and metabolic issues can arise from neonatal hypoglycemia, feeding difficulties, rickets of prematurity, hypocalcemia, inguinal hernia, and necrotizing enterocolitis (nec). hematologic complications include anemia of prematurity, thrombocytopenia, and hyperbilirubinemia (jaundice) that can lead to kernicterus. infection, including sepsis, pneumonia, and urinary tract infection survival the chance of survival at 22 weeks is about 6%, while at 23 weeks it is 26%, 24 weeks 55% and 25 weeks about 72% as of 2016. with extensive treatment up to 30% of those who survive birth at 22 weeks survive longer term as of 2019. the chances of survival without long-term difficulties is less. of those who survive following birth at 22 weeks 33% have severe disabilities. in the developed world, overall survival is about 90% while in low-income countries survival rates are about 10%. some children will adjust well during childhood and adolescence, although disability is more likely nearer the limits of viability. a large study followed children born between 22 and 25 weeks until the age of 6 years old. of these children, 46% had moderate to severe disabilities such as cerebral palsy, vision or hearing loss and learning disabilities, 34% had mild disabilities, and 20% had no disabilities; 12% had disabling cerebral palsy. up to 15% premature infants have significant hearing loss. as survival has improved, the focus of interventions directed at the newborn has shifted to reduce long-term disabilities, particularly those related to brain injury. some of the complications related to prematurity may not be apparent until years after the birth. a long-term study demonstrated that the risks of medical and social disabilities extend into adulthood and are higher with decreasing gestational age at birth and include cerebral palsy, intellectual disability, disorders of psychological development, behavior, and emotion, disabilities of vision and hearing, and epilepsy. standard intelligence tests showed that 41% of children born between 22 and 25 weeks had moderate or severe learning disabilities when compared to the test scores of a group of similar classmates who were born at full term. it is also shown that higher levels of education were less likely to be obtained with decreasing gestational age at birth. people born prematurely may be more susceptible to developing depression as teenagers. some of these problems can be described as being within the executive domain and have been speculated to arise due to decreased myelinization of the frontal lobes. studies of people born premature and investigated later with mri brain imaging, demonstrate qualitative anomalies of brain structure and grey matter deficits within temporal lobe structures and the cerebellum that persist into adolescence. throughout life they are more likely to require services provided by physical therapists, occupational therapists, or speech therapists. they are more likely