Editing Preterm birth (section)

===Nutrition===
Meeting the appropriate nutritional needs of preterm infants is important for long-term health. Optimal care may require a balance of meeting nutritional needs and preventing complications related to feeding. The ideal growth rate is not known; however, preterm infants usually require a higher energy intake compared to babies who are born at term.<ref name="Abiramalatha_2021">{{cite journal | vauthors = Abiramalatha T, Thomas N, Thanigainathan S | title = High versus standard volume enteral feeds to promote growth in preterm or low birth weight infants | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 3 | pages = CD012413 | date = March 2021 | pmid = 33733486 | pmc = 8092452 | doi = 10.1002/14651858.CD012413.pub3 }}</ref> The recommended amount of milk is often prescribed based on approximated nutritional requirements of a similar aged fetus who is not compromised.<ref name="Walsh_2020">{{cite journal | vauthors = Walsh V, Brown JV, Copperthwaite BR, Oddie SJ, McGuire W | title = Early full enteral feeding for preterm or low birth weight infants | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 12 | pages = CD013542 | date = December 2020 | pmid = 33368149 | pmc = 8094920 | doi = 10.1002/14651858.CD013542.pub2 }}</ref> An immature [[gastrointestinal tract]] (GI tract), medical conditions (or [[Comorbidity|co-morbidities]]), risk of aspirating milk, and [[necrotizing enterocolitis]] may lead to difficulties in meeting this high nutritional demand and many preterm infants have nutritional deficits that may result in growth restrictions.<ref name="Walsh_2020" /> In addition, very small preterm infants cannot coordinate sucking, swallowing, and breathing.<ref name="Sadrudin Premji_2021">{{cite journal | vauthors = Sadrudin Premji S, Chessell L, Stewart F | title = Continuous nasogastric milk feeding versus intermittent bolus milk feeding for preterm infants less than 1500 grams | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 6 | pages = CD001819 | date = June 2021 | pmid = 34165778 | pmc = 8223964 | doi = 10.1002/14651858.CD001819.pub3 }}</ref> Tolerating a full enteral feeding (the prescribed volume of milk or formula) is a priority in neonatal care as this reduces the risks associated with [[venous catheter]]s including infection, and may reduce the length of time the infant requires specialized care in the hospital.<ref name="Walsh_2020" /> Different strategies can be used to optimize feeding for preterm infants. The type of milk/formula and fortifiers, route of administration (by mouth, tube feeding, venous catheter), timing of feeding, quantity of milk, continuous or intermittent feeding, and managing gastric residuals are all considered by the neonatal care team when optimizing care. The evidence in the form of high quality randomized trials is generally fairly weak in this area, and for this reason different neonatal intensive care units may have different practices and this results in a fairly large variation in practice. The care of preterm infants also varies in different countries and depends on resources that are available.<ref name="Walsh_2020" />

==== Human breast milk and formula ====
The [[American Academy of Pediatrics]] recommended feeding preterm infants [[Breastfeeding|human milk]], finding "significant short- and long-term beneficial effects," including lower rates of [[necrotizing enterocolitis]] (NEC).<ref>{{cite journal | title = Breastfeeding and the use of human milk | journal = Pediatrics | volume = 129 | issue = 3 | pages = e827–e841 | date = March 2012 | pmid = 22371471 | doi = 10.1542/peds.2011-3552 | quote = Meta-analyses of 4 randomized clinical trials performed over the period 1983 to 2005 support the conclusion that feeding preterm infants human milk is associated with a significant reduction (58%) in the incidence of NEC. | doi-access = free | last1 = Eidelman | first1 = Arthur I. | last2 = Schanler | first2 = Richard J. | last3 = Johnston | first3 = Margreete | last4 = Landers | first4 = Susan | last5 = Noble | first5 = Larry | last6 = Szucs | first6 = Kinga | last7 = Viehmann | first7 = Laura }}</ref> In the absence of evidence from randomised controlled trials about the effects of feeding preterm infants with formula compared with mother's own breast milk, data collected from other types of studies suggest that mother's own breast milk is likely to have advantages over formula in terms of the baby's growth and development.<ref>{{cite journal | vauthors = Brown JV, Walsh V, McGuire W | title = Formula versus maternal breast milk for feeding preterm or low birth weight infants | journal = The Cochrane Database of Systematic Reviews | volume = 8 | issue = 8 | pages = CD002972 | date = August 2019 | pmid = 31452191 | pmc = 6710607 | doi = 10.1002/14651858.CD002972.pub3 }}</ref><ref name="Abiramalatha_2021" /> Milk from human donors also reduces the risk of NEC by half in very low birth rate infants and very preterm infants.<ref name=":1" />

Breast milk or formula alone may not be sufficient to meet the nutritional needs of some preterm infants. Fortification of breast milk or formula by adding extra nutrients is an approach often taken for feeding preterm infants, with the goal of meeting the high nutritional demand.<ref name="Abiramalatha_2021" /> High quality randomized controlled trials are needed in this field to determine the effectiveness of fortification.<ref name="Brown_2016" /> It is unclear if fortification of breast milk improves outcomes in preterm babies, though it may speed growth.<ref name="Brown_2016">{{cite journal | vauthors = Brown JV, Embleton ND, Harding JE, McGuire W | title = Multi-nutrient fortification of human milk for preterm infants | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD000343 | date = May 2016 | pmid = 27155888 | doi = 10.1002/14651858.CD000343.pub3 | hdl = 2292/57382 | hdl-access = free }}</ref> Supplementing human milk with extra protein may increase short-term growth but the longer-term effects on body composition, growth and brain development are uncertain.<ref>{{cite journal | vauthors = Amissah EA, Brown J, Harding JE | title = Protein supplementation of human milk for promoting growth in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 9 | pages = CD000433 | date = September 2020 | pmid = 32964431 | pmc = 8094919 | doi = 10.1002/14651858.CD000433.pub3 }}</ref><ref>{{cite journal | vauthors = Gao C, Miller J, Collins CT, Rumbold AR | title = Comparison of different protein concentrations of human milk fortifier for promoting growth and neurological development in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 11 | pages = CD007090 | date = November 2020 | pmid = 33215474 | pmc = 8092673 | doi = 10.1002/14651858.CD007090.pub2 }}</ref> Higher protein formula (between 3 and 4 grams of protein per kilo of body weight) may be more effective than low protein formula (less than 3 grams per kilo per day) for weight gain in formula-fed low-birth-weight infants.<ref>{{cite journal | vauthors = Fenton TR, Al-Wassia H, Premji SS, Sauve RS | title = Higher versus lower protein intake in formula-fed low birth weight infants | journal = The Cochrane Database of Systematic Reviews | volume = 6 | issue = 6 | pages = CD003959 | date = June 2020 | pmid = 32573771 | pmc = 7387284 | doi = 10.1002/14651858.CD003959.pub4 }}</ref> There is insufficient evidence about the effect on preterm babies' growth of supplementing human milk with carbohydrate,<ref>{{cite journal | vauthors = Amissah EA, Brown J, Harding JE | title = Carbohydrate supplementation of human milk to promote growth in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 9 | issue = 9 | pages = CD000280 | date = September 2020 | pmid = 32898300 | pmc = 8094174 | doi = 10.1002/14651858.CD000280.pub3 }}</ref> fat,<ref>{{cite journal | vauthors = Amissah EA, Brown J, Harding JE | title = Fat supplementation of human milk for promoting growth in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 8 | issue = 8 | pages = CD000341 | date = August 2020 | pmid = 32842164 | pmc = 8236752 | doi = 10.1002/14651858.CD000341.pub3 }}</ref><ref>{{cite journal | vauthors = Perretta L, Ouldibbat L, Hagadorn JI, Brumberg HL | title = High versus low medium chain triglyceride content of formula for promoting short-term growth of preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 2 | pages = CD002777 | date = February 2021 | pmid = 33620090 | pmc = 8094384 | doi = 10.1002/14651858.CD002777.pub2 }}</ref> and branched-chain amino acids.<ref>{{cite journal | vauthors = Amari S, Shahrook S, Namba F, Ota E, Mori R | title = Branched-chain amino acid supplementation for improving growth and development in term and preterm neonates | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 10 | pages = CD012273 | date = October 2020 | pmid = 33006765 | pmc = 8078205 | doi = 10.1002/14651858.CD012273.pub2 }}</ref> Conversely, there is some indication that preterm babies who cannot breastfeed may do better if they are fed only with diluted formula compared to full strength formula but the clinical trial evidence remains uncertain.<ref>{{cite journal | vauthors = Basuki F, Hadiati DR, Turner T, McDonald S, Hakimi M | title = Dilute versus full-strength formula in exclusively formula-fed preterm or low birth weight infants | journal = The Cochrane Database of Systematic Reviews | volume = 6 | issue = 6 | pages = CD007263 | date = June 2019 | pmid = 31246272 | pmc = 6596360 | doi = 10.1002/14651858.CD007263.pub3 }}</ref>

Individualizing the nutrients and quantities used to fortify [[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.<ref name="Fabrizio_2020">{{cite journal | vauthors = Fabrizio V, Trzaski JM, Brownell EA, Esposito P, Lainwala S, Lussier MM, Hagadorn JI | title = Individualized versus standard diet fortification for growth and development in preterm infants receiving human milk | journal = The Cochrane Database of Systematic Reviews | volume = 11 | issue = 11 | pages = CD013465 | date = November 2020 | pmid = 33226632 | pmc = 8094236 | doi = 10.1002/14651858.CD013465.pub2 }}</ref> 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).<ref name="Fabrizio_2020" />

Multi-nutrient fortifier used to fortify human milk and formula has traditionally been derived from [[bovine milk]].<ref name="Premkumar_2019">{{cite journal | vauthors = Premkumar MH, Pammi M, Suresh G | title = Human milk-derived fortifier versus bovine milk-derived fortifier for prevention of mortality and morbidity in preterm neonates | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 11 | date = November 2019 | pmid = 31697857 | pmc = 6837687 | doi = 10.1002/14651858.CD013145.pub2 }}</ref> 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.<ref name="Premkumar_2019" />

==== 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, it is not clear if starting full enteral feeding early affects the risk of necrotising enterocolitis.<ref name="Walsh_2020" /> 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.<ref name="Walsh_2020" /> 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.<ref name="Walsh_2020" /> 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.<ref>{{cite journal | vauthors = Yeo KT, Kong JY, Sasi A, Tan K, Lai NM, Schindler T | title = Stopping enteral feeds for prevention of transfusion-associated necrotising enterocolitis in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 10 | date = October 2019 | pmid = 31684689 | pmc = 6815687 | doi = 10.1002/14651858.CD012888.pub2 }}</ref> 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.<ref name="Walsh_2020" />

Regarding the timing of starting fortified milk, preterm infants are often started on fortified milk/formula once they are fed 100&nbsp;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.<ref name="Thanigainathan_2020">{{cite journal | vauthors = Thanigainathan S, Abiramalatha T | title = Early fortification of human milk versus late fortification to promote growth in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 7 | pages = CD013392 | date = July 2020 | pmid = 32726863 | pmc = 7390609 | doi = 10.1002/14651858.CD013392.pub2 }}</ref> The risks of feeding intolerance and necrotising enterocolitis related to early versus later fortification of human milk are not clear.<ref name="Thanigainathan_2020" /> Once the infant is able to go home from the hospital there is limited evidence to support prescribing a preterm (fortified) formula.<ref>{{cite journal | vauthors = Young L, Embleton ND, McGuire W | title = Nutrient-enriched formula versus standard formula for preterm infants following hospital discharge | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 12 | pages = CD004696 | date = December 2016 | pmid = 27958643 | pmc = 6463855 | doi = 10.1002/14651858.CD004696.pub5 }}</ref>

==== Intermittent feeding versus continuous feeding ====
For infants who weigh less than 1500 grams, tube feeding is usually necessary.<ref name="Sadrudin Premji_2021" /> 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.<ref name="Sadrudin Premji_2021" /> 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.<ref name="Sadrudin Premji_2021" /> 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.<ref name="Sadrudin Premji_2021" />

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]].<ref>{{cite journal | vauthors = Richards R, Foster JP, Psaila K | title = Continuous versus bolus intermittent intragastric tube feeding for preterm and low birth weight infants with gastro-oesophageal reflux disease | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 8 | pages = CD009719 | date = August 2021 | pmid = 34355390 | pmc = 8407337 | doi = 10.1002/14651858.CD009719.pub3 }}</ref>

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.<ref>{{cite journal | vauthors = Dawson JA, Summan R, Badawi N, Foster JP | title = Push versus gravity for intermittent bolus gavage tube feeding of preterm and low birth weight infants | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 8 | pages = CD005249 | date = August 2021 | pmid = 34346056 | pmc = 8407046 | doi = 10.1002/14651858.CD005249.pub3 }}</ref><ref>{{cite journal | vauthors = Akindolire A, Talbert A, Sinha I, Embleton N, Allen S | title = Evidence that informs feeding practices in very low birthweight and very preterm infants in sub-Saharan Africa: an overview of systematic reviews | journal = BMJ Paediatrics Open | volume = 4 | issue = 1 | pages = e000724 | date = 2020 | pmid = 32821859 | pmc = 7422638 | doi = 10.1136/bmjpo-2020-000724 }}</ref>

==== High volume feeds ====
High-volume (more than 180&nbsp;mL per kilogram per day) [[Enteral administration|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.<ref name="Abiramalatha_2021" /> The risks or adverse effects associated with high-volume enteral feeding of preterm infants including [[aspiration pneumonia]], [[Gastroesophageal reflux disease|reflux]], [[apnea]], and sudden oxygen desaturation episodes have not been reported in the trials considered in a 2021 [[systematic review]].<ref name="Abiramalatha_2021" />

==== Parenteral (intraveneous) nutrition ====
For preterm infants who are born after 34 weeks of gestation ("[[late preterm infant]]s") 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.<ref>{{cite journal | vauthors = Moon K, Athalye-Jape GK, Rao U, Rao SC | title = Early versus late parenteral nutrition for critically ill term and late preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 4 | pages = CD013141 | date = April 2020 | pmid = 32266712 | pmc = 7138920 | doi = 10.1002/14651858.CD013141.pub2 }}</ref>

==== Gastric residuals ====
For preterm infants in neonatal intensive care on [[Gavage|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.<ref name="Abiramalatha_2023">{{cite journal |last1=Abiramalatha |first1=T |last2=Thanigainathan |first2=S |last3=Ramaswamy |first3=VV |last4=Rajaiah |first4=B |last5=Ramakrishnan |first5=S |title=Re-feeding versus discarding gastric residuals to improve growth in preterm infants. |journal=The Cochrane Database of Systematic Reviews |date=30 June 2023 |volume=2023 |issue=6 |pages=CD012940 |doi=10.1002/14651858.CD012940.pub3 |pmid=37387544 |pmc=10312053 |ref=Abiramalatha_2023 }}</ref> Gastric residual often contains gastric acid, hormones, enzymes, and other substances that may help improve digestion and mobility of the gastrointestinal tract.<ref name="Abiramalatha_2023" /> Analysis of gastric residuals may help guide timing of feeds.<ref name="Abiramalatha_2023" /> Increased gastric residual may indicate feeding intolerance or it may be an early sign of necrotizing enterocolitis.<ref name="Abiramalatha_2023" /> 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 [[Gastroesophageal reflux disease|reflux]], formula, medications, and/or illness.<ref name="Abiramalatha_2023" /> The clinical decision to discard the gastric residuals (versus re-feeding) is often individualized based on the quantity and quality of the residual.<ref name="Abiramalatha_2023" /> Some experts also suggest replacing the fresh milk or curded milk and bile-stained aspirates, but not replacing haemorrhagic residual.<ref name="Abiramalatha_2023" /> Evidence to support or refute the practice of re-feeding preterm infants with gastric residuals is lacking.<ref name="Abiramalatha_2023" />