Enteral Nutrition inPreterm Neonates Dr Varsha Atul Shah
Introduction Proper nutrition in infancy is essential for – normal growth – immunity to infection – optimal neurologic and cognitive development. Providing adequate nutrition to preterm infants is challenging because of several problems, some of them unique to these small infants. These problems include: – immaturity of bowel function – inability to suck and swallow – high risk of necrotizing enterocolitis (NEC) – illnesses that may interfere with adequate enteral feeding (e.g. RDS, patent ductus arteriosus) – medical interventions that preclude feeding (e.g., umbilical vessel catheters, exchange transfusion, indomethacin therapy)
Long term outcome and Barker’s Hypothesis There is evidence that adaptations in the metabolic and hormonal milieu in the fetal and immediate neonatal period can result in immediate benefit but adverse long-term outcome. Nutritional insults at a vulnerable period of brain development, for example, have been shown to be associated with effects on brain size, cell number, behavior and learning memory. The emergence of cardiovascular disease, hypertension, insulin resistance and obesity in low birth weight infants is another concern raising the issue of long-term ‘‘programming.’’ In addition, there may be transgenerational effects as evidenced by the association of low maternal birth weight and higher offspring hypertension in adulthood. These changes may be exacerbated by postnatal malnutrition and poor growth that preterm infants experience.
PHYSIOLOGY AND PATHOPHYSIOLOGY The gut has formed and has completed its rotation back into the abdominal cavity by 10 weeks of gestation. By 16 weeks, the fetus can swallow amniotic fluid. GI motor activity is present before 24 weeks, but organized peristalsis is not established until 29-30 weeks and is facilitated by antenatal corticosteroid treatment. Coordinated sucking and swallowing develops at 32-34 weeks. By term, the fetus swallows about 150 cc/kg/day of amniotic fluid, which has 275 mOsm/L, contains carbohydrates, protein, fat, electrolytes, immunoglobulins and growth factors, and plays an important role in development of GI function. Preterm birth interrupts this development.
Importance of Enteral Feeding Even if nutrients are provided parenterally, lack of enteric intake leads to – decreased circulating gut peptides – slower enterocyte turnover and nutrient transport – decreased bile acid secretion – increased susceptibility to infection due to impaired barrier function by intestinal epithelium, lack of colonization by normal commensal flora and colonization by pathogenic organisms. For fat digestion, the newborn depends on lingual lipase, which is stimulated by sucking and swallowing and by nutrients in the stomach but not the small bowel.
Trophic feedings for parenterally fed infants (Review) 2008 The Cochrane Collaboration Trophic feeding defined as dilute or full strength feedings providing < = 25 ml/kg/d for > = 5d (5-10days) Trophic feedings vs. no feedings (10 trials): Among infants given trophic feedings, there was an overall reduction in days to full feeding (weighted mean difference [WMD] = -2.6 [95% confidence limits = -4.1, -1.0]), total days that feedings were held (WMD = -3.1 [-4.6, -1.6]), and total hospital stay (WMD = -11.4 [-17.2, -5.7] compared to infants given no enteral nutrient intake. Tests for heterogeneity were significant in analyses of days to full enteral feedings, days to regain birth weight, days of phototherapy, and hospital stay. There was no significant difference in necrotizing enterocolitis, although the findings do not exclude an important effect (relative risk = 1.16 [0.75, 1.79]; risk difference = 0.02 [-0.03, 0.06]. Trophic feedings vs. advancing feedings (one trial): Infants given trophic feedings required more days to reach full enteral feeding (13.4 [8.2, 18.6]) and tended to have a longer hospital stay (11.0 [-1.4, 23.4]) than did infants given advancing feedings. With only eight total cases of necrotizing enterocolitis, trophic feedings were associated with a marginally significant reduction in necrotizing enterocolitis (relative risk =0.14 [0.02, 1.07]; risk difference = -0.09 [-0.16, -0.01].
Authors’ conclusions In both comparisons, the group with the greater enteral intake (trophic feedings in the first comparison and advancing feedings in the second comparison) required significantly less time to reach full feedings and had a significant or near significant reduction in hospital stay. In both comparisons, the group with the greater intake also had a higher incidence of NEC although the difference was not statistically significant. The concern is greatest for the advancing feeding regimen. Even when trophic feedings were compared to no feedings, the relative risk for NEC was 1.16 (0.75 - 1.79), a finding consistent with a 16% increase in NEC and a NNH of 50. A true increase of this magnitude might outweigh any shorter or long-term benefits of trophic feedings. Moreover, the 95% CI does not exclude the possibility that trophic feedings increase NEC by as much as 79% with a NNH of 17. Whether no feedings, trophic feedings, or advancing feedings should initially be used is difficult to discern for a variety of reasons—the inherent difficulty of assessing enteral feedings in high-risk infants, the limited sample size and methodologic limitations of most studies to date, unexplained heterogeneity with respect to a number of outcomes, the potential for bias to affect the findings in unblinded studies, and the large number of infants who must be studied to assess the effect on necrotizing enterocolitis. One or more large, well designed, multi-center trials are needed to compare these approaches to early feeding with respect to important clinical outcomes. A conclusive evaluation would assess effects on not only the survival rate without necrotizing enterocolitis prior to discharge from the neonatal unit but also on the survival rate without severe gastrointestinal or neurodevelopmental disability at >= 18 months age.
Nasal versus oral route for placing feeding tubes inpreterm or low birth weight infants. 2008 Cochrane CollaborationMain results Two small randomised trials were identified. Only one trial reported data on the pre-specified primary outcomes for this review. This trial found no evidence of effect on the time taken to establish enteral feeding nor the time taken to regain birth weight. However, the trial was underpowered (N= 46) to exclude modest effect sizes.Authors’ conclusions There are insufficient data available to inform practice. A large randomised controlled trial is required to determine if the use of naso vs oro-enteric feeding tubes affects feeding, growth and development, and the incidence of adverse consequences in preterm or low birth weight infants.
Continuous nasogastric milk feeding versus intermittent bolus milk feeding for premature infants less than 1500 grams, 2008 Cochrane collaborationMain results Overall, the seven included trials, involving 511 infants, found no differences in time to achieve full enteral feeds between feeding methods (weighted mean difference (WMD 2 days; 95%CI -0.3, 3.9) . In the subgroup analysis of those studies comparing continuous nasogastric vs. intermittent bolus nasogastric milk feedings the findings remained unchanged (WMD 2 days, 95% CI -0.4, 4.1). There was no significant difference in somatic growth and incidence of NEC between feeding methods irrespective of tube placement. One study noted a trend toward more apneas during the study period in infants fed by the continuous tube feeding method compared to those fed by intermittent feedings delivered predominantly by orogastric tube placements [mean difference (MD) 14.0 apneas during study period; 95% CI -0.2, 28.2]. In subgroup analysis based on weight groups, one study suggested that infants less than 1000 grams and 1000 - 1250 grams birth weight gained weight faster when fed by the continuous nasogastric tube feeding method compared to intermittent nasogastric tube feeding method (MD 2.0 g/day; 95% CI 0.5, 3.5; MD 2.0 g/day; 95% CI 0.2, 3.8, respectively).
A trend toward earlier discharge for infants less than 1000 grams birth weight fed by the continuous tube feeding method compared to intermittent nasogastric tube feeding method (MD -11 days; 95% CI -21.8, -0.2).Authors’ conclusions Small sample sizes, methodologic limitations, inconsistencies in controlling variables that may affect outcomes, and conflicting results of the studies to date make it difficult to make universal recommendations regarding the best tube feeding method for premature infants less than 1500 grams. The clinical benefits and risks of continuous vs. intermittent nasogastric tube milk feeding cannot be reliably discerned from the limited information available from randomized trials to date.
Transpyloric versus gastric tube feeding for preterm infants. 2008 Cochrane Collaboration Data from nine trials were available. No evidence of an effect on short term growth rates was found: weight:WMD -0.7 g/week (95% confidence interval (CI) -25.2, 23.8); crown heel length: WMD -0.7 mm/week (95% CI -2.4, 1.0); head circumference: WMD 0.6 mm/week (95% CI -0.9, 2.1). Longer term growth was reported in one study. There were not any statistically significant differences between the groups in the mean body weight or occipitofrontal head circumference at three months or at six months corrected age. None of the included studies provided data on neurodevelopmental outcomes. Transpyloric feeding was associated with a greater incidence of gastro- intestinal disturbance (RR 1.45, 95% CI 1.05, 2.09). There was some evidence that feeding via the transpyloric route increased mortality (RR 2.46, 95% CI 1.36, 4.46). However, the outcomes of the study that contributed most to this finding were likely to have been affected by selective allocation of the less mature and sicker infants to transpyloric feeding.
No statistically significant differences in the incidence of other adverse events, including necrotising enterocolitis, intestinal perforation, and aspiration pneumonia was found.Authors’ conclusions No evidence of any beneficial effect of transpyloric feeding in preterm infants was found. However, evidence of adverse effects was noted. Feeding via the transpyloric route cannot be recommended for preterm infants
Ad libitum or demand/semi-demand feeding versus scheduled interval feeding for preterm infants, 2008 Cochrane collaboration Seven randomised controlled trials that compared ad libitum or demand/semi- demand regimes with scheduled interval regimes in preterm infants in the transition phase from intragastric tube to oral feeding were found. The trials were generally small and of variable methodological quality. The duration of the intervention and the duration of data collection and follow up in most of the trials is not likely to have allowed detection of measurable effects on growth. The single trial that assessed growth for longer than one week found that the rate of weight gain was lower in the ad libitum fed infants [mean difference -3.30 (95% confidence interval -6.2 to -0.4) grams per kilogram per day]. Two trials reported that feeding preterm infants using an ad libitum or demand/semi- demand feeding regime allowed earlier discharge from hospital, but the other trials did not confirm this finding. Not able to undertake meta-analyses because of differences in study design and in the way the findings were reported.Authors’ conclusions There are insufficient data at present to guide clinical practice. A large randomised controlled trial is needed to determine if ad libitum of demand/semi-demand feeding of preterm infants affects clinically important outcomes. This trial should focus on infants in the transition phase from intragastric tube to oral feeding and should be of sufficient duration to assess effects on growth and time to oral feeding and hospital discharge.
Formula milk versus maternal breast milk for feeding preterm or low birth weight infants 2008 Cochrane Collaboration.Main results No eligible trials were identified.Authors’ conclusions There are no data from randomised trials of formula milk versus maternal breast milk for feeding preterm or low birth weight infants. This may relate to a perceived difficulty of allocating an alternative feed to an infant whose mother wishes to feed with her own breast milk. Maternal breast milk remains the default choice of enteral nutrition because observational studies, and meta-analyses of trials comparing feeding with formula milk versus donor breast milk, suggest that feeding with breastmilk has major non-nutrient advantages for preterm or low birth weight infants.
Donor breast milk versus infant formula for preterminfants: systematic review and meta-analysisCochrane collaboration 2006Results:•Seven studies (including five randomised controlled trials), all from the 1970sand 1980s, fulfilled the inclusion criteria. All studies compared the effect of soledonor breast milk with formula (combined n = 471). One of these also comparedthe effect of donor breast milk with formula given as a supplement to mother’sown milk (n = 343). No studies examined fortified donor breast milk.•A meta-analysis based on three studies found a lower risk of NEC in infantsreceiving donor breast milk compared with formula (combined RR 0.21, 95% CI0.06 to 0.76).•Donor breast milk was associated with slower growth in the early postnatalperiod, but its long-term effect is unclear.Conclusion:•Donor breast milk is associated with a lower risk of NEC and slower growth inthe early postnatal period, but the quality of the evidence is limited. Furtherresearch is needed to confirm these findings and measure the effect of fortifiedor supplemented donor breast milk.
Protein supplementation of human milk for promoting growth in preterm infants Cochrane collaboration 2000MAIN RESULTS:•Protein supplementation of human milk results in increases in short termweight gain (WMD 3.6 g/kg/day, 95% CI 2.4 to 4.8 g/kg/day), linear growth(WMD 0.28 cm/week, 95% CI 0.18 to 0.38 cm/week) and head growth (WMD0.15 cm/week, 95% CI 0.06 to 0.23 cm/week).•There are insufficient data to evaluate long term neurodevelopmental andgrowth outcomes. There are too few infants studied to be certain that adverseeffects of protein supplementation are not increased. Blood urea levels areincreased (WMD 1.0 mmol/l, 95% CI 0.8 to 1.2 mmol/l).REVIEWERS CONCLUSIONS:•Protein supplementation of human milk in relatively well preterm infants resultsin increases in short term weight gain, linear and head growth. Urea levels areincreased, which may reflect adequate rather than excessive dietary proteinintake.•Further research should be directed towards the evaluation of specific levelsof protein intake in preterm infants and the clinical effects of supplementationwith protein, including long term growth and neurodevelopmental outcomes.This may best be done in the context of refinement of available multicomponentfortifier preparations.
Multicomponent fortified human milk for promoting growth inpreterm infants.Cochrane collaboration 2004MAIN RESULTS• Supplementation of human milk with multicomponent fortifiers (in the form of protein,calcium, phosphate, and carbohydrate, as well as vitamins and trace minerals) isassociated with short term increases in weight gain, linear and head growth. There is noeffect on serum alkaline phosphatase levels; it is not clear if there is an effect on bonemineral content. Nitrogen retention and blood urea levels appear to be increased.•There are insufficient data to evaluate long term neurodevelopmental and growthoutcomes, although there appears to be no effect on growth beyond one year of life.•Use of multicomponent fortifiers does not appear to be associated with adverse effects,although the total number of infants studied and the large amount of missing datareduces confidence in this conclusion. Blood urea levels are increased and blood pHlevels minimally decreased, but the clinical significance of this is uncertain.REVIEWERS CONCLUSIONS:•Multicomponent fortification of human milk is associated with short-term improvements inweight gain, linear and head growth. Despite the absence of evidence of long-termbenefit and insufficient evidence to be reassured that there are no deleterious effects, it isunlikely that further studies evaluating fortification of human milk versus nosupplementation will be performed.•Further research should be directed toward comparisons between different proprietarypreparations and evaluating both short-term and long-term outcomes in search of the"optimal" composition of fortifiers.
Fortification of Preterm Human Milk for Feeding Preterm Infants – Yale Pediatric Protocol Preterm human milk (PTHM) is milk expressed by a mother for her infant following a preterm delivery. – may be stored in the Breast Milk Refrigerator for up to 48 hours. – If the milk will not be fed to the infant within that time, it should be frozen as early as possible after expression in appropriate-sized volumes and then gently thawed prior to use. Once thawed, it should be used within about 4 hours. Infants should be fed full strength human milk as their initial enteral feeding. When to fortify: – After an infant tolerates full enteral feeding of full-strength human milk for 5-7 days – Or, after he/she tolerates about 75% his/her total daily volume (IV + NG) as full strength human milk How to fortify – adding a powdered Human Milk Fortifier – by mixing human milk with an equal volume of Premature Formula Mixing equal volumes of human milk and Premature Formula or Natural Care results in a nutrient concentration that equals an average between human milk and formula – Or, by mixing human milk with an equal volume of Natural Care(similac) Human Milk Fortifier. The decision on which method of fortification to use will depend upon the mothers milk production with discussion with Lactation Consultant. Why fortify – Increases the content of nutrients in the infants diet, esp calcium and phosphorus. (See table next page) – The composition of PTHM varies with the duration of lactation; an approximate composition of "mature" PTHM is also shown
Special Formula Use RecommendationsNutrition Practice Care Guidelines for Preterm Infants In the Community. Revised August 2006.Developed by Child Development and Rehabilitation Center, Nutrition Services, Oregon Department of Human Services, Nutrition & HealthScreening – WIC Program. Oregon Pediatric Nutrition Practice Group Preterm formula and Human Milk Fortifier: generally for infants weighing less than 1,850 to 2,000 gm (about 4 to 4 ½ lbs). It is inappropriate for most infants who weigh more than 2.5 kg (5 ½ lbs) or are taking in over 500 ml daily to be fed premature formulas (Enfamil Premature Lipil or Similac Special Care) or Human Milk Fortifiers (Similac HMF, Similac Natural Care or Enfamil HMF) for all their feeds because of the higher vitamin A and vitamin D content of these formulas and the possible risk of hypervitaminosis. Transitional Formulas: (also called “post-discharge premature formulas”) Formulas such as Enfamil EnfaCare Lipil and Similac Neosure Advance provide 22 kcal/oz and have higher levels of protein, calcium, phosphorus, vitamins and other minerals than standard infant formulas. Research has shown that premature infants fed these formulas have improved growth and bone mineralization compared to those fed standard infant formulas. *See recommendation below for length of time an infant needs to remain on a transitional formula.
Specialized formulas – These include Pregestimil, Alimentum, Nutramigen, Neocate and Elecare, and may be indicated based on feeding intolerance. – Enfamil AR is not indicated for preterm infants due to the risk of the formation of lactobezoars (hard clumps of undigested milk curds). These are “term” formulas and thus have less calcium, phosphorus, and protein than transitional formulas. If preterm infants are given these formulas, they should be followed more closely by an RD and the appropriate labs should be checked. Soy-based formulas are not recommended for preterm infants. Preterm infants receiving soy formula have suboptimal carbohydrate and mineral absorption and utilization than cow’s milk-based formula. AAP doesn’t recommend soy formula for infants born < 1800 g since preterm infants showed significantly less weight gain, less linear growth, and lower serum albumin levels than those infants receiving cow’s milk-based formulas. Studies also have shown lower levels of bone marker formation in the premature population which can lead to osteopenia. Goat’s milk is not recommended for preterm infants. Goat’s milk is deficient in folic acid and vitamin B6. It is also higher in protein than human milk and infant formula which puts the premature infant at risk for dehydration due to the higher renal solute load.
Dorset County Hospital Neonatal Unit Guidelines for enteral feeding (Mar05) Milk of choice, in order of preference, is: – 1. Breast milk – suckled by baby from the breast – 2. Mother’s expressed breast milk (EBM), fresh – 3. Mother’s EBM, frozen – 4. Donor EBM* – 5. Formula feed appropriate to gestational age and birth weight * consider using when: baby deemed at high risk of developing necrotising enterocolitis (NEC) – see section 3 if it is available, to intensive care babies poor tolerance of formula feeds NB parental consent should be sought prior to a baby being given donor EBM This hospital actively promotes the benefits of breast feeding for all infants. There are particular benefits of breast milk for the preterm infant and sick neonate (eg reduced incidence of necrotising enterocolitis - ref 1).
Dorset County (cont’d) Early nutrition in the preterm group All mothers should be encouraged to produce milk for their baby as soon as possible after delivery if their baby is not able to feed naturally. Even if the mother is not planning to breast feed in the longer term or unwilling to breast feed, they should be advised why EBM is the best nutritional support for their baby. For premature infants whose mother’s wish to breast feed in the longer term, skin to skin contact should be strongly encouraged from an early stage. Cup feeding is often possible from 30 weeks gestation. Bottle feeding should be avoided if at all possible given the different technique a baby uses to bottle feed compared to feeding at the breast. If formula feeds are being used, the baby should not be started on a preterm formula until they are tolerating 150 ml/kg/day of a standard formula feed.
Dorset County (cont’d) Early nutrition in the preterm groupa) Under 2kg For babies with a birth weight of less than 1.2 kg (and occasionally larger babies) parenteral nutrition will normally be necessary during the first 1-2 weeks of life. This should be written up as soon as possible after delivery so that it can be commenced within 1-2 days of delivery (see TPN guidelines). i) Non-nutritive feeding (minimal enteral nutrition): – Small amounts of breast milk started in the first few days of life (day 1 if possible) – encourage gut maturity (ref 2) – Start at 1ml every 4-6 hours if <1kg (ref 5) and 1ml/hr if >1kg (ref 3). Maternal EBM is preferable to donor breast milk. – Please note section on management of infants at high risk of NEC (section 3) ii) Rate of increase of feed: – Once tolerating minimal enteral nutrition, increase the volume given at each feed. The rate of increase should be decided for each individual baby but would normally be less than 35ml/kg per 24 hours for babies less than 1200gm (ref 4). Larger babies will possibly tolerate faster increments in feed volume.
Dorset County (cont’d) Early nutrition in the preterm group iii) Final feed volume: – Increase feed volumes up to a maximum of: – 200-220 ml/kg/day for EBM – 180 ml/kg for term formula (or Nutriprem 2) – 160 ml/kg/day for preterm formula* Once an infant is tolerating >50% of their total fluid volume enterally, lipid can be discontinued in the TPN (see TPN guidelines). * If formula feeds are being used, the baby should not be started on a preterm formula until they are tolerating 150 ml/kg/day of a standard formula feed.b) greater than 2kg Where possible allow to demand feed. For well infants below 37 weeks gestation, consider starting feeds at 60ml/kg/day on day 1 of feeding aiming to reach 150ml/kg/day within 4 days depending on progress.
Dorset County (cont’d) Early nutrition in the preterm group3. High risk groups for NEC Particular high risk groups include: – Preterm infants < 1kg – Severe intrauterine growth retardation – Absent/reversed end diastolic flow on umbilical artery Doppler – Sepsis For infants with absent or reversed end diastolic flow do not feed enterally for 3 days. For at risk groups consider waiting for maternal EBM before starting feeds. In these circumstances feeding human milk at a rate 1 ml every 4-6 hours is recommended (ref 5). If maternal EBM is not available for these groups consider the use of donor EBM. For babies at high risk of necrotising enterocolitis (NEC) there is some evidence that a rate of increase not exceeding 20ml/kg per 24 hours reduces the incidence of NEC (ref 6). * After a suspected episode of NEC feeds should be reintroduced using EBM (maternal if possible but donor if not available). If maternal EBM not available and mother refused permission to use donor EBM, consider using Pregestimil (see section 9 for advise on increasing calorie intake if inadequate growth on this formula).
References: 1. Lucas A, Cole TJ. Breast milk and neonatal necrotising enterocolitis. Lancet 1990; 336: 1519-1523. 2. McClure RJ and Newell SJ. Randomised controlled trial of trophic feedingand gut motility. Arch Dis Child Neonatal Ed 1999; 80: F54-58. 3. Child Nutrition Panel “Feeding the preterm infant”. Z740127 May 2002 4. Kennedy KA et al. Rapid versus slow rate of advancement of feeding in parenterally fed low birth weight infants. Cochrane Review. 2001. 5. King C. Neonatal Unit Enteral Feeding Policy. Hammersmith Hospital NHS Trust 2000. 6. Anderson DM and Kliegman RM. The relationship of neonatal alimentation practice to the occurrence of endemic necrotising enterocolitis. Am J Perinatol 1991; 8: 62-67. 7. Cooke RJ and Embleton ND. Feeding issues in preterm infants. J. Pediat. Neonatal Ed 2000; 83: F215-218. 8. Nutrition in low birth weight infants. Clinical Paediatric Dietetics 2001.
Enteral Feedingguidelines for thepreterm infantwithin the neonatalservice ofthe LeedsTeaching HospitalsNHS Trust
GROUP 1. 34-36 weeks gestational age and birthweight > 1.5Kg who is on the neonatal unit due to a lack of transitional care capacity. Timing of enteral: Immediately Mode of enteral: NG or oral Type of milk: EBM or Nutriprem (as per policy) Rate of increase: Full feeds as soon as ableGROUP 2. 34-36 weeks gestational age and birthweight > 1.5Kg admitted to Neonatal Unit for whatever reason Feeding will depend on primary pathology. If considered ready for feeding, then feed as Feeding Group 1.GROUP 3. 34-36 weeks gestational age and birthweight < 1.5Kg These infants are under the 2nd centile. Timing of enteral: Delay for up to 24 hours in marked IUGR, or make decision to feed immediately Mode of enteral: NG or oral Type of milk: EBM or Nutriprem 1 (as per policy) Rate of increase: 60mls/kg increasing at a maximum of 1ml/Kg per day (0.5ml 12 hourly) up to total of 150/ml/kg/dayGROUP 4. 31-33 weeks, NO IUGR or A/REDF on antenatal Doppler Timing of enteral: Immediately Mode of enteral: NG Type of milk: EBM or Nutriprem 1(as per policy) Rate of increase: 60mls/kg, max increase per day < 25ml/kg (0.5ml/h, 8 hourly) as tolerated*
GROUP 5. <= 30 weeks, No IUGR (> 2nd centile) or A/REDF on antenatal Doppler Timing of enteral: Delay for 24 hours after birth Mode of enteral: NG Type of milk: EBM or Nutriprem 1(as per policy) Rate of increase: 1ml/kg, increasing maximum 8 hourly as tolerated* for first 72 hours. Increase to 0.5ml/kg 6 hourly maximum as tolerated* after 72 hours of age. Note: Slow feeding to 12 hourly if evidence of failure to tolerate*. Maximum daily increase not to exceed 25 mls/kg per day.GROUP 6. <= 33 weeks, IUGR (<= 2nd centile) or A/REDF on antenatal Doppler Timing of enteral: Delay at least 24 hours Mode of enteral: NG Type of Milk: EBM or Donor EBM (see below) Rate of increase: – <= 1kg: 0.5ml/hr initially increasing by 0.5 ml/24 hours as tolerated – > 1kg 1ml/hr initially increasing by 1ml/24 hours as tolerated When full feeds established continue, if using Donor EBM, continue on full feeds (maximum 165ml/Kg per day) for at least 5 days. Switch to Nutriprem 1 after this time. Parenteral Nutrition (PN) will be required for this group (see PN protocol)*Tolerating enteral feeds Babies are considered to be tolerating enteral feeds if • 4 hourly NG aspirates are < 25% of total infused in the preceding 4 hours • No significant abdominal distension • No significant vomiting • No bile-stained aspirates
Longchain polyunsaturated fatty acid supplementation in preterm infants Cochrane collaboration 2003Main results•Of the eleven randomised trials included in the review, two of these were notclassified as of high quality despite blinded assessment and complete follow-up, due toproblems with assessment methodology.Visual acuityVisual acuity over the first year was measured by Teller acuity cards in six studies, byVEP in four studies and by ERG in two studies. Most studies found no significantdifferences in any visual assessment between supplemented and control infants.DevelopmentMost of the trials have used Bayley Scales of Infant Development (BSID) at 12 to 24months postterm and shown no significant effect following supplementation. Meta-analysis of BSID of three studies (Fewtrell 2002, OConnor 2001, van Wezel 2002)shows no significant effect of supplementation on development. Carlson 1993 andCarlson 1996 demonstrated lower novelty preferences (possibly predictive of lowerintelligence) in the supplemented compared with the control group. The investigatorshowever concluded that supplemented infants may have more rapid visual informationprocessing given that they had more looks and each look was of shorter duration.
GrowthMost trials have reported no significant effect of LCPUFA supplementation on growthof preterm infants. Two trials (Carlson 1993, Carlson 1996) suggest that LCPUFAsupplemented infants grow less well than controls, possibly due to a reduction in AAlevels which occurs when n-3 supplements are used without n-6 supplements. Recenttrials with addition of AA to the supplement have reported no significant effect ongrowth. Fewtrell 2002 reported mild reductions in length and weight z scores at 18months.Contrary to these results, the meta-analysis of five studies (Uauy 1992, Carlson 1996,Hansen 1997, Vanderhoof 1999, Innis 2002) showed increased weight and length attwo months post-term in supplemented infants.Side effectsUauy 1992 reported no significant effect of LCPUFA supplementation on bleeding timeand red cell membrane fragility.Reviewers conclusionsInfants enrolled in the trials were relatively mature and healthy preterm infants.Assessment schedule and methodology, dose and source of supplementation and fattyacid composition of the control formula varied between trials. No long-term benefitswere demonstrated for infants receiving formula supplemented with LCPUFA. Therewas no evidence that supplementation of formula with n-3 and n-6 LCPUFA impairedthe growth of preterm infants.
Is supplementary iron useful when preterm infants are treated with erythropoietin? BestBets 2006 In [a preterm infant who is receiving rHuEPO therapy] does [iron supplementation] reduce the requirement for [blood transfusion]? If so, what method of administration and dose reduces it most successfully
Comment(s)•Anaemia in premature infants is a common problem. Although erythropoietin isnot used widely in neonatal practice, there is evidence of its efficacy in reducingthe need for transfusion in preterm infants,(Shannon) especially if they are notextremely small or sick.(Soubasi). It is regularly used in situations where bloodtransfusion is unacceptable.•Iron supplementation has been a standard in neonatal care for preterm infantsfor many years and helps to reduce late anaemia (Franz) if given with vitamins,especially vitamin E.(Jansson). However, when stimulating erythropoiesis withrHuEpo to reduce the need for transfusion, iron availability becomes critical.• Several studies have investigated rHuEpo efficacy in preterm infants and mostof them have used supplementary iron in either the oral or parenteral routes. Theliterature on the use of rHuEpo and iron mostly consists of studies on dosevariation of rHuEpo rather than variation in the iron supplementation.•Our search yielded seven studies, but one(Pollak) was excluded owing to poormethodological quality. Two studies by Carnielli et al and Fujiu et al comparedrHuEpo and oral iron supplementation with rHuEpo alone; however, theinterpretation of the data is difficult because Carnielli et al reported their resultsonly as mean values and logarithms, making statistical analysis difficult. Fujiu etal found that no infants in either arm of their study required a blood transfusion.
•Although this may suggest that there was no difference between the groups, thesample size was small, with only 24 infants in total, and the clinical equivalence couldnot be shown. In addition, the authors state that losses due to phlebotomy in theirstudy were lower than those in other similar studies. This may be relevant, as one ofthe most common causes of the anaemia of prematurity is iatrogenic blood loss.•Kivivuori et al and Meyer et al compared rHuEPO treatment and parenteral ironsupplementation with rHuEPO treatment and oral iron supplementation. Combineddata from the two studies showed that there was no significant difference between thegroups for the number of blood transfusions given (odds ratio (OR) 1.65, 95%confidence interval (CI) 0.41 to 6.64). This seems to suggest that oral ironsupplementation is at least sufficient. However, one study used intravenous ironsupplementation whereas the other used intramuscular iron supplementation.Differences in absorption of these two different routes may be relevant, but no studyhas been carried out comparing intravenous with intramuscular iron supplementation.•Bader et al and Nazir et al compared infants receiving rHuEPO treatment and high-dose oral iron supplementation with those receiving rHuEPO treatment and low-doseoral iron supplementation. There was no significant difference between the two groups,when combining data for the two studies, regarding the number of blood transfusions(OR 0.46, 95% CI 0.04 to 5.75).
Preterm infants on special-care baby units frequently become anaemic and require top-up blood transfusions. Preterm infants often have low iron stores; this becomes more evident if they do not receive transfusions or iron supplementation. Erythropoietin is used occasionally to stimulate red cell production and prevent anaemia, and the increased erythropoiesis that occurs as a result of rHuEPO treatment will deplete iron stores. The studies currently available do not give an adequate answer to the question as to which is the best mode and dose of iron supplementation with rHuEpo treatment. On the basis of the principle of using the lowest effective dose and the least invasive mode of administration, at present, low-dose oral iron would seem appropriate for supplementation when rHuEpo is used in preterm infants.Clinical Bottom Line Evidence available to strongly support any specific recommendation for iron supplementation with recombinant erythropoietin treatment in premature infants (grade D) is insufficient. Low-dose oral iron supplementation is not inferior to other treatment regimens (grade B).
Glutamine supplementation to prevent morbidity and mortality in preterm infants Cochrane collaboration 2008Main results•2365 preterm infants have participated in seven randomised controlled trials. All ofthe participating infants were of very low birth weight.•Three trials assessed enteral glutamine supplementation and four trials assessedparenteral glutamine supplementation.•The trials were generally of good methodological quality with adequate allocationconcealment, blinding of caregivers and assessors to the intervention, and completeor near-complete follow-up of recruited infants.•Glutamine supplementation does not have a statistically significant effect onmortality: typical relative risk 0.98 (95% confidence interval 0.80 to 1.20); typical riskdifference 0.00 (95% confidence interval -0.03 to 0.02).•The only trial that assessed long-term outcomes did not find any statisticallysignificant differences in various assessments of neurodevelopment at 18 monthscorrected age. Glutamine supplementation does not have a statistically significanteffect on other neonatal morbidities including invasive infection, necrotisingenterocolitis, time to achieve full enteral nutrition, or duration of hospital stay.Authors conclusions•The available data from good quality randomised controlled trials indicate thatglutamine supplementation does not confer benefits for preterm infants. The narrowconfidence intervals for the effect size estimates suggest that a further trial of thisintervention is not a research priority.
Probiotics for prevention of necrotizing enterocolitis in preterm infants Cochrane review 2007Main results Nine eligible trials randomizing 1425 infants were included. Included trials were highly variable with regard to enrollment criteria (i.e. birth weight and gestational age), baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. Data regarding extremely low birth weight infants (ELBW) could not be extrapolated. In a meta-analysis of trial data, enteral probiotics supplementation significantly reduced the incidence of severe NEC (stage II or more) [typical RR 0.32 (95% CI 0.17, 0.60)] and mortality [typical RR 0.43 (95% CI 0.25, 0.75]. There was no evidence of significant reduction of nosocomial sepsis [typical RR 0.93 (95% CI 0.73, 1.19)] or days on total parenteral nutrition (TPN) [WMD -1.9 (95% CI -4.6, 0.77)]. The included trials reported no systemic infection with the probiotics supplemental organism. The statistical test of heterogeneity for NEC, mortality and sepsis was insignificant.Reviewers conclusions Enteral supplementation of probiotics reduced the risk of severe NEC and mortality in preterm infants. This analysis supports a change in practice in premature infants > 1000 g at birth. Data regarding outcome of ELBW infants could not be extracted from the available studies; therefore, a reliable estimate of the safety and efficacy of administration of probiotic supplements cannot be made in this high risk group. A large randomized controlled trial is required to investigate the potential benefits and safety profile of probiotics supplementation in ELBW infants.
The Role of Nutrition in the Prevention and Management of BPDSeminars in Perinatology 30:200-208
Nutritional Intake Preterm infants with BPD are at risk for undernutrition due to difficulties maintaining appropriate nutritional intake – as a result of co-morbidities (Carlson, 2004) eg swallowing dysfunction, fatigue during feeding, GERD, dysfunction of other organ system eg NEC, prolonged TPN – medically indicated fluid restriction (Carlson, 2004; Oh et al., 2005), – and elevated energy expenditure (Bauer et al., 2003; Leitch & Denne, 2000). – Use of dexamethasone – Anemia of prematurity – Medications eg methyl xanthines and beta sympthomimetics can increase energy consumption BPD patients can have increased energy expenditure up to 25% above total caloric needs – Increased work of breathing – Higher resting metabolic rates
Calories Breast milk requires HMF, multivitamin and iron supplements Alternatively use prem formula – Provides additional calories, proteins, calcium, phosphorus and vitamins Additional fat may be desirable – Increases calories – Less CO2 production than carbohydrates – However, additional fat slows gastric emptying and may worsen GERD Glucose polymers – Provide additional 4kcal/g – May cause hyperosmolar diarrhoea Protein supplementation can be considered or provided by using a high caloric formula eg 30 kcal/oz
Calcium, Phosphorus and Vit D Osteopenia of prem more common in BPD – Limited solubility of Ca and phosphorus in TPN – Low enteral intake – Loop diuretics/urinary loss Provide above via prem formula or fortified BM
Nutrients Vit A – Deficiency associated with impaired clearance of lung secretions, impaired water homeostasis across tracheobronchial epithelium, loss of cilia, diminished lung injury repair and lack of airway distensability – Well documented to result in BPD/death in Vit A deficiency (NICHD study). – Dose of IM 5000 IU per dose 3x/week (12 doses) for ELBW. Oral does not work. Under study: inositol, Vit E
Discharge in BPD 67% continue to have growth failure post discharge Individualised nutrition plan Continue 22kcal/oz prem formula for 6-8 months Low salt/low volume/high calorie diet may be necessary Achieve solid intake slower than chronological age, often tolerate spoon feeding (thicker consistency) better than nipple (liquid). This may begin at 3-4 mths post gestation
Early discharge with home support of gavage feeding for stable preterm infants who have not established full oral feeds 2008 Cochrane CollaborationMain results Data from one quasi-randomised trial with 88 infants from 75 families were included in the review. Infants in the early discharge program with home gavage feeding had a mean hospital stay that was 9.3 days shorter [MD -9.3 (-18.49 to -0.11)] than infants in the control group. Infants in the early discharge program also had a lower risk of clinical infection during the home gavage period compared with the corresponding time in hospital for the control group [relative risk 0.35 (0.17 to 0.69)]. There were no significant differences between groups in duration and extent of breast feeding, weight gain, re-admission within the first 12 months post discharge from the home gavage program or from hospital, scores reflecting parental satisfaction, or health service use.Authors’ conclusions Experimental evidence to evaluate the benefits and risks in preterm infants of early discharge from hospital with home gavage feeding compared with later discharge upon attainment of full sucking feeds is limited to the results of one small quasi- randomised controlled trial. High quality trials with concealed allocation, complete follow-up of all randomised infants and adequate sample size are needed before practice recommendations can be made.
Use of transitional formula: the evidence Post discharge Nutrition of Preterm Infants, Journal of Perinatology 2005; 25:S15–S16 feeding of specially designed post discharge formulas has demonstrated better weight (at 9 but not at 18 months) and length (at 9 and 18 months) as well as higher bone mineral content when compared to term infant formula – Lucas A, King F, Bishop NB. Postdischarge formula consumption in infants born preterm. Arch Dis Child 1992;67:691–2. – Lucas A, Fewtrell MS, Morley R, Singhal A, Abbott RA, Isaacs E. Randomized trial of nutrient-enriched formula versus standard formula for post discharge preterm infants. Pediatrics 2001;107:683–9. the benefit appears restricted to males, a finding similar to that of Cooke et al. – Cooke RJ, Griffin IJ, McCormick K, Wells JC, Smith JS, Robinson SJ. Feeding preterm infants after hospital discharge: effect of dietary manipulation on nutrient intake and growth. Pediatr Res 1998;43:355–60 From the NICHD network, data demonstrate that in virtually all infants less than 1500 g, appropriate-for-gestational-age infants are ‘‘converted’’ to small for-gestational-age infants by 36 weeks postmenstrual age. Some recovery in these parameters has been reported Chronic lung disease adds an additional burden as demonstrated by 73% of infants in one study experiencing a decrease in weight z score between hospital discharge and 7 months
Use of transitional formula: Guidelines Post discharge Nutrition of Preterm Infants, Journal of Perinatology 2005; 25:S15–S16Until more optimal strategies are developed, striving toward achieving the best possible gain without adverse effects may be appropriate.Guideline: <1800 g: 24 kcal/oz preterm infant formula Transition to 22 kcal/oz at >1800 g if all growth parameters are 25th percentile or greater and infant is gaining 15 to 40 g/day Transition from 22 kcal/oz to 20 kcal/oz term formula at 4–6 months corrected gestational age if all growth parameters are above 25th percentile
Nutrition Practice CareGuidelines for Preterm Infants In the Community (Revised August 2006) Developed by: Child Development and Rehabilitation Center, Nutrition Services Oregon Department of Human Services, Nutrition & Health Screening – WIC Program Oregon Pediatric Nutrition Practice Group
Referral CriteriaThese “red flags” should alert the community nutritionist of the need forfurther assessment, referral and follow-upAnthropometric “Red Flags”:• Weight loss or significant decline in percentile ranking (“falling away”from expected growth curve percentile)• Poor rate of weight gain for corrected age as listed below:Age Weight Gainterm – 3 mos < 20 gm/day (< 5 oz/wk)3 – 6 mos < 15 gm/day (< 3½ oz/wk)6 – 9 mos < 10 gm/day (< 2 oz/wk)9 – 12 mos < 6 gm/day (< 1½ oz/wk)1 – 2 yrs < 1 kg or < 2 lbs in 6 mos2 – 5 yrs < 0.7 kg or < 1½ lbs in 6 mos
VITAMIN-MINERAL SUPPLEMENTATION Vitamins: Supplementation with a standard infant multivitamin (with vitamins A, D, B1, B2, B3, B6, B12, C, and iron) is generally needed initially after NICU discharge to meet the preterm infant’s vitamin needs, until the infant is consuming larger volumes of feeds. Vitamin D: Per the American Academy of Pediatrics (AAP), all infants fed unfortified breast milk should continue to receive a supplement of 200 IU of Vitamin D for the first year. – This 200 IU of Vitamin D can be provided by continuing the 0.5 ml daily of the standard infant multivitamin, or by changing to 0.5 ml daily of a tri-vitamin supplement (vitamins A, C, and D). Infants receiving 17 oz. (500 ml) or more of a vitamin D-fortified infant formula do not need any additional Vitamin D supplementation. Iron: Preterm infants have lower iron stores than term infants. By 2 months post birth (not 2 months corrected age), preterm infants should have an intake of 2-4 mg iron/kg/day (up to a maximum of 40 mg/day) from an iron-fortified infant formula and/or supplement. This iron dose should be continued for the first year of life.
Osteopenia of prematurity is most commonly seen in: • Very-low-birth-weight infants (BW < 1500g). • Any IUGR infant with a birthweight < 1800 g regardless of gestational age. • Infants with chronic lung disease/bronchopulmonary dysplasia. • Infants requiring long-term parenteral nutrition at birth. • Infants on certain medications, including diuretics & corticosteroids, that affect mineral absorption. • Infants starting feedings of unfortified breastmilk or standard formula too early, or soy formula.Recommendation for checking labs: • 1-month post-discharge for the infants born < 1500g and IUGR with birthweight < 1800 g. • 1-month post-discharge if any of the labs at discharge (if known) are outside the reference range. • If the premie is transitioning to the breast or a term formula < 3-6 months corrected age. • If the premie has had marginal intake and slower growth.Bone health can be assessed using the following labs.•In the absence of other disease conditions, alkaline phosphatase provides an indirectindicator of bone cell activity.•Higher alkaline phosphatase along with lower calcium and phosphorus levels mayindicate a need for further assessment and supplementation. These labs are usuallydone in the hospital setting, and may be done in the community up until 6-9 monthscorrected age.
One last example to put it all together …the ADHB (Auckland District Health Board) guidelines
Nutrition Practice Care Guidelines for Preterm Infants In the Community. Revised August 2006. Developed by Child Development and Rehabilitation Center, Nutrition Services, Oregon Department of Human Services, Nutrition & Health Screening – WIC Program. Oregon Pediatric Nutrition Practice GroupAPPENDIX E: SELECTION OF FEEDING AT DISCHARGEFeeding strategies for the preterm infant need to be evaluated on an individual basis. These guidelines are designed to helpthe practitioner in making feeding selections to promote optimal nutrition. Birth weight, weight at discharge, and NICU courseare usually better predictors of risk than gestational age at birth. Breastfeeding after premature birth is recommended andencouraged whenever possible. Lactation consultation is encouraged to promote successful breastfeeding and use of a breastpump if needed.1. High Risk – Very Low Birth Weight InfantCategory Definition:• Birth weight < 1500gm (3.3 lbs)• History of TPN and diuretics• Demonstrates poor growth• Poor intake (< 150 ml/kg/day)• Elevated alkaline phosphatase (> 500 U/L) and/or low phosphorus (< 4)Formula Feeding Recommendations:• In majority of cases, these infants will need transitional formulas (EnfaCare or Neosure) until 9 months corrected age. Ifchange to a term formula, check labs and monitor growth.• Continue on transitional formula unless:o Infant cannot tolerate formulao Excessive rate of weight gaino Calcium and Phosphorus exceed normal limitsBreastfeeding Recommendations:• Supplement breastfeeding with a transitional formula (Similac Neosure or Enfamil EnfaCare) until infant able to sustaingrowth, ad lib milk intake, and lab values are within normal limits• Discuss family’s breastfeeding goals in order to support breastfeeding while still maintaining infant’s growth and lab values.
Moderate Risk – Low Birth Weight InfantCategory Definition: • Infant had BW > 1500 gm (3.3 lbs), has good growth, use of TPN and diuretics was minimal and alkaline phosphatase level WNL • Osteopenia evidenced by serum phosphorous <4mg/dl, alkaline phosphatase > 500 U/L • Weight for corrected age is less than 5th percentile on CDC 2000 growth grids • Infant has bronchopulmonary dysplasia/chronic lung disease with steroid useFormula Feeding Recommendations: • Provide transitional formulas (EnfaCare or Neosure) to 9 months corrected age. • Continue on transitional formula unless: o Infant cannot tolerate formula o Excessive rate of weight gain o Calcium and Phosphorus exceed normal limits o If change to a term formula, check labs and monitor growthBreastfeeding Recommendations: • Supplement breastfeeding with a transitional formula (Similac Neosure or Enfamil EnfaCare) until infant able to sustain growth, ad lib milk intake, and lab values are within normal limits • Discuss family’s breastfeeding goals in order to support breastfeeding while still maintaining infant’s growth and lab values.
Low Risk – Low Birth Weight InfantBreastfeeding Recommendations: • Breastfeed on demand. • If milk intake or supply is insufficient, as evidenced by slow growth on CDC growth grid, assess the need for lactation support or supplementation with standard formula such as Enfamil Lipil or Similac Advance.Formula Feeding Recommendations: • Offer standard 20 kcal/oz iron fortified infant formula such as Enfamil Lipil or Similac Advance until 1 year corrected age.Category Definition: • Birth weight > 2000 gm (4.4 lbs)