1. Steven A. Abrams, MD Professor of Pediatrics Baylor College of Medicine sabrams@bcm.edu Post-discharge nutrition for high risk infants

2. Disclosure Information In the past 12 months, I have had the following financial relationships with the manufacturer of any commercial products and/or providers of commercial services discussed in this CME activity: Receives research funding from Mead-Johnson. I do not intent to discuss an unapproved/investigative use of a commercial product/device in my presentation.

3.  Discuss how to evaluate and promote growth in premature infants after hospital discharge.  Evaluate current research and recommendations regarding use of nutrient-enriched feedings for premature infants post-discharge.  Understand nutritional options in special case situations of intestinal failure, chronic lung disease and other nutritional limitations after hospital discharge. Objectives

4. Failure to Thrive Case Study #1  Former 30 4/7 week female  Infant was discharged home around 36 weeks PMA with the following feeding plan:  Breastfeeding 4 times per day and 4 bottles of EBM + transitional formula = 27 kcal/oz  Now 40 3/7 wks PMA admitted with FTT

5. Failure to Thrive Case Study #1 Birth Anthros Birth Percentiles D/C #1D/C #1 Percentiles Gest Age: 30 4/7PMA: 37 5/7 Weight1280 g10-50 th %ile1982 g<3 rd %ile Length39 cm10-50 th %ilen/a FOC26 cm3-10 th %ilen/a ReadmitReadmit Percentiles PMA: 40 3/7 Weight2040 g<3 rd %ile Length46 cm<3 rd %ile FOC33.2 cm<3 rd %ile

6. Failure to Thrive Case Study #1  Mother reported:  Baby breastfed for approximately 10-20 minutes, 4 times per day  Taking 30-60 mL of the 4 bottle feeds of EBM + transitional formula = 27 kcal/oz (proper mixing was verified).  Calculated calorie concentration is probably overestimated  Mother reported that when she pumps she is only getting 0.5- 1.5 ounces per breast. During her baby’s first hospitalization she was getting up to 3 ounces per breast.  Overall probably receiving about 100-120 mL/kg/d

7. Failure to Thrive Case Study #1  Intervention: 4 bottles of EBM and 4 bottles of powder transitional formula mixed to 24 kcal/oz.  Infant began taking > 200 mL/kg/day  Weights during admission  Day 1: 2.04 kg  Day 2: 2.135 kg  Day 3: 2.2 kg

8. Failure to Thrive Case Study #1 Birth D/C Readmit Weight

9. Failure to Thrive Case Study #1: Take home  Often breastfeeding is often not well established at discharge. One or two days of one or two bedside attempts at nursing is not enough to assure adequacy.  Ineffective breastfeeding and limited pumping can decrease volume and lead to FTT.  If a few formula feeds are given, need to ensure mom is pumping regularly and has good milk volume.  Careful growth measurements needed after discharge.  Many moms will benefit from established plan to contact lactation support services after discharge.

10. Failure to Thrive Case Study #2  Former 27 week BB discharged home on amino acid based formula.  Per mother she was told that this formula was used because it is high in protein and good for premature infants (no reported history of bloody stools, feeding intolerance).  ER admission at 45 1/7 PMA for cough (weight obtained)  Admitted at 47 4/7 PMA for FTT

11. Failure to Thrive Case Study #2  Mother reports that infant:  Drinks 4 ounces of formula every 3 hours  7 dirty diapers on average  Mother reports that formula mixing was changed from 2 scoops:4 oz water to 1 scoop formula: 4 oz water (half strength or 10 kcal/oz) at the recommendation of her pediatrician about 2-4 weeks prior to admission.  Mom had received multiple mixing lessons at PCP office. She missed last week’s appointment.  PCP office and parents both believe the other initiated the improper change in mixing.

12. Failure to Thrive Case Study #2 Birth D/C ER Readmit D/C Weight Half-Strength Formula

13. Failure to Thrive Case Study #2: Intervention and summary  Intervention:  Change from 4 oz half-strength amino acid based formula every 3 hours to transitional formula 22 kcal/oz ad lib.  In the first 24 hours of admission infant took 264 mL/kg/day of formula and gained 160 grams.  Combination of specialized formulas and novel mixing instructions can be a problem.  High cost might have led mom to try to over-dilute? Up to 15% of families may do this.  Written instructions are crucial.

14. Planning for discharge  Transition to home feeding plan at least 3 days before discharge  Weight gain should be demonstrated over 3 days, not “can go home if gains weight overnight”  Training for family in special feeds/techniques  Especially mixing powder formula  Written instructions are best  Consider 24 hour pre-discharge care by parents  Purchase nutritional products as needed  Infant formulas: Identify stores with formula  Multivitamins and iron  Other equipment such as feeding tubes

15. Oral feeding before discharge  Breast-feeding (if planned) as much as possible  Arrange lactation support as needed for post-discharge.  Use ad lib feeds when possible  If not, be very clear about ranges of feedings and timing range for feeds.  Transition if possible to more physiological feeding schedule. Does the baby need to eat every 3 hours? Why? Give family a plan for spacing feeds during night.

16. Decision making: What to feed at home?  Premature, especially VLBW infants have unique nutritional needs that continue after hospital discharge.  Nutrient deficits accumulate during hospitalization.  Human milk feedings extremely important, but nutrient intake may be limited in some cases.  Ongoing health issues, BPD, reflux, neurological impairments will affect feeding choices, strategies.

17.  Born with low nutrient stores  Often fluid restricted (BPD, PDA)  Glucose and lipid intolerance may have limited provision of adequate IV nutrition  Inadequate oral intake due to immature p.o. feeding  Suspension of feedings for procedures, sepsis, feeding intolerance Why do premature infants exhibit suboptimal nutrition at discharge?

18. Protein deficit: develops rapidly during hospitalization Denne and Poindexter, Sem Perinatol 2007 Dusick et al, Sem Perinatol 2003

19. Post-discharge formula-feeding: Use of Transitional formulas  Formulas have nutrient contents that are mostly mid- range between term and preterm formulas  About 10 studies in infants < 1800 g BW  Most show growth benefits in at least a subgroup  Large safety margin in use of these formulas  Evidence strongest for:  Males < 1250g BW  Other findings  Increased bone mineral content  No effect on neuro-development (small studies?)

20. Carver 2001  N = 125, Birthweight < 1800g  Term formula or transitional formula (22kcal/oz) to 12 months PMA  Significant benefits:  Weight, length, head circumference (6 months)  Head circumference (12 months)  But only in those BW < 1250g  Other studies suggest some benefit 1250-1800 g BW Carver JD, Pediatrics 2001, 107,683-9.

21.  Studies very heterogeneous  Did not have access to original data  Data synthesis limited The available data do not provide strong evidence that feeding preterm infants following hospital discharge with nutrient-enriched formula compared with standard term formula affects growth rates or development up to 18 months post-term. This remains controversial. What is “strong evidence” compared to just plain evidence? 18 months is not likely long enough to show this benefit. Cochrane Database Syst Rev. 2007 (and again in 2012)

22. Recommendations for using transitional (post-discharge) formulas  Transition to these formulas from 24 kcal/oz preterm formula if < 1500 -1800 g BW at about 2.0 kg  May delay if serum alk phos > 600 IU/dL or BPD with fluid restriction.  Preterm formulas are available for home use but difficult to obtain/expensive and may have excess of some nutrients, esp. Vitamin A (for > 3 kg infants) and minerals.  Usually transition to these formulas when ready to be fed “ad lib”.

23. Preterm infants over 1800 g at birth?  Minimal research and outcome data  These formulas are often more expensive for government payment sources (WIC) and may be slightly more expensive for families.  Long-term use or use in late preterm babies can lead to excessive weight gain.  No good guidance  Some use for infants > 1800 g BW but use of routine formulas is also acceptable.  We do not encourage their use in infants > 2.2-2.4 kg or 34 0/7 weeks unless has other conditions.

24. Not generally recommended for most former preterms  Soy formulas  Lactose-free formulas  Partially hydrolyzed casein formulas without clear evidence of protein intolerance  Amino acid based formula except intestinal failure patients or protein intolerance not responsive to partial hydrolyzed casein  Reflux/spitting thickened formulas  Non-pasteurized donor milk  Goat milk, almond milk, etc  Early introduction of solid foods

25.  Faster weight gain (upward percentile crossing for weight) in infancy is associated with a greater risk of long-term obesity and possibly cardiovascular disease  More rapid and more complete “catch up” in preterm infants fed with the nutrient-enriched formula (preterm formula), is not associated with altered adiposity.(Cooke et al, Pediatr Research 2010).  SGA fullterm infants are an area of controversy. Feed for brain or long-term cardiovascular health? (Singhal et al, AJCN 2010)  Be cautious of over-use of high energy dense formulas after discharge. Long-term risk of obesity? Current recommendation is to target catch-up in preterm infants, but to be more cautious in SGA fullterm infants

26. Thickeners  “The Food and Drug Administration (FDA) wants parents, caregivers and health care professionals to be aware that infants of any age may face an increased risk of developing a life-threatening condition if fed a thickening product called SimplyThick.” (Xanthan gum).  “Since May 2011….has identified 22 infants who developed necrotizing enterocolitis (NEC).” Seven of those infants died. One was a full-term infant.  In May 2011, FDA advised against feeding SimplyThick to infants born before 37 weeks gestation. J Pediatr 2012;161:354-6 and http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm256250.ht m

27. Thickeners  Uncertain when it might be “safe” to use thickeners.  Company says “SimplyThick® thickener is NOT intended for use with preterm or infants under 12 months of age. Or children under the age of 12 years with a history of NEC.” (http://www.simplythick.com/, accessed July 2013).http://www.simplythick.com/  We do not use any commercial thickeners in high risk infants.  Alternatives?  Rice cereal  Safe but often does not work very well  Others including Carob bean flour  Inadequately tested  Carefully paced feeding is usually best

28. Breast feeding post-discharge

29. Nutrients limited in human milk for preterm infants  Protein: Need extra to continue to resolve deficit and to support catch-up growth  Minerals: Especially calcium, phosphorus, iron and zinc  Vitamins: Especially Vitamin D  Unless mom receiving very high dose (6400 IU/d) Vitamin D supplementation, there is negligible Vitamin D in human milk.  Energy: Primarily limited by feeding volume, also caloric density

30. Supporting human milk feeding after discharge  Several studies have shown human milk-fed infants grow more slowly than formula-fed preterm infants after d/c.  Few interventions have been studied in breastfed infants.  An evolving area  Former preterms who are breastfed drop %iles on growth curve. May lead to stopping breast feeding.  Slow(er) growth may or may not be harmful.

31.  Infants discharged with a subnormal weight-for-age are at increased risk for long term growth failure  Such infants should receive a special post-discharge formula  The human milk they consume should be supplemented, for example with a human milk fortifier.  Frequently done in Europe but US practitioners prefer not to add powder and substitute some feedings for formula. Also, HMF is not easy to obtain at home and is expensive. J Pediatr Gastroenterol Nutr. 2006 May;42(5):596-603.

32. No significant effect seen for development but very small sample size (Aimone et al, JPGN 2009). Fortification of human milk post-discharge

33. Some studies show no effect Zachariassen et al., Pediatrics 2011;127;e995. Avg. BW about 1300 g,30 weeks PMA, some over 2 kg. No effect of home fortification in a study in Denmark. However, bigger babies than we might use in research.

34. Young L, et al. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD004866. Not enough data for conclusions

35. Fortification of breast milk at home?  No ideal product available for consumers  Significant disruption of breast-feeding dyad  Accurate measurement of milk volume?  Accurate measurement of amount of fortificant?  Bacterial contamination potential for powders  Effect of fortificant on absorption and other nutritional factors from HM

36. Safety of powder fortifiers or formula  All US formula manufacturers recommend against use of powder infant formula in at-risk patients (VLBW, immunocompromised) and NICU settings unless no alternative is available.  Risk of E. sakazakii (now Cronobacter sakazakii) in babies fed powder. About 50 such cases in last 30-40 years, including several recently.  High-risk period may extend past hospitalization

37. “Complementary” formula feeds  Relatively less interruption of breast-feeding  No concerns about sterility if use liquid formulas.  Small but definite benefit for nutrient intake.  Our usual current approach  5-6 feedings/day of breast-milk or breast-feeding  2-3 feedings/day of transitional formula  Re-evaluate need for formula at 48-52 weeks PMA  If mother does not wish to use any formula, can follow baby closely for growth, serum total alk phos activity post-discharge.  Individualize for infants needing fluid restriction or with poor growth history.

38. Growth monitoring  Should monitor weight, length and FOC using current growth curve data and length board. Use gender-specific WHO curves when possible.  Recognition that some drop-off, especially in weight %iles will occur in breast-fed preterms.  Drop in length %iles is not desirable.  Monitor for excessive weight gain or weight/length.  Bone catch-up is usual in first 2-3 months after d/c.  Do not routinely check alk phos unless < 1500 g birthweight AND not receiving any supplement to HM.  Smallest infants have poorer catch-up.

39.  > 2000 g bodyweight  Goal is 20 – 30 g/day averaged over a week  Length and FOC should be plotted and monitored weekly. TWO people are needed to measure length properly using a length board.  Length goal: 0.8 – 1.2 cm/wk  FOC goal: 0.8-1.0 cm/wk Growth Parameters

40.  New gender specific Fenton curves (Fenton T, Kim JH. BMC Pediatrics 2013)  Curves equal the WHO Growth Standards at 50 weeks Fenton growth curves (22-50 wk PMA)

41. Is the baby growing?  Plot with Fenton curves to 50 weeks, then CDC/ WHO curves.  Day-to-day weight changes don’t mean much.  Variation in scales, IV, tubes in/out of baby, stool, urine or feeding before weights affect day-to-day weights.  If a feeding change is made, it takes at least 3 days to evaluate its effects.  Not necessary to keep a baby in the hospital who is feeding well an extra day to “see if s/he gains weight overnight.”  Long-term outcomes are likely more related to length and FOC growth than weight gain.

42. Example: 27 week infant with moderate BPD, full feeds

43. Easy to do, but this isn’t accurate http://www.quickmedical.com/seca/pediatrics/210.html http://www.topendsports.com/testing/tests/height-baby.htm

44. Closer, but still not quite right Lesotho, Africa 2012

45. Bingo!! It takes two people to do this http://www.nursing-help.com/2011/07/growth- measurement-and-procedures.html

46. Post-discharge: How long to continue transitional formula or complementary feeds?  One guidance is to stop at 4-6 mo corrected age if all growth parameters are > 25%ile (Bhatia, J Perinatol 2005).  If not gaining excessive weight, then continuing until 9 mo CGA is reasonable.  Emphasis should be on monitoring length, FOC  AAP suggests “weight for length maintained above the 25%ile.”  Rarely wish to stop at less than 48 weeks PMA as 40-48 weeks are critical catch-up time period (Adamkin, J Perinatol 2006).

47. Iron  Iron status should be monitored: Recommend both serum ferritin and CBC.  Preterm infants and those < 2500 g birthweight should be supplemented with iron at time of hospital discharge or at 6 to 8 weeks postnatal age.  Iron intake of 2-4 mg/kg/day, higher range of this in smallest infants.  For formula-fed infants, may need small supplement to achieve at least 3 mg/kg/day, can be combined with vitamin D.  We provide formula-fed infants ½ ml MVI with iron until about 3 kg.

48. Lab testing post-discharge  There is no need for any routine lab testing in most preterm infants after discharge except iron status.  Consider checking total alk phos activity at 40-48 weeks PMA if last alk phos was > 600 IU/L OR history of rickets OR < 1250 g BW and exclusive HM feeding.  No need for routine vitamin D (serum 25-OHD) testing if receiving appropriate dietary intake of at least 400 IU/day.  If discharged with conjugated bilirubin > 0.3 mg/dL, this should be followed. It is not uncommon for TPN cholestasis to persist for several months.

49.  LBW infants often exhibit suboptimal nutrition at discharge  Transitional (22 kcal/oz) formulas are recommended for premature infants with birth weight <1800g  Continue until 4-6 mo corrected age or until all growth parameters are >25%ile. Do not usually stop < 48 wks PMA.  Common strategy for baby < 1500-1800 g BW whose mother has breast milk available for use or is breast-feeding:  5-6 feedings/day of breast-milk or breast-feeding  2-3 feedings/day of transitional formula  If discharged on transitional formula: consider ½ mL of MVI with iron for total of 3 mg/kg/d iron and 400 IU/d vitamin D.  If discharged on ANY human milk: 1 mL MVI with iron. Summary

50. That’s the End…. sabrams@bcm.edu