Impact of macronutrient supplements for children born preterm or small for gestational age on developmental and metabolic outcomes: A systematic review and meta-analysis

English version

Autoři: Luling Lin ^aff001; Emma Amissah ^aff001; Gregory D. Gamble ^aff001; Caroline A. Crowther ^aff001; Jane E. Harding ^aff001
Působiště autorů: Liggins Institute, University of Auckland, Auckland, New Zealand ^aff001
Vyšlo v časopise: Impact of macronutrient supplements for children born preterm or small for gestational age on developmental and metabolic outcomes: A systematic review and meta-analysis. PLoS Med 16(10): e32767. doi:10.1371/journal.pmed.1002952
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pmed.1002952

Souhrn

Background

Nutritional supplements may improve development of infants born small (preterm or small for gestational age [SGA]) but may increase the risk of later metabolic disease. We conducted a systematic review and meta-analysis to assess the effects of macronutrient supplements for infants born small on later development and metabolism.

Methods and findings

We searched OvidMedline, Embase, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews from inception to April 1, 2019, and controlled-trials.com, clinicaltrials.gov, and anzctr.org.au. Randomised or quasirandomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born small and assessed post-discharge outcomes. Co-primary outcomes were cognitive impairment and metabolic risk, evaluated in toddlers (<3 years), childhood (3 to 8 years), and adolescence (9 to 18 years). Two reviewers independently extracted data. Quality was assessed using the Cochrane Risk of Bias tool, and data were pooled using random-effect models.

Twenty-one randomised and one quasirandomised trial of variable methodological quality involving 3,680 infants were included. In toddlers born small, supplementation did not alter cognitive impairment (relative risk [RR] 1.00; 95% confidence interval [CI] 0.67 to 1.49; P = 0.99), and there were no differences in cognitive scores (mean difference [MD] 0.57; 95% CI −0.71 to 1.84; P = 0.38) or motor scores (MD 1.16; 95% CI −0.32 to 2.65; P = 0.12) between supplemented and unsupplemented groups. However, fewer supplemented children had motor impairment (RR 0.76; 95% CI 0.62 to 0.94; P = 0.01). In subgroup analyses, supplementation improved cognitive scores in boys (MD 5.60; 95% CI 1.07 to 10.14; P = 0.02), but not girls born small (MD −2.04; 95% CI −7.04 to 2.95; P = 0.42), and did not alter cognitive or motor scores in the subgroup of children born SGA. In childhood, there was no difference in cognitive impairment (RR 0.81; 95% CI 0.26 to 2.57; P = 0.72) or cognitive scores (MD 1.02; 95% CI −1.91 to 3.95; P = 0.50) between supplemented and unsupplemented groups. There were also no differences in blood pressure, triglyceride, and low-density lipoprotein (LDL) concentrations (all P > 0.05). However, supplemented children had lower fasting glucose (mmol/L: MD −0.20; 95% CI −0.34 to −0.06; P = 0.005) and higher high-density lipoprotein (HDL) concentrations (mmol/L: MD 0.11; 95% CI 0.02 to 0.19; P = 0.02). In subgroup analyses, there was no evidence of differences in blood pressure between supplemented and unsupplemented groups in boys or girls born small, or in SGA children. In adolescence, there was no difference between supplemented and unsupplemented groups in blood pressure, triglycerides, LDL and HDL concentrations, fasting blood glucose, insulin resistance, and fasting insulin concentrations (all P > 0.05). Limitations include considerable unexplained heterogeneity, low to very low quality of the evidence, and limited data beyond early childhood.

Conclusions

In this systematic review and meta-analysis of randomised trials, we found no evidence that early macronutrient supplementation for infants born small altered later cognitive function, although there was some evidence that supplementation may decrease motor impairment in toddlers. Contrary to the findings from observational studies, evidence from randomised trials suggests that early macronutrient supplementation for infants born small improves some metabolic outcomes in childhood.

PROSPERO registration

CRD42019127858.

Klíčová slova:

Blood pressure – Breast milk – Carbohydrates – Cognitive impairment – Congenital anomalies – Fats – Infants – Toddlers

Zdroje

1. Blencowe H, Cousens S, Chou D, Oestergaard M, Say L, Moller AB, et al. Born too soon: the global epidemiology of 15 million preterm births. Reprod Health. 2013;10 Suppl 1:S2.

2. Scharf RJ, Stroustrup A, Conaway MR, DeBoer MD. Growth and development in children born very low birthweight. Arch Dis Child Fetal Neonatal Ed. 2016;101(5):F433–F8. doi: 10.1136/archdischild-2015-309427 26627552

3. Katz J, Lee ACC, Kozuki N, Lawn JE, Cousens S, Blencowe H, et al. Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis. Lancet. 2013;382(9890):417–25. doi: 10.1016/S0140-6736(13)60993-9 23746775

4. Christian P, Lee SE, Angel MD, Adair LS, Arifeen SE, Ashorn P, et al. Risk of childhood undernutrition related to small-for-gestational age and preterm birth in low- and middle-income countries. Int J Epidemiol. 2013;42(5):1340–55. doi: 10.1093/ije/dyt109 23920141

5. Mericq V, Martinez-Aguayo A, Uauy R, Iniguez G, Van der Steen M, Hokken-Koelega A. Long-term metabolic risk among children born premature or small for gestational age. Nat Rev Endocrinol. 2017;13(1):50–62. doi: 10.1038/nrendo.2016.127 27539244

6. Lucas A, Fewtrell MS, Morley R, Lucas PJ, Baker BA, Lister G, et al. Randomized outcome trial of human milk fortification and developmental outcome in preterm infants. Am J Clin Nutr. 1996;64(2):142–51. doi: 10.1093/ajcn/64.2.142 8694013

7. Lucas A, Morley R, Cole TJ. Randomised trial of early diet in preterm babies and later intelligence quotient. BMJ. 1998;317(7171):1481–7. doi: 10.1136/bmj.317.7171.1481 9831573

8. Lucas A, Morley R, Cole TJ, Gore SM. A randomised multicentre study of human milk versus formula and later development in preterm infants. Arch Dis Child Fetal Neonatal Ed. 1994;70(2):F141–6. doi: 10.1136/fn.70.2.f141 8154907

9. Kumar RK, Singhal A, Vaidya U, Banerjee S, Anwar F, Rao S. Optimizing nutrition in preterm low birth weight infants-consensus summary. Front Nutr. 2017;4:20. doi: 10.3389/fnut.2017.00020 28603716

10. Isaacs EB, Morley R, Lucas A. Early diet and general cognitive outcome at adolescence in children born at or below 30 weeks gestation. J Pediatr. 2009;155(2):229–34. doi: 10.1016/j.jpeds.2009.02.030 19446846

11. Brown JVE, Embleton ND, Harding JE, McGuire W. Multi-nutrient fortification of human milk for preterm infants. Cochrane Database Syst Rev. 2016(5):CD000343. doi: 10.1002/14651858.CD000343.pub3 27155888

12. Belfort MB, Rifas-Shiman SL, Sullivan T, Collins CT, McPhee AJ, Ryan P, et al. Infant growth before and after term:eEffects on neurodevelopment in preterm infants. Pediatrics. 2011;128(4):E899–E906. doi: 10.1542/peds.2011-0282 21949135

13. Belfort MB, Gillman MW, Buka SL, Casey PH, McCormick MC. Preterm infant linear growth and adiposity gain: trade-offs for later weight status and intelligence quotient. J Pediatr. 2013;163(6):1564–U71. doi: 10.1016/j.jpeds.2013.06.032 23910982

14. Ong KK, Loos RJ. Rapid infancy weight gain and subsequent obesity: systematic reviews and hopeful suggestions. Acta Paediatr. 2006;95(8):904–8. doi: 10.1080/08035250600719754 16882560

15. Peacock JL, Marston L, Marlow N, Calvert SA, Greenough A. Neonatal and infant outcome in boys and girls born very prematurely. Pediatr Res. 2012;71(3):305–10. doi: 10.1038/pr.2011.50 22258087

16. Lucas A, Morley R, Cole TJ, Gore SM, Lucas PJ, Crowle P, et al. Early diet in preterm babies and developmental status at 18 months. Lancet. 1990;335(8704):1477–81. doi: 10.1016/0140-6736(90)93026-l 1972430

17. Young L, Embleton ND, McGuire W. Nutrient-enriched formula versus standard formula for preterm infants following hospital discharge. Cochrane Database Syst Rev. 2016(12): CD004696.

18. Young L, Embleton ND, McCormick FM, McGuire W. Multinutrient fortification of human breast milk for preterm infants following hospital discharge. Cochrane Database of Syst Rev. 2013(2):CD004866.

19. Higgins JPT, Green S (editors), The Cochrane Collaboration. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011] 2011. Available from: www.cochrane-handbook.org. [cited ].

20. Schünemann H, Brozek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. 2013.

21. Review Manager (RevMan) [Computer program]. Version 5.3. The Nordic Cochrane Centre, The Cochrane Collaboration, 2014: Copenhagen.

22. Fewtrell MS, Morley R, Abbott RA, Singhal A, Stephenson T, MacFadyen UM, et al. Catch-up growth in small-for-gestational-age term infants: a randomized trial. Am J Clin Nutr. 2001;74(4):516–23. doi: 10.1093/ajcn/74.4.516 11566651

23. Bellagamba MP, Carmenati E, D'Ascenzo R, Malatesta M, Spagnoli C, Biagetti C, et al. One extra gram of protein to preterm infants from birth to 1800 g: a single-blinded randomized clinical trial. J Pediatr Gastroenterol Nutr. 2016;62(6):879–84. doi: 10.1097/MPG.0000000000000989 26418211

24. Biasini A, Marvulli L, Neri E, China M, Stella M, Monti F. Growth and neurological outcome in ELBW preterms fed with human milk and extra-protein supplementation as routine practice: do we need further evidence? J Matern Fetal Neonatal Med. 2012;25 Suppl 4:72–4.

25. Cooper PA, Rothberg AD, Davies VA. Three year growth and developmental follow up of very low birthweight infants fed own mother's milk (OMM), a premature infant formula (PF) or one of two standard formulas. Pediatr Res. 1988;23:445A.

26. Dogra S, Thakur A, Garg P, Kler N. Effect of differential enteral protein on growth and nurodevelopment in infants <1500 g: a randomized controlled trial. J Pediatr. 2017;64(5):e126–e32.

27. Goldman HI, Freudenthal R, Holland B, Karelitz S. Clinical effects of two different levels of protein intake on low-birth-weight infants. J Pediatr. 1969;74(6):881–9. doi: 10.1016/s0022-3476(69)80222-2 5781798

28. Lucas A, Morley R, Cole TJ, Gore SM, Davis JA, Bamford MF, et al. Early diet in preterm babies and developmental status in infancy. Arch Dis Child. 1989;64(11):1570–8. doi: 10.1136/adc.64.11.1570 2690739

29. Morgan C, McGowan P, Herwitker S, Hart AE, Turner MA. Postnatal head growth in preterm infants: a randomized controlled parenteral nutrition study. Pediatrics. 2014;133(1):e120–8. doi: 10.1542/peds.2013-2207 24379229

30. Tan MJ, Cooke RW. Improving head growth in very preterm infants—a randomised controlled trial I: neonatal outcomes. Arch Dis Child Fetal Neonatal Ed. 2008;93(5):F337–41. doi: 10.1136/adc.2007.124230 18252814

31. Agosti M, Vegni C, Calciolari G, Marini A, Group GS. Post-discharge nutrition of the very low-birthweight infant: interim results of the multicentric GAMMA study. Acta Paediatr Suppl. 2003;91(441):39–43. 14599040

32. Amesz EM, Schaafsma A, Cranendonk A, Lafeber HN. Optimal growth and lower fat mass in preterm infants fed a protein-enriched postdischarge formula. J Pediatr Gastroenterol Nutr. 2010;50(2):200–7. doi: 10.1097/MPG.0b013e3181a8150d 19881394

33. Cooke RJ, Embleton ND, Griffin IJ, Wells JC, McCormick KP. Feeding preterm infants after hospital discharge: growth and development at 18 months of age. Pediatr Res. 2001;49(5):719–22. doi: 10.1203/00006450-200105000-00018 11328958

34. da Cunha RD, Lamy Filho F, Rafael EV, Lamy ZC, de Queiroz AL. Breast milk supplementation and preterm infant development after hospital discharge: a randomized clinical trial. J Pediatr (Rio J). 2016;92(2):136–42.

35. Friel JK, Andrews WL, Matthew JD, McKim E, French S, Long DR. Improved growth of very low birthweight infants. Nutr Res. 1993;13(6):611–20.

36. Jeon GW, Jung YJ, Koh SY, Lee YK, Kim KA, Shin SM, et al. Preterm infants fed nutrient-enriched formula until 6 months show improved growth and development. Pediatr Int. 2011;53(5):683–8. doi: 10.1111/j.1442-200X.2011.03332.x 21342352

37. Lucas A, Fewtrell MS, Morley R, Singhal A, Abbott RA, Isaacs E, et al. Randomized trial of nutrient-enriched formula versus standard formula for postdischarge preterm infants. Pediatrics. 2001;108(3):703–11. doi: 10.1542/peds.108.3.703 11533340

38. O'Connor DL, Khan S, Weishuhn K, Vaughan J, Jefferies A, Campbell DM, et al. Growth and nutrient intakes of human milk-fed preterm infants provided with extra energy and nutrients after hospital discharge. Pediatrics. 2008;121(4):766–76. doi: 10.1542/peds.2007-0054 18381542

39. Roggero P, Gianni ML, Amato O, Liotto N, Morlacchi L, Orsi A, et al. Growth and fat-free mass gain in preterm infants after discharge: a randomized controlled trial. Pediatrics. 2012;130(5):e1215–21. doi: 10.1542/peds.2012-1193 23109680

40. Zachariassen G, Faerk J, Grytter C, Esberg BH, Hjelmborg J, Mortensen S, et al. Nutrient enrichment of mother's milk and growth of very preterm infants after hospital discharge. Pediatrics. 2011;127(4):e995–e1003. doi: 10.1542/peds.2010-0723 21402642

41. Svenningsen NW, Lindroth M, Lindquist B. A comparative study of varying protein intake in low birthweight infant feeding. Acta Paediatr Suppl. 1982;296:28–31.

42. Cormack BE, Bloomfield FH, Dezoete A, Kuschel CA. Does more protein in the first week of life change outcomes for very low birthweight babies? J Paediatr Child Health. 2011;47(12):898–903. doi: 10.1111/j.1440-1754.2011.02106.x 21658149

43. Stephens BE, Walden RV, Gargus RA, Tucker R, McKinley L, Mance M, et al. First-week protein and energy intakes are associated with 18-month developmental outcomes in extremely low birth weight infants. Pediatrics. 2009;123(5):1337–43. doi: 10.1542/peds.2008-0211 19403500

44. Mattsson N, Ronnemaa T, Juonala M, Viikari JS, Raitakari OT. Childhood predictors of the metabolic syndrome in adulthood. The cardiovascular risk in young Finns Study. Ann Med. 2008;40(7):542–52. doi: 10.1080/07853890802307709 18728920

45. Juonala M, Viikari JSA, Kahonen M, Taittonen L, Laitinen T, Hutri-Kahonen N, et al. Life-time risk factors and progression of carotid atherosclerosis in young adults: the cardiovascular risk in Young Finns study. Eur Heart J. 2010;31(14):1745–51. doi: 10.1093/eurheartj/ehq141 20501481

46. McNeal CJ, Underland L, Wilson DP, Blackett PR. Pediatric lipid screening. Clin Lipidol. 2013;8(4):425–36.

47. Nguyen QM, Srinivasan SR, Xu JH, Chen W, Berenson GS. Fasting plasma glucose levels within the normoglycemic range in childhood as a predictor of prediabetes and type 2 diabetes in adulthood: the Bogalusa Heart Study. Arch Pediatr Adolesc Med. 2010;164(2):124–8. doi: 10.1001/archpediatrics.2009.268 20124140

48. Martin RM, Gunnell D, Smith GD. Breastfeeding in infancy and blood pressure in later life: systematic review and meta-analysis. Am J Epidemiol. 2005;161(1):15–26. doi: 10.1093/aje/kwh338 15615909

49. Horta BL, Bahl R, Martines JC, Victora CG, World Health Organization. Evidence on the long-term effects of breastfeeding: systematic reviews and meta-analyses. World Health Organization. 2007.

50. Uwaezuoke SN, Eneh CI, Ndu IK. Relationship between exclusive breastfeeding and lower risk of childhood obesity: a narrative review of published evidence. Clin Med Insights Pediatr. 2017;11.

51. Amissah E, Lin L, Gamble GD, Crowther CA, Bloomfield FH, Harding JE. Macronutrient supplements in preterm and small-for-gestational-age animals: a systematic review and meta-analysis. Sci Rep. 2019;9(1):14715. doi: 10.1038/s41598-019-51295-6 31605011

52. Berry MJ, Jaquiery AL, Oliver MH, Harding JE, Bloomfield FH. Neonatal milk supplementation in lambs has persistent effects on growth and metabolic function that differ by sex and gestational age. Br J Nutr. 2016;116(11):1912–25. doi: 10.1017/S0007114516004013 27974050

53. Georgieff MK, Ramel SE, Cusick SE. Nutritional influences on brain development. Acta Paediatr. 2018;107(8):1310–21. doi: 10.1111/apa.14287 29468731

54. Ramel SE, Georgieff MK. Preterm nutrition and the brain. World Rev Nutr Diet. 2014;110:190–200. doi: 10.1159/000358467 24751630

55. Fewtrell MS, Kennedy K, Singhal A, Martin RM, Ness A, Hadders-Algra M, et al. How much loss to follow-up is acceptable in long-term randomised trials and prospective studies? Arch Dis Child. 2008;93(6):458–61. doi: 10.1136/adc.2007.127316 18495909

56. Bender R, Bunce C, Clarke M, Gates S, Lange S, Pace NL, et al. Attention should be given to multiplicity issues in systematic reviews. J Clin Epidemiol. 2008;61(9):857–65. doi: 10.1016/j.jclinepi.2008.03.004 18687287