Infant Milk Formula with Large, Milk Phospholipid-coated Lipid Droplets Enriched in Dairy Lipids Affects Body Mass Index Trajectories and Blood Pressure at School Age: Follow-up of a Randomized Controlled Trial.
[en] BACKGROUND: Human milk comprises large fat globules enveloped by a native phospholipid membrane, whereas infant formulas contain small, protein-coated lipid droplets. Previous experimental studies indicated that mimicking the architecture of human milk lipid droplets in infant milk formula (IMF) alters lipid metabolism with lasting beneficial impact on later metabolic health.
OBJECTIVES: To evaluate in a follow-up (FU) study of a randomized, controlled trial whether a Concept IMF with large, milk phospholipid-coated lipid droplets enriched with dairy lipids beneficially impacts long-term body mass index (BMI in kg/m2) trajectories and blood pressure at school age.
METHODS: Fully formula-fed infants were randomly assigned to Concept IMF (n = 115) or Control IMF with conventional, small lipid droplets containing vegetable oils (n = 108) for the first 4 mo of age. A group of 88 breastfed infants served as a reference. During FU, anthropometrics were collected at 1, 3, 4, and 5 y of age, and blood pressure only at the last visit.
RESULTS: Compared to Control, Concept group children had consistently lower mean BMI values during FU, with the most marked difference at 1 y of age (difference in means -0.71 kg/m2, 95% confidence interval (CI): -1.13, -0.29; P = 0.001); mean values were close to the breastfed group (P > 0.05). Contrary, the mean BMI values of the Control group were higher compared with the breastfed group during FU from 1 to 5 y of age (differences in means from 0.59 to 0.96 kg/m2, respectively; P < 0.02). At 5 y of age, the Concept group had a lower mean diastolic and arterial blood pressure compared with the Control group; -4.3mm Hg (95% CI: -7.3, -1.3; P = 0.005) and -3.7 mm Hg (95% CI: -6.5, -0.9; P = 0.01), respectively.
CONCLUSIONS: Early life feeding of an innovative IMF with large, milk phospholipid-coated lipid droplets enriched with dairy lipids results in a BMI trajectory closer to breastfed infants and a lower blood pressure at school age. This trial was registered at the Dutch Trial Register as NTR3683 and NTR5538.
Jespers, Sabine Nj; Clinique et Maternité Sainte-Elisabeth, Namur, Belgium
Khoo, Poh Choo; KK Women's and Children's Hospital, Singapore
Rigo, Vincent ; Centre Hospitalier Universitaire de Liège - CHU > > Service néonatologie (CHR) ; Université de Liège - ULiège > Département des sciences cliniques > Néonatologie
Infant Milk Formula with Large, Milk Phospholipid-coated Lipid Droplets Enriched in Dairy Lipids Affects Body Mass Index Trajectories and Blood Pressure at School Age: Follow-up of a Randomized Controlled Trial.
The research was financially supported by Danone Nutricia Research . Its employees (MA-B, SS, MM-P, and EMvdB) were involved in the design, data analysis, interpretation, and dissemination of the clinical trial.
Commentary :
Open access sur le site de l'éditeur: https://www.sciencedirect.com/science/article/pii/S000291652366191X?via%3Dihub
GBD 2015 Obesity Collaborators Afshin, A., Forouzanfar, M.H., Reitsma, M.B., Sur, P., Estep, K., et al. Health effects of overweight and obesity in 195 countries over 25 years. N. Engl. J. Med. 377:1 (2017), 13–27, 10.1056/NEJMoa1614362.
Zimmet, P., Alberti, K.G., Kaufman, F., Tajima, N., Silink, M., Arslanian, S., et al. The metabolic syndrome in children and adolescents - an IDF consensus report. Pediatr. Diabetes. 8:5 (2007), 299–306, 10.1111/j.1399-5448.2007.00271.x 2007.
Ahrens, W., Moreno, L.A., Mårild, S., Molnár, D., Siani, A., De Henauw, S., et al. Metabolic syndrome in young children: definitions and results of the IDEFICS study. Int. J. Obes. (Lond.). 38:Suppl 2 (2014), S4–14, 10.1038/ijo.2014.130.
Baker, J.L., Olsen, L.W., Sørensen, T.I., Childhood body-mass index and the risk of coronary heart disease in adulthood. N. Engl. J. Med. 357:23 (2007), 2329–2337, 10.1056/NEJMoa072515.
Thomas, N.E., Cooper, S.M., Williams, S.P., Baker, J.S., Davies, B., Relationship of fitness, fatness, and coronary-heart-disease risk factors in 12- to 13-year-olds. Pediatr. Exerc. Sci. 19:1 (2007), 93–101, 10.1123/pes.19.1.93.
Druet, C., Stettler, N., Sharp, S., Simmons, R.K., Cooper, C., Smith, G.D., et al. Prediction of childhood obesity by infancy weight gain: an individual-level meta-analysis. Paediatr. Perinat. Epidemiol. 26:1 (2012), 19–26, 10.1111/j.1365-3016.2011.01213.x.
Woo Baidal, J.A., Locks, L.M., Cheng, E.R., Blake-Lamb, T.L., Perkins, M.E., Taveras, E.M., Risk factors for childhood obesity in the first 1,000 days: A systematic review. Am. J. Prev. Med. 50:6 (2016), 761–779, 10.1016/j.amepre.2015.11.012.
Leunissen, R.W., Kerkhof, G.F., Stijnen, T., Hokken-Koelega, A., Timing and tempo of first-year rapid growth in relation to cardiovascular and metabolic risk profile in early adulthood. JAMA 301:21 (2009), 2234–2242, 10.1001/jama.2009.761.
Kramer, M.S., Guo, T., Platt, R.W., Vanilovich, I., Sevkovskaya, Z., Dzikovich, I., et al. Feeding effects on growth during infancy. J. Pediatr. 145:5 (2004), 600–605, 10.1016/j.jpeds.2004.06.069.
Gale, C., Logan, K.M., Santhakumaran, S., Parkinson, J.R., Hyde, M.J., Modi, N., Effect of breastfeeding compared with formula feeding on infant body composition: a systematic review and meta-analysis. Am. J. Clin. Nutr. 95:3 (2012), 656–669, 10.3945/ajcn.111.027284.
Breij, L.M., Abrahamse-Berkeveld, M., Acton, D., De Lucia Rolfe, E., Ong, K.K., Hokken-Koelega, A.C.S., Impact of early infant growth, duration of breastfeeding and maternal factors on total body fat mass and visceral fat at 3 and 6 months of age. Ann. Nutr. Metab. 71:3–4 (2017), 203–210, 10.1159/000481539.
Dewey, K.G., Güngör, D., Donovan, S.M., Madan, E.M., Venkatramanan, S., Davis, T.A., et al. Breastfeeding and risk of overweight in childhood and beyond: a systematic review with emphasis on sibling-pair and intervention studies. Am. J. Clin. Nutr. 114:5 (2021), 1774–1790, 10.1093/ajcn/nqab206.
Wisnieski, L., Kerver, J., Holzman, C., Todem, D., Margerison-Zilko, C., Breastfeeding and risk of metabolic syndrome in children and adolescents: A systematic review. J. Hum. Lact. 34:3 (2018), 515–525, 10.1177/0890334417737038.
Horta, B.L., Loret de Mola, C., Victora, C.G., Long-term consequences of breastfeeding on cholesterol, obesity, systolic blood pressure and type 2 diabetes: a systematic review and meta-analysis. Acta. Paediatr. 104:467 (2015), 30–37, 10.1111/apa.13133.
Mazzocchi, A., Giannì, M.L., Morniroli, D., Leone, L., Roggero, P., Agostoni, C., et al. Hormones in breast milk and effect on infants’ growth: A systematic review. Nutrients, 11(8), 2019, 10.3390/nu11081845.
Maessen, S.E., Derraik, J.G.B., Binia, A., Cutfield, W.S., Perspective: human milk oligosaccharides: fuel for childhood obesity prevention?. Adv. Nutr. 11:1 (2020), 35–40, 10.1093/advances/nmz093.
Koletzko, B., von Kries, R., Closa, R., Escribano, J., Scaglioni, S., Giovannini, M., et al. Can infant feeding choices modulate later obesity risk?. Am. J. Clin. Nutr. 89:5 (2009), 1502S–1508S, 10.3945/ajcn.2009.27113D.
Lemaire, M., Le Huërou-Luron, I., Blat, S., Effects of infant formula composition on long-term metabolic health. J. Dev. Orig. Health Dis. 9:6 (2018), 573–589, 10.1017/S2040174417000964.
Delplanque, B., Gibson, R., Koletzko, B., Lapillonne, A., Strandvik, B., Lipid quality in infant nutrition: current knowledge and future opportunities. J. Pediatr. Gastroenterol. Nutr. 61:1 (2015), 8–17, 10.1097/MPG.0000000000000818.
Michalski, M.C., Briard, V., Michel, F., Tasson, F., Poulain, P., Size distribution of fat globules in human colostrum, breast milk, and infant formula. J. Dairy Sci. 88:6 (2005), 1927–1940, 10.3168/jds.S0022-0302(05)72868-X.
Gallier, S., Vocking, K., Post, J.A., Van De Heijning, B., Acton, D., Van Der Beek, E.M., et al. A novel infant milk formula concept: mimicking the human milk fat globule structure. Colloids. Surf. B Biointerfaces. 136 (2015), 329–339, 10.1016/j.colsurfb.2015.09.024.
Oosting, A., Kegler, D., Wopereis, H.J., Teller, I.C., van de Heijning, B.J., Verkade, H.J., et al. Size and phospholipid coating of lipid droplets in the diet of young mice modify body fat accumulation in adulthood. Pediatr. Res. 72:4 (2012), 362–369, 10.1038/pr.2012.101.
Abrahamse, E., Thomassen, G., Van De Heijning, B., Balvers, M., Knol, J., Renes, I.B., In vitro lipid digestion of infant formula with large milk phospholipid-coated fat droplets is slower than standard infant formula and closer to human milk. J. Pediatr. Gastroenterol. Nutr., 2021 72(6th World Congress of PGHAN):N-ePwP-001.
Baumgartner, S., van de Heijning, B.J.M., Acton, D., Mensink, R.P., Infant milk fat droplet size and coating affect postprandial responses in healthy adult men: a proof-of-concept study. Eur. J. Clin. Nutr. 71:9 (2017), 1108–1113, 10.1038/ejcn.2017.50.
Schipper, L., van Dijk, G., Broersen, L.M., Loos, M., Bartke, N., Scheurink, A.J., et al. A postnatal diet containing phospholipids, processed to yield large, phospholipid-coated lipid droplets, affects specific cognitive behaviors in healthy male mice. J. Nutr. 146:6 (2016), 1155–1161, 10.3945/jn.115.224998.
Breij, L.M., Abrahamse-Berkeveld, M., Vandenplas, Y., Jespers, S.N.J., de Mol, A.C., Khoo, P.C., et al. An infant formula with large, milk phospholipid-coated lipid droplets containing a mixture of dairy and vegetable lipids supports adequate growth and is well tolerated in healthy, term infants. Am. J. Clin. Nutr. 109:3 (2019), 586–596, 10.1093/ajcn/nqy322.
Visser, G.H., Eilers, P.H., Elferink-Stinkens, P.M., Merkus, H.M., Wit, J.M., New Dutch reference curves for birthweight by gestational age. Early Hum. Dev. 85:12 (2009), 737–744, 10.1016/j.earlhumdev.2009.09.008.
WHO Multicentre Growth Reference Study Group. WHO Child growth standards based on length/height, weight and age. Acta Paediatr Suppl 450 (2006), 76–85.
Slaughter, M.H., Lohman, T.G., Boileau, R.A., Horswill, C.A., Stillman, R.J., Van Loan, M.D., et al. Skinfold equations for estimation of body fatness in children and youth. Hum. Biol. 60:5 (1988), 709–723 1988.
Flynn, J.T., Kaelber, D.C., Baker-Smith, C.M., Blowey, D., Carroll, A.E., Daniels, S.R., et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics, 140(3), 2017, 10.1542/peds.2017-1904.
Roy, S.M., Spivack, J.G., Faith, M.S., Chesi, A., Mitchell, J.A., Kelly, A., et al. Infant BMI or weight-for-length and obesity risk in early childhood. Pediatrics, 137(5), 2016, 10.1542/peds.2015-3492.
Dewey, K.G., Heinig, M.J., Nommsen, L.A., Peerson, J.M., Lönnerdal, B., Growth of breast-fed and formula-fed infants from 0 to 18 months: the DARLING Study. Pediatrics 89:6 Pt 1 (1992), 1035–1041, 10.1542/peds.89.6.1035.
Singhal, A., Does breastfeeding protect from growth acceleration and later obesity?. Nestlé Nutr. Workshop Ser. Pediatr. Program. 60 (2007), 15–29 [discussion] -9.
Koletzko, B., von Kries, R., Closa, R., Escribano, J., Scaglioni, S., Giovannini, M., et al. Lower protein in infant formula is associated with lower weight up to age 2 y: a randomized clinical trial. Am. J. Clin. Nutr. 89:6 (2009), 1836–1845, 10.3945/ajcn.2008.27091.
Zheng, M., Campbell, K.J., Baur, L., Rissel, C., Wen, L.M., Infant feeding and growth trajectories in early childhood: the application and comparison of two longitudinal modelling approaches. Int. J. Obes. (Lond.). 45:10 (2021), 2230–2237, 10.1038/s41366-021-00892-5.
Koo, W.W., Walters, J.C., Hockman, E.M., Body composition in human infants at birth and postnatally. J. Nutr. 130:9 (2000), 2188–2194, 10.1093/jn/130.9.2188.
Vidulich, L., Norris, S.A., Cameron, N., Pettifor, J.M., Infant programming of bone size and bone mass in 10-year-old black and white South African children. Paediatr. Perinat. Epidemiol. 21:4 (2007), 354–362, 10.1111/j.1365-3016.2007.00806.x.
Mølgaard, C., Larnkjær, A., Mark, A.B., Michaelsen, K.F., Are early growth and nutrition related to bone health in adolescence? The Copenhagen Cohort Study of infant nutrition and growth. Am. J. Clin. Nutr. 94:6 (2011), 1865S–1869S, 10.3945/ajcn.110.001214 Suppl.
van Beijsterveldt, I.A.L.P., de Fluiter, K.S., Breij, L.M., van der Steen, M., Hokken-Koelega, A.C.S., Fat mass and fat-free mass track from infancy to childhood: new insights in body composition programming in early life. Obesity (Silver Spring) 29:11 (2021), 1899–1906, 10.1002/oby.23271 PMID 34549538.
Billeaud, C., Puccio, G., Saliba, E., Guillois, B., Vaysse, C., Pecquet, S., et al. Safety and tolerance evaluation of milk fat globule membrane-enriched Infant Formulas: a randomized controlled multicenter non-inferiority trial in healthy term infants. Clin. Med. Insights Pediatr. 8 (2014), 51–60, 10.4137/CMPed.S16962 PMID 25452707.
Li, Y., Peng, X., Li, Z., Christensen, B., Heckmann, A.B., Stenlund, H., et al. Feeding infants formula with probiotics or milk fat globule membrane: A double-blind, randomized controlled trial. Front Pediatr, 7, 2019, 347, 10.3389/fped.2019.00347.
Timby, N., Domellöf, E., Hernell, O., Lönnerdal, B., Domellöf, M., Neurodevelopment, nutrition, and growth until 12 mo of age in infants fed a low-energy, low-protein formula supplemented with bovine milk fat globule membranes: a randomized controlled trial. Am. J. Clin. Nutr. 99:4 (2014), 860–868, 10.3945/ajcn.113.064295.
Hedrick, J., Yeiser, M., Harris, C.L., Wampler, J.L., London, H.E., Patterson, A.C., et al. Infant formula with added bovine milk fat globule membrane and modified iron supports growth and normal iron status at one year of age: A randomized controlled trial. Nutrients, 13(12), 2021, 10.3390/nu13124541.
Jiang, B., Xia, Y., Zhou, L., Liang, X., Chen, X., Chen, M., et al. Safety and tolerance assessment of milk fat globule membrane-enriched Infant Formulas in healthy term Chinese infants: a randomised multicenter controlled trial. BMC Pediatr, 22(1), 2022, 465, 10.1186/s12887-022-03507-8.
Nieto-Ruiz, A., García-Santos, J.A., Bermúdez, M.G., Herrmann, F., Diéguez, E., Sepúlveda-Valbuena, N., et al. Cortical visual evoked potentials and growth in infants fed with bioactive compounds-enriched infant formula: results from COGNIS randomized clinical trial. Nutrients, 11(10), 2019, 10.3390/nu11102456.
Venkat, M., Chia, L.W., Lambers, T.T., Milk polar lipids composition and functionality: a systematic review. Crit. Rev. Food Sci. Nutr., 2022, 1–45, 10.1080/10408398.2022.2104211.
Ambrożej, D., Dumycz, K., Dziechciarz, P., Ruszczyński, M., Milk fat globule membrane supplementation in children: systematic review with meta-analysis. Nutrients, 13(3), 2021, 10.3390/nu13030714.
Smith, M.E., Cisbani, G., Lacombe, R.J.S., Bazinet, R.P., A scoping review of clinical studies in infants fed formulas containing palm oil or palm olein and Sn-2 palmitate. J. Nutr. 151:10 (2021), 2997–3035, 10.1093/jn/nxab246.
Oosting, A., van Vlies, N., Kegler, D., Schipper, L., Abrahamse-Berkeveld, M., Ringler, S., et al. Effect of dietary lipid structure in early postnatal life on mouse adipose tissue development and function in adulthood. Br. J. Nutr. 111:2 (2014), 215–226, 10.1017/S0007114513002201.
Baars, A., Oosting, A., Engels, E., Kegler, D., Kodde, A., Schipper, L., et al. Milk fat globule membrane coating of large lipid droplets in the diet of young mice prevents body fat accumulation in adulthood. Br. J. Nutr. 115:11 (2016), 1930–1937, 10.1017/S0007114516001082.
Oosting, A., Harvey, L., Ringler, S., van Dijk, G., Schipper, L., Beyond ingredients: supramolecular structure of lipid droplets in infant formula affects metabolic and brain function in mouse models. Plos One, 18(8), 2023, e0282816, 10.1371/journal.pone.0282816 eCollection 2023.
Smolinska, A., Baranska, A., Dallinga, J.W., Mensink, R.P., Baumgartner, S., van de Heijning, B.J.M., et al. Comparing patterns of volatile organic compounds exhaled in breath after consumption of two infant formulae with a different lipid structure: a randomized trial. Sci. Rep., 9(1), 2019, 554, 10.1038/s41598-018-37210-5.
Weber, M., Grote, V., Closa-Monasterolo, R., Escribano, J., Langhendries, J.P., Dain, E., et al. Lower protein content in infant formula reduces BMI and obesity risk at school age: follow-up of a randomized trial. Am. J. Clin. Nutr. 99:5 (2014), 1041–1051, 10.3945/ajcn.113.064071.
Beyerlein, A., Toschke, A.M., von Kries, R., Breastfeeding and childhood obesity: shift of the entire BMI distribution or only the upper parts?. Obesity (Silver Spring) 16:12 (2008), 2730–2733, 10.1038/oby.2008.432.
Beyerlein, A., Toschke, A.M., von Kries, R., Risk factors for childhood overweight: shift of the mean body mass index and shift of the upper percentiles: results from a cross-sectional study. Int. J. Obes. (Lond). 34:4 (2010), 642–648, 10.1038/ijo.2009.301.
Hosaka, M., Asayama, K., Ohkubo, T., Nakai, K., Imai, Y., Children's home blood pressure and growth environment. Hypertension, 61(4), 2013, e33, 10.1161/HYPERTENSIONAHA.111.00843.
Forsyth, J.S., Willatts, P., Agostoni, C., Bissenden, J., Casaer, P., Boehm, G., Long chain polyunsaturated fatty acid supplementation in infant formula and blood pressure in later childhood: follow up of a randomised controlled trial. BMJ, 326(7396), 2003, 953, 10.1136/bmj.326.7396.953.
Schipper, L., Bartke, N., Marintcheva-Petrova, M., Schoen, S., Vandenplas, Y., Hokken-Koelega, A., Infant formula containing large, milk phospholipid-coated lipid droplets and dairy lipids affects cognitive performance at school age. Front Nutr, 5(10), 2023, 1215199, 10.3389/fnut.2023.1215199 eCollection 2023.
Chen, X., Wang, Y., Tracking of blood pressure from childhood to adulthood: a systematic review and meta-regression analysis. Circulation 117:25 (2008), 3171–3180, 10.1161/CIRCULATIONAHA.107.730366.