Breastfeeding, Breast Milk Composition, and Growth Outcomes

Editor(s): M. Vendelbo Lind, A. Larnkjær, C. Mølgaard, and K. Fleischer Michaelsen.

Breastfed infants have a growth pattern which is different from formula-fed infants. This pattern is regarded as an optimal growth pattern and is reflected in the WHO growth standards from 2006, which were based on infants exclusively breastfed for at least 4 months and partly breastfed up to at least 12 months [1]. Compared to formula-fed infants, breastfed infants gain more weight, length, and BMI during the first 2–3 months of life and then have a slower growth velocity up to 12 months of life. Studies examining body composition during infancy showed higher fat accumulation in breastfed infants during the first part of infancy and more fat accumulation in formula-fed infants during the last part of infancy [2]. Blood levels of hormones related to growth and appetite regulation are influenced by infant feeding, which is likely to be part of the explanation for the differences in growth between breastfed and formulafed infants. Both IGF-I and insulin are considerably lower in breastfed infants [3, 4].

Examining the effects of breastfeeding on growth can be difficult, as it is unethical to randomize infants to breastfeeding or no breastfeeding; randomized controlled trials randomizing mothers to a breastfeeding promotion intervention are the preferable design in these situations. However, this design might have challenges related with noncompliance and large overlaps in the duration and degree of breastfeeding, ultimately limiting the ability to find potential differences between groups.

Controlled trials from low- and middle-income countries randomizing mothers to breastfeeding counseling found no major overall effects on early growth. However, there was a modest positive effect on early growth in middle-income countries [5]. As breastfeeding has a marked reducing effect on infectious diseases in low- and middle-income countries, there could potentially be positive effects on growth during the first years of life.

Multiple meta-analyses of observational cohorts from high- and middle-income countries suggest a dose-dependent lower risk of later obesity for breastfed compared to formula-fed infants [6, 7]. However, it is difficult to explore how breastfeeding is influencing growth, and it has been argued that these findings from observational studies could be due to residual confounding and reverse causality, i.e., that the growth velocity of an infant has an effect on feeding choices [8]. In the PROBIT cluster randomized intervention study, there was no effect of breastfeeding on later BMI [9].

Previous studies aimed to explore if and to what extent the slower linear growth during infancy in breastfed infants, which is in line with the lower IGF-I levels, affects stature in the long term. A few studies have suggested that there is programming of the IGF-I axis resulting in breastfed infants having higher stature and IGF-I levels later in childhood than infants not breastfed [4, 10, 11], but other studies have not been able to confirm this.

An increasing number of recent studies have examined breast milk composition and found associations with infant growth. Regarding the macronutrient content of breast milk, some studies support the pattern found in studies on infant formula and complementary feeding indicating that a higher total content of protein is associated with a higher growth velocity, and that the total fat content is either not or negatively associated with growth velocity [12]. The amino acid composition of breast milk might have an effect on growth. Leucine stimulates the release of IGF-I and insulin, and it has been suggested that the content of the free amino acids glutamine and glutamate has a satiety-regulating effect, but at present there is no evidence that this has an effect on growth [13, 14]. The content of human milk oligosaccharides in breast milk has also been associated with growth presumably through modulation of the gut microbiota [15]. Hormones in breast milk, especially adiponectin, might also affect growth. Positive associations between breast milk adiponectin and infant growth and adiposity up to 2 years of age have been found [16].

Breastfeeding has a marked effect on growth. However, as the vast majority of studies are observational and as residual confounding and reverse causality are likely to play important roles, it is difficult to assess the exact effect of breastfeeding on growth. The increasing knowledge of the effects of breast milk composition on growth is likely to provide a better insight into the mechanisms by which breastfeeding influences growth.

References

  1. WHO Multicentre Growth Reference Study Group: Assessment of differences in linear growth among populations in the WHO Multicentre Growth Reference Study. Acta Paediatr Suppl 2006;450:56–65.
  2. Gale C, Logan KM, Santhakumaran S, et al: Effect of breastfeeding compared with formula feeding on infant body composition: a systematic review and meta-analysis. Am J Clin Nutr 2012;95:656–669.
  3. Madsen AL, Schack-Nielsen L, Larnkjaer A, et al: Determinants of blood glucose and insulin in healthy 9-month-old term Danish infants; the SKOT cohort. Diabet Med 2010;27:1350–1357.
  4. Madsen AL, Larnkjær A, Mølgaard C, et al: IGF-I and IGFBP-3 in healthy 9 month old infants from the SKOT cohort: breastfeeding, diet, and later obesity. Growth Horm IGF Res 2011;21:199–204.
  5. Giugliani ERJ, Horta BL, Loret de Mola C, et al: Effect of breastfeeding promotion interventions on child growth: a systematic review and meta-analysis. Acta Paediatr 2015;104:20–29.
  6. Horta BL, Loret de Mola C, Victora CG: Long-term consequences of breastfeeding on cholesterol, obesity, systolic blood pressure and type 2 diabetes: a systematic review and meta-analysis. Acta Paediatr 2015;104:30–37.
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  8. Kramer MS, Matush L, Vanilovich I, et al: A randomized breast-feeding promotion intervention did not reduce child obesity in Belarus. J Nutr 2008;139:417S–421S.
  9. Martin RM, Patel R, Kramer MS, et al: Effects of promoting longer-term and exclusive breastfeeding on adiposity and insulin-like growth factor-I at age 11.5 years: a randomized trial. JAMA 2013;309:1005.
  10. Martin RM, Holly JMP, Smith GD, et al: Could associations between breastfeeding and insulin-like growth factors underlie associations of breastfeeding with adult chronic disease? The Avon Longitudinal Study of Parents and Children. Clin Endocrinol (Oxf) 2005;62:728–737.
  11. Larnkjaer A, Ingstrup HK, Schack-Nielsen L, et al: Early programming of the IGF-I axis: negative association between IGF-I in infancy and late adolescence in a 17-year longitudinal follow-up study of healthy subjects. Growth Horm IGF Res 2009;19:82–86.
  12. Prentice P, Ong KK, Schoemaker MH, et al: Breast milk nutrient content and infancy growth. Acta Paediatr 2016;105:641–647.
  13. Larnkjær A, Bruun S, Pedersen D, et al: Free amino acids in human milk and associations with maternal anthropometry and infant growth. J Pediatr Gastroenterol Nutr 2016;63:374–378.
  14. Lind MV, Larnkjær A, Mølgaard C, et al: Dietary protein intake and quality in early life: impact on growth and obesity. Curr Opin Clin Nutr Metab Care 2017;20:71–76.
  15. Alderete TL, Autran C, Brekke BE, et al: Associations between human milk oligosaccharides and infant body composition in the first 6 mo of life. Am J Clin Nutr 2015;102:1381–1388.
  16. Brunner S, Schmid D, Zang K, et al: Breast milk leptin and adiponectin in relation to infant body composition up to 2 years: milk adipokines and infant body composition. Pediatr Obes 2015;10:67–73. 
Abstract

Breastfed infants have a growth pattern that is different from formula-fed infants, which is regarded as the optimal growth pattern. Breastfed infants increase more in weight, length, and BMI during the first 2–3 months of life and then have a slower growth velocity up to 12 months. They also have a higher accumulation of fat during early infancy. Breastfed infants have lower levels of circulating IGF-I and insulin, which could be part of the explanation of their growth pattern. Many studies and meta-analyses have examined the association between breastfeeding and later obesity. Most find a moderate reduction in the risk of later obesity, but it has been argued that this could be biased due to residual confounding and reverse causation. From studies in low- and middle-income countries randomizing women to breastfeeding promotion, there was only little effect on early growth. Recent studies have found associations between breast milk composition (total fat, protein, human milk oligosaccharides, adiponectin, leptin, and insulin) and growth. However, the studies are few, and the results are inconsistent. More studies, including studies of maternal factors influencing breast milk composition, are needed to better understand how breastfeeding influences current and later growth and thereby short- and long-term health.