Nutrition

A Closer Look: Impact of Soy Infant Formula On Growth and Development

By August 17, 2018 No Comments
A Closer Look: Impact of Soy Infant Formula On Growth and Development
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There has been a lot of discussion of late about the impact of soy infant formula (SIF) on growth and development, primarily because soyfoods, including SIF, are uniquely-rich sources of isoflavones. Experience and scientific data support the use of SIF.

Consider the following: soy infant formula has been in use for more than 50 years.  The American Academy of Pediatrics says that soy infant formula promotes normal growth and development.1 In  2014, the first systematic review and meta-analysis to focus on the safety of SIF concluded that in normal full-term infants – even during the most rapid phase of growth – SIF produces normal anthropometric growth, adequate protein status, bone mineralization and normal immune development.2 More recently, a very small Israeli study found soy infant formula use wasn’t associated with puberty onset in boys or girls.3

And yet, there continues to be much controversy surrounding soy infant formula.

Contributing to this controversy are the results of an epidemiologic study by Adgent et al.4 published earlier this year which suggest that soy infant formula may exert modest estrogenic effects in infant girls (not boys). Not surprisingly, this study garnered considerable media attention. However, a subsequently published study not involving SIF should give considerable pause about drawing any long-term conclusions about the health effects of SIF based on studies in infants.5

The Adgent et al.4 study enrolled 410 infants born in Philadelphia-area hospitals between 2010 and 2014 that were exclusively fed SIF, cow-milk formula or breast milk throughout the study (birth to 28 or 36 weeks for boys and girls, respectively).4 Maternal demographics did not differ between cow milk-fed and soy formula-fed infants but did differ markedly between formula-fed and breastfed infants. Vaginal-cell maturation index (a marker of estrogen exposure) trended higher and uterine volume decreased more slowly in SIF girls compared with cow milk-fed girls; however, their trajectories of breast bud diameter and hormone concentrations did not differ. The authors concluded that soy infant formula “demonstrated tissue and organ-level developmental trajectories consistent with response to exogenous estrogen exposure” but readily acknowledged that the long-term implications of these differences, if any, are unknown.

This study makes an important contribution to the literature.4 But because it is an epidemiologic study rather than a randomized controlled trial, it is important to recognize its inherent limitations. Furthermore, the effects in girls contrast with results from the Beginnings study, which have shown SIF does not produce estrogenic effects in girls or boys in comparison to infants fed cow-milk formula or breast milk.6 Interestingly, at four months of age, the ovarian volume of the cow-milk formula-fed infants was significantly larger than infants in the other two groups, which is suggestive of an estrogenic effect.7 However, by five years of age this difference in ovarian size was no longer evident.8 Thus, the impact of cow’s milk formula was transient.

The transient effect of cow’s milk formula on ovarian volume is a nice segue into a recent study by Fleddermann et al.5 that was published in PloS One. This study found there were no long-term effects of differences in growth patterns up to 4 months of age due to differences in formula feeding on anthropometry at 4 years of age.5 The Belgrade-Munich infant milk trial was a randomized controlled trial in which healthy term infants received either a protein-reduced infant formula or a standard formula. Non-randomized breastfed infants were used as a reference group.

This study found that the increase in weight and length z-scores between 1 and 4 months of age was higher for low protein-formula-fed infants than for the standard formula-fed infants. However, after 4 months of age a significantly lower increase in z-scores (for weight and length) was observed in the infants fed low-protein formula compared with the infants fed the standard formula. Consequently, there were no differences at 4 years of age.

The transient effects in infants resulting from differences in dietary intake in the Beginnings study8 and The Belgrade-Munich infant milk study5 should give considerable pause about drawing conclusions about the long-term health implications of formula feeding based on differences observed in infants. Insights about infant feeding patterns may need to come from long-term prospective studies or carefully controlled retrospective studies.

References

  1. Bhatia J, Greer F. Use of soy protein-based formulas in infant feeding. Pediatrics. 2008;121(5):1062-8.
  2. Vandenplas Y, Castrellon PG, Rivas R, et al. Safety of soya-based infant formulas in children. Br J Nutr. 2014;111(8):1340-60.
  3. Sinai T, Ben-Avraham S, Guelmann-Mizrahi I, et al. Consumption of soy-based infant formula is not associated with early onset of puberty. Eur J Nutr. 2018.
  4. Adgent MA, Umbach DM, Zemel BS, et al. A longitudinal study of estrogen-responsive tissues and hormone concentrations in infants fed soy formula. J Clin Endocrinol Metab. 2018;103(5):1899-909.
  5. Fleddermann M, Demmelmair H, Hellmuth C, et al. Association of infant formula composition and anthropometry at 4 years: Follow-up of a randomized controlled trial (BeMIM study). PloS one. 2018;13(7):e0199859.
  6. Andres A, Cleves MA, Bellando JB, et al. Developmental status of 1-year-old infants fed breast milk, cow’s milk formula, or soy formula. Pediatrics. 2012;129(6):1134-40.
  7. Gilchrist JM, Moore MB, Andres A, et al. Ultrasonographic patterns of reproductive organs in infants fed soy formula: comparisons to infants fed breast milk and milk formula. J Pediatr. 2010;156(2):215-20.
  8. Andres A, Moore MB, Linam LE, et al. Compared with feeding infants breast milk or cow-milk formula, soy formula feeding does not affect subsequent reproductive organ size at 5 years of age. J Nutr. 2015;145(5):871-5.
Dr. Mark Messina

Author Dr. Mark Messina

PhD in Nutrition, Executive Director, Soy Nutrition Institute. Expert in soyfoods and isoflavones.

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