Food and Behaviour Research

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A longitudinal study of estrogen-responsive tissues and hormone concentrations in infants fed soy formula

Adgent MA, Umbach DM, Zemel BS, Kelly A, Schall J, Ford EG, James K, Darge K, Botelho JC, Vesper HW, Chandler DW, Nakamoto JM, Rogan WJ, Stallings VA (2018) Send to J Clin Endocrinol Metab.  2018 Mar 1.  doi: 10.1210/jc.2017-02249. [Epub ahead of print] 

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Chemicals with hormone-like activity, such as estrogenic isoflavones, may perturb human development. Infants exclusively fed soy-based formula are highly exposed to isoflavones, but their physiologic responses remain uncharacterized. Here, we compare estrogen-responsive postnatal development in infants exclusively fed soy formula, cow-milk formula and breast milk.


We enrolled 410 infants born in Philadelphia area hospitals, 2010-2013; 283 infants were exclusively fed soy formula (n=102), cow-milk formula (n=111), or breast milk (n=70) throughout the study (birth to 28 [boys] or 36 [girls] weeks). We repeatedly measured maturation index (MI) in vaginal and urethral epithelial cells using standard cytological methods, uterine volume and breast-bud diameter using ultrasound, serum estradiol and, in girls, follicle-stimulating hormone. We estimated MI, organ-growth and hormone trajectories by diet using mixed-effects regression splines.


Maternal demographics did not differ between cow-milk-fed and soy-fed infants but did differ between formula-fed and breastfed infants. Vaginal cell MI trended higher (p=0.01) and uterine volume decreased more slowly (p=0.01) in soy-fed girls compared to cow-milk-fed girls; however, their trajectories of breast-bud diameter and hormone concentrations did not differ. We observed no significant differences between boys fed cow-milk formula versus soy formula; estradiol was not detectable. Breastfed infants differed from soy-formula-fed infants in vaginal cell MI, uterine volume, girls' estradiol and boys' breast-bud diameter trajectories.


Relative to cow-milk formula-fed girls, soy formula-fed girls demonstrated tissue and organ-level developmental trajectories consistent with response to exogenous estrogen exposure. Additional studies are needed to further evaluate the effects of soy on child development.


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