Pilot studies of estrogen-related physical findings in infants

Soy formula containing estrogenic isoflavones is widely used in the United States. Infants consuming soy formula exclusively have high isoflavone exposures. We wanted to study whether soy formula prolonged the physiologic estrogenization of newborns, but available quantitative descriptions of the natural history of breast and genital development are inadequate for study design.

We piloted techniques for assessing infants' responses to the withdrawal from maternal estrogen and gathered data on breast and genital development in infants at different ages.

We studied 37 boys and 35 girls, from term pregnancies with normal birth weights, who were < 48 hr to 6 months of age, and residents of Philadelphia, Pennsylvania, during 2004-2005. One-third of the children of each sex and age interval were exclusively fed breast milk, soy formula, or cow-milk formula. Our cross-sectional study measured breast adipose tissue, breast buds, and testicular volume; observed breast and genital development; and collected vaginal wall cells and information on vaginal discharge. We assessed reliability of the measures.

Breast tissue was maximal at birth and disappeared in older children, consistent with waning maternal estrogen. Genital development did not change by age. Breast-milk secretion and withdrawal bleeding were unusual. Vaginal wall cells showed maximal estrogen effect at birth and then reverted; girls on soy appeared to show reestrogenization at 6 months.

Examination of infants for plausible effects of estrogens is valid and repeatable. Measurement of breast tissue and characterization of vaginal wall cells could be used to evaluate exposures with estrogen-like effects.