Study of Estrogen Activity and Development (SEAD) Soy Study

Epidemiology Branch

The Study of Estrogen Activity and Development (SEAD) Soy Study is a series of cross-sectional pilot studies designed to establish methods for future larger studies on the estrogenic effects of soy infant formulas on the developing infant. The study was designed to help researchers understand whether the ingredients in soy infant formula had long-term effects on children.

Term newborns have anatomic and sonographic evidence of estrogen exposure in utero. Over the first six months to a year of life, as the influence of maternal hormone wanes, the effects of estrogen on the child recede. However, soy infant formula contains large amounts of isoflavones—daidzein and genistein—that can occupy estrogen receptors and act as estrogens in the laboratory. A food substance with estrogen activity might prolong the effect of maternal hormones, or interfere with hormonal homeostasis in the child.

To this end, Rogan and collaborators developed a series of three cross-sectional pilot studies—SEAD 1, 2, and 3—to help establish methods for future larger studies of the estrogenic effects of soy infant formulas on the developing infant. The studies were designed to establish protocols for sonograms, physical examinations, and sampling methods for specimen collection for later studies. The goal: to investigate whether exposure to soy estrogen compared to breast milk and non-soy formulas prolongs anatomical evidence of estrogen exposure and response. The fieldwork for all three  cross-sectional pilot studies was done in the latter half of 2004. Data analysis began in February 2005.

SEAD 1: Sonography

The SEAD 1 Sonography study was conducted at The Children's Hospital of Boston. In the SEAD 1 pilot study, 156 sonography examinations were completed on full-term infants, ages 0-12 months, who were on one of three feeding regimens: soy formula, breast milk or cow’s milk formula. The purpose of SEAD 1 was twofold: to develop and finalize recruitment strategies and sonography procedures for organs not commonly measured in infants and to assess, using ultrasound technology, the dimensions of the hormonally responsive organs—uterus, ovaries, breast, thyroid, kidneys, testes, thymus and prostate—in full term infants.

SEAD 2: Physical Examination

The SEAD 2 Physical Examination study was conducted at the Children's Hospital of Philadelphia. In the SEAD 2 study, 84 physical examinations of full-term infants, ages 0-6 months, on one of three feeding regimens were conducted. The physical examinations were in part extensions of the Ballard examinations of neonates, used to assess gestational age based on the conditions of estrogen-responsive tissues. In addition to the physical examination, vaginal cells were collected for cytology analysis. Although the scientists had planned to collect breast nipple secretions to analyze for protein and sugar levels, this aspect of the study was unsuccessful, as most infants did not present with nipple secretions.

SEAD 3: Biochemistry

The SEAD 3 Biochemistry study was also conducted at the Children's Hospital of Philadelphia. In the SEAD 3 study, 372 evaluations on full-term infants were conducted in parallel with SEAD 2. SEAD 3 was designed to assess the hormonal and biochemical status of full-term infants, age 0-12 months, and to establish a protocol for sampling methods for collection of non-serum tests—urine, saliva, serum and hair samples. Endogenous hormone levels such as testosterone, estradiol, and isoflavone levels were measured in serum; the results will be compared against the non-serum tests.

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