Ultrasonographic Patterns of Reproductive Organs in Infants Fed Soy Formula: Comparisons to Infants Fed Breast Milk and Milk Formula Janet M. Gilchrist, PhD, RD, Mary Beth Moore, MD, MS, Aline Andres, PhD, Judy A. Estroff, MD, and Thomas M. Badger, PhD Objective To determine if differences exist in hormone-sensitive organ size between infants who were fed soy formula (SF), milk formula (MF), or breast milk (BF). Study design Breast buds, uterus, ovaries, prostate, and testicular volumes were assessed by ultrasonography in 40 BF, 41 MF, and 39 SF infants at age 4 months. Results There were no significant feeding group effects in anthropometric or body composition. Among girls, there were no feeding group differences in breast bud or uterine volume. MF infants had greater (P < .05) mean ovar- ian volume and greater (P < .01) numbers of ovarian cysts per ovary than did BF infants. Among boys, there were no feeding group differences in prostate or breast bud volumes. Mean testicular volume did not differ between SF and MF boys, but both formula-fed groups had lower volumes than BF infants. Conclusions Our data do not support major diet-related differences in reproductive organ size as measured by ultrasound in infants at age 4 months, although there is some evidence that ovarian development may be advanced in MF-fed infants and that testicular development may be slower in both MF and SF infants as compared with BF. There was no evidence that feeding SF exerts any estrogenic effects on reproductive organs studied. (J Pediatr 2010;156:215-20). See related articles, p 209 and p 221 E stimates suggest that soy-based infant formulas (SF) are fed to 20% to 25% of all formula-fed infants in the United States at some point during the first year of life, 1,2 amounting to more than 1 million infants each year. Concerns have been raised about potential adverse consequences of SF related to estrogenic effects of isoflavones associated with the soy pro- tein isolate used as their sole protein source. 2 Similar reports have appeared in the lay press and on Internet web sites. Although the American Academy of Pediatrics (AAP) recommends breast-feeding (BF) rather than formula feeding and cow’s milk formula (MF) over SF, it does not find any adverse effects of SF. 3 The AAP position is essentially that milk formula, although not as good as human breast milk, has been in use for decades, has been reformulated several times to meet nutrient and safety requirements, and has a long track record of safety and efficacy. Therefore, the AAP does not see an advantage of SF over milk formula for general use and recommends SF only for a few medical indications (infants with galactosemia, hereditary lactase deficiency, and secondary lactose intolerance) as well as in situations in which a vegetarian diet is preferred. This stance is prudent in view of international controversy over SF, and it provides the middle ground of ‘‘error on the side of safety without appropriate data in children.’’ This is also the standpoint taken by Australia, Canada, France, Ireland, New Zealand, Switzer- land, and the United Kingdom, where SF use is limited because of concerns about potential estrogenic effects of soy isofla- vones. 3,4 One clear message from the AAP is that breast feeding is the gold standard against which MF is compared, and MF is the standard against which SF is compared. A recent report of an expert panel selected by the National Toxicology Program Center for the Evaluation of Risks to Human Reproduction (NTP-CERHR) concluded that ‘‘There are insufficient human or experimental animal data available to permit a determination of the developmental or reproductive toxicity of soy infant formula.’’ 3 Several studies in rodents have shown that purified isoflavones added to the diet will affect development of reproductive tissues, including the mammary gland and uterus. 5-9 However, very few studies have evaluated the potential effects of SF on human reproduction, and data from those reports are difficult to interpret or ex- trapolate to human infants. 10-12 Two recent studies in human infants that as- sessed breast development were based on physical examination by palpation with comparison to a standardized object (beads/coin) for assessing breast size. 11,12 Both studies suggest minor SF effects on breast tissue, but there were multiple limitations, including examiners were not blinded to infant feeding From the Arkansas Children’s Nutrition Center (J.M.G., A.A., T.M.B.), Departments of Pediatrics (A.A., T.M.B.) and Radiology (M.B.M.), University of Arkansas for Medical Sciences, Little Rock, AR; and Department of Radiology (J.A.E.), Children’s Hospital Boston, Harvard Medical School, Boston, MA Supported by USDA CRIS # 6251-51000-005-03S. T.M.B. was a scientific advisor for the Soy Nutrition Institute. The other authors declare no conflicts of interest. Participants were in The Beginnings Study, which is registered as a clinical trial at www.clinicaltrial.gov. ID #: NCT00616395. 0022-3476/$ - see front matter. Copyright Ó 2010 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2009.08.043 BF Breast-fed MF Milk-based formula–fed SF Soy-based formula–fed 215