Exposure to Soy-Based Formula in Infancy

To the Editor: Dr Strom and colleagues¹ found no differences in later pubertal maturation or growth between infants who had been fed soy-based vs milk-based formula. However, this does not prove that soy-based formulas are safe. In fact, the authors found that infants who had been given soy-based formula later used more asthma and allergy medications (P = .047 and .08 for female and male subjects, respectively). This important observation was not mentioned in the abstract, which stated that "[n]o statistically significant differences were observed . . . for more than 30 outcomes."¹

This conclusion contradicts the findings of both human and animal studies. A retrospective epidemiological study by Fort et al² found that children with autoimmune disease were significantly more likely to have received soy formula as infants than were healthy siblings or control subjects. A recent study from the National Toxicology Program found that rats receiving dietary genistein (an isoflavone found in soybeans) had increased T-cell immune responses.³ These findings suggest that soy consumption could adversely affect the course of autoimmune disease in children by modulating immune function. Since asthma is a potentiated immune response to an antigen, this finding of Strom et al should not be ignored; clearly, additional studies are warranted before confidence in the safety of soy formula is complete.

Strom et al also found that women who had been fed soy formula as infants had a small average increase in the duration of their menstrual cycles (0.37 days) and greater discomfort with menstruation. The authors suggested these effects were small and could be disregarded. Both findings, however, might reflect endometriosis or uterine fibroids, which could theoretically result from early life exposure to estrogens. In fact, these conditions were among several reproductive problems that the authors controlled in their analyses, suggesting that their distribution may have differed in the 2 exposure groups. However, the number of cases in exposed and unexposed subjects was not stated. In addition, the authors reported a 4-fold increase of multiple births in women who had received soy formula. Although the absolute numbers were small, a recent study found an excess of multioocyte follicles in the ovaries of genistein-fed mice.⁴

There are several other limitations to this study. First, fertility was assessed by using total numbers of live births and whether subjects reported "attempting pregnancy without success." In this young population, only 74 soy-fed women had ever tried to become pregnant. Although fewer of these women succeeded in becoming pregnant than women fed cows' milk as infants, the numbers are too small to draw any conclusions about infertility. The number of men with fertility difficulty was not stated. In addition, the authors did not assess time to pregnancy, which is a more sensitive measure of reproductive impairment, nor did they ask whether women used fertility technologies in order to become pregnant. Second, there was no discussion of male reproduction except pubertal onset, and there was no indication of possible impact of exposure on fertility or semen quality. Third, most of the outcome measures were subjective, such as whether menstrual pain was nonexistent, mild, or severe. Fourth, the authors did not assess the cancer risks that might have resulted from soy-based formulas. However, a recent animal study⁵ raises this concern. Finally, this study did not address the actual exposures to estrogenic compounds in the various soy-based formulas.

Strom et al state that "[e]ven if the adverse outcomes under consideration here were relatively uncommon, the potential for a major public health impact is large. Conversely, insupportable allegations of adverse effects can affect a large proportion of the population, denying them access to a useful type of infant feeding product." We agree that the potential public health impacts should be taken seriously and that alarmist positions should be avoided. However, there is now ample reason to question the safety of soy proteins in the diets of infants. Just as scientists should avoid insupportable allegations, they should also avoid absolute declarations of safety in areas whose risks have yet to be assessed.