A new study revealed babies who were fed soy-based formula as newborns showed minor differences in some reproductive-system cells and tissues, compared to those who were fed cow-milk formula or breast milk. The study was funded and led by the National Institute of Environmental Health Sciences (NIEHS), a part of the National Institute of Health.

"Modern soy formula has been used safely for decades. However, our observational study found subtle effects in estrogen-responsive tissues in soy-fed infants, and we don’t know if these differences are associated with long-term health effects," said first author Margaret A. Adgent, formerly from the NIEHS and currently at Vanderbilt University Medical Center.

Mothers may opt for soy milk for reasons such as lactose intolerance or breastfeeding difficulties. But experts have debated the nature of its impact on children, raising particular concern over the presence of genistein, an estrogen-like compound that was proven to cause abnormal reproductive development in rodents. Infants may be more vulnerable to the compound than adults who consume soy milk. 

"Soy formula contains high concentrations of plant-based estrogen-like compounds, and because this formula is the sole food source for many babies in the first six months of life, it’s important to understand the effects of exposure to such compounds during a critical period in development," said Virginia A. Stallings, Director of the Nutrition Center at Children’s Hospital of Philadelphia and senior author of the study.

Researchers compared soy-fed infants to those who were fed breast milk or cow-milk formula. Enrollments comprised of 410 infant-mother pairs of which 283 pairs completed the study. Of those, 102 infants were exclusively fed soy formula, 111 were fed cow-milk formula, and 70 were fed breast milk.

Stallings highlighted the study was observational and not a randomized trial. "All of the mothers had decided on their feeding preferences before we enrolled them in the study," she said.

The babies were born between 2010 and 2013 in Philadelphia area hospitals with 50% of the babies being girls and 70% being African-American. Researchers from the study performed repeated measurements up to age 28 weeks for the boys and up to age 36 weeks for the girls.

While no significant changes were observed between boys based on the formula they consumed, differences were found based on the feeding preferences among the girls.

Compared to those who were fed cow milk or breast milk, girls who were fed soy formula had estrogen-like responses — Vaginal cell MI trended higher and uterine volume decreased more slowly. The study concluded: "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."

"We don’t know whether the effects we found have long-term consequences for health and development, but the question merits further study," Stallings said, adding the children in this cohort should ideally be recruited for follow-ups in childhood and adolescence.