Effects of Infant Diets on Estrogen Activity and Development
Effects of Infant Diets on Estrogen Activity and Development
This study, conducted at the Children's Hospital of Boston and the Brigham and Women's
 Hospital in Boston, will examine the natural history of infant development in the first year
 of life and how different types of infant feeding may affect that development. During
 pregnancy, babies are exposed to the female hormone estrogen from their mothers. Estrogen
 affects development of breasts and milk production, as well as the development of the uterus,
 ovaries and possibly other hormonally responsive organs in both males and females. Between 6
 and 12 months of age, the effects are reduced. Breast milk and some infant formulas may
 contain compounds that can act like female hormones in the body and may prolong the estrogen
 effects. This study will examine the natural history of estrogen activity in infants on
 different feeding regimens, breast milk, cow's milk, and soy milk and will serve as
 preparation for a larger study of the effects of soy formula on estrogen activity in infants.

 Full-term female babies (37 to 41 weeks gestational age at birth) from 0 to 12 months of age
 and male babies from birth to 6 months of age who weigh from 2501 to 4499 grams (about 5.5 to
 10 pounds) at birth and who have no chromosomal abnormalities, major malformations, or
 endocrine problems may be eligible for this study. Males must have palpable testes. Babies
 being fed a diet of breast milk, soy milk, or cow's milk will be included. Study procedures
 include the following:

 -  History of the baby's dietary intake since birth, provided by the parent;

 -  Ultrasound measurement of the uterus, ovaries, and breasts in female babies; the testes,
 prostate, and breasts in males; and the thymus, thyroid, and kidneys in all babies;

 -  Measurements of all babies' weight, length, and head circumference.
Term newborns have anatomic and sonographic evidence of in utero estrogen exposure. Over the
 first six months to a year of life, as the influence of maternal hormone wanes, these
 findings recede. 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. This cross-sectional pilot study will be undertaken
 in order to establish methods for a future multi center study designed to assess the
 potential effects of soy formula on estrogen activity in infants. In this pilot study (SEAD
 1), 156 examinations on full-term infants, ages 0-12 months and on one of three feeding
 regimens (soy formula, breast milk or cow's milk formula) will be completed to see if their
 exposure to soy estrogen compared to breast milk and non-soy formulas prolongs anatomical
 evidence of estrogen exposure and response. A schedule of visits for SEAD 1 is included in
 Appendix A. In addition to SEAD 1, two other cross-sectional studies (SEAD 2 and SEAD 3) will
 be undertaken to evaluate anatomical evidence by physical examination (SEAD 2) and assess the
 hormonal and biochemical status of full-term infants ages 0-12 months (SEAD 3). These studies
 will be conducted at Children's Hospital of Philadelphia (CHOP) in parallel with the SEAD 1
 study. Further details of SEAD 2 and 3 will not be presented in this protocol. The purpose of
 the SEAD 1 pilot study is twofold. The first is to develop and finalize recruitment and
 collections procedures in preparation for a larger, comprehensive trial of biological
 response in children to soy formula with and without the estrogenic isoflavones. The second
 is to study the natural history of estrogen activity in infants on a variety of feeding
 regimens.
-  INCLUSION CRITERIA:

 Full term infants defined as age 37-41 weeks gestational age at birth. Ultrasound evidence
 or reliable reporting of last menstrual period (LMP) by infant's mother.

 Can be categorized into one of the feeding definitions:

 Breastmilk Category:

 0-48 hours old (Age-Interval: 1) - Breastmilk exclusively;

 49 hours - 3 months (Age-Interval: SEAD1 = 2 through 7) - Breastmilk exclusively;

 Greater than 3 months (Age-Interval: SEAD1 = 8 through 19) - Breastmilk exclusively OR
 Breastmilk and Cow-based formula.

 Restriction: Babies in the Breastmilk category are not allowed to have had any SOY foods
 including SOY formula and solid foods containing SOY in their lifetime.

 Cow-Based Formula Category:

 0-48 hours old (Age-Interval: 1) - Cow-based formula exclusively;

 49 hours - 3 months (Age-Interval: SEAD1 = 2 through 7) - Cow-based formula exclusively;

 Greater than 3 months (Age-Interval: SEAD1 = 8 through 19) - Cow-based formula exclusively.

 Exception: If a baby was Breastfed in the nursery, the baby must have gone home on
 Cow-based formula and have been on Cow-based formula exclusively ever since. Such a child
 cannot participate in the SEAD study until s/he has been exclusively Cow-based formula fed
 for at last 2 weeks.

 Restriction: Babies in the Cow-based formula category are not allowed to have had any SOY
 foods including SOY formula and solid foods containing SOY in their lifetime.

 Soy Formula Category:

 0-48 hours old (Age-Interval: 1) - Soy formula exclusively;

 49 hours - 3 months (Age-Interval: SEAD1 = 2 through 7) - Soy formula exclusively;

 Greater than 3 months (Age-Interval: SEAD1 = 8 through 19) - 2/3 of lifetime on Soy formula
 exclusively & continuously, and including the two weeks up to the exam.

 Exception: If a baby was fed something other than Soy formula in the nursery, the baby must
 have gone home on Soy and been on Soy exclusively ever since. Such a child cannot
 participate in the SEAD study until s/he has been exclusively Soy-fed for at least 2 weeks.

 Birth weight between 2501 - 4499 grams.

 Age 0-12 months for girls and age 0-6 months for boys.

 EXCLUSION CRITERIA:

 Chromosomal anomalies.

 Major malformations.

 Non-palpable testis (males only).

 Presence of an endocrinopathy (i.e., ambiguous genitalia, congenital hypothyroidism).