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      Pilot Studies of Estrogen-Related Physical Findings in Infants

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          Abstract

          Background

          Soy formula containing estrogenic isoflavones is widely used in the United States. Infants consuming soy formula exclusively have high isoflavone exposures. We wanted to study whether soy formula prolonged the physiologic estrogenization of newborns, but available quantitative descriptions of the natural history of breast and genital development are inadequate for study design.

          Objective

          We piloted techniques for assessing infants’ responses to the withdrawal from maternal estrogen and gathered data on breast and genital development in infants at different ages.

          Methods

          We studied 37 boys and 35 girls, from term pregnancies with normal birth weights, who were < 48 hr to 6 months of age, and residents of Philadelphia, Pennsylvania, during 2004–2005. One-third of the children of each sex and age interval were exclusively fed breast milk, soy formula, or cow-milk formula. Our cross-sectional study measured breast adipose tissue, breast buds, and testicular volume; observed breast and genital development; and collected vaginal wall cells and information on vaginal discharge. We assessed reliability of the measures.

          Results

          Breast tissue was maximal at birth and disappeared in older children, consistent with waning maternal estrogen. Genital development did not change by age. Breast-milk secretion and withdrawal bleeding were unusual. Vaginal wall cells showed maximal estrogen effect at birth and then reverted; girls on soy appeared to show reestrogenization at 6 months.

          Conclusions

          Examination of infants for plausible effects of estrogens is valid and repeatable. Measurement of breast tissue and characterization of vaginal wall cells could be used to evaluate exposures with estrogen-like effects.

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          Most cited references32

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          Categorical Data Analysis

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            New Ballard Score, expanded to include extremely premature infants.

            The Ballard Maturational Score was refined and expanded to achieve greater accuracy and to include extremely premature neonates. To test validity, accuracy, interrater reliability, and optimal postnatal age at examination, the resulting New Ballard Score (NBS) was assessed for 578 newly born infants and the results were analyzed. Gestational ages ranged from 20 to 44 weeks and postnatal ages at examination ranged from birth to 96 hours. In 530 infants, gestational age by last menstrual period was confirmed by agreement within 2 weeks with gestational age by prenatal ultrasonography (C-GLMP). For these infants, correlation between gestational age by NBS and C-GLMP was 0.97. Mean differences between gestational age by NBS and C-GLMP were 0.32 +/- 1.58 weeks and 0.15 +/- 1.46 weeks among the extremely premature infants (less than 26 weeks) and among the total population, respectively. Correlations between the individual criteria and C-GLMP ranged from 0.72 to 0.82. Interrater reliability of NBS, as determined by correlation between raters who rated the same subgroup of infants, ws 0.95. For infants less than 26 weeks of gestational age, the greatest validity (97% within 2 weeks of C-GLMP) was seen when the examination was performed before 12 hours of postnatal age. For infants at least 26 weeks of gestational age, percentages of agreement with C-GLMP remained constant, averaging 92% for all postnatal age categories up to 96 hours. The NBS is a valid and accurate gestational assessment tool for extremely premature infants and remains valid for the entire newborn infant population.
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              A simplified score for assessment of fetal maturation of newly born infants.

              A simplified scoring system for clinically determining fetal maturation of newly born infants has been developed and provides accurate assessment of gestational age in either well or sick babies. Certain conditions render individual criteria within the score less reliable but do not significantly lessen the reliability of the total assessment. The optimal age for maturational assessment is between 30 and 42 hours of age.
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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                March 2008
                12 December 2007
                : 116
                : 3
                : 416-420
                Affiliations
                [1 ] Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA
                [2 ] Biostatistics Branch and
                [3 ] Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
                [4 ] Department of Neonatology, Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA
                [5 ] Survey & Epidemiology Services Division, Social & Scientific Systems, Inc. (formerly Coda, Inc.), Durham, North Carolina, USA
                [6 ] Westat Inc., Durham, North Carolina, USA
                Author notes
                Address correspondence to W.J. Rogan, NIEHS, Post Office Box 12233, Mail Drop A3-05, Research Triangle Park, NC 27709 USA. Telephone: (919) 541–4578. Fax: (919) 541–2511. E-mail: rogan@ 123456niehs.nih.gov

                W.J.R. accepted travel funds from Nestlé in 1998, and from the American Oil Chemists’ Society in 2005 to give talks at meetings. Findings were presented in a poster at the 2006 Pediatric Academic Societies’ Annual Meeting, San Francisco, CA, USA, and at the 2006 Children’s Environmental Health: Endocrine Disruptors/Risk Assessment and Children symposium in Berkeley, CA, USA. All other authors declare they have no competing financial interests.

                Article
                ehp0116-000416
                10.1289/ehp.10409
                2265048
                18335112
                1137c1a8-2daf-4803-b97c-1caada536cb0
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.
                History
                : 25 April 2007
                : 11 December 2007
                Categories
                Research
                Children's Health

                Public health
                infant formula,estrogen,human milk,breast bud,vaginal maturation index,testis
                Public health
                infant formula, estrogen, human milk, breast bud, vaginal maturation index, testis

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