Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 105, Issue 9, Pages 2996-3004Publisher
ENDOCRINE SOC
DOI: 10.1210/clinem/dgaa393
Keywords
anogenital distance; reference ranges; endocrine disrupting chemicals; disorders of sexual development
Categories
Funding
- National Institute of Environmental Health Sciences [R01ES016863-04, R01 ES016863-02S4, P30 ES023515]
- European Union Framework V programme
- World Cancer Research Fund International
- Medical Research Council (UK)
- Newlife the Charity for Disabled Children
- Mothercare Group Foundation
- Mead Johnson Nutrition
- National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre
- Danish Council for Independent Research medical sciences [4004-00352B_ FSS, 8020-00123B_FSS]
- Odense University Hospital
- Region of Southern Denmark
- Municipality of Odense
- Mental Health Service of the Region of Southern Denmark
- Odense University Hospital Research Foundation
- Odense Patient data Explorative Network (OPEN)
- Novo Nordisk Foundation [NNF15OC00017734, NNF17OC0029404]
- Helsefonden
- Rigshospitalet
- research foundation of Rigshospitalet
- Capital Region of Copenhagen
- Danish Environmental Agency
- International Research and Research Training Centre for Male Reproduction and Child Health (EDMaRC)
- Absalon Foundation
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Context: The use of anogenital distance (AGD) in clinical and epidemiological settings is increasing; however, sex-specific reference data on AGD and data on longitudinal changes in AGD in children is scarce. Objective: To create age-, sex-, and method-related reference ranges of AGD in healthy boys and girls aged 0-24 months, to assess the age-related changes in AGD and to evaluate the 2 predominantly used methods of AGD measurement. Design: The International AGD consortium comprising 4 centers compiled data from 1 cross-sectional and 3 longitudinal cohort studies (clinicaltrials.gov [NCT02497209]). Setting: All data were collected from population-based studies, recruiting from 4 maternity or obstetric centers (United States, Cambridge [United Kingdom], Odense, and Copenhagen [Denmark]). Subjects: This study included a total of 3705 healthy, mainly Caucasian children aged 0-24 months on whom 7295 measurements were recorded. Main Outcome Measures: AGD(AS) (ano-scrotal), AGD(AF) (ano-fourchette), AGD(AP) (ano-penile), AGD(AC) (ano-clitoral), AGD body size indices (weight, body mass index [BMI], body surface area, and length), and intra- and interobserver biases. Results: We created age-specific reference ranges by centers. We found that AGD increased from birth to 6 months of age and thereafter reached a plateau. Changes in AGD/BMI during the first year of life were minor (0-6% and 0-11% in boys and girls, respectively). Conclusions: Reference ranges for AGD can be used in future epidemiological research and may be utilized clinically to evaluate prenatal androgen action in differences-in-sex-development patients. The increase in AGD during the first year of life was age-related, while AGD/BMI was fairly stable. The TIDES and Cambridge methods were equally reproducible.
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