Anogenital Distance in Healthy Infants: Method-, Age- and Sex-related Reference Ranges
Margit Bistrup Fischer, Marie Lindhardt Ljubicic, Casper P. Hagen, Ajay Thankamony, Ken K. Ong, Ieuan A. Hughes, Tina Kold Jensen, Katharina M. Main, Jørgen Holm Petersen, Alexander S. Busch, Emmie N. Upners, Sheela Sathyanarayana, Shanna H. Swan, Anders Juul
Abstract
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: AGDAS (ano-scrotal), AGDAF (ano-fourchette), AGDAP (ano-penile), AGDAC (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.