Anogenital Distance in Healthy Infants: Method-, Age- and Sex-related Reference Ranges

Author:

Fischer Margit Bistrup12ORCID,Ljubicic Marie Lindhardt12,Hagen Casper P12,Thankamony Ajay3,Ong Ken34,Hughes Ieuan3,Jensen Tina Kold56ORCID,Main Katharina M12,Petersen Jørgen Holm7,Busch Alexander S12,Upners Emmie N12,Sathyanarayana Sheela89,Swan Shanna H10,Juul Anders12ORCID

Affiliation:

1. Deptartment of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

2. International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

3. Department of Paediatrics, University of Cambridge, Cambridge, UK

4. MRC Epidemiology Unit, University of Cambridge, Cambridge, UK

5. Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, dense, Denmark

6. Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, Denmark

7. Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark

8. Department of Pediatrics/Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington

9. Department of Pediatrics, Seattle Children’s Research Institute, Seattle, Washington

10. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York

Abstract

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.

Funder

National Institute of Environmental Health Sciences

European Union Framework V programme

World Cancer Research Fund

Medical Research Council

Newlife Foundation for Disabled Children

Mothercare Group Foundation

Mead Johnson Nutrition

National Institute for Health Research

Danish Council for Independent Research medical sciences

Odense Universitetshospital

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

Novo Nordisk Fonden

Rigshospitalet

Danish Environmental Agency

Absalon Foundation

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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