Sukran Poyrazoglu1, Feyza Darendeliler1, S Faisal Ahmed2, Ieuan Hughes3, Jillian Bryce2, Jipu Jiang2, Martina Rodie2, Olaf Hiort4, Sabine E Hannema5,6, Silvano Bertelloni7, Lidka Lisa8, Tulay Guran9, Martine Cools10, An Desloovere10, Hedi L Claahsen-van der Grinten11, Anna Nordenstrom12, Paul-Martin Holterhus13, Birgit Kohler14, Marek Niedziela15, Nils Krone16,17. 1. Istanbul University, Istanbul Faculty of Medicine, 34093 Istanbul, Turkey. 2. University of Glasgow, Glasgow G51 4TF, United Kingdom. 3. University of Cambridge, Cambridge CB2 1TN, United Kingdom. 4. Division of Pediatric Endocrinology and Diabetes, University of Luebeck, 23562 Luebeck, Germany. 5. Sophia Children's Hospital, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands. 6. Leiden University Medical Center, 2300 RC Leiden, The Netherlands. 7. Adolescent Medicine, Pediatric Division, Azienda Ospedaliera Universitaria Pisana, 56125 Pisa, Italy. 8. Institute of Endocrinology, Prague 1, CZ-116 94, Czech Republic. 9. Marmara University, 34899 Istanbul, Turkey. 10. University Hospital Ghent, B-9000 Ghent University, Ghent, Belgium. 11. Radboudumc Amalia Children's Hospital, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands. 12. Karolinska University Hospital, SE-171 77 Stockholm, Sweden. 13. University Hospital Schleswig-Holstein, 24105 Kiel, Germany. 14. University Children's Hospital, Charite, Humboldt University, 13353 Berlin, Germany. 15. Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, 60-572 Poznan, Poland. 16. Birmingham Children's Hospital, Birmingham B15 2TT, United Kingdom; and. 17. Academic Unit of Child Health, University of Sheffield, Sheffield S10 2T4, United Kingdom.
Abstract
CONTEXT: It is well established that boys are heavier than girls at birth. Although the cause of birth weight (BW) difference is unknown, it has been proposed that it could be generated from prenatal androgen action. OBJECTIVE: The aim of the current study was to determine the BW of children with disorders of sex development (DSD) of different etiologies and to evaluate the effects of androgen action on BW. METHODS: Data regarding diagnosis, BW, gestational age, karyotype, and concomitant conditions were collected from the International Disorders of Sex Development (I-DSD) Registry (www.i-dsd). BW standard deviation score was calculated according to gestational age. Cases were evaluated according to disorder classification in I-DSD (i.e., disorders of gonadal development, androgen excess, androgen synthesis, androgen action, nonspecific disorder of undermasculinization groups, and Leydig cell defect). RESULTS: A total of 533 cases were available; 400 (75%) cases were 46,XY, and 133 (25%) cases were 46,XX. Eighty cases (15%) were born small for gestational age (SGA). Frequency of SGA was higher in the 46,XY group (17.8%) than in the 46,XX (6.7%) group (P = 0.001). Mean BW standard deviation scores of cases with androgen excess and androgen deficiency [in disorders of gonadal development, androgen synthesis, and Leydig cell defect groups and androgen receptor gene (AR) mutation-positive cases in disorders of androgen action groups] were similar to normal children with the same karyotype. SGA birth frequency was higher in the AR mutation-negative cases in disorders of androgen action group and in the nonspecific disorders of the undermasculinization group. CONCLUSIONS: BW dimorphism is unlikely to be explained by fetal androgen action per se. 46,XY DSDs due to nonspecific disorders of undermasculinization are more frequently associated with fetal growth restriction, SGA, and concomitant conditions.
CONTEXT: It is well established that boys are heavier than girls at birth. Although the cause of birth weight (BW) difference is unknown, it has been proposed that it could be generated from prenatal androgen action. OBJECTIVE: The aim of the current study was to determine the BW of children with disorders of sex development (DSD) of different etiologies and to evaluate the effects of androgen action on BW. METHODS: Data regarding diagnosis, BW, gestational age, karyotype, and concomitant conditions were collected from the International Disorders of Sex Development (I-DSD) Registry (www.i-dsd). BW standard deviation score was calculated according to gestational age. Cases were evaluated according to disorder classification in I-DSD (i.e., disorders of gonadal development, androgen excess, androgen synthesis, androgen action, nonspecific disorder of undermasculinization groups, and Leydig cell defect). RESULTS: A total of 533 cases were available; 400 (75%) cases were 46,XY, and 133 (25%) cases were 46,XX. Eighty cases (15%) were born small for gestational age (SGA). Frequency of SGA was higher in the 46,XY group (17.8%) than in the 46,XX (6.7%) group (P = 0.001). Mean BW standard deviation scores of cases with androgen excess and androgen deficiency [in disorders of gonadal development, androgen synthesis, and Leydig cell defect groups and androgen receptor gene (AR) mutation-positive cases in disorders of androgen action groups] were similar to normal children with the same karyotype. SGA birth frequency was higher in the AR mutation-negative cases in disorders of androgen action group and in the nonspecific disorders of the undermasculinization group. CONCLUSIONS: BW dimorphism is unlikely to be explained by fetal androgen action per se. 46,XY DSDs due to nonspecific disorders of undermasculinization are more frequently associated with fetal growth restriction, SGA, and concomitant conditions.
Authors: Martine van Zoest; Else M Bijker; Barbara B M Kortmann; Marlies Kempers; Antonius E van Herwaarden; Janiëlle van der Velden; Hedi L Claahsen-van der Grinten Journal: Sex Dev Date: 2019-08-08 Impact factor: 1.824