Are anogenital distance and external female genitalia development changed in neural tube defects? Study in human fetuses

Abstract

Anogenital distance (AGD), the distance from the anus to the genitals, is a marker of normal genital development. AGD and other biometric parameters of external female genitalia are important as ultrasonographic markers that can determine fetal gender in the first trimester. Neural tube defects are one of the commonest congenital malformations of the central nervous system, with anencephaly being the most severe defect. Female genitalia development and their association with anencephaly have not been previously described. The aim of this study was to compare the biometric parameters of external female genitalia in fetuses with anencephaly and compare it to the parameters of normocephalic fetuses at different gestational ages. We studied 34 female fetuses, 22 normocephalic and 12 anencephalic, aged between 12 and 22 weeks post-conception. The fetuses were placed in the classic lithotomy position and before the fetal dissection, the external female genitalia were photographed with a digital camera. Biometric parameters were recorded and measurements were performed using the Image J software, version 1.46r. Clitoral length and width, clitoris to anus distance, vaginal opening length and width, vaginal opening to labia majora distance, and AGD were measured (Figure). For statistical analysis, the Wilcoxon-Mann-Whitney test was used (p<0.05). We observed a significant difference between some measurements of the groups: the vaginal opening width was significantly greater in anencephalic fetuses and the vaginal opening length, clitoris to anus distance and vaginal opening to labia majora distance were significantly greater in normocephalic fetuses. For the clitoris length and width, we did not find statistical differences. We also did not find statistical significance in AGD between groups (normocephalic 2.32mm [2.46-6.42/SD=2.17] vs. anencephalic 3.93mm [1.15-6.65/SD=1.93]; p=0.499). The linear regression analysis indicated that AGD increased more with age in anencephalic than in the normocephalic group, but without significant differences (r2=0.01677; p<0.318). This article is the first to report the female external genitalia parameters in fetuses with anencephaly. In our study we observed some alterations in biometry of the external genitalia in anencephalic fetuses, with a pattern of morphological reduction in this group. The vaginal opening length, clitoris to anus distance and vaginal opening to labia majora distance were significantly lower in anencephalic fetuses but we did not find statistical significance in clitoris measurements and AGD. Anencephalic fetuses had some alterations in external genitalia development, but the anogenital distances did vary significantly between the groups.