Gestational age correlates to genotype in girls with CYP21 deficiency

The mechanisms behind onset of labor and prolongation of pregnancy are not fully understood, but steroid hormones are thought to contribute. 17-Hydroxyprogesterone has been shown to prolong pregnancy in humans. Male fetuses have been reported to have longer gestation than females.

The objective of the study was to investigate whether severity of 21-hydroxylase gene (CYP21) deficiency in fetuses with congenital adrenal hyperplasia (CAH) correlates with length of pregnancy.

The gestational age (GA) of a cohort of CAH patients born between 1978 and 2004 was studied retrospectively. The GA was correlated to the severity of disease indicated by CYP21 genotype in 114 patients. The results were compared with respect to sex and the normal Swedish population data.

In female fetuses with CAH, we found a correlation between GA and CYP21 genotype. Females with the most severe form of the disease, null mutation, had the longest GA and differed significantly from the normal population. No difference between the sexes was detected for fetuses with CAH as a group. There were no significant differences between CYP21 genotype groups for males.

Female patients with severe CYP21 deficiency had longer GA than patients with the milder form of the disease, indicating that androgen excess, increased 17-hydroxyprogesterone levels, or cortisol deficiency or a combination of these factors is of importance for prolongation of pregnancy. The same correlation was not observed for male patients. The results of this study support the notion that steroid hormones affect the prolongation of pregnancy or onset of labor or both.