Background: In order to prevent virilization in CAH female fetuses, physicians have during the last thirty years used the synthetic glucocorticoid dexamethasone (DEX) as a therapeutic approach administered during early pregnancy. Due to the fact that treatment has to be started before the genotype of the fetus is known, seven out of eight treated fetuses will be subjected to high doses of DEX during early embryogenesis without benefit. Therefore, negative side effects cannot be tolerated.
Objective and hypotheses: To evaluate the long-term effects of prenatal DEX therapy in the context of CAH focusing on neuropsychological functions.
Method: In Sweden, 77 cases were treated prenatally with DEX from 1984 through 2010. We evaluated cognitive functions in 135 subjects aged 717 years (mean 11.0±2.8 years). The cohort comprises 45 prenatally DEX treated children (34 short-term treated healthy boys and girls, five short-term treated boys with CAH, and six long-term treated girls with CAH). The control group comprises 66 healthy children from the general Swedish population and 24 children with CAH. The children were assessed with standardized neuropsychological tests: vocabulary, coding, block design, digit span, processing speed (WISC-III); memory encoding and long term memory (NEPSY); and span-board test (WNV). We report significant and trend findings on a three-way ANOVA with factors CAH (no CAH and CAH), DEX (non-treated and treated), and sex (male and female) as well as specific contrasts of DEX or CAH vs healthy control subjects. Analyses were carried out with test age as covariate of no interest. Omitted main effects and interactions were not significant at P>0.10. Reported group scores are estimated marginal means±S.E.M. for specific contrasts.
Results: DEX treatment significantly affected performance for both, male and female subjects, on visuospatial working memory assessed with the span-board test ((F(1,124)=6.40, P=0.013) and on speed of processing as measured by the stroop-speeded reading (F(1,112)=5.90, P=0.017). Moreover, DEX treatment significantly affected performance for females on all of the sub scores of the WISC-III scale, coding (F(1,60)=3.60, P=0.063), block design (F(1,60)=4.55, P=0.037), vocabulary (F(1,60)=8.30, P=0.005), and digit span (F(1,48)=12.55, P=0.001) but not for males. For verbal working memory, assessed with the test digit span, the effect was restricted to girls without CAH, but it should be noted that female CAH subjects without DEX treatment already performed poorer than healthy controls, pointing to a possible flooring effect (F(1,47)=4.76, P=0.034). In tests assessing long term memory, NEPSY-LTM for faces, DEX treatment did not affect performance, but CAH-patients performed significantly worse than healthy controls (F(1,126)=8.94, P=0.003). In conclusion, prenatal exposure to glucocorticoids has a negative impact on several cognitive functions, especially in girls. CAH-patients perform poorer than healthy controls regardless of prenatal DEX treatment.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology