ESPE Yearbook of Paediatric Endocrinology

J Clin Endocrinol Metab. 2021; 106(2): e957–e965.https://pubmed.ncbi.nlm.nih.gov/33135723/

The authors investigated the reproductive and perinatal outcomes in women with congenital adrenal hyperplasia (CAH) compared with control women in the largest such population-based study to date. Women with CAH had lower birth rates, were more likely to develop gestational diabetes, and had other adverse perinatal outcomes.

CAH is one of the most common monogenic autosomal recessive disorders. Its mild form has a prevalence of 1-10%, depending on the population. The disorder is characterized by impaired glucocorticoid and often mineralocorticoid secretion, and increased adrenal androgen production. Reportedly, both men and women with CAH exhibit reduced fertility and birth rate. In women with CAH, there are many possible underlying causes. Under- and overtreatment with glucocorticoids may disturb normal ovulation by causing hormone imbalances, e.g. increased androgen production. But other causes, such as anatomical barriers and psychosocial factors, may also play an important role.

This study included 272 women with CAH due to 21-hydroxylase deficiency (median age 31 years) and 27,200 controls (100 controls per patient) matched by sex, age, and place of birth. Outcome measures, i.e., pregnancy, births and neonatal outcomes were retrieved from the Swedish Medical Birth Registry. On average, women with CAH had fewer children and a lower proportion of birth rate, especially patients with the most severe phenotypes. Patients with CAH were also older at the birth of their first child and were more prone to develop gestational diabetes. Cesarean section was the most common mode of delivery in CAH patients, especially in women with the most severe phenotype. Perinatal outcome was comparable with the controls in general, but the simple virilizing CAH subgroup showed a slightly increased risk of small for gestational age infants. This study provides valuable information regarding the reproductive and perinatal outcomes of women with CAH due to 21-hydroxylase deficiency.

Reference: 1. Gomes LG, Bachega TASS, Mendonca BB. Classic congenital adrenal hyperplasia and its impact on reproduction. Fertil Steril. 2019; 111(1): 7–12.2. Słowikowska-Hilczer J, Hirschberg AL, Claahsen-van der Grinten H, et al.; dsd-LIFE Group. Fertility outcome and information on fertility issues in individuals with different forms of disorders of sex development: findings from the DSD-LIFE study. Fertil Steril. 2017; 108(5): 822–831.3. Falhammar H, Frisen L, Norrby C, Falhammar H, Frisén L, Norrby C, Almqvist C, Hirschberg AL, Nordenskjöld A, Nordenström A. Reduced frequency of biological and increased frequency of adopted children in males with 21-hydroxylase deficiency: a Swedish population-based national cohort study. J Clin Endocrinol Metab. 2017; 102(11): 4191–4199.