Pregnancy and Prenatal Management of Congenital Adrenal Hyperplasia

Abstract

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases that may cause cortisol insufficiency together with other hormonal alterations. The most common form is 21-hydroxylase deficiency, in which the lack of pituitary negative feedback causes an increase in ACTH and adrenal androgens. Classical forms of CAHs can lead to severe adrenal failure and female virilization. To date, the appropriate management of pregnant CAH patients is still debated regarding appropriate maternal therapy modifications during pregnancy and the risks and benefits of prenatal treatment of the fetus. We conducted a literature search of relevant papers to collect current evidence and experiences on the topic. The most recent and significant articles were selected, and current international guidelines were consulted to update current recommendations and guide clinical practice. Given the lack of randomized clinical trials and other high-quality scientific evidence, the issue is still debated, and great heterogeneity exists in current practice in terms of risk/benefit evaluation and pharmacological choices for pregnancy and prenatal treatment. Glucocorticoid therapy is advised not only in classical CAH patients but also in non-classical, milder forms. The choice of which glucocorticoid to use, and the safety and benefits of dexamethasone therapy aimed at preventing genital virilization are still debated issues. Several advances, however, have been made, especially in terms of fertility and reproduction. This review aims to present the most recent scientific and real-world updates on pregnancy and prenatal management of CAH, with the presentation of various clinical scenarios and specific case-by-case recommendations.

Prenatal diagnosis and in utero treatment of congenital adrenal hyperplasia: An up‐to‐date comprehensive review

“…The concern arises regarding the continued use of DEX in unaffected females and affected male fetuses, as animal studies suggest that long duration treatment with DEX can potentially lead to adverse effects on the developing fetal brain, highlighting the need to stop the DEX therapy as soon as it is deemed to be clinically unnecessary 47 . The dose regimen given to mothers at risk of possible virilization is 20 μg/kg/day, based on the maternal pre‐pregnancy weight administered in three divided doses to receive a total value of about 1.5 mg/day 4,48 . In 2021, Stachanow et al 49 .…”

“…As with any treatment, treating the developing fetus with DEX is not without risk, as studies have demonstrated that there can be possible maladaptive effects on the fetus's metabolism and intellect 53 . This prompts the following question: “Do the benefits of using steroid therapy to prevent fetal virilization in utero outweigh the risks?” This question is critical to consider as while steroid intervention can defer virilization and prevent the need for genital feminization surgery, complications related to the therapy can cause long‐standing physical and mental complications to both mother and baby, considered to be substantially worse off than genital masculinization 48 …”

“…While their findings were inconclusive, the studies that followed showed that DEX‐treated children tended to be diagnosed with mental disorders 1.4 years younger compared to their non‐steroid‐treated counterparts 58 . In addition to an increase in mental disorders, Swedish authors have reported alterations in social and cognitive functioning, particularly in females treated prenatally with DEX compared to cohorts that were not exposed 48 …”

Hiperplasia Adrenal Congênita

“…Como o NCCAH não é o alvo primário da triagem neonatal e raramente é detectado por essa estratégia, a verdadeira prevalência desse distúrbio mais leve não é clara. Tem uma prevalência de 1:300 a 1:27 em diferentes grupos étnicos, tornando potencialmente a 21-OHD uma das doenças autossômicas recessivas mais comuns em humanos (CHATZIAGGELOU A, et al, 2019; CLAAHSEN- CERA G, et al, 2022).…”

Caring for Patients With Congenital Adrenal Hyperplasia Throughout the Lifespan

“…For patients with CAH who desire pregnancy, prepregnancy counseling is essential so that their partner can undergo testing and subsequently assess the risk of having a fetus with CAH. 44 Assisted reproductive technology and preimplantation genetics offer couples at risk of having a fetus with CAH the opportunity to transfer an unaffected embryo. 45…”