Identifying and clinically managing DSD can begin before a child is born. Expectations of the family and healthcare providers regarding the somatic sex of the child are increasingly driven by advances in technology; for example, remarkably clear ultrasound images and genetic testing that can noninvasively and reliably ascertain fetal chromosomal sex between 7 and 12 weeks are widely available in industrialized countries. Discordance between prenatal test findings (e.g., genital appearance by ultrasound and karyotype) can initiate the DSD counseling process even at this early stage. Evidence from studies of prenatal diagnostic counseling suggests that termination of a pregnancy is dependent upon the professional background of the healthcare provider delivering post-diagnostic counseling.[8–10] There is substantial variation in healthcare providers' knowledge regarding DSD. Because these conditions are rare and, historically, understudied and misunderstood, parents are at risk of receiving outdated or incomplete information unless major efforts are made in the context of interdisciplinary care teams.
Beyond diagnosis, the prenatal period has seen efforts at medical intervention to avert phenotypic changes associated with DSD; a case in point is prenatal suppression of adrenal androgens that masculinize the genitalia in 46, XX congenital adrenal hyperplasia (CAH). CAH comprises a family of autosomal recessive disorders involving impaired synthesis of cortisol. In 21-hydroxylase deficiency (21-OH CAH), the most common form comprising as many as 95% of new cases, excessive adrenal androgen biosynthesis results in masculinization of the genitals of 46, XX offspring. If a woman has previously had a child with CAH and again becomes pregnant with the same partner (assuming both are carriers), the fetus has a one in four chance of acquiring the genotype associated with CAH. Suppression of fetal adrenal androgens in CAH is achievable by administering glucocorticoids (dexamethasone, DEX) during the pregnancy. The goal is to reduce genital masculinization of female offspring and obviate the need for reconstructive surgery and presumed distress associated with the birth of a child with atypical genitalia.
Criticism of this intervention centers around several issues: first, the treatment is experimental and, yet, not characteristically delivered in the context of a clinical trial with necessary human subject oversight as called for in CAH practice guidelines;[13,14] second, to be effective, DEX treatment must be initiated between gestational weeks 6 to 7 and before it can be determined whether the fetus carries the CAH gene mutation. Treatment continues until chorionic villi sampling can be employed for genotyping. If the fetus is 46, XY or 46, XX without the CAH genotype, then treatment is discontinued. Accordingly, 7 out of 8 fetuses (all 46, XY and three out of four 46, XX) gain no benefit from the treatment but are exposed to potential risks; third, the safety of prenatal DEX for outcomes such as metabolism, cognitive function and behavioral-emotional adaptation is in question based on animal experimental and human clinical research;[15–21] fourth, prenatal treatment does not change the need for lifelong glucocorticoid replacement therapy, the need for careful medical monitoring, or the risk of life-threatening salt-losing crises if treatment adherence is poor. Finally, concern over prenatal DEX treatment has been expressed by bioethicists who have questioned whether treatment introduced to "normalize" genital anatomy is confounded with the goal of making gender-role behavior and sexual orientation more typical.
Opportunities for systematic research and theory development that examine the influence of timing of diagnosis (prenatal versus later) on treatment choices (e.g., gender assignment, genital surgery, etc.) and HRQoL outcomes for patients and families are as yet untapped.
Semin Reprod Med. 2012;30(5):443-452. © 2012 Thieme Medical Publishers