Prenatal Dexamethasone for Congenital Adrenal Hyperplasia An Ethics Canary in the Modern Medical Mine (original) (raw)
Related papers
Prenatal Dexamethasone for Congenital Adrenal Hyperplasia
Journal of Bioethical Inquiry, 2012
Following extensive examination of published and unpublished materials, we provide a history of the use of dexamethasone in pregnant women at risk of carrying a female fetus affected by congenital adrenal hyperplasia (CAH). This intervention has been aimed at preventing development of ambiguous genitalia, the urogenital sinus, tomboyism, and lesbianism. We map out ethical problems in this history, including: misleading promotion to physicians and CAH-affected families; de facto experimentation without the necessary protections of approved research; troubling parallels to the history of prenatal use of diethylstilbestrol (DES); and the use of medicine and public monies to attempt prevention of benign behavioral sex variations. Critical attention is directed at recent investigations by the U.S. Food and Drug Administration (FDA) and Office of Human Research Protections (OHRP); we argue that the weak and unsupported conclusions of these investigations indicate major gaps in the systems meant to protect subjects of high-risk medical research.
Challenges in Prenatal Treatment with Dexamethasone
Pediatric endocrinology reviews : PER, 2018
Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency causes elevated androgen levels, which can lead to virilization of female external genitalia. Prenatal dexamethasone treatment has been shown to be effective in preventing virilization of external genitalia when started prior to 7-9 weeks of gestation in females with classic CAH. However, CAH cannot be diagnosed prenatally until the end of the first trimester. Treating pregnant women with a fetus at risk of developing classic CAH exposes a significant proportion of fetuses unnecessarily, because only 1 in 8 would benefit from treatment. Consequently, prenatal dexamethasone treatment has been met with much controversy due to the potential adverse outcomes when exposed to high-dose steroids in utero. Here, we review the short- and long-term outcomes for fetuses and pregnant women exposed to dexamethasone treatment, the ethical considerations that must be taken into account, and current practice recommendations.
Paediatrica Indonesiana, 2021
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder commonly caused by mutation of the CYP21A2 gene, resulting in deficiency of an enzyme required for cortisol synthesis in the adrenal cortex. In 90-95% of cases, the deficient enzyme is 21-hydroxylase (21-OH), with an incidence ranging from 1 in 5,000 to 15,000 live births across various ethnic and racial backgrounds. In classical 21-OH deficiency (21-OHD) CAH, excessive androgen exposure in the fetus results in virilization at birth.1 The management of ambiguous genitalia in children with CAH presents a unique and ethically challenging decision-making dilemma for the medical team. Insensitive and poorly informed statements made in the delivery room may cause long-term psychological problems for the families. It is important to refrain from assigning gender until sufficient diagnostic information can be gathered. Parents, as guardians, and the supporting medical team must make decisions on behalf of the child, wi...
Perceptions in Reproductive Medicine, 2018
This is the case of a newborn son of a 26-year-old primigravida woman. Pregnancy was apparently normal, nevertheless prenatal control results are unknown. The woman had a vaginal delivery at term (41 weeks) and no complications were mentioned. In the first evaluation the doctor observed that the newborn has male genital appearance; however, the mother notices that the urethral opening is at the base of the phallic axis and the phallus is short. It is evaluated by a pediatrician, who, based on the doubts of the mother, suspects the diagnosis of congenital adrenal hyperplasia (CAH). The physician provides explanations to parents about the findings and possible condition of the newborn, as well as information about the controversies regarding to gender allocation, parenting, and early surgery. An independent pediatric urologist examines the newborn and concludes that the baby should be a virilized girl and therefore considered as a real male child; so he resolves the case in this way: the surgical procedure of reassignment of sex must be consider. Meanwhile the pediatrician indicates that the result of the ultrasound performed to the newborn reports a formed uterus and presence of ovaries. A sample of umbilical cord blood is taken to evaluate the karyotype, but its result is not mentioned. The parents, their personal friends and the relatives have doubts about the appropriate time to schedule the hypospadia correction surgery; to which the doctor has no satisfactory answer for them. Considerations Based on the principles that govern clinical ethics, Jonsen [1] proposes that there are some questions that must be answered or clarified by the professional or the team of professionals who face decision making. Thus, medical indications should be primarily governed by the principles of beneficence and non-maleficence. From this perspective, it must be taken into account that this is a newborn diagnosed with a probable Disorder of Sex Development (DSDs), possibly a virilising congenital adrenal hyperplasia (HSC), in which the objectives of the surgical treatment would be to correct the appearance of the genitals (surgical reassignment of the anatomical sex) and to improve the urogenital function. First it is important to note that this is not a medical emergency, since there is no risk of urogenital malignancy, infection or acute cardio respiratory or metabolic decompensation, hence its resolution and decision regarding to the allocation of phenotypic sex can be deferred. And secondly, according to the American Academy of Pediatrics, it is relevant to have the result of karyotype in order to make a more precise diagnosis of DSDs to achieve more accuracy and provide a correct treatment. In addition, other paraclinical exams such as blood glucose, blood electrolyte levels, among others might be necessary [2-4]. Also, regarding the patient preferences, the principle of respect for Autonomy must be considered. For the case, it is obvious that the patient does not have mental or legal abilities to decide for herself, so she would be incompetent to make the decision to undergo medical and surgical treatment. Her parents, who serve as her legal representatives and those in charge of the newborn, must be well informed about the terms of the diagnosis and treatment
American Journal of Obstetrics and Gynecology, 2005
Ethics Fetus as a patient Clinical research Pregnant women Informed consent Objective: We present and defend ethically justified guidelines for pharmacologic research that involves pregnant women. Study design: We explain the ethical concept of the fetus as a patient and identify its ethical implications for the design and conduct of pharmacologic research that is intended to benefit pregnant women. Results: This concept justifies criteria for the initiation of early-phase clinical investigation, the initiation of controlled trials, the use of placebo control subjects, the stopping of randomized controlled trials, the determination of when an experimental intervention should be regarded as standard of care, and research that involves adolescents. The informed consent process should be shaped by the pregnant patient's obligation to take in to account her beneficence-based obligations to a fetal patient. Selection criteria should not be based on abortion preference. And, physicians are justified ethically in referring pregnant women to trials. Conclusion: The concept of the fetus as a patient plays an essential role in the ethically justified design and conduct of pharmacologic research in pregnant women.
Clinical Endocrinology, 2010
Context Prenatal treatment with dexamethasone to prevent virilization in pregnancies at risk for classical congenital adrenal hyperplasia (CAH) remains controversial. Objective To conduct a systematic review and meta-analyses of studies that evaluated the effects of dexamethasone administration during pregnancies at risk for classical CAH because of 21-hydroxylase deficiency (CYP21A2). Data Sources We searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception through August 2009. Review of reference lists and contact with CAH experts further identified candidate studies. Study Selection Reviewers working independently and in duplicate determined trial eligibility. Eligible studies reported the effects on either foetal or maternal outcomes of dexamethasone administered during pregnancy compared to a control group that did not receive any treatment. Data Extraction Reviewers working independently and in duplicate determined the methodological quality of studies and collected data on patient characteristics, interventions, and outcomes. Data Synthesis We identified only four eligible observational studies (325 pregnancies treated with dexamethasone). The methodological quality of the included studies was overall low. Metaanalysis demonstrates a reduction in foetus virilization measured by Prader score in female foetuses treated with dexamethasone initiated early during pregnancy (weighted mean difference, )2AE33, 95% CI, )3AE38, )1AE27). No deleterious effects of dexamethasone on stillbirths, spontaneous abortions, foetal malformations, neuropsy-chological or developmental outcomes were found although these data are quite sparse. There was increased oedema and striae in the mothers treated with dexamethasone. There were no data on longterm follow-up of physical and metabolic outcomes in children exposed to dexamethasone. Conclusions The observational nature of the available evidence and the overall small sample size of the whole body of the literature significantly weaken inferences about the benefits and harms of dexamethasone in this setting. Dexamethasone seems to be associated with reduction in foetus virilization without significant maternal or foetal adverse effects. However, this review underscores the current uncertainty and further investigation is clearly needed. The decision about initiating treatment should be based on patients' values and preferences and requires fully informed and consenting parents.