XX Congenital Adrenal Hyperplasia Research Articles

Recommendations for 46,XX Congenital Adrenal Hyperplasia Across Two Decades: Insights from the North American Differences of Sex Development Clinician Survey.

Several aspects of clinical management of 46,XX congenital adrenal hyperplasia (CAH) remain unsettled and controversial. The North American Disorders/Differences of Sex Development (DSD) Clinician Survey investigated changes, over the last two decades, in clinical recommendations by specialists involved in the management of newborns with DSD. Members of the (Lawson Wilkins) Pediatric Endocrine Society and the Societies for Pediatric Urology participated in a web-based survey at three timepoints: 2003-2004 (T1, n = 432), 2010-2011 (T2, n = 441), and 2020 (T3, n = 272). Participants were presented with two clinical case scenarios-newborns with 46,XX CAH and either mild-to-moderate or severe genital masculinization-and asked for clinical recommendations. Across timepoints, most participants recommended rearing the newborn as a girl, that parents (in consultation with physicians) should make surgical decisions, performing early genitoplasty, and disclosing surgical history at younger ages. Several trends were identified: a small, but significant shift toward recommending a gender other than girl; recommending that adolescent patients serve as the genital surgery decision maker; performing genital surgery at later ages; and disclosing surgical details at younger ages. This is the first study assessing physician recommendations across two decades. Despite variability in the recommendations, most experts followed CAH clinical practice guidelines. The observation that some of the emerging trends do not align with expert opinion or empirical evidence should serve as both a cautionary note and a call for prospective studies examining patient outcomes associated with these changes.

Extensive Literature Review of 46, XX Newborns with Congenital Adrenal Hyperplasia (CAH) and Severe Genital Masculinization: Should They be Assigned and Reared Male?

46, XX individuals born with severely masculinized genitals due to congenital adrenal hyperplasia (CAH) who have been assigned males at birth and reared male can successfully establish a male gender identity/role, find employment, marry, function sexually with a female partner, and develop positive mental health status. While there were a few individuals who reportedly did not fare well or who changed gender to female, the majority of those identifying as males appear to have an overall good quality of life. Parental/family support, along with the support of others, appears essential to a positive outcome as a male or as a female. Reasons are given to support why serious consideration of a male gender assignment and rearing, in certain situations, is justified and should be seriously considered. Disorders of Sex Differentiation (DSD) teams should inform parents of the option of male assignment and rearing in 46, XX CAH infants with severe genital masculinization, a rare condition. To provide this option is concordant with the principles of ethics, transparency and with the Endocrine Society Guidelines and the American Academy of Pediatrics' policy of fully informed consent.

Challenges in the treatment of late-identified untreated congenital adrenal hyperplasia due to CYP11B1 deficiency: Lessons from a developing country.

Congenital Adrenal Hyperplasia (CAH) due to CYP11B1 is a rare autosomal recessive adrenal disorder that causes a decrease in cortisol production and accumulation of adrenal androgens and steroid precursors with mineralocorticoid activity. Clinical manifestations include cortisol deficiency, ambiguous genitalia in females (differences of sex development (DSD)), and hypertension. Medical treatment recommendations are well defined, consisting of glucocorticoid treatment to substitute glucocorticoid deficiency and consequently normalize adrenal androgen and precursors levels. Current guidelines also emphasize the need for specialized multidisciplinary DSD teams and psychosocial support. In many developing countries, care for DSD patients, especially when caused by an adrenal disease, is challenging due to the lack of infrastructure, knowledge, and medication. The study aims to report the conflicting decision-making process of medical treatment and sex assignment in late-identified CAH patients in developing countries. We describe the clinical and biochemical findings and the psychological assessment of five affected but untreated family members with CAH due to CYP11B1 deficiency. All patients had a 46,XX karyotype, ambiguous genitalia, low cortisol levels, and hypertension. Two identified as males, two as females, and one had undecided gender. The patients were counselled that refusing treatment will lead to infertility and the potential risk of developing Addisonian crisis and severe hypertension. However, all 46,XX CAH males refused treatment with glucocorticoids due to the expected lowering of adrenal androgens as their main source of testosterone. None of the patients developed Addisonian crisis, probably due to some residual cortisol activity and glucocorticoid activity of elevated adrenal steroid precursors. Medical treatment and sex assignment in late-identified 46,XX CAH patients in Indonesia may often depend on local and cultural factors. The management of DSD conditions may have to be individualized and integrated into the psychological and social context of the affected family.

46 XX Congenital Adrenal Hyperplasia (CAH) after Clitoroplasty, Labioplasty, and Vaginoplasty

Congenital adrenal hyperplasia (CAH) is the most common cause (60%) of Disorder of Sex Development (DSD), which causes three problems: symptoms and conditions arising due to adrenal endocrine disorders, long-term treatment, and quality of life due to genital ambiguity. An 18-year-old female patient was diagnosed with simple virilizing CAH and had genital ambiguity from birth. The patient was raised as a male. Overall, the examination results indicated a female. Physical examination before surgery showed virilization, such as external genital pigmentation, precocious pubic hair, and bilateral impalpable testis. The karyotype genetic examination confirmed female: 46, XX. Eventually, the patient decided as a female and underwent surgical management consisting of clitoroplasty, labioplasty, and vaginoplasty, followed by long-term corticosteroid therapy. Observations were made for three years after surgery to see the progress of the patient's condition. After undergoing glucocorticoid therapy and surgery, the patient had not experienced menstruation. Her breasts did not enlarge, and mustache and beard were still growing on her face. The patient was concerned about her condition, especially about the risk of infertility and inappropriate physical changes. The management of virilization in CAH with genital ambiguity should be seen from psychological and surgical perspectives. Understanding the disease, the goals of surgery, long-term treatment, and social adaptation help improve quality of life and reduce negative stigma.

Diagnosis and Management of Adrenal Crisis in 46XX Congenital Adrenal Hyperplasia Infant

Highlight: The diagnosis and therapy of Congenital Adrenal Hyperplasia (CAH) children with Adrenal crisis (AC) case report. Adrenal crisis (AC) is a life-threatening emergency that contributes to the high death rate of children with adrenal insufficiency. The early detection and prompt treatment can improve the outcomes of patients with CAH and AC.   Abstract: Adrenal crisis is the acute complication of the patient with congenital adrenal hyperplasia. Congenital adrenal hyperplasia (CAH) is a rare condition. Children with CAH commonly come to the emergency room due to acute complications. The condition has high mortality and thus needs early recognition. Newborn screening for CAH in Indonesia is not routinely performed and has not been suggested yet. The purpose of this case report was to report a case of adrenal crisis in a congenital adrenal hyperplasia patient focused on diagnosis and therapy. A female, 10 months old infant, was admitted to the emergency department with a chief complaint of a decrease of consciousness for 3 hours before admission and frequent vomiting since born. On physical examination, there was clitoromegaly. Laboratory showed 17-OH progesterone: 173 ng/dL (7-77 ng/dL) and karyotyping: 46 XX. Management of adrenal crisis is a stress dose of hydrocortisone and rehydration. Education is the key to optimal outcomes and normal growth and development.

45 years’ experience with early childhood anatomical technique of feminising genitoplasty for 46 XX Congenital Adrenal Hyperplasia –observations of vaginal introital anatomy and its relationship to the perineal body

In Manchester, feminising genitoplasty is offered to children with 46XX Congenital Adrenal Hyperplasia (CAH) when there is a single perineal opening and/or enlarged clitoris. Our aims are to describe the anatomical reconstructive technique and present long-term outcomes. Our hypothesis is that 'the common channel (CC) length and distance to the vagina from perineal skin is mostly due to virilisation and hypertrophy of perineal tissue over the almost normally positioned vaginal introitus (V-I) in relation to the perineal body (PB)'. METHOD AND RESULTS: This is a retrospective notes review of all consecutive 46XX CAH operations from 1976 to December 2021. 99 patients, who had feminising genitoplasty and being followed-up, were included. 15 patients who were lost to follow up were excluded. Median age at surgery was 15 months. In 91, midline division of the labia majora, spongiosum, bulbo-spongiosus muscle (BSM) and CC down to PB was performed. This was sufficient to expose the V-I at the same level or within 5mm depth of PB in 88. In 78V-I was adequate taking 10/12fr dilator (Type 1). In 10, CC resembled a male urethra and V-I was narrow (Type 2), requiring widening by 5-10mm incision at 6 o'clock position. Dartos of labia majora was attached to BSM to reduce the distance to V-I from perineal skin and the gap was lined with inner foreskin to create a vestibule. Out of 70 who were post-pubertal, 75% (53/70) had adequate calibre vaginal openings. 5 had introitoplasty and 2 had dilatation under anaesthesia. 10 needed self dilators only. 29 patients, of one of the three surgeons, had measurements of clitoris, CC, urethra and vagina. A hymen was found in 86% (25/29). There was significant strong, inverse correlation between the CC length and the urethral length (r=-0.708, p<0.001, n=27) but not between CC and vaginal lengths. After adjusting for age, the urethral length of Type 2 patients was 3.825mm shorter than those of Type 1 (p=0.017). CONCLUSION: Our data show that 'high' confluence is mostly due to virilisation of genitalia; and the anatomical technique of reversing the fusion of the urethral folds, spongiosum and bulbo-spongiosus muscle could be performed with all degrees of virilisation with success in early childhood with no need of local flaps or mobilisation of the urethro-vaginal complex. About 10% require surgery to treat narrowing of vaginal opening post puberty.

Fully Masculinized 46,XX Individuals with Congenital Adrenal Hyperplasia: Perspective Regarding Sex of Rearing and Surgery.

Current guidelines for gender assignment for all 46,XX congenital adrenal hyperplasia (CAH) continue to be female. This decision is most challenging for individuals with a 46,XX karyotype born with (CAH) having severely masculin- ized genitalia (Prader 4 or 5). They may be at significant risk for quality of life (QoL) and psychological health. More outcome information currently exists for such individuals assigned male than female. Most available data for those raised females do not indicate the extent of masculinization at birth, so there are minimal outcome data to compare with those raised males. Gender dissatisfaction among those raised females may be related to the degree of prenatal androgen excess in the brain evidenced by external genital masculinization. Also, additional brain maturation after birth, especially during puberty, is impacted by postnatal androgen excess resulting from inadequate androgen sup- pression. The purpose of this perspective is to suggest that both female and male assignment be considered. Most who have been raised male at birth have positive adult outcomes. This consideration should occur after discussions with full disclosure to the parents. The lack of more outcome data highlights the need for further information. This perspective also suggests that surgery should be deferred whether assigned female or male at least until gender identity is apparent to preserve the potential for male sexual function and prevent irrevocable loss of sensitive erotic tissue. While the gender fluidity is recognized, it is important to consider potential subsequent need for gender reassignment and extent of masculinization, particularly at the time of gender determination.

Complete corporeal preservation clitoroplasty: new insights into feminizing genitoplasty.

ABSTRACTIntroduction:46,XX Congenital adrenal hyperplasia (CAH) remains the first cause of genital virilization and current surgical techniques aim to restore female aspect of genitalia while preserving dorsal neurovascular bundle but not at the expense of not preserving erectile tissue. We aim to report our experience with a new surgical technique for clitoroplasty, completely preserving corporeal bodies, neurovascular bundles without dismembering the clitoris, in four patients with over a year follow up.Materials and Methods:After IRB approval four patients with 46,XX CAH and Prader 5 and 3 external genitalia, underwent feminizing genitoplasty. Complete preservation of erectile tissue was accomplished without a need to dissect dorsal neurovascular bundle. Glans size allowed no need for glanular reduction and there was no need to dismember the corporeal bodies.Results:Four patients 12 to 24-months-old underwent complete corporeal preservation clitoroplasty (CCPC), mean age was 18.5 months, mean follow up was 10.25 months. Vaginoplasty was performed in all patients with partial urogenital mobilization (PUM) and Urogenital Sinus flap (UF), only one severely virilized patient required a parasagittal pre-rectal approach to mobilize the vagina. We had no complications until last follow up.Conclusion:To our knowledge, we are introducing the concept of CCPC without the need of disassembling the corporeal bodies, neurovascular bundle and glans. It stands as a new alternative for feminizing genitoplasty with complete preservation of erectile tissue and no dissection of neurovascular bundle. Although there is still lacking long-term follow-up, it represents a new step in conservative reconfiguration of the external virilized female genitalia.

Surgical Practice in Girls with Congenital Adrenal Hyperplasia: An International Registry Study

In this article international trends in surgical practice in girls with congenital adrenal hyperplasia (CAH) are evaluated. All cases that had been classified in the I-CAH/I-DSD registry as 46,XX CAH and who were born prior to 2017 were identified. Centers were approached to obtain information on surgical decision making. Of the 330 included participants, 208 (63.0%) presented within the first month of life, and 326 (98.8%) cases were assigned female. Genital surgery had been performed in 250 (75.8%). A total of 64.3, 89.2, and 96.8% of cases residing in Europe, South America and Asia, respectively, had at least one surgery. In a logistic regression model for the probability of surgery before the second birthday (early surgery) over time an increase of probability for early vaginal surgery could be identified, but not for clitoral surgery or both surgeries combined. Genitoplasty in girls with CAH remains controversial. This large international study provides a snapshot of current practice and reveals geographical and temporal differences. Fewer surgeries were reported for Europe, and there seems to be a significant trend towards aiming for vaginal surgery within the first 2 years of life.

Clinical Characteristics of 46,XX Males with Congenital Adrenal Hyperplasia

Objective:To retrospectively evaluate the follow-up data in patients with 46,XX congenital adrenal hyperplasia (CAH) who were raised male.Methods:A national database was created. The data of patients were asked to be recorded in the data form.Results:The median (range) age of diagnosis was three (0.1-18.3) years in 44 patients. Twenty nine cases were diagnosed after the age of two years. Most (95.4%) cases were stage 4-5 virilized. Hysterectomy and bilateral salpingoopherectomy, at a median age of 7.25 (2.4-25.3) years, was performed in 35 cases. Testicular prostheses were placed in 11 (25%) cases at a median age of 11.2 (2.8-17) years. The median final height was 149.2 (132.8-172) cms in 38 patients, including simple virilizing (n=18), salt-wasting (n=6), and 11-beta hydroxylase (n=12). Of the 16 patients above the age of eighteen, university education was completed in 25%.Conclusion:It was seen that most (65.9%) of the 46,XX CAH cases raised male were diagnosed after two years of age. In these cases, hysterectomy and bilateral salpingoopherectomy, genital corrective surgeries and testicular prosthesis operations were performed in a very wide age rage.

Effects of Pre and Post-Natal Androgen Exposure on Psychosexual Aspects and Gender Change in Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency

Introduction: Congenital Adrenal Hyperplasia (CAH) is defined as a group of autosomal recessive disorders characterized by a deficiency of the enzyme required to synthesize cortisol by the adrenal cortex. Defects in the 21-hydroxylase enzyme make up 90% of CAH. These defects impaired cortisol synthesis leading to an ACTH increase resulting in androgen excess in both salt-wasting (SW) or simple virilizing (SV) forms. As androgens play a role in the human psychosexual development favoring male psychosexuality, this study was designed to evaluate the impact of androgen exposure on the psychosexuality of individuals with CAH due 21-hydroxylase deficiency. Methods: This retrospective cohort includes 46,XX individuals (115 female-assigned; 8 male-assigned) with a molecular diagnosis of CAH due to CYP21A2 pathogenic variants in homozygous or compounds heterozygous state. External genitalia virilization was scored using Prader scale. Phenotype, time at diagnosis, sex assignment, and gender change were assessed. The gender role at childhood was assessed through the playmates and toys profile at childhood. Gender identity was assessed by a projective psychological test (HTP). Sexual orientation was assessed by self-report sexual identity. Compliance of glucocorticoid replacement was assessed by adequate testosterone and androstenedione serum levels for age. Results: CAH was diagnosed at the neonatal time in 73% (n=78). Fifth-nine (51%) had the SW form and 49% (n=56) had the SV form. While all cases of SW were diagnosed at the neonatal time (0.12 ± 0.14 months), the mean age at diagnosis among SV was 6.03 ± 8.45 years (p=<.001). The median of Prader score was 3 in both forms. Male sex assignment was associated with more virilized external genitalia (p=.002). Gender change occurred in 6 cases (female to male), all with SV form. The prader score was higher among those who changed gender (p=.01). All of those who changed their gender had poor treatment compliance. A total of 13% (n=15) of all groups defined themselves as homosexual. There was a strong association between male toys and preference for male playmates in childhood with homosexuality and male gender identity in adulthood with both gender change from female to male and homosexuality. Conclusion: Prenatal androgen exposure favors male psychosexuality in 46,XX CAH individuals as observed by the association between highest Prader scores and all assessed psychosexual outcomes. This influence is also substantiated by post-natal androgen exposure as observed by compliance issues and late diagnosis among those who changed from female to male gender.

The associations of genital-normalizing surgery and assigned gender in predicting gender outcomes: A pooled nested case study analysis of 282 adults with differences of sex development in 58 academic articles

Purpose: The purpose was to systematically analyze the associations of childhood gender assignment and genital normalizing surgeries with adult gender in case reports of adults with differences of sex development (DSD). We did this using a pooled nested analysis of DSD adult cases reported in the academic literature. Materials and Methods: A search of academic databases uncovered 282 adult DSD cases reported in 58 academic articles that met the criteria for inclusion in the analysis. These were cases with 46, XX congenital adrenal hyperplasia, partial androgen insensitivity, mixed or partial gonadal dysgenesis, and micropenis where data about the assigned gender, childhood genital-normalizing surgery, and adult gender could be extracted. We conducted a generalized logistic mixed-model regression analysis, with multiple predictors of adult assigned gender incongruence. Results: Controlling for assigned gender, age, year of article publication, and DSD type, childhood genital surgery was not significantly associated with adult assigned gender incongruence. Cases assigned female had more than five times greater likelihood of assigned gender incongruence (95% confidence interval = 1.96–14.92). Conclusion: This study did not find evidence that childhood genital surgery is related to assigned gender incongruence; it also found that assigning a child as a female increased this possibility. These findings may inform decisions taken by clinicians and family members about the early management of DSD cases. The study was limited by publication bias in the types of cases that get published. Ethical considerations should always take precedence in decision-making regarding these surgeries.

Vocal profile of 46,XX individuals with congenital adrenal hyperplasia.

Describe the vocal profile of 46,XX congenital adrenal hyperplasia (CAH) patients followed up at the Genetics Outpatient Clinic of the Federal University Bahia (GOC-UFBA). This is a descriptive, exploratory, cross-sectional study. The study sample consisted of 28 volunteers: 14 individuals diagnosed with CAH, followed up by the multiprofessional team of the GOC-UFBA, and 14 46,XX individuals without vocal changes and endocrine and/or genetic pathologies. Voice sample collection was performed individually in a quiet environment with participants properly seated. Acoustic (PRAAT program) and auditory-perceptual (Consensus Auditory-Perceptual Evaluation of Voice - CAPE-V) analyses were conducted. In the qualitative assessment of pitch, eight (61.54%) patients in the CAH group showed low vocal pattern and eight (61.54%) individuals in the group without CAH presented high vocal pattern. There were statistically significant differences between the groups only for the following vocal attributes of the CAPE-V: overall severity (p=0.01), roughness (p=0.00), and pitch (p=0.01). No statistically significant difference was observed in the other acoustic parameters investigated (p>0.05). The present study demonstrated that 46,XX CAH individuals, even when submitted to hormone therapy, present rough, low, deviant voice.

Recommendations of patients and families of girls with 46XX congenital adrenal hyperplasia in the United Kingdom regarding the timing of surgery.

The timing of surgery for congenital adrenal hyperplasia (CAH) is contentious. We aimed to survey expert families and patients for their recommendations regarding timing of surgery for a family with a newly diagnosed CAH child. A Survey Monkey questionnaire was performed at the 2017 meeting of the CAH support group, "Living with CAH", and also sent to the members of the CAH support group. The surgical-timing responses were a Likert score from 1 (strongly disagree) to 5 (strongly agree). Data were analysed by Kruskal-Wallis test. p < 0.05 taken as significant. Of the 61 respondents, 12 were CAH patients, 43 were CAH parents, 3 were physicians, 1 surgeon and 2 others. For all respondents, the Likert score was 3 for infant, toddler and adult timing of surgery (neutral), not statistically significant (ns). For parents and/or children who had surgery (n = 26), the score was 4 (3-5) for infant vs. 4 (3-4) for toddler-years vs. 2 (1-3) for adulthood. This was statistically significant (p = 0.0002). When only patients who had CAH surgery were included, there were only 8 respondents and their scores were: infancy 3 (2-4) vs. toddler-years 4 (2-4) vs. adulthood 1 (1-4), ns. Expert families and patients in the United Kingdom who have had CAH surgery, recommend surgery in the first few years of life vs. adulthood. There is a selection bias, however this may support MDTs in continuing to discuss surgery as an option in childhood.

Early Feminizing Genitoplasty in Girls with Congenital Adrenal Hyperplasia (CAH)—Analysis of Unified Surgical Management

Aim: To analyze a single-centre experience in feminizing genitoplasty in virilized girls with congenital adrenal hyperplasia (CAH). Methods: Review of medical records of all 46, XX CAH patients undergoing single stage feminizing genitoplasty between 2003 and 2018 was performed. Results: A total of 31 girls aged from 4 months to 10 years were included in the study. The majority (n = 26/31, 84%) were operated before 2 years of age (median 8 months). External virilization was rated as Prader 3 (n = 7/31), Prader 4 (n = 21/31) and Prader 5 (n = 3/31). The urethrovaginal confluence location was low in 19 and high in 12 girls with a percentage distribution similar in Prader 4 and 5 (p > 0.05) but significantly different in Prader 3 (p = 0.017). The follow-up ranged from 12 months to 15 years. All parents assessed the cosmetic result as satisfactory. Perioperative complications occurred in two patients and included rectal injury (n = 1/31) and prolonged bleeding (n = 1/31). Three patients developed late complications including labial atheromas (n = 2/31) and vaginal stricture requiring surgical dilatation (n = 1/31). Low confluence did not decrease the risk of complications. Conclusions: Early feminizing genitoplasty in girls with congenital adrenal hyperplasia, irrespective of virilization severity, gives satisfactory cosmetic results and is characterized by low and acceptable surgical risk. Nevertheless, the most important determinant of the effectiveness of such management would be future patients’ satisfaction.

Gynecological assessment in young adults with 46,XX congenital adrenal hyperplasia

Gynecological assessment in young adults with 46,XX congenital adrenal hyperplasia

Simple Virilizing Congenital Adrenal Hyperplasia: A case Report of Sudanese 46, XY DSD male with G293D variant in CYP21A2

Congenital Adrenal Hyperplasia (CAH) is a family of inherited disorders that constitute the largest group of Disorders of Sexual Development (DSDs). The classical CAH has two types; the salt-wasting (SW-CAH) and the simple virilizing (SV-CAH). This study is a report of an SV-CAH regarding 46, XY DSD Sudanese male with early signs of puberty at the age of six years. We designed a customized panel that included 48 genes associated with Disorders of Sexual Development (DSDs) and using Next Generation Sequencing (NGS) technology, detected the pathogenic G293D alteration in the CYP21A2 gene. This variant has been reported in the salt-wasting (SW) form of 46, XX CAH.

Recurrent haematuria; a rare presentation of 46XX Congenital adrenal hyperplasia presenting late and reared as males – two cases

Congenital adrenal hyperplasia (CAH) is a group of inherited autosomal recessive disorders characterized by a defect in enzymes involved in biosynthesis of cortisol, aldosterone or both. We report two patients presented with recurrent haematuria with two different forms of CAH who presented late and reared as males. We describe the challenges posed on managing them and how the quality of life will be improved by offering hormonal and surgical remedies without changing or reassigning the gender to females.

Gender dysphoria and XX congenital adrenal hyperplasia: how frequent is it? Is male-sex rearing a good idea?

Gender dysphoria and XX congenital adrenal hyperplasia: how frequent is it? Is male-sex rearing a good idea?

Frequency of Ambiguous Genitalia in 14,177 Newborns in Turkey.

ContextLimited data are available on the exact incidence of disorders of sex development (DSD) with genital ambiguity at birth.ObjectiveTo determine frequency of ambiguous genitalia in newborns.DesignProspective multicenter study.SettingThree tertiary care hospitals.Patients or Other ParticipantsAll 14,177 babies born during the study period were included.Main Outcome MeasuresAll newborns were examined at birth; data on weeks of gestation, birth weight, and length were collected. A structured questionnaire was used for data collection. Quigley and Prader scales were used for phenotypic grading. Clinical and genetic investigations were performed.ResultsEighteen babies with ambiguous genitalia were found among 14,177 newborns (1.3/1000). Fifteen newborns had 46,XY DSD, one had 46,XX congenital adrenal hyperplasia, and one had 45,X/46,XY mixed gonadal dysgenesis. Karyotype analysis was not done in one baby who died in the neonatal period. The ratio of prematurity was higher in the DSD group (44% vs 11%; P < 0.001) and the ratio of small for gestational age was also higher in the DSD group (22% vs 5%; P = 0.007). Eight babies with DSD had mothers who had additional medical conditions, such as preeclampsia, depression, insulin resistance, and gestational diabetes mellitus.ConclusionThe frequency of ambiguous genitalia was higher than in previous studies, but, as with any experiment, the finding should be met with caution because this study was conducted in tertiary care hospitals. In addition, lower birth weight in the DSD group supports the hypothesis that early placental dysfunction might be important in the etiology of male genital anomalies.