Exploring Factors Associated with Decisions about Feminizing Genitoplasty in Differences of Sex Development.

STUDY OBJECTIVE: Infants with genital development considered atypical for assigned female sex may undergo feminizing genitoplasty (clitoroplasty and/or vaginoplasty) in early life. We sought to identify factors associated with parent/caregiver decisions regarding genitoplasty for their children with genital virilization. DESIGN: Longitudinal, observational study SETTING: Twelve pediatric centers in the United States with multidisciplinary differences/disorders of sex development clinics, 2015-2020 PARTICIPANTS: Children under 2 years old with genital appearance atypical for female sex of rearing and their parents/caregivers INTERVENTIONS/OUTCOME MEASURES: Data on the child's diagnosis and anatomic characteristics before surgery were extracted from the medical record. Parents/caregivers completed questionnaires on psychosocial distress, experience of uncertainty, cosmetic appearance of their child's genitalia, and demographic characteristics. Urologists rated cosmetic appearance. For 58 patients from the study cohort with genital virilization being raised as girls or gender-neutral, we compared these data across 3 groups based on the child's subsequent surgical intervention: (i) no surgery (n = 5), (ii) vaginoplasty without clitoroplasty (V-only) (n = 15), and (iii) vaginoplasty and clitoroplasty (V+C) (n = 38). RESULTS: Fathers' and urologists' ratings of genital appearance were more favorable in the no-surgery group than in the V-only and V+C groups. Clitorophallic length was greater in the V+C group compared with the V-only group, with substantial overlap between groups. Mothers' depressive and anxious symptoms were lower in the no-surgery group compared with the V-only and V+C groups. CONCLUSIONS: Surgical decisions were associated with fathers' and urologists' ratings of genital appearance, the child's anatomic characteristics, and mothers' depressive and anxious symptoms. Further research on surgical decision-making is needed to inform counseling practices.

Stigma, Intrusiveness, and Distress in Parents of Children with a Disorder/Difference of Sex Development.

OBJECTIVE: The impact of parent-reported stigma due to their child's disorder/difference of sex development (DSD) on parent psychosocial adjustment is poorly understood. In other pediatric populations, perceived interference of medical conditions into daily activities (i.e., illness intrusiveness ) mediates the relationship of stigma to adjustment. This study assessed relationships between parent-focused and child-focused stigma → illness intrusiveness → depressive and anxious symptoms . Exploratory analyses sought to identify patient characteristics associated with stigma. METHOD: Caregivers (59 women and 43 men) of 63 children diagnosed with a DSD up to age 4 years completed measures of demographics, parent-focused and child-focused stigma, illness intrusiveness, and depressive and anxious symptoms. RESULTS: Increased parent-focused and child-focused stigma were associated with increased illness intrusiveness, which, in turn, was associated with increased depressive and anxious symptoms for parents nested within dyads. Among children with DSD family histories, parents reported greater child-focused stigma. CONCLUSION: Parents who experience DSD-related stigma report greater interference of their child's DSD into their daily activities, which is associated with poorer psychosocial adjustment. Findings support developing clinical interventions related to parents' perceptions of stigma and illness intrusiveness to improve parent adjustment.

Distress Trajectories for Parents of Children With DSD: A Growth Mixture Model.

OBJECTIVE: This study identifies trajectories of parent depressive symptoms after having a child born with genital atypia due to a disorder/difference of sex development (DSD) or congenital adrenal hyperplasia (CAH) and across the first year postgenitoplasty (for parents who opted for surgery) or postbaseline (for parents who elected against surgery for their child). Hypotheses for four trajectory classes were guided by parent distress patterns previously identified among other medical conditions. METHODS: Participants included 70 mothers and 50 fathers of 71 children diagnosed with a DSD or CAH with reported moderate to high genital atypia. Parents were recruited from 11 US DSD specialty clinics within 2 years of the child's birth and prior to genitoplasty. A growth mixture model (GMM) was conducted to identify classes of parent depressive symptoms over time. RESULTS: The best fitting model was a five-class linear GMM with freely estimated intercept variance. The classes identified were termed "Resilient," "Recovery," "Chronic," "Escalating," and "Elevated Partial Recovery." Four classes have previously been identified for other pediatric illnesses; however, a fifth class was also identified. The majority of parents were classified in the "Resilient" class (67.6%). CONCLUSIONS: This study provides new knowledge about the trajectories of depressive symptoms for parents of children with DSD. Future studies are needed to identify developmental, medical, or familial predictors of these trajectories.

Illness Uncertainty Longitudinally Predicts Distress Among Caregivers of Children Born With DSD.

OBJECTIVE: A subset of parents of children with disorders/differences of sex development (DSD) including ambiguous genitalia experience clinically elevated levels of anxious and depressive symptoms. Research indicates that uncertainty about their child's DSD is associated with parent psychosocial distress; however, previous studies have been cross-sectional or correlational in nature. The current study is the first to examine the longitudinal trajectory of the relationship between caregiver-perceived uncertainty about their child's DSD and caregiver anxious and depressive symptoms across the first 12 months following genital surgery in young children, or if surgery was not performed, the first 12 months following study entry. METHODS: One hundred and thirteen caregivers (Mage = 32.12; 57.5% mothers; 72.6% Caucasian) of children (N = 70; Mage = 9.81 months; 65.7% female) with DSD were recruited from 12 DSD specialty clinics in the United States. Caregivers completed psychosocial measures at baseline, 6 and 12 months following genitoplasty, or study entry if parents elected not to have surgery for their child. RESULTS: Caregiver illness uncertainty and both anxious and depressive symptoms were highest at baseline and decreased over time (ps < .05). Caregiver illness uncertainty predicted symptoms of anxious and depressive symptoms across all time points (ps < .05). CONCLUSIONS: Caregivers' perceptions of uncertainty about their child's DSD are highest soon after diagnosis, and uncertainty continues to predict both anxious and depressive symptoms across time. Thus, the initial diagnostic period is a critical time for psychological assessment and intervention, with parent illness uncertainty being an important clinical target.

Post-operative complications following feminizing genitoplasty in moderate to severe genital atypia: Results from a multicenter, observational prospective cohort study.

Disorders/differences of sex development (DSD) are congenital conditions in which there is atypical chromosomal, gonadal and/or phenotypic sex. While there remains controversy around the traditionally binary concept of sex, most patients with DSD are reared either male or female depending on their genetic sex, gonadal sex, genital phenotype and status of their internal genital tract. This study uses prospective data from 12 institutions across the United States that specialize in DSD care. We focused on patients raised female. Eligible patients had moderate to severe genital atypia (defined as Prader score >2), were ≤2 years of age at entry, and had no prior genitoplasty. The aim of this study is to describe early post operative complications for young patients undergoing modern approaches to feminizing genitoplasty. Of the 91 participants in the cohort, 57 (62%) were reared female. The majority had congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (n = 52), 1 had ovo-testicular syndrome, 2 had mixed gonadal dysgenesis and 2 had partial androgen insensitivity syndrome (PAIS). Of the 50 participants who received early genitoplasty, 43 (86%) had follow-up at 6-12 months post-surgery. Thirty-two participants (64%) received a clitoroplasty, 31 (62%) partial urogenital mobilization and 4 (8%) total urogenital sinus mobilization. Eighteen percent (9/50) experienced post-surgical complications with 7 (14%) being rated as Clavien-Dindo grade III. Both parents and surgeons reported improved satisfaction with genital appearance of participants following surgery compared to baseline. This information on post-operative complications associated with contemporary approaches to feminizing genitoplasty performed in young children will help guide families when making decisions about whether or not to proceed with surgery for female patients with moderate to severe genital atypia.

Predictors of Psychosocial Distress in Parents of Young Children with Disorders of Sex Development.

PURPOSE: We evaluated demographic, financial and support predictors of distress for parents of young children with disorders of sex development including atypical genital development, and characterized early parental experiences. This work extends our previous findings to identify those parents at risk for distress. MATERIALS AND METHODS: Participants included mothers (76) and fathers (63) of a child (78) diagnosed with disorders of sex development characterized by moderate to severe genital atypia. Parents completed a demographic questionnaire, measures of anxious and depressive symptoms, quality of life, illness uncertainty and posttraumatic stress symptoms, and rated their satisfaction with the appearance of their child's genitalia. RESULTS: Depressive and posttraumatic stress symptoms of caregivers were comparable to standardized norms while levels of anxious symptoms were below norms. A subset of parents reported clinically elevated symptoms. Overall 26% of parents reported anxious symptoms, 24% reported depressive symptoms and 17% reported posttraumatic stress symptoms. Levels of illness uncertainty were lower than those of parents of children with other chronic illnesses. Differences by parent sex emerged, with mothers reporting greater distress. Lower income, increased medical care and travel expenses, and having no other children were related to increased psychosocial distress. CONCLUSIONS: Early psychosocial screening is recommended for parents of children with disorders of sex development. Clinicians should be aware that financial burden and lack of previous parenting experience are risk factors for distress.

Uncertainty and Posttraumatic Stress: Differences Between Mothers and Fathers of Infants with Disorders of Sex Development.

Parents of children with disorders of sex development (DSD) report significant psychological distress, including posttraumatic stress symptoms (PTSS), with mothers consistently reporting higher rates of psychological distress than fathers. However, psychological factors contributing to PTSS in both parents are not well understood. The present study sought to fill this gap in knowledge by examining PTSS and illness uncertainty, a known predictor of psychological distress, in parents of children recently diagnosed with DSD. Participants were 52 mothers (Mage = 32.55 years, SD = 5.08) and 41 fathers (Mage = 35.53 years, SD = 6.78) of 53 infants (Mage = 9.09 months, SD = 6.19) with DSD and associated atypical genital development. Participants were recruited as part of a larger, multisite study assessing parents' psychosocial response to their child's diagnosis of DSD. Parents completed measures of illness uncertainty and PTSS. Mothers reported significantly greater levels of PTSS, but not illness uncertainty, than fathers, and were more likely than fathers to report clinical levels of PTSS (21.2% compared to 7.3%). Hierarchical regression revealed that parent sex, undiagnosed or unclassified DSD status, and illness uncertainty were each associated with PTSS. The overall model accounted for 23.5% of the variance associated with PTSS. Interventions targeting illness uncertainty may be beneficial for parents of children with newly diagnosed DSD.

Baseline Characteristics of Infants With Atypical Genital Development: Phenotypes, Diagnoses, and Sex of Rearing.

PURPOSE: Little is known about the phenotypes, diagnoses, and sex of rearing of infants with atypical genital development in the United States. As part of a multicenter study of these infants, we have provided a baseline report from US difference/disorder of sex development clinics describing the diagnoses, anatomic features, and sex of rearing. We also determined whether consensus guidelines are followed for sex designation in the United States. METHODS: Eligible participants had moderate-to-severe genital atypia, were aged <3 years, and had not undergone previous genitoplasty. Karyotype, genetic diagnosis, difference/disorder of sex development etiology, family history, and sex of rearing were collected. Standardized examinations were performed. RESULTS: Of 92 subjects, the karyotypes were 46,XX for 57%, 46,XY for 34%, and sex chromosome abnormality for 9%. The median age at the baseline evaluation was 8.8 months. Most 46,XX subjects (91%) had congenital adrenal hyperplasia (CAH) and most 46,XY subjects (65%) did not have a known diagnosis. Two individuals with CAH underwent a change in sex of rearing from male to female within 2 weeks of birth. The presence of a uterus and shorter phallic length were associated with female sex of rearing. The most common karyotype and diagnosis was 46,XX with CAH, followed by 46,XY with an unknown diagnosis. Phenotypically, atypical genitalia have been most commonly characterized by abnormal labioscrotal tissue, phallic length, and urethral meatus location. CONCLUSIONS: An increased phallic length was positively associated with rearing male. Among the US centers studied, sex designation followed the Consensus Statement recommendations. Further study is needed to determine whether this results in patient satisfaction.

Parent-Rated Severity of Illness and Anxiety among Caregivers of Children Born with a Disorder of Sex Development Including Ambiguous Genitalia.

BACKGROUND/AIMS: Parents of children born with disorders of sex development (DSD) often experience anxiety, but risk factors, including parental perception of the severity of their child's DSD, have not been examined. We hypothesized that severity of illness (SOI) ratings would relate to parental anxiety, and would be higher for parents of children with a potentially life-threatening DSD (e.g., 21-hydroxylase deficiency). METHODS: Eighty-nine parents (Mage = 33.0, 56.2% mothers) of 51 children (Mage in months = 8.7) with a DSD including ambiguous genitalia were recruited from 12 specialized DSD clinics. Parents completed questionnaires prior to genitoplasty, 6 months post-genitoplasty, and 12 months post-genitoplasty (if completed). Data were analyzed with linear mixed modeling. RESULTS: Parental anxiety decreased over time, χ2(1) = 10.14, p < 0.01. A positive relationship between SOI and anxiety was found, with SOI being a strong predictor of anxiety (b = 0.53, p < 0.01; χ2[1] = 5.33, p < 0.05). An SOI by time interaction indicated SOI had an increasing effect on anxiety over time, b = 0.06, p < 0.05; χ2(1) = 6.30, p < 0.05. There was no diagnosis by SOI interaction. CONCLUSION: Parental anxiety decreased over time, but those with higher SOI ratings reported greater initial anxiety followed by slower resolution over time. Underlying etiology of DSD had no effect on the relationship between SOI and anxiety.

Psychological Adjustment of Parents of Children Born with Atypical Genitalia 1 Year after Genitoplasty.

PURPOSE: We examined the psychological adjustment of parents of children born with moderate to severe genital atypia 12 months after their child underwent genitoplasty. MATERIALS AND METHODS: Parents were recruited longitudinally from a multicenter collaboration of 10 pediatric hospitals with specialty care for children with disorders/differences of sex development and/or congenital adrenal hyperplasia. Parents completed measures of depressive and anxious symptoms, illness uncertainty, quality of life, posttraumatic stress and decisional regret. RESULTS: Compared to levels of distress at baseline (before genitoplasty) and 6 months after genitoplasty, data from 25 mothers and 20 fathers indicated significant improvements in all psychological distress variables. However, a subset of parents continued endorsing clinically relevant distress. Some level of decisional regret was endorsed by 28% of parents, although the specific decision that caused regret was not specified. CONCLUSIONS: Overall the majority of parents were coping well 1 year after their child underwent genitoplasty. Level of decisional regret was related to having a bachelor's level of education, increased levels of illness uncertainty preoperatively and persistent illness uncertainty at 12 months after genitoplasty but was unrelated to postoperative complications.

Changes in levels of parental distress after their child with atypical genitalia undergoes genitoplasty.

BACKGROUND: The birth of a child with a disorder of sex development (DSD) and atypical genitalia can be traumatizing and isolating for families. Parents of children with DSD are at risk for increased levels of psychological distress, including depression, anxiety, illness uncertainty (IU), post-traumatic stress symptoms (PTSS), and impairments in quality of life (QOL). Our previous report indicated that although the majority of parents of children with atypical genitalia were coping well prior to the child's genitoplasty, approximately 25% of them reported experiencing some type of psychological distress. OBJECTIVE: The current study sought to examine the trajectory of parental psychological distress prior to, and 6 months after their child underwent genitoplasty. METHODS: Parents were recruited as part of an ongoing, prospective, multi-site study involving 10 pediatric hospitals with specialized care for children with atypical genitalia. Results from 49 parents (27 mothers, 22 fathers) of 28 children (17 female sex of rearing, 11 male sex of rearing) born with atypical genitalia (Prader rating of 3-5 in 46,XX DSD or by a Quigley rating of 3-6 in 46,XY DSD or 45,XO/46,XY) were included in the study. RESULTS: There were no significant changes in level of depressive or anxious symptoms or quality of life between baseline and 6-month post-operative follow-up, although mothers continued to report significantly higher levels of depressive symptoms than fathers, and as a group, these parents reported lower QOL than published norms. The level of PTSS significantly decreased for all parents, suggesting that parents may have come through the acute stress phase associated with their child's diagnosis. Finally, while there were no significant changes in IU over the time period, the level of IU for parents of boys actually increased, while parents of girls reported no change (Figure). CONCLUSION: Six months after their child has undergone genitoplasty, the majority of parents report minimal levels of psychological distress. However, a subset of these parents continue to experience significant distress related to their child's diagnosis. Specifically, parents of boys appear to be at increased risk for difficulties, which may be related to either the lack of clinical diagnosis for almost half of these children or the necessity of two-stage surgeries for the majority of them. We will continue collecting data on these families to better understand the trajectory of these adjustment variables.

Characterizing Early Psychosocial Functioning of Parents of Children with Moderate to Severe Genital Ambiguity due to Disorders of Sex Development.

PURPOSE: We examined the psychosocial characteristics of parents of children with disorders of sex development at early presentation to a disorders of sex development clinic. Parental anxiety, depression, quality of life, illness uncertainty and posttraumatic stress symptoms were assessed. Additionally we evaluated the relationship of assigned child gender to parental outcomes. MATERIALS AND METHODS: A total of 51 parents of children with ambiguous or atypical genitalia were recruited from 7 centers specializing in treatment of disorders of sex development. At initial assessment no child had undergone genitoplasty. Parents completed the Cosmetic Appearance Rating Scale, Beck Anxiety Inventory, Beck Depression Inventory, SF-36, Parent Perception of Uncertainty Scale and Impact of Event Scale-Revised. RESULTS: A large percentage of parents (54.5%) were dissatisfied with the genital appearance of their child, and a small but significant percentage reported symptoms of anxiety, depression, diminished quality of life, uncertainty and posttraumatic stress. Few gender differences emerged. CONCLUSIONS: Although many parents function well, a subset experience significant psychological distress around the time of diagnosis of a disorder of sex development in their child. Early screening to assess the need for psychosocial interventions is warranted.