Laboratory Findings After Urinary Tract Infection and Antimicrobial Prophylaxis in Children With Vesicoureteral Reflux.

It is a common practice to monitor blood tests in patients receiving long-term trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis for recurrent urinary tract infections. This multicenter, randomized, placebo-controlled trial enrolled 607 children aged 2 to 71 months with vesicoureteral reflux diagnosed after symptomatic urinary tract infection. Study participants received TMP-SMZ (n = 302) or placebo (n = 305) and were followed for 2 years. Serum electrolytes (n ≥ 370), creatinine (n = 310), and complete blood counts (n ≥ 206) were measured at study entry and at the 24-month study conclusion. We found no significant electrolyte, renal, or hematologic abnormalities when comparing the treatment and placebo groups. We observed changes in several laboratory parameters in both treatment and placebo groups as would normally be expected with physiologic maturation. Changes were within the normal range for age. Long-term use of TMP-SMX had no treatment effect on complete blood count, serum electrolytes, or creatinine. Our findings do not support routine monitoring of these laboratory tests in children receiving long-term TMP-SMZ prophylaxis.

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.

Cost-Utility of Antimicrobial Prophylaxis for Treatment of Children With Vesicoureteral Reflux.

Objective: Antimicrobial prophylaxis for children with vesicoureteral reflux (VUR) reduces recurrences of urinary tract infection (UTI) but requires daily antimicrobials for extended periods. We used a cost-utility model to evaluate whether the benefits of antimicrobial prophylaxis outweigh its risks and, if so, to investigate whether the benefits and risks vary according to grade of VUR. Methods: We compared the cost per quality-adjusted life-year (QALY) gained in four treatment strategies in children aged <6 years diagnosed with VUR after a first UTI, considering these treatment strategies: (1) prophylaxis for all children with VUR, (2) prophylaxis for children with Grade III or Grade IV VUR, (3) prophylaxis for children with Grade IV VUR, and (4) no prophylaxis. Costs and effectiveness were estimated over the patient's lifetime. We used $100,000/QALY gained as the threshold for considering a treatment strategy cost effective. Results: Based on current data and plausible ranges to account for data uncertainty, prophylaxis of children with Grades IV VUR costs $37,903 per QALY gained. Treating children with Grade III and IV VUR costs an additional $302,024 per QALY gained. Treating children with all grades of VUR costs an additional $339,740 per QALY gained. Conclusions: Treating children with Grades I, II, and III VUR with long-term antimicrobial prophylaxis costs substantially more than interventions typically considered economically reasonable. Prophylaxis in children with Grade IV VUR is cost effective.

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.

Cryptorchidism: experience and reason.

INTRODUCTION: To characterize our contemporary clinical experience with cryptorchidism. MATERIALS AND METHODS: The records of boys referred for cryptorchidism were reviewed from 2001 to 2011. Data regarding the incidence of retractile testes, testicular ascent, surgical approach and outcomes were tabulated. Follow up was both early (< 12 weeks) and late (> 12 weeks). RESULTS: A total of 1885 patients, or 2593 testes, were identified. Eight hundred and forty-one children (45%) or 1204 testes (46%) were retractile on initial exam-57% bilateral; 187 testes (7%) later 'ascended' on re-examination and underwent surgery--15% bilateral; 1340 (85%) testes were palpable in the inguinal canal and underwent inguinal orchidopexy--98% were successful; 69 (4%) of initially palpable testes were found to be atrophic and removed; 167 (11%) testes were non-palpable and underwent laparoscopy-46 were atrophic and removed; 31 were vanishing; 33 were brought down using an inguinal approach at the same sitting with 97% success; 47 underwent staged Fowler-Stephens orchidopexy (FSO) and 10 underwent non-staged FSO, with 82% and 78% success respectively. All second stages were performed open. CONCLUSIONS: Almost half of children referred for cryptorchidism had retractile testes. Surgery for later ascent was required in 16% of testes judged to be retractile at a median age of 8 years, emphasizing the need for repeat examination. High success rates with inguinal orchidopexy were achieved, even in non-palpable testes. Testes requiring FSO were uncommonly encountered-approximately 5 testes/year or 4% of testes undergoing surgery-and success was achieved in approximately 80%.

Interobserver variability for interpretation of DMSA scans in the RIVUR trial.

INTRODUCTION: Technetium-99m dimercaptosuccinic acid (DMSA) renal scans are used in the diagnosis of renal scarring. In the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial that randomized 607 children, DMSA renal scans were used for evaluating the presence and the severity of renal scarring. OBJECTIVE: The aim was to determine interobserver variability in reporting of DMSA renal scans in the RIVUR trial. STUDY DESIGN: We compared DMSA renal scan reports for renal scarring and acute pyelonephritis from all non-reference local radiologists (ALRs) at study sites with adjudicated as well as non-adjudicated reports from two reference radiologists (RRs) of the RIVUR trial. Two-way comparisons of concordant and discrepant responses were analyzed using an unweighted kappa statistic between the ALR and the adjudicated RR interpretations. All analyses were performed using SAS v 9.4 (SAS institute 2015) and significance was determined at the 0.05 level. RESULTS: Of the 2872 kidneys evaluated, adjudicated RR reports had 119 (4%) kidneys with renal scarring compared with 212 (7%) by the ALRs. For 79% kidneys the grading for scarring reported by ALRs was either upgraded (24%) or downgraded (55%) by RRs. For acute pyelonephritis (n = 2924), adjudicated RR reports had 85 (3%) kidneys with pyelonephritis compared with 151 (5%) by the ALRs. For 85% kidneys, the grading for pyelonephritis reported by the ALRs was either upgraded (28%) or downgraded (57%) by the RRs. A three-way comparison revealed that all three (RR1, RR2, and ALR) agreed over presence of renal scarring in 19% cases and two of the three agreed in 80% cases. The respective numbers for pyelonephritis were 13% and 84%. The agreement rate for all DMSA scan reports between the RRs and the ALRs was 93%. DISCUSSION: The study revealed significant interobserver variability in the reporting of abnormal DMSA renal scans compared with the previously published studies. A noteworthy limitation was a lack of uniformity in local reporting of the scans. CONCLUSIONS: Our study highlights the need for optimizing the clinical yield of DMSA renal scans by more specific guidelines, particularly for standardized and uniform interpretation.

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.

Variation in the level of detail in pediatric voiding cystourethrogram reports.

INTRODUCTION: Voiding cystourethrogram (VCUG) provides a wealth of data on urinary tract function and anatomy, but few standards exist for reporting VCUG findings. OBJECTIVE: We aimed to assess variability in VCUG reports and to test our hypothesis that VCUG reports from pediatric facilities and pediatric radiologists are more complete than those performed at other facilities or by non-pediatric radiologists. STUDY DESIGN: We analyzed original VCUG reports from children enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial. A 23-item checklist was created and used to evaluate reporting of technical (e.g. catheter size), anatomic (e.g. vesicoureteral reflux (VUR) presence and grade, bladder shape), and functional information (e.g. bladder emptying). Radiologists were classified as pediatric or non-pediatric radiologists. Facilities were categorized as to whether they were a free-standing pediatric hospital (FSPH), a pediatric "hospital within a hospital" (PHWH), a non-pediatric hospital (NPH), or an outpatient radiology facility (ORF). Multivariate linear regression was used to analyze factors associated with the completeness of the VCUG reports (percent of items reported from the 23-item checklist). RESULTS: Six-hundred and two VCUGs were performed at 90 institutions. Of those, 76% were read by a pediatric radiologist, and 49% were performed at a FSPH (Table). On average, less than half of the 23 items in our standardized assessment tool were included in VCUG reports (mean 48%, SD 12). The completeness of reports varied by facility type: 51% complete at FSPH (SD 11), 50% at PHWH (SD 10), 36% at NPH (SD 11), and 43% at ORF (SD 8) (p < 0.0001). In multivariate analysis, VCUG reports generated at NPH or ORF had 8% fewer items included (95% CI 3.0-12.8, p < 0.01), and those generated at PHWH did not differ from those generated at FSPH. Reports read by a non-pediatric radiologist had 6% fewer items included (95% CI 3-9.7; p < 0.01) compared with those read by a pediatric radiologist. DISCUSSION: There is substantial underreporting of findings in VCUG reports when assessing a widely represented sample of routine, community-generated reports using an idealized standard. Although VUR was often reported, other crucial anatomic and functional findings of the VCUG were consistently underreported across all facility types. CONCLUSION: Although pediatric radiologist and pediatric hospitals generated more complete VCUG reports compared with those having non-pediatric origins, the differences are small when considering the substantial underreporting of VCUG findings in general. This underscores the opportunities for improvement in reporting of VCUG findings.

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.

Reliability of grading of vesicoureteral reflux and other findings on voiding cystourethrography.

INTRODUCTION: Voiding cystourethrography (VCUG) is the modality of choice to diagnose vesicoureteral reflux (VUR). Although grading of VUR is essential for prognosis and clinical decision-making, the inter-observer reliability for grading has been shown to vary substantially. The Randomized Intervention for Children with VesicoUreteral Reflux (RIVUR) trial provides a large cohort of children with VUR to better understand the reliability of VCUG findings. OBJECTIVE: To determine the inter-observer consistency of the grade of VUR and other VCUG findings in a large cohort of children with VUR. STUDY DESIGN: The RIVUR trial is a randomized controlled trial of antimicrobial prophylaxis in children with VUR diagnosed after UTI. Each enrollment VCUG was read by a local clinical (i.e. non-reference) radiologist, and independently by two blinded RIVUR reference radiologists. Reference radiologists' disagreements were adjudicated for trial purposes. The grade of VUR and other VCUG findings were extracted from the local clinical radiologist's report. The unit of analysis included individual ureters and individual participants. We compared the three interpretations for grading of VUR and other VCUG findings to determine the inter-observer reliability. RESULTS: Six-hundred and two non-reference radiology reports from 90 institutions were reviewed and yielded the grade of VUR for 560 left and 524 right ureters. All three radiologists agreed on VUR grade in only 59% of ureters; two of three agreed on 39% of ureters; and all three disagreed on 2% of ureters (Table). Agreement was better (≥92%) for other VCUG findings (e.g. bladder shape "normal"). The non-reference radiologists' grade of VUR differed from the reference radiologists' adjudicated grade by exactly one grade level in 19% of ureters, and by two or more grade levels in 2.2% of ureters. When the participant was the unit of analysis, all three radiologists agreed on the grade of VUR in both ureters in just 43% of cases. DISCUSSION: Our study shows considerable and clinically relevant variability in grading VUR by VCUG. This variability was consistent when comparing non-reference to the adjudicated reference radiologists' assessment and the reference radiologists to each other. This study was limited to children with a history of UTI and grade I-IV VUR and may not be generalizable to all children who have a VCUG. CONCLUSION: The considerable inter-observer variability in VUR grading has both research and clinical implications, as study design, risk stratification, and clinical decision-making rely heavily on grades of VUR.

Establishing a standard protocol for the voiding cystourethrography.

The voiding cystourethrogram (VCUG) is a frequently performed test to diagnose a variety of urologic conditions, such as vesicoureteral reflux (VUR). The test results determine whether continued observation or an interventional procedure is indicated. VCUGs are ordered by many specialists and primary care providers, including pediatricians, family practitioners, nephrologists, hospitalists, emergency room physicians, and urologists. Current protocols for performing and interpreting a VCUG are based on the International Reflux Study in 1985. However, more recent information provided by many national and international institutions suggests a need to refine those recommendations. The lead author of the 1985 study, R.L. Lebowitz, agreed to and participated in the current protocol. In addition, a recent survey directed to the chairpersons of pediatric radiology of 65 children's hospitals throughout the United States and Canada showed that VCUG protocols vary substantially. Recent guidelines from the American Academy of Pediatrics (AAP) recommend a VCUG for children between 2 and 24 months of age with urinary tract infections but did not specify how this test should be performed. To improve patient safety and to standardize the data obtained when a VCUG is performed, the AAP Section on Radiology and the AAP Section on Urology initiated the current VCUG protocol to create a consensus on how to perform this test.