Adverse Birth Experiences and Parent Adjustment Associated With Atypical Genital Appearance Due to Differences of Sex Development.

OBJECTIVE: Differences/disorders of sex development (DSDs) are rare, congenital conditions involving discordance between chromosomes, gonads, and phenotypic sex and are often diagnosed in infancy. A key subset of parents of children newly diagnosed with a DSD experience clinically elevated distress. The present study examines the relationship between perinatal factors (i.e., gestational age, delivery method) and trajectories of parental adjustment. METHODS: Parent participants (mothers = 37; fathers = 27) completed measures at baseline, 6- and 12-month follow-up. Multilevel linear regression controlled for clustering of the data at three levels (i.e., time point, parent, and family) and examined the relationship between perinatal factors and trajectories of depressive and anxious symptoms. Two-way interactions between perinatal factors and parent type were evaluated. RESULTS: Overall depressive and anxious symptoms decreased over time. There were significant interactions between gestational age and parent type for depressive and anxious symptoms, with younger gestational age having a stronger negative effect on mothers vs. fathers. There was a significant interaction between time and gestational age for depressive symptoms, with 36 weeks' gestational age demonstrating a higher overall trajectory of depressive symptoms across time compared to 38 and 40 weeks. Findings for the delivery method were not significant. CONCLUSIONS: Findings uniquely demonstrated younger gestational age was associated with increased depressive symptoms, particularly for mothers compared to fathers. Thus, a more premature birth may predispose parents of infants with DSD to distress. Psychosocial providers should contextualize early diagnosis-related discussions within stressful birth experiences when providing support.

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.

Survey of COVID-19 impact on pediatric urology services.

INTRODUCTION: To better understand how the COVID-19 pandemic has forced rapid operational changes in the global healthcare industry, changes implemented on an individual, institutional basis must be considered. There currently is not adequate literature about the overall impact COVID-19 has had on pediatric urology services worldwide. We believe that they have dramatically decreased during the COVID-19 crisis, but have adapted to accommodate changes. We hypothesize that patient care was widely variant due to inadequate standardized recommendations or crisis planning. MATERIALS AND METHODS: A web-based survey was deployed to 377 pediatric urologists globally via email to analyze COVID-19's impact on various types of pediatric urology practices. Key categories included impacts on elective services, telemedicine use, finances, and recovery operations. A total of 114 responses were collected between April 29th - May 22nd, 2020. RESULTS: The widespread cancellation of elective surgical procedures caused significant disturbances in the field. There was a uniform, significant increase (75%) in telemedicine use across practices. The pandemic has created many changes in care provision for physicians, institutions, and patients themselves. Furthermore, the sudden economic burden on healthcare facilities could lead to cost-cutting measures, creating further strain within institutions. Though telemedicine has its limitations, it is a very viable option when traditional services are unavailable. CONCLUSIONS: Immediate steps should be taken to ensure that the recovery phases of pediatric urology practices are as efficient as possible. Institutions should develop task forces to develop critical workflow processes in the event of health crises, while still maintaining patient-centered care. This will be essential in maximizing appropriate care allocation.

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.

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.

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.

Marked increase in urinary excretion of apolipoproteins in children with nephrolithiasis associated with hypercalciuria.

BACKGROUND: Using a proteomic approach, we aimed to identify and compare the urinary excretion of proteins involved in lipid transport and metabolism in children with kidney stones and hypercalciuria (CAL), hypocitraturia (CIT), and normal metabolic work-up (NM), and in healthy controls (HCs). Additionally, we aimed to confirm these results using ELISA, and to examine the relationship between the urinary excretion of selected proteins with demographic, dietary, blood, and urinary parameters. METHODS: Prospective, controlled, pilot study of pooled urine from CAL, CIT, and NM versus age- and gender-matched HCs, using liquid chromatography-mass spectrometry. Relative protein abundance was estimated using spectral counting. Results were confirmed by ELISA performed on individual samples. RESULTS: Of the 1,813 proteins identified, 230 met the above criteria. Of those, 5 proteins (apolipoprotein A-II [APOA2]; apolipoprotein A-IV [APOA4]; apolipoprotein C-III [APOA3]; fatty acid-binding protein, liver [FABPL]; fatty acid-binding protein, adipocyte [FABP4]) involved in lipid metabolism and transport were found in the CAL group, with significant differences compared with HCs. ELISA analysis indicated statistically significant differences in the urinary excretion of APOC3, APOA4, and FABPL in the CAL group compared with HCs. Twenty-four-hour urinary calcium excretion correlated significantly with concentrations of ApoC3 (r = 0.77, p < 0.001), and FABPL (r = 0.80, p = 0.005). CONCLUSIONS: We provide proteomic data showing increased urinary excretion of lipid metabolism/transport-related proteins in children with kidney stones and hypercalciuria. These findings suggest that abnormalities in lipid metabolism might play a role in kidney stone formation.

Evidence of Need to Use Self-Report Measures of Psychosocial Functioning in Older Children and Adolescents with Voiding Dysfunction.

PURPOSE: Previous reports have revealed significantly higher rates of psychosocial difficulties in children and adolescents with voiding dysfunction compared to their healthy peers. However, these findings are based solely on parental reporting and do not include self-reporting of psychosocial problems in older pediatric patients. MATERIALS AND METHODS: We collected data from 200 consecutive patients 11 to 16 years old during outpatient clinic visits. Patients completed the Pediatric Symptom Checklist-Youth Report, parents completed the parental report of the same measure, and patients and parents collaboratively completed the Dysfunctional Voiding Scoring System. RESULTS: Of the patients 25.5% met the cutoff score for clinically significant levels of psychosocial difficulties. However, only a fourth of those patients met the cutoff on the parent and self-report measures. Additionally patient self-reports of internalizing and externalizing problems were significantly related to severity of voiding dysfunction. CONCLUSIONS: Screening for psychosocial problems in older children and adolescents with voiding dysfunction should include reports from the parent and the child. In our sample 37.3% of patients needing a mental health followup would have been missed if only 1 version of the measure had been administered.

Treatment patterns, testicular loss and disparities in inpatient surgical management of testicular torsion in boys: a population-based study 1998-2010.

OBJECTIVES: To examine temporal trends in inpatient testicular torsion (TT) treatment and testicular loss (TL), and to identify risk factors for TL using a large nationally representative paediatric cohort, stratified to established high prevalence TT cohorts (neonatal TT [NTT]; age <1 years) and adolescent TT (ATT; age 12-17 years). METHODS: Boys (age ≤17 years, n = 17 478) undergoing surgical exploration for TT were identified within the Nationwide Inpatient Sample (1998-2010). Temporal trends in inpatient TT management (salvage surgery vs orchiectomy) and TL were examined using estimated annual percent change methodology. Multivariable logistic regression models were used to identify risk factors for TL. RESULTS: Teaching hospitals treated 90% of boys with NTT, compared with 55% with ATT (P < 0.001). Of boys with NTT, 85% lost their testis, compared with 35% with ATT (P < 0.001). Inpatient management of NTT declined during the study period, from 7.5/100 000 children in 1998 to 3/100 000 in 2010 (estimated annual percent change -4.95%; P < 0.001). The decrease was similar but less dramatic in ATT. TL patterns did not improve. In adjusted analyses, for NTT, orchiectomy was more likely at teaching hospitals. For ATT, orchiectomy was more likely in children with comorbidities (odds ratio 5.42; P = 0.045), Medicaid coverage or self-pay (P < 0.05) and weekday presentation (P = 0.001). Regional or racial disposition was not associated with TL. CONCLUSIONS: There has been a gradual decrease in inpatient surgical treatment for both NTT and ATT, presumably as a result of increased outpatient and/or non-operative management of these children. Concerningly, TL patterns have not improved; targeted interventions such as parental and adolescent male health education may lead to timely recognition/intervention in children at-risk for ATT. We noted no regional/racial disparities in contrast to earlier studies.

National practice patterns and outcomes of pediatric nephrectomy: comparison between urology and general surgery.

PURPOSE: In adults nephrectomy is under the purview of urologists, but pediatric urologists and pediatric general surgeons perform extirpative renal surgery in children. We compared the contemporary performance and outcome of all-cause nephrectomy at pediatric hospitals as performed by pediatric urologists and pediatric general surgeons. MATERIALS AND METHODS: We queried the Pediatric Health Information System to identify patients 0 to 18 years old who were treated with nephrectomy between 2004 and 2013 by pediatric urologists and pediatric general surgeons. Data points included age, gender, severity level, mortality risk, complications and length of stay. Patients were compared by APR DRG codes 442 (kidney and urinary tract procedures for malignancy) and 443 (kidney and urinary tract procedures for nonmalignancy). RESULTS: Pediatric urologists performed more all-cause nephrectomies. While pediatric urologists were more likely to operate on patients with benign renal disease, pediatric general surgeons were more likely to operate on children with malignancy. Patients on whom pediatric general surgeons operated had a higher average severity level and were at greater risk for mortality. After controlling for differences patients without malignancy operated on by pediatric urologists had a shorter length of stay, and fewer medical and surgical complications. There was no difference in length of stay, or medical or surgical complications in patients with malignancy. CONCLUSIONS: Overall compared to pediatric general surgeons more nephrectomies are performed by pediatric urologists. Short-term outcomes, including length of stay and complication rates, appear better in this data set in patients without malignancy who undergo nephrectomy by pediatric urologists but there is no difference in outcomes when nephrectomy is performed for malignancy.

Why does adenotonsillectomy not correct enuresis in all children with sleep disordered breathing?

PURPOSE: We analyzed the outcome of nocturnal enuresis after adenotonsillectomy in children with sleep disordered breathing. We also evaluated differences in demographic, clinical, laboratory and polysomnography parameters between responders and nonresponders after adenotonsillectomy. MATERIALS AND METHODS: We prospectively evaluated children 5 to 18 years old diagnosed with sleep disordered breathing (snoring or obstructive sleep apnea syndrome) on polysomnography and monosymptomatic primary nocturnal enuresis requiring adenotonsillectomy to release upper airway obstruction. Plasma antidiuretic hormone and brain natriuretic peptide were measured preoperatively and 1 month postoperatively. RESULTS: Sleep studies were done in 46 children and 32 also underwent blood testing preoperatively and postoperatively. Mean ± SD patient age was 8.79 ± 2.41 years and the mean number of wet nights weekly was 6.39 ± 1.26. Polysomnography revealed obstructive sleep apnea syndrome in 71.7% of patients and snoring in 28.3%. After adenotonsillectomy 43.5% of patients became dry. Preoperative polysomnography findings indicated that responders, who were dry, had significantly more arousals and obstructive apnea episodes but fewer awakenings than nonresponders, who were wet. Significant increases in plasma antidiuretic hormone and significant decreases in plasma brain natriuretic peptide were seen in all children with no difference between responders and nonresponders. No difference between the groups was noted in age, gender, race, body mass index, constipation, preoperative number of wet nights weekly or type of sleep disordered breathing. CONCLUSIONS: Nocturnal enuresis resolved after adenotonsillectomy in almost half of the children with sleep disordered breathing. Those who became dry had more frequent arousal episodes caused by apnea events than those who remained wet.

Classic bladder exstrophy: Frequent 22q11.21 duplications and definition of a 414 kb phenocritical region.

BACKGROUND: Classic bladder exstrophy (CBE) is the most common form of the bladder exstrophy and epispadias complex. Previously, we and others have identified four patients with a duplication of 22q11.21 among a total of 96 unrelated CBE patients. METHODS: Here, we investigated whether this chromosomal aberration was commonly associated with CBE/bladder exstrophy and epispadias complex in an extended case-control sample. Multiplex ligation-dependent probe amplification and microarray-based analysis were used to identify 22q11.21 duplications in 244 unrelated bladder exstrophy and epispadias complex patients (including 217 CBE patients) and 665 healthy controls. RESULTS: New duplications of variable size were identified in four CBE patients and one control. Pooling of our previous and present data (eight duplications in 313 CBE patients) yielded a combined odds ratio of 31.86 (95% confidence interval, 4.24-1407.97). Array-based sequence capture and high-throughput targeted re-sequencing established that all breakpoints resided within the low-copy repeats 22A to 22D. Comparison of the eight duplications revealed a 414 kb phenocritical region harboring 12 validated RefSeq genes. Characterization of these 12 candidate genes through whole-mount in situ hybridization of mouse embryos at embryonic day 9.5 suggested that CRKL, THAP7, and LZTR1 are CBE candidate genes. CONCLUSION: Our data suggest that duplication of 22q11.21 increases CBE risk and implicate a phenocritical region in disease formation.

Renal bladder ultrasound evaluation in monosymptomatic primary nocturnal enuresis: is it really necessary?

BACKGROUND: Published guidelines regarding radiographic imaging in the evaluation of monosymptomatic primary nocturnal enuresis (MPNE) are not followed. We aimed to evaluate the prevalence of urological abnormalities on renal/bladder ultrasound (RBUS) in children with MPNE and to compare the RBUS findings in children with and without MPNE. METHODS: Retrospective data collection in all children aged 5-17 years seen for the initial evaluation of MPNE. Control group consisted of age- and sex-matched children who had abdominal ultrasound for other than bladder-/kidney-related causes. RBUS findings were analyzed with regard to the need for intervention and/or follow-up. RESULTS: While abnormalities on RBUS were seen in 12.54% of enuretic children and in 5.38% of controls (p = 0.004), the majority of these findings were clinically insignificant. Of those with abnormalities, only 4 enuretic children (1.43%) required intervention and 8 (2.87%) needed follow-up studies. These rates were not significantly different from the controls. However, enuretic children with RBUS abnormalities appear to be more resistant to treatment than enuretic children with normal RBUS (p = 0.002). CONCLUSIONS: A small proportion of abnormalities seen on RBUS in children with MPNE require intervention and/or further evaluation. The identification of insignificant RBUS findings could lead to unnecessary additional investigations owing to parental concern. Detailed history and a voiding diary may be sufficient in the initial evaluation of children with MPNE, although RBUS may play an important role in patients who are resistant to treatment.

Factor analysis of the pediatric symptom checklist in a population of children with voiding dysfunction and/or nocturnal enuresis.

The research objective was to identify the factor structure of the pediatric symptom checklist (PSC) in children with voiding dysfunction and/or nocturnal enuresis who were seen in a pediatric urology clinic. Retrospective chart reviews were conducted for 498 consecutive patients, ages 6-16, who were seen over a 13-month period. The PSC, a 35-item measure used to screen for psychosocial difficulties, was completed by the patient's caregiver. Confirmatory factor analyses using three previous models were conducted. A four factor model comprised of internalizing, externalizing, attention problems, and chronic illness factors represented the best fit to the data. Within this population, the PSC appears to capture internalizing and externalizing problems, difficulties with attention, and possible side effects of a medical condition. This information could aid clinicians in assessing adjustment difficulties within this population and concurrently allow researchers to examine whether these specific factors are related to other relevant outcomes.

Lower health related quality of life and psychosocial difficulties in children with monosymptomatic nocturnal enuresis--is snoring a marker of severity?

PURPOSE: Sleep disordered breathing in children is linked to numerous negative psychosocial consequences, including lower health related quality of life, increased behavioral problems and impaired neuropsychological functioning. We examined whether snoring, which is the least severe form of sleep disordered breathing, or health related quality of life could account for the increased rate of psychosocial difficulty in children with monosymptomatic nocturnal enuresis. MATERIALS AND METHODS: Patients diagnosed with monosymptomatic nocturnal enuresis seen at an outpatient pediatric urology clinic completed measures of health related quality of life (Obstructive Sleep Apnea Syndrome-18-Item Questionnaire), sleep disordered breathing (Pediatric Sleep Questionnaire) and psychosocial difficulty (Pediatric Symptom Checklist). Patients were categorized into 2 groups (snoring vs no snoring) based on the Pediatric Symptom Checklist snoring subscale score. RESULTS: Included in the study were 62 males and 45 females with a mean ± SD age of 9.09 ± 2.58 years and a mean body mass index of 21.00 ± 6.93 kg/m(2) (range 13 to 49). The sample was evenly split between 56 snorers (52.3%) and 51 nonsnorers (47.7%). Compared to children with monosymptomatic nocturnal enuresis who did not snore, MANCOVA results revealed that patients with monosymptomatic nocturnal enuresis who snored had significantly more externalizing problems and total psychosocial problems, in addition to significantly more impairment in all areas of health related quality of life. CONCLUSIONS: Snoring in children with monosymptomatic nocturnal enuresis puts them at increased risk for behavioral and psychosocial problems, in addition to impaired health related quality of life. These findings support the need for future studies of the neurological links between sleep disordered breathing and monosymptomatic nocturnal enuresis.

Bladder and bowel dysfunction: evidence for multidisciplinary care.

PURPOSE: We examined the symptoms of bladder-bowel dysfunction (ie severity of voiding dysfunction and stool consistency) and psychosocial difficulties in children presenting to the pediatric urology clinic for voiding dysfunction and to the pediatric gastroenterology clinic for functional constipation. MATERIALS AND METHODS: Parents of children seen at the gastroenterology clinic were recruited during the outpatient clinic appointment, and parents of children seen at the urology clinic were randomly selected from the research database and matched to the gastroenterology sample based on age and gender of the child. All parents completed the Dysfunctional Voiding Scoring System, Bristol Stool Form Scale, Pediatric Symptom Checklist and Parenting Stress Index™-Short Form, which assessed severity of voiding dysfunction, stool consistency, level of psychosocial difficulties and level of parenting stress, respectively. RESULTS: Children seen at the urology and gastroenterology clinics did not differ significantly on any of the measures, indicating that the severity of their bladder-bowel dysfunction is similar. However, they had significantly more severe voiding dysfunction, more constipated stool and more psychosocial difficulties than historical healthy controls. Additionally, level of parenting stress was significantly correlated with patient level of psychosocial difficulties and severity of voiding dysfunction. CONCLUSIONS: Patients with bladder and bowel dysfunction represent a homogeneous group that would potentially benefit from a multidisciplinary treatment approach involving urology, gastroenterology and psychology professionals.

Candidate gene association study implicates p63 in the etiology of nonsyndromic bladder-exstrophy-epispadias complex.

BACKGROUND: Bladder-exstrophy-epispadias complex (BEEC) is a severe congenital anomaly that represents a spectrum of urological abnormalities where parts or all of the distal urinary tract fail to close during development. Multiple lines of evidence strongly suggested p63 as a plausible candidate gene. We conducted a candidate gene association study to further investigate the role of p63 in human BEEC. METHODS: We conducted a family-based association study of p63 using 154 Caucasian patients with nonsyndromic BEEC and their unaffected parents. High throughput single nucleotide polymorphism (SNP) genotyping was carried out using Illumina's Golden Gate Assay for 109 selected tagging SNPs localized within p63 with a minor allele frequency > 0.01. Individual and haplotype SNP transmission disequilibrium tests were conducted using Plink and Haploview, respectively. We also examined parent-of-origin effects using paternal asymmetry tests implemented in FAMHAP (http://famhap.meb.uni-bonn.de/index.html). RESULTS: Nominally significant associations were identified between BEEC and six SNPs (rs17447782, rs1913720, rs6790167, rs9865857, rs1543969, rs4687100), and four haplotype blocks including or near these significant SNPs. Analysis of parent-of-origin effects showed significant results for seven SNPs (rs4118375, rs12696596, rs6779677, rs13091309, rs7642420, rs1913721, and rs1399774). None of these results remained significant after multiple testing correction. CONCLUSION: The altered transmission of p63 variants in nonsyndromic BEEC patients may be suggestive of its involvement in the disease etiology. Further and large multi-institutional collaborative studies are required to elucidate the role of p63 in nonsyndromic BEEC.

History of recurrent urinary tract infection is not predictive of abnormality on voiding cystourethrogram.

PURPOSE: The American Academy of Pediatrics recently recommended against routine voiding cystourethrograms (VCUGs) in children 2 to 24 months with initial febrile UTI, raising concern for delayed diagnosis and increased risk of UTI-related renal damage from vesicoureteral reflux (VUR). We assessed factors potentially associated with higher likelihood of abnormal VCUG, including UTI recurrence, which could allow for more judicious test utilization. METHODS: We retrospectively reviewed all initial VCUGs performed at Children's Hospital of Michigan between January and June, 2010. History of recurrent UTI was ascertained by evidence of two or more prior positive cultures or history of "recurrent UTI" on VCUG requisition. Outcomes assessed included rates of VUR or any urologic abnormality on VCUG. RESULTS: Two hundred and sixty-two patients met inclusion criteria. VUR was detected in 21.3 %, urologic abnormality including VUR in 27.4 %. Degree of bladder distension, department of referring physician, study indication, positive documented urine culture, and history of recurrent UTI or UTI and other abnormality were all not associated with increased likelihood of VUR or any urologic abnormality on VCUG. CONCLUSION: VUR and VCUG abnormality are no more likely when performed after recurrent UTI or for UTI plus other abnormality. This reasons against postponing VCUG until after UTI recurrence, as positive findings are no more likely in this setting.