Age- and sex-dependent clinical equations to estimate glomerular filtration rates in children and young adults with chronic kidney disease.

Using data (2655 observations from 928 participants) from the Chronic Kidney Disease in Children Study, we developed and internally validated new glomerular filtration rate estimating equations for clinical use in children and young adults: two forms of K × [heigh(ht) / serum creatinine(sCr)] and two forms of K × [1 / cystatin C(cysC)]. For each marker, one equation used a sex-dependent K; in the other, K is sex-and age-dependent. Glomerular filtration rate (GFR) was measured directly by plasma iohexol disappearance. The equations using ht/sCr had sex-specific constants of 41.8 for males and 37.6 for females. In the age- dependent models, K increased monotonically for children 1-18 years old and was constant for young adults 18-25 years. For males, K ranged from 35.7 for one-year-olds to 50.8 for those 18 and older. For females, the values of K ranged from 33.1 to 41.4. Constant K values for cystatin-C equations were 81.9 for males and 74.9 for females. With age-dependency, K varied non-monotonically with the highest values at age 15 for males (K of 87.2) and 12 years for females (K of 79.9). Use of an age-dependent K with ht/sCr models reduced average bias, notably in young children and young adults; age-dependent cystatin-C models produced similar agreement to using a constant K in children under 18 years, but reduced bias in young adults. These age-dependent proposed equations were evaluated alongside estimated GFRs from 11 other published equations for pediatrics and young adults. Only our proposed equations yielded non- significant bias and within 30% accuracy values greater than 85% in both the pediatric and young adult subpopulations.

Longitudinal changes in overactive bladder and stress incontinence among parous women.

AIMS: To describe longitudinal changes in symptoms of overactive bladder (OAB) and stress urinary incontinence (SUI) among parous women. METHODS: At annual examinations, beginning at least 5 years from first delivery, OAB and SUI were assessed using the Epidemiology of Prolapse and Incontinence Questionnaire. Published thresholds were used to define "bothersome" symptom scores. The prevalence, the incidence of bothersome symptoms, and treatment rates were calculated. In separate analyses for women who delivered by cesarean versus vaginal delivery, odds of SUI or OAB symptoms (score > 0) were modeled as a function of time since childbirth, age, race, and obesity. Among those with persistent symptoms, severity symptom score was modeled as a function of time since childbirth and these same covariates. RESULTS: One thousand four hundred and eighty-one participants completed up to 5 annual assessments (2,722 woman-years). During follow-up, the incidences of bothersome SUI and OAB were 2.5/100 woman-years and 1.7/100 woman-years, respectively. Although SUI and OAB symptoms were more common in the vaginal birth group (P < 0.001), the odds of symptoms increased since increasing time from delivery in the cesarean group. Symptom severity did not change substantially over time in either group. Obesity was strongly associated with symptoms related to SUI and OAB. CONCLUSIONS: Five years from first delivery, symptoms related to SUI and OAB were more common and of greater severity after vaginal than cesarean birth. However, differences between these two groups lessen as time from childbirth increases. Obesity control should be a primary target for reduction of incontinence and incontinence severity among parous women.

Long-term cumulative incidence of cervical intraepithelial neoplasia grade 3 or worse after abnormal cytology: impact of HIV infection.

To estimate the long term cumulative risk for cervical intraepithelial neoplasia grade 3 or worse after an abnormal cervical Pap test and to assess the effect of HIV infection on that risk. Participants in the Women's Interagency HIV Study were followed semiannually for up to 10 years. Pap tests were categorized according to the 1991 Bethesda system. Colposcopy was prescribed within 6 months of any abnormality. Risk for biopsy-confirmed CIN3 or worse after abnormal cytology and at least 12 months follow-up was assessed using Kaplan-Meier curves and compared using log-rank tests. Risk for CIN2 or worse was also assessed, since CIN2 is the threshold for treatment. After a median of 3 years of observation, 1,947 (85%) women subsequently presented for colposcopy (1,571 [81%] HIV seropositive, 376 [19%] seronegative). CIN2 or worse was found in 329 (21%) of HIV seropositive and 42 (11%) seronegative women. CIN3 or worse was found in 141 (9%) of seropositive and 22 (6%) seronegative women. In multivariable analysis, after controlling for cytology grade HIV seropositive women had an increased risk for CIN2 or worse (H.R. 1.66, 95% C.I 1.15, 2.45) but higher risk for CIN3 or worse did not reach significance (H.R. 1.33, 95% C.I. 0.79, 2.34). HIV seropositive women with abnormal Paps face a marginally increased and long-term risk for cervical disease compared to HIV seronegative women, but most women with ASCUS and LSIL Pap results do not develop CIN2 or worse despite years of observation.

Nephrotic-range proteinuria is strongly associated with poor blood pressure control in pediatric chronic kidney disease.

Despite the importance of blood pressure (BP) control in chronic kidney disease (CKD), few longitudinal studies on its trends exist for pediatric patients with CKD. Here we longitudinally analyzed casual data in 578 children with CKD and annual BP measurements standardized for age, gender, and height. At baseline, 124 children were normotensive, 211 had elevated BP, and 243 had controlled hypertension. Linear mixed-effects models accounting for informative dropout determined factors associated with BP changes over time and relative sub-hazards (RSH) identified factors associated with the achievement of controlled BP in children with baseline elevated BP. Younger age, black children, higher body mass index, and higher proteinuria at baseline were associated with higher standardized BP levels. Overall average BP decreased during follow-up, but nephrotic-range proteinuria and increased proteinuria and body mass index were risk factors for increasing BP over time. Only 46% of hypertensive patients achieved controlled BP during follow-up; least likely were those with nephrotic-range proteinuria (RSH 0.19), black children (RSH 0.42), and children with baseline glomerular filtration rate under 40 ml/min per 1.73 m(2) (RSH 0.58). Thus, of many coexisting factors, nephrotic-range proteinuria was most strongly associated with poor BP control and worsening BP over time. Future research should focus on strategies to reduce proteinuria, as this may improve BP control and slow the progression of CKD.

Reliability of resting blood pressure measurement and classification using an oscillometric device in children with chronic kidney disease.

OBJECTIVE: To compare the reliability of blood pressure (BP) readings obtained with an oscillometric device with those obtained by auscultation and assess for differences in BP status classification based on the 2 techniques. STUDY DESIGN: Resting BP was measured by auscultation and with an oscillometric device at the same encounter in 235 subjects enrolled in the Chronic Kidney Disease in Children study. Resting auscultatory BP values were averaged and compared with averaged oscillometric readings. BP agreement by the 2 methods was assessed using Bland-Altman plots, and BP status classification agreement was assessed by calculation of kappa statistics. RESULTS: Oscillometric BP readings were higher than auscultatory readings, with a median paired difference of 9 mm Hg for systolic BP (SBP) and 6 mm Hg for diastolic BP (DBP). Correlation for mean SBP was 0.624 and for mean DBP was 0.491. The bias for oscillometric BP measurement was 8.7 mm Hg for SBP (P < .01) and 5.7 mm Hg for DBP (P < .01). BP status classification agreement was 61% for SBP and 63% for DBP, with Kappa values of .31 for SBP and .20 for DBP. CONCLUSIONS: Compared with auscultation, the oscillometric device significantly overestimated both SBP and DBP, leading to frequent misclassification of BP status.

Association between common iron store markers and hemoglobin in children with chronic kidney disease.

BACKGROUND: Serum ferritin and transferrin saturation (TSAT) are used to assess iron status in children with chronic kidney disease (CKD), but their sensitivity in identifying those at risk of lower hemoglobin (HGB) values is unclear. METHODS: We assessed the association of iron status markers (ferritin, TSAT, and serum iron) with age- and gender-related HGB percentile in mild-to-moderate CKD in 304 children in the Chronic Kidney Disease in Children (CKiD) Study. Standardized HGB percentile values were examined by KDOQI-recommended ferritin (≥ 100 ng/ml) and TSAT (≥ 20 %) thresholds. Regression tree methods were used to identify iron status markers and clinical characteristics most associated with lower HGB percentiles. RESULTS: The cohort was 62 % male, 23 % African American, and 12 % Hispanic, median age 12 years, and median HGB 12.9 g/dl. 34 % had low TSAT and 93 % low ferritin as defined by KDOQI. Distribution of HGB percentile values was lower in those with ferritin ≥ 100 ng/ml, while TSAT ≥ 20 % was associated with only modest increase in HGB percentile. In regression tree analysis, lower glomerular filtration rate (GFR), serum iron <50 µg/dl and ferritin ≥ 100 ng/ml were most strongly associated with lower HGB percentile. CONCLUSIONS: The level of GFR was significantly associated with HGB. Higher serum ferritin was associated with lower HGB in this cohort. Low serum iron in the context of normal/increased ferritin and low HGB may be a useful indicator of iron-restricted erythropoiesis.

Breastfeeding practices among first-time mothers and across multiple pregnancies.

To investigate maternal characteristics associated with breastfeeding initiation and success. Women enrolled in the Mothers Outcomes After Delivery study reported breastfeeding practices 5-10 years after a first delivery. Women were classified as successful breastfeeding initiators, unsuccessful initiators, or non-initiators. For the first birth, demographic and obstetrical characteristics were compared across these three breastfeeding groups. For multiparous women, agreement in breastfeeding status between births was evaluated. Multivariate regression analysis was used to identify characteristics associated with non-initiation and unsuccessful breastfeeding across all births. Of 812 participants, 740 (91%) mothers tried to breastfeed their first child and 593 (73%) reported breastfeeding successfully. In a multivariate analysis, less educated women were less likely to initiate breastfeeding (odds ratio (OR) for non-initiation 1.97; 95% confidence interval (CI) 1.23, 3.14). There was a notable decrease in breastfeeding initiation with increasing birth order: compared to the first birth, the odds for non-initiation after a second delivery almost doubled (OR 1.83, 95% CI 1.42, 2.35) and the odds for non-initiation after a third delivery were further increased (OR 2.44, 95% CI 1.56, 3.82). Successful breastfeeding in a first pregnancy was a predictor of subsequent breastfeeding initiation and success. Specifically, women who did not attempt breastfeeding or who reported unsuccessful attempts to breastfeed at first birth were unlikely to initiate breastfeeding at later births. Cesarean delivery was not associated with breastfeeding initiation (OR 1.01; 95% CI 0.68, 1.48) or success (OR 1.33; 95% CI 0.92, 1.94). Breastfeeding practices after a first birth are a significant predictor of breastfeeding in subsequent births.

Methods for characterizing differences in longitudinal glomerular filtration rate changes between children with glomerular chronic kidney disease and those with nonglomerular chronic kidney disease.

The rate of decline of glomerular filtration rate (GFR) in children with chronic kidney disease (CKD) can vary, even among those with similar diagnoses. Classic regression methods applied to the log-transformed GFR (i.e., lognormal) quantify only rigid shifts in a given outcome. The generalized gamma distribution offers an alternative approach for characterizing the heterogeneity of effect of an exposure on a positive, continuous outcome. Using directly measured GFR longitudinally assessed between 2005 and 2010 in 529 children enrolled in the Chronic Kidney Disease in Children Study, the authors characterized the effect of glomerular CKD versus nonglomerular CKD diagnoses on the outcome, measured as the annualized GFR ratio. Relative percentiles were used to characterize the heterogeneity of effect of CKD diagnosis across the distribution of the outcome. The rigid shift assumed by the classic mixed models failed to capture the fact that the greatest difference between the glomerular and nonglomerular diagnosis' annualized GFR ratios was in children who exhibited the fastest GFR declines. Although this difference was enhanced in children with an initial GFR level of 45 mL/minute/1.73 m(2) or less, the effect of diagnosis on outcome was not significantly modified by level. Generalized gamma models captured heterogeneity of effect more richly and provided a better fit to the data than did conventional lognormal models.

Kidney Disease Progression in Children and Young Adults With Pediatric CKD: Epidemiologic Perspectives and Clinical Applications.

Chronic kidney disease (CKD) progression is typically characterized as either time to a clinically meaningful event (such as dialysis or transplant), or longitudinal changes in kidney function. This review describes pediatric kidney disease progression using these two distinct frameworks by reviewing and discussing data from the Chronic Kidney Disease in Children study. We first describe new equations to estimate glomerular filtration rate (GFR) for patients younger than age 25 years, and how the average of serum creatinine-based and cystatin C-based GFR equations yield valid estimates than either alone. Next, we present a life course description of CKD onset to kidney replacement therapy, prediction models based on clinical measurements, and show the importance of diagnosis (broadly classified as nonglomerular and glomerular in origin), GFR level, and proteinuria on progression. Literature on longitudinal GFR in children and young adults are reviewed and new data are presented to characterize nonlinear changes in estimated GFR in patients younger than age 25 years. These models showed accelerated progression associated with glomerular diagnosis, lower GFR level, and higher proteinuria, which was congruent with time-to-event analyses. Descriptions of online tools for GFR estimation and risk stratification for clinical applications are presented and we offer key epidemiologic considerations for the analysis of longitudinal pediatric CKD studies.

Dyslipidemia in children with chronic kidney disease.

Dyslipidemia, a known risk factor for atherosclerosis, is frequent among both adults and children with chronic kidney disease. Here, we describe the prevalence and pattern of dyslipidemia from a cross-sectional analysis of 391 children aged 1-16 years, enrolled in the multicenter Chronic Kidney Disease in Children (CKiD) study, with a median glomerular filtration rate (GFR), measured by the plasma disappearance of iohexol, of 43 ml/min per 1.73 m2. Multivariate analysis was applied to adjust for age, gender, body mass index (BMI), GFR, and the urinary protein/creatinine ratio. Proteinuria was in the nephrotic range in 44 and the BMI exceeded the 95th percentile in 57 patients of this cohort. Baseline lipid analysis found a high prevalence of hypertriglyceridemia in 126, increased non-HDL-C in 62, and reduced HDL-C in 83. Overall, 177 children had dyslipidemia, of whom 79 had combined dyslipidemia. Lower GFR was associated with higher triglycerides, lower HDL-C, and higher non-HDL-C. Nephrotic-range proteinuria was significantly associated with dyslipidemia and combined dyslipidemia. Compared with children with a GFR>50, children with a GFR<30 had significantly increased odds ratios for any dyslipidemia or for combined dyslipidemia. Hence, among children with moderate chronic kidney disease, dyslipidemia is common and is associated with lower GFR, nephrotic proteinuria, and non-renal factors including age and obesity.

Hemoglobin differences by race in children with CKD.

BACKGROUND: There are known racial disparities in the prevalence of anemia in adults with chronic kidney disease (CKD), but these differences have not been well described in children. STUDY DESIGN: Cohort study, cross-sectional analysis. SETTING & PARTICIPANTS: The Chronic Kidney Disease in Children (CKiD) Study is a multicenter prospective cohort study of children with mild to moderate CKD. This analysis included 429 children of African American or white race. PREDICTOR: Race. OUTCOMES & MEASUREMENTS: This study examined the association of race with hemoglobin level. Both multiple linear regression and generalized gamma modeling techniques were used to characterize the association between race and hemoglobin level. RESULTS: 79% of the cohort was white, 21% was African American. Neither median hemoglobin level nor frequency of erythropoiesis-stimulating agent use differed by race. In multivariate analysis, lower levels of iohexol-measured glomerular filtration rate, African American race, and glomerular disease (vs nonglomerular disease) as the underlying cause of CKD were independently associated with decreased hemoglobin levels; independent of glomerular filtration rate and CKD diagnosis, African American children had average hemoglobin levels that were 0.6 g/dL (95% CI, -0.9 to -0.2 g/dL) lower than those of white children. Generalized gamma modeling showed that differences in hemoglobin levels observed by race become more pronounced when moving from high to low in the overall hemoglobin level distribution. LIMITATIONS: Cross-sectional analysis cannot establish causality, and data for iron stores were not available for all patients. CONCLUSIONS: African American compared with white children have lower hemoglobin values in CKD independent of the underlying cause of CKD. These racial differences in hemoglobin levels appear to increase at the lower end of the hemoglobin level distribution in this population.

Change in Dyslipidemia with Declining Glomerular Filtration Rate and Increasing Proteinuria in Children with CKD.

BACKGROUND AND OBJECTIVES: Dyslipidemia, a risk factor for cardiovascular disease, is common in CKD but its change over time and how that change is influenced by concurrent progression of CKD have not been previously described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In the CKD in Children study we prospectively followed children with progressive CKD and utilized multivariable, linear mixed-effects models to quantify the longitudinal relationship between within-subject changes in lipid measures (HDL cholesterol, non-HDL cholesterol, triglycerides) and within-subject changes in GFR, proteinuria, and body mass index (BMI). RESULTS: A total of 508 children (76% nonglomerular CKD, 24% glomerular CKD) had 2-6 lipid measurements each, with a median follow-up time of 4 (interquartile range [IQR], 2.1-6.0) years. Among children with nonglomerular CKD, dyslipidemia was common at baseline (35%) and increased significantly as children aged; 43% of children with glomerular CKD had dyslipidemia at baseline and demonstrated persistent levels as they aged. Longitudinal increases in proteinuria were independently associated with significant concomitant increases in non-HDL cholesterol (nonglomerular: 4.9 [IQR, 3.4-6.4] mg/dl; glomerular: 8.5 [IQR, 6.0-11.1] mg/dl) and triglycerides (nonglomerular: 3% [IQR, 0.8%-6%]; glomerular: 5% [IQR, 0.6%-9%]). Decreases in GFR over follow-up were significantly associated with concomitant decreases of HDL cholesterol in children with nonglomerular CKD (-1.2 mg/dl; IQR, -2.1 to -0.4 mg/dl) and increases of non-HDL cholesterol in children with glomerular CKD (3.9 mg/dl; IQR, 1.4-6.5 mg/dl). The effects of increased BMI also affected multiple lipid changes over time. Collectively, glomerular CKD displayed stronger, deleterious associations between within-subject change in non-HDL cholesterol (9 mg/dl versus 1.2 mg/dl; P<0.001) and triglycerides (14% versus 3%; P=0.004), and within-subject change in BMI; similar but quantitatively smaller differences between the two types of CKD were noted for associations of within-subject change in lipids to within-subject change in GFR and proteinuria. CONCLUSIONS: Dyslipidemia is a common and persistent complication in children with CKD and it worsens in proportion to declining GFR, worsening proteinuria, and increasing BMI.

Cervical cancer screening intervals and management for women living with HIV: a risk benchmarking approach.

OBJECTIVE: We suggested cervical cancer screening strategies for women living with HIV (WLHIV) by comparing their precancer risks to general population women, and then compared our suggestions with current Centers for Disease Control and Prevention (CDC) guidelines. DESIGN: We compared risks of biopsy-confirmed cervical high-grade squamous intraepithelial neoplasia or worse (bHSIL+), calculated among WLHIV in the Women's Interagency HIV Study, to 'risk benchmarks' for specific management strategies in the general population. METHODS: We applied parametric survival models among 2423 WLHIV with negative or atypical squamous cell of undetermined significance (ASC-US) cytology during 2000-2015. Separately, we synthesized published general population bHSIL+ risks to generate 3-year risk benchmarks for a 3-year return (after negative cytology, i.e. 'rescreening threshold'), a 6-12-month return (after ASC-US), and immediate colposcopy [after low-grade squamous intraepithelial lesion (LSIL)]. RESULTS: Average 3-year bHSIL+ risks among general population women ('risk benchmarks') were 0.69% for a 3-year return (after negative cytology), 8.8% for a 6-12-month return (after ASC-US), and 14.4% for colposcopy (after LSIL). Most CDC guidelines for WLHIV were supported by comparing risks in WLHIV to these benchmarks, including a 3-year return with CD4 greater than 500 cells/µl and after either three negative cytology tests or a negative cytology/oncogenic human papillomavirus cotest (all 3-year risks≤1.3%); a 1-year return after negative cytology with either positive oncogenic human papillomavirus cotest (1-year risk = 1.0%) or CD4 cell count less than 500 cells/µl (1-year risk = 1.1%); and a 6-12-month return after ASC-US (3-year risk = 8.2% if CD4 cell count at least 500 cells/µl; 10.4% if CD4 cell count = 350-499 cells/µl). Other suggestions differed modestly from current guidelines, including colposcopy (vs. 6-12 month return) for WLHIV with ASC-US and CD4 cell count less than 350 cells/µl (3-year risk = 16.4%) and a lengthened 2-year (vs. 1-year) interval after negative cytology with CD4 cell count at least 500 cells/µl (2-year risk = 0.98%). CONCLUSIONS: Current cervical cancer screening guidelines for WLHIV are largely appropriate. CD4 cell count may inform risk-tailored strategies.

Liver Fibrosis Linked to Cognitive Performance in HIV and Hepatitis C.

OBJECTIVE: Because HIV impairs gut barriers to pathogens, HIV-infected adults may be vulnerable to minimal hepatic encephalopathy in the absence of cirrhosis. BACKGROUND: Cognitive disorders persist in up to one-half of people living with HIV despite access to combination antiretroviral therapy. Minimal hepatic encephalopathy occurs in cirrhotic patients with or without HIV infection and may be associated with inflammation. DESIGN/METHODS: A cross-sectional investigation of liver fibrosis severity using the aspartate aminotransferase to platelet ratio index (APRI) and neuropsychological testing performance among women from the Women's Interagency HIV Study. A subset underwent liver transient elastography (FibroScan, n = 303). RESULTS: We evaluated 1479 women [mean (SD) age of 46 (9.3) years]: 770 (52%) only HIV infected, 73 (5%) only hepatitis C virus (HCV) infected, 235 (16%) HIV/HCV coinfected, and 401 (27%) uninfected. Of these, 1221 (83%) exhibited APRI ≤0.5 (no or only mild fibrosis), 206 (14%) exhibited APRI >0.5 and ≤1.5 (moderate fibrosis), and 52 (3%) exhibited APRI >1.5 (severe fibrosis). Having moderate or severe fibrosis (APRI >0.5) was associated with worse performance in learning, executive function, memory, psychomotor speed, fluency, and fine motor skills. In these models that adjusted for fibrosis, smaller associations were found for HIV (learning and memory) and HCV (executive functioning and attention). The severity of fibrosis, measured by FibroScan, was associated with worse performance in attention, executive functioning, and fluency. CONCLUSIONS: Liver fibrosis had a contribution to cognitive performance independent of HCV and HIV; however, the pattern of neuropsychological deficit associated with fibrosis was not typical of minimal hepatic encephalopathy.

Do symptoms of pelvic floor disorders bias maternal recall of obstetrical events up to 10 years after delivery?

OBJECTIVES: The aim of this prospective study was to investigate whether symptoms of incontinence and prolapse bias maternal recall of obstetrical events up to 10 years after delivery. METHODS: In this secondary analysis of data gathered from the Mothers' Outcomes After Delivery study, we compared obstetrical medical records with maternal recall of delivery events. We calculated the agreement between maternal recall and the medical record across 1821 deliveries from 1011 participants for events including macrosomia, mode of delivery, prolonged second of labor, episiotomy, spontaneous laceration, anal sphincter laceration, and operative delivery. Women with symptomatic pelvic floor disorders were identified through administration of the Epidemiology of Prolapse and Incontinence Questionnaire or a clinical history of therapy for a pelvic floor disorder. We determined whether agreement between maternal recall and the medical record differed for those with or without symptoms using the medical record as a criterion standard. RESULTS: Agreement between maternal recall and the medical record was excellent for macrosomia and forceps deliveries (κ > 0.8), fair to good for episiotomy (κ = 0.61) and anal sphincter laceration (κ = 0.57), and poor for spontaneous perineal laceration (κ = 0.41). Symptomatic pelvic floor disorders did not impact maternal recall of macrosomia, prolonged second stage, episiotomy, spontaneous laceration, or operative delivery. However, recall of anal sphincter lacerations was biased by symptoms of pelvic floor disorders. Specifically, symptomatic women were significantly more likely to report a history of anal sphincter laceration, regardless of whether a sphincter laceration was documented (P = 0.025). CONCLUSIONS: Maternal recall of anal sphincter laceration may be biased by symptomatic pelvic floor disorders. In research based on maternal recall of obstetrical events, this could strengthen the apparent association between sphincter laceration and pelvic floor disorders.

Comparison of levator ani muscle avulsion injury after forceps-assisted and vacuum-assisted vaginal childbirth.

OBJECTIVE: Using three-dimensional transperineal ultrasonography, we compared the prevalence of levator ani muscle injury after forceps with vacuum-assisted vaginal delivery. METHODS: This was a retrospective cohort study. Women who experienced at least one forceps delivery (across all deliveries) were compared with women who had at least one vacuum birth. On average, participants were 10 years from the index delivery. Three-dimensional transperineal ultrasound volumes were captured as cine loops at rest with Valsalva and with pelvic floor muscle contraction. The primary outcome was levator ani muscle avulsion. Secondary outcomes included hiatal diameter and area. Prevalence of pelvic floor disorders was also compared between the two delivery groups. RESULTS: Among 45 participants in the forceps group and 28 participants in the vacuum group, there were no differences between groups in maternal age at first delivery, parity, body mass index, birth weight, episiotomy, or duration of second stage. History of anal sphincter laceration was more common in the forceps group. The prevalence of levator ani muscle avulsion was significantly higher after forceps compared with vacuum delivery (22/45 [49%] compared with 5/28 [18%], P=.012, prevalence ratio 2.74, 95% confidence interval [CI] 1.17-6.40, odds ratio 4.40 [95% CI 1.42-13.62]). Controlling for delivery type, levator ani muscle avulsion was associated with symptoms of prolapse (P=.036), although objective evidence of prolapse was not significantly different between groups (P=.20). CONCLUSION: Ten years after delivery, the prevalence of levator avulsion is almost tripled after forceps compared with vacuum-assisted vaginal delivery. LEVEL OF EVIDENCE: II.

Progression of pediatric CKD of nonglomerular origin in the CKiD cohort.

BACKGROUND AND OBJECTIVES: Congenital anomalies of the kidney and urinary tract and genetic disorders cause most cases of CKD in children. This study evaluated the relationships between baseline proteinuria and BP and longitudinal changes in GFR in children with these nonglomerular causes of CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Urine protein-to-creatinine ratio, casual systolic and diastolic BP (normalized for age, sex, and height), and GFR decline were assessed in the prospective CKD in Children cohort study. RESULTS: A total of 522 children, median age 10 years (interquartile range, 7, 14 years) with nonglomerular CKD were followed for a median of 4.4 years. The mean baseline GFR in the cohort was 52 ml/min per 1.73 m(2) (95% confidence interval [95% CI], 50 to 54) and declined 1.3 ml/min per 1.73 m(2) per year on average (95%CI, 1.6 to 1.1). A 2-fold higher baseline urine protein-to-creatinine ratio was associated with an accelerated GFR decline of 0.3 ml/min per 1.73 m(2) per year (95% CI, 0.4 to 0.1). A 1-unit higher baseline systolic BP z-score was associated with an additional GFR decline of 0.4 ml/min per 1.73 m(2) per year (95% CI, 0.7 to 0.1). Among normotensive children, larger GFR declines were associated with larger baseline urine protein-to-creatinine ratios; eGFR declines of 0.8 and 1.8 ml/min per 1.73 m(2) per year were associated with urine protein-to-creatinine ratio <0.5 and ≥0.5 mg/mg, respectively. Among children with elevated BP, average GFR declines were evident but were not larger in children with higher levels of proteinuria. CONCLUSIONS: Baseline proteinuria and systolic BP levels are independently associated with CKD progression in children with nonglomerular CKD.

Medication treatment complexity and adherence in children with CKD.

BACKGROUND AND OBJECTIVES: The complexity of CKD management in children is increased by the number of comorbid conditions. This study assessed the prevalence of comorbidities in pediatric CKD and the frequency with which multiple comorbidities present together by assessing prevalent medication use by CKD stage and diagnosis and their association with clinical or sociodemographic factors. The association between number and frequency of dosing of medications prescribed and self-report of nonadherence was also assessed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional analysis of the Chronic Kidney Disease in Children study, medication use at study entry grouped by indication was examined by CKD stage, diagnosis, age, race, ethnicity, income, and CKD duration. Multivariate adjusted predictors of medication use and clustering were examined. Nonadherence was assessed by self-report of missed medications in the past 7 days. RESULTS: The 558 eligible participants had a median age of 11 years and median GFR of 44 ml/min per 1.73 m(2); 62% of participants were male and 78% had nonglomerular kidney disease. The number of medications for treatment of CKD comorbidities increased with advanced CKD stage (2.5-fold for stages IV versus II; P<0.001) and glomerular disease (1.4-fold versus nonglomerular; P<0.001). Three distinct medication clusters were identified that corresponded to treatment of glomerular disease, advanced renal tubular dysfunction, and proteinuric complications, respectively. Nonadherence was associated with increased medication dosing frequency (administration >2 times/d; P<0.001) but not the number of medications. CONCLUSIONS: Medical therapy for children with CKD is complex and is affected by glomerular diagnosis, CKD stage, and medication frequency. The need for CKD-related medication treatment cannot be easily predicted by CKD staging alone. Poorer adherence was associated with increased medication frequency, but not with the number of medical problems needing treatment. Consolidating medical treatment and reducing medication frequency may improve adherence rates in children with CKD.

Longitudinal changes in pelvic organ support among parous women.

OBJECTIVE: The objective of this study was to characterize changes in pelvic organ support and symptoms of prolapse over time and identify characteristics associated with worsening of support. METHODS: Participants were recruited based on the mode of delivery (cesarean vs vaginal delivery) of their first child. The Pelvic Organ Prolapse Quantification system was used to describe support at baseline and 12 to 18 months later. Symptoms were assessed using a validated questionnaire. Outcomes of interest included the proportion of women with a change in support greater than 1 cm at the anterior vaginal wall (Ba) or posterior vaginal wall (Bp) and a change in support greater than 2 cm at the apex (C). Characteristics associated with worsening of support were identified using 2-sided Fisher's exact test and multivariable logistic regression. RESULTS: Among 749 participants, 60% had delivered by cesarean delivery only. Worsening support at Ba, Bp, and C was observed in 8%, 2%, and 6%, respectively. Worsening at any point was observed in 110 women (15%). Women with prolapse symptoms at baseline were not more likely to experience worsening of support. In a multivariable model, age older than 40 years (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.09-2.49), vaginal delivery (OR, 3.12; 95% CI, 1.38-7.07), and genital hiatus greater than or equal to 2 (OR, 2.36; 95% CI, 1.03-5.43) were all associated with worsening support in at least 1 compartment. CONCLUSIONS: Over 12 to 18 months, characteristics most strongly associated with worsening of pelvic support include genital hiatus size, vaginal birth, and age.