Secular Trends in Patent Ductus Arteriosus Management in Infants Born Preterm in the National Institute of Child Health and Human Development Neonatal Research Network.

We evaluated changes in patent ductus arteriosus (PDA) diagnosis and treatment from 2012 through 2021 in a network of US academic hospitals. PDA treatment decreased among infants born at 26-28 weeks but not among infants born at 22-25 weeks. Rates of indomethacin use and PDA ligation decreased while acetaminophen use and transcatheter PDA closure increased.

Vaginal morphology and position associated with prolapse recurrence after vaginal surgery: A secondary analysis of the DEMAND study.

OBJECTIVE: To identify vaginal morphology and position factors associated with prolapse recurrence following vaginal surgery. DESIGN: Secondary analysis of magnetic resonance images (MRI) of the Defining Mechanisms of Anterior Vaginal Wall Descent cross-sectional study. SETTING: Eight clinical sites in the US Pelvic Floor Disorders Network. POPULATION OR SAMPLE: Women who underwent vaginal mesh hysteropexy (hysteropexy) with sacrospinous fixation or vaginal hysterectomy with uterosacral ligament suspension (hysterectomy) for uterovaginal prolapse between April 2013 and February 2015. METHODS: The MRI (rest, strain) obtained 30-42 months after surgery, or earlier for participants with recurrence who desired reoperation before 30 months, were analysed. MRI-based prolapse recurrence was defined as prolapse beyond the hymen at strain on MRI. Vaginal segmentations (at rest) were used to create three-dimensional models placed in a morphometry algorithm to quantify and compare vaginal morphology (angulation, dimensions) and position. MAIN OUTCOME MEASURES: Vaginal angulation (upper, lower and upper-lower vaginal angles in the sagittal and coronal plane), dimensions (length, maximum transverse width, surface area, volume) and position (apex, mid-vagina) at rest. RESULTS: Of the 82 women analysed, 12/41 (29%) in the hysteropexy group and 22/41 (54%) in the hysterectomy group had prolapse recurrence. After hysteropexy, women with recurrence had a more laterally deviated upper vagina (p = 0.02) at rest than women with successful surgery. After hysterectomy, women with recurrence had a more inferiorly (lower) positioned vaginal apex (p = 0.01) and mid-vagina (p = 0.01) at rest than women with successful surgery. CONCLUSIONS: Vaginal angulation and position were associated with prolapse recurrence and suggestive of vaginal support mechanisms related to surgical technique and potential unaddressed anatomical defects. Future prospective studies in women before and after prolapse surgery may distinguish these two factors.

Correlation Between Mobile-Application Electronic Bowel Diary and Validated Questionnaires in Women with Fecal Incontinence.

INTRODUCTION AND HYPOTHESIS: Despite growing interest in a mobile-app bowel diary to assess fecal incontinence (FI) symptoms, data are limited regarding the correlation between mobile-app diary and questionnaire-based outcomes. The primary aim is to determine whether percentage reduction in FI episodes (FIEs)/week recorded on a mobile-app diary correlates with changes in scores of validated FI-symptom measures from baseline to 12 weeks in women with FI undergoing percutaneous tibial nerve stimulation (PTNS) versus sham. METHODS: This is a planned secondary analysis of a multicenter randomized trial in which women with FI underwent PTNS or sham. FIEs were collected using a mobile-app diary at baseline and after 12 weekly sessions. FI-symptom-validated measures included St. Mark's, Accidental Bowel Leakage Evaluation, FI Severity Index (FISI), Colorectal Anal Distress Inventory, Colorectal Anal Impact Questionnaire, FI Quality of Life, Patient Global Impression of Improvement (PGI-I), and Patient Global Symptom Control (PGSC) rating. Spearman's correlation coefficient (ρ) was computed between %-reduction in FIEs/week and change in questionnaire scores from baseline to 12 weeks. Significance was set at 0.005 to account for multiple comparisons. RESULTS: Baseline characteristics of 163 women (109 PTNS, 54 sham) include mean age 63.4±11.6, 81% white, body mass index 29.4±6.6 kg/m2, 4% previous FI surgeries, 6.6±5.5 FIEs/week, and St. Mark's score 17.4±2.6. A significant correlation was demonstrated between %-reduction in FIEs/week and all questionnaires (p<0.005). A moderate-strength correlation (|ρ|>0.4) was observed for St. Mark's (ρ=0.48), FISI (ρ=0.46), PGI-I (ρ=0.51), and PGSC (ρ=-0.43). CONCLUSIONS: In women with FI randomized to PTNS versus sham, a moderate correlation was noted between FIEs measured via mobile-app diary and FI-symptom-validated questionnaire scores.

Dietary Intake and Symptom Severity in Women with Fecal Incontinence.

INTRODUCTION AND HYPOTHESIS: The goal of this study was to determine whether dietary fat/fiber intake was associated with fecal incontinence (FI) severity. METHODS: Planned supplemental analysis of a randomized clinical trial evaluating the impact of 12-week treatment with percutaneous tibial nerve stimulation versus sham in reducing FI severity in women. All subjects completed a food screener questionnaire at baseline. FI severity was measured using the seven-item validated St. Mark's (Vaizey) FI severity scale. Participants also completed a 7-day bowel diary capturing the number of FI-free days, FI events, and bowel movements per week. Spearman's correlations were calculated between dietary, St. Mark's score, and bowel diary measures. RESULTS: One hundred and eighty-six women were included in this analysis. Mean calories from fats were 32% (interquartile range [IQR] 30-35%). Mean dietary fiber intake was 13.9 ± 4.3 g. The percentage of calories from fats was at the higher end of recommended values, whereas fiber intake was lower than recommended for adult women (recommended values: calories from fat 20-35% and 22-28 g of fiber/day). There was no correlation between St. Mark's score and fat intake (r = 0.11, p = 0.14) or dietary fiber intake (r = -0.01, p = 0.90). There was a weak negative correlation between the number of FI-free days and total fat intake (r = -0.20, p = 0.008). Other correlations between dietary fat/fiber intake and bowel diary measures were negligible or nonsignificant. CONCLUSION: Overall, in women with moderate to severe FI, there was no association between FI severity and dietary fat/fiber intake. Weak associations between FI frequency and fat intake may suggest a role for dietary assessment in the evaluation of women with FI.

Characteristics associated with subjective and objective measures of treatment success in women undergoing percutaneous tibial nerve stimulation vs sham for accidental bowel leakage.

INTRODUCTION AND HYPOTHESIS: In randomized trials both percutaneous tibial nerve stimulation (PTNS) and sham result in clinically significant improvements in accidental bowel leakage (ABL). We aimed to identify subgroups who may preferentially benefit from PTNS in women enrolled in a multicenter randomized trial. METHODS: This planned secondary analysis explored factors associated with success for PTNS vs sham using various definitions: treatment responder using three cutoff points for St. Mark's score (≥3-, ≥4-, and ≥5-point reduction); Patient Global Impression of Improvement (PGI-I) of ≥ much better; and ≥50% reduction in fecal incontinence episodes (FIEs). Backward logistic regression models were generated using elements with significance of p<0.2 for each definition and interaction terms assessed differential effects of PTNS vs sham. RESULTS: Of 166 women randomized, 160 provided data for at least one success definition. Overall, success rates were 65% (102 out of 158), 57% (90 out of 158), and 46% (73 out of 158) for ≥3-, ≥4-, and ≥5-point St Mark's reduction respectively; 43% (68 out of 157) for PGI-I; and 48% (70 out of 145) for ≥50% FIEs. Of those providing data for all definitions of success, 77% (109 out of 142) met one success criterion, 43% (61 out of 142) two, and 29% (41 out of 142) all three success criteria. No reliable or consistent factors were associated with improved outcomes with PTNS over sham regardless of definition. CONCLUSIONS: Despite exploring diverse success outcomes, no subgroups of women with ABL differentially responded to PTNS over sham. Success results varied widely across subjective and objective definitions. Further investigation of ABL treatment success definitions that consistently and accurately capture patient symptom burden and improvement are needed.

Percutaneous Tibial Nerve Stimulation vs Sham Stimulation for Fecal Incontinence in Women: NeurOmodulaTion for Accidental Bowel Leakage Randomized Clinical Trial.

INTRODUCTION: To determine whether percutaneous tibial nerve stimulation (PTNS) is superior to sham stimulation for the treatment of fecal incontinence (FI) in women refractory to first-line treatments. METHODS: Women aged 18 years or older with ≥3 months of moderate-to-severe FI that persisted after a 4-week run-in phase were randomized 2:1 (PTNS:sham stimulation) to 12 weekly 30-minute sessions in this multicenter, single-masked, controlled superiority trial. The primary outcome was change from baseline FI severity measured by St. Mark score after 12 weeks of treatment (range 0-24; minimal important difference, 3-5 points). The secondary outcomes included electronic bowel diary events and quality of life. The groups were compared using an adjusted general linear mixed model. RESULTS: Of 199 women who entered the run-in period, 166 (of 170 eligible) were randomized, (111 in PTNS group and 55 in sham group); the mean (SD) age was 63.6 (11.6) years; baseline St. Mark score was 17.4 (2.7); and recording was 6.6 (5.5) FI episodes per week. There was no difference in improvement from baseline in St. Mark scores in the PTNS group when compared with the sham group (-5.3 vs -3.9 points, adjusted difference [95% confidence interval] -1.3 [-2.8 to 0.2]). The groups did not differ in reduction in weekly FI episodes (-2.1 vs -1.9 episodes, adjusted difference [95% confidence interval] -0.26 [-1.85 to 1.33]). Condition-specific quality of life measures did not indicate a benefit of PTNS over sham stimulation. Serious adverse events occurred in 4% of each group. DISCUSSION: Although symptom reduction after 12 weeks of PTNS met a threshold of clinical importance, it did not differ from sham stimulation. These data do not support the use of PTNS as conducted for the treatment of FI in women.

Placental protein levels in maternal serum are associated with adverse pregnancy outcomes in nulliparous patients.

BACKGROUND: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be was established to investigate the underlying causes and pathophysiological pathways associated with adverse pregnancy outcomes in nulliparous gravidas. OBJECTIVE: This study aimed to study placental physiology and identify novel biomarkers concerning adverse pregnancy outcomes, including preterm birth (medically indicated and spontaneous), preeclampsia, small-for-gestational-age neonates, and stillbirth. We measured levels of placental proteins in the maternal circulation in the first 2 trimesters of pregnancy. STUDY DESIGN: Maternal serum samples were collected at 2 study visits (6-13 weeks and 16-21 weeks), and levels of 9 analytes were measured. The analytes we measured were vascular endothelial growth factor, placental growth factor, endoglin, soluble fms-like tyrosine kinase-1, A disintegrin and metalloproteinase domain-containing protein 12, pregnancy-associated plasma protein A, free beta-human chorionic gonadotropin, inhibin A, and alpha-fetoprotein. The primary outcome was preterm birth between 20 0/7 and 36 6/7 weeks of gestation. The secondary outcomes were spontaneous preterm births, medically indicated preterm births, preeclampsia, small-for-gestational-age neonates, and stillbirth. RESULTS: A total of 10,038 eligible gravidas were enrolled in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort, from which a nested case-control study was performed comparing 800 cases with preterm birth (466 spontaneous preterm births, 330 medically indicated preterm births, and 4 unclassified preterm births), 568 with preeclampsia, 406 with small-for-gestational-age birth, and 49 with stillbirth with 911 controls who delivered at term without complications. Although levels of each analyte generally differed between cases and controls at 1 or 2 visits, the odds ratios revealed a <2-fold difference between cases and controls in all comparisons. Receiver operating characteristic curves, generated to determine the relationship between analyte levels and preterm birth and the other adverse pregnancy outcomes, resulted in areas under the receiver operating characteristic curves that were relatively low (range, 0.50-0.64) for each analyte. Logistic regression modeling demonstrated that areas under the receiver operating characteristic curves for predicting adverse pregnancy outcomes were greater using baseline clinical characteristics and combinations of analytes than baseline characteristics alone, but areas under the receiver operating characteristic curves remained relatively low for each outcome (range, 0.65-0.78). CONCLUSION: We have found significant associations between maternal serum levels of analytes evaluated early in pregnancy and subsequent adverse pregnancy outcomes in nulliparous gravidas. However, the test characteristics for these analytes do not support their use as clinical biomarkers to predict adverse pregnancy outcomes, either alone or in combination with maternal clinical characteristics.

Association between the urogenital microbiome and surgical treatment response in women undergoing midurethral sling operation for mixed urinary incontinence.

BACKGROUND: The urogenital microbiome is associated with urgency and mixed urinary incontinence symptoms and differential treatment responses to pharmacotherapy for urgency urinary incontinence. OBJECTIVE: This study aimed to describe whether the preoperative urinary and vaginal microbiomes were associated with surgical treatment responses at 12 months after a midurethral sling operation in women with mixed urinary incontinence. STUDY DESIGN: This cohort study compared the preoperative microbiome compositions of urine and vaginal samples from a subset of women undergoing a midurethral sling operation in the Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence trial (NCT01959347) and compared the microbiota in women who were surgical responders vs surgical nonresponders. Twelve-month objective response was defined as a ≥70% reduction from baseline urinary incontinence episodes on a 3-day diary. Subjective response was defined as a change from baseline in the Urogenital Distress Inventory scores. Bacterial abundance and beta diversity were assessed using 16S ribosomal RNA sequencing. The primary differential abundance analysis described predominant bacterial operational taxonomic units associated with responders vs nonresponders using unadjusted and age-adjusted linear models. RESULTS: Objective nonresponders (n=28) compared with responders (n=72) were older (58.5±10.7 vs 51.6±10.2 years) and more likely postmenopausal without hormone use (odds ratio, 6.4; 95% confidence interval, 1.8-22.6). Vaginal and urinary microbiota beta diversities were associated with age (P<.05) for both responders and nonresponders. Overall, predominant operational taxonomic units (genera) were Lactobacillus, Gardnerella, Tepidimonas, Escherichia, Streptococcus, and Prevotella. Operational taxonomic units from baseline urine samples were not significantly associated (P threshold=.05) with surgical treatment responses. A greater abundance of baseline vaginal Lactobacillus was associated with an objective response (P=.04) and Prevotella with an objective nonresponse (P=.01). Adjusting for age, only a greater abundance of baseline vaginal Prevotella was associated with an objective nonresponse (P=.01). Moreover, less abundant vaginal operational taxonomic units were associated with objective and subjective responses and persistent urinary incontinence symptoms (P<.05). CONCLUSION: Women meeting a 70% reduction of urinary incontinence treatment episodes (objective responders) had greater vaginal Lactobacillus at the time of the surgical procedure; however, controlling for age diminished this association. Women not meeting a 70% reduction of urinary incontinence episodes 1 year after a midurethral sling operation had greater vaginal Prevotella at the time of the midurethral sling operation. Further research is needed to determine whether therapy altering the vaginal microbiome may impact surgical treatment responses in women with mixed urinary incontinence.

Impact of treatment for fecal incontinence on constipation symptoms.

OBJECTIVE: Defecatory symptoms, such as a sense of incomplete emptying and straining with bowel movements, are paradoxically present in women with fecal incontinence. Treatments for fecal incontinence, such as loperamide and biofeedback, can worsen or improve defecatory symptoms, respectively. The primary aim of this study was to compare changes in constipation symptoms in women undergoing treatment for fecal incontinence with education only, loperamide, anal muscle exercises with biofeedback or both loperamide and biofeedback. Our secondary aim was to compare changes in constipation symptoms among responders and nonresponders to fecal incontinence treatment. STUDY DESIGN: This was a planned secondary analysis of a randomized controlled trial comparing 2 first-line therapies for fecal incontinence in a 2 × 2 factorial design. Women with at least monthly fecal incontinence and normal stool consistency were randomized to 4 groups: (1) oral placebo plus education only, (2) oral loperamide plus education only, (3) placebo plus anorectal manometry-assisted biofeedback, and (4) loperamide plus biofeedback. Defecatory symptoms were measured using the Patient Assessment of Constipation Symptoms questionnaire at baseline, 12 weeks, and 24 weeks. The Patient Assessment of Constipation Symptoms consists of 12 items that contribute to a global score and 3 subscales: stool characteristics/symptoms (hardness of stool, size of stool, straining, inability to pass stool), rectal symptoms (burning, pain, bleeding, incomplete bowel movement), and abdominal symptoms (discomfort, pain, bloating, cramps). Scores for each subscale as well as the global score range from 0 (no symptoms) to 4 (maximum score), with negative change scores representing improvement in defecatory symptoms. Responders to fecal incontinence treatment were defined as women with a minimally important clinical improvement of ≥5 points on the St Mark's (Vaizey) scale between baseline and 24 weeks. Intent-to-treat analysis was performed using a longitudinal mixed model, controlling for baseline scores, to estimate changes in Patient Assessment of Constipation Symptoms scores from baseline through 24 weeks. RESULTS: At 24 weeks, there were small changes in Patient Assessment of Constipation Symptoms global scores in all 4 groups: oral placebo plus education (-0.3; 95% confidence interval, -0.5 to -0.1), loperamide plus education (-0.1, 95% confidence interval, -0.3 to0.0), oral placebo plus biofeedback (-0.3, 95% confidence interval, -0.4 to -0.2), and loperamide plus biofeedback (-0.3, 95% confidence interval, -0.4 to -0.2). No differences were observed in change in Patient Assessment of Constipation Symptoms scores between women randomized to placebo plus education and those randomized to loperamide plus education (P = .17) or placebo plus biofeedback (P = .82). Change in Patient Assessment of Constipation Symptoms scores in women randomized to combination loperamide plus biofeedback therapy was not different from that of women randomized to treatment with loperamide or biofeedback alone. Responders had greater improvement in Patient Assessment of Constipation Symptoms scores than nonresponders (-0.4; 95% confidence interval, -0.5 to -0.3 vs -0.2; 95% confidence interval, -0.3 to -0.0, P < .01, mean difference, 0.2, 95% confidence interval, 0.1-0.4). CONCLUSION: Change in constipation symptoms following treatment of fecal incontinence in women are small and are not significantly different between groups. Loperamide treatment for fecal incontinence does not worsen constipation symptoms among women with normal consistency stool. Women with clinically significant improvement in fecal incontinence symptoms report greater improvement in constipation symptoms.

Defining the relationship between vaginal and urinary microbiomes.

BACKGROUND: Although the vaginal and urinary microbiomes have been increasingly well-characterized in health and disease, few have described the relationship between these neighboring environments. Elucidating this relationship has implications for understanding how manipulation of the vaginal microbiome may affect the urinary microbiome and treatment of common urinary conditions. OBJECTIVE: To describe the relationship between urinary and vaginal microbiomes using 16S rRNA gene sequencing. We hypothesized that the composition of the urinary and vaginal microbiomes would be significantly associated, with similarities in predominant taxa. STUDY DESIGN: This multicenter study collected vaginal swabs and catheterized urine samples from 186 women with mixed urinary incontinence enrolled in a parent study and 84 similarly aged controls. Investigators decided a priori that if vaginal and/or urinary microbiomes differed between continent and incontinent women, the groups would be analyzed separately; if similar, samples from continent and incontinent women would be pooled and analyzed together. A central laboratory sequenced variable regions 1-3 (v1-3) and characterized bacteria to the genus level. Operational taxonomic unit abundance was described for paired vaginal and urine samples. Pearson's correlation characterized the relationship between individual operational taxonomic units of paired samples. Canonical correlation analysis evaluated the association between clinical variables (including mixed urinary incontinence and control status) and vaginal and urinary operational taxonomic units, using the Canonical correlation analysis function in the Vegan package (R version 3.5). Linear discriminant analysis effect size was used to find taxa that discriminated between vaginal and urinary samples. RESULTS: Urinary and vaginal samples were collected from 212 women (mean age 53±11 years) and results from 197 paired samples were available for analysis. As operational taxonomic units in mixed urinary incontinence and control samples were related in canonical correlation analysis and since taxa did not discriminate between mixed urinary incontinence or controls in either vagina or urine, mixed urinary incontinence and control samples were pooled for further analysis. Canonical correlation analysis of vaginal and urinary samples indicated that that 60 of the 100 most abundant operational taxonomic units in the samples largely overlapped. Lactobacillus was the most abundant genus in both urine and vagina (contributing on average 53% to an individual's urine sample and 64% to an individual's vaginal sample) (Pearson correlation r=0.53). Although less abundant than Lactobacillus, other bacteria with high Pearson correlation coefficients also commonly found in vagina and urine included: Gardnerella (r=0.70), Prevotella (r=0.64), and Ureaplasma (r=0.50). Linear discriminant analysis effect size analysis identified Tepidimonas and Flavobacterium as bacteria that distinguished the urinary environment for both mixed urinary incontinence and controls as these bacteria were absent in the vagina (Tepidimonas effect size 2.38, P<.001, Flavobacterium effect size 2.15, P<.001). Although Lactobacillus was the most abundant bacteria in both urine and vagina, it was more abundant in the vagina (linear discriminant analysis effect size effect size 2.72, P<.001). CONCLUSION: Significant associations between vaginal and urinary microbiomes were demonstrated, with Lactobacillus being predominant in both urine and vagina. Abundance of other bacteria also correlated highly between the vagina and urine. This inter-relatedness has implications for studying manipulation of the urogenital microbiome in treating conditions such as urgency urinary incontinence and urinary tract infections.

Performance, acceptability, and validation of a phone application bowel diary.

AIMS: To assess performance, acceptability, external validity, and reliability of a phone application electronic bowel diary (PFDN Bowel eDiary). METHODS: Women reporting refractory accidental bowel leakage (ABL) were enrolled in a randomized, crossover trial evaluating paper versus eDiary documentation of bowel movements (BM) and fecal incontinence episodes (FIE). Events were characterized by the presence or absence of urgency and Bristol stool scale consistency. The eDiary entries were date/time stamped and prompted by twice-daily phone notifications. Women were randomized to complete up to three consecutive 14-day diaries in two sequences. Diary events were compared between formats using the Pearson correlation. System usability scale (SUS) assessed eDiary usability. The eDiary test-retest reliability was assessed with intraclass correlations (ICCs). RESULTS: Paired diary data were available from 60/69 (87%) women 63.8 ± 9.8 years old with mean 13.2 BM per week and 6.5 FIE per week (nearly half with urgency). Among those providing diaries, adherence did not differ by paper or eDiary (93.3% vs. 95.0%). Notifications prompted 29.6% of eDiary entries, improving adherence from 70% to 95%. Paper and eDiaries were moderate to-strongly correlated for BMs per week (r = .61), urgency BMs per week (r = .76), FIE per week (r = .66), urgency FIE per week (r = .72). Test-retest reliability was good (ICC = .81 BMs per week, .79 urgency BMs per week, .74 FIE per week, and .62 urgency FIE per week). The mean SUS score was high, 82.3 ± 17.5 (range, 0-100) with 91.4% rating it easy to use, and 75.9% preferring the eDiary over paper. CONCLUSION: The PFDN Bowel eDiary correlated well with paper diary was considered easy to use, preferred to paper diaries, had high rates of confirmed real-time diary completion that obviated staff data entry.

Association between Policy Changes for Oxygen Saturation Alarm Settings and Neonatal Morbidity and Mortality in Infants Born Very Preterm.

OBJECTIVE: To determine the impact of policy changes for pulse oximetry oxygen saturation (SpO2) alarm limits on neonatal mortality and morbidity among infants born very preterm. STUDY DESIGN: This was a retrospective cohort study of infants born very preterm in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants were classified based on treatment at a hospital with an SpO2 alarm policy change and study epoch (before vs after policy change). We used a generalized linear mixed model to determine the effect of hospital group and epoch on the primary outcomes of mortality and severe retinopathy of prematurity (ROP) and secondary outcomes of necrotizing enterocolitis, bronchopulmonary dysplasia, and any ROP. RESULTS: There were 3809 infants in 10 hospitals with an SpO2 alarm policy change and 3685 infants in 9 hospitals without a policy change. The nature of most policy changes was to narrow the SpO2 alarm settings. Mortality was lower in hospitals without a policy change (aOR 0.63; 95% CI 0.50-0.80) but did not differ between epochs in policy change hospitals. The odds of bronchopulmonary dysplasia were greater for hospitals with a policy change (aOR 1.65; 95% CI 1.36-2.00) but did not differ for hospitals without a policy change. Severe ROP and necrotizing enterocolitis did not differ between epochs for either group. The adjusted odds of any ROP were lower in recent years in both hospital groups. CONCLUSIONS: Changing SpO2 alarm policies was not associated with reduced mortality or increased severe ROP among infants born very preterm.

Effect of Behavioral and Pelvic Floor Muscle Therapy Combined With Surgery vs Surgery Alone on Incontinence Symptoms Among Women With Mixed Urinary Incontinence: The ESTEEM Randomized Clinical Trial.

Importance: Mixed urinary incontinence, including both stress and urgency incontinence, has adverse effects on a woman's quality of life. Studies evaluating treatments to simultaneously improve both components are lacking. Objective: To determine whether combining behavioral and pelvic floor muscle therapy with midurethral sling is more effective than sling alone for improving mixed urinary incontinence symptoms. Design, Setting, and Participants: Randomized clinical trial involving women 21 years or older with moderate or severe stress and urgency urinary incontinence symptoms for at least 3 months, and at least 1 stress and 1 urgency incontinence episode on a 3-day bladder diary. The trial was conducted across 9 sites in the United States, enrollment between October 2013 and April 2016; final follow-up October 2017. Interventions: Behavioral and pelvic floor muscle therapy (included 1 preoperative and 5 postoperative sessions through 6 months) combined with midurethral sling (n = 209) vs sling alone (n = 207). Main Outcomes and Measures: The primary outcome was change between baseline and 12 months in mixed incontinence symptoms measured by the Urogenital Distress Inventory (UDI) long form; range, 0 to 300 points; minimal clinically important difference, 35 points, with higher scores indicating worse symptoms. Results: Among 480 women randomized (mean [SD] age, 54.0 years [10.7]), 464 were eligible and 416 (86.7%) had postbaseline outcome data and were included in primary analyses. The UDI score in the combined group significantly decreased from 178.0 points at baseline to 30.7 points at 12 months, adjusted mean change -128.1 points (95% CI, -146.5 to -109.8). The UDI score in the sling-only group significantly decreased from 176.8 to 34.5 points, adjusted mean change -114.7 points (95% CI, -133.3 to -96.2). The model-estimated between-group difference (-13.4 points; 95% CI, -25.9 to -1.0; P = .04) did not meet the minimal clinically important difference threshold. Related and unrelated serious adverse events occurred in 10.2% of the participants (8.7% combined and 11.8% sling only). Conclusions and Relevance: Among women with mixed urinary incontinence, behavioral and pelvic floor muscle therapy combined with midurethral sling surgery compared with surgery alone resulted in a small statistically significant difference in urinary incontinence symptoms at 12 months that did not meet the prespecified threshold for clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT01959347.

Predictors of sleep-disordered breathing in pregnancy.

BACKGROUND: Sleep-disordered breathing (SDB) is common in pregnancy, but there are limited data on predictors. OBJECTIVES: The objective of this study was to develop predictive models of sleep-disordered breathing during pregnancy. STUDY DESIGN: Nulliparous women completed validated questionnaires to assess for symptoms related to snoring, fatigue, excessive daytime sleepiness, insomnia, and restless leg syndrome. The questionnaires included questions regarding the timing of sleep and sleep duration, work schedules (eg, shift work, night work), sleep positions, and previously diagnosed sleep disorders. Frequent snoring was defined as self-reported snoring ≥3 days per week. Participants underwent in-home portable sleep studies for sleep-disordered breathing assessment in early (6-15 weeks gestation) and mid pregnancy (22-31 weeks gestation). Sleep-disordered breathing was characterized by an apnea hypopnea index that included all apneas, plus hypopneas with ≥3% oxygen desaturation. For primary analyses, an apnea hypopnea index ≥5 events per hour was used to define sleep-disordered breathing. Odds ratios and 95% confidence intervals were calculated for predictor variables. Predictive ability of the logistic models was estimated with area under the receiver-operating-characteristic curves, along with sensitivities, specificities, and positive and negative predictive values and likelihood ratios. RESULTS: Among 3705 women who were enrolled, data were available for 3264 and 2512 women in early and mid pregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%, respectively. At each time point in gestation, frequent snoring, chronic hypertension, greater maternal age, body mass index, neck circumference, and systolic blood pressure were associated most strongly with an increased risk of sleep-disordered breathing. Logistic regression models that included current age, body mass index, and frequent snoring predicted sleep-disordered breathing in early pregnancy, sleep-disordered breathing in mid pregnancy, and new onset sleep-disordered breathing in mid pregnancy with 10-fold cross-validated area under the receiver-operating-characteristic curves of 0.870, 0.838, and 0.809. We provide a supplement with expanded tables, integrated predictiveness, classification curves, and an predicted probability calculator. CONCLUSION: Among nulliparous pregnant women, logistic regression models with just 3 variables (ie, age, body mass index, and frequent snoring) achieved good prediction of prevalent and incident sleep-disordered breathing. These results can help with screening for sleep-disordered breathing in the clinical setting and for future clinical treatment trials.

Patterns of leisure-time physical activity across pregnancy and adverse pregnancy outcomes.

BACKGROUND: Although leisure-time physical activity (PA) contributes to overall health, including pregnancy health, patterns across pregnancy have not been related to birth outcomes. We hypothesized that women with sustained low leisure-time PA would have excess risk of adverse pregnancy outcomes, and that changing patterns across pregnancy (high to low and low to high) may also be related to risk of adverse pregnancy outcomes. METHODS: Nulliparous women (n = 10,038) were enrolled at 8 centers early in pregnancy (mean gestational age in weeks [SD] = 12.05 [1.51]. Frequency, duration, and intensity (metabolic equivalents) of up to three leisure activities reported in the first, second and third trimesters were analyzed. Growth mixture modeling was used to identify leisure-time PA patterns across pregnancy. Adverse pregnancy outcomes (preterm birth, [PTB, overall and spontaneous], hypertensive disorders of pregnancy [HDP], gestational diabetes [GDM] and small-for-gestational-age births [SGA]) were assessed via chart abstraction. RESULTS: Five patterns of leisure-time PA across pregnancy were identified: High (35%), low (18%), late decreasing (24%), early decreasing (10%), and early increasing (13%). Women with sustained low leisure-time PA were younger and more likely to be black or Hispanic, obese, or to have smoked prior to pregnancy. Women with low vs. high leisure-time PA patterns had higher rates of PTB (10.4 vs. 7.5), HDP (13.9 vs. 11.4), and GDM (5.7 vs. 3.1, all p < 0.05). After adjusting for maternal factors (age, race/ethnicity, BMI and smoking), the risk of GDM (Odds ratio 2.00 [95% CI 1.47, 2.73]) remained higher in women with low compared to high patterns. Early and late decreasing leisure-time PA patterns were also associated with higher rates of GDM. In contrast, women with early increasing patterns had rates of GDM similar to the group with high leisure-time PA (3.8% vs. 3.1%, adjusted OR 1.16 [0.81, 1.68]). Adjusted risk of overall PTB (1.31 [1.05, 1.63]) was higher in the low pattern group, but spontaneous PTB, HDP and SGA were not associated with leisure-time PA patterns. CONCLUSIONS: Sustained low leisure-time PA across pregnancy is associated with excess risk of GDM and overall PTB compared to high patterns in nulliparous women. Women with increased leisure-time PA early in pregnancy had low rates of GDM that were similar to women with high patterns, raising the possibility that early pregnancy increases in activity may be associated with improved pregnancy health. TRIAL REGISTRATION: Registration number NCT02231398 .

The urinary microbiome in women with mixed urinary incontinence compared to similarly aged controls.

INTRODUCTION & HYPOTHESIS: Previous studies have suggested that women with urinary incontinence have an altered urinary microbiome. We hypothesized that the microbiome in women with mixed urinary incontinence (MUI) differed from controls and tested this hypothesis using bacterial gene sequencing techniques. METHODS: This multicenter study compared the urinary microbiome in women with MUI and similarly aged controls. Catheterized urine samples were obtained; v4-6 regions of the 16S rRNA gene were sequenced to identify bacteria. Bacterial predominance (> 50% of an individual's genera) was compared between MUI and controls. Bacterial sequences were categorized into "community types" using Dirichlet multinomial mixture (DMM) methods. Generalized linear mixed models predicted MUI/control status based on clinical characteristics and community type. Post-hoc analyses were performed in women < 51 and ≥ 51 years. Sample size estimates required 200 samples to detect a 20% difference in Lactobacillus predominance with P < 0.05. RESULTS: Of 212 samples, 97.6% were analyzed (123 MUI/84 controls, mean age 53 ± 11 years). Overall Lactobacillus predominance did not differ between MUI and controls (45/123 = 36.6% vs. 36/84 = 42.9%, P = 0.36). DMM analyses revealed six community types; communities differed by age (P = 0.001). A High-Lactobacillus (89.2% Lactobacillus) community had a greater proportion of controls (19/84 = 22.6%, MUI 11/123 = 8.9%). Overall, bacterial community types did not differ in MUI and controls. However, post-hoc analysis of women < 51 years found that bacterial community types distinguished MUI from controls (P = 0.041); Moderate-Lactobacillus (aOR 7.78, CI 1.85-32.62) and Mixed (aOR 7.10, CI 1.32-38.10) community types were associated with MUI. Community types did not differentiate MUI and controls in women ≥ 51 years (P = 0.94). CONCLUSIONS: Women with MUI and controls did not differ in overall Lactobacillus predominance. In younger women, urinary bacterial community types differentiated MUI from controls.

Impact of age on acute post-TBI neuropathology in mice expressing humanized tau: a Chronic Effects of Neurotrauma Consortium Study.

OBJECTIVES: We hypothesized that polypathology is more severe in older than younger mice during the acute phase following repetitive mild traumatic brain injury (r-mTBI). METHODS: Young and aged male and female mice transgenic for human tau (hTau) were exposed to r-mTBI or a sham procedure. Twenty-four hours post-last injury, mouse brain tissue was immunostained for alterations in astrogliosis, microgliosis, tau pathology, and axonal injury. RESULTS: Quantitative analysis revealed a greater percent distribution of glial fibrillary acid protein and Iba-1 reactivity in the brains of all mice exposed to r-mTBI compared to sham controls. With respect to axonal injury, the number of amyloid precursor protein-positive profiles was increased in young vs aged mice post r-mTBI. An increase in tau immunoreactivity was found in young and aged injured male hTau mice. CONCLUSIONS: We report the first evidence in our model that r-mTBI precipitates a complex sequelae of events in aged vs young hTau mice at an acute time point, typified by an increase in phosphorylated tau and astroglisosis, and a diminished microgliosis response and axonal injury in aged mice. These findings suggest differential age-dependent effects in TBI pathobiology.

Association between Use of Prophylactic Indomethacin and the Risk for Bronchopulmonary Dysplasia in Extremely Preterm Infants.

OBJECTIVE: To assess the association between prophylactic indomethacin and bronchopulmonary dysplasia (BPD) in a recent, large cohort of extremely preterm infants. STUDY DESIGN: Retrospective cohort study using prospectively collected data for infants with gestational ages < 29 weeks or birth weights of 401-1000 g born between 2008 and 2012 at participating hospitals of the National Institute of Child Health and Human Development Neonatal Research Network. Infants treated with indomethacin in the first 24 hours of life were compared with those who were not. Study outcomes were BPD, defined as use of supplemental oxygen at 36 weeks postmenstrual age among survivors to that time point, death, and the composite of death or BPD. Prespecified subgroup analyses were performed. RESULTS: Prophylactic indomethacin use varied by hospital. Treatment of a patent ductus arteriosus after the first day of life was less common among 2587 infants who received prophylactic indomethacin compared with 5244 who did not (21.0% vs 36.1%, P < .001). After adjustment for potential confounders, use of prophylactic indomethacin was not associated with higher or lower odds of BPD (OR 0.89, 95% CI 0.72-1.10), death (OR 0.80, 95% CI 0.64-1.01), or death or BPD (OR 0.87, 95% CI 0.71-1.05). The only evidence of subgroup effects associated with prophylactic indomethacin were lower odds of death among infants with birth weights above the 10th percentile and those who were not treated for a patent ductus arteriosus after the first day of life. CONCLUSIONS: Prophylactic indomethacin was not associated with either reduced or increased risk for BPD or death. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00063063.

Markers of Successful Extubation in Extremely Preterm Infants, and Morbidity After Failed Extubation.

OBJECTIVES: To identify variables associated with successful elective extubation, and to determine neonatal morbidities associated with extubation failure in extremely preterm neonates. STUDY DESIGN: This study was a secondary analysis of the National Institute of Child Health and Human Development Neonatal Research Network's Surfactant, Positive Pressure, and Oxygenation Randomized Trial that included extremely preterm infants born at 240/7 to 276/7 weeks' gestation. Patients were randomized either to a permissive ventilatory strategy (continuous positive airway pressure group) or intubation followed by early surfactant (surfactant group). There were prespecified intubation and extubation criteria. Extubation failure was defined as reintubation within 5 days of extubation. RESULTS: Of 1316 infants in the trial, 1071 were eligible; 926 infants had data available on extubation status; 538 were successful and 388 failed extubation. The rate of successful extubation was 50% (188/374) in the continuous positive airway pressure group and 63% (350/552) in the surfactant group. Successful extubation was associated with higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within the first 24 hours of age and prior to extubation, lower partial pressure of carbon dioxide prior to extubation, and non-small for gestational age status after adjustment for the randomization group assignment. Infants who failed extubation had higher adjusted rates of mortality (OR 2.89), bronchopulmonary dysplasia (OR 3.06), and death/ bronchopulmonary dysplasia (OR 3.27). CONCLUSIONS: Higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within first 24 hours of age, lower partial pressure of carbon dioxide and fraction of inspired oxygen prior to extubation, and nonsmall for gestational age status were associated with successful extubation. Failed extubation was associated with significantly higher likelihood of mortality and morbidities. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00233324.

Role of early second-trimester uterine artery Doppler screening to predict small-for-gestational-age babies in nulliparous women.

BACKGROUND: Trophoblastic invasion of the uterine spiral arteries substantially increases compliance to accommodate increased blood flow to the placenta. Failure of this process impedes uterine artery blood flow, and this may be detected by uterine artery Doppler flow studies. However, the clinical utility of uterine artery Doppler flow studies in the prediction of adverse pregnancy outcomes in a general population remains largely unknown. OBJECTIVE: We sought to determine the utility of early second-trimester uterine artery Doppler studies as a predictor of small-for-gestational-age neonates. STUDY DESIGN: Nulliparous women with a viable singleton pregnancy were recruited during their first trimester into an observational prospective cohort study at 8 institutions across the United States. Participants were seen at 3 study visits during pregnancy and again at delivery. Three indices of uterine artery Doppler flow (resistance index, pulsatility index, and diastolic notching) were measured in the right and left uterine arteries between 16 weeks 0 days' and 22 weeks 6 days' gestation. Test characteristics for varying thresholds in the prediction of small for gestational age (defined as birthweight <5th percentile for gestational age [Alexander growth curve]) were evaluated. RESULTS: Uterine artery Doppler indices, birthweight, and gestational age at birth were available for 8024 women. Birthweight <5th percentile for gestational age occurred in 358 (4.5%) births. Typical thresholds for the uterine artery Doppler indices were all associated with birthweight <5th percentile for gestational age (P < .0001 for each), but the positive predictive values for these cutoffs were all <15% and areas under receiver operating characteristic curves ranged from 0.50-0.60. Across the continuous scales for these measures, the areas under receiver operating characteristic curves ranged from 0.56-0.62. Incorporating maternal age, early pregnancy body mass index, race/ethnicity, smoking status prior to pregnancy, chronic hypertension, and pregestational diabetes in the prediction model resulted in only modest improvements in the areas under receiver operating characteristic curves ranging from 0.63-0.66. CONCLUSION: In this large prospective cohort, early second-trimester uterine artery Doppler studies were not a clinically useful test for predicting small-for-gestational-age babies.