Pelvic floor symptoms according to the severity of second-degree perineal tears within 12 months post-partum: A longitudinal prospective cohort study.

INTRODUCTION: Second-degree perineal tears following vaginal birth are common and presumed to be of little clinical importance. However, the extent of damage to the perineal body varies widely, and there is reason to believe that larger second-degree tears may be associated with more pelvic floor symptoms, compared to lesser form. Therefore, the aim of this study was to assess differences in pelvic floor symptoms according to the severity of second-degree perineal tears up to 12 months post-partum, stratified by parity. MATERIAL AND METHODS: This was a prospective cohort study conducted at Akershus University Hospital, a tertiary referral hospital in Norway. The study sample consisted of 409 primiparas and 394 multiparas with vaginal births. Perineal tears were classified using the classification system recommended by the Royal College of Obstetricians and Gynecologists. Further, second-degree tears were subclassified as 2A, 2B, or 2C, depending on the percentage of damage to the perineal body. Episiotomies were analyzed as a separate group. Pelvic floor symptoms were assessed using the Karolinska Symptoms After Perineal Tear Inventory (KAPTAIN). A linear mixed model was estimated to assess the trend in pelvic floor symptom scores according to perineal tear category and stratified by parity. The primary and secondary outcome measures were the mean sum scores of the KAPTAIN-Inventory, measured in pregnancy (at 18 weeks of gestation), at 3- and 12 months post-partum, and the reported impact of genital discomfort on quality of life measured in pregnancy and at 12 months post-partum. RESULTS: There were no significant differences in pelvic floor symptom scores over time, or at any timepoint, between no tear, first-degree tear, or second-degree tear subcategories, for primi-, and multiparas. Pelvic floor symptoms increased from pregnancy to 3 months post-partum and remained higher at 12 months post-partum compared to pregnancy in all perineal tear categories. Compared to primiparas, multiparas reported a significantly higher impact of genital discomfort on quality of life in pregnancy and at 12 months post-partum. CONCLUSIONS: There were no statistically significant differences in pelvic floor symptoms according to the severity of second-degree perineal tears.

Three-dimensional endovaginal ultrasound assessment using the levator ani deficiency score in primiparas: A replication study.

INTRODUCTION: It is essential to assess the levator ani properly as part of clinical care in patients presenting with pelvic floor dysfunction. The levator ani deficiency scoring system is a previously published method to assess levator ani defects with three-dimensional endovaginal ultrasound. The primary aim of this study was to determine the intra- and interrater reliability of the levator ani deficiency score in a cohort of non-instrumentally delivered primiparas. MATERIAL AND METHODS: Primiparas (n = 141) were examined at least 1 year after vaginal birth. Three-dimensional endovaginal ultrasound volumes were acquired by a single examiner using two different automated ultrasound probes. The volumes were analyzed by two separate raters who were blinded to each other's assessments. Descriptive statistics were calculated for levator ani deficiency score and categorized into three levels (mild, moderate, severe). Kendall's tau-b was calculated for intra- and interrater comparisons. RESULTS: Intrarater comparisons of levator ani deficiency score and levator ani deficiency category were high (Kendall's tau-b ≥0.80 for Rater 1; >0.79 for Rater 2). Interrater comparisons of levator ani deficiency score and levator ani deficiency category were also high (Kendall's tau-b >0.9 for assessment 1 and >0.78 for assessment 2). Varying by rater, probe and assessment, 75.9%-80.1% of the study population had no/mild deficiency, 6.4%-9.2% had moderate deficiency, and 4.3%-6.4% had severe levator ani deficiency. CONCLUSIONS: The levator ani deficiency scoring system is a feasible method to assess defects of the levator ani muscle and can be reproduced with high intra- and interrater correlations. Using the scoring system in clinical practice may facilitate concordant assessment between different examiners. However, the system should be used to support clinical findings and symptomatology and not as a screening tool, as the score is lacking the category of no levator ani deficiency.

One-year follow-up after standardized perineal reconstruction in women with deficient perineum after vaginal delivery.

INTRODUCTION: Perineal tears are common after childbirth and, if not surgically repaired, they may result in a deficient perineum that can cause symptoms of pelvic floor dysfunction. Perineal reconstruction aims to restore the perineal body and increase the support of the pelvic floor. The objective of the present study was to estimate symptom reduction after perineal reconstruction in patients with deficient perineum after vaginal delivery and to compare outcomes between participants with or without concomitant levator ani muscle deficiency. MATERIAL AND METHODS: Participants presenting at the Karolinska Pelvic Floor Center with symptoms of deficient perineum at least 1 year after vaginal birth were invited to the study. Inclusion criteria were a visible perineal scar and confirmed anatomic defect. Levator ani defects were assessed using the Levator Ani Deficiency score. A perineal reconstruction was performed in a standardized way. Subjective symptoms were evaluated using the validated "Karolinska Symptoms After Perineal Tear Inventory" at baseline and 1-year follow-up. A score difference in the symptom of an acquired sensation of a wide vagina was the primary outcome. Results were stratified by the presence or absence of a levator ani deficiency. RESULTS: A perineal reconstruction was performed in 131 patients and 128 patients completed the Karolinska Symptoms After Perineal Tear Inventory at baseline and 119 at follow-up. Median age was 36.1 (interquartile range [IQR] 7.9), median body mass index 22.3 (IQR 5.1) and a median of two vaginal deliveries. Fifty-four women (41.2%) had a levator ani deficiency. The mean score reduction for the item "Do you feel that your vagina is too wide/loose?" was -1.56 (SD 0.96; P < 0.001) from a mean score of 2.75 (maximum 3) at baseline. The mean total score reduction was -9.1 points (SD 5.3; P < 0.001) from a mean score of 18.4 (maximum 33) points at baseline. There were no significant differences between groups when stratifying by levator ani deficiency. CONCLUSIONS: Our results show that perineal reconstructive surgery significantly decreases symptoms of deficient perineum after vaginal delivery. A concomitant levator ani defect does not affect the symptom reduction of an acquired sensation of a wide vagina or the total score reduction after surgery.

Development and initial validation of a Swedish inventory to screen for symptoms of deficient perineum in women after vaginal childbirth: 'Karolinska Symptoms After Perineal Tear Inventory'.

BACKGROUND: Perineal tears are common after vaginal birth and may result in pelvic floor symptoms. However, there is no validated questionnaire that addresses long-term symptoms in women with a deficient perineum after vaginal birth. Thus, the objective of this study was to develop and psychometrically evaluate a clinical screening inventory that estimates subjective symptoms in women with a deficient perineum more than one year after vaginal delivery. MATERIAL AND METHODS: The development and psychometric evaluation employed both qualitative and quantitative methods. Qualitative strategies involved content validity and Think Aloud protocol for generation of items. The psychometric evaluation employed principal component analysis to reduce the number of items. The inventory was completed by women with persistent symptoms after perineal tears (N = 170). Results were compared to those of primiparous women giving birth by caesarean section (N = 54) and nulliparous women (N = 338). RESULTS: A preliminary 41-item inventory was developed, and the psychometric evaluation resulted in a final 11-item inventory. Women with confirmed deficient perineum after perineal trauma scored significantly higher on the symptoms inventory than women in control groups. A cut-off value of ≥ 8 could distinguish patients from controls with high sensitivity (100%) and specificity (87-91%). CONCLUSIONS: The Karolinska Symptoms After Perineal Tear Inventory, is a psychometrically valid 11-item patient-reported outcome measure for symptoms of deficient perineum more than one year after vaginal birth. More research is needed to validate the inventory in various patient populations as well as its use in pelvic floor interventions. The inventory has the potential to improve patient counseling and care in the future.

Posterior compartment symptoms in primiparous women 1 year after non-assisted vaginal deliveries: a Swedish cohort study.

INTRODUCTION AND HYPOTHESIS: This is a prospective cohort follow-up study based on the hypothesis that primiparous women with non-assisted vaginal deliveries and a second-degree perineal tear have more posterior compartment symptoms 1 year after delivery than those with no or first-degree tears. METHODS: A follow-up questionnaire, including validated questions on pelvic floor dysfunction, was completed 1 year postpartum by 410 healthy primiparas, delivered without instrumental assistance at two maternity wards in Stockholm between 2013 and 2015. Main outcome measures were posterior compartment symptoms in women with second-degree perineal tears compared with women with no or only minor tears. RESULTS: Of 410 women, 20.9% had no or only minor tears, 75.4% had a second-degree tear, and 3.7% had a more severe tear. Of women presenting with second-degree tears, 18.9% had bowel-emptying difficulties compared with 20.0% of women with minor tears. Furthermore, almost 3% of them with second-degree tears complained of faecal incontinence (FI) of formed stool, 7.2% of FI of loose stool compared with 1.2% and 3.5% respectively in women with no or only minor tears. CONCLUSIONS: Symptomatic pelvic floor dysfunction is common among primiparous women within 1 year following uncomplicated vaginal delivery, and there are no significant differences between second-degree perineal tears and minor tears. These symptoms should be addressed in all women after delivery to improve pelvic floor dysfunction and quality of life.

A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy.

Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.

Transplantation of Human Neural Precursor Cells Reverses Syrinx Growth in a Rat Model of Post-Traumatic Syringomyelia.

Posttraumatic syringomyelia (PTS) is a serious condition of progressive expansion of spinal cord cysts, affecting patients with spinal cord injury years after injury. To evaluate neural cell therapy to prevent cyst expansion and potentially replace lost neurons, we developed a rat model of PTS. We combined contusive trauma with subarachnoid injections of blood, causing tethering of the spinal cord to the surrounding vertebrae, resulting in chronically expanding cysts. The cysts were usually located rostral to the injury, extracanalicular, lined by astrocytes. T2*-weighted magnetic resonance imaging (MRI) showed hyperintense fluid-filled cysts but also hypointense signals from debris and iron-laden macrophages/microglia. Two types of human neural stem/progenitor cells-fetal neural precursor cells (hNPCs) and neuroepithelial-like stem cells (hNESCs) derived from induced pluripotent stem cells-were transplanted to PTS cysts. Cells transplanted into cysts 10 weeks after injury survived at least 10 weeks, migrated into the surrounding parenchyma, but did not differentiate during this period. The cysts were partially obliterated by the cells, and cyst walls often merged with thin layers of cells in between. Cyst volume measurements with MRI showed that the volumes continued to expand in sham-transplanted rats by 102%, while the cyst expansion was effectively prevented by hNPCs and hNESCs transplantation, reducing the cyst volumes by 18.8% and 46.8%, respectively. The volume reductions far exceeded the volume of the added human cells. Thus, in an animal model closely mimicking the clinical situation, we provide proof-of-principle that transplantation of human neural stem/progenitor cells can be used as treatment for PTS.

Hormone Production by Human First-Trimester Gonads in a Functional In Vitro System.

In the past, explant tissue-culture methodologies have been used to grow gonads and study their development. Results from in vitro cultures of human gonads showed limited progress toward gonadal cell differentiation and were focused mainly on germ-cell differentiation. Thus, detailed studies focusing on human first-trimester gonadal tissue functionality in vitro are still missing. In this study we investigated the endocrine function of human first-trimester gonads in vitro. We included 27 female and 28 male gonadal samples, derived from a total of 55 cases, at postconceptional ages of 4.5 to 10.5 weeks. Tissues were cultured using an explant tissue-culture system for 14 days. Assays for testosterone (liquid chromatography-tandem mass spectrometry), anti-Müllerian hormone (AMH; ELISA), and inhibin B (ELISA) were performed using media collected after 7 and 14 days of culture. We demonstrated sex- and age-dependent secretion profiles of testosterone, AMH, and inhibin B in the culture media, which resemble the pattern of hormone production in human gonads in vivo, from the few available studies at the same age range. Our study shows that explant tissue-culture conditions are robust for culture of human first-trimester gonadal somatic cells. Thus, it can be used to study human gonadal development and related diseases as well as the effect of potentially hormone-disturbing substances in human gonads during development. However, detailed molecular studies are needed for better understanding of the mechanistic control of the endocrine function of human first-trimester gonads.