Postpartum pelvic organ prolapse and pelvic floor muscle training: secondary analysis of a randomized controlled trial of primiparous women.

INTRODUCTION AND HYPOTHESIS: Pelvic floor dysfunction is common after childbirth. We hypothesize that physiotherapist-guided pelvic floor muscle training (PFMT) is effective regarding pelvic organ prolapse (POP) symptoms during the first postpartum year. METHODS: This was a secondary analysis from a randomized controlled trial (RCT), carried out at a physiotherapy clinic, Reykjavik. Participants were eighty-four primiparous women with a singleton delivery. They were screened for eligibility 6-13 weeks postpartum. Women in a training group conducted 12 weekly individual sessions with a physiotherapist within an RCT, starting on average 9 weeks postpartum. Outcomes were assessed after the last session (short term) and at approximately 12 months postpartum (long term). The control group received no instructions after the initial assessment. Main outcome measures were self-evaluated POP symptoms by the Australian Pelvic Floor Questionnaire. RESULTS: Forty-one and 43 women were in the training and control groups, respectively. At recruitment, 17 (42.5%) of the training group and 15 (37%) of the control group reported prolapse symptoms (p = 0.6). Five (13%) from the training group and nine (21%) controls were bothered by the symptoms (p = 0.3). There was a gradual decrease in the number of women with symptoms and no significant short-term (p = 0.08) or long-term (p = 0.6) differences between the groups regarding rates of women with POP symptoms. The difference between groups regarding bother in the short (p = 0.3) or longer term (p = 0.4) was not significant. Repeated-measures analyses using Proc Genmod in SAS did not indicate a significant effect of the intervention over time (p > 0.05). CONCLUSIONS: There was an overall decrease in postpartum symptoms of POP and bother during the first year. Physiotherapist-led PFMT did not change the outcomes. CLINICAL TRIAL REGISTRATION: The trial was registered 30 March 2015 at https://register. CLINICALTRIALS: gov (NCT02682212). Initial participant enrollment was on 16 March 2016 and reported following CONSORT guidelines for randomized controlled trials.

Cross-sectional study of early postpartum pelvic floor dysfunction and related bother in primiparous women 6-10 weeks postpartum.

INTRODUCTION AND HYPOTHESIS: To study the prevalence of pelvic floor dysfunction and related bother in primiparous women 6-10 weeks postpartum, comparing vaginal and cesarean delivery. METHODS: Cross-sectional study of 721 mothers with singleton births in Reykjavik, Iceland, 2015 to 2017, using an electronic questionnaire. Information on urinary and anal incontinence, pelvic organ prolapse and sexual dysfunction with related bother (trouble, nuisance, worry, annoyance) was collected. Main outcome measures were prevalence of pelvic floor dysfunction and related bother. RESULTS: The overall prevalence of urinary and anal incontinence was 48% and 60%, respectively. Bother regarding urinary symptoms was experienced by 27% and for anal symptoms by 56%. Pelvic organ prolapse was noted by 29%, with less than half finding this bothersome. Fifty-five percent were sexually active, of whom 66% reported coital pain. Of all the women, 48% considered sexual issues bothersome. Urinary incontinence and pelvic organ prolapse were more prevalent in women who delivered vaginally compared to cesarean section, but no differences were observed for anal incontinence and coital pain. Compared to women with BMI < 25, obesity was a predictor for urinary incontinence after vaginal delivery (OR 1.94; 95% CI 1.20-3.14). Birthweight > 50th percentile was predictive for urgency incontinence after vaginal delivery (OR 1.53; 95% CI 1.05-2.21). Episiotomy predicted more anal incontinence (OR 2.19; 95% CI 1.30-3.67). No associations between maternal and delivery characteristics were found for pelvic floor dysfunction after cesarean section. CONCLUSIONS: Bothersome pelvic floor dysfunction symptoms are prevalent among first-time mothers in the immediate postpartum period.

Can postpartum pelvic floor muscle training reduce urinary and anal incontinence?: An assessor-blinded randomized controlled trial.

BACKGROUND: Pelvic floor dysfunction, including urinary and anal incontinence, is a common postpartum complaint and likely to reduce quality of life. OBJECTIVE: To study the effects of individualized physical therapist-guided pelvic floor muscle training in the early postpartum period on urinary and anal incontinence and related bother, as well as pelvic floor muscle strength and endurance. MATERIALS AND METHODS: This was an assessor-blinded, parallel-group, randomized controlled trial evaluating effects of pelvic floor muscle training by a physical therapist on the rate of urinary and/or anal leakage (primary outcomes); related bother and muscle strength and endurance in the pelvic floor were secondary outcomes. Between 2016 and 2017, primiparous women giving birth at Landspitali University Hospital in Reykjavik, Iceland, were screened for eligibilty 6-10 weeks after childbirth. Of those identified as urinary incontinent, 95 were invited to participate, of whom 84 agreed. The intervention, starting at ∼9 weeks postpartum consisted of 12 weekly sessions with a physical therapist, after which the main outcomes were assessed (endpoint, ∼6 months postpartum). Additional follow-up was conducted at ∼12 months postpartum. The control group received no instructions after the initial assessment. The Fisher exact test was used to test differences in the proportion of women with urinary and anal incontinence between the intervention and control groups, and independent-sample t tests were used for mean differences in muscle strength and endurance. Significance levels were set as α = 0.05. RESULTS: A total of 41 and 43 women were randomized to the intervention and control groups, respectively. Three participants and 1 participant withdrew from these respective groups. Measurement variables and main delivery outcomes were not different at recruitment. At the endpoint, urinary incontinence was less frequent in the intervention group, with 21 participants (57%) still symptomatic, compared to 31 controls (82%) (P = .03), as was bladder-related bother with 10 participants (27%) in the intervention vs 23 (60%) in the control group (P = .005). Anal incontinence was not influenced by pelvic floor muscle training (P = .33), nor was bowel-related bother (P = .82). The mean differences between groups in measured pelvic floor muscle strength changes at endpoint was 5 hPa (95% confidence interval, 2-8; P = .003), and for pelvic floor muscle endurance changes, 50 hPa/s (95% confidence interval, 23-77; P = .001), both in favor of the intervention group. The mean between-group differences for anal sphincter strength changes was 10 hPa (95% confidence interval, 2-18; P = .01) and for anal sphincter endurance changes 95 hPa/s (95% confidence interval, 16-173; P = .02), both in favor of the intervention. At the follow-up visit 12 months postpartum, no differences were observed between the groups regarding rates of urinary and anal incontinence and related bother. Pelvic floor- and anal muscle strength and endurance favoring the intervention group were maintained. CONCLUSION: Postpartum pelvic floor mucle training decreased the rate of urinary incontinence and related bother 6 months postpartum and increased muscle strength and endurance.

Do female elite athletes experience more complicated childbirth than non-athletes? A case-control study.

OBJECTIVE: Previous studies have suggested that female athletes might be at higher risk of experiencing complications such as caesarean sections and perineal tears during labour than non-athletes. Our aim was to study delivery outcomes, including emergency caesarean section rates, length of the first and second stages of labour and severe perineal tears, in first-time pregnant elite athletes compared with non-athletes. METHODS: This is a retrospective case-control study comparing birth outcomes of primiparous female elite athletes engaging in high-impact and low-impact sports compared with non-athletic controls. The athletes had prior to birth competed at a national team level or equivalent. Participant characteristics and frequency of training for at least 3 years before a first pregnancy were collected via a self-administered questionnaire. Information on delivery outcome was retrieved from the Icelandic Medical Birth Registry. RESULTS: In total, 248 participated, 118 controls, 41 low-impact and 89 high-impact elite athletes. No significant differences were found between the groups with regard to incidence of emergency caesarean section or length of the first and second stages of labour. The incidence of third-degree to fourth-degree perineal tears was significantly higher (23.7%) among low-impact athletes than in the high-impact group (5.1%, p=0.01), but no significant differences were seen when the athletes were compared with the controls (12%; p=0.09 for low-impact and p=0.12 for high-impact athletes). CONCLUSION: Participation in competitive sports at the elite level was not related to adverse delivery outcome, including length of labour, the need for caesarean section during delivery and severe perineal tears.

[Comparison of pelvic floor muscle strength in competition-level athletes and untrained women].

INTRODUCTION: Exercise can stress the pelvic floor muscles. Numerous women experience urinary incontinence while exercising or competing in sports. This study investigated pelvic floor muscle strength, urinary incontinence, and knowledge in contracting pelvic floor muscles among female athletes and untrained women. MATERIALS AND METHODS: This was a prospective case-control study measuring pelvic floor muscle strength using vaginal pressure meas-urement. Participants answered questions regarding general health, urinary incontinence, and knowledge on pelvic floor muscles. Partici-pants were healthy nulliparous women aged 18-30 years, athletes and untrained women. The athletes had competed in their sport for at least three years; including handball, soccer, gymnastics, badminton, BootCamp and CrossFit. RESULTS: The women were comparable in age and height. The athletes (n=18) had a body mass index (BMI) of 22.8 kg/m² vs. 25 kg/m² for the untrained (n=16); p<0.05. The athletes trained on average 11.4 hours/week while the untrained women participated in some activity on average for 1.3 hours/week; p< 0.05. Mean pelvic floor strength was 45±2 hPa in the athletes vs. 43±4 hPa in the untrained; p=0.36 for whether the athletes were stronger. Of the athletes, 61.1% experienced urinary incontinence (n=11) compared with 12.5% of the untrained women (n=2); p<0.05. Incontinence usually occurred during high intensity exercise. The athletes were more knowledgeable about the pelvic floor muscles; p<0.05. CONCLUSION: There was not a significant difference in the strength of pelvic floor muscles of athletes and untrained women. This suggests that pelvic floor muscles are not strengthened during general training but require specific exercises. This holds especially for football, handball and sports with high physical intensity. Coaches need to pay special attention to training and strengthening women's pelvic floor muscles to reduce the occurrence of urinary incontinence.

Pelvic floor muscle function before and after first childbirth.

INTRODUCTION AND HYPOTHESIS: Pregnancy and vaginal delivery are considered to be the main risk factors for development of pelvic floor dysfunction. We hypothesize that; 1) pelvic floor muscle (PFM) strength and endurance is significantly reduced by first delivery in general, and 2) changes in PFM strength and endurance are influenced by mode of delivery. METHODS: Prospective repeated measures observational study. Thirty-six women completed the study. PFM function was measured as vaginal squeeze pressure. Paired t-test was used to compare PFM function before and after first childbirth for all participants as a group. One-way ANOVA was used to compare changes between different modes of delivery. RESULTS: A significant reduction in PFM strength (p < 0.0001) and endurance (p < 0.0001) was found for all participants after first childbirth. The reduction in strength was 20.1 hPa (CI:16.2; 24.1), 31.4 hPa (CI: 7.4; 55.2) 5.2 hPa (CI: -6.6; 17.0) in the normal vaginal, instrumental vaginal and acute cesarean groups, respectively. The difference was significant between normal vaginal and acute cesarean birth (p = 0.028) and instrumental vaginal and acute cesarean birth (p = 0.003). CONCLUSION: PFM strength is significantly reduced after vaginal delivery, both normal and instrumental, 6 to 12 weeks postpartum. Acute cesarean section resulted in significantly less muscle strength reduction.

M1 protein from streptococcus pyogenes induces nitric oxide-mediated vascular hyporesponsiveness to phenylephrine: involvement of toll-like receptor activation.

Streptococcus pyogenes carrying M1 protein causes the severe and increasingly prevalent streptococcal toxic shock syndrome and necrotizing fasciitis. M1 protein is an important virulence factor of S. pyogenes and induces an inflammatory response in human monocytes. We wanted to investigate if purified M1 protein in solution could induce vascular NO production leading to vasopressor hyporesponsiveness. Rat aortic segments were incubated with M1 protein or LPS in vitro. M1 protein (10 microg mL) and LPS (1 ng mL) to a similar extent induced NO production and hyporesponsiveness to the vasoconstrictor phenylephrine. Immunogold electron microscopy demonstrated that M1 protein binds to Toll-like receptor 2 (TLR2) as well as TLR4 in mouse aorta but only to TLR2 in human omental artery. Incubation with M1 protein caused a reduction in the contractile response to phenylephrine in aortic segments from wild-type and TLR2-knockout but not from TLR4-knockout mice. In conclusion, M1 protein causes vascular NO production leading to hyporesponsiveness to vasopressors via a mechanism involving TLR, but the subtypes may be species dependent. M1 protein could contribute to the circulatory disturbances accompanying severe invasive streptococcal infections.

Test-retest intra-rater reliability of vaginal measurement of pelvic floor muscle strength using Myomed 932.

OBJECTIVES: To investigate test-retest intra-rater reliability of measurements of pelvic floor muscle (PFM) strength using Myomed 932 (Enraf-Nonius, Delft, the Netherlands). DESIGN: Test-retest intra-rater reliability test with a 2-7 day interval. SETTING: Physiotherapy outpatient clinic in association with the Department of Physiotherapy, University of Iceland. POPULATION: Twenty healthy female volunteers in Reykjavik metropolitan area, Iceland, with a mean age of 43.8 (SD 9.8) years, mean body mass index (BMI) 26.2 (SD 5.3), and mean parity 2.1 children (SD 1.0). MAIN OUTCOME MEASURES: PFM strength during two attempts of maximal voluntary contraction (MVC) measured as vaginal squeeze pressure in hectoPascals (hPa). RESULTS: Mean MVC was 34.45 hPa (95% CI: 26.07-42.83) on Day 1 and 34.05 hPa (95% CI: 26.66-41.44) on Day 2. The measurements ranged from 5-74 hPa interindividually on Day 1 and 5-62 hPa on Day 2. Intraclass Correlation Coefficient (ICC) was 0.97; p < 0.001 and coefficient of variation (CV%) was 11.09%. There was no significant difference between the first and second tests (p = 0.74). CONCLUSION: This test-retest intra-rater reliability study for Myomed 932 showed a very good reliability using ICC. The CV%, however, indicated some degree of intra-individual variation. We suggest that this device can be used both in practice and clinical trials for assessing female PFM strength.

In silico identification and biological evaluation of antimicrobial peptides based on human cathelicidin LL-37.

Bacterial lipopolysaccharides (LPS) are important triggers of the widespread inflammatory response, which contributes to the development of multiple organ failure during sepsis. The helical 37-amino-acid-long human antimicrobial peptide LL-37 not only possesses a broad-spectrum antimicrobial activity but also binds and neutralizes LPS. However, the use of LL-37 in sepsis treatment is hampered by the fact that it is also cytotoxic. To find a less toxic analog of LL-37, we used in silico analysis to identify amphipathic helical regions of LL-37. A 21-amino-acid fragment (GKE) was synthesized, the biological actions of which were compared to those of two equally long peptides derived from the N and C termini of LL-37 as well as native LL-37. GKE displayed antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Candida parapsilosis that was similar to or even stronger than LL-37. GKE, as well as the equally long control peptides, attracted granulocytes in a fashion similar to that of LL-37, while only GKE was as potent as LL-37 in inhibiting LPS-induced vascular nitric oxide production. GKE caused less hemolysis and apoptosis in human cultured smooth muscle cells than LL-37. In summary, we have identified an active domain of LL-37, GKE, which displays antimicrobial activity in vitro and LPS-binding activity similar to those of LL-37 but is less toxic. GKE therefore holds promise as a template for the development of peptide antibiotics for the treatment of sepsis.

Antimicrobial and chemoattractant activity, lipopolysaccharide neutralization, cytotoxicity, and inhibition by serum of analogs of human cathelicidin LL-37.

Antimicrobial peptides have been evaluated in vitro and in vivo as alternatives to conventional antibiotics. Apart from being antimicrobial, the native human cathelicidin-derived peptide LL-37 (amino acids [aa] 104 to 140 of the human cathelicidin antimicrobial peptide) also binds and neutralizes bacterial lipopolysaccharide (LPS) and might therefore have beneficial effects in the treatment of septic shock. However, clinical trials have been hampered by indications of toxic effects of LL-37 on mammalian cells and evidence that its antimicrobial effects are inhibited by serum. For the present study, LL-37 was compared to two less hydrophobic fragments obtained by N-terminal truncation, named 106 (aa 106 to 140) and 110 (aa 110 to 140), and to a previously described more hydrophobic variant, the 18-mer LLKKK, concerning antimicrobial properties, lipopolysaccharide neutralization, toxicity against human erythrocytes and cultured vascular smooth muscle cells, chemotactic activity, and inhibition by serum. LL-37, fragments 106 and 110, and the 18-mer LLKKK inhibited the growth of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans in a radial diffusion assay, inhibited lipopolysaccharide-induced vascular nitric oxide production, and attracted neutrophil granulocytes similarly. While fragments 106 and 110 caused less hemolysis and DNA fragmentation in cultured cells than did LL-37, the 18-mer LLKKK induced severe hemolysis. The antibacterial effect of fragments 106 and 110 was not affected by serum, while the effect of LL-37 was reduced. We concluded that the removal of N-terminal hydrophobic amino acids from LL-37 decreases its cytotoxicity as well as its inhibition by serum without negatively affecting its antimicrobial or LPS-neutralizing action. Such LL-37-derived peptides may thus be beneficial for the treatment of patients with sepsis.