Tourniquet use in lower limb trauma and fracture surgery.

The use of tourniquets in lower limb trauma surgery to control bleeding and improve the surgical field is a long established practice. In this article, we review the evidence relating to harms and benefits of tourniquet use in lower limb fracture fixation surgery and report the results of a survey on current tourniquet practice among trauma surgeons in the UK.

The risks associated with tourniquet use in lower limb trauma surgery: a systematic review and meta-analysis.

PURPOSE: Tourniquet use in lower limb fracture surgery may reduce intra-operative bleeding, improve surgical field of view and reduce length of procedure. However, tourniquets may result in pain and the production of harmful metabolites cause complications or affect functional outcomes. This systematic review aimed to compare outcomes following lower limb fracture surgery performed with or without tourniquet. METHODS: We searched databases for RCTs comparing lower limb fracture surgery performed with versus without tourniquet reporting on outcomes pain, physical function, health-related quality of life, complications, cognitive function, blood loss, length of stay, length of procedure, swelling, time to union, surgical field of view, volume of anaesthetic agent, biochemical markers of inflammation and injury, and electrolyte and acid-base balance. Random-effects meta-analysis was performed. PROSPERO ID CRD42020209310. RESULTS: Six RCTs enabled inclusion of 552 procedures. Pooled analysis demonstrated that tourniquet use reduced length of procedure by 6 minutes (95% CI -10.12 to -1.87; p < 0.010). We were unable to exclude increased harms from tourniquet use. Pooled analysis showed post-operative pain score was higher in tourniquet group by 12.88 on 100-point scale (95% CI -1.25-27.02; p = 0.070). Risk differences for wound infection, deep venous thrombosis and re-operation were 0.06 (95% CI -0.00-0.12; p = 0.070), 0.05 (95% CI -0.02-0.11; p = 0.150) and 0.03 (95% CI -0.03-0.09; p = 0.340). CONCLUSION: Tourniquet use was associated with a reduced length of procedure. It is possible that tourniquets also increase incidence of important complications, but the data are too sparse to draw firm conclusions. Methodological weaknesses of the included RCTs prevent any solid conclusions being drawn for outcomes investigated. Further studies are required to address these limitations.

Time to reconsider the routine use of tourniquets in total knee arthroplasty surgery.

AIMS: Many surgeons choose to perform total knee arthroplasty (TKA) surgery with the aid of a tourniquet. A tourniquet is a device that fits around the leg and restricts blood flow to the limb. There is a need to understand whether tourniquets are safe, and if they benefit, or harm, patients. The aim of this study was to determine the benefits and harms of tourniquet use in TKA surgery. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled trials, and trial registries up to 26 March 2020. We included randomized controlled trials (RCTs), comparing TKA with a tourniquet versus without a tourniquet. Outcomes included: pain, function, serious adverse events (SAEs), blood loss, implant stability, duration of surgery, and length of hospital stay. RESULTS: We included 41 RCTs with 2,819 participants. SAEs were significantly more common in the tourniquet group (53/901 vs 26/898, tourniquet vs no tourniquet respectively) (risk ratio 1.73 (95% confidence interval (CI) 1.10 to 2.73). The mean pain score on the first postoperative day was 1.25 points higher (95% CI 0.32 to 2.19) in the tourniquet group. Overall blood loss did not differ between groups (mean difference 8.61 ml; 95% CI -83.76 to 100.97). The mean length of hospital stay was 0.34 days longer in the group that had surgery with a tourniquet (95% CI 0.03 to 0.64) and the mean duration of surgery was 3.7 minutes shorter (95% CI -5.53 to -1.87). CONCLUSION: TKA with a tourniquet is associated with an increased risk of SAEs, pain, and a marginally longer hospital stay. The only finding in favour of tourniquet use was a shorter time in theatre. The results make it difficult to justify the routine use of a tourniquet in TKA surgery. Cite this article: Bone Joint J 2021;103-B(5):830-839.

The prevalence of obstructive sleep apnoea in women with polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Obesity is a common risk factor for polycystic ovary syndrome (PCOS) and obstructive sleep apnoea (OSA). Both PCOS and OSA are associated with increased risk of type 2 diabetes and cardiovascular disease. Hence, it is important to determine the burden of OSA in women with PCOS. METHODS: We searched electronic databases (MEDLINE, Embase, CINAHL, PsycINFO, Scopus, Web of Science, OpenGrey, CENTRAL), conference abstracts, and reference lists of relevant articles, up to January 2019. No restriction for language or publication status. Studies that examined the presence of OSA in women with PCOS using polysomnography and/or level III devices were eligible for inclusion. RESULTS: Seventeen studies involving 648 participants were included. Our meta-analysis showed that 35.0% (95% CI 22.2-48.9%) of women with PCOS had OSA. This prevalence was not affected by variation in PCOS definition between studies. Approximately one-tenth of the variation in OSA prevalence was related to differences in study population (higher in adults than adolescents and mixed populations), and around one-tenth was related to sample size (higher in smaller studies). OSA prevalence was markedly higher in obese versus lean women with PCOS, and in women with PCOS compared to controls (odds ratio = 3.83, 95% CI 1.43-10.24, eight studies, 957 participants (349 PCOS and 608 controls)). However, most of the studies were at high risk of selection bias, did not account for important confounders, included predominantly women with class II obesity, and were conducted in one country (USA). CONCLUSIONS: Future studies need to examine the true prevalence of OSA in a more representative sample of women with PCOS. Nevertheless, our results suggest that the prevalence of OSA in women with PCOS and obesity is high and clinicians should have a high index of suspicion of OSA in these women.

Hip arthroscopy versus best conservative care for the treatment of femoroacetabular impingement syndrome (UK FASHIoN): a multicentre randomised controlled trial.

BACKGROUND: Femoroacetabular impingement syndrome is an important cause of hip pain in young adults. It can be treated by arthroscopic hip surgery, including reshaping the hip, or with physiotherapist-led conservative care. We aimed to compare the clinical effectiveness of hip arthroscopy with best conservative care. METHODS: UK FASHIoN is a pragmatic, multicentre, assessor-blinded randomised controlled trial, done at 23 National Health Service hospitals in the UK. We enrolled patients with femoroacetabular impingement syndrome who presented at these hospitals. Eligible patients were at least 16 years old, had hip pain with radiographic features of cam or pincer morphology but no osteoarthritis, and were believed to be likely to benefit from hip arthroscopy. Patients with bilateral femoroacetabular impingement syndrome were eligible; only the most symptomatic hip was randomly assigned to treatment and followed-up. Participants were randomly allocated (1:1) to receive hip arthroscopy or personalised hip therapy (an individualised, supervised, and progressive physiotherapist-led programme of conservative care). Randomisation was stratified by impingement type and recruiting centre and was done by research staff at each hospital, using a central telephone randomisation service. Patients and treating clinicians were not masked to treatment allocation, but researchers who collected the outcome assessments and analysed the results were masked. The primary outcome was hip-related quality of life, as measured by the patient-reported International Hip Outcome Tool (iHOT-33) 12 months after randomisation, and analysed in all eligible participants who were allocated to treatment (the intention-to-treat population). This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN64081839, and is closed to recruitment. FINDINGS: Between July 20, 2012, and July 15, 2016, we identified 648 eligible patients and recruited 348 participants: 171 participants were allocated to receive hip arthroscopy and 177 to receive personalised hip therapy. Three further patients were excluded from the trial after randomisation because they did not meet the eligibility criteria. Follow-up at the primary outcome assessment was 92% (319 of 348 participants). At 12 months after randomisation, mean iHOT-33 scores had improved from 39·2 (SD 20·9) to 58·8 (27·2) for participants in the hip arthroscopy group, and from 35·6 (18·2) to 49·7 (25·5) in the personalised hip therapy group. In the primary analysis, the mean difference in iHOT-33 scores, adjusted for impingement type, sex, baseline iHOT-33 score, and centre, was 6·8 (95% CI 1·7-12·0) in favour of hip arthroscopy (p=0·0093). This estimate of treatment effect exceeded the minimum clinically important difference (6·1 points). There were 147 patient-reported adverse events (in 100 [72%] of 138 patients) in the hip arthroscopy group) versus 102 events (in 88 [60%] of 146 patients) in the personalised hip therapy group, with muscle soreness being the most common of these (58 [42%] vs 69 [47%]). There were seven serious adverse events reported by participating hospitals. Five (83%) of six serious adverse events in the hip arthroscopy group were related to treatment, and the one in the personalised hip therapy group was not. There were no treatment-related deaths, but one patient in the hip arthroscopy group developed a hip joint infection after surgery. INTERPRETATION: Hip arthroscopy and personalised hip therapy both improved hip-related quality of life for patients with femoroacetabular impingement syndrome. Hip arthroscopy led to a greater improvement than did personalised hip therapy, and this difference was clinically significant. Further follow-up will reveal whether the clinical benefits of hip arthroscopy are maintained and whether it is cost effective in the long term. FUNDING: The Health Technology Assessment Programme of the National Institute of Health Research.

Do outcomes reported in randomised controlled trials of joint replacement surgery fulfil the OMERACT 2.0 Filter? A review of the 2008 and 2013 literature.

BACKGROUND: It is not known, whether outcome reporting in trials of total joint arthroplasty in the recent years is adequate or not. Our objective was to assess whether outcomes reported in total joint replacement (TJR) trials fulfil the Outcome Measures in Rheumatology (OMERACT) Filter 2.0. METHODS: We systematically reviewed all TJR trials in adults, published in English in 2008 or 2013. Searches were conducted in the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE. Two authors independently applied the inclusion criteria for the studies, and any disagreement was resolved with a third review author. All outcome measures were abstracted using a pre-piloted standardised data extraction form and assessed for whether they mapped to one of the three OMERACT Filter 2.0 core areas: pathophysiological, life impact, and death. RESULTS: From 1635 trials identified, we included 70 trials (30 in 2008 and 40 in 2013) meeting the eligibility criteria. Twenty-two (31%) trials reported the three essential OMERACT core areas. Among the 27 hip replacement surgery trials and 39 knee replacement surgery trials included, 11 hip (41%) and nine knee (23%) trials reported all three essential OMERACT core areas. The most common outcome domains/measures were pain (20/27, 74%) and function (23/27, 85%) in hip trials and pain (26/39, 67%) and function (27/39, 69%) in knee trials. Results were similar for shoulder and hand joint replacement trials. CONCLUSIONS: We identified significant gaps in the measurement of OMERACT core outcome areas in TJR trials, despite the majority reporting outcome domains of pain and function. An international consensus of key stakeholders is needed to develop a core domain set for reporting of TJR trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014009216.

Outcome Measures Used in Arthroplasty Trials: Systematic Review of the 2008 and 2013 Literature.

OBJECTIVE: Previously published literature assessing the reporting of outcome measures used in joint replacement randomized controlled trials (RCT) has revealed disappointing results. It remains unknown whether international initiatives have led to any improvement in the quality of reporting and/or a reduction in the heterogeneity of outcome measures used. Our objective was to systematically assess and compare primary outcome measures and the risk of bias in joint replacement RCT published in 2008 and 2013. METHODS: We searched MEDLINE, EMBASE, and CENTRAL for RCT investigating adult patients undergoing joint replacement surgery. Two authors independently identified eligible trials, extracted data, and assessed risk of bias using the Cochrane tool. RESULTS: Seventy RCT (30 in 2008, 40 in 2013) met the eligibility criteria. There was no significant difference in the number of trials judged to be at low overall risk of bias (n = 6, 20%) in 2008 compared with 2013 [6 (15%); chi-square = 0.302, p = 0.75]. Significantly more trials published in 2008 did not specify a primary outcome measure (n = 25, 83%) compared with 18 trials (45%) in 2013 (chi-square = 10.6316, p = 0.001). When specified, there was significant heterogeneity in the measures used to assess primary outcomes. CONCLUSION: While less than a quarter of trials published in both 2008 and 2013 were judged to be at low overall risk of bias, significantly more trials published in 2013 specified a primary outcome. Although this might represent a temporal trend toward improvement, the overall frequency of primary outcome reporting and the wide heterogeneity in primary outcomes reported remain suboptimal.

Does total hip replacement affect sexual quality of life?

BACKGROUND: Total Hip Replacement (THR) is an effective treatment for end-stage hip osteoarthritis. Since the introduction of total joint replacement, the effect on the Sexual Quality of Life (SQoL) following THR has been addressed in scant studies. The aim of our study was to systematically review the literature, to summarise effects of THR on patients' SQoL. METHODS: We searched PubMed, EMBASE and PsycINFO between January 1970 and February 9th, 2015 with search terms including Total Hip, Osteoarthritis, SQoL, and THR. Eligible studies were identified and two independent authors extracted data including details of SQoL, study quality and risk of bias. RESULTS: There were 12 eligible studies, which included a total of 2099 patients with an age range of 20-85 years. The methodological quality of ten studies was rated as low, and of two as moderate. Amongst the majority of patients, SQoL improved after surgery, both in terms of physical-functional and psychosocial well-being. However, changes between pre-operative and postoperative SQoL ranged extensively: for example, Sexual Dysfunction Δ 8-51% and Sexual Activity (SA) Δ 0-77%. Three studies reported that some patients never resumed SA again after surgery. CONCLUSION: In over 40 years of THR treatment, scant studies have examined the effect of THR on patients' SQoL. This review suggests that SQol improves after THR, although the magnitude of effects varies highly. However, the quality of the supporting evidence was rated as low to moderate. This suggests a need for more high quality evidence about the effects of THR on SQoL.

Outcome Domains and Measures in Total Joint Replacement Clinical Trials: Can We Harmonize Them? An OMERACT Collaborative Initiative.

OBJECTIVE: To develop a plan for harmonizing outcomes for people undergoing total joint replacement (TJR), to achieve consensus regarding TJR outcome research. METHODS: The TJR working group met during the 2014 Outcome Measures in Rheumatology (OMERACT) 12 meeting in Budapest, Hungary. Multiple conference calls preceded the face-to-face meeting. Brief presentations were made during a 1.5-h meeting, which included an overview of published systematic reviews of TJR trials and the results of a recent systematic review of TJR clinical trial outcome domains and measures. This was followed by discussion of potential core set areas/domains for TJR clinical trials (as per OMERACT Filter 2.0) as well as the challenges associated with the measurement of these domains. RESULTS: Working group participants discussed which TJR clinical trial outcome domains/areas map to the inner versus outer core for core domain set. Several challenges were identified with TJR outcomes including how to best measure function after TJR, elucidating the source of the pre- and post-TJR joint pain being measured, joint-specific versus generic quality of life instruments and the importance of patient satisfaction and revision surgery as outcomes. A preliminary core domain set for TJR clinical trials was proposed and included pain, function, patient satisfaction, revision, adverse events, and death. This core domain set will be further vetted with a broader audience. CONCLUSION: An international effort with active collaboration with the orthopedic community to standardize key outcome domains and measures is under way with the TJR working group. This effort will be further developed with new collaborations.

Surgery for treating hip impingement (femoroacetabular impingement).

BACKGROUND: Surgery is sometimes recommended for femoroacetabular impingement where non-operative interventions have failed. OBJECTIVES: To determine the benefits and safety of surgery for femoroacetabular impingement. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11); MEDLINE (Ovid) (1946 to 19 November 2013); and EMBASE (Ovid) (1980 to 19 November 2013) for studies, unrestricted by language. SELECTION CRITERIA: Randomised and quasi-randomised clinical trials assessing surgical intervention compared with placebo treatment, non-operative treatment or no treatment in adults with femoroacetabular impingement. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion, assessed risk of bias and extracted data. MAIN RESULTS: There were no studies that met the inclusion criteria, with 11 studies that were excluded following detailed review. There were four ongoing studies identified that may meet the inclusion criteria when they are completed; the results from these ongoing studies may begin to become available within the next five years. Three of the four ongoing studies are comparing hip arthroscopy versus non-operative care. The fourth study is comparing hip arthroscopy versus a sham arthroscopic hip procedure. All of the ongoing studies are recording at least one of our preferred clinical outcome measures for benefit and safety. AUTHORS' CONCLUSIONS: There is no high quality evidence examining the effectiveness of surgery for femoroacetabular impingement. There are four ongoing studies, which may provide evidence for the benefit and safety of this type of surgery in the future.

Hip shape and long-term hip function: a study of patients with in-situ fixation for slipped capital femoral epiphysis.

Slipped capital femoral epiphysis (SCFE) is a rare adolescent hip disease that leads to a hip shape abnormality. Typical treatment involves in-situ fixation. It is not known if the degree of initial hip shape abnormality associated with SCFE has a significant effect on long-term hip function. A cohort of patients aged 18-50 who had undergone in-situ fixation for SCFE from 1970 onwards in our institution provided IHOT-33 (hip function) outcome data. Frog lateral radiographs from the time of surgery were used to measure radiological hip shape using both Southwick angle and alpha angle. There were 38 patients (46 hips) SCFE patients who met the eligibility criteria. We obtained follow-up data for 32 patients (38 hips), 83% follow-up. Ten patients (20 hips) had bilateral SCFE. The mean follow-up was 12.7 years (95% CI 10.7-14.7). 32 patients matched for age and sex who had no history of SCFE provided control IHOT-33 outcome data. There was a significant difference (p<0.05) in long-term hip function between patients undergoing in-situ fixation for SCFE and the control population (mean IHOT-33 scores of 71.8 and 95.8 respectively). There was no significant (p>0.05) correlation between long-term hip function and Southwick angle or lateral alpha angle. The initial severity of hip shape abnormality due to SCFE was not a strong predictor of long-term hip function. Other extraneous factors not related to hip shape may have an equally if not more important role to play in the subsequent long-term outcome of SCFE.

The effect of locomotion on the outcome following total hip arthroplasty.

The relationship between contralateral hip arthritis and co-morbid medical conditions that affect a patient's ability to walk, and outcome following total hip arthroplasty (THA) is not fully understood. We investigated this relationship in a prospective, multi-centre study. 1497 hips (1428 patients) were recruited. At five years follow-up there was complete data for 1053 hips. We recorded Oxford Hip Score (OHS) and Charnley Class (CC) both preoperatively and at one and five years after surgery. Preoperatively there was a significant difference in OHS between CC categories and OHS deteriorated from CC-A to CC-C (p<0.001). The absolute OHS was significantly worse in CC-C compared to CC-A. Patients who remained in CC-A at five year follow-up had a larger change in OHS (mean 24) compared to those who had changed from CC-A to CC-C at five years (mean 21) p<0.001. The OHS an outcome measure frequently used for THA is influenced by several extraneous factors which may be present preoperatively but also change over time. These factors include the condition of the opposite hip as well as other disease processes that affect a patient's locomotion and therefore interpretation of OHS in isolation without additional information may not be appropriate.

Nonoperative treatment for femoroacetabular impingement: a systematic review of the literature.

OBJECTIVE: Femoroacetabular impingement (FAI) has been identified as a common cause of hip pain in young adults. However, it is not known whether an effective nonoperative treatment exists and whether there is any evidence to support such a treatment. The purpose of this review is to establish whether nonoperative treatments exist for FAI in the published literature and whether there is any evidence to support their use. TYPE: A systematic review. LITERACY SURVEY: PubMed, Medline, EMBASE, CINAHL, AMED, and Cochrane Library databases were searched by using the following terms: femoroacetabular impingement, femoro-acetabular impingement, and hip impingement. The search was limited to English only but with no time constraints. METHODOLOGY: The review was undertaken at 2 academic institutions within the United Kingdom; any article that described or provided evidence that related to a nonoperative treatment for FAI was included. Fifty-three articles met our criteria, of which, 48 were review and/or discussion based. SYNTHESIS: Five articles summarized primary experiments that described or evaluated nonoperative treatment, of which, 3 reported favorable outcomes. Many review and/or discussion articles (31 [65%]) indicated that a trial of conservative care was appropriate. Activity modification was most frequently recommended (39 [81%]), and nearly half promoted physical therapy as a treatment (23 [48%]). CONCLUSION: The review literature appears to promote initial nonoperative treatment for FAI. Although the available literature with experimental data is limited, there is a suggestion that physical therapy and activity modification confer some benefit to patients. Nonoperative treatment regimens, particularly physical therapy, need to be evaluated more extensively and rigorously, preferably against operative care, to determine the true clinical effectiveness.

Sexual activity and total hip arthroplasty: a survey of patients' and surgeons' perspectives.

It is not clear if regaining sexual activity is important for patients undergoing total hip arthroplasty (THA) or whether hip surgeons are aware of and manage the concerns of their patients in this context. A questionnaire survey was conducted on 100 patients undergoing THA immediately before and six months after surgery. All members of the British Hip Society with a valid email address were surveyed. 86 patients responded. 71 were sexually active and of these, 55 (77%) believed their hip pathology had been limiting their sex lives. 39 (55%) would have preferred further information than was provided. 51 (72%) patients had recommenced sexual activity by six months post operation. 83 of 140 surgeons responded. 30 (36%) surgeons enquired preoperatively if symptoms were interfering with patients' sex lives and 32 (39%) provided written information about sexual activity following THA. 55 (66%) surgeons believed four weeks after surgery patients could resume sexual activity but only 21 (25%) surgeons regularly advised patients about an appropriate time to resume sexual activity. Sexual activity is adversely affected in many patients awaiting THA and regaining sexual function is important to these patients. Most surgeons do not discuss this with their patients and may not be aware of their patients' expectations in this respect.

Inflammatory cytokines and antioxidants in midtrimester amniotic fluid: correlation with pregnancy outcome.

OBJECTIVE: Elevated interleukin-6 (IL-6) level in midtrimester amniotic fluid is associated with preterm delivery. We hypothesized that, in patients with elevated IL-6, vitamin C and alpha-fetoprotein may provide protection from spontaneous preterm delivery through antioxidant functions. STUDY DESIGN: Antioxidant potential of alpha-fetoprotein was assessed in vitro. Amniotic fluid was collected from a prospective cohort of patients who underwent midtrimester amniocentesis. In patients with IL-6 >600 pg/mL, alpha-fetoprotein, vitamin C, tumor necrosis factor-alpha, tumor necrosis factor receptors, and antioxidant capacity were compared between subjects with spontaneous preterm and term deliveries. RESULTS: Alpha-fetoprotein demonstrated 75% the antioxidant capacity of albumin in vitro. Of 388 subjects, 73 women had elevated IL-6 levels. Among these subjects, alpha-fetoprotein, but not vitamin C, was significantly lower in 9 women with preterm birth. Antioxidant capacity correlated with vitamin C and tumor necrosis factor receptors, but not with alpha-fetoprotein or pregnancy outcome. CONCLUSION: Amniotic fluid alpha-fetoprotein, but not vitamin C, may protect against preterm birth in patients with elevated midtrimester IL-6 levels.

Vertical skin incisions and wound complications in the obese parturient.

OBJECTIVE: To examine the relationship between the type of skin incision and postoperative wound complications in an obese population. METHODS: A hospital-based perinatal database was used to identify women with a body mass index (BMI) of greater than 35 undergoing their first cesarean delivery. Hospital and outpatient medical records were reviewed for the following variables: age, insurance status, BMI, gestational age at delivery, birth weight, smoking history, prior abdominal surgery, existing comorbidities, preoperative hematocrit, chorioamnionitis, duration of labor and membrane rupture, dilation at time of cesarean delivery, type of skin and uterine incision, estimated blood loss, operative time, antibiotic prophylaxis, use of subcutaneous drains or sutures, endometritis, and length of stay. The primary outcome variable was any wound complication requiring opening the incision. Multiple logistic regression analysis was completed to determine which of these factors contributed to the incidence of wound complications. RESULTS: From 1994 to 2000, 239 women with a BMI greater than 35 undergoing a primary cesarean delivery were identified. The overall incidence of wound complications in this group of severely obese patients was 12.1%. Factors associated with wound complications included vertical skin incisions (odds ratio [OR] 12.4, P < .001) and endometritis (OR 3.4, P = .03). A high preoperative hematocrit was protective (OR .87, P = .03). No other factors were found to impact wound complications. CONCLUSION: Primary cesarean delivery in the severely obese parturient has a high incidence of wound complications. Our data indicate that a vertical skin incision is associated with a higher rate of wound complications than a transverse incision.

Preterm premature rupture of the membranes and antioxidants: the free radical connection.

AIM: To discuss the role of oxidant stress in preterm, premature rupture of the membranes (PPROM). RESULTS: There is evidence to suggest that preterm, premature rupture of the membranes occurs secondary to focal collagen damage in the fetal membranes. CONCLUSION: Oxidant stress caused by increased ROS formation and/or antioxidant depletion may disrupt collagen and cause premature membrane rupture. We propose that supplementation with vitamins C and E may synergistically protect the fetal membranes, and decrease the risks of PPROM.