Risk of thrombosis and bleeding in gynecologic noncancer surgery: systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide procedure-specific estimates of the risk for symptomatic venous thromboembolism and major bleeding in noncancer gynecologic surgeries. DATA SOURCES: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar. Furthermore, we performed separate searches for randomized trials that addressed the effects of thromboprophylaxis. STUDY ELIGIBILITY CRITERIA: Eligible studies were observational studies that enrolled ≥50 adult patients who underwent noncancer gynecologic surgery procedures and that reported the absolute incidence of at least 1 of the following: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding that required reintervention (including re-exploration and angioembolization), bleeding that led to transfusion, or postoperative hemoglobin level <70 g/L. METHODS: A teams of 2 reviewers independently assessed eligibility, performed data extraction, and evaluated the risk of bias of the eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine the cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors and used the Grading of Recommendations Assessment, Development and Evaluation approach to rate the evidence certainty. RESULTS: We included 131 studies (1,741,519 patients) that reported venous thromboembolism risk estimates for 50 gynecologic noncancer procedures and bleeding requiring reintervention estimates for 35 procedures. The evidence certainty was generally moderate or low for venous thromboembolism and low or very low for bleeding requiring reintervention. The risk for symptomatic venous thromboembolism varied from a median of <0.1% for several procedures (eg, transvaginal oocyte retrieval) to 1.5% for others (eg, minimally invasive sacrocolpopexy with hysterectomy, 1.2%-4.6% across patient venous thromboembolism risk groups). Venous thromboembolism risk was <0.5% for 30 (60%) of the procedures; 0.5% to 1.0% for 10 (20%) procedures; and >1.0% for 10 (20%) procedures. The risk for bleeding the require reintervention varied from <0.1% (transvaginal oocyte retrieval) to 4.0% (open myomectomy). The bleeding requiring reintervention risk was <0.5% in 17 (49%) procedures, 0.5% to 1.0% for 12 (34%) procedures, and >1.0% in 6 (17%) procedures. CONCLUSION: The risk for venous thromboembolism in gynecologic noncancer surgery varied between procedures and patients. Venous thromboembolism risks exceeded the bleeding risks only among selected patients and procedures. Although most of the evidence is of low certainty, the results nevertheless provide a compelling rationale for restricting pharmacologic thromboprophylaxis to a minority of patients who undergo gynecologic noncancer procedures.

Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery.

OBJECTIVE: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. BACKGROUND: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. METHODS: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. RESULTS: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. CONCLUSIONS: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

Risk of thrombosis and bleeding in gynecologic cancer surgery: systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide procedure-specific estimates of the risk of symptomatic venous thromboembolism and major bleeding in the absence of thromboprophylaxis, following gynecologic cancer surgery. DATA SOURCES: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar for observational studies. We also reviewed reference lists of eligible studies and review articles. We performed separate searches for randomized trials addressing effects of thromboprophylaxis and conducted a web-based survey on thromboprophylaxis practice. STUDY ELIGIBILITY CRITERIA: Observational studies enrolling ≥50 adult patients undergoing gynecologic cancer surgery procedures reporting absolute incidence for at least 1 of the following were included: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding requiring reintervention (including reexploration and angioembolization), bleeding leading to transfusion, or postoperative hemoglobin <70 g/L. METHODS: Two reviewers independently assessed eligibility, performed data extraction, and evaluated risk of bias of eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors. The GRADE approach was applied to rate evidence certainty. RESULTS: We included 188 studies (398,167 patients) reporting on 37 gynecologic cancer surgery procedures. The evidence certainty was generally low to very low. Median symptomatic venous thromboembolism risk (in the absence of prophylaxis) was <1% in 13 of 37 (35%) procedures, 1% to 2% in 11 of 37 (30%), and >2.0% in 13 of 37 (35%). The risks of venous thromboembolism varied from 0.1% in low venous thromboembolism risk patients undergoing cervical conization to 33.5% in high venous thromboembolism risk patients undergoing pelvic exenteration. Estimates of bleeding requiring reintervention varied from <0.1% to 1.3%. Median risks of bleeding requiring reintervention were <1% in 22 of 29 (76%) and 1% to 2% in 7 of 29 (24%) procedures. CONCLUSION: Venous thromboembolism reduction with thromboprophylaxis likely outweighs the increase in bleeding requiring reintervention in many gynecologic cancer procedures (eg, open surgery for ovarian cancer and pelvic exenteration). In some procedures (eg, laparoscopic total hysterectomy without lymphadenectomy), thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding venous thromboembolism and bleeding.

Timing of symptomatic venous thromboembolism after surgery: meta-analysis.

BACKGROUND: The timing at which venous thromboembolism (VTE) occurs after major surgery has major implications for the optimal duration of thromboprophylaxis. The aim of this study was to perform a systematic review and meta-analysis of the timing of postoperative VTE up to 4 weeks after surgery. METHODS: A systematic search of MEDLINE, Scopus, and CINAHL databases was performed between 1 January 2009 and 1 April 2022. Prospective studies that recruited patients who underwent a surgical procedure and reported at least 20 symptomatic, postoperative VTE events by time were included. Two reviewers independently selected studies according to the eligibility criteria, extracted data, and evaluated risk of bias. Data were analysed with a Poisson regression model, and the GRADE approach was used to rate the certainty of evidence. RESULTS: Some 6258 studies were evaluated, of which 22 (11 general, 5 urological, 4 mixed, and 2 orthopaedic postoperative surgical populations; total 1 864 875 patients and 24 927 VTE events) were eligible. Pooled evidence of moderate certainty showed that 47.1 per cent of the VTE events occurred during the first, 26.9 per cent during the second, 15.8 per cent during the third, and 10.1 per cent during the fourth week after surgery. The timing of VTE was consistent between individual studies. CONCLUSION: Although nearly half of symptomatic VTE events in first 4 weeks occur during the first postoperative week, a substantial number of events occur several weeks after surgery. These data will inform clinicians and guideline developers about the duration of postoperative thromboprophylaxis.

Hundreds of millions of surgical procedures are performed annually worldwide. Blood clots in legs and lungs represent serious, and sometimes fatal, complications of surgery. To prevent these complications, clinicians often give blood thinners to patients. To optimize the starting time and duration of use of blood thinners, it is crucial to know when blood clots occur after surgery. This study summarized the timing of blood clots after surgery based on a systematic review and meta-analysis of 22 prospective studies including thousands of patients with blood clots from various surgical fields. Of blood clots occurring within 4 weeks after surgery, 47 per cent occurred by the first, 74 per cent by the second, and 90 per cent by the third week after surgery. These research results are useful for patients, clinicians, and guideline developers to guide the starting time and duration of use of blood thinners after surgery.

Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS): introduction and methodology.

BACKGROUND: Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. METHODS: We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. DISCUSSION: This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021234119.

Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis.

OBJECTIVE: To estimate the regression, persistence, and progression of untreated cervical intraepithelial neoplasia grade 2 (CIN2) lesions managed conservatively as well as compliance with follow-up protocols. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1 January 1973 to 20 August 2016. ELIGIBILITY CRITERIA: Studies reporting on outcomes of histologically confirmed CIN2 in non-pregnant women, managed conservatively for three or more months. DATA SYNTHESIS: Two reviewers extracted data and assessed risk of bias. Random effects model was used to calculate pooled proportions for each outcome, and heterogeneity was assessed using I2 statistics. MAIN OUTCOME MEASURES: Rates of regression, persistence, or progression of CIN2 and default rates at different follow-up time points (3, 6, 12, 24, 36, and 60 months). RESULTS: 36 studies that included 3160 women were identified (seven randomised trials, 16 prospective cohorts, and 13 retrospective cohorts; 50% of the studies were at low risk of bias). At 24 months, the pooled rates were 50% (11 studies, 819/1470 women, 95% confidence interval 43% to 57%; I2=77%) for regression, 32% (eight studies, 334/1257 women, 23% to 42%; I2=82%) for persistence, and 18% (nine studies, 282/1445 women, 11% to 27%; I2=90%) for progression. In a subgroup analysis including 1069 women aged less than 30 years, the rates were 60% (four studies, 638/1069 women, 57% to 63%; I2=0%), 23% (two studies, 226/938 women, 20% to 26%; I2=97%), and 11% (three studies, 163/1033 women, 5% to 19%; I2=67%), respectively. The rate of non-compliance (at six to 24 months of follow-up) in prospective studies was around 10%. CONCLUSIONS: Most CIN2 lesions, particularly in young women (<30 years), regress spontaneously. Active surveillance, rather than immediate intervention, is therefore justified, especially among young women who are likely to adhere to monitoring. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2014: CRD42014014406.

Reoperations for Female Stress Urinary Incontinence: A Finnish National Register Study.

BACKGROUND: Subjective and objective cure rates after primary surgery for female stress urinary incontinence are good. Still, some women will undergo repeated operations for incontinence. OBJECTIVE: To study the reoperation rate after incontinence surgery and to compare the reoperation rates between different surgery types. DESIGN, SETTING, AND PARTICIPANTS: This national register-based study included all Finnish women who had surgery for stress urinary incontinence during a 23-yr study period (1987-2009), both in inpatient and outpatient hospital settings. Subcohorts for follow-up times of 5-yr and 10-yr were evaluated separately. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary operations, reoperation rate, patient age, time until reoperation. RESULTS AND LIMITATIONS: A total of 38 500 women had surgery for stress urinary incontinence from 1987 to 2009. Two thousand and seventy-six women (7.2%) had a reoperation with a rate of 7.8/1000 woman-yr. The reoperation rate was 8.3/1000 women-yr after a Burch colposuspension and 4.8/1000 after a retropubic midurethral sling. In the 10-yr follow-up, reoperation was more common after a Burch compared with a retropubic midurethral sling (odds ratio: 1.6, 95% confidence interval: 1.3-1.9). There was no difference in the reoperation rate between retropubic and transobturator midurethral slings in the 5-yr follow-up. CONCLUSIONS: Reoperation rate is lower after midurethral slings compared with Burch colposuspension. PATIENT SUMMARY: Mesh slings are surgically effective treatments for stress urinary incontinence. There are fewer reoperations after implanting these slings compared with older methods that do not use synthetic material. Different mesh slings have equally good results.

Pelvic organ prolapse surgery in Finland from 1987 to 2009: A national register based study.

OBJECTIVES: To establish the trends in pelvic floor surgery in Finnish female population and to evaluate the age-specific incidence as well as the lifetime risk for pelvic organ prolapse surgery. STUDY DESIGN: We conducted a population-based register study, which includes all Finnish women (n=77 906), who underwent surgery for pelvic organ prolapse in Finland 1987-2009. The women were identified in the Care Register for Health Care based on the procedure codes. Number of procedures, age-adjusted incidence, age-specific incidence, cumulative incidence, lifetime risk were calculated. RESULTS: A total of 93 226 surgical procedures for POP were performed. The age-adjusted incidence of prolapse surgery was 1.3/1000 women in 1987. After that there was an increase which peaked in 1996 with 1.9/1000, and a decline thereafter back to 1.3/1000 in 2009. The lifetime risk for a woman to have undergone at least one surgical procedure for prolapse was 12.8%. Surgery was most common within women aged 70 to 79 years, followed by women aged 60 to 69 years. The most popular procedure until 1991 was cervix amputation with colporraphies, surpassed thereafter by colporraphies only or with combined vaginal hysterectomy. CONCLUSION: Surgery for pelvic organ prolapse is common and more than every tenth woman underwent such surgery during lifetime.

Long-term outcome after transvaginal mesh repair of pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to report long-term subjective and objective outcomes after the transvaginal mesh (TVM) procedure in long-term. Possible late-onset complications were of particular interest. METHODS: This was a retrospective analysis of TVM performed using Prolift™ transvaginal mesh measuring subjective outcome using validated questionnaires. Objective outcome was assessed using the Pelvic Organ Prolapse Quantification (POP-Q) system using two definitions: POP-Q stage ≤ 1, and vaginal wall prolapse at or above the hymen or vaginal apex not descending below the upper third of the vagina. Complications were reported with the Prosthesis/Graft Complication Classification Code designed by the International Continence Society/International Urogynecological Association (ICS/IUGA). RESULTS: Of 195 patients, 161 (82.6 %) participated this study after a median of 7 years. The scores in questionnaires evaluating urinary (UI) or anal incontinence and constipation or pelvic floor symptoms were low, indicating favorable surgical outcomes. Altogether, 80.1 % of patients were satisfied with the procedure. Anatomical cure was 56.4 % and 69.3 % depending on the definition used. Reoperation due to POP in any compartment was performed in 16.2 % of patients. Mesh exposure rate was 23 %, most of these being asymptomatic and of late onset. CONCLUSIONS: Outcome of the TVM procedure was satisfactory. Anatomical cure was inferior to subjective cure. Mesh exposure rate was high; most exposures observed in the long-term were of late onset and were asymptomatic.

Long-term Impact of Mode of Delivery on Stress Urinary Incontinence and Urgency Urinary Incontinence: A Systematic Review and Meta-analysis.

CONTEXT: Stress urinary incontinence (SUI) and urgency urinary incontinence (UUI) are associated with physical and psychological morbidity, and large societal costs. The long-term effects of delivery modes on each kind of incontinence remain uncertain. OBJECTIVE: To investigate the long-term impact of delivery mode on SUI and UUI. EVIDENCE ACQUISITION: We searched Medline, Scopus, CINAHL, and relevant major conference abstracts up to October 31, 2014, including any observational study with adjusted analyses or any randomized trial addressing the association between delivery mode and SUI or UUI ≥1 yr after delivery. Two reviewers extracted data, including incidence/prevalence of SUI and UUI by delivery modes, and assessed risk of bias. EVIDENCE SYNTHESIS: Pooled estimates from 15 eligible studies demonstrated an increased risk of SUI after vaginal delivery versus cesarean section (adjusted odds ratio [aOR]: 1.85; 95% confidence interval [CI], 1.56-2.19; I(2)=57%; risk difference: 8.2%). Metaregression demonstrated a larger effect of vaginal delivery among younger women (p=0.005). Four studies suggested no difference in the risk of SUI between spontaneous vaginal and instrumental delivery (aOR: 1.11; 95% CI, 0.84-1.45; I(2)=50%). Eight studies suggested an elevated risk of UUI after vaginal delivery versus cesarean section (aOR: 1.30; 95% CI, 1.02-1.65; I(2)=37%; risk difference: 2.6%). CONCLUSIONS: Compared with cesarean section, vaginal delivery is associated with an almost twofold increase in the risk of long-term SUI, with an absolute increase of 8%, and an effect that is largest in younger women. There is also an increased risk of UUI, with an absolute increase of approximately 3%. PATIENT SUMMARY: In this systematic review we looked for the long-term effects of childbirth on urinary leakage. We found that vaginal delivery is associated with an almost twofold increase in the risk of developing leakage with exertion, compared with cesarean section, with a smaller effect on leakage in association with urgency.

Surgery for stress urinary incontinence in Finland 1987-2009.

INTRODUCTION AND HYPOTHESIS: To estimate the incidence rates of stress urinary incontinence (SUI) surgery among Finnish women from 1987 to 2009 by age, and to evaluate the trends in SUI surgery. METHODS: We conducted a retrospective register-based study. All SUI procedures on adult women over age 18 years in Finland were identified from the nationwide Care Register for Health Care. Age-specific incidence rates per 1,000 women were calculated for each year. The cumulative incidence of SUI surgery was calculated. RESULTS: There were 38,340 procedures for SUI in 1987-2009. The overall age-adjusted incidence rate increased 2.6-fold from 0.5/1,000 women in 1987 to 1.3/1,000 in 2002, but declined thereafter by 2009 to 0.8/1,000. There was a six-fold increase in the incidence rate in the age group 60-69 years and a ten-fold increase in the age group 70-79 years from 1987 to 2002. These marked increases in operation rates coincided with the increased use of tension-free vaginal tape (TVT). In 2002, TVT accounted for 96 % of all SUI procedures. Mid-urethral slings with transobturator techniques surpassed TVT in popularity in 2007. The life-long cumulative incidence of SUI surgery was 9.9 % in 2002 and 6.3 % in 2009. CONCLUSIONS: The incidence rates of SUI surgery increased significantly in Finland, especially among women aged 60 to 79 years. Mid-urethral slings have become the dominant procedure.

Quantification of Ureaplasma urealyticum DNA in the amniotic fluid from patients in PTL and pPROM and its relation to inflammatory cytokine levels.

OBJECTIVE: To study the effect of the amniotic fluid quantity of Ureaplasma urealyticum DNA on inflammatory response levels in women with preterm labor (PTL) and preterm prelabor rupture of membranes (pPROM). DESIGN: A prospective multi-center follow up study. SETTING: Sahlgrenska University Hospital, Goteborg, Sweden and Turku University Hospital, Turku, Finland. SAMPLE: Eleven U. urealyticum positive samples obtained after transabdominal amniocenteses in 197 women presenting with PTL and pPROM. METHODS: The U. urealyticum positive samples were analyzed with real-time polymerase chain reaction, using the Lightcycler instrument with primers specific for U. urealyticum 16 S rDNA. The amniotic fluid samples were analyzed for tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1beta and IL-10 with enzyme-linked immunosorbent assays. MAIN OUTCOME MEASURES: Correlation between U. urealyticum DNA concentrations in the amniotic fluid and inflammatory cytokine levels. RESULTS: The concentrations of U. urealyticum DNA varied between 0.024 and 934 microg/mL. A significant correlation between U. urealyticum DNA and TNF-alpha level was observed. No correlation with the other cytokines was found. Women with PTLhad higher levels of U. urealyticum DNA and a different cytokine pattern than women with pPROM. CONCLUSIONS: U. urealyticum in the amniotic fluid induces an inflammatory reaction in a dose dependent manner and the quantity of U. urealyticum DNA is well correlated with the level of the inflammatory cytokine TNF-alpha.

Ureaplasma urealyticum: no independent role in the pathogenesis of bronchopulmonary dysplasia.

BACKGROUND: Ureaplasma urealyticum has been linked to short and long-term morbidity of preterm infants. We wanted to analyze if it has an independent role in the pathogenesis of bronchopulmonary dysplasia if prenatal history with possible exposure to intrauterine infection is taken into account. METHODS: Lower respiratory tract colonization with U. urealyticum was analyzed from 49 infants born before the 30th week of gestation. The need for supplemental oxygen at the age of 28 days and 36 gestational weeks was studied. RESULTS: Forty-five percent of the 33 infants born after spontaneous onset of labor were colonized with U. urealyticum, while none of the electively born were. If analyzed based on the Ureaplasma colonization, bronchopulmonary dysplasia was more common in the colonized infants at the age of 28 days (OR 4.57, 95% CI 1.18-17.68), but not at the gestational age of 36 weeks (OR 1.00). Based on the prenatal history, the OR of bronchopulmonary dysplasia in infants born after spontaneous onset of labor was greater than in infants born electively both at the age of 28 days (OR 4.33, 95% CI 0.83-22.75) and at 36 weeks of gestation (OR 2.8, 95% CI 0.30-26.42). CONCLUSIONS: If possible exposure to intra-amniotic inflammation is taken into account, U. urealyticum seems not to have an independent role in the pathogenesis of bronchopulmonary dysplasia. Its role has been overemphasized, as it is the most common cause of intra-amniotic bacterial infection.

Transfer of proinflammatory cytokines across term placenta.

OBJECTIVE: Increased concentrations of proinflammatory cytokines in amniotic fluid indicate the presence of intra-amniotic inflammation and increase the risk of preterm birth, cerebral palsy, and bronchopulmonary dysplasia. The purpose of this study was to find out if the proinflammatory cytokines, tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, transfer across the placenta, and thereby determine whether intra-amniotic inflammatory response, measured from the amniotic fluid, is of maternal or fetal origin. METHODS: Nineteen placentas from healthy women undergoing elective cesarean delivery at term with intact membranes and without labor, were dually perfused ex vivo in an open circulation system for either 30 minutes or 2 hours. Tumor necrosis factor-alpha, IL-1beta, and IL-6 were added to maternal or fetal circulation in a concentration usually found in chorioamnionitis. As a reference, placentas without added cytokine were also perfused. The concentrations of cytokines were determined by enzyme immunoassays (enzyme-linked immunosorbent assay [ELISA]). RESULTS: After the addition of the cytokine to the arterial perfusate, the venous concentration on the same side of the placenta increased rapidly and reached a plateau at 10 minutes. No transfer of any cytokine in either direction was detected. Some endogenous release of IL-6 was observed in response to the perfusion. CONCLUSION: Proinflammatory cytokines do not cross normal term placenta.