Does amniotic fluid alpha-fetoprotein have diagnostic or prognostic value at the time of second midtrimester genetic amniocentesis?

In order to assess the usefulness of amniotic fluid alpha-fetoprotein (AFP) levels at the time of midtrimester genetic amniocentesis, 4,430 cases were retrospectively studied to compare the high, normal or low AFP values with the karyotype characteristics and fetal anatomy using ultrasound (US) scanning and confirmed by postnatal evaluation or necroscopy in the case of termination of pregnancy. All the cases presenting malformations were correctly diagnosed by US examinations. AFP levels over the 2nd standard deviation (SD) were found in 112 cases (2.52%) and below the 2nd SD in 11 cases (0.24%). The characteristics of these cases are presented and discussed. According to our results, it is concluded that routine assessment of AFP at the time of midtrimester genetic amniocentesis, if coupled with optimal US scanning, is no longer justified.     

Is pregnancy loss after amniocentesis related to the volume of amniotic fluid obtained?

Objective  The objective was to determine whether pregnancy loss after amniocentesis is related to the amount of amniotic fluid obtained during the procedure. Study design  The study enrolled 2,400 women, all in their sixteenth to twentieth week of pregnancy. A 22G spinal needle was inserted for amniocentesis. The amount of amniotic fluid obtained from 1,200 patients in Group 1 was 4 ml and from 1,200 patients in Group 2 was 20 ml. In Group 1, the amniotic fluid was analyzed with a quantitative fluorescent polymerase chain reaction technique, whereas in Group 2, conventional cytogenetic analysis was used. SPSS 16.0 (chi-square and t tests) was used for statistical analyses. Results  In Group 1, postamniocentesis premature rupture of membranes (PROM) occurred in four patients (0.3%). There was one unintended fetal loss and postamniocentesis miscarriage rate was 0.08%. In Group 2, postamniocentesis PROM occurred in 12 patients (1%). Eight of these patients experienced fetal loss (0.67%). Fetal loss rates were higher in Group 2 compared with Group 1. These results did not show statistical differences between the groups according to chi-square test (P > 0.05). Conclusion  Although statistical analysis denies the positive effect of obtaining small amounts of amniotic fluid to reduce fetal loss rates in patients after amniocentesis, six to eight times lower fetal loss rates based on the amount of fluid obtained cannot be undervalued.     

Amniotic fluid interleukin-6 and tumor necrosis factor-α at mid-trimester genetic amniocentesis: Relationship to intra-amniotic microbial invasion and preterm delivery

Objective

To determine the value of amniotic fluid interleukin-6 (AF IL-6) and tumor necrosis factor-α (AF TNF-α) in the diagnosis of microbial invasion of the amniotic cavity and in the prediction of preterm delivery (PTD).

Study design

Following amniocentesis, a sample of amniotic fluid was sent for aerobic and anaerobic bacterial cultures along with Ureaplasma urealyticum culture and it was also assessed for IL-6 and TNF-α.

Results

Forty-eight women who delivered preterm (<37 weeks) were matched with 96 controls. The AF IL-6 and TNF-α concentrations of women with spontaneous PTD were significantly higher than those who delivered at term (IL-6: 176.3 pg/ml [130.6–208.6] vs. 52.3 pg/ml [37.2–92.3]; TNF-α: 8.8 pg/ml [7.2–10.7] vs. 5.5 pg/ml [5.0–6.3]). AF IL-6 and TNF-α concentrations of >99.3 pg/ml and of >6.6 pg/ml respectively, had a sensitivity of 89.6% and 81.3% and a specificity of 80.3% and 79.2% for the prediction of spontaneous PTD. Moreover, AF IL-6 and TNF-α concentrations of >99.3 pg/ml and of 6.3 pg/ml respectively, had a sensitivity of 91.9% and 78.4% and a specificity of 73.8% and 70.1% for the prediction of a positive AF culture.

Conclusions

Elevated mid-trimester concentrations of AF IL-6, or/and of TNF-α can identify women at risk for intra-amniotic infection and for spontaneous PTD.     

Are vaginal fluid procalcitonin levels useful for the prediction of subclinial infection in patients with preterm premature rupture of membranes?

AIM: To compare vaginal fluid procalcitonin concentrations in cases of preterm premature rupture of membranes (pPROM) and premature rupture of membranes (PROM) at term, and to determine whether the procalcitonin concentrations are of value in the diagnosis of pPROM cases suspected of subclinical intrauterine infection or in the prediction of the pPROM-to-delivery interval. METHODS: Forty-eight patients with pPROM and 30 with PROM at term were enrolled in this study. In pPROM group, analysis was conducted of procalcitonin concentrations with reference to serum leucocytosis, serum C-reactive protein levels and vaginal fluid culture, as well as to the presence/absence of neonatal congenital infection or histological chorioamnionitis. The outcomes of pPROM cases were also recorded with reference to pPROM-to-delivery interval. RESULTS: Procalcitonin levels in the pPROM group were significantly higher than in cases of amniorrhexis at term (1.50 vs 0.83 ng/mL; P < 0.001). In the pPROM group procalcitonin concentrations between the patients with and without positive laboratory indices of infection were comparable. Also, no significant correlation was observed between procalcitonin and leucocytosis (r = -0.14; P = 0.33) or C-reactive protein (r = -0.17; P = 0.24). Procalcitonin concentrations of patients who gave birth to newborns with infection were comparable to those in women whose newborns were healthy. In patients with histological chorioamnionitis, procalcitonin concentrations were comparable to those without inflammatory changes. CONCLUSION: These findings suggest that the value of vaginal fluid procalcitonin determinations is unsatisfactory in the diagnostics of pPROM cases suspected of subclinical intrauterine infection, as well as for the prediction of pPROM-to-delivery interval, newborn's congenital infection or histological chorioamnionitis.     

Are reported preterm birth rates reliable? An analysis of interhospital differences in the calculation of the weeks of gestation at delivery and preterm birth rate

We investigated the possibility of preterm birth misclassification as a determinant of variation in its reported rates. Using a database of 497,105 deliveries from 17 hospitals, the best estimate of gestational age made at delivery and entered into the database at that time was recalculated from the menstrual dates and mid-trimester ultrasound scan. The recalculated completed weeks of gestation at delivery was compared with that made at birth. Calculation of estimated gestational age varied between hospitals due to inconsistencies in 'rounding' and 'truncating' the weeks of gestation at delivery. This resulted in preterm birth misclassification rates of up to 10.1%.     

Maternal plasma interleukin-6, interleukin-1β and C-reactive protein as indicators of tocolysis failure and neonatal outcome after preterm delivery

Objective. To investigate whether maternal serum interleukin-6 (IL-6), interleukin-1β (IL-1β) and high sensitive C-reactive protein (CRP) could be used as markers of tocolysis failure and adverse neonatal outcome in pregnancies with preterm labor (PL).

Methods. Forty-seven maternal blood samples taken because of PL at admission and delivery were analyzed. Control samples were taken from 20 gravidas with normal pregnancies. Differences in interleukins and CRP levels with or without chorioamnionitis, connatal infection or periventricular leukomalacia (PVL) were analyzed. Cut-off values were estimated for prediction of tocolysis failure and adverse neonatal outcome.

Results. All three parameters were significantly higher in patients delivering prematurely than in patients delivering at term. All three parameters were significantly higher with than without histologic chorioamnionitis (p < 0.001), with than without connatal infection (p < 0.01), with than without PVL (p < 0.01 for IL-6 and IL-1β, p < 0.05 for CRP), and in pregnancies with preterm premature rupture of membranes (PPROM) delivered within 48 hours compared to those more prolonged (p < 0.01). Choosing 50.9 pg/mL of IL-6 and a CRP of 19.7 as cut-offs in maternal blood admission concentrations for neonatal PVL, resulted in sensitivity of 81% and specificity of 91% and sensitivity of 91% and specificity of 81%, respectively. At respective maternal blood admission cut-off levels of 27.8 pg/mL of IL-6 and 8.9 of CRP, both parameters were effective predictors of connatal infection.

Conclusions. Maternal blood IL-6 and CRP could become useful in predicting tocolysis failure and intrauterine treat for the fetus.     

An elevated amniotic fluid prostaglandin F2α concentration is associated with intra-amniotic inflammation/infection,and clinical and histologic chorioamnionitis,as well as impending preterm delivery in patients with preterm labor and intact membranes

Objective: To determine whether an elevated amniotic fluid concentration of prostaglandin F_2α (PGF_2α) is associated with intra-amniotic inflammation/infection and adverse pregnancy outcomes in patients with preterm labor and intact membranes.

Materials and methods: The retrospective cohort study included 132 patients who had singleton pregnancies with preterm labor (<?35 weeks of gestation) and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as for genital mycoplasmas. Intra-amniotic inflammation was defined by an elevated amniotic fluid matrix metalloproteinase-8 (MMP-8) concentration (>23?ng/mL). PGF_2α was measured with a sensitive and specific immunoassay. The amniotic fluid PGF_2α concentration was considered elevated when it was above the 95th percentile among pregnant women at 15–36 weeks of gestation who were not in labor (≥170?pg/mL).

Results: (1) The prevalence of an elevated amniotic fluid PGF_2α concentration was 40.2% (53/132) in patients with preterm labor and intact membranes; (2) patients with an elevated amniotic fluid PGF_2α concentration had a significantly higher rate of positive amniotic fluid culture [19% (10/53) versus 5% (4/79); p?=?0.019], intra-amniotic inflammation/infection [49% (26/53) versus 20% (16/79); p?=?0.001], spontaneous preterm delivery, clinical and histologic chorioamnionitis, and funisitis, as well as a higher median amniotic fluid MMP-8 concentration and amniotic fluid white blood cell count and a shorter amniocentesis-to-delivery interval than those without an elevated concentration of amniotic fluid PGF_2α (p?<?0.05 for each); and (3) an elevated amniotic fluid PGF_2α concentration was associated with a shorter amniocentesis-to-delivery interval after adjustment for the presence of intra-amniotic inflammation/infection [hazard ratio 2.1, 95% confidence interval (CI) 1.4–3.1; p?=?0.001].

Conclusion: The concentration of PGF_2α was elevated in the amniotic fluid of 40.2% of patients with preterm labor and intact membranes and is an independent risk factor for intra-amniotic inflammation/infection, impending preterm delivery, chorioamnionitis, and funisitis.     

Relationship between estrogen receptor-α polymorphism and serum levels of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, C-reactive protein and homocysteine in postmenopausal women

Background and aim. Genetic variation in the estrogen receptor-α gene (ERα) may influence the risk of cardiovascular diseases in postmenopausal women. This effect, at least in part, may be dependent on the decrease in expression of injury and inflammatory markers in the vascular wall. The aim of the present study was to evaluate the relationship between ERα PvuII and XbaI polymorphisms and serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP) and homocysteine in postmenopausal women.

Subjects and methods. Subjects of the study were 64 postmenopausal women. PvuII and XbaI ERα gene polymorphisms were analyzed by polymerase chain reaction–restriction fragment length polymorphism.

Results. Mean sVCAM-1 level was significantly higher in pp homozygotes in comparison with PP homozygotes and Pp heterozygotes, as well as higher in xx homozygotes in comparison with XX homozygotes and Xx heterozygotes. Levels of sVCAM-1 were also significantly higher in women with px haplotype compared with PX and Px haplotypes. There were no relationships between investigated genotypes or haplotypes and levels of sICAM-1, CRP and homocysteine.

Conclusion. The results of our study suggest that genetic variation in ERα gene may influence blood levels of VCAM-1 in women after the menopause.     

Does ligation of the hypogastric artery at the time of radical hysterectomy and lymphadenectomy decrease blood loss? Results of a prospective randomized trial

A prospective, randomized study of patients undergoing radical hysterectomy for gynecologic malignancies was undertaken from 10/95 to 11/96 to determine if ligation of the hypogastric arteries at the time of radical hysterectomy decreases blood loss. Patients were randomized to either ligation of the hypogastric artery (Group 1) or no ligation (Group 2) prior to a standard Piver type III radical hysterectomy. Surgeries were performed by Board certified gynecologic oncologists with gynecologic oncology fellows and/or OB/GYN residents. Patients were analyzed for demographic characteristics and intraoperative and postoperative parameters. Statistical analysis was performed with independent samples t -test, Mann-Whitney rank sum test, Chi square and Fisher exact test. Twenty-one patients were randomized to group 1 and 22 to group 2. Groups were similar with respect to demographics and preoperative parameters except for age. There were no differences among the groups with respect to intraoperative and postoperative parameters. The mean estimated blood loss for group 1 was 600 ml and 550 ml for group 2 ( P = NS). Hypogastric artery ligation (HAL) at the time of radical hysterectomy for gynecologic malignancy does not reduce blood loss.     

Are plasma levels of visfatin and retinol-binding protein 4 (RBP4) associated with body mass,metabolic and hormonal disturbances in women with polycystic ovary syndrome?

Objective

To analyze potential interactions of visfatin and retinol-binding protein 4 (RBP4) levels with body mass, metabolic, and hormonal status in normal weight and obese women with PCOS.

Study design

Body composition was determined by bioimpedance in 83 women (44 obese) diagnosed with PCOS and in 67 women (36 obese) without PCOS. In addition, serum glucose, lipids, androgens, FSH, LH, SHBG, insulin, visfatin, and RBP4 were measured in a fasting state and the free androgen index (FAI) was calculated, as was insulin resistance using the HOMA-IR assessment.

Results

Plasma RBP4 levels were significantly higher in women of normal weight compared to obese subjects when both were diagnosed with PCOS (14.1 ± 4.6 vs.10.9 ± 4.5 ng/mL, p < 0.001); while in non-PCOS subjects the opposite was found (10.8 ± 4.5 vs. 18.4 ± 11.6 ng/mL, p < 0.01; respectively). Plasma visfatin levels were similar in PCOS and non-PCOS subjects. In non-PCOS subjects, positive correlations between RBP4 level and anthropometric parameters were observed. In PCOS, RBP4 levels inversely correlated with serum insulin levels and HOMA-IR values. No correlation was found between plasma visfatin levels and anthropometric parameters in all study groups. Similarly, no correlation was found in PCOS and non-PCOS subgroups. Additionally, there was an inverse correlation between RBP4 and LH concentrations and LH/FSH ratio in all study subjects.

Conclusions

Plasma visfatin level is not a useful biomarker of insulin resistance and hyperandrogenism. RBP4 level reflects visceral body fat content in non-PCOS women. Decreasing RBP4 release along with increasing insulin resistance and hormonal disturbances may be a compensatory mechanism preventing deterioration in obese PCOS.     

Amniotic cavity cultures, blood cultures, and surface swabs in preterm infants--useful tools for the management of early-onset sepsis?

AIMS: To evaluate the potential benefit of amniotic fluid and amniotic/placental membrane cultures for the management of early-onset sepsis in preterm infants. METHODS: The results of amniotic cavity cultures obtained during cesarean section and of peripheral blood cultures and surface swabs obtained from the preterm infant at the time of admission were analyzed with respect to the diagnosis of clinical sepsis in 221 preterm infants <34 weeks of gestation. RESULTS: 136 (61.5%) patients had negative amniotic cavity culture results or growth of contaminants, 56 (25.3%) had growth of Ureaplasma urealyticum, and 29 (13.1%) of other pathogens. The corresponding numbers for surface swabs were 82.8%, 11.6%, and 5.6%. A positive blood culture was found in only two neonates. Fifty-four patients (24.4%) had clinical early-onset sepsis. Patients with amniotic cavity culture results that were positive for other pathogens were significantly more likely to experience clinical sepsis than patients with negative culture results (51.7% vs 15.1%, OR 6.1, p<0.0001). Regarding surface swabs, this correlation did not reach statistical significance. CONCLUSION: The strong association between positive amniotic cavity culture results and clinical early-onset sepsis supports the existence of a causal relation and provides evidence for the potential value of amniotic and/or placental membrane sampling in the management of early-onset sepsis in preterm infants. Surface swabs add no additional information and hence should not be performed routinely.     

Does intra-operative radiation at the time of pelvic exenteration improve survival for patients with recurrent,previously irradiated cervical,vaginal, or vulvar cancer?

Objective

To determine whether intra-operative radiation therapy (IORT) at the time of pelvic exenteration (PE) or laterally extended endopelvic resection (LEER) improves progression-free survival (PFS) in patients with recurrent, previously irradiated gynecologic cancers.

Methods

We conducted a single institution retrospective review of patients who had undergone a complete PE for locally recurrent gynecologic cancer. Demographic and clinicopathologic data were collected.

Results

32 patients were identified (2000–2012); 21 (66%) cervical cancer, 8 (25%) vaginal, and 3 (9%) vulvar cancer. All patients were previously irradiated. Twenty-one (66%) received IORT. Mean age was 51. Eight patients had a LEER, all with IORT. Median PFS and OS, respectively, for those with PE alone was 33 and 41 vs. 10 and 10 months for PE + IORT compared to 9 and 17 months for LEER + IORT (P = .04). Increasing tumor size negatively impacted PFS (hazard ratio 1.3; 95%CI 1.12–1.52). Margin status was not associated with survival. No patients undergoing LEER + IORT recurred only locally whereas 62% recurred with a distant component (+/− local). Patients with PE alone had mainly local (36%) and few (9%) distant recurrences compared to 31% local and 38% distant (+/− local) recurrences for those with PE + IORT.

Conclusions

We failed to demonstrate that IORT changes survival and recurrence outcomes. However, patients with clinical indications for IORT at the time of PE have worse prognosis compared to those who do not require IORT. If the need for IORT is anticipated, the surgeon may consider performing a LEER to decrease local recurrence if cure is the goal or consider palliative treatment options.