The Frequency and Clinical Significance of Intra-Uterine Infection and Inflammation in Patients with Placenta Previa and Preterm Labor and Intact Membranes

ObjectiveHistologic placental and/or intra-amniotic inflammation is frequently documented during ascending intra-uterine infections in patients with preterm labor and intact membranes. Placenta previa can be a clinical situation that shows the successive schema of histologic placental and intra-amniotic inflammation during the process of ascending intra-uterine infections. However, a paucity of information exists about the frequency and clinical significance of intra-uterine infections and inflammation in patients with placenta previa and preterm labor and intact membranes. The purpose of this study was to examine this issue.Study designAmniocentesis was performed on 42 patients with placenta previa and preterm labor and intact membranes (gestational age < 37 weeks). Amniotic fluid (AF) was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and AF white blood cell (WBC) count and matrix metalloproteinase-8 (MMP-8) concentrations were determined. The diagnosis of intra-amniotic inflammation was made in patients with an elevated AF MMP-8 (≥23 ng/ml). Non-parametric statistics were used for analysis.Results1) Intra-amniotic inflammation was present in 16.7% (7/42), proven AF infection in 4.9% (2/41), and histologic chorioamnionitis in 19.0% (8/42) of patients with placenta previa and preterm labor; 2) Patients with intra-amniotic inflammation had significantly higher rates of a positive AF culture, histologic chorioamnionitis, funisitis, and a shorter interval-to-delivery than those without intra-amniotic inflammation (p < 0.05 for each); 3) Among patients with histologic chorioamnionitis, inflammation of the choriodecidua, which was exposed to the cervical canal, existed in all cases (8/8), but inflammation of the chorionic plate existed in 63% of patients (5/8); 4) Patients with inflammation of the chorionic plate had significantly higher median AF MMP-8 concentrations and WBC counts, and higher rates of intra-amniotic inflammation than those in whom inflammation was restricted to choriodecidua (p < 0.05 for each).ConclusionsPlacental inflammation was present in 19.0% and intra-amniotic inflammation was present in 16.7% of patients with placenta previa and preterm labor and intact membranes. The intra-amniotic inflammatory response was stronger when inflammation was present in the chorionic plate and choriodecidua, than when it was restricted to the choriodecidua only, which was exposed to the cervical canal in placenta previa.     

An elevated maternal serum C-reactive protein in the context of intra-amniotic inflammation is an indicator that the development of amnionitis,an intense fetal and AF inflammatory response are likely in patients with preterm labor: clinical implications

Abstracts

Objective: We propose that an elevated maternal serum C-reactive protein (CRP) concentration in the context of intra-amniotic inflammation (IAI) is a predictor for amnionitis development, known to be the most advanced stage of maternal inflammatory response during the progression of acute histologic chorioamnionitis in preterm gestations.

Methods: Study population consisted of 53 singleton gestations with IAI, who underwent amniocentesis due to preterm labor and intact membranes (PTL) and delivered preterm-neonates (<34.5 weeks) within 5?days of amniocentesis. The frequency of amnionitis and the intensity of fetal and amniotic fluid (AF) inflammatory response were examined according to the presence or absence of an elevated maternal serum CRP (≥0.7?mg/dL) at the time of amniocentesis. IAI was defined as an elevated AF matrix metalloproteinase-8 (MMP-8) (≥23?ng/mL), and fetal inflammatory response syndrome (FIRS) defined as an elevated umbilical cord plasma CRP (≥200?ng/mL).

Results: (1) Patients (73.6%, 39/53) with an elevated maternal serum CRP had a significantly higher rate of amnionitis (59.0% versus 7.1%; p?<?0.005), but not funisitis (46.2% versus 28.6%; p?>?0.05), and higher median AF MMP-8 and umbilical cord plasma CRP concentration at birth than patients (26.4%,14/53) without that (AF MMP-8 (ng/mL): 373.1 versus 138.6: p?=?0.05; umbilical cord plasma CRP (ng/mL): 363.4 versus 15.5: p?<?0.05); (2) Multiple logistic regression analysis demonstrated that an elevated maternal serum CRP was a better independent predictor of amnionitis (odds ratio (OR), 12.5: 95% confidence interval (CI), 1.1–141.0; p?<?0.05) than FIRS (OR, 3.6: 95% CI, 0.6–20.2; p?=?0.150) and any other AF tests.

Conclusions: An elevated maternal serum CRP concentration in the context of IAI is an indicator that the development of amnionitis, an intense fetal and AF inflammatory response are likely in patients with PTL.     

Necrotizing funisitis is an indicator that intra-amniotic inflammatory response is more severe and amnionitis is more frequent in the context of the extension of inflammation into Wharton's jelly

ObjectiveNecrotizing funisitis (NF) is defined as the presence of an arc (i.e., crescent/band/ring/halos) of infiltrated neutrophils and/or associated debris in Wharton's jelly (WJ) of umbilical-cord (UC). However, no information exists about the comparison in intra-amniotic inflammatory-response (IAIR) and inflammation in extra-placental membranes between the presence and absence of NF in the context of inflammation in WJ among spontaneous preterm births (PTBs). The objective of current study is to examine this issue.Materials and methodsWe examined IAIR and the frequency of amnionitis according to the progression of inflammation in UC (i.e. stage-1, umbilical phlebitis [inflammation in umbilical-vein(UV)] only; stage-2, involvement of at least one umbilical-artery[UA] and either the other UA or UV without extension into WJ; stage-3, the extension of inflammation into WJ without NF; stage-4, the extension of inflammation into WJ with NF) in 120singleton spontaneous PTBs (<37weeks). IAIR was gauged by AF MMP-8 (ng/ml) within 3days before birth.Results1) Stage-1, stage-2, stage-3, and stage-4 were present in 20%(24/120), 6%(7/120), 61%(73/120), and 13%(16/120) of cases respectively; 2) AF MMP-8 continuously increased (stage-1 vs. stage-2 vs. stage-3 vs. stage-4; median[ng/ml], range[ng/ml]; 207.2[16.8–1196.5] vs. 444.1[8.5–2608.0] vs. 458.8[0.4–3116.7] vs. 1859.7[912.3–5304.8]; Spearman's rank correlation-test, α = 0.454, P = 0.006), and the frequency of increased AF MMP-8 (≥854.1 ng/ml) elevated (stage-1 vs. stage-2 vs. stage-3 vs. stage-4; 13%[1/8] vs. 33%[1/3] vs. 32%[6/19] vs. 100%[5/5]; Linear-by-linear-association, P = 0.012) with the progression of inflammation in UC; 3) Moreover, there was a stepwise increase in the frequency of amnionitis according to the progression of inflammation in UC (stage-1, 33%[8/24]; stage-2, 43%[3/7]; stage-3, 62%[45/73]; stage-4, 81%[13/16]; Linear-by-linear-association, P = 0.001).ConclusionNF is an indicator that IAIR is more severe and amnionitis is more frequent in the context of the extension of inflammation into WJ. Therefore, current study confirms that NF is the most advanced stage in the progression of inflammation within UC.     

Cervicovaginal matrix metalloproteinase-9 and cervical ripening in human term parturition

ObjectiveTo investigate the changes of matrix metalloproteinase-9 (MMP-9) in cervicovaginal fluid during pregnancy and its association with parturition.Study designA prospective study was conducted on nulliparous women between 16 and 42 weeks with normal singleton pregnancies in the following categories: (1) preterm control (n = 39); (2) term labor induction without labor or rupture of membranes (n = 68); (3) term spontaneous labor with intact membranes (n = 42); (4) term premature rupture of membranes (n = 24). The MMP-9 concentration in the cervicovaginal fluid was measured by immunoassay.Results(1) Cervicovaginal MMP-9 did not change significantly with advancing gestation until 37 weeks, and significantly increased after 37 weeks. (2) Cervicovaginal MMP-9 levels were similar in women with no labor, spontaneous labor, and premature rupture of membranes at term. (3) For the induced labor group, a high Bishop score (≥4) was significantly correlated with cervicovaginal MMP-9. However, an elevated cervicovaginal MMP-9 did not predict achieving active phase of labor or vaginal delivery after labor induction.ConclusionCervicovaginal MMP-9 correlated with cervical ripening before labor at term. However, cervicovaginal MMP-9 did not change with spontaneous labor or rupture of membranes at term and did not predict success of labor induction.     

Acute chorioamnionitis and intra-amniotic inflammation are more severe according to outside-in neutrophil migration within the same chorio-decidua

ObjectiveNo information exists about whether acute histologic chorioamnionitis (acute-HCA) is more advanced and severe, and intra-amniotic inflammation is more frequent and intense according to outside in neutrophil migration within the same chorio-decidua. The objective of current study is to examine this issue.Materials and methodsWe included 106 singleton preterm-births (gestational age at delivery: 20–34 weeks) due to either preterm-labor or preterm-PROM in the context of acute chorio-deciduitis. Study-population was divided into 3 groups according to outside-in neutrophil migration within chorio-decidua as follows: 1) group-1: ‘inflammation restricted to the decidua’ (n = 22); 2) group-2: ‘inflammation restricted to the MT of chorion and the decidua’ (n = 31); 3) group-3: ‘inflammation in the CT of chorion’ (n = 53). We examined the frequency of inflammation in each placental compartment beyond chorio-decidua (i.e., amnion, umbilical cord, and chorionic-plate), and total grade (1–8) of acute-HCA. Moreover, the frequency of intra-amniotic infection (defined as positive amniotic-fluid culture for aerobic and anaerobic bacteria and genital mycoplasmas) and intra-amniotic inflammation (defined as amniotic fluid WBC ≥ 19 cells/mm³), and an intra-amniotic inflammatory response gauged by amnioticfluid WBC count (cells/mm³) were examined in 50 amniotic fluid samples within 7 days of birth.ResultsAmnionitis, funisitis and chorionic plate inflammation were more frequent (each for P < 0.01) and median total grade of acute-HCA was increased (P < 0.001) according to outside-in neutrophil migration within chorio-decidua (group-1vs.group-2vs.group-3). Moreover, intra-amniotic infection and inflammation were more frequent (each-for P < 0.05) and median amniotic-fluid WBC count was increased (P < 0.01) according-to outside-in neutrophil-migration within chorio-decidua (group-1 vs. group-2 vs. group-3).ConclusionAcute-HCA is more advanced and severe, and intra-amniotic inflammation is more frequent and intense according to outside in neutrophil migration within the same chorio-decidua. This finding suggests that what is now acute chorio-deciduitis should be subdivided.     

The role of matrix metalloproteinase-2 in the culture media in embryo implantation rate in normogonadotrophic cases undergoing ICSI

ObjectiveThe aim of the study is to correlate the changes in the biochemical marker MMP-2 in the culture media with the outcome of normogonadotrophic cases undergoing ICSI.MethodologyA prospective study of infertile females was conducted in El-Shatby Maternity University Hospital between October 2011 and May 2012 utilizing a sample of 40 normogonadotrophic infertile women (22 females with unexplained infertility and 18 females with tubal factor infertility).ResultsClinical pregnancy was 57.5%; 15 out of the 22 females with unexplained infertility and 8 out of the 18 females with tubal factor infertility. There was no abortion, ectopic or chemical pregnancy. Ongoing pregnancy after 14 weeks of gestational age was 100%.Total (MMP-2) ranged between (4.1 and 21.1) and (3.5–37) ng/ml with the mean of (9.91 ± 5.48) and (13.91 ± 8.87) ng/ml for non pregnant and pregnant groups respectively. There were no statistical significant differences between the two groups regarding total MMP-2 (P = 0.055).The mean of MMP-2/embryo/h ranged between (0.05 ± 0.05) and (0.06 ± 0.08) ng/ml/embryo/h for non pregnant and pregnant groups respectively. There were no statistical significant differences between the two groups regarding MMP-2/embryo/h (P = 0.234).ConclusionsMMP-2 concentration in the culture media cannot be used as a biochemical marker for embryo selection or prediction of implantation in the normogonadotrophic cases undergoing ICSI.RecommendationsResults of the present study suggest searching for other markers in the culture media for better embryo selection and for prediction of implantation in the normogonadotrophic cases undergoing ICSI.     

Immunoexpression of Matrix Metalloproteinase-2 (MMP-2) in Malignant Ovarian Epithelial Tumours

ObjectivesThis study was designed to evaluate the expression of matrix metalloproteinase-2 (MMP-2) in malignant ovarian epithelial tumours and to detect the relation between the degree of MMP-2 expression and the histological grade and surgical stage of the studied cases.MethodsThis study was conducted in Ain Shams University Maternity Hospital in Cairo, Egypt, between March 2004 and December 2005.Thirty patients with malignant ovarian epithelial tumours diagnosed after histopathological examination of the specimens were included in this study. The pathological specimens were additionally stained by the immunoperoxidase technique for MMP-2 using a monoclonal antibody against activated MMP-2. The staining intensity of MMP-2 was correlated with the clinical and pathological parameters of the studied cases, including patient’s age, surgical stage, histological grade, omental metastasis, and lymph node metastasis.ResultsFour of the 30 cases (13.3%) were entirely negative for MMP-2, 14 (46.7%) showed weak staining for MMP-2, five (16.7%) showed moderate staining, and seven cases (23.3%) showed intense staining. The results were compared with the clinical and pathological parameters, including patient’s age, tumour stage, and histological grade.The MMP-2 expression was found to be significantly correlated with the histological grade (r = 0.52, P < 0.05) and with the surgical stage (r = 0.72, P < 0.001) of the studied tumours, but not with the age of the patients. Patients with advanced ovarian tumours, ascites, omental metastasis, distant metastasis, or uterine metastasis had a significantly higher incidence of MMP-2 expression (P< 0.05).There was no significant difference in MMP-2 expression between patients when compared in terms of lymph node metastasis or the presence of bilateral tumours.ConclusionMMP-2 is a marker of proliferation, invasiveness, and metastasis. In this study, there was a direct correlation between the degree of expression of MMP-2 and histologically undifferentiated or advanced stages of ovarian epithelial tumours.     

Funisitis in term pregnancy is associated with microbial invasion of the amniotic cavity and intra-amniotic inflammation

Objective.?Funisitis is the histologic counterpart of the fetal inflammatory response syndrome, which is a multisystemic disorder associated with impending preterm delivery and adverse neonatal outcome. The purpose of this study was to examine the relationship between funisitis and the microbiologic status of amniotic fluid (AF) and AF white blood cell (WBC) count in patients at term.

Methods.?The relationship between the presence of funisitis, AF culture, and AF WBC count was examined in 832 consecutive patients who delivered a term neonate within 72 hours of amniocentesis. AF was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton's jelly. AF WBC count was analyzed in a hemocytometer chamber. Nonparametric statistics were used for data analysis.

Results.?Funisitis was present in 4% (30/832) of cases. A positive AF culture was more common in cases with funisitis than in those without funisitis (17% vs. 5%; p < 0.05). Patients with funisitis had a significantly higher median AF WBC count than those without funisitis (median >1000 cells/mm³ vs. median 2 cells/mm³; p < 0.001). The frequency of funisitis and of a positive AF culture was 1% in women without labor and with intact membranes and the frequencies and the median AF WBC count increased in the presence of labor or rupture of membranes.

Conclusion.?Funisitis is present in 4% of women at term and is associated with microbial invasion of the amniotic cavity (MIAC) and inflammation as reflected by increased AF WBC count.     

Prise en charge et issues des grossesses compliquées d’une rupture prématurée des membranes avant 26 semaines d’aménorrhée

ObjectiveTo evaluate short-term outcomes of pregnancies complicated by preterm premature rupture of membranes (PPROM) before 26 weeks of gestation (wg).Patients and methodsForty patients were included in a retrospective study from 1998 to 2008.ResultsFifty percent of PPROM occurred before 23 wg. Survival rate was 21.4% when PPROM occurred before 22 wg versus 54.5% when it occurred between 22 and 23 + 6 wg and reached 80% after 24 wg (P = 0.006). Perinatal mortality affected more frequently primigravida women (OR = 5.16; IC95%[0.99–36.59]). Invasive procedures before PPROM did not affect survival rates. Smoking induced shorter latency (19.1 ± 13.8 vs. 40.3 ± 2.3j; P = 0.01). Chorioamnionitis complicated all pregnancies terminated before 26wg versus 50% of pregnancies terminated after 26 wg (P = 0.02). In case of chorioamnionitis, 70% of the germs were identified prenatally. Patients whose CRP was higher than 6 mg/L at the time of PPROM had a higher fetal mortality rate (63.6% vs. 27.8%; P = 0.02; OR = 4.3; IC95%[0,99–22,1]). No significant difference was found in the occurrence of chorioamnionitis based on gestational age at PPROM, result of the vaginal swab on admission or the amount of amniotic fluid.Discussion and conclusionThe gestational age of PPROM and the one of delivery are the major prognostic factors. Primigravida women are more exposed to perinatal mortality. CRP appears to be a predictive factor of perinatal mortality.     

Sonographic evaluation of fetal abdominal circumference and cerebroplacental Doppler indices for the prediction of fetal macrosomia in full term pregnant women. Cohort study

ObjectivesThe aim of the study was to explore the relationship between cerebroplacental Doppler ratio and birth weight in cases of suspected fetal macrosomia.MethodsThe pulsatility indices of the umbilical (UA-PI) and middle cerebral (MCA-PI) arteries, the cerebroplacental pulsatility index ratio (CPR) and the estimated fetal weight (EFW) were obtained in a cohort of 150 ultrasound-dated pregnancies at ⩾ 37 weeks’ gestation divided into two groups as follows; large for gestational age (LGA, n = 50) and average for gestational age (AGA, n = 100).ResultsThere is a significant difference between groups in abdominal circumference (AC), head circumference (HC), biparital diameter (BPD), estimated fetal weight (EFW) and actual fetal weight with a mean difference of 92.7 g in the LGA group and 84 g in the AGA group. MCA-RI and PI were significantly lower in the LGA group with no difference in UA-RI, PI and CPR-PI between both groups.ConclusionsCPR-PI could not differentiate between LGA and AGA.     

Predictive value of intra-amniotic and serum markers for inflammatory lesions of preterm placenta

Objective

To compare the relative predictive values of amniotic fluid (AF) matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and serum C-reactive protein (CRP) for histologic chorioamnionitis and intra-amniotic infection in women with preterm labor or preterm premature rupture of membranes (PROM).

Study design

This retrospective cohort study included 99 consecutive women with preterm labor or preterm PROM (21–35 weeks’ gestation) who delivered within 72 h of transabdominal amniocentesis. The AF was cultured for aerobic and anaerobic bacteria and for genital mycoplasmas and was assayed for MMP-9 and IL-6 levels. Maternal serum CRP was measured immediately after amniocentesis. The placentas were examined histologically.

Main outcome measures

histologic chorioamnionitis and intra-amniotic infection.

Results

The prevalence of histologic chorioamnionitis and a positive AF culture was 44% (44/99) and 28% (28/99), respectively. In predicting intra-amniotic infection, AF MMP-9 had a significantly higher area under the curve (AUC: 0.94 [95% CI, 0.87–0.98]) than AF IL-6 (0.87 [95% CI, 0.78–0.84]; P < 0.05) and serum CRP (0.76 [95% CI, 0.66–0.84]; P < 0.001) and a higher sensitivity and specificity than serum CRP (P < 0.01, respectively). However, in predicting histologic chorioamnionitis, there were no significant differences in AUCs among the three tests (AF MMP-9: 0.78 [95% CI, 0.68–0.85]; AF IL-6: 0.76 [95% CI, 0.66–0.84]; serum CRP: 0.76 [95% CI, 0.66–0.84]). In a sub-analysis of 71 women without intra-amniotic infection, histologic chorioamnionitis was associated with an elevated serum CRP level (P < 0.05), but not with the level of AF IL-6 or MMP-9 (P = 0.232 and P = 0.402, respectively).

Conclusions

The AF MMP-9 has a better overall diagnostic performance than the AF IL-6 and maternal serum CRP in predicting intra-amniotic infection. However, the serum CRP level obtained up to 72 h before delivery appears to be an important marker for early identification of histologic chorioamnionitis in women without intra-amniotic infection.     

Association between maternal haemoglobin at 27–29 weeks gestation and intrauterine growth restriction

ObjectiveTo examine the relationship between maternal haemoglobin concentration (Hb) at 27–29 weeks’ gestation and fetal growth restriction (FGR).DesignThis was a retrospective, case control study.SettingA University hospital in London, UK.PopulationPregnant women attending for routine antenatal care at 27–29 weeks of pregnancy.MethodsMaternal Hb, measured routinely at 27–29 weeks in pregnancies complicated by FGR (n = 491) was compared to normal controls (n = 491). Multiple regression analysis was used to examine the association between Hb and maternal characteristics.Main outcome measuresBirthweight z-score, admission to the Neonatal Unit (NNU) and adverse perinatal outcome.ResultsIncreased Hb at 27–29 weeks gestation is associated with reduced birthweight, with an inverse relationship between maternal Hb and fetal birthweight z-score (R² = 0.10, p < 0.0001). In addition, for the prediction of admission to the NNU (R² = 0.24, p < 0.0001) and serious adverse neonatal outcome (R² = 0.10, p < 0.0001), maternal Hb is an independent predictor with a linear and quadratic relationship, respectively. Therefore, both increased and decreased maternal Hb levels increase the risk of serious neonatal complications.ConclusionsRaised Hb at 27–29 weeks gestation is associated with FGR and with an increased risk of admission to the NNU and adverse fetal outcome.     

Funisitis in term pregnancy is associated with microbial invasion of the amniotic cavity and intra-amniotic inflammation.

OBJECTIVE: Funisitis is the histologic counterpart of the fetal inflammatory response syndrome, which is a multisystemic disorder associated with impending preterm delivery and adverse neonatal outcome. The purpose of this study was to examine the relationship between funisitis and the microbiologic status of amniotic fluid (AF) and AF white blood cell (WBC) count in patients at term. METHODS: The relationship between the presence of funisitis, AF culture, and AF WBC count was examined in 832 consecutive patients who delivered a term neonate within 72 hours of amniocentesis. AF was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton's jelly. AF WBC count was analyzed in a hemocytometer chamber. Nonparametric statistics were used for data analysis. RESULTS: Funisitis was present in 4% (30/832) of cases. A positive AF culture was more common in cases with funisitis than in those without funisitis (17% vs. 5%; p < 0.05). Patients with funisitis had a significantly higher median AF WBC count than those without funisitis (median >1000 cells/mm3 vs. median 2 cells/mm3; p < 0.001). The frequency of funisitis and of a positive AF culture was 1% in women without labor and with intact membranes and the frequencies and the median AF WBC count increased in the presence of labor or rupture of membranes. CONCLUSION: Funisitis is present in 4% of women at term and is associated with microbial invasion of the amniotic cavity (MIAC) and inflammation as reflected by increased AF WBC count.     

Fetal and maternal leptin in pre-gestational diabetic pregnancy

ObjectiveTo compare maternal and fetal leptin among women without diabetes, women with type 1 diabetes, and women with type 2 diabetes.MethodsIn a prospective study at the National Maternity Hospital, Dublin, 40 women with type 1 diabetes, 10 with type 2 diabetes, and 30 without diabetes were enrolled between July 2006 and July 2008. Maternal (36-week) and cord blood leptin was measured by enzyme-linked immunoassay.ResultsNo difference was found in maternal leptin among the groups: without diabetes (mean, range): 325 pg/mL, 36–1492 pg/mL; type 1 diabetes: 343.2 pg/mL, 55.5–1108.2 pg/mL; type 2 diabetes: 202.2 pg/mL, 35.1–1553.3 pg/mL (P > 0.05). Leptin levels were higher among fetuses of women with type 1 (223 pg/mL, 25.7–810 pg/mL) and type 2 (447.2 pg/mL, 136.3–679 pg/mL) diabetes than among women without diabetes (80.3 pg/mL, 27.3–623.1 pg/mL; P < 0.05). The single significant predictor of fetal leptin for the whole cohort was maternal body mass index (BMI; r = 0.39, P = 0.01). Only third-trimester glycosylated hemoglobin (HbA1c) was significantly related to fetal leptin after controlling for maternal BMI among women with diabetes (r = 0.28, P = 0.04).ConclusionFetuses of women with diabetes might have some degree of leptin resistance. This might be important in appetite regulation in extrauterine life.     

Evaluation of isosorbide mononitrate for cervical ripening prior to induction of labor for postdated pregnancy in an outpatient setting

ObjectiveTo determine the safety and effectiveness of self-administered treatment with isosorbide mononitrate (IMN) for cervical ripening in Indian women with postdated pregnancies.MethodsA randomized, placebo-controlled study was conducted with 200 women with postdated pregnancies and unfavorable cervices who self-administered vaginally either 2 40-mg tablets of IMN or 2 40-mg tablets of pyridoxine as placebo prior to admission for induction of labor. The main outcome variables were change in Bishop score, time from admission to delivery, and presence or absence of fetal and maternal morbidity.ResultsThe Bishop score was significantly improved 24 hours after initiation of the outpatient IMN treatment (P < 0.001) and the needs for further cervical ripening and oxytocin infusion were less in the study than in the control group (P < 0.001 and P = 0.008). The time from admission to delivery was also less (P < 0.001). Moreover, the IMN treatment had no major adverse maternal or fetal effects. The vast majority of women in both groups were either satisfied or very satisfied with the outpatient treatment.ConclusionThe self-administration, at home, of isosorbide mononitrate leads to a safe and effective cervical ripening prior to labor induction in women with postdated pregnancies.CTRI Registration No.: CTRI/2011/091/000121     

Evaluation of the use of anti-TNF-α in an LPS-induced murine model

ObjectiveTumor necrosis factor α (TNF-α) may play a critical role in inflammatory-mediated preterm labor. Medications blocking the activity of TNF-α have been shown to be effective in the treatment of conditions such as rheumatoid arthritis; however, the use of these medications for an event like preterm birth or fetal death is unknown. We hypothesized that treatment with anti-TNF-α may decrease the rate of fetal death and preterm birth in a LPS-induced murine model.MethodsPregnant C57BL/6J mice received intraperitoneal (IP) injections of either vehicle or 2 mg anti-TNF-α. After 24 h, 10 μg of LPS was administered IP. Mice were sacrificed 24 h later and outcomes between groups were assessed. A second set of experiments utilizing RT-PCR was performed to determine the influence of anti-TNF-α on production of inflammatory cytokines in response to LPS.ResultsThere were 72 resultant pups in the LPS + saline group, and 91 in the group receiving LPS + anti-TNF-α. Pretreatment with anti-TNF-α reduced the rate of fetal death and preterm birth after LPS administration (p < 0.01). Expression of IL-6, IL-1beta, TLR-2, CD14 and COX-1 were found to be significantly reduced in mice treated with anti-TNF-α and LPS compared to LPS alone.ConclusionThe use of anti-TNF-α decreased fetal deaths and preterm deliveries in an LPS-induced model of preterm birth. In addition, there were critical gene expression alterations in the group receiving anti-TNF-α. Further evaluation of TNF-α blockade as a potential treatment for preterm labor is warranted.     

Position-related injury is uncommon in robotic gynecologic surgery

ObjectiveTo assess the rate and risk factors for position-related injury in robotic gynecologic surgery.MethodsA prospective database from 12/2006 to 1/2014 of all planned robotic gynecologic procedures was retrospectively reviewed for patients who experienced neurologic injury, musculoskeletal injury, or vascular compromise related to patient positioning in the operating room. Analysis was performed to determine risk-factors and incidence for position-related injury.ResultsOf the 831 patients who underwent robotic surgery during the study time period, only 7 (0.8%) experienced positioning-related injury. The injuries included minor head contusions (n = 3), two lower extremity neuropathies (n = 2), brachial plexus injury (n = 1) and one large subcutaneous ecchymosis on the left flank and thigh (n = 1). There were no long term sequelae from the positioning-related injuries. The only statistically significant risk factor for positioning-related injury was prior abdominal surgery (P = 0.05). There were no significant associations between position-related injuries and operative time (P = 0.232), body mass index (P = 0.847), age (P = 0.152), smoking history (P = 0.161), or medical comorbidities (P = 0.229–0.999).ConclusionsThe incidence of position-related injury among women undergoing robotic surgery was extremely low (0.8%). Due to the low incidence we were unable to identify modifiable risk factors for position-related injury following robotic surgery. A standardized, team-oriented approach may significantly decrease position-related injuries following robotic gynecologic surgery.     

Maternal serum CA-125 level is elevated in severe preeclampsia

AimThe aim of this study was to determine the relationship between serum concentrations of cancer antigen-125 (CA-125) and pre-eclampsia severity.MethodsWe evaluated 91 females with a singleton pregnancy. Serum CA-125 levels were measured in subjects with severe pre-eclampsia (n = 34) and those with mild pre-eclampsia (n = 24). Females with healthy pregnancies (n = 31) served as the control group. The three study groups were statistically similar in terms of maternal age, gestational age, and body mass index.ResultsThe CA-125 level was significantly higher in the severe pre-eclampsia group than that in the mild pre-eclampsia and control groups (p < 0.05). No significant difference in CA-125 levels between the mild pre-eclampsia and control groups was observed. CA-125 level was positively correlated with proteinuria (r = 0.489, p = 0.000), systolic blood pressure (r = 0.503, p = 0.018), and diastolic blood pressure (r = 0.532, p = 0.000). In contrast, CA-125 was negatively correlated with birth weight (r = 0.266, p = 0.012) and gestational age at birth (r = 0.250, p = 0.018).ConclusionsCA-125 level increased in severe pre-eclampsia, which reflected abnormal trophoblastic invasion and chronic inflammation. Elevated levels of CA-125 in pre-eclamptic patients may be a marker of the disease severity.     

The Relationship between Androgens,Regulators of Collagen Metabolism,and Peyronie's Disease: A Case Control Study

IntroductionChanges in collagen metabolism have been postulated to play a pivotal role in the pathogenesis of Peyronie's Disease (PD). Androgens such as dehydroepiandrosterone sulfate (DHEA-S) and testosterone influence collagen metabolism by modulating the activity of matrix metalloproteases (MMP) and tissue inhibitors of metalloproteases (TIMP).AimThe aim of this study was to evaluate the interrelationship between androgens (DHEA-S and testosterone), key regulators of collagen metabolism such as insulin-like growth factor (IGF) 1 and IGF Binding Protein 3 (IGF-BP3), the MMP/TIMP system, and PD.MethodsAge matched PD patients (14) and healthy men (10) who acted as controls were recruited. Blood samples were collected from all subjects in the early morning hours after an overnight fast.Main Outcome MeasuresSerum levels of testosterone, sex hormone binding globulin, DHEA-S, 3-α-androstanediol glucuronide, pro-MMP-1, MMP-1, MMP-2, TIMP-1, TIMP-2, IGF-1 and IGF-BP3 were measured in both groups. Statistical methods included univariate, bivariate, and multivariate regression models.ResultsLevels of DHEA-S (114.5 vs. 169.5 µg/dL; p = 0.03), IGF-BP3 (2.96 vs. 3.79 µg/mL; p = 0.01), and TIMP-1 (173.1 vs. 195 ng/mL; p = 0.01) were significantly lower in PD patients. In contrast, the level of TIMP-2 (102 vs. 85 ng/mL; p = 0.001) was significantly lower in the control group. Using stepwise regression analysis, only TIMP-2 (p < 0.001) and DHEA-S (p = 0.04) were significantly related to PD in the final model (R² = 0.63). TIMP-1 and DHEA-S (r = 0.55, p < 0.05) were positively correlated in the PD group, whereas IGF-1 and testosterone (r = ?0.54, p < 0.05), and IGF-BP3 and testosterone (r = ?0.68, p < 0.05) were negatively correlated in PD patients.ConclusionsOur findings suggest that decreased levels of adrenal androgens may be implicated in the pathogenesis of PD. The mechanism and clinical relevance of this observation remain to be established. Karavitakis M, Komninos C, Simaioforidis V, Kontos S, Lefakis G, Politis V, Koritsiadis G, Konstantellou K, and Doumanis G. The relationship between androgens, regulators of collagen metabolism, and peyronie's disease: A case control study.     

Serial fetal abdominal circumference measurements in predicting normal birth weight in gestational diabetes mellitus

ObjectivesTo construct a clinical management matrix using serial fetal abdominal circumference measurements (ACMs) that will predict normal birth weight in pregnancies complicated by gestational diabetes (GDM) and reduce unnecessary ultrasound examination in women with GDM.Study designRetrospective cohort study of 144 women with GDM in a specialist obstetric-diabetes clinic. Women with GDM who delivered singleton infants were identified from a clinical register. Regression analysis was used to identify associations between serial ACMs, maternal parameters and normal birth weight (birth weight between the 10th and 90th percentiles). Predictive clinical models were designed with the aim of identifying normal birth weight infants with the lowest number of fetal ultrasound scans.ResultsCompared to mothers of large-for-gestational-age (LGA) infants, mothers of normal weight infants had lower fasting glucose measurements at diagnosis (5.9 mmol/l ± 1.0 vs. 6.6 mmol/l ± 0.7, p < 0.05), lower maternal weight at delivery (90 kg ± 17 vs. 96 kg ± 17, p < 0.05), and a lower rate of prior LGA infants (31% vs. 60%, p < 0.05). Maternal weight and a history of prior LGA delivery were identified as useful predictors of fetal birth weight in predictive models. Serial ACMs below the 50th, 75th and 90th percentiles could predict normal birth weight with 100%, 97% and 96% positive predictive value respectively when used in these risk factor based models. Two measurements sufficed in low-risk pregnancies.ConclusionSerial ACMs can predict normal birth weight in GDM.