Alessandra Capponi

The value of fetal fibronectin in cervical and vaginal secretions and of ultrasonographic examination of the uterine cervix in predicting premature delivery for patients with preterm labor and intact membranes.

OBJECTIVE We compared the diagnostic performances of fetal fibronectin assay of cervical and vaginal secretions and of transvaginal ultrasonographic evaluation of the uterine cervix in the prediction of preterm delivery of patients presenting with preterm labor and intact membranes. STUDY DESIGN One hundred eight patients admitted to the hospital for preterm labor and with intact membranes underwent assay of fibronectin in the cervical and vaginal secretions and transvaginal ultrasonographic evaluation of the uterine cervix. The ultrasonographic parameters evaluated were cervical length, presence of funneling, and cervical index ([Funnel length + 1]/Cervical length). Outcome measures were occurrence of preterm delivery, defined as birth before the thirty-seventh week of gestation, and the admission-to-delivery interval. RESULTS Forty-seven patients (43.5%) were delivered preterm. Receiver characteristic curve analysis showed that a level of fetal fibronectin in cervical secretions > or = 60 ng/ml had the highest diagnostic performance in predicting preterm delivery (sensitivity 80.9%, specificity 83.6%). Multiple stepwise logistic regression analysis indicated that the cervical index significantly improved the prediction of preterm delivery achieved by the fetal fibronectin assay. In patients with cervical secretion fibronectin levels > or = 60 ng/ml, survival analysis showed a shorter admission-to-delivery interval in the presence of an abnormal cervical index (p < or = 0.001). CONCLUSIONS The assay of fetal fibronectin in cervical secretions is more accurate than ultrasonographic evaluation of the uterine cervix in the prediction of preterm delivery. Combined use of the fetal fibronectin assay and the cervical index improves the diagnostic efficiency and allows prediction of the admission-to-delivery interval, identifying a subgroup of patients who may require aggressive treatment.

Interleukin-6 concentrations in cervical secretions identify microbial invasion of the amniotic cavity in patients with preterm labor and intact membranes

OBJECTIVE The objectives of this study were to determine whether cytokine levels in cervical secretions were increased in the presence of microbial invasion of the amniotic cavity in patients with preterm labor and intact membranes and to relate concentrations to cytokine levels in amniotic fluid, cervicovaginal microflora, and the presence of chorioamnionitis. STUDY DESIGN Cervical secretions were sampled immediately before amniocentesis in 92 patients admitted for preterm labor with singleton pregnancies and intact membranes. Amniotic fluid was cultured and the following cytokines were measured in amniotic fluid and cervical secretions: interleukin-1 beta, interleukin-1 receptor antagonist, tumor necrosis factor-alpha, and interleukin-6. The cervicovaginal microflora and placentas (n = 42) were also analyzed. RESULTS A total of 19.56% (18/92) of the amniotic fluid cultures had positive results. All the cytokines tested showed significantly higher levels in cervical secretions in the presence of intraamniotic infection. There were significant relationships between the concentrations of interleukin-6 and interleukin-1 receptor antagonist in amniotic fluid and cervical secretions. A concentration of interleukin-6 in cervical secretions > 410 pg/ml had a sensitivity of 66.8% and a specificity of 90.5% and a relative risk of 7.7 for intraamniotic infection, higher than the other cytokines tested. There were no relationships between the presence of bacterial vaginosis and cervicovaginal pathogens and cervical cytokine levels. In the presence of chorioamnionitis, cervical concentrations of interleukin-6 and interleukin-1 receptor antagonist were significantly increased in spite of negative amniotic fluid culture results. CONCLUSION The measurement of interleukin-6 in cervical secretions may help to noninvasively identify intraamniotic infection among pregnancies with preterm labor and intact membranes.

The value of fetal arterial, cardiac and venous flows in predicting pH and blood gases measured in umbilical blood at cordocentesis in growth retarded fetuses

Objective To assess the value of Doppler indices, calculated from fetal arterial peripheral vessels, cardiac outflow tracts and venous vessels, in the identification of acidaemia, hypercapnia and hypoxaemia as determined by pH and gas analysis of fetal blood obtained by cordocentesis in growth retarded fetuses.

Ductus venosus velocity waveforms in appropriate and small for gestational age fetuses

The objective of this study was to evaluate differences in ductus venosus velocity waveforms between appropriate and small for gestational age fetuses by using a new index based on the ratio between systolic and atrial peak velocities. Ductus venosus velocity waveforms were cross-sectionally recorded in 164 appropriate for gestational age fetuses at 16-42 weeks of gestation and in 97 small for gestational age fetuses free from structural and chromosomal abnormalities between 24-36 weeks of gestation. Small for gestational age fetuses were divided according to the Doppler findings in arterial peripheral vessels: group A (n = 33), normal ratio between umbilical artery and middle cerebral artery Pulsatility Indices; group B (n = 41), umbilical artery/middle cerebral artery ratio > 95th centile but presence of end diastolic flow in umbilical artery; group C (n = 23), umbilical artery/middle cerebral artery ratio > 95th centile and absence of end diastolic flow in umbilical artery. Eighteen small for gestational age fetuses (10 from group B and 8 from group C) were also serially studied until delivery due to fetal distress. Ductus venosus velocity waveforms were recorded at the level of its origin from umbilical vein and the ratio between systolic and atrial peak velocities (systolic/atrial ratio) calculated. In appropriate for gestational age fetuses, systolic/atrial ratio values significantly decrease with gestation. No significant differences were found in systolic/atrial ratio between appropriate for gestational age fetuses and group A small for gestational age fetuses while, after correction for gestational age, significantly higher values were found in group B (P < or = 0.01) and group C (P < or = 0.001) fetuses. Among these fetuses, those with systolic/atrial ratio above the 95th confidence interval showed a poorer perinatal outcome. No relationships were found between systolic/atrial ratio and Pulsatility Index values from fetal arterial peripheral vessels, while a positive relationship was found with the percentage reverse flow in inferior vena cava. In fetuses serially followed, the systolic/atrial ratio progressively increased approaching the onset of abnormal fetal heart rate patterns. The systolic/atrial ratio allows the evaluation of ductus venosus hemodynamics in small for gestational age fetuses and this index may be useful in the monitoring of such fetuses.

First-Trimester Placental Volume and Vascularization Measured by 3-Dimensional Power Doppler Sonography in Pregnancies With Low Serum Pregnancy-Associated Plasma Protein A Levels

Objective. The purpose of this study was to investigate the first‐trimester placental volume and 3‐dimensional (3D) power Doppler vascularization of pregnancies with low serum pregnancy‐associated plasma protein A (PAPP‐A) levels and to relate these findings to pregnancy outcomes. Methods. Three‐dimensional power Doppler sonography of the placenta was performed at gestational ages of 11 weeks to 13 weeks 6 days in 84 pregnancies with PAPP‐A concentrations of less than 0.4 multiple of the median (MoM). With a standardized setting, the placental volume and vascularization index (VI), flow index (FI), and vascularization‐flow index (VFI) were calculated and related to pregnancy outcomes. Results. Pregnancy outcomes were as follows: 57 pregnancies with birth weights at or above the 10th percentile (group A), 16 pregnancies with birth weights below the 10th percentile and normal Doppler findings in the umbilical artery throughout gestation (group B), and 11 pregnancies with birth weights below the 10th percentile and abnormal umbilical Doppler findings later in gestation (group C). No differences were found in PAPP‐A levels among groups. Placental volume values were significantly lower than reference limits, but no differences were found between groups. In groups A and B, there were no significant differences in 3D Doppler indices. However, these indices were significantly lower in group C (VI mean difference, −1.904; P < .001; FI mean difference, −1.939; P < .001; VFI mean difference, −1.944; P < .001). Placental vascular indices were significantly related to the severity of intrauterine growth restriction (IUGR; VI, r = 0.438; P < .001; FI, r = 0.482; P < .001; VFI, r = 0.497; P < .001) but not to the PAPP‐A MoM and placental volume values. Conclusions. Low serum maternal PAPP‐A levels are associated with altered 3D placental Doppler indices, and these changes are related to subsequent development of IUGR and adverse pregnancy outcomes.

Interleukin-6 Concentrations in Cervical Secretions in the Prediction of Intrauterine Infection in Preterm Premature Rupture of the Membranes

The objective of this study was to determine the value of interleukin-6 (IL-6) in cervical secretion to diagnose microbial invasion of the amniotic cavity in patients with premature rupture of the membranes. Cervical secretions were sampled immediately before amniocentesis in 124 patients with singleton pregnancies and preterm premature rupture of the membranes. Gestational age ranged between 24 and 32 weeks. Amniotic fluid was cultured and IL-6 measured in amniotic fluid and cervical secretions. A total of 33.8% (21/124) of the amniotic fluid cultures had positive results. In cervical secretions the median concentration of IL-6 was 672 pg/ml (range 5–1,250) in the presence of intra-amniotic infection in contrast to 95.5 pg/ml (range 12–640) in women with negative amniotic fluid culture (p ≤0.001). There were no differences between IL-6 concentrations in the cervical secretions of patients with or without obvious leakage of amniotic fluid. A significant relationship was found between IL-6 levels in amniotic fluid and in cervical secretions (ρ = 0.74, p ≤0.001). An IL-6 level in cervical secretions >200 pg/ml had a sensitivity of 78.5%, a specificity of 73.1% and a relative risk of 4.6 for intra-amniotic infection. Receiver-operator characteristics curve analysis showed that IL-6 assay in cervical secretions is comparable to IL-6 assay in amniotic fluid in predicting intra-amniotic infection (p = 0.468).In conclusion, intra-amniotic infection is associated with increased levels of IL-6 and concentrations in cervical secretions are related to amniotic levels. The measurement of IL-6 in cervical secretions may help to noninvasively identify intra-amniotic infection among pregnancies with preterm premature rupture of membranes.

The diagnostic value of interleukin-8 and fetal fibronectin concentrations in cervical secretions in patients with preterm labor and intact membranes

The objectives of this study were 1) to evaluate interleukin-8 concentrations in cervical secretions in predicting preterm delivery, microbial invasion of the amniotic cavity and histologic chorioamnionitis in patients with preterm labor and intact membranes and 2) to compare the diagnostic value of interleukin-8 with fetal fibronectin determinations in predicting preterm delivery, microbial invasion of the amniotic cavity and histologic chorioamnionitis in patients with preterm labor and intact membranes. Interleukin-8 and fetal fibronectin were assayed in cervical secretions in 106 patients with singleton pregnancies and intact membranes admitted for preterm labor. Amniotic fluid obtained by amniocentesis was cultured and placentas (No = 43) analyzed for the presence of chorioamnionitis. The prevalence of pregnancies delivered preterm was 46.2% (49/106) and 15.09% (16/106) of amniotic fluid cultures were positive. Interleukin-8 levels in cervical secretions were significantly increased in patients who delivered preterm (p < or = 0.0001), in presence of positive amniotic fluid culture (p = 0.0016) and histological chorioamnionitis (p = 0.008) than in patients with negative findings. Receiver-operator characteristics curve analysis showed that an interleukin-8 value > 450 pg/ml is comparable to that of a fetal fibronectin value > 50 ng/ml in predicting preterm delivery (p = 0.247). Among patients who delivered preterm interleukin-8 concentrations > 860 pg/ml predicted a positive amniotic fluid culture with a sensitivity of 81.2% and a specificity 66.6%. Further, in patients who delivered preterm and had a negative amniotic fluid culture, IL-8 concentrations > 480 pg/ml predicted histological chorioamnionitis with a sensitivity 78.5% and specificity 61.5%. A positive fetal fibronectin > 50 ng/ml was not predictve of either a positive amniotic fluid culture or the presence of histological chorioamnionitis. In conclusion, increased concentrations of interleukin-8 and fetal fibronectin are associated with impending delivery and their diagnostic value seems comparable. However, interleukin-8 concentrations identify patients at risk of a positive amniotic fluid culture and the presence of histological chorioamnionitis. Measurement of interleukin-8 in cervical secretion is a non-invasive method to identify patients at risk for both preterm delivery and intrauterine infection.

Effects of maternal cigarette smoking on placental volume and vascularization measured by 3-dimensional power Doppler ultrasonography at 11+0 to 13+6 weeks of gestation

OBJECTIVE We sought to establish the effect of maternal smoking on placental volume and vascularization in early gestation. STUDY DESIGN Three-dimensional power Doppler ultrasonography of the placenta was performed at 11+0 to 13+6 weeks in 80 pregnancies categorized according to cigarette consumption: group A never smoked, B smoking < 10 cigarettes/day, C smoking 10-20 cigarettes/day, and D smoking > 20 cigarettes/day. Using a standardized setting, placental volume and vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were calculated. RESULTS No differences were found in placental volume among groups. In groups C and D lower values were found for VI (group C: t = 4.52, P = .0002; group D: t = 3.72, P = .0014), FI (group C: t = 5.06, P = .0001; group D: t = 4.59, P = .0002), and VFI (group C: t = 3.49, P = .0024; group D: t = 2.88, P = .0095). Placental vascular indices were significantly related to birthweight (VI r = 0.563, FI r = 0.580, VFI r = 0.601; P < .001). CONCLUSION Maternal smoking is associated with altered 3-dimensional placental Doppler indices and these changes are related to birth weight.

Placental vascularization measured by three‐dimensional power Doppler ultrasound at 11 to 13 + 6 weeks' gestation in normal and aneuploid fetuses

To establish the potential role of three‐dimensional (3D) power Doppler evaluation of the placental circulation in aneuploidy screening at 11 to 13 + 6 weeks of gestation.

Cardiac and venous blood flow in fetuses of insulin-dependent diabetic mothers: Evidence of abnormal hemodynamics in early gestation

OBJECTIVE Our purpose was to determine whether in early gestation cardiac and venous blood flow patterns of fetuses of insulin-dependent diabetic mothers differ from those of normal fetuses. STUDY DESIGN Serial recordings were obtained at 12, 16, and 20 weeks of gestation in 11 normal fetuses, 16 fetuses of insulin-dependent diabetic mothers with first-trimester glycosylated hemoglobin levels < or = 8.5% (group 1), and 11 fetuses of insulin-dependent diabetic mothers with first-trimester glycosylated hemoglobin levels > 8.5% (group 2). Velocity waveforms at the level of atrioventricular valves, inferior vena cava, and umbilical vein were recorded by means of color and pulsed Doppler equipment by either transvaginal or transabdominal approaches. The following variables were measured: ratio between the peak velocities during early passive ventricular filling and active atrial filling at the level of atrioventricular valves, percent reverse flow during atrial contraction in inferior vena cava, and pulsations in umbilical vein. RESULTS In all the fetuses the ratios between early and active ventricular filling increased linearly with advancing gestation, whereas the percent reverse flow in the inferior vena cava decreased linearly. However, fetuses of diabetic mothers showed significant differences in the slope of the functions describing the development with gestation of these index values, resulting in lower values of the ratios between early and active ventricular filling at the level of both ventricular valves and higher values of percent reverse flow in inferior vena cava. These differences were more evident in group 2 fetuses of diabetic mothers, and statistically significant differences were found in the slope values compared with group 1 fetuses. In normal fetuses umbilical vein pulsations were present only in two fetuses at 12 weeks of gestation (18.18%) and were never evidenced later in gestation. A significantly higher incidence of pulsations was found at 12 weeks in fetuses of diabetic mothers (group 1, 56.25%; group 2, 81.81%) and pulsations were present until 16 weeks (group 1, 37.5%; group 2, 45.47%). CONCLUSIONS An impaired development of cardiac and venous blood flow patterns occurs in fetuses in insulin-dependent diabetic mothers. These abnormalities are more evident in pregnancies with poorer glycemic control but still occur in the presence of stricter metabolic control.