Increased Sylvian fissure angle as early sonographic sign of malformation of cortical development.

OBJECTIVE: To evaluate Sylvian fissure development by assessing Sylvian fissure angles in fetuses with malformation of cortical development (MCD). METHODS: This was a retrospective study of 22 fetuses with MCD. Cases with a stored three-dimensional (3D) brain volume acquired at 18 + 0 to 30 + 6 weeks of gestation at an ultrasound-based research clinic between January 2010 and December 2017 were identified through a database. Of the 22 fetuses, seven had an extracranial abnormality, such as cardiac, renal, gastrointestinal and/or digital anomalies, and five had a minor abnormality such as micrognathia, low-set ears and/or single umbilical artery. To confirm the final clinical diagnosis of brain abnormality, postmortem histological findings or prenatal or postnatal magnetic resonance images were used. For measurement of Sylvian fissure angle, an anterior coronal plane of the fetal brain on transvaginal 3D volume multiplanar imaging was visualized as a single image from the three orthogonal views. The right and left Sylvian fissure angles were measured between a horizontal reference line (0°) and a line drawn along the upper side of the respective Sylvian fissure. The Sylvian fissure angle on both sides was plotted on the graphs of the reference ranges for gestational age in weeks. RESULTS: In 21 (95.5%; 95% CI, 86.8-100.0%) of 22 fetuses with MCD, the Sylvian fissure angle on one or both sides was larger than the 90th percentile of the normal reference. There was one case with apparent focal MCD in the parietal lobe, but the Sylvian fissure angles were normal. A case with apparent unilateral cortical dysplasia and one with apparent unilateral schizencephaly had conspicuous discrepancies between the left and right Sylvian fissure angles. Abnormal genetic test results were obtained in six cases, including four cases with a mutation in a single gene. CONCLUSIONS: This study has shown that the Sylvian fissures, as defined by the Sylvian fissure angle, have delayed development in most MCD cases prior to the diagnosis of the condition. The Sylvian fissure angle may potentially be a strong indicator for the subsequent development of cortical malformation, before the time point at which the gyri and sulci become obvious on the fetal brain surface. Further research is required to validate these findings. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Plasma natriuretic peptide levels in fetuses with congenital heart defect and/or arrhythmia.

OBJECTIVE: Diagnosing fetal heart failure remains challenging because it is difficult to know how well the fetal myocardium will perform as loading conditions change. In adult cardiology, natriuretic peptides (NPs) are established markers of heart failure. However, the number of studies investigating NP levels in fetuses is quite limited. The aim of this study was to evaluate the significance of plasma NP levels in the assessment of heart failure in fetuses with a congenital heart defect (CHD) and/or arrhythmia. METHODS: This was a prospective observational study conducted at a tertiary pediatric cardiac center. A total of 129 singletons with CHD and/or arrhythmia and 127 controls were analyzed between 2012 and 2015. Umbilical cord plasma atrial NP, brain NP and N-terminal pro-brain NP levels at birth were compared with ultrasonography findings indicating fetal heart failure, such as cardiovascular profile (CVP) score and morphological characteristics. RESULTS: Fetuses with CHD and/or arrhythmia had higher NP levels than did controls (P < 0.01). NP levels of fetuses with CHD and/or arrhythmia were correlated inversely with CVP score (P for trend < 0.01). No differences in NP levels were found in fetuses with CHD and/or arrhythmia and a CVP score of ≥ 8 in comparison to controls. Multivariate analysis showed that a CVP score of ≤ 5, tachy- or bradyarrhythmia at birth, preterm birth and umbilical artery pH < 7.15 were associated independently with high NP levels (P < 0.01). Among fetuses with a CVP score of ≤ 7, abnormal venous Doppler sonography findings were significantly more common and more severe in fetuses with tachy- or bradyarrhythmia than in those with CHD, and those with tachy- or bradyarrhythmia had higher NP levels than did those with CHD (P = 0.01). Fetuses with right-heart defect and moderate or severe tricuspid valve regurgitation had significantly higher NP levels than did fetuses with other types of CHD (P < 0.01). CONCLUSIONS: Plasma NP levels in fetuses with CHD and/or arrhythmia are correlated with the severity of fetal heart failure. Elevated NP levels are attributed mainly to an increase in central venous pressure secondary to arrhythmia or atrioventricular valve regurgitation due to CHD, rather than to the morphological abnormality itself. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Acute aortic dissection (Stanford type B) during pregnancy.

We report a case of acute aortic dissection (Stanford type B) that occurred in pregnant woman at 34-week gestation. She had no systemic characteristics of Marfan syndrome, however she exhibited a mutation of FBN1, Arg 545 Cys, which has been found to correlate with ectopia lentis but not with aortic dissection.

Risk factors for maternal outcome in pregnancy complicated with dilated cardiomyopathy.

OBJECTIVE: The goal of the study was to determine risk factors for maternal cardiac failure in pregnancy complicated with dilated cardiomyopathy (DCM). STUDY DESIGN: The subjects were 29 patients diagnosed with DCM before conception or during the first 7 months of pregnancy. DCM was defined as left ventricle end-diastolic dimension (LVDd)≥48 mm and/or fractional shortening (%FS)≤30% on echocardiography. Patients were followed until at least 1 year after delivery and were categorized into a poor prognosis group (n=6; death or end stage heart failure of New York Heart Association (NYHA) class III and IV) and a good prognosis group (n=23; all other cases). RESULT: DCM was initially diagnosed during pregnancy in 6/6 and 8/23 patients in the poor and good prognosis groups, respectively (P<0.005). The %FS of the first test during pregnancy was 17.5±6.2 and 27.4±9.3% in the respective groups (P<0.005). In eight abortion cases with %FS 15.2±3.1%, %FS, cardiac function and NYHA class were maintained until 20 months after abortion. There was no relationship between LVDd and maternal outcome. CONCLUSION: Onset during pregnancy and decreased %FS are risk factors for a poor maternal outcome in patients with DCM. Abortion prevents further deterioration of cardiac function in patients with a very low %FS.

Unexplained fetal death is associated with changes in the adaptive limb of the maternal immune response consistent with prior antigenic exposure.

OBJECTIVE: The causes of fetal death are largely unknown. CD4 T cells have been classified according to the expression of the CD45 isoforms into 'naive-like' T cells (CD45RA) and 'memory-like' T cells (CD45RO). An increase in the percentage of the CD45RO has been interpreted as indicating prior antigenic exposure of the host and, in newborns, evidence of infection. The purpose of this study was to determine whether unexplained fetal death was associated with a change in the proportion of 'naive-like' and 'memory-like T cells' in the maternal blood, as determined by the CD45 isoforms on the surface of CD4+ lymphocytes. STUDY DESIGN: A prospective study was conducted to compare the CD45 sub-population of lymphocytes in patients with intrauterine fetal death (n = 26) and normal pregnancy (n = 89). The percentages of CD45RA+, CD45RO+ and CD45RA+/CD45RO+ on CD4+ T lymphocytes were determined in maternal blood using flow cytometry and monoclonal antibodies. Results were reported as a percentage of CD4+ lymphocytes. Non-parametric statistics were used for analysis. A p value of < 0.05 was considered significant. RESULTS: Patients with intrauterine fetal death had a higher percentage of CD45RO+ CD4+ T lymphocytes than normal pregnant women (fetal death: median 57.7%, range 35.4-78.6 vs. normal pregnancy: median 49.9%, range 19.1-86.8; p = 0.004). Fetal death was associated with a lower median percentage of CD45RA+ CD4+ lymphocytes than in normal pregnant women (fetal death: median 32.3%, range 15.3-58.0 vs. normal pregnancy: median 40.2%, range 11.2-67.3; p = 0.01). There was no significant difference in the percentage of cells with dual expression (CD45RA+/CD45RO+) between the study groups. CONCLUSION: Prior exposure to microbial products (bacterial or viral) or other unidentified antigens may result in a shift of the sub-population of 'naive-like' T cells to 'memory-like' T cells in mothers with unexplained fetal death.

Soluble adhesion molecule profile in normal pregnancy and pre-eclampsia.

OBJECTIVE: An exaggerated inflammatory response has been implicated as the cause of endothelial cell dysfunction and the maternal syndrome of pre-eclampsia. Adhesion molecules play a central role in the adherence of leukocytes to endothelial cells and the subsequent migration of white blood cells into perivascular tissue. Cellular forms of adhesion molecules mediate specific steps of leukocyte-endothelial cell interaction, and have been implicated in the pathophysiology of preeclampsia. Soluble forms of these molecules can be detected in plasma, and their concentrations are thought to reflect the degree of activation of a particular cell type. Elevations in soluble P-selectin (sP-selectin) reflect platelet activation; changes in soluble L-selectin (sL-selectin) suggest leukocyte activation; and an increase in soluble forms of E-selectin (sE-selectin), vascular cell adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule 1 (sICAM-1) and platelet endothelial cell adhesion molecule (sPECAM-1) indicate endothelial cell activation/dysfunction. The objective of this study was to determine whether normal pregnancy and pre-eclampsia were associated with changes in the concentrations of soluble selectins and members of the immunoglobulin superfamily of adhesion molecules. STUDY DESIGN: A cross-sectional study was conducted to determine the plasma concentrations of sL-selectin, sE-selectin, sP-selectin, sVCAM-1, sICAM-1 and sPECAM-1 in peripheral blood obtained from non-pregnant women (n = 20), normal pregnant women (n = 100) and patients with pre-eclampsia (n = 55). Concentrations of soluble adhesion molecules were determined with enzyme-linked immunoassays. Parametric statistics were used for data analysis. RESULTS: Normal pregnancy was associated with a significant increase in the maternal plasma concentration of sP-selectin, a decrease in sL-selectin, and no change in sE-selectin, sVCAM-1, sICAM-1 and sPECAM-1. In contrast, pre-eclampsia was associated with a significant increase in sP-selectin, sE-selectin and sVCAM-1, a decrease in sL-selectin, but no change in sICAM-1 and sPECAM-1 concentrations. CONCLUSIONS: The increased concentration of sP-selectin and decreased sL-selectin, as well as the lack of change in endothelial cell-associated soluble adhesion molecules suggest that pregnancy is associated with platelet and leukocyte activation, but not endothelial cell activation. In contrast, pre-eclampsia appears to be characterized by activation of platelets, leukocytes and endothelial cells.

Maternal intravascular inflammation in preterm premature rupture of membranes.

OBJECTIVE: Intrauterine inflammation has been implicated in the mechanisms responsible for preterm premature rupture of membranes (PROM). However, it is unclear whether this inflammatory process remains localized to the uterus, at the site of membrane rupture, or extends to the maternal compartment. Flow cytometric analysis is a sensitive method to assess the presence and magnitude of in vivo inflammation. This study was conducted to determine whether preterm PROM is associated with changes in the phenotypic and metabolic characteristics of maternal granulocytes and monocytes consistent with the presence of maternal intravascular inflammation. STUDY DESIGN: A prospective cross-sectional study was performed including patients with preterm PROM (n = 43) and normal pregnancy (n = 51). Maternal intravascular inflammation was studied using flow cytometry. Maternal blood was assayed to determine granulocyte and monocyte phenotype using monoclonal antibodies, which included cluster differentiation (CD) markers CD11b, CD14, CD15, CD16, CD18, CD49d, CD62L, CD64, CD66b and human leukocyte antigen (HLA)-DR. The quantities of basal intracellular reactive oxygen species (iROS) and oxidative burst was assessed. Statistical analysis was conducted with the use of non-parametric methods. A p value < 0.01 was considered significant. RESULTS: Preterm PROM was associated with a significant increase in the median mean channel brightness (MCB) of CD11b, CD14, CD64 and CD66b on granulocytes and median MCB of CD11b on monocytes. The oxidative burst and the stimulation index in both cell types were higher in preterm PROM than in normal pregnancy (p < 0.01). CONCLUSION: Preterm PROM is associated with phenotypic and metabolic changes in circulating granulocytes and monocytes.

Evidence of in vivo generation of thrombin in patients with small-for-gestational-age fetuses and pre-eclampsia.

OBJECTIVE: Thrombotic lesions in the maternal or fetal compartments are frequently observed in the placentas of patients with small-for-gestational-age (SGA) fetuses and in pre-eclampsia. The objective of this study was to determine whether there was evidence of in vivo generation of thrombin, the rate-limiting enzyme responsible for the formation of fibrin. The plasma concentrations of thrombin-antithrombin (TAT) complexes were used as an index of thrombin generation. METHODS: TAT complexes were measured in the plasma from 68 women from the following groups: normal pregnancy (n = 29); pre-eclampsia (n = 26); and SGA (defined as estimated fetal weight below the 10th centile for gestational age, which was confirmed by neonatal birth weight) (n = 13). TAT complex plasma concentrations were determined with a specific and sensitive immunoassay. Statistical analysis was performed with non-parametric statistics. RESULTS: The median plasma TAT complex concentrations were significantly higher in patients who delivered SGA neonates than in normal pregnant women (SGA, median 24.2 microg/l; range 11.9-788.7 vs. normal pregnancy, median: 14.4 microg/l; range 6.8-26.9; p = 0.001). Patients with pre-eclampsia had a higher median plasma TAT complex concentration than normal pregnant women (pre-eclampsia, median 18.1 microg/l; range 10.0-75.2 vs. normal pregnancy, median 14.4 microg/l; range 6.8-26.9; p = 0.02). CONCLUSION: In vivo generation of thrombin, determined by the plasma concentrations of TAT complexes, is higher in patients with SGA fetuses and patients with pre-eclampsia than in normal pregnancy.

Activation of coagulation system in preterm labor and preterm premature rupture of membranes.

OBJECTIVE: Thrombin, originally discovered as a coagulation factor, is a multifunctional protease capable of inducing myometrial contractions in vitro and in vivo. This enzyme has been implicated in the mechanisms of premature labor. Plasma concentrations of thrombin-antithrombin (TAT) complexes are an index of in vivo thrombin generation. The purpose of this study was to determine whether patients with premature labor and preterm premature rupture of membranes (PROM) have evidence of increased thrombin generation in maternal blood, as determined by the TAT complex concentrations. METHODS: A cross-sectional study was designed to determine plasma concentrations of TAT complexes in 110 women in the following groups: non-pregnant women (n = 20); normal pregnant women (n = 30); women in preterm labor with intact membranes (n = 30); and women with preterm PROM (n = 30). TAT complex concentrations were determined with a sensitive and specific immunoassay. Statistical analysis was conducted with non-parametric statistics. RESULTS: Patients with preterm labor and intact membranes had a significantly higher median plasma TAT complex concentration than normal pregnant women (women in preterm labor, median 19.1 microg/l; range 7.4-406 vs. normal pregnant women, median 15 microg/l; range 6.8-32.5; p = 0.03). Patients with preterm PROM had a higher median TAT complex concentration than normal pregnant women (preterm PROM, median 19.1 microg/l; range 4.7-738.6 vs. normal pregnant women, median 15 microg/l; range 6.8-32.5; p = 0.03). Normal pregnancy was associated with a higher median plasma TAT complex concentration than the non-pregnant state (normal pregnant women, median 15 microg/l; range 6.8-32.5 vs. non-pregnant women, median 2.7 microg/l; range 0.9-14.2; p < 0.001). CONCLUSION: Preterm labor and preterm PROM are associated with an excess generation of thrombin.

Subclinical myocardial injury in small-for-gestational-age neonates.

OBJECTIVE: Small-for-gestational-age (SGA) infants are at risk for premature death from cardiovascular disease (myocardial infarction and stroke), hypertension, and diabetes in adult life. Severe intrauterine growth restriction is often associated with subclinical cardiovascular abnormalities detectable during fetal echocardiography. The objective of this study was to determine whether SGA newborns have evidence of myocardial injury at birth. STUDY DESIGN: Cardiac troponin I, a specific marker of myocardial injury widely used for the diagnosis of myocardial infarction in adults, was determined in umbilical cord blood. Umbilical cord venous blood was obtained at the time of birth from 72 SGA newborns (birth weight below the 10th centile for gestational age) and 309 newborns whose birth weights were appropriate for gestational age (AGA). Cardiac troponin I was determined with a commercially available immunoassay (sensitivity 0.2 ng/ml) employed in clinical laboratories (Immulite 2000, Diagnostic Products Corp., Los Angeles, CA). RESULTS: Cardiac troponin I was not detectable in any of the blood samples from AGA infants. In contrast, 4.2% (3/72) of SGA infants had detectable cardiac troponin I in umbilical cord blood (Fisher's exact test, p = 0.007). CONCLUSION: A subgroup of SGA newborns undergoes myocardial injury before birth. This insult may predispose to the development of adult premature cardiovascular disease and death.

Evidence of participation of soluble CD14 in the host response to microbial invasion of the amniotic cavity and intra-amniotic inflammation in term and preterm gestations.

OBJECTIVE: Endotoxin has been implicated in the mechanism responsible for the setting of infection in preterm labor. To exert its biological effects, endotoxin binds to a circulating protein known as lipopolysaccharide binding protein (LBP) and presents endotoxin monomers to CD14, which may be a membrane-bound receptor or a soluble molecule. The endotoxin-LBP-CD14 complex interacts with Toll-like receptor 4 and other regulatory proteins leading to cellular activation and an inflammatory response. The purpose of this study was to determine whether microbial invasion of the amniotic cavity (MIAC)/intra-amniotic inflammation (both preterm and term) and parturition at term are associated with changes in the amniotic fluid and umbilical plasma soluble concentrations of CD14 (sCD14). STUDY DESIGN: Amniotic fluid was retrieved by amniocentesis from 88 patients in the following groups: group 1, preterm labor with intact membranes with MIAC/intra-amniotic inflammation (n = 18) and without these conditions (n = 26); group 2, term gestations not in labor without MIAC/intra-amniotic inflammation (n = 11), in labor without MIAC/intra-amniotic inflammation (n = 12) and in labor with MIAC/intra-amniotic inflammation (n = 13); and group 3, patients who underwent genetic amniocentesis at mid-trimester (n = 8). A sample of cord blood was obtained after delivery in all patients except those in group 3. sCD14 was assayed with a sensitive and specific immunoassay. Non-parametric statistics were used for analysis. A p value of < 0.05 was considered significant. RESULTS: sCD14 was detectable in 97% (85/88) of the amniotic fluid samples. Amniotic fluid sCD14 concentrations were lower in patients at term than in the mid-trimester of pregnancy (mid-trimester: median 482 ng/ml, range 258-838 ng/ml vs. term no labor: median 7 ng/ml, range 2-274 ng/ml, p = 0.01). Among patients with preterm labor with intact membranes, the median amniotic fluid sCD14 level of patients with MIAC/intra-amniotic inflammation was higher than in patients without these conditions (median 1568 ng/ml, range 98-5887 ng/ml vs. median 645 ng/ml, range 0-3961 ng/ml, respectively; p = 0.01). Among women at term in labor, those with MIAC/intra-amniotic inflammation had a higher median amniotic fluid sCD14 concentration than those without these conditions (median 85 ng/ml, range 2-1113 ng/ml vs. median 17 ng/ml, range 0-186 ng/ml; p = 0.01). MIAC/intra-amniotic inflammation in women with preterm labor with intact membranes was associated with a higher median umbilical venous plasma sCD14 concentration (median 744 ng/ml, range 0-3620 ng/ml vs. median 0 ng/ml, range 0-2060 ng/ml; p = 0.04). sCD14 was undetectable in plasma from umbilical cords of all neonates born to women at term. An increase in amniotic fluid concentration of sCD14 was observed in cases of intrauterine infection, not only by gram-negative bacteria, but also gram-positive bacteria and Ureaplasma spp. CONCLUSION: sCD14 is a physiological constituent of amniotic fluid, and its concentrations at term are lower than in the mid-trimester. Intrauterine infection/inflammation is associated with a higher median amniotic fluid sCD14 concentration in both preterm and term parturition. Neonates born from mothers with preterm labor with intact membranes and MIAC/intra-amniotic inflammation had a higher median concentration of sCD14 in umbilical cord plasma than those without these conditions. sCD14 concentrations are increased in the amniotic fluid and umbilical cord blood even in the absence of a microbiologically proven gram-negative infection. CD14 appears to participate in the host response to intrauterine infection even in cases involving genital mycoplasmas.

Lipopolysaccharide-binding protein in microbial invasion of the amniotic cavity and human parturition.

OBJECTIVE: Lipopolysaccharide-binding protein (LBP) is an acute-phase protein of predominantly hepatic origin, capable of binding the lipid A fraction of bacterial lipopolysaccharide (LPS). The complex LBP-LPS binds to CD14, and has been implicated in the host response to gram-negative infection. The purpose of this study was to determine whether microbial invasion of the amniotic cavity (MIAC) and parturition (term and preterm) are associated with changes in the amniotic fluid concentration of LBP. STUDY DESIGN: Amniotic fluid was retrieved by amniocentesis from 343 patients in the following groups: (1) those in mid-trimester with a subsequent normal pregnancy outcome (n = 84); (2) those in mid-trimester with a fetal loss after the procedure (n = 10); (3) those with preterm labor and intact membranes without MIAC who delivered at term (n = 36) or prematurely (n = 52), and those with preterm labor with MIAC (n = 26); (4) those with preterm premature rupture of membranes (PROM) with (n = 26) and without (n = 26) MIAC; and (5) those delivering at term with intact membranes in the absence of MIAC, in labor (n = 52) and not in labor (n = 31). The concentration of LBP in amniotic fluid was determined with a specific and sensitive immunoassay. Non-parametric statistics were used. A p value of < 0.05 was considered significant. RESULTS: LBP was detected in 98% (335/343) of the amniotic fluid samples. MIAC was associated with a significant increase in amniotic fluid concentration of LBP in women with preterm labor and intact membranes, but not in preterm PROM. Spontaneous preterm parturition was associated with a significant increase in amniotic fluid concentration of LBP. Patients who had a spontaneous fetal loss after a mid-trimester amniocentesis had a significantly higher median amniotic fluid LBP concentration than those who had a mid-trimester amniocentesis and a normal perinatal outcome. CONCLUSION: Preterm labor with MIAC and preterm parturition are associated with higher amniotic fluid concentrations of LBP than those with sterile amniotic fluid.

Elevated monocyte chemotactic protein-1 in amniotic fluid is a risk factor for pregnancy loss.

OBJECTIVE: Pregnancy loss after mid-trimester amniocentesis occurs in 0.5-1% of cases and is frequently attributed to the procedure. Accumulating evidence implicates a pre-existing, but clinically silent, intra-amniotic inflammation in the etiology of adverse pregnancy outcome after mid-trimester amniocentesis. Monocyte chemotactic protein-1 (MCP-1) is a potent chemokine produced by a wide variety of cells during the course of an inflammatory response. This study was designed to assess if the amniotic fluid concentration of this chemokine identifies patients at risk for spontaneous abortion and/or fetal death. METHOD: A retrospective case-control study of women who had a mid-trimester amniocentesis was designed. Cases (n = 10) consisted of patients who had a spontaneous pregnancy loss after the procedure, while the control group (n = 84) consisted of patients who had a normal pregnancy outcome after mid-trimester amniocentesis. MCP-1 was measured by a specific enzyme immunoassay (sensitivity, 18.3 pg/ml). The Kolmogorov-Smirnov test was utilized to assess normal distribution of the data. Logarithmic transformation was applied to achieve normality. Statistical analysis was performed using Student's t test. A receiver operating characteristic (ROC) curve analysis was used to select a cut-off to dichotomize amniotic fluid concentrations of MCP-1. RESULTS: MCP-1 was detectable in all amniotic fluid samples. Patients who had a mid-trimester amniocentesis and a subsequent pregnancy loss had a higher mean amniotic fluid log MCP-1 concentration than those with a normal pregnancy outcome (pregnancy loss, mean 2.95 +/- 0.19 pg/ml vs. normal outcome, mean 2.78 +/- 0.19 pg/ml; p = 0.01). A cut-off of > 765 pg/ml was selected by ROC curve analysis (area under the curve, 0.74; p = 0.01). An amniotic fluid concentration of MCP-1 above this level was strongly associated with pregnancy loss (odds ratio, 7.35; 95% confidence interval, 1.7-31.1), a sensitivity of 70%, and a specificity of 76%. CONCLUSION: A subset of women who had a pregnancy loss after a mid-trimester amniocentesis had higher concentrations of the chemokine MCP-1 than those who had a normal pregnancy outcome. Subclinical intra-amniotic inflammation is a risk factor for pregnancy loss after mid-trimester amniocentesis. This observation may have medicolegal and clinical implications. An elevated MCP-1 concentration in amniotic fluid of patients with a pregnancy loss after a mid-trimester amniocentesis indicates that a pathological condition was present at the time of the procedure.

Platelet-activating factor-induced intracellular calcium waves in human uterine myometrial cells.

OBJECTIVE: We visualized and investigated the intracellular calcium waves propagated by platelet-activating factor (PAF) in cultured human myometrial cells. STUDY DESIGN: Myometrial cells were stimulated with PAF ranging between 10(-8) and 10(-15) M. For the observation of calcium waves, calcium green-1 and a confocal laser microscopy were used. Cells were also stimulated with 10(-9) M of PAF in a calcium-free solution. RESULTS: In physiological solution, PAF at concentrations ranging between 10(-9) and 10(-15) M induced intracellular calcium waves. Mean wave speed was 16.1+/-5.6 microm/s. Wave speeds were independent of the PAF concentration. Similar results were observed in the absence of added calcium, with the exception that the wave speeds were significantly slower (7.3+/-3.3 microm/s). CONCLUSIONS This is the first study to demonstrate the calcium waves propagated by PAF stimulation in human myometrial cells. These observations further support the proposed role of PAF in parturition.