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Showing papers by "Roberto Romero published in 2003"


Journal ArticleDOI
TL;DR: Failure of physiologic transformation of the spiral arteries in the myometrial and decidual segments of the placental bed is frequent in patients with preterm labor and intact membranes.

359 citations


Journal ArticleDOI
TL;DR: Dynamic multiplanar slicing and surface rendering of the fetal heart are feasible with STIC technology and may assist in the evaluation of fetal cardiac anatomy.

220 citations


Journal ArticleDOI
TL;DR: The pathophysiology of the fetal inflammatory response syndrome is reviewed, as is its relationship to long-term handicap, such as cerebral palsy and bronchopulmonary dysplasia.
Abstract: Prematurity is the leading cause of perinatal morbidity and mortality worldwide. Intrauterine infection has emerged as a major cause of premature labor and delivery. It has been estimated that 25% of all preterm deliveries occur to mothers who have microbial invasion of the amniotic cavity, although these infections are mostly subclinical in nature. This article describes the pathways leading to intrauterine infection, microbiology, frequency and clinical consequences of infection. The pathophysiology of the fetal inflammatory response syndrome is reviewed, as is its relationship to long-term handicap, such as cerebral palsy and bronchopulmonary dysplasia. A possible role for two micronutrients, vitamins C and E, in the prevention of the preterm prelabor rupture of membranes and the consequences of fetal inflammation is considered. Research needs are listed.

211 citations


Journal ArticleDOI
TL;DR: In this article, a study was conducted to determine the clinical significance of a detection of Ureaplasma urealyticum by using the polymerase chain reaction (PCR) in the amniotic fluid of patients with preterm labor and intact membranes.

195 citations


Journal ArticleDOI
TL;DR: Umbilical cord plasma CRP concentrations were elevated in patients with amniotic fluid infection, congenital neonatal sepsis and funisitis, which was similar to that of interleukin-6.
Abstract: Objective: The purpose of this study was to determine whether concentrations of C-reactive protein (CRP) in umbilical cord plasma at birth were elevated in neonates with sepsis, an inflammatory lesion of the umbilical cord (funisitis) or who were born to mothers with microbial invasion of the amniotic cavity. Methods: Umbilical cord plasma was collected at birth from 313 singleton preterm neonates (20-35 weeks of gestation). The results of amniotic fluid culture performed within 5 days of birth, the occurrence of congenital neonatal sepsis and the presence of funisitis were assessed. Amniocentesis was performed in 152 patients within 5 days of birth. Amniotic fluid was cultured for aerobic and anaerobic bacteria and for mycoplasmas. The CRP concentration was measured with a highly sensitive immunoassay. Results: The median cord plasma CRP concentration was significantly higher in neonates with a positive amniotic fluid culture than in those with negative culture (median 245.9 (range 11.6-4885.5) ng/ml vs....

121 citations


Journal ArticleDOI
TL;DR: This study was designed to compare a conventional multiplanar technique for three‐dimensional ultrasound measurement of fetal lung volume with a rotational method using VOCAL™ (Virtual Organ Computer‐aided AnaLysis).
Abstract: Objectives This study was designed to compare a conventional multiplanar technique for three-dimensional (3D) ultrasound measurement of fetal lung volume with a rotational method using VOCAL™ (Virtual Organ Computer-aided AnaLysis). Methods Thirty-two fetuses with a variety of conditions at risk for pulmonary hypoplasia were studied. 3D volume data sets of the fetal lungs were acquired using a commercially available ultrasound system. The right and left lung volumes were calculated separately using VOCAL and the multiplanar technique. The level of agreement between two independent observers in categorizing the 3D volume data set as measurable or non-measurable was determined. The interobserver and intermethod variabilities were also evaluated for both methods. Results The intermethod variability was excellent (correlation r = 0.93 and r = 0.96 for the left and right lung, respectively), and there was substantial agreement between the results of both approaches (limits of agreement − 4.4 to 8.9 and − 3.4 to 4.8 mL for the right and left lung, respectively). Fetal lung estimation with VOCAL had a significantly higher interobserver variability than the multiplanar technique. Interobserver agreement in categorizing lung volume data sets as measurable or non-measurable was lower when VOCAL was used. Conclusion Fetal lung volume measurements can be undertaken interchangeably using the multiplanar technique or the rotational method with VOCAL. However, the latter was less reproducible (lower degree of agreement and significantly higher interobserver variability) than the former. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.

118 citations


Journal ArticleDOI
TL;DR: MMP-3 is a physiologic constituent of amniotic fluid and may play a role in the mechanisms of human parturition and in the regulation of the host response to intrauterine infection.
Abstract: Objective. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are expressed in many inflammatory conditions and contribute to connective tissue breakdown. Stromelysin 1 [matrix metalloproteinase 3 (MMP-3)], a novel member of this family, is produced in in the context of infection and is able to activate the latent forms of other MMPs. The purpose of this study was to determine if parturition (either term or preterm), premature rupture of the membranes (PROM), and microbial invasion of the amniotic cavity are associated with changes in amniotic fluid concentrations of MMP-3. Study design. A cross-sectional study was conducted, which included women who underwent transabdominal amniocentesis (n = 365) in the following categories: (1) mid-trimester with a subsequent normal pregnancy outcome (n = 84) and a subsequent fetal loss (n = 10); (2) preterm labor with intact membranes without microbial invasion of the amniotic cavity who delivered at term (n = 36), or prematurely (n = 50), and preterm labor with microbial invasion of the amniotic cavity (n = 25); (3) preterm PROM with (n = 25) and without (n = 26) microbial invasion of the amniotic cavity; (4) term with intact membranes in the absence of microbial invasion of the amniotic cavity, in labor (n = 52) and not in labor (n = 31); and (5) term with PROM in the absence of microbial invasion of the amniotic cavity and not in labor (n = 26). MMP-3 concentrations in amniotic fluid were measured by a sensitive and specific immunoassay that was validated for amniotic fluid. MMP-3 concentrations were normalized using logarithmic transformation for statistical analysis. Parametric statistics were used and a p value <0.05 was considered statistically significant. Results. (1) MMP-3 was detected in 99.5 % (363/365) of amniotic fluid samples, and its concentration did not change with advancing gestational age. (2) Spontaneous parturition at term and preterm was associated with a significant increase in amniotic fluid MMP-3 concentrations (p = 0.04 and p = 0.002, respectively). (3) Spontaneous rupture of membranes in term and preterm gestations was not associated with significant changes in amniotic fluid MMP-3 concentrations. (4) Intra-amniotic infection was associated with a significant increase in amniotic fluid MMP-3 concentrations in both women with preterm labor and intact membranes (p = 0.03), and women with preterm PROM (p = 0.02). (5) Subsequent fetal loss after genetic amniocentesis was not associated with significant changes in mid-trimester concentrations of amniotic fluid MMP-3. Conclusions. (1) MMP-3 is a physiologic constituent of amniotic fluid. (2) MMP-3 may play a role in the mechanisms of human parturition and in the regulation of the host response to intrauterine infection.

85 citations


Journal ArticleDOI
TL;DR: The preterm fetus is capable of mounting a systemic cytokine response as measured by IL-6 in its peripheral blood, and in the setting of MIAC, a fetal IL- 6 response is higher in preterm than in term gestation.
Abstract: Background/objective: Fetal inflammatory response has been implicated as a mechanism of multi-system organ injury in preterm and term neonates. Microbial invasion of the amniotic cavity (MIAC) is frequently associated with a fetal inflammatory response. However, there are no studies comparing the fetal response to MIAC in term and preterm gestations. The purpose of this study was to compare the umbilical cord plasma interleukin-6 (IL-6) concentrations in term and preterm neonates in the presence or absence of MIAC. Study design: Umbilical cord blood was obtained at birth from 252 neonates whose mothers had an amniocentesis within 48 h of delivery (preterm delivery, n = 62; term delivery, n = 190). MIAC was defined as a positive amniotic fluid culture for bacteria or genital mycoplasmas. IL-6 was measured by a sensitive and specific immunoassay. Results: The median IL-6 concentration in umbilical cord plasma was significantly higher in preterm neonates than in term neonates (median 13.4 pg/ml, range 0.1‐ 676 pg/ml vs. median 3.2 pg/ml, range 0.1‐ 408 pg/ml; p < 0.0001). In the context of MIAC, the median umbilical cord plasma IL-6 concentration was significantly higher in preterm than in term neonates (median 31.6 pg/ml, range 1.4‐ 676 pg/ml vs. median 11.7 pg/ml, range 1.3‐ 82 pg/ml, respectively; p < 0.05). Neonates born to mothers with a positive amniotic fluid culture had a significantly higher median IL-6 concentration than neonates born to mothers with a negative amniotic fluid culture (preterm: median 31.6, range 1.4‐ 676 pg/ml vs. median 8.0, range 0.1‐ 656 pg/ml; p < 0.05 and term: median 11.7, range 1.3‐ 82 pg/ml vs. median 3.1, range 0.1‐ 408 pg/ml; p < 0.01, respectively). Conclusions: The preterm fetus is capable of mounting a systemic cytokine response as measured by IL-6 in its peripheral blood. In the setting of MIAC, a fetal IL-6 response is higher in preterm than in term gestation.

70 citations


Journal ArticleDOI
TL;DR: The “parvo biovar” is more frequently isolated from amniotic fluid of preterm gestations than the “T960 biovars”, and biavar diversity of U. urealyticum in amniotics fluid was not associated with different pregnancy outcome and magnitude of the intraamniotic inflammatory response.
Abstract: OBJECTIVE: The objective of this study was to determine the distribution of two biovars of Ureaplasma urealyticum (parvo and T960) in human amniotic fluid and to examine whether the magnitude of the intrauterine inflammatory response and pregnancy outcomes are different between patients with microbial invasion of the amniotic cavity with "parvo biovar" and those with "T960 biovar". STUDY DESIGN: This cohort included 77 preterm singleton pregnancies (gestational age < 37 weeks) in whom U. urealyticum was detected from amniotic fluid using the polymerase chain reaction (PCR). Amniotic fluid was obtained by transabdominal amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as mycoplasmas. U. urealyticum was biotyped by PCR methods. Amniotic fluid inflammatory response was determined by amniotic fluid white blood cell count and interleukin-6 concentration. RESULTS: 1) The "parvo biovar" was detected in 82% (63/77) and "T960 biovar" was in 18% (14/77) of cases; 2) U. urealyticum was isolated by conventional culture method from amniotic fluid in 56% (35/63) of cases with positive for "parvo biovar" and in 50% (7/14) of cases with positive for "T960 biovar"; 3) There were no significant differences in the median gestational age at amniocentesis, gestational age at delivery, birth weight, amniotic fluid white blood cell count, amniotic fluid interleukin-6 concentration and the rates of clinical chorioamnionitis, histologic chorioamnionitis, funisitis and neonatal morbidity between patients in the two biovar groups. CONCLUSIONS: 1) The "parvo biovar" is more frequently isolated from amniotic fluid of preterm gestations than the "T960 biovar"; 2) Biovar diversity of U. urealyticum in amniotic fluid was not associated with different pregnancy outcome and magnitude of the intraamniotic inflammatory response.

63 citations


Journal ArticleDOI
TL;DR: In this paper, TNF-related apoptosis-inducing ligand (TRAIL) and its membrane-bound (R1-R4) and soluble receptors [osteoprotegerin (OPG)] in gestational membranes were assessed to assess their significance in preterm parturition and premature rupture of membranes (PROM).
Abstract: We have studied TNF-related apoptosis-inducing ligand (TRAIL) and its membrane-bound (R1–R4) and soluble receptors [osteoprotegerin (OPG)] in gestational membranes to assess their significance in preterm parturition and premature rupture of membranes (PROM). TRAIL was detected by ELISA in extracts of term choriodecidual (but not amnion) tissues and explant-conditioned media. Concentrations of OPG (determined using ELISA) in gestational membranes were 20- to 50-fold greater than those of TRAIL. Median OPG concentrations in amniotic fluid (AF) at 15–17 wk gestation were similar to those at term before and during labor, whereas levels in pregnancies sampled preterm were significantly elevated. OPG levels in AF from women with preterm PROM were similar to those from women in preterm labor. In contrast, in pooled AF samples (n = 23–33), TRAIL concentrations at term with and without labor were elevated compared with samples from preterm deliveries. TRAIL-R3 and -R4 decoy receptors were detected in term amnion a...

59 citations


Journal ArticleDOI
TL;DR: The prevalence of microbial invasion of the amniotic cavity (MIAC) and the frequency of maternal and/or fetal inflammation in patients presenting with a fetal death was determined and MIAC could be demonstrated with conventional microbiological techniques in only one case.
Abstract: Objective: The role of intra-amniotic infection in the etiology of fetal death has been proposed. This study was conducted to determine the prevalence of microbial invasion of the amniotic cavity (MIAC) and the frequency of maternal and/or fetal inflammation in patients presenting with a fetal death. Methods: A prospective study was conducted in patients with a fetal death. Amniocenteses were performed for clinical indications (karyotype), as well as to assess the microbiological and cytological state of the amniotic cavity. Fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. An amniotic fluid white blood cell count and glucose determinations were also performed. Histological examination of the placenta was conducted to identify a maternal inflammatory response (acute chorioamnionitis) or a fetal inflammatory response (funisitis). Results: This study included 44 patients with intrauterine fetal death. The median gestational age at diagnosis was 30.1 weeks (range 16.3-40.4 weeks)...

Journal ArticleDOI
TL;DR: In this paper, a genome-wide approach was used to identify differentially expressed genes in patients with preterm premature rupture of membranes to improve the understanding of underlying molecular mechanisms, which demonstrated the usefulness of functional genomics for the dissection of mechanisms of disease and identification of differentially regulated genes that were not suspected previously to play a role in parturition.

Journal ArticleDOI
TL;DR: The hypothesis that MCP-1 may play a role in the final common pathway of spontaneous labor is supported, as the amniotic fluid levels of immunoreactive M CP-1 increase during spontaneous labor at term.
Abstract: Objective: Parturition is characterized by an influx of inflammatory cells into gestational tissues, a phenomenon conducive to increased myometrial contractility, cervical ripening and decidual/membrane activation. Monocyte chemotactic protein-1 (MCP-1), a potent chemoattractant and activator of monocytes/macrophages, is expressed in gestational tissues and, thus, may participate in the final common pathway of labor. This study was undertaken to determine whether the amniotic fluid concentrations of immunoreactive MCP-1 are altered with gestational age or spontaneous labor at term with and without prelabor rupture of the gestational membranes. We also sought to identify intrapartum differences in the concentrations of immunoreactive MCP-1 between the upper and lower amniotic fluid compartments. Methods: A cross-sectional study was conducted to assess the concentrations of immunoreactive MCP-1 in amniotic fluid. Amniotic fluid samples were obtained from 225 women as follows: (1) women undergoing mid-trimes...

Journal ArticleDOI
TL;DR: Three‐dimensional ultrasonography can be used to evaluate the fetal nasal bone with substantial interobserver agreement during the second and early third trimesters of pregnancy and identified 40% to 45% of fetuses with Down syndrome in this study.
Abstract: Objective. This study examined the use of three-dimensional ultrasonography for evaluating the fetal nasal bone, as a sonographic marker of Down syndrome, during the second and early third trimesters of pregnancy. Methods. Forty fetuses, including 20 with trisomy 21, were scanned once by threedimensional ultrasonography. A midline sagittal view of the facial profile was used to analyze the volume data. Independent examiners reviewed blinded and randomly allocated volume data sets for the nasal bone. Interobserver reliability was evaluated for the sonographic presence or absence of the nasal bone. Logistic regression determined the contribution of this parameter to the presence of Down syndrome. Results. Both examiners showed substantial agreement in scoring whether the nasal bone was visualized by three-dimensional ultrasonography (P < .001). They identified 40% to 45% of fetuses with abnormalities using the absence of the nasal bone as a sonographic marker. However, a substantial number of fetuses with abnormalities were also found to have a nasal bone present. The nasal bone was visualized in 80% to 90% of fetuses without abnormalities. Conclusions. Three-dimensional ultrasonography can be used to evaluate the fetal nasal bone with substantial interobserver agreement during the second and early third trimesters of pregnancy. A nonvisualized nasal bone identified 40% to 45% of fetuses with Down syndrome in this study. Key words: fetus; nasal bone; prenatal diagnosis; three-dimensional ultrasonography; trisomy 21.

Journal ArticleDOI
TL;DR: In this article, the use of three-dimensional power Doppler ultrasonography to identify vascular congenital anomalies of fetal portosystemic and umbilical venous systems was described.

Journal ArticleDOI
TL;DR: Bi-directional fetomaternal trafficking of cells and nucleic acids during pregnancy is now well established, through the use of molecular techniques including conventional and real-time polymerase chain reaction, as well as fluorescence in situ hybridization.
Abstract: Objective: The National Institute of Child Health and Human Development (NICHD) held a workshop on 27-28 July 2000 to bring together investigators working in the field of fetomaternal cellular and nucleic acid trafficking with the hope that this would stimulate further research into the biological implications of such phenomena. Methods: Invited speakers from all over the world presented their latest (unpublished) data. The conference proceedings were delayed until the present time to allow independent publication of the primary data. Results and conclusions: Bi-directional fetomaternal trafficking of cells and nucleic acids during pregnancy is now well established, through the use of molecular techniques including conventional and real-time polymerase chain reaction, as well as fluorescence in situ hybridization. In addition, human leukocyte antigen (HLA) is deposited in the skin of pregnant women. Feto-maternal trafficking is increased in some complications of pregnancy, such as pre-eclampsia, polyhydra...

Journal ArticleDOI
TL;DR: It is concluded that AF MIC-1 is derived from the fetal membranes and decidua, but that MIC- 1 is unlikely to be involved in the pathophysiology of preterm birth or PROM.
Abstract: The placenta and fetal membranes are the site of expression of macrophage inhibitory cytokine (MIC-1), a member of the transforming growth factor (TGF)-b superfamily. We hypothesized that MIC-1 may act as an immune regulator in pregnancy complications associated with intrauterine inflammation. Decidual cells, chorionic trophoblasts and amnion epithelial cells were identified by immunohistochemistry as the predominant MIC-1-containing cell type in term membranes. Amnion and choriodecidual explants all produced MIC-1 in culture, the latter having the greatest production rate (206 6 74.5 pg/mg tissue/24 h, n = 6; mean 6 6 SEM). Production was not responsive to stimulation by pro-inflammatory cytokines. MIC-1 was detectable in 217 transabdominal amniotic fluid (AF) samples taken from 15 to 41 weeks gestation, concentrations ranging from 0.9‐51.1 ng/ml. AF MIC-1 concentrations in pregnancies with premature rupture of membranes (PROM) or preterm labour, either with or without microbial invasion of the amniotic cavity, were not significantly different from those delivered at term either with or without labour. Treatment with MIC-1 (0.25‐25 ng/ml) did not alter production of interleukin-6 or -8 by amnion or choriodecidual cells in vitro. We conclude that AF MIC-1 is derived from the fetal membranes and decidua, but that MIC-1 is unlikely to be involved in the pathophysiology of preterm birth or PROM.

Journal ArticleDOI
TL;DR: Pre-eclampsia is associated with a higher NK cell (CD3-/CD56+16+) subset of lymphocytes in umbilical cord blood than in the control group, which cannot be explained by fetal acidosis or the presence of labor.
Abstract: Objective: Maternal endothelial dysfunction and intravascular inflammation have been implicated in the mechanisms of disease responsible for the clinical syndrome of pre-eclampsia. Recently, the activation of the innate limb of the immune response (neutrophils and monocytes) in the fetal circulation has been reported in neonates born to mothers with pre-eclampsia. Natural killer (NK) cells are identified morphologically as a subpopulation of lymphocytes, but functionally as one component of the innate immune system. NK cells participate in the control of viral or bacterial infection, regulation of hematopoiesis, production of cytokines and cytotoxicity of neoplastic cells. Accumulating evidence suggests that the innate system is required for mounting an adequate adaptive response. NK cells, originally defined as effector cells of the innate immune system, may also play a role as regulatory cells for the adaptive immune system. This study was designed to determine the proportion of the NK cell subset of ly...

Journal ArticleDOI
TL;DR: STIC can be reproducibly used to evaluate fetal cardiac outflow tracts by independent examiners and slightly better image quality rating scores during the intraobserver variability trial suggests the presence of a learning curve for the manipulation and analysis of volume data obtained by STIC.
Abstract: OBJECTIVE To test the agreement between observers and reproducibility of a technique to display standard cardiac views of the left and right ventricular outflow tracts from four-dimensional volume datasets acquired with Spatiotemporal Image Correlation (STIC). METHODS A technique was developed to obtain dynamic multiplanar images of the left ventricular outflow tract (LVOT) and right ventricular outflow tract (RVOT) from volume datasets acquired with STIC. Volume datasets were acquired from fetuses with normal cardiac anatomy. Twenty volume datasets of satisfactory quality were pre-selected by one investigator. The data was randomly assigned for a blinded review by two independent observers with previous experience in fetal echocardiography. Only one volume dataset was used for each fetus. After a training session, the observers obtained standardized cardiac views of the LVOT and RVOT, which were scored on a scale of 1 to 5, based on diagnostic value and image quality (1=unacceptable, 2=marginal, 3=acceptable, 4=good, and 5=excellent). Median scores and interquartile range, as well as inter- and intraobserver agreement were calculated for each view. RESULTS The mean menstrual age at the time of volume acquisition was 25.5+/-4.5 weeks. Median scores (interquartile range) for LVOT images, obtained by the first and second observers, were 3.5 (2.25-5.00) and 4 (3.00-5.00), respectively. The median scores (interquartile range) for RVOT images obtained by the first and second observers were 3 (3.00-5.00) and 3 (2.00-4.00), respectively. The interobserver intraclass correlation coefficient for the LVOT was 0.693 (95% CI 0.380-0.822), and 0.696 (95% CI 0.382-0.866) for the RVOT. For the intraobserver agreement analysis, observer 1 gave higher scores to the LVOT the second time the volumes were analyzed [LVOT: 3.50 (2.25-5.00) vs. 5.00 (4.00-5.00, p=0.008)]. CONCLUSION STIC can be reproducibly used to evaluate fetal cardiac outflow tracts by independent examiners. Slightly better image quality rating scores during the intraobserver variability trial suggests the presence of a learning curve for the manipulation and analysis of volume data obtained by STIC.

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TL;DR: Histamine increases spontaneous, but inhibits tonic, contractions of uterine strips from term pregnant nonlaboring women, both effects are mediated through activation of H(1) receptors.

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TL;DR: Three‐dimensional power Doppler ultrasonography is an important adjunctive method that can be used to characterize normal vascular development and circulatory anomalies of the fetus.
Abstract: Objectives: to present the appearance of fetal and placental vascular anatomic structures by three-dimensional power Doppler ultrasonography. Methods: three-dimensional multiplanar imaging, surface rendering, and volume rendering were combined with power Doppler ultrasonography to show the methods, imaging artifacts, and diagnostic potential of this technology during pregnancy. Results: fetuses with normal and abnormal vascular anatomic structures were evaluated by three-dimensional power Doppler ultrasonography. The combination of several imaging modalities (e.g., threedimensional multiplanar imaging, surface rendering, and volume rendering) with power Doppler ultrasonography is shown. Conclusions: three-dimensional power Doppler ultrasonography is an important adjunctive method that can be used to characterize normal vascular development and circulatory anomalies of the fetus.

Journal ArticleDOI
TL;DR: A case of dilated coronary sinus with persistent left superior vena cava diagnosed at 33 weeks in a fetus with trisomy 18 is reported and the features of this cardiac anomaly on prenatal ultrasonography are discussed.
Abstract: A case of dilated coronary sinus with persistent left superior vena cava diagnosed at 33 weeks in a fetus with trisomy 18 is reported. The features of this cardiac anomaly on prenatal ultrasonography and its association with trisomy 18 are discussed. Published in 2003 John Wiley & Sons, Ltd.

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TL;DR: A policy of offering genetic sonography followed by amniocentesis to patients 35 years of age and older who originally had triple‐marker maternal serum screening findings that were negative for the diagnosis of trisomy 21 results in a higher overall detection rate of tr isomy 21.
Abstract: Objective. To determine whether offering genetic sonography to patients 35 years of age and older with negative maternal serum triple-marker screening results will result in an increase in the detection rate of trisomy 21. Methods. The detection rate of trisomy 21 was determined in women 35 years of age and older whose pregnancies were managed according to the following 3 policies: policy I, universal amniocentesis; policy II, maternal serum triple-marker screening followed by amniocentesis only in high-risk women (risk >1:190); and policy III, genetic sonography in women with negative maternal serum screening results (policy II). Policy III included the offering of genetic amniocentesis to patients with abnormal genetic sonographic findings. The rate of acceptance of genetic amniocentesis was modeled, as was the sensitivity (50%‐90%) and false-positive rate (5%‐25%) of genetic sonography. Results. The number of fetuses expected to have trisomy 21 was 784. For patients evaluated under policy II, 86.3% of fetuses with trisomy 21 were detected. On the basis of the detection rate for trisomy 21 of policy II, the addition of fetuses with trisomy 21 identified under policy III was significantly (P < .01) increased (93.2% to 98.6%) for genetic sonographic sensitivities ranging between 50% and 90%. Conclusions. A policy of offering genetic sonography followed by amniocentesis to patients 35 years of age and older who originally had triple-marker maternal serum screening findings that were negative for the diagnosis of trisomy 21 results in a higher overall detection rate

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TL;DR: 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.
Abstract: 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+ lymphocy...

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TL;DR: Kim et al. as mentioned in this paper reported the first putative disease-causing mutations in an analysis of the DBH locus in two unrelated patients and their families, who were compound heterozygotes who each carried a single copy of a T!C transition at the donor splice site of intron 1 (IVS1þ 2T!C) that resulted in an aberrantly spliced product containing a premature stop codon in an in vitro splicing assay.
Abstract: Dopamine beta-hydroxylase (DBH; OMIM 223360) catalyzes the conversion of dopamine (DA) to norepinephrine (NE) in the central and peripheral nervous systems. DBH deficiency is a very rare genetic disorder characterized by severe sympathetic failure in which circulating levels ofNEandepinephrine (E)areundetectable, but DA levels are greatly elevated [Robertson et al., 1986]. The onset of symptoms occurs at birth or in early childhood and as adults all affected individuals suffer from profound postural hypotension and exercise intolerance. Only six patients from five families with the disorder, all of Western European descent, are well described in the literature [Robertson et al., 1986; Man in ’t Veld et al., 1987, 1988; Biaggioni et al., 1990; Mathias et al., 1990]. We recently reported the first putative disease-causing mutations in an analysis of the DBH locus in two unrelated patients and their families [Kim et al., 2002]. Both patients were compound heterozygotes who each carried a single copy of a T!C transition at the donor splice site of intron 1 (IVS1þ 2T!C) that resulted in an aberrantly spliced product containing a premature stop codon in an in vitro splicing assay. On the homologous chromosome, a total of three different missense mutations in the DBH gene were detected: one in patient 1 (exon 2) and two in patient 2 (exons 1and6). Themechanismbywhich these missensemutations produce a loss of DBH function is as yet unknown. In our initial analysis, we genotyped a small sample of 88 healthy European-American (EA) subjects, and found no carriers of any of the threemissensemutations [Kim et al., 2002]. However, we found two subjects heterozygous for IVS1þ2T!C, which yielded an unexpectedly high C allele frequency of 0.011 0.008. This suggested a large discrepancy between the prevalence of homozygotes for the C allele and individuals affected with DBH deficiency. One possible explanation is that these homozygotes are frequently embryonic lethal, which is consistent with the low survival rate observed inmouse embryos lackingDBH [Thomas et al., 1995]. Given our initial allele frequency estimate, these data indicated that DBH deficiency might thus be an epidemiologically significant cause of fetal demise. However, more extensive genotyping studies were clearly warranted in order to accurately estimate the frequency of DBH deficiency-related mutations in the general population.Herewe report frequencies for these mutations in a substantially larger sample of subjects of both European and African-American (AA) heritage. DNA samples from a total of 801 unrelated adults were collected in the course of several genetic studies as previously described [Zabetian et al., 2000; Kohnke et al., 2002] from the following groups: 122 AAs, 456 EAs, and223 individuals ofGermandescent.Thegroups included healthy individuals and those with psychiatric and substance-use disorders. However, none of these subjects reported severe disturbances in autonomic function and thus all were considered as controls for the purpose of this study. The EA and German population samples were combined to simplify data analysis and are abbreviated as ‘‘EA/G.’’ In order to supplement theAAsample,we includedDNAcollected froma total of 260 AA mothers and infants during an ongoing study of genetic risk factors for preterm labor. DNA from two EA patients with DBHdeficiency and their familymembers was obtained as previously reported [Kim et al., 2002]. None of the four putative disease-causing mutations (IVS1þ2T!C,V87M,D100E,D331N)weredetected in any of the 122 AA or 679 EA/G adult controls genotyped in this study. IVS1þ2T!C was also genotyped in the AA mother–infant group, and a single preterm infant was found to be heterozygous for the mutation. This suggests that the C allele frequency of IVS1þ2T!C that we initially reported in EAs [Kim et al., 2002] was Grant sponsor: NARSAD; Grant sponsor: NASA; Grant sponsor: the Nathan Blaser Shy-Drager Research Program; Grant sponsor: NIH; Grant sponsor: Tuebingen University; Grant sponsor: the US.


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TL;DR: HB, viscosity (represented by HCT), pO2, and oxygen content each influence the MCA-PSV of the human fetus and diminish the reliability of fetal anemia prediction.

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TL;DR: Proteomic analysis of amniotic fluid revealed unique differential expression of proteins in three subsets of preterm labor, and can be used for the identification of biomarkers and to improve the understanding of the mechanisms of disease in preterm parturition.

Journal ArticleDOI
TL;DR: Sonographic measurement of cervical length helps to avoid over-diagnosis of preterm labour in women with preterm contractions and intact membranes and may be helpful to avoid unnecessary intervention.
Abstract: Objective: In threatened preterm labour less than 15% of the women will progress to active labour and delivery. This study investigates if cervical length measurements by transvaginal ultrasound can discriminate between true and false labour in women presenting with preterm contractions. Methods: Cervical length was measured by transvaginal ultrasound in 253 women with singleton pregnancies presenting with painful uterine contractions at 24–36 (median 30.5) weeks of gestation. Women presenting in active labour defined by cervical dilatation, with ruptured membranes and those that underwent prior or subsequent cervical cerclage were excluded from the study. The clinical management was determined by the attending obstetrician without taking into account the cervical length. Primary outcome of the study was delivery within seven days of presentation. Results: Delivery within seven days of presentation occurred in 21 of the 253 (8.2%) pregnancies and this was inversely related to cervical length. In 209 cases the cervical length was 15 mm or more and only two of these (1%) delivered within seven days. In the 44 with cervical length less than 15 mm delivery within seven days of presentation occurred in 19 (43.2%). Logistic regression analysis demonstrated that significant independent contribution in the prediction of delivery within seven days was provided by cervical length (p < 0.0001), previous contraction frequency at presentation (p < 0.009), history of preterm delivery (p < 0.01) and vaginal bleeding (p < 0.019) with no significant contribution from gestation at presentation, ethnic origin, maternal age, parity, cigarette smoking or the administration of tocolysis, antibiotics or steroids. Conclusions: Sonographic measurement of cervical length helps to avoid over-diagnosis of preterm labour in women with preterm contractions and intact membranes and may be helpful to avoid unnecessary intervention.