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Biomedical subjects

E Maymon

Publications and source records attributed to E Maymon.

At least 37 records · Page 2Linked to original sources

Evidence of in vivo differential bioavailability of the active forms of matrix metalloproteinases 9 and 2 in parturition, spontaneous rupture of membranes, and intra-amniotic infection.

OBJECTIVE: Matrix metalloproteinases (MMP-9 and MMP-2) have been implicated in the digestion of fetal membranes. The purpose of this study was to determine the amniotic fluid concentrations of active forms of MMP-2 and MMP-9 and to explore the participation of these enzymes in labor (term and preterm), rupture of membranes (term and preterm), and microbial invasion of the amniotic cavity. STUDY DESIGN: A cross-sectional study was conducted with 291 women in the following categories: (1) term not in labor, (2) term in labor, (3) preterm labor and intact membranes who delivered at term, (4) preterm labor who delivered preterm, (5) preterm labor with microbial invasion of the amniotic cavity, (6) preterm premature rupture of membranes without microbial invasion of the amniotic cavity, (7) preterm premature rupture of membranes with microbial invasion of the amniotic cavity, (8) term premature rupture of membranes not in labor, and (9) mid trimester. Active forms of MMP-2 and MMP-9 were measured by a novel assay that uses a substrate developed by protein engineering. RESULTS: (1) MMP-2 and MMP-9 were detected in 88% and 96% of amniotic fluid samples, respectively (255/291 and 279/291). (2) The concentrations of active forms of MMP-2 and MMP-9 changed with advancing gestational age. (3) Spontaneous term parturition was associated with a significant increase in the median concentration of the active forms of MMP-9 (P <.005) and a significant decrease in the median concentration of the active forms of MMP-2 (P <.003). (4) Preterm labor with intact membranes leading to preterm delivery in the absence of infection was associated with a significant increase in the median concentration of the active forms of MMP-9 (P <.005) but not of the active forms of MMP-2 (P =.2). (5) Rupture of membranes (either term or preterm) was associated with a significant increase in the concentration of the active forms of MMP-9 and with a significant decrease in the concentration of the active forms of MMP-2 (P <.005 for term and P <.03 and P <.003 for preterm, respectively). (6) Microbial invasion of the amniotic cavity in women with preterm premature rupture of membranes was also associated with a significant increase in the concentration of the active forms of MMP-9 (P <.03) and a decrease in the concentration of the active forms of MMP-2 (P <.05). (7) Microbial invasion of the amniotic cavity in patients with preterm labor was associated with a significant increase in the median concentration of the active forms of MMP-9 (P <.005) but not of the active forms of MMP-2 (P =.6). CONCLUSION: Spontaneous rupture of membranes (either term or preterm), parturition (either term or preterm), and microbial invasion of the amniotic cavity were associated with significant increases in the amniotic fluid concentration of the active forms of MMP-9. In contrast, the concentration of the active forms of MMP-2 either decreased or remained the same in these conditions. Our observations provide evidence for a novel regulation of gelatinolytic activity in vivo.

Amnion↗

Evidence for the participation of interstitial collagenase (matrix metalloproteinase 1) in preterm premature rupture of membranes.

OBJECTIVE: Rupture of membranes is thought to result from the effects of physical forces in localized areas of the membranes weakened by the degradation of structural collagens. Matrix metalloproteinases are enzymes that degrade extracellular matrix components and have been implicated in membrane rupture. The objective of this study was to determine whether spontaneous rupture of membranes is associated with a change in the amniotic fluid concentration of interstitial collagenase (matrix metalloproteinase 1 [MMP-1]), a major collagenase. STUDY DESIGN: A cross-sectional study was conducted to determine MMP-1 concentrations in amniotic fluid from 353 women in the following categories: (1) term with intact membranes not in labor and in labor, (2) preterm labor who delivered at term, (3) preterm labor who delivered preterm without microbial invasion of the amniotic cavity, (4) preterm labor who delivered preterm with microbial invasion of the amniotic cavity, (5) preterm premature rupture of membranes with and without microbial invasion of the amniotic cavity, (6) term premature rupture of membranes not in labor and in labor, and (7) mid trimester of pregnancy. Microbial invasion of the amniotic cavity was determined by an amniotic fluid culture positive for microorganisms. MMP-1 concentrations in amniotic fluid were determined by means of sensitive and specific immunoassays. RESULTS: (1) MMP-1 was detectable in 81.3% of amniotic fluid samples (287/353), and its concentrations increased with advancing gestational age (r = 0.4; P <.001). (2) Preterm premature rupture of membranes was associated with a significant increase in the median amniotic fluid concentration of MMP-1 (P =.02). (3) Women with term premature rupture of membranes had a significantly lower amniotic fluid MMP-1 concentration than those with intact membranes at term not in labor (P <.001). (4) Microbial invasion of the amniotic cavity in patients in preterm labor with intact membranes and in patients with preterm premature rupture of membranes was also associated with significant increases in the median amniotic fluid MMP-1 concentrations (P <.05 and P <.01, respectively). (5) Patients with preterm premature rupture of membranes and microbial invasion of the amniotic cavity had a significantly higher median amniotic fluid MMP-1 concentration than those with intact membranes and microbial invasion of the amniotic cavity (P =.01). (6) Neither term nor preterm parturition was associated with changes in amniotic fluid MMP-1 concentrations (P =.6 and P =.3, respectively). CONCLUSION: (1) Collagenase 1 (MMP-1) is a physiologic constituent of amniotic fluid. (2) Preterm premature rupture of membranes (in both the presence and absence of infection) was associated with an increase in the amniotic fluid MMP-1 concentrations. (3) Neither term nor preterm parturition was associated with a significant increase in the amniotic fluid concentration of MMP-1.

Amnion↗

Participation of the novel cytokine interleukin 18 in the host response to intra-amniotic infection.

OBJECTIVE: Interleukin 18 is a proinflammatory pleiotropic cytokine that has been implicated in the host defense against infection. This study was undertaken to determine whether interleukin 18 concentrations change in the maternal, fetal, and amniotic fluid compartments with labor (term and preterm) and microbial invasion of the amniotic cavity. STUDY DESIGN: Amniotic fluid was assayed for interleukin 18 in samples obtained from 285 patients in the following groups: (1) term not in labor (n = 22), in labor (n = 19), and with microbial invasion of the amniotic cavity (n = 16); (2) preterm labor who delivered at term (n = 38), who delivered preterm but without microbial invasion of the amniotic cavity (n = 41), and preterm labor with microbial invasion of the amniotic cavity (n = 24); (3) preterm premature rupture of membranes without microbial invasion of the amniotic cavity (n = 30) and with microbial invasion of the amniotic cavity (n = 34); (4) term premature rupture of membranes not in labor (n = 20) and term premature rupture of membranes in labor (n = 19); and (5) midtrimester (n = 22). In addition, cord and maternal plasma samples from women at term not in labor (n = 20) and in labor (n = 20) were assayed for interleukin 18. RESULTS: (1) Interleukin 18 was detectable in all amniotic fluid samples and maternal and umbilical cord blood samples. (2) Interleukin 18 concentrations increased with advancing gestational age (r = 0.47; P <.0001). (3) Microbial invasion of the amniotic cavity in either preterm or term parturition was associated with a significant increase in the amniotic fluid concentration of interleukin 18 (preterm labor without microbial invasion of the amniotic cavity: median, 14.95 pg/mL; range, 3.9-277.0 pg/mL; vs preterm labor with microbial invasion of the amniotic cavity: median, 20.75 pg/mL; range, 5.53-160.21 pg/mL; P <.02; term labor without microbial invasion of the amniotic cavity: median, 18.73 pg/mL; range, 5.09-95.44 pg/mL; vs term labor with microbial invasion of the amniotic cavity: median, 24.35 pg/mL; range, 10.07-144.42 pg/mL; P<.004). (4) Both term and preterm parturition were associated with a modest increase in amniotic fluid interleukin 18 concentrations, although this trend did not reach statistical significance. (5) Rupture of membranes at term was associated with a significant decrease in amniotic fluid interleukin 18 concentrations (intact membranes: median, 14.96 pg/mL; range, <3.89-26.07 pg/mL; vs rupture of membranes: median, 10.1 pg/mL; range, 4.29-21.44 pg/mL; P <.001). CONCLUSION: (1) Interleukin 18 is increased in cases of microbial invasion of the amniotic cavity. (2) Interleukin 18 is detectable in the amniotic, maternal, and fetal compartments. (3) We propose that this novel cytokine plays a role in the host defense against infection.

Amnion↗

Lactoferrin in intrauterine infection, human parturition, and rupture of fetal membranes.

OBJECTIVE: Lactoferrin is an iron-binding protein with antimicrobial properties. This study was undertaken to determine whether amniotic fluid concentrations of this protein change with gestational age, infection, labor, and rupture of membranes. STUDY DESIGN: This cross-sectional study included women who underwent transabdominal amniocentesis (n = 268) in the following groups: (1) mid trimester of pregnancy; (2) preterm labor who delivered at term, preterm labor who delivered preterm with intra-amniotic infection, and preterm labor who delivered preterm without intra-amniotic infection; (3) preterm premature rupture of membranes in the presence or absence of intra-amniotic infection; (4) term with intact membranes not in labor, in labor, and in labor with intra-amniotic infection; and (5) premature rupture of membranes at term not in labor. In addition, lactoferrin concentrations were determined in maternal plasma and cord blood of patients at term not in labor. Lactoferrin concentration was measured with an immunoassay. RESULTS: (1) Lactoferrin was detectable in 85.4% (229/268) of amniotic fluid samples, not detectable in all fluid obtained in the mid trimester, and detectable in all maternal and cord plasma samples. (2) The concentration of lactoferrin increased with advancing gestational age (r = 0.68; P <.0001). (3) Intra-amniotic infection was associated with significant increases in amniotic fluid lactoferrin concentrations in patients with preterm labor (no intra-amniotic infection median, 1641.2 ng/mL; range, <1.24-35,090.0 ng/mL; vs intra-amniotic infection median, 3833.6 ng/mL; range, 746.0-47,020.0 ng/mL; P <.001), term labor (no intra-amniotic infection median, 2085.8 ng/mL; range, 425.0-23,230.0 ng/mL; vs intra-amniotic infection median, 5627.0 ng/mL; range, <1.24-19,220.0 ng/mL; P <. 001), and preterm premature rupture of membranes (no intra-amniotic infection median, 2190 ng/mL; range, <1.24-7456.1 ng/mL; vs intra-amniotic infection median, 3449.3 ng/mL; range, <1.24-83,600. 0; P <.01). (4) Spontaneous labor at term but not preterm was associated with a significant decrease in amniotic fluid lactoferrin concentration (P <.05). (5) Spontaneous term parturition was associated with a significant increase in umbilical cord plasma lactoferrin concentration (P <.005). CONCLUSION: (1) Intra-amniotic infection was consistently associated with dramatically increased concentrations of lactoferrin in amniotic fluid. (2) Term parturition was associated with a significant increase in lactoferrin concentration in the fetal compartment (umbilical cord blood) and a decrease in the amniotic compartment. We propose that lactoferrin is part of the repertoire of host defense mechanisms against intra-amniotic infection.

Cross-Sectional Studies↗

Further observations on the fetal inflammatory response syndrome: a potential homeostatic role for the soluble receptors of tumor necrosis factor alpha.

OBJECTIVE: The fetal inflammatory response syndrome is a subclinical condition frequently present in preterm labor and preterm premature rupture of the membranes and is associated with increased perinatal morbidity and mortality. Tumor necrosis factor alpha is a mediator of septic shock and death, and it exerts its biologic effects by interacting with 2 receptors, TNF-R1 and TNF-R2. Soluble tumor necrosis factor receptors can buffer the biologic activity and protect against the deleterious effects of tumor necrosis factor alpha. The purpose of this study was to determine the behavior of soluble tumor necrosis factor receptors in fetuses with and without fetal inflammatory response syndrome. STUDY DESIGN: Fetal blood sampling was performed in patients with preterm labor (n = 95) and preterm premature rupture of the membranes (n = 39). Control samples were obtained from fetuses who were undergoing blood sampling for clinical indications and had normal outcomes (n = 21). Fetal inflammatory response syndrome was defined as a fetal plasma interleukin 6 concentration >11 pg/mL. Concentrations of interleukin 6 and TNF-R1 and TNF-R2 were determined by use of sensitive and specific immunoassays. Analysis of covariance was used for statistical analysis. RESULTS: (1) TNF-R1 and TNF-R2 were detectable in all samples, and their concentrations decreased with advancing gestational age (r = -0.8 and r = -0.7; P<.0001 and P<.001, respectively). (2) The mean fetal plasma concentrations of TNF-R1 and TNF-R2 were significantly higher in fetuses with fetal inflammatory response syndrome than in those without the syndrome after adjustment for gestational age and fetal membrane status (TNF-R1: no fetal inflammatory response syndrome, mean +/- SE, 3473.7+/-128.8 pg/mL; vs fetal inflammatory response syndrome, mean +/- SE, 4079.9+/-190.7 pg/mL; P<.005; TNF-R2: no fetal inflammatory response syndrome, mean +/- SE, 6033.2+/-235.4 pg/mL; vs. fetal inflammatory response syndrome, mean +/- SE, 7783.1+/-342.8 pg/mL; P<.0001). (3) Fetuses of patients who delivered within 72 hours of cordocentesis had significantly higher concentrations of TNF-R1 and TNF-R2 receptors than those with longer latency periods (P<.05 for each). CONCLUSION: The fetal inflammatory response syndrome is associated with increased availability of the soluble receptors of tumor necrosis factor alpha in fetal plasma. These factors may attenuate the deleterious effects of tumor necrosis factor alpha.

Adult↗

Hydramnios and small for gestational age: prevalence and clinical significance.

OBJECTIVE: To investigate the clinical significance of combined obstetrical pathology of small for gestational age and hydramnios as a predictor of peripartum complications, intrapartum morbidity and poor neonatal outcome. METHODS: The study population consisted of 152 small for gestational age neonates with hydramnios out of 67,806 singleton deliveries during the study period (0.22%). We compared the 152 small for gestational age neonates with hydramnios (hydramnios/small for gestational age) to a sample of 1% of the appropriate for gestational age neonates with normal amniotic fluid (normal amniotic fluid/appropriate for gestational age) (582 cases). Analyses were conducted for the entire cohort as well as for the cohort in which all cases with congenital malformations were excluded. RESULTS: There was a significantly higher rate of congenital anomalies in the hydramnios/small for gestational age group compared with the normal amniotic fluid/appropriate for gestational age group (25% vs. 2.4%, p<0.001). There were significantly more previous perinatal deaths, infertility treatments and diabetes type B-R among the hydramnios/small for gestational age group. These findings remained significant after exclusion of the neonates with congenital malformations. The rates of labor dystocia, placental abruptio, abnormal presentations, prolapse of cord and cesarean sections were significantly higher in the hydramnios/ small for gestational age group compared with normal amniotic fluid/appropriate for gestational age group (5.9/2.4%, p<0.05; 5.9/0.7%, p<0.001; 14.5/3.2%, p<0.001; 2/0.2%, p<0.01; 24.3/8.2%,p<0.001; respectively). Rates of ante partum death and post partum death as well as low 1 and 5 minute Apgar scores were significantly higher in the hydramnios/small for gestational age group (9.9/0.3%; 14.5/0.3%; 12.8/2.1%; 11.7/0.6%, p<0.001, respectively). CONCLUSIONS: The combination of small for gestational age and hydramnios is a risk factor for peripartum complications and perinatal mortality even in the absence of congenital malformations.

Adult↗

The tumor necrosis factor alpha and its soluble receptor profile in term and preterm parturition.

OBJECTIVE: The common terminal pathway of parturition describes the anatomic, biochemical, endocrine, and clinical events present in the fetus and mother in both term and preterm labor. Labor at term is thought to result from physiologic activation of this pathway, whereas preterm labor is the result of pathologic activating events. The purpose of this study was to determine whether physiologic and pathologic activation could be discerned by the analysis of a cytokine-receptor signaling system. Tumor necrosis factor alpha and its soluble receptors were used as probes because of their pivotal role in the regulation of several processes activated during parturition. Soluble receptors are thought to buffer the biologic and potentially deleterious effects of tumor necrosis factor alpha in pathologic conditions. STUDY DESIGN: The in vivo concentrations of tumor necrosis factor alpha and its soluble receptors were studied in patients in term labor and preterm labor. Amniotic fluid was retrieved from 175 women and tumor necrosis factor alpha, tumor necrosis factor receptor 1, and tumor necrosis factor receptor 2 concentrations were measured by highly sensitive immunoassays. Patients were classified in the following groups: (1) term labor (n = 29), (2) term not in labor (n = 29), (3) preterm labor leading to term delivery (n = 34), (4) preterm labor without infection resulting in preterm delivery (n = 34), (5) preterm labor with intra-amniotic infection (n = 23), and (6) second trimester (n = 26). RESULTS: Tumor necrosis factor alpha and tumor necrosis factor receptor 1 concentrations decreased with advanced gestational age (r = -0.51 and r = -0.7; P <.01 for each). (1) Patients in spontaneous term labor had a higher median concentration of tumor necrosis factor alpha than those at term not in labor (median, 6.4 pg/mL; range, 2.4->500 pg/mL vs median, 4.1 pg/mL; range, 1.1-22.7 pg/mL; P <.01) but had lower concentrations of tumor necrosis factor receptor 1 (median, 3.2 ng/mL; range, 1.3-9.1 ng/mL vs median, 4.2 ng/mL; range, 1.6-8.3; P <.001) and tumor necrosis factor receptor 2 (median, 5.5 ng/mL; range, 0.73-12.8 ng/mL vs median, 6.8 ng/mL; range, 2.9-12.9 ng/mL; P <.01). (2) In contrast, patients with preterm labor leading to preterm delivery had higher concentrations of tumor necrosis factor alpha (median, 12.3 pg /mL; range, 1.5->500 pg/mL vs median, 4.8 pg/mL; range, 1-60.9 pg/mL; P <.01), tumor necrosis factor receptor 1 (median, 8.8 ng/mL; range, 2.5-38 ng/mL vs median, 6.2 ng/mL; range, 1.4-28 ng/mL; P <.05), and tumor necrosis factor receptor 2 (median, 8.5 ng/mL; range, 3.5-45.4 ng/mL vs median, 6.1 ng/mL; range, 1.99-14.1 ng/mL; P <.01) than patients with preterm labor who delivered at term. (3) Microbial invasion of the amniotic cavity was associated with dramatic increases in the concentrations of tumor necrosis factor alpha (median, 93.5 pg/mL; range, 1.2->500 pg/mL) and its soluble receptors tumor necrosis factor receptor 1 (median, 8.8 ng/mL; range, 2.1-36.7 ng/mL) and tumor necrosis factor receptor 2 (median, 11.8 ng/mL; range, 3.4-46. 3 ng/mL), concentrations that were significantly higher than in those with preterm labor who delivered at term and those who delivered preterm but were not infected. CONCLUSION: The tumor necrosis factor alpha and tumor necrosis factor alpha soluble receptor profiles are different in term and preterm parturition. Our observations provide support for the thesis that preterm parturition is a pathologic condition. Increased tumor necrosis factor alpha soluble receptor concentrations may attenuate the deleterious effects of the excess of tumor necrosis factor alpha found in pathologic labor.

Amniotic Fluid↗

A role for the novel cytokine RANTES in pregnancy and parturition.

OBJECTIVE: RANTES (regulated on activation, normal T cell expressed and secreted), a potent and versatile chemokine, is capable of attracting monocytes, lymphocytes, basophils, and eosinophils. This cytokine has been implicated in the regulation of the inflammatory response and in the recruitment of macrophages to the implantation site in early pregnancy. RANTES messenger ribonucleic acid and protein have been detected in fetal tissue and first-trimester trophoblast in response to bacterial endotoxin. The purpose of this study was to determine whether intrauterine infection, parturition (preterm and term), and gestational age affect the amniotic fluid concentrations of RANTES in human pregnancy. STUDY DESIGN: A cross-sectional study was designed to examine the relationship between labor, microbial invasion of the amniotic cavity, gestational age, and RANTES expression in amniotic fluid. Amniotic fluid was obtained from 214 women in the following groups: (1) midtrimester (n = 22), (2) preterm labor with intact membranes in the presence (n = 20) or absence (n = 74) of microbial invasion of the amniotic cavity, (3) term, not in labor (n = 44) and term, in labor in the presence (n = 27) and absence (n = 27) of microbial invasion of the amniotic cavity. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture for microorganisms. RANTES concentrations were determined by use of a sensitive and specific immunoassay. RESULTS: (1) Amniotic fluid RANTES concentrations decrease with advancing gestational age (r = 0. 43; P <.01). (2) Labor at term was associated with an increase in median concentrations of RANTES (labor-median, 8.4 pg/mL; range, <1.3-94.4 vs no labor-median, <1.3 pg/mL; range, <1.3-230.3; P <.01). (3) Women with preterm labor who delivered preterm (no microbial invasion of the amniotic cavity) had a higher median concentration of amniotic fluid RANTES than those who delivered at term (median, 12.7 pg/mL; range, <1.3-928 vs median, <1.3 pg/mL; range, <1.3-127. 5; P <.001). (4) Microbial invasion of the amniotic cavity was associated with a significant increase in median amniotic fluid RANTES in both preterm and term labor (preterm labor with microbial invasion of the amniotic cavity-median, 51.6 pg/mL; range, <1.3-2290 vs preterm labor without microbial invasion of the amniotic cavity-median, 12.7 pg/mL; range, <1.3-928 and vs preterm labor with delivery at term-median, <1.3 pg/mL; range, <1.3-127.5; P <.001 for each; term labor with microbial invasion of the amniotic cavity-median, 16.8 pg/mL; range, <1.3-171.4 vs term labor without microbial invasion of the amniotic cavity-median, 8.4 pg/mL; range, <1.3-94.4; P <.05 and vs no labor and no microbial invasion of the amniotic cavity-median, 1.4 pg/mL; range, <1.3-230.3; P <.001 and P <.05, respectively). CONCLUSION: These results support a role for RANTES in the mechanisms of human parturition and in the regulation of the host response to intrauterine infection.

Amnion↗

Perinatal outcome and peripartum complications in preterm singleton and twins deliveries: a comparative study.

OBJECTIVE: Multiple pregnancy is one of the major risk factors for preterm births. The aim of the present study was to compare perinatal outcome and peripartum complications between twins and singletons, born preterm. STUDY DESIGN: The study population consisted of preterm deliveries of 435 pairs of twins (870 neonates) and the comparison group included 4754 preterm deliveries of singletons, born in the same period (January 1, 1989-December 31, 1996). Exclusion criteria were lack of prenatal care and births following infertility treatments. The three steps in statistical analysis consisted of (1) degree of concordance between the twins; (2) comparison between each twin (I and II) to their singleton comparison groups using SPSS computer program; (3) stratified analysis to examine perinatal mortality rates at different gestational age groups. RESULTS: The prevalence of preterm deliveries was 7.9% (6192/77610). Perinatal mortality was lower in twins of both birth orders, however, it was statistically significant only when APD is considered. Mortality rates in all gestational age groups and for both twin groups were lower than that of singleton [OR=0.45 (0.26-0.75; 95% CI) for twin-I; OR=0.36 (0.21-0.59; 95% CI) for twin-II]. Compared to singletons, twin gestations had less congenital malformations. Twin gestation had statistically lower rates of preterm premature rupture of membranes, severe pregnancy induced hypertension, oligohydramnios, placenta previa, placental abruption and clinical chorioamnionitis [12.2 vs.17.3%, 2.5 vs. 6.3%, 2.3 vs. 4.7%, 0.9 vs. 2.9%, 1.8 vs. 5%, 1.8 vs. 5.2%, respectively (P<0.01)]. Mothers of twins had less diabetes mellitus class B-R, hydramnios and chronic hypertension than that of singleton (1.8 vs. 2.6%, 5.5 vs. 7.4%, 3.7 vs. 4.8%, respectively). Cesarean section rates were significantly higher in twin's gestation. Mothers of twins tended to be older and of higher birth and gravidity order. CONCLUSIONS: Perinatal mortality rates and peripartum complications were lower in twin compared to singleton gestations.

Adult↗

Prenatal diagnosis of a lean umbilical cord: a simple marker for the fetus at risk of being small for gestational age at birth.

OBJECTIVE: The purpose of this study was to investigate whether the prenatal diagnosis of a 'lean' umbilical cord in otherwise normal fetuses identifies fetuses at risk of being small for gestational age (SGA) at birth and of having distress in labor. The umbilical cord was defined as lean when its cross-sectional area on ultrasound examination was below the 10th centile for gestational age. METHOD: Pregnant women undergoing routine sonographic examination were included in the study. Inclusion criteria were gestational age greater than 20 weeks, intact membranes, and singleton gestation. The sonographic cross-sectional area of the umbilical cord was measured in a plane adjacent to the insertion into the fetal abdomen. Umbilical artery Doppler waveforms were recorded during fetal apnea and fetal anthropometric parameters were measured. RESULTS: During the study period, 860 patients met the inclusion criteria, of whom 3.6% delivered a SGA infant. The proportion of SGA infants was higher among fetuses who had a lean umbilical cord on ultrasound examination than among those with a normal umbilical cord (11.5% vs. 2.6%, p < 0.05). Fetuses with a lean cord had a risk 4.4-fold higher of being SGA at birth than those with a normal umbilical cord. After 25 weeks of gestation, this risk was 12.4 times higher when the umbilical cord was lean than when it was of normal size. The proportion of fetuses with meconium-stained amniotic fluid at delivery was higher among fetuses with a lean cord than among those with a normal umbilical cord (14.6% vs. 3.1%, p < 0.001). The proportion of infants who had a 5-min Apgar score < 7 was higher among those who had a lean cord than among those with normal umbilical cord (5.2% vs. 1.3%, p < 0.05). Considering only patients admitted in labor with intact membranes and who delivered an appropriate-for-gestational-age infant, the proportion of fetuses who had oligohydramnios at the time of delivery was higher among those who had a lean cord than among those with a normal umbilical cord (17.6% versus 1.3%, p < 0.01). CONCLUSION: We conclude that fetuses with a lean umbilical cord have an increased risk of being small for gestational age at birth and of having signs of distress at the time of delivery.

Adult↗

A review of the role of trials of the use of antibiotics in women with preterm labor and intact membranes.

This updated review addresses the administration of antibiotics in women presenting with preterm labor and intact membranes as well as with bacterial vaginosis. 11 randomized controlled trials dealing with this question have been published since 1986. The results are disappointing. The probable reasons are the small number of patients in the different studies and universal use of antibiotics without performing amniocentesis to isolate the organisms involved.

Chorioamnionitis↗

A review of randomized clinical trials of antibiotic therapy in preterm premature rupture of the membranes.

Rupture of membranes before 37 completed weeks of gestation, and before the onset of contractions occurs among 2-3% of pregnancies, and in about 30%-40% of women who deliver preterm. It is known as preterm premature rupture of membranes (PPROM) and is associated with maternal and neonatal morbidity. It has been postulated that antibiotic therapy may significantly decrease the complications associated with infection. The aim of the present review is to summarize the available data about the value of antibiotic therapy in PPROM.

Anti-Bacterial Agents↗

Primary hepatoid carcinoma of ovary in pregnancy.

We report a rare case of a 35-year-old woman with primary hepatoid carcinoma of the ovary during pregnancy associated with abnormal levels of maternal serum alpha-fetoprotein. This tumor should be considered in the differential diagnosis of pregnant women with very high levels of maternal serum alpha-fetoprotein whenever other maternal or fetal sources are excluded.

Adult↗

An increase in fetal plasma cortisol but not dehydroepiandrosterone sulfate is followed by the onset of preterm labor in patients with preterm premature rupture of the membranes.

OBJECTIVE: The role of steroid hormones in the control of human parturition has been a subject of debate. Activation of the fetal hypothalamic-pituitary-adrenal axis leading to an increase in plasma cortisol is followed by the onset of parturition in sheep. In contrast, androgens, specifically, dehydroepiandrosterone sulfate, have been implicated in the control of parturition in nonhuman primates. The purpose of this study was to determine the relationship between human fetal plasma cortisol and dehydroepiandrosterone sulfate and the onset of preterm labor in patients with preterm premature rupture of the membranes. STUDY DESIGN: Fetal blood sampling was performed in 51 patients with preterm premature rupture of membranes who were not in labor on admission. Amniotic fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. Corticosteroids had not been administered before fetal blood sampling. Cortisol and dehydroepiandrosterone sulfate were measured with sensitive and specific immunoassays. Analysis was conducted with nonparametric statistics and survival analysis. RESULTS: (1) Patients who went into spontaneous labor and delivered within 7 days of cordocentesis had a significantly higher median level of fetal plasma cortisol but not of dehydroepiandrosterone sulfate than those delivered after 7 days (for fetal plasma cortisol: median 8.35 [4.7 to 12.4] micrograms/dL vs median 4.75 [3.0 to 10.4] micrograms/dL, P <.0001; for fetal plasma dehydroepiandrosterone sulfate: median 154.4 [8.6 to 333.8] micrograms/dL vs median 194.6 [96.7 to 402.5] micrograms/dL, P =.09). (2) The cordocentesis-to-delivery interval was significantly shorter in patients with a fetal plasma cortisol value of >/=7 micrograms/dL (derived by receiver-operating characteristic curve analysis) than in those with fetal cortisol <7 micrograms/dL (median 49 [4 to 1849] hours vs median 325 [11 to 2590] hours, P <.001). (3) Fetal plasma cortisol, but not maternal cortisol, was an independent predictor of the duration of pregnancy after we adjusted for gestational age and the results of amniotic fluid culture (hazards ratio 2.9, P <.05). (4) There was a significant correlation between fetal plasma cortisol and fetal plasma interleukin-6 (r = 0.3, P <.05). (5) A strong relationship was found between the fetal plasma cortisol/dehydroepiandrosterone sulfate ratio and the interval to delivery (P <.005). CONCLUSION: An elevation in fetal plasma cortisol but not dehydroepiandrosterone sulfate was followed by the onset of spontaneous preterm labor in patients with preterm premature rupture of the membranes.

Adult↗

A role for matrix metalloproteinase-9 in spontaneous rupture of the fetal membranes.

OBJECTIVES: Preterm premature rupture of fetal membranes is responsible for 30% to 40% of preterm deliveries. Fetal membranes are composed primarily of collagen. Matrix metalloproteinases are enzymes capable of degrading extracellular matrix macromolecules, including collagens. Expression of matrix metalloproteinase-9 (gelatinase B, 92 kd) and its tissue inhibitor (tissue inhibitor of metalloproteinase-1) has been localized in amnion and chorion. The objective of this study was to determine whether rupture of fetal membranes and intrauterine infection are associated with changes in the expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1. STUDY DESIGN: Two hundred one women in the following categories had amniotic fluid retrieved: (1) preterm labor and intact membranes in the presence (n = 42) or absence (n = 21) of microbial invasion of the amniotic cavity, (2) preterm premature rupture of the membranes with (n = 29) or without (n = 23) microbial invasion of the amniotic cavity, and (3) term gestation with intact membranes (n = 50) or with premature rupture of the membranes (n = 40). Women in groups 1 and 2 were matched for gestational age at amniocentesis. Microbial invasion of the amniotic cavity was defined by a positive amniotic fluid culture for micro-organisms. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were measured with use of sensitive and specific immunoassays that were validated for amniotic fluid. RESULTS: Spontaneous rupture of membranes at term is associated with a significant increase in the amniotic fluid concentrations of matrix metalloproteinase-9 (premature rupture of membranes, no labor: median 3.9 ng/mL, range 2. 7 to 11.1 ng/mL vs no premature rupture of membranes, no labor: median <0.4 ng/mL, range <0.4 to 22.4 ng/mL; P <.001). Patients with preterm premature rupture of the membranes had higher median matrix metalloproteinase-9 concentrations than those with preterm labor and intact membranes who were delivered at term (7.6 ng/mL, range <0.4 to 230.81 ng/mL vs <0.4 ng/mL, range <0.4 to 1650 ng/mL; P =.06). Women with microbial invasion of the amniotic cavity had higher median matrix metalloproteinase-9 concentrations than did those without microbial invasion regardless of membrane status (preterm labor: 54.5 ng/mL, range <0.4 to 3910 ng/mL vs <0.4 ng/mL, range <0. 4 to 1650 ng/mL; P <.01; preterm premature rupture of membranes: 179. 8 ng/mL, range <0.4 to 611 ng/mL vs 7.6 ng/mL, range <0.4 to 230.81; P <.001). CONCLUSION: Our data support a role for matrix metalloproteinase-9 in the mechanisms responsible for membrane rupture in term and preterm gestations.

Amnion↗

Disturbed feto-maternal cell traffic in preeclampsia.

OBJECTIVE: To investigate whether the transfer of fetal blood cells to the maternal circulation is perturbed in pregnancies affected by preeclampsia. METHODS: Fetal erythroblasts were isolated from eight women with clinically diagnosed preeclampsia (blood pressure values of at least 140/90 mmHg and associated proteinuria) and an equal number of matched corresponding controls. All patients in both groups were pregnant with male singleton fetuses. The presence of fetal cells was evaluated histologically and by fluorescence in situ hybridization for X and Y chromosomes. RESULTS: The number of fetal cells was higher in preeclamptic patients than in controls, with respect to both nucleated red blood cells (median per 200 cells 38 versus 7; P < .001) and the proportion of these cells that were of fetal origin (median per 2000 cells 9 versus 2; P = .001). CONCLUSION: These results suggest that the trafficking of fetal cells into the maternal periphery is disturbed in patients with preeclampsia. Because it is unlikely that such an altered flow of cells is restricted to the erythroblasts examined in this study, these findings also may lead to interesting new concepts regarding the development of preeclampsia and possibly the associated syndrome of hemolysis, elevated liver enzymes, and low platelets.

Erythroblasts↗

Isolated hydramnios at term gestation and the occurrence of peripartum complications.

OBJECTIVE: To determine if hydramnios at term gestation is an independent risk factor for poor pregnancy outcome and perinatal death. STUDY DESIGN: The study population consisted of 60,702 patients with singleton gestation who delivered at term (>37 weeks). Patients were classified into two groups according to the presence or the absence of hydramnios. Hydramnios was diagnosed in the presence of an amniotic fluid index greater than 25 cm or of a maximum vertical pocket of amniotic fluid of at least 8 cm or by subjective assessment. Logistic regression analysis was used to evaluate the unique contribution of hydramnios to fetal death and to perinatal and maternal morbidity. RESULTS: The prevalence of hydramnios was 1211/60,702 (2%). Patients with hydramnios had a higher incidence of complications than those with a normal amount of amniotic fluid: cesarean section (22.8 vs. 8.5%, P<0.01), antepartum death (0.6 vs. 0.2%, P<0.005), postpartum death (2.8 vs. 0.4%, P<0.01), abruptio placenta (0.9 vs. 0.3%, P<0.001), fetal distress (6.1 vs. 3.65%, P<0.0015), meconium-stained amniotic fluid (17.8 vs. 15%, P<0.001), low Apgar score at 5 min (2.95 vs. 1%, P<0.01), malpresentation (6.8 vs. 2.9%, P<0.01), clinical chorioamnionitis (0.3 vs. 0.1%, P<0.05), prolapse of cord (2.2 vs. 0.3%, P<0.01), and large-for-gestational-age infant (LGA) (23.8 vs. 8.1%, P<0.01). When adjusted for confounding variables, the presence of hydramnios remained strongly associated with perinatal mortality (odds ratio 5.5 (95% CI 3.2-9.3)) and neonatal and maternal morbidity (odds ratios 2.1 (CI 1.1-3.7) and 2.3 (CI 1.9-2.7), respectively). CONCLUSIONS: (1) Hydramnios at term is an independent risk factor for perinatal death; (2) Fetal surveillance is warranted in patients with hydramnios even in the absence of other known risk factors for adverse pregnancy outcome.

Adult↗