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Objective: To evaluate whether the presence of cervical funneling or intra-amniotic debris identified in the second trimester is associated with a higher rate of preterm birth (PTB) in asymptomatic nulliparous pregnant women with a midtrimester cervical length (CL) less than 30 mm (i.e. below the 10th percentile).Methods: This was a secondary cohort analysis of data from a multicenter trial in nulliparous women between 16 and 22 weeks' gestation with a singleton gestation and CL less than 30 mm on transvaginal ultrasound, randomized to treatment with either 17-alpha-hydroxyprogesterone caproate or placebo. Sonographers were centrally certified in CL measurement, as well as in identification of intra-amniotic debris and cervical funneling. Univariable and multivariable analysis was performed to assess the associations of cervical funneling and intra-amniotic debris with PTB.Results: Of the 657 women randomized, 112 (17%) had cervical funneling only, 33 (5%) had intra-amniotic debris only and 45 (7%) had both on second-trimester ultrasound. Women with either of these findings had a shorter median CL than those without (21.0 mm vs 26.4 mm; P < 0.001). PTB prior to 37 weeks was more likely in women with cervical funneling (37% vs 21%; odds ratio (OR), 2.2 (95% CI, 1.5-3.3)) or intra-amniotic debris (35% vs 23%; OR, 1.7 (95% CI, 1.1-2.9)). Results were similar for PTB before 34 and before 32 weeks' gestation. After multivariable adjustment that included CL, PTB < 34 and < 32 weeks continued to be associated with the presence of intra-amniotic debris (adjusted OR (aOR), 1.85 (95% CI, 1.00-3.44) and aOR, 2.78 (95% CI, 1.42-5.45), respectively), but not cervical funneling (aOR, 1.17 (95% CI, 0.63-2.17) and aOR, 1.45 (95% CI, 0.71-2.96), respectively).Conclusions: Among asymptomatic nulliparous women with midtrimester CL less than 30 mm, the presence of intra-amniotic debris, but not cervical funneling, is associated with an increased risk for PTB before 34 and 32 weeks' gestation, independently of CL. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Global climate change is expected to alter seasonal patterns and rates of evapotranspiration in dry regions. Although climate change will involve elevated CO2 and increased temperatures, independently, these factors may have different impacts on actual evapotranspiration (AET) due to their opposing effects on transpiration. We used canopy gas exchange chambers to quantify AET in a semiarid grassland experimentally altered by elevated CO2 and warming over 3 years with contrasting ambient precipitation. Seasonal and interannual variations in AET due to background climate variability were larger than the effects of climate manipulation treatments. However, in a year with average precipitation, cumulative growing season AET was suppressed by warming by 23%. Across years, warming increased AET early in the growing season and suppressed it later in the growing season. By contrast, elevated CO2 suppressed AET early in the growing season and enhanced it later, but only in years with average or above-average precipitation. Vegetation greenness (a proxy for photosynthetically active leaf area) was consistently the strongest predictor of AET, whereas soil moisture and vapor pressure deficit were secondary drivers. Our research demonstrates that effects of increased atmospheric CO2 and temperature on AET will be mediated by plant phenological development and seasonal climatic conditions. [ABSTRACT FROM AUTHOR]

Objective: Smoking and pre-eclampsia (PE) are associated with increases in preterm birth, placental abruption and low birthweight. We evaluated the relationship between prenatal vitamin C and E (C/E) supplementation and perinatal outcomes by maternal self-reported smoking status focusing on outcomes known to be impacted by maternal smoking.Design/setting/population: A secondary analysis of a multi-centre trial of vitamin C/E supplementation starting at 9-16 weeks in low-risk nulliparous women with singleton gestations.Methods: We examined the effect of vitamin C/E by smoking status at randomisation using the Breslow-Day test for interaction.Main Outcome Measures: The trial's primary outcomes were PE and a composite outcome of pregnancy-associated hypertension (PAH) with serious adverse outcomes. Perinatal outcomes included preterm birth and abruption.Results: There were no differences in baseline characteristics within subgroups (smokers versus nonsmokers) by vitamin supplementation status. The effect of prenatal vitamin C/E on the risk of PE (P = 0.66) or PAH composite outcome (P = 0.86) did not differ by smoking status. Vitamin C/E was protective for placental abruption in smokers (relative risk [RR] 0.09; 95% CI 0.00-0.87], but not in nonsmokers (RR 0.92; 95% CI 0.52-1.62) (P = 0.01), and for preterm birth in smokers (RR 0.76; 95% CI 0.58-0.99) but not in nonsmokers (RR 1.03; 95% CI 0.90-1.17) (P = 0.046).Conclusion: In this cohort of women, smoking was not associated with a reduction in PE or the composite outcome of PAH. Vitamin C/E supplementation appears to be associated with a reduction in placental abruption and preterm birth among smokers. [ABSTRACT FROM AUTHOR]

Objective To determine whether β2-adrenoceptor ( β2 AR) genotype is associated with shortening of the cervix or with preterm birth ( PTB) risk among women with a short cervix in the second trimester. Design A case-control ancillary study to a multicentre randomised controlled trial. Setting Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Population Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length. Methods Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. β2 AR genotype was determined at positions encoding for amino acid residues 16 and 27. Main outcome measures Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks. Results Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity ( OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity ( OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited. Conclusions β2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with β2 AR genotype do not appear to involve a short cervix pathway. [ABSTRACT FROM AUTHOR]

Objective To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. Design A nested case-control study of change in maternal plasma soluble Flt-1 ( sFlt-1), soluble endoglin ( sEng) and placenta growth factor ( PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls. Setting A multicentre study in 16 academic medical centres in the USA. Population Low-risk nulliparous women. Methods Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9-12, 15-18 and 23-26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. Main outcome measures Change in PlGF, sFlt-1 and sEng. Results Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64-99), 77% (95% CI 50-93) and 77% (95% CI 50-93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. Conclusion Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Thorp J, Camargo C, McGee P, Harper M, Klebanoff M, Sorokin Y, Varner M, Wapner R, Caritis S, Iams J, Carpenter M, Peaceman A, Mercer B, Sciscione A, Rouse D, Ramin S, Anderson G. Vitamin D status and recurrent preterm birth: a nested case-control study in high-risk women. BJOG 2012;119:1617-1623. Objective To determine whether vitamin D status is associated with recurrent preterm birth, and any interactions between vitamin D levels and fish consumption. Design A nested case-control study, using data from a randomised trial of omega-3 fatty acid supplementation to prevent recurrent preterm birth. Setting Fourteen academic health centres in the USA. Population Women with prior spontaneous preterm birth. Methods In 131 cases (preterm delivery at <35 weeks of gestation) and 134 term controls, we measured serum 25-hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography-tandem mass spectrometry (LC-MS) from samples collected at baseline (16-22 weeks of gestation). Logistic regression models controlled for study centre, maternal age, race/ethnicity, number of prior preterm deliveries, smoking status, body mass index, and treatment. Main outcome measures Recurrent preterm birth at <37 and <32 weeks of gestation. Results The median mid-gestation serum 25(OH)D concentration was 67 nmol/l, and 27% had concentrations of <50 nmol/l. Serum 25(OH)D concentration was not significantly associated with preterm birth (OR 1.33; 95% CI 0.48-3.70 for lowest versus highest quartiles). Likewise, comparing women with 25(OH)D concentrations of 50 nmol/l, or higher, with those with <50 nmol/l generated an odds ratio of 0.80 (95% CI 0.38-1.69). Contrary to our expectation, a negative correlation was observed between fish consumption and serum 25(OH)D concentration (−0.18, P < 0.01). Conclusions In a cohort of women with a prior preterm birth, vitamin D status at mid-pregnancy was not associated with recurrent preterm birth. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine whether the risk of early spontaneous preterm delivery (PTD) in asymptomatic women with a sonographic cervical length of ≤ 15 mm in the mid-trimester changes as a function of gestational age at diagnosis.Methods: This cohort study included 109 asymptomatic patients with a sonographic cervical length of ≤ 15 mm diagnosed at 14-24 weeks of gestation. Women with a multifetal gestation, cerclage and a cervical dilatation of > 2 cm were excluded. The study population was stratified by gestational age at diagnosis (< 20 weeks vs. 20-24 weeks) and by cervical length (≤ 10 mm vs. 11-15 mm). The primary outcome variables were PTD at < 28 and < 32 weeks of gestation and the diagnosis-to-delivery interval.Results: The median gestational age at diagnosis of a short cervix before 20 weeks and at 20-24 weeks was 18.9 and 22.7 weeks, respectively. Women diagnosed before 20 weeks had a higher rate of PTD at < 28 weeks (76.9% vs. 30.9%; P < 0.001) and at < 32 weeks (80.8% vs. 48.1%; P = 0.004), and a shorter median diagnosis-to-delivery interval (21 vs. 61.5 days, P = 0.003) than those diagnosed at 20-24 weeks. The rate of amniotic fluid sludge was higher among patients diagnosed with a short cervix at < 20 weeks of gestation than in those in whom it was diagnosed between 20 and 24 weeks (92.3% vs. 48.2%; P < 0.001).Conclusions: Asymptomatic women with a sonographic cervical length of ≤ 15 mm diagnosed before 20 weeks of gestation have a dramatic and significantly higher risk of early preterm delivery than women diagnosed at 20-24 weeks. These findings can be helpful to physicians in counseling these patients, and may suggest different mechanisms of disease leading to a sonographic short cervix before or after 20 weeks of gestation. [ABSTRACT FROM AUTHOR]

The article presents a cohort study that determine whether the risk of early spontaneous preterm delivery (PTD) in asymptomatic women with a sonographic cervical length of less than equal to 15 mm in the mid-trimester alters as a function of gestational age at diagnosis. It states that the study population comprise of 109 asymptomatic patients. The study finds that asymptomatic women have a dramatic and significantly higher risk of early preterm delivery than women diagnosed at 20-24 weeks.

The article presents a cross-sectional study which examines the relation between flow impedance in the maternal and fetal circulation, and the concentration of plasma soluble endoglin (sEng) in pre-eclampsia (PE) patients. It says the study divided the subjects accordingly to Doppler abnormalities in the uterine and umbilical arteries and their sEng concentrations were determined. Results show high plasma concentrations sEng among PE patients and suggests sEng association with PE mothers.

An abstract of the conference paper "A link between an anti-angiogenic state in the first trimester and abnormal uterine artery Doppler in the midtrimester," by T. Chaiworapongsa, and colleagues is presented.

An abstract of the conference paper "Late-onset preeclampsia cannot be identified with either an anti-angiogenic profile in maternal plasma or uterine artery Doppler velocimetry," by T. Chaiworapongsa and colleagues is presented.

An abstract of the conference paper "Abnormal Doppler velocimetry and SGA: Evidence for the relationship between utero-placental insufficiency and a maternal anti-angiogenic state," by T. Chaiworapongsa and colleagues is presented.

An abstract of the article "Can the severity of the maternal anti-angiogenic state of pre-eclampsia be detected by Doppler velocimetry?," by T. Chaiworapongsa and colleagues, is presented.

An abstract of the article "The clinical significance of early (< 20 weeks) versus late (20-24 weeks) detection of a sonographic short cervix in asymptomatic women," by E. Vaisbuch and colleagues, is presented.

Objective: Smoking and pre-eclampsia (PE) are associated with increases in preterm birth, placental abruption and low birthweight. We evaluated the relationship between prenatal vitamin C and E (C/E) supplementation and perinatal outcomes by maternal self-reported smoking status focusing on outcomes known to be impacted by maternal smoking., Design/setting/population: A secondary analysis of a multi-centre trial of vitamin C/E supplementation starting at 9-16 weeks in low-risk nulliparous women with singleton gestations., Methods: We examined the effect of vitamin C/E by smoking status at randomisation using the Breslow-Day test for interaction., Main Outcome Measures: The trial's primary outcomes were PE and a composite outcome of pregnancy-associated hypertension (PAH) with serious adverse outcomes. Perinatal outcomes included preterm birth and abruption., Results: There were no differences in baseline characteristics within subgroups (smokers versus nonsmokers) by vitamin supplementation status. The effect of prenatal vitamin C/E on the risk of PE (P = 0.66) or PAH composite outcome (P = 0.86) did not differ by smoking status. Vitamin C/E was protective for placental abruption in smokers (relative risk [RR] 0.09; 95% CI 0.00-0.87], but not in nonsmokers (RR 0.92; 95% CI 0.52-1.62) (P = 0.01), and for preterm birth in smokers (RR 0.76; 95% CI 0.58-0.99) but not in nonsmokers (RR 1.03; 95% CI 0.90-1.17) (P = 0.046)., Conclusion: In this cohort of women, smoking was not associated with a reduction in PE or the composite outcome of PAH. Vitamin C/E supplementation appears to be associated with a reduction in placental abruption and preterm birth among smokers., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Objective: To determine whether β2 -adrenoceptor (β2 AR) genotype is associated with shortening of the cervix or with preterm birth (PTB) risk among women with a short cervix in the second trimester., Design: A case-control ancillary study to a multicentre randomised controlled trial., Setting: Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development., Population: Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length., Methods: Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. β2 AR genotype was determined at positions encoding for amino acid residues 16 and 27., Main Outcome Measures: Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks., Results: Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity (OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity (OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited., Conclusions: β2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with β2 AR genotype do not appear to involve a short cervix pathway., (© 2015 Royal College of Obstetricians and Gynaecologists.)

Objective: To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women., Design: A nested case-control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls., Setting: A multicentre study in 16 academic medical centres in the USA., Population: Low-risk nulliparous women., Methods: Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9-12, 15-18 and 23-26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics., Main Outcome Measures: Change in PlGF, sFlt-1 and sEng., Results: Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64-99), 77% (95% CI 50-93) and 77% (95% CI 50-93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester., Conclusion: Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia., (© Published 2013 This article is a U.S. Government work and is in the public domain in the USA © 2013 RCOG.)

Objective: To determine whether vitamin D status is associated with recurrent preterm birth, and any interactions between vitamin D levels and fish consumption., Design: A nested case-control study, using data from a randomised trial of omega-3 fatty acid supplementation to prevent recurrent preterm birth., Setting: Fourteen academic health centres in the USA., Population: Women with prior spontaneous preterm birth., Methods: In 131 cases (preterm delivery at <35 weeks of gestation) and 134 term controls, we measured serum 25-hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography-tandem mass spectrometry (LC-MS) from samples collected at baseline (16-22 weeks of gestation). Logistic regression models controlled for study centre, maternal age, race/ethnicity, number of prior preterm deliveries, smoking status, body mass index, and treatment., Main Outcome Measures: Recurrent preterm birth at <37 and <32 weeks of gestation., Results: The median mid-gestation serum 25(OH)D concentration was 67 nmol/l, and 27% had concentrations of <50 nmol/l. Serum 25(OH)D concentration was not significantly associated with preterm birth (OR 1.33; 95% CI 0.48-3.70 for lowest versus highest quartiles). Likewise, comparing women with 25(OH)D concentrations of 50 nmol/l, or higher, with those with <50 nmol/l generated an odds ratio of 0.80 (95% CI 0.38-1.69). Contrary to our expectation, a negative correlation was observed between fish consumption and serum 25(OH)D concentration (-0.18, P < 0.01)., Conclusions: In a cohort of women with a prior preterm birth, vitamin D status at mid-pregnancy was not associated with recurrent preterm birth., (© Published 2012. This article is a U.S. Government work and is in the public domain in the USA. © 2012 RCOG.)

Problem: Adhesive interaction between trophoblast cells and uterine endometrial basement membrane is one of the critical processes in embryo implantation. This interaction is directly or indirectly regulated by hormones, growth factors, and cytokines. Since tumor necrosis factor-alpha (TNF-alpha) is synthesized by both decidual and trophoblast cells, we hypothesized that TNF-alpha may play a regulatory role in trophoblast cell invasion. To test this hypothesis, we have used in vitro models to determine the effect of TNF-alpha on human trophoblast cell adhesion and motility, two major steps in trophoblast invasion., Methods: The effect of TNF-alpha on the motility of extended-lifespan first trimester trophoblasts (HTR) and JEG-3 choriocarcinoma cells was tested using the phagokinetic track motility assay. An in vitro adhesion assay was used to determine the effect of TNF-alpha on the adhesion of HTR and JEG-3 cells to laminin, a major basement membrane component. In addition, the effect of TNF-alpha on the surface expression of the laminin receptor beta 1 integrin subunit was examined using flow cytometry., Results: HTR or JEG-3 cells strongly adherent to laminin which was not significantly altered by TNF-alpha treatment. We also measured the effect of TNF-alpha on the surface expression of beta 1 integrin on HTR and JEG-3 cells; no difference was observed between control and treatment groups. Interestingly, the motility of both HTR and choriocarcinoma JEG-3 cells was significantly inhibited by TNF-alpha., Conclusions: The role of TNF-alpha in human embryo implantation is currently unknown. Our data demonstrate that TNF-alpha does alter trophoblast cell adhesion to laminin, but significantly inhibits trophoblast cell motility in vitro, suggesting that TNF-alpha may play a regulatory role in trophoblast cell invasion.