三维能量多普勒超声鉴别宫颈过短孕妇先兆早产的作用研究

目的：使用三维能量多普勒超声比较先兆早产和无症状宫颈过短单胎孕妇的宫颈体积和血管指数。方法：预先扫描妊娠 24-34.6 周的300 例无症状健康孕妇的宫颈长度。将宫颈长度过短，小于孕周的10%的孕妇纳入无症状宫颈短组，测量该组孕妇宫 颈体积和血管指数（Ⅵ）、血管血流指数（VFI）和血流指数（FI）。先兆早产组患者入院的24 小时内测量同样的超声参数。记录孕妇 的体重指数、孕周、吸烟状况、经产状况、早产家族史、母亲为早产出生者以及之前的早产情况等数据。比较两组孕妇超声检查结 果和病史参数。结果：29 例无症状健康妇女（9.6%）宫颈较短。两组间的病史参数或宫颈长度无显著差异。先兆早产组的宫颈体积 较小（12.90 vs 17.168 cm3，P = 0.005）。无症状宫颈过短孕妇的VI 和VFI 均较低（VI：4.369% vs 15.939%，P<0.001；VFI：1.514 vs 4.878，P<0.001）。宫颈过短组的FI较高（33.581 vs 30.311，P=0.006）。结论：无症状宫颈过短组孕妇与先兆早产组孕妇之间的宫颈 长度类似，但两组间宫颈体积和血管指数存在差异。     

microRNA expression in the cervix during pregnancy is associated with length of gestation

Preterm birth is a leading cause of infant mortality and can lead to poor life-long health and adverse neurodevelopmental outcomes. The pathophysiologic mechanisms that precede preterm labor remain elusive, and the role that epigenetic phenomena play is largely unstudied. The objective of this study was to assess the association between microRNA (miRNA) expression levels in cervical cells obtained from swabs collected during pregnancy and the length of gestation. We analyzed cervical samples obtained between 16 and 19 weeks of gestation from 53 women in a prospective cohort from Mexico City, and followed them until delivery. Cervical miRNA was extracted and expression was quantified using the NanoString nCounter Analysis System. Linear regression models were used to examine the association between miRNA expression levels and gestational age at delivery, adjusted for maternal age, education, parity, body mass index, smoke exposure, and inflammation assessed on a Papanicolaou smear. We identified 6 miRNAs that were significantly associated with gestational age at the time of delivery, including miR-21, 30e, 142, 148b, 29b, and 223. Notably, per each doubling in miR-21 expression, gestations were 0.9 (95% CI: 0.2–1.5) days shorter on average (P = 0.009). Per each doubling in miR-30e, 142, 148b, 29b, and 223 expression, gestations were shorter by 1.0 to 1.6 days. The predicted targets of the miRNAs were enriched for molecules involved in DNA replication and inflammatory processes. The levels of specific miRNAs in the human cervix during pregnancy are predictive of gestational age at delivery, and should be validated in future studies as potential biomarkers of preterm birth risk.Key words: Cervix, delivery, gestational age, labor, microRNA, Pap smear, preterm     

Long noncoding RNA expression in the cervix mid-pregnancy is associated with the length of gestation at delivery

Infants born preterm are at increased risk of multiple morbidities and mortality. Why some women deliver preterm remains poorly understood. Prior studies have shown that cervical microRNA expression and DNA methylation are associated with the length of gestation. However, no study has examined the role of long noncoding RNAs (lncRNAs) in the cervix during pregnancy. To determine whether expression of lncRNAs is associated with length of gestation at delivery, we analyzed RNA from cervical swabs obtained from 78 women during pregnancy (mean 15.5, SD 5.0, weeks of gestation) who were participating in the Spontaneous Prematurity and Epigenetics of the Cervix (SPEC) Study in Boston, MA, USA. We used a PCR-based platform and found that 9 lncRNAs were expressed in at least 50% of the participants. Of these, a doubling of the expression of TUG1, TINCR, and FALEC was associated with shorter lengths of gestation at delivery [2.8 (95% CI: 0.31, 5.2); 3.3 (0.22, 6.3); and 4.5 (7.3, 1.6) days shorter respectively]. Of the lncRNAs analyzed, none was statistically associated with preterm birth, but expression of FALEC was 2.6-fold higher in women who delivered preterm vs. term (P = 0.051). These findings demonstrate that lncRNAs can be measured in cervical samples obtained during pregnancy and are associated with subsequent length of gestation at delivery. Further, this study supports future work to replicate these findings in other cohorts and perform mechanistic studies to determine the role of lncRNAs in the cervix during pregnancy.     

Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2): An open-label randomised trial and updated meta-analysis

BackgroundPreterm-labour-associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce preterm-labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix.Methods and findingsWe conducted an open-label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. From 1 April 2015 to 14 February 2019, 2,228 women with a twin pregnancy underwent cervical length screening between 18 weeks 0 days and 20 weeks 6 days of gestation. In total, 503 women with cervical length ≤ 35 mm were randomly assigned to pessary in addition to standard care (n = 250, mean age 32.4 years, mean cervical length 29 mm, with pessary inserted in 230 women [92.0%]) or standard care alone (n = 253, mean age 32.7 years, mean cervical length 30 mm). The pessary was inserted before 21 completed weeks of gestation and removed at between 35 and 36 weeks or before birth if earlier. The primary obstetric outcome, spontaneous onset of labour and birth before 34 weeks 0 days of gestation, was present in 46/250 (18.4%) in the pessary group compared to 52/253 (20.6%) following standard care alone (adjusted odds ratio [aOR] 0.87 [95% CI 0.55–1.38], p = 0.54). The primary neonatal outcome—a composite of any of stillbirth, neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis, or proven sepsis, from birth to 28 days after the expected date of delivery—was present in 67/500 infants (13.4%) in the pessary group compared to 76/506 (15.0%) following standard care alone (aOR 0.86 [95% CI 0.54–1.36], p = 0.50). The positive and negative likelihood ratios of a short cervix (≤35 mm) to predict preterm birth before 34 weeks were 2.14 and 0.83, respectively. A meta-analysis of data from existing publications (4 studies, 313 women) and from STOPPIT-2 indicated that a cervical pessary does not reduce preterm birth before 34 weeks in women with a short cervix (risk ratio 0.74 [95% CI 0.50–1.11], p = 0.15). No women died in either arm of the study; 4.4% of babies in the Arabin pessary group and 5.5% of babies in the standard treatment group died in utero or in the neonatal period (p = 0.53). Study limitations include lack of power to exclude a smaller than 40% reduction in preterm labour associated preterm birth, and to be conclusive about subgroup analyses.ConclusionsThese results led us to reject our hypothesis that the Arabin pessary would reduce the risk of the primary outcome by 40%. Smaller treatment effects cannot be ruled out.Trial registrationISRCTN Registry ISRCTN 02235181.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02235181","term_id":"NCT02235181"}}NCT02235181.

Jane Norman and co-workers report an evaluation of a cervical pessary for prevention of preterm birth in women with a short cervix bearing twins.     

Vaginal sonography of the cervix for the prediction of "time to delivery" in ART twins gestations.

The present study aimed to determine a reliable tool to estimate the interval time to delivery in assisted conception twin pregnancies. Mid-gestation cervical length was prospectively measured using transvaginal sonography (TVS) during routine antenatal care. Fifty-seven of 101 suitable women were longitudinally followed and two TVS measurements of their cervical length were obtained, first at approximately 24 weeks gestation and then at approximately 27 weeks gestation. The mean cervical length decreased from 37 +/- 12mm at first measurement to 34 +/- 11mm at the second one. A linear regression model was found between the time interval of the first (R = 0.656, p < 0.001) and the second (R = 0.435, p < 0.001) assessments and the week of delivery. The current data confirm that the length of the preserved segment of the cervix is an important indicator of its competence. A simple equation using the cervical length (mm) divided by 3 can predict mid gestation scan-to-delivery interval in twin gestation.     

Limited Relationship between Cervico-Vaginal Fluid Cytokine Profiles and Cervical Shortening in Women at High Risk of Spontaneous Preterm Birth

Objective

To determine the relationship between high vaginal pro-inflammatory cytokines and cervical shortening in women at high risk of spontaneous preterm labor and to assess the influence of cervical cerclage and vaginal progesterone on this relationship.

Methods

This prospective longitudinal observational study assessed 112 women with at least one previous preterm delivery between 16 and 34 weeks’ gestation. Transvaginal cervical length was measured and cervico-vaginal fluid sampled every two weeks until 28 weeks. If the cervix shortened (<25 mm) before 24 weeks’ gestation, women (cases) were randomly assigned to cerclage or progesterone and sampled weekly. Cytokine concentrations were measured in a subset of cervico-vaginal fluid samples (n = 477 from 78 women) by 11-plex fluid-phase immunoassay.

Results

All 11 inflammatory cytokines investigated were detected in cervico-vaginal fluid from women at high risk of preterm birth, irrespective of later cervical shortening. At less than 24 weeks’ gestation and prior to intervention, women destined to develop a short cervix (n = 36) exhibited higher cervico-vaginal concentrations than controls (n = 42) of granulocyte-macrophage colony-stimulating factor [(GM-CSF) 16.2 fold increase, confidence interval (CI) 1.8–147; p = 0.01] and monocyte chemotactic protein-1 [(MCP-1) 4.8, CI 1.0–23.0; p = 0.05]. Other cytokines were similar between cases and controls. Progesterone treatment did not suppress cytokine concentrations. Interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon (IFN)-γ and tumour necrosis factor (TNF)-α concentrations were higher following randomization to cerclage versus progesterone (p<0.05). Cerclage, but not progesterone treatment, was followed by a significant increase in cervical length [mean 11.4 mm, CI 5.0–17.7; p<0.001].

Conclusions

Although GM-CSF and MCP-1 cervico-vaginal fluid concentrations were raised, the majority of cervico-vaginal cytokines did not increase in association with cervical shortening. Progesterone treatment showed no significant anti-inflammation action on cytokine concentrations. Cerclage insertion was associated with an increase in the majority of inflammatory markers and cervical length.     

Raised Trappin2/elafin Protein in Cervico-Vaginal Fluid Is a Potential Predictor of Cervical Shortening and Spontaneous Preterm Birth

Early spontaneous preterm birth is associated with inflammation/infection and shortening of the cervix. We hypothesised that cervico-vaginal production of trappin2/elafin (peptidase inhibitor 3) and cathelicidin antimicrobial peptide (cathelicidin), key components of the innate immune system, are altered in women who have a spontaneous preterm birth. The aim was to determine the relationship between cervico-vaginal fluid (CVF) trappin2/elafin and cathelicidin protein concentrations with cervical length in woman at risk of spontaneous preterm birth. Trappin2/elafin and cathelicidin were measured using ELISA in longitudinal CVF samples (taken between 13 to 30 weeks'' gestation) from 74 asymptomatic high risk women (based on obstetric history) recruited prospectively. Thirty six women developed a short cervix (<25 mm) by 24 weeks'' and 38 women did not. Women who developed a short cervix had 2.71 times higher concentrations of CVF trappin2/elafin from 14 weeks'' versus those who did not (CI 1.94–3.79, p<0.0005). CVF trappin2/elafin before 24 weeks'' was 1.79 times higher in women who had a spontaneous preterm birth <37 weeks'' (CI: 1.05–3.05, p = 0.034). Trappin2/elafin (>200 ng/ml) measured between 14⁺⁰–14⁺⁶ weeks'' of pregnancy predicted women who subsequently developed a short cervix (n = 11, ROC area = 1.00, p = 0.008) within 8 weeks. Cathelicidin was not predictive of spontaneous delivery. Vitamin D status did not correlate with CVF antimicrobial peptide concentrations. Raised CVF trappin2/elafin has potential as an early pregnancy test for prediction of cervical shortening and spontaneous preterm birth. This justifies validation in a larger cohort.     

Use of prostaglandin E2 to ripen the cervix of the mare prior to induction of parturition

Eleven light-breed pregnant mares (335 to 347 d gestaton) were used to evaluate the use of prostaglandin E2 as a cervical ripening agent prior to induction of parturition during the months of April and May. Six hours prior to induction, each mare's cervix was examined per vagina for softness and dilation. Each mare was then assigned to 1 of 2 treatment groups: Group PGE mares (n = 7) received 2.0 to 2.5 mg prostaglandin E2 deposited intracervically; Group SAL mares (n = 4) received 0.5 mL of sterile NaCl deposited intracervically. Six hours later, the mares were readied for parturition by wrapping the tail, scrubbing and rinsing the perineum and udder, and examining the cervix as previously described. Each mare was then administered 15 U, i.v. oxytocin at 15-min intervals until the chorioallantois ruptured. Intervals from initial oxytocin injection until rupture of the chorioallantois, from initial oxytocin injection until delivery of the foal, from delivery of the foal until the foal stood unassisted, and from delivery of the foal until the foal suckled were recorded. Mean cervical dilation immediately prior to induction of parturition tended to be greater in Group PGE mares (3.9 +/- 1.7 cm) than in Group SAL mares (1.9 +/- 1.9 cm; P = 0.10). Mean change in cervical dilation over the 6-h period prior to induction (3.4 +/- 1.9 cm vs 1.5 +/- 2.1 cm), mean number of injections of oxytocin required until the chorioallantois ruptured (1.9 +/- 0.7 vs 2.5 +/- 1.0), and mean intervals from initial injection of oxytocin to rupture of the chorioallantois (20 +/- 10 min vs 28 +/- 19 min) and delivery of the foal (28 +/- 7 min vs 34 +/- 22 min) were not different between Group PGE and SAL mares, respectively (P > 0.10). The proportion of foals that stood within 1 h of birth also did not differ between Group PGE foals (6/7; 86%) and Group SAL foals (3/4; 75%; Chi-square = 0.17; P > 0.10). The proportion of foals that nursed within 2 h of birth was higher in Group PGE foals (6/7; 86%) than in Group SAL foals (1/4; 25%; Chi-square = 4.02; P < 0.05). Premature separation requiring manual rupture of the chorioallantois at the vulvar labia occurred in 1 Group PGE mare (cervical dilation of 1.5 cm at time of induction) and 1 Group SAL mare (cervix closed and firm at time of induction). Foals born from the 2 mares with premature placental separation had the longest intervals from initial oxytocin injection to delivery, delivery to ability to stand unassisted, and delivery to suckling within their respective treatment groups. In summary, it appears that cervical ripening prior to induction of parturition favors shorter deliveries and foal vigor. Intracervical administration of prostaglandin E2 may prove useful for ripening the cervix of the mare prior to induction of parturition. Further studies are indicated to determine optimal dosage and method of administration of prostaglandin E2.     

Proteomic analysis of amniotic fluid to identify potential targets predicting preterm delivery

Preterm delivery is a common complication of pregnancy which leads to significant neonatal mortality and morbidity. Identifying predictive markers linked to spontaneous preterm delivery (SPTD) is important for effective treatment and prevention of PTD. To explore potential biomarkers related to SPTD, we performed proteomics analysis in amniotic fluid (AF). In total, we enrolled 30 pregnant women with singleton gestation who underwent clinically indicated amniocentesis at 15–24 weeks of gestation. LC-MS analysis was used to analyze the AF samples of 10 women with SPTD < 34 weeks after cervix cerclage (Preterm group), 10 women with term delivery (TD) ≥ 34 weeks after cervix cerclage (Term group), and 10 women who delivered at term (Normal group). ELISA validation was performed for candidate proteins in a second independent cohort. As a result, we identified 44 differentially expressed proteins (DEPs, P < 0.05) via proteomic analysis, and based on that, 9 primary pathways were also determined in SPTD. Results of the ELISA assay confirmed that the increased concentration of Serpin A1, decreased concentrations of Renin and IGFBP4 were significantly associated with SPTD at ≤34 weeks.     

The effect of gestational age and labour on markers of lipid and protein oxidation in cord plasma

There are many potential sources of reactive oxidants around the time of birth and pre-term infants are considered to be particularly vulnerable to oxidative injury. To gain insight into these processes, we have measured biomarkers of lipid and protein oxidation in umbilical cord plasma and related concentrations to mode of delivery and gestational age. Protein carbonyls were measured by ELISA and malondialdehyde (MDA) by HPLC after reaction with thiobarbituric acid, for 54 pre-term (< or = 36 weeks gestational age) and 43 term infants. Protein carbonyls were significantly lower in pre-term (median for < 32 weeks gestational age 0.048nmol/mg protein) than in term infants (0.105 nmol/mg, p = 0.004), and were unrelated to mode of delivery. In contrast, MDA concentrations were higher in the very pre-term (<32 weeks gestation) group (2.47 compared with 1.83 microM for term infants, p < 0.0001). MDA concentrations were higher in infants who were born with labour compared with elective caesarean section. Pre-eclampsia in the mother was associated with higher cord blood MDA concentrations. The MDA results are consistent with other studies of this marker and could be interpreted as indicating increased oxidative stress associated with prematurity and labour. However, the lower protein carbonyls in pre-term infants would lead to an opposite interpretation. More information is needed on the source and fate of these and other biomarkers before drawing strong conclusions on how they reflect oxidative stress in this and other clinical situations.     

Estrogen and progesterone receptors in the ovine cervix during the postpartum period

Cervical estrogen (E) and progesterone (P) receptors were characterized and quantified during the postpartum period in Corriedale ewes lambing in the late breeding season. Cervices and uteri were collected after ovariohysterectomy at 1 d (n = 2), 5 d (n = 4), 17 d (n = 2) or 30 d (n = 2) post partum. The estrogen and progesterone receptors were measured using binding assays with tritiated hormones, dextran charcoal separation and inverse Scatchard analysis. Similar kinetic parameters in cytosolic binding sites for both hormones were found in all cervical and uterine samples, indicating that the binding protein in both tissues is of the same nature. Receptor concentrations (fmol/mg cytosolic protein) in the cervix of early (1 to 5 d, n = 6) and late (17 to 30 d, n = 4) postpartum ewes were 348 +/- 66 vs 994 +/- 145 (P < 0.05) for E and 618 +/- 126 vs 1170 +/- 201 (P < 0.05) for P, respectively. These data suggest an increased synthesis of receptors, probably due to the presence of ovarian estrogen-active follicles. Cervical E and P receptor concentrations were similar or higher than those in the uterus (1.40 +/- 0.15, n = 10 and 1.51 +/- 0.19, n = 10; for E and P respectively), and these receptor ratios did not differ between the early and late postpartum period. The high ratio between cervical/uterine receptors suggests that the ovine cervix may be a very sensitive to steroid action. In conclusion, it was shown that restoration of steroid receptors during the postpartum period in the ovine cervix is similar to receptor dynamics in the uterus, and is probably associated with the recovery of ovarian cyclicity.     

Total matrix metalloproteinase-8 serum levels in patients labouring preterm and patients with threatened preterm delivery

Preterm labour and prematurity are still a main cause of perinatal morbidity nowadays. The aim of our study was to assess the role of MMP-8 as a predictive marker of preterm delivery. Four groups of patients were involved to the study: I - pregnant women at 24-34 weeks of gestation with any symptoms of threatened preterm labour; II - threatened preterm labour patients between 24-34 weeks of gestation; III - preterm vaginal delivery patients; IV - healthy term vaginal delivery patients. Serum concentration of total MMP-8 was measured using two enzyme-linked immunosorbent assays. There were no significant differences in the median concentrations of total MMP-8 between physiological pregnancy and threatened preterm labour patients with existing uterine contractility. No significant differences of total MMP-8 were either found between healthy term and preterm labouring patients. The studies on a larger population are needed to reject the hypothesis that preterm labour is connected with increased MMP-8 plasma concentrations of women in preterm labour and threatened preterm delivery.     

The Effect of Polyhydramnios on Cervical Length in Twins: A Controlled Intervention Study in Complicated Monochorionic Pregnancies

Objective

To test the hypothesis that cervical shortening in polyhydramnios reflects the degree of excess amniotic fluid, and increases with normalisation of amniotic fluid volume.

Study Design

Prospective cohort study of 40 women with monochorionic twins undergoing interventional procedures between 16–26 weeks. Cervical length was assessed via transvaginal sonography pre-procedure, 1 and 24 hours post-procedure, and results compared between amnioreduction and control procedures. Amniotic fluid index (AFI) was measured pre- and post-procedure.

Results

Pre-procedural cervical length correlated with AFI (linear fit = 5.07 -0.04x, R² = 0.17, P = 0.03) in patients with polyhydramnios (n = 28). Drainage of 2000ml fluid (range 700–3500ml), reduced AFI from 42cm to 21cm (P<0.001). Their pre-procedural cervical length did not change at one (mean Δ:−0.1cm, 95%CI, −0.4 to 0.2) or 24 hours (0.2cm, −0.1 to 0.6) after amnioreduction. There was no change in cervical length at control procedures.

Conclusion

Cervical shortening in twins with polyhydramnios does not appear to be an acute process; cervical length can be measured before or after therapeutic procedures.     

Identification of bactenecin-1 in cervicovaginal fluid by two-dimensional electrophoresis in an ovine model of preterm labour

Preterm labour is a major problem in obstetrics. Timely intervention with available treatments is hampered by the lack of a reliable test of imminent preterm delivery. Current methods of diagnosis are based on the detection of breakdown products of foetal membranes or structural changes to the cervix when preterm labour is well established. The aim of this study was to screen the cervicovaginal fluid (CVF) proteome to identify labour-associated proteins that could be used as markers of imminent preterm delivery. Labour was induced in sheep at 135 days of gestation (term 147 days) by foetal infusion of dexamethasone (1 mg/24 h). CVF samples were collected before and 28 h after the start of infusion as well as at delivery (58.7 +/- 1.9 after the start of infusion, n = 5). One protein that was upregulated eight-fold, was bactenecin-1, a member of the cathelicidin family of antimicrobial proteins. This antimicrobial protein warrants further investigation as a marker of preterm labour, particularly during the period after the initiation of labour but before there is marked cervical connective tissue breakdown.     

Investigating the mechanical function of the cervix during pregnancy using finite element models derived from high-resolution 3D MRI

Preterm birth is a strong contributor to perinatal mortality, and preterm infants that survive are at risk for long-term morbidities. During most of pregnancy, appropriate mechanical function of the cervix is required to maintain the developing fetus in utero. Premature cervical softening and subsequent cervical shortening are hypothesized to cause preterm birth. Presently, there is a lack of understanding of the structural and material factors that influence the mechanical function of the cervix during pregnancy. In this study we build finite element models of the pregnant uterus, cervix, and fetal membrane based on magnetic resonance imagining data in order to examine the mechanical function of the cervix under the physiologic loading conditions of pregnancy. We calculate the mechanical loading state of the cervix for two pregnant patients: 22 weeks gestational age with a normal cervical length and 28 weeks with a short cervix. We investigate the influence of (1) anatomical geometry, (2) cervical material properties, and (3) fetal membrane material properties, including its adhesion properties, on the mechanical loading state of the cervix under physiologically relevant intrauterine pressures. Our study demonstrates that membrane–uterus interaction, cervical material modeling, and membrane mechanical properties are factors that must be deliberately and carefully handled in order to construct a high quality mechanical simulation of pregnancy.     

Association between length of gestation and cervical DNA methylation of PTGER2 and LINE 1-HS

Worldwide, more than 1 in 10 infants is born prior to 37 weeks gestation. Preterm birth can lead to increased mortality risk and poor life-long health and neurodevelopmental outcomes. Whether environmental risk factors affect preterm birth through epigenetic phenomena is largely unstudied. We sought to determine whether preterm risk factors, such as smoke exposure and education, were associated with cervical DNA methylation in the prostaglandin E receptor 2 gene (PTGER2) and a repetitive element, long interspersed nuclear element-1 Homo sapiens-specific (LINE 1-HS). Second, we aimed to determine whether mid-pregnancy DNA methylation of these regions in cervical samples could predict the length of gestation. We obtained a cervical swab between 16–19 weeks gestation from 80 women participating in a Mexico City birth cohort, used pyrosequencing to analyze DNA methylation of PTGER2 and LINE 1-HS, and examined associations with maternal covariates. We used accelerated failure time models to analyze associations of DNA methylation with the length of gestation. DNA methylation of both sequences was associated with Pap smear inflammation. LINE 1-HS methylation was associated with smoke exposure, BMI and parity. In adjusted models, gestations were 3.3 days longer (95%CI 0.6, 6.0) for each interquartile range of PTGER2 DNA methylation. Higher LINE 1-HS methylation was associated with shorter gestations (-3.3 days, 95%CI -6.5, -0.2). In conclusion, cervical DNA methylation was associated with risk factors for preterm birth and the length of gestation.     

Association between length of gestation and cervical DNA methylation of PTGER2 and LINE 1-HS

Worldwide, more than 1 in 10 infants is born prior to 37 weeks gestation. Preterm birth can lead to increased mortality risk and poor life-long health and neurodevelopmental outcomes. Whether environmental risk factors affect preterm birth through epigenetic phenomena is largely unstudied. We sought to determine whether preterm risk factors, such as smoke exposure and education, were associated with cervical DNA methylation in the prostaglandin E receptor 2 gene (PTGER2) and a repetitive element, long interspersed nuclear element-1 Homo sapiens-specific (LINE 1-HS). Second, we aimed to determine whether mid-pregnancy DNA methylation of these regions in cervical samples could predict the length of gestation. We obtained a cervical swab between 16–19 weeks gestation from 80 women participating in a Mexico City birth cohort, used pyrosequencing to analyze DNA methylation of PTGER2 and LINE 1-HS, and examined associations with maternal covariates. We used accelerated failure time models to analyze associations of DNA methylation with the length of gestation. DNA methylation of both sequences was associated with Pap smear inflammation. LINE 1-HS methylation was associated with smoke exposure, BMI and parity. In adjusted models, gestations were 3.3 days longer (95%CI 0.6, 6.0) for each interquartile range of PTGER2 DNA methylation. Higher LINE 1-HS methylation was associated with shorter gestations (-3.3 days, 95%CI -6.5, -0.2). In conclusion, cervical DNA methylation was associated with risk factors for preterm birth and the length of gestation.     

择期经阴道宫颈环扎术与期待疗法治疗宫颈机能不全的效果比较

目的:比较择期经阴道宫颈环扎术以及期待疗法治疗宫颈机能不全的效果。方法:选择2017年10月~2019年10月我院收治的201例宫颈机能不全患者,将其随机分为两组。对照组100例患者采取期待疗法,即卧床休息,口服地屈孕酮,每次服用的剂量为10 mg,每日2次,一直服药到30孕周;观察组101例患者择期经阴道宫颈环扎术,比较两组的早产率、成功妊娠率、新生儿出生体重以及分娩孕周。结果:对照组100例宫颈机能不全患者中,22例患者流产(占22.00%),78例患者获得活婴(占78.00%),78例成功分娩的患者中,47例患者≥37周分娩,31例患者<37周分娩,早产率为39.74%(31/78)。观察组的101例患者中,8例患者流产(占7.92%),93例患者获得活婴(占92.08%)。93例成功分娩的患者中,81例患者≥37周分娩,12例患者<37周分娩,早产率为12.90%(12/93);12例早产的患者中,4例患者由于胎膜早破和胎儿窘迫,而在孕32~33周采取剖宫产手术,2例患者由于胎膜早破臀位,而在孕35~36周时采取剖宫产手术,6例患者在孕35~36周早产。观察组宫颈机能不全患者的早产率明显低于对照组(P<0.05),且成功妊娠率、新生儿出生体重以及分娩孕周明显高于或长于对照组(P<0.05)。结论:与期待疗法相比较,择期经阴道宫颈环扎术不但可以明显延长宫颈机能不全患者的分娩孕周,提高成功妊娠率,还能改善新生儿的预后、降低早产的风险。     

Corticotropin releasing hormone concentrations in umbilical cord blood of preterm fetuses.

Corticotrophin releasing hormone (CRH), dehydroepiandrosterone sulfate (DHEAS) and cortisol were measured in umbilical cord plasma obtained from 90 preterm and 98 term fetuses. Maternal plasma was obtained from 23 women who delivered preterm and from 23 women matched for gestational age who ultimately delivered term infants. Mean umbilical cord plasma CRH concentration was significantly higher in the preterm fetuses (n = 69, 538 +/- 63 pg/ml) compared to the term fetuses (n = 98, 280 +/- 22 pg/ml, P < 0.01). Mean DHEAS level in the preterm fetuses was 208 +/- 22 mg/dl (n = 56), cortisol level was 7 +/- 1 mg/dl (n = 58). Umbilical plasma CRH concentrations (808 +/- 170 pg/ml) were significantly higher at 24-27 weeks than at 28-31 or 31-34 weeks gestation. Cortisol levels (12 +/- 3 micrograms/dl) were highest at 24-27 weeks. Mode of delivery and the presence of labor did not affect fetal CRH levels. The highest fetal CRH levels were measured in the pregnancies complicated by hypertension as well as prematurity; however, fetal CRH levels remained higher in the preterm group compared to the term group when hypertensive pregnancies were excluded. Maternal plasma CRH levels were significantly higher in the group that delivered preterm compared to women who delivered at term matched for gestational age (1058 +/- 184 pg/ml compared to 456 +/- 71 pg/ml, P < 0.00).(ABSTRACT TRUNCATED AT 250 WORDS)     

The Effect of Gestational Age and Labour on Markers of Lipid and Protein Oxidation in Cord Plasma

There are many potential sources of reactive oxidants around the time of birth and pre-term infants are considered to be particularly vulnerable to oxidative injury. To gain insight into these processes, we have measured biomarkers of lipid and protein oxidation in umbilical cord plasma and related concentrations to mode of delivery and gestational age. Protein carbonyls were measured by ELISA and malondialdehyde (MDA) by HPLC after reaction with thiobarbituric acid, for 54 pre-term (≤36 weeks gestational age) and 43 term infants. Protein carbonyls were significantly lower in pre-term (median for <32 weeks gestational age 0.048?nmol/mg protein) than in term infants (0.105?nmol/mg, p=0.004), and were unrelated to mode of delivery. In contrast, MDA concentrations were higher in the very pre-term (<32 weeks gestation) group (2.47 compared with 1.83?μM for term infants, p<0.0001). MDA concentrations were higher in infants who were born with labour compared with elective caesarean section. Pre-eclampsia in the mother was associated with higher cord blood MDA concentrations. The MDA results are consistent with other studies of this marker and could be interpreted as indicating increased oxidative stress associated with prematurity and labour. However, the lower protein carbonyls in pre-term infants would lead to an opposite interpretation. More information is needed on the source and fate of these and other biomarkers before drawing strong conclusions on how they reflect oxidative stress in this and other clinical situations.