Subsequent Spontaneous Preterm Delivery Research Articles

Screening for spontaneous preterm birth by cervical length and shear-wave elastography in the first trimester of pregnancy

First-trimester cervical length for the prediction of spontaneous preterm delivery remains controversial. A better method for the measurement of the first-trimester cervical length and additional cervical ultrasound parameters for the identification of women at high risk for spontaneous preterm delivery are needed. This study aimed to compare the predictive value of cervical length measured by 2 different methods in the first trimester of pregnancy to predict spontaneous preterm delivery and to explore the potential value of first-trimester cervical shear-wave elastography for the prediction of spontaneous preterm delivery. This was a prospective study in unselected singleton pregnancies at 11+0 to 13+6 weeks' gestation. Cervical length was measured by the following 2 methods in the base-cohort population: (1) a linear distance between the 2 ends of the glandular area around the endocervical canal (single-line method: cervical length-s) and (2) a sum of the linear distance from the internal os to the greatest cervical curvature and the linear distance from this point to the external os (2-line method: cervical length-t). In a substudy, cervical shear-wave elastography scores for 9 regions of interest (inner, middle, and external parts of anterior lip, endocervical canal, and posterior lip) in midsagittal plane were also obtained by transvaginal ultrasonography. The screening performance of the first-trimester cervical length measured by the 2 different methods for the prediction of spontaneous preterm delivery was assessed by receiver operating characteristics curve analysis. The areas under the curves were compared using a DeLong test. The predictive performance of a soft cervix (mean elastography scores with multiple of median <5th, 10th, 15th, 20th, and 25th percentile) for spontaneous preterm delivery was also determined. Among a total of 2316 included pregnancies, spontaneous delivery at <37 and <34 weeks' gestation occurred in 111 cases (4.8%) and 20 cases (0.9%), respectively. In the total study population, when compared with the term delivery group, the median cervical length-t was shorter in women with spontaneous delivery at <34 weeks' gestation (36.9 mm vs 35.1 mm; P=.015), but there was no clear correlation for cervical length-s. Receiver operating characteristics curves demonstrated that cervical length-t achieved better performance in predicting spontaneous delivery at <34 weeks' gestation (area under the curve, 0.658 vs 0.573; P<.01) than cervical length-s. The best combined model to predict spontaneous delivery at <34 weeks' gestation was provided by cervical length-t and history of preterm delivery (area under the curve, 0.692). In the substudy, a soft cervix with a mean elastography scores multiple of median <10th percentile had a relative risk of 7.8 (95% confidence interval, 2.1-28.6) for spontaneous delivery at <34 weeks' gestation; the detection rate was 44.4% at a false-positive rate of 9.0%. The 2-line approach provides a better estimate of the actual first-trimester cervical length and achieves better performance as a screening tool for spontaneous preterm delivery at <34 weeks' gestation than the conventional measurement. A soft cervix as determined by shear-wave elastograpthy in the first trimester is associated with an increased risk for subsequent spontaneous preterm delivery.

Metabolomic profiles of mid-trimester amniotic fluid are not associated with subsequent spontaneous preterm delivery or gestational duration at delivery

Introduction Spontaneous preterm delivery (<37 gestational weeks) has a multifactorial etiology with still incompletely identified pathways. Amniotic fluid is a biofluid with great potential for insights into the feto-maternal milieu. It is rich in metabolites, and metabolic consequences of inflammation is yet researched only to a limited extent. Metabolomic profiling provides opportunities to identify potential biomarkers of inflammatory conditioned pregnancy complications such as spontaneous preterm delivery. Objective The aim of this study was to perform metabolomic profiling of amniotic fluid from uncomplicated singleton pregnancies in the mid-trimester to identify potential biomarkers associated with spontaneous preterm delivery and gestational duration at delivery. A secondary aim was to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers of spontaneous preterm delivery in asymptomatic women. Method A nested case-control study was performed within a larger cohort study of asymptomatic pregnant women undergoing mid-trimester genetic amniocentesis at 14–19 gestational weeks in Gothenburg, Sweden. Medical records were used to obtain clinical data and delivery outcome variables. Amniotic fluid samples from women with a subsequent spontaneous preterm delivery (n = 37) were matched with amniotic fluid samples from women with a subsequent spontaneous delivery at term (n = 37). Amniotic fluid samples underwent untargeted metabolomic analyses using liquid chromatography-mass spectrometry. Multivariate random forest analyses were used for data processing. A secondary targeted analysis was performed, aiming to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers in women with a subsequent spontaneous preterm delivery. Results Multivariate analysis did not distinguish the samples from women with a subsequent spontaneous preterm delivery from those with a subsequent term delivery. Neither was the metabolic profile associated with gestational duration at delivery. Potential metabolic biomarker candidates were identified from four publications by two different research groups relating mid-trimester amniotic fluid metabolomes to spontaneous PTD, of which fifteen markers were included in the secondary analysis. None of these were replicated. Conclusions Metabolomic profiles of early mid-trimester amniotic fluid were not associated with spontaneous preterm delivery or gestational duration at delivery in this cohort.

Comparison of Bacterial DNA Profiles in Mid-Trimester Amniotic Fluid Samples From Preterm and Term Deliveries.

Infection and inflammation are well recognized causes of spontaneous preterm delivery (PTD) (<37 gestational weeks) and adverse infant outcomes. To date, there has been very little investigation into bacterial communities in amniotic fluid using next generation sequencing technology. In particular, it is important to characterize amniotic fluid bacterial profiles in complicated pregnancies as well as in asymptomatic women to identify predictive bacterial DNA signatures. Here, 1198 mid-trimester amniotic fluid samples from a cohort of Swedish women undergoing mid-trimester genetic amniocentesis were screened for bacterial DNA using qPCR protocols specifically designed to reduce the impacts of reagent contamination and human DNA mispriming. The majority of samples were devoid of detectable bacterial DNA; however, approximately a fifth of the cohort (19.9%) were 16S rRNA gene positive in duplicate screening. Among these, nine women had a spontaneous PTD. These nine women were matched with 18 healthy women with a delivery at term. We used PacBio SMRT technology, coupled with appropriate negative extraction and PCR controls, to sequence the full-length 16S rRNA gene in this subset of 27 women. The amniotic fluid samples contained low-abundance and low-diversity bacterial DNA profiles. Species typically associated with spontaneous PTD were absent. We were not able to identify any differences in the amniotic fluid bacterial DNA profiles of women with a subsequent spontaneous PTD compared to women who delivered at term. The findings suggest that, in a minor proportion of pregnancies, DNA from non-pathogenic bacteria may be present in the amniotic fluid far earlier than previously reported. Early detection of bacterial DNA in the amniotic fluid was, in this study, not associated with spontaneous PTD.

Women with threatened preterm labour followed by term delivery have an increased risk of spontaneous preterm birth in subsequent pregnancies: a population-based cohort study.

To evaluate the association of a history of threatened preterm labour (TPL) followed by term delivery with the risk of spontaneous preterm delivery (PTD) in subsequent pregnancy. Population-based cohort study. Data of the National Health Insurance Claims Database and a national health-screening programme for infants and children in South Korea. Women who had their first singleton delivery in 2010 and a subsequent second singleton delivery between 2011 and 2015. Multivariable analysis adjusting for maternal age and interval between first and second deliveries was used to assess the risk of PTD based on PTD, TPL followed by term delivery, and term delivery in the first pregnancy. The risk of PTD during the second pregnancy. This study included 115629 women with two consecutive deliveries during the study period. Spontaneous PTD rates in the second pregnancy were 7.71, 2.22 and 1.02% in women with PTD, TPL followed by term delivery, and term delivery in the first pregnancy, respectively. Threatened preterm labour followed by term delivery in the first pregnancy was associated with increased risk of PTD in the subsequent pregnancy after adjustment for potential confounding factors (adjusted odds ratio 2.21; 95% CI 1.76-2.78). Although women with a history of TPL followed byterm delivery had a lower risk of PTD during a subsequentpregnancy compared with those with history of previous PTD, they still had a significantly increased risk ofPTD compared with those who delivered at term without TPL. The history of threatened preterm labour followed by term delivery is related to increased risk of subsequent spontaneous preterm delivery.

The association between selected mid-trimester amniotic fluid candidate proteins and spontaneous preterm delivery

Objective: The aim of this study was to explore inflammatory response and identify early potential biomarkers in mid-trimester amniotic fluid associated with subsequent spontaneous preterm delivery (PTD).Methods: A cohort study was performed at Sahlgrenska University Hospital/Östra, Gothenburg, Sweden, between 2008 and 2010. Amniotic fluid was collected from consecutive women undergoing mid-trimester transabdominal genetic amniocentesis at 14–19 gestational weeks. Clinical data and delivery outcome variables were obtained from medical records. The analysis included 19 women with spontaneous PTD and 118 women who delivered at term. A panel of 26 candidate proteins was analyzed using Luminex xMAP technology. Candidate protein concentrations were analyzed with ANCOVA and adjusted for plate effects.Results: The median gestational age at delivery was 35 + 3 weeks in women with spontaneous PTD and 40 + 0 weeks in women who delivered at term. Nominally significantly lower amniotic fluid levels of adiponectin (PTD: median 130,695 pg/mL (IQR 71,852–199,414) vs term: median 185,329 pg/mL (IQR (135,815–290,532)), granulocyte-macrophage colony stimulating factor (PTD: median 137 pg/mL (IQR 74–156) vs term: median 176 pg/mL (IQR 111–262)), and macrophage migration inhibitory factor (PTD: median 3025 pg/mL (IQR 1885–3891) vs term: median 3400 pg/mL (IQR 2181–5231)) were observed in the spontaneous PTD group, compared with the term delivery group, after adjusting for plate effects. No significant differences remained after Bonferroni correction for multiple comparisons.Conclusions: Our results are important in the process of determining the etiology behind spontaneous PTD but due to the non-significance after Bonferroni correction, the results should be interpreted with caution. Further analyses of larger sample size will be required to determine whether these results are cogent and to examine whether microbial invasion of the amniotic cavity or intra-amniotic inflammation occurs in asymptomatic women in the mid-trimester with subsequent spontaneous PTD.

Cesarean Delivery in the Second Stage of Labor and the Risk of Subsequent Premature Birth

(Am J Obstet Gynecol. 2017;217(1):63.e1–63.e10) Cesarean delivery rates are on the rise in the United States, in part because of the increased use of cesarean delivery rather than forceps and vacuum deliveries for fetal distress and arrest disorders in the second stage of labor. However, cesarean delivery in the second stage of labor can be risky due to the difficulty of delivering a deeply impacted fetal head. Cohort studies have shown increased risk of extensions of the uterine incision, bladder injury, and postpartum hemorrhage in such deliveries. Surgical trauma to the cervix from other procedures has been demonstrated to significantly increase the risk of subsequent premature delivery. For these reasons, the authors hypothesized that second-stage cesarean deliveries may increase the rate of subsequent spontaneous preterm delivery.

Early second trimester maternal plasma levels of thrombin‐inhibitor complexes and subsequent spontaneous preterm delivery

Increased thrombin generation has been implicated as a mechanism for several obstetric syndromes including preterm birth preceded by preterm labor (PTL) and preterm premature rupture of membranes (PPROM). In this study, we attempted to determine whether PTL or PPROM are associated with changes in the maternal plasma thrombin level during the early second trimester. This is a case-control study in which maternal thrombin-antithrombin (TAT) III complex concentrations at 15-21 weeks were compared between normal controls (n = 85) and women subsequently delivering preterm, due to either PTL with intact membranes (n = 21) or PPROM (n = 20). Statistical analysis was conducted using non-parametric statistics. PTL patients with intact membranes showed non-significant differences in median plasma TAT level (110.1 µg/L) compared with the control group (107.9 µg/L). Similarly, women destined to deliver preterm because of PPROM had non-significantly higher plasma TAT level (134.3 µg/L) than those in the control group (107.9 µg/L) (p > 0.05). Logistic regression analysis demonstrated that after controlling for confounders including vaginal bleeding, TAT levels remained not significantly associated with subsequent spontaneous preterm birth (p = 0.27). Maternal plasma TAT level is unsuitable as an early second trimester predictor of preterm birth preceded by PTL or PPROM.

Large loop excision of transformation zone and cervical length in the prediction of spontaneous preterm delivery

To investigate the association between previous large loop excision of transformation zone (LLETZ) and risk for subsequent spontaneous preterm delivery (sPD) and whether this effect is reflected in the measurement of cervical length at mid-gestation. A secondary analysis of data from women recruited for clinical trials of interventions to prevent preterm labour. A total of 26,867 women with singleton pregnancies attending for routine antenatal care. Transvaginal sonographic measurement of cervical length was carried out at 20(+0) to 24(+6) weeks. Logistic regression analysis was used to determine the significant predictors of sPD among maternal characteristics, obstetric history, previous history of LLETZ and cervical length. Spontaneous preterm delivery. In the 473 women who had undergone LLETZ, compared with the 25,772 without a history of LLETZ, the rate of sPD before 34 weeks of gestation was higher (3.4 versus 1.3%, P = 0.0002) and the median cervical length was shorter (32 mm versus 34 mm, P < 0.0001). Regression analysis demonstrated that in the prediction of sPD there were significant contributions from racial origin, cigarette smoking, previous preterm delivery and LLETZ and the detection rate of sPD was 29.8%, at a false-positive rate of 10%. However, after addition of cervical length, LLETZ did not remain a significant predictor in the model, which detected 52.6% of sPD, at a false-positive rate of 10%. LLETZ increases the risk of sPD, even after adjustment for maternal risk factors. The effect of a previous LLETZ on sPD in a subsequent pregnancy is reflected in the measurement of cervical length at mid-gestation.

470: Fetal fibronectin levels at 24 weeks are predictive of recurrent PPROM and subsequent spontaneous preterm delivery (SPTD) in asymptomatic patients with a history of PPROM

470: Fetal fibronectin levels at 24 weeks are predictive of recurrent PPROM and subsequent spontaneous preterm delivery (SPTD) in asymptomatic patients with a history of PPROM

Loop Electrosurgical Excision of the Cervix and Risk for Spontaneous Preterm Delivery in Twin Pregnancies

To investigate the association between three cervical procedures (biopsy with no treatment, ablation, and loop electrosurgical excision procedure [LEEP]) and subsequent spontaneous preterm delivery in twin pregnancies using population-based data from various nationwide registries. : The study population consisted of all twin deliveries in Denmark during a 9-year period, 1997-2005. Information on the deliveries, including cervical procedures, was obtained from various national registries. In all, 9,868 deliveries were eligible for analyses, of which 3,228 were delivered spontaneously preterm (32.7%). Preterm delivery was defined as gestational age between 21 weeks and 37 weeks. Logistic regression analyses were used to evaluate the association between cervical procedures and preterm delivery. Twin pregnancies subsequent to LEEP had a significantly increased risk of overall subsequent spontaneous preterm delivery (43.4%) with an adjusted odds ratio of 1.58 (95% confidence interval 1.16-2.14) compared with pregnancies with no prior LEEP (32.5%). The association was consistent in various secondary analyses and especially strong for the very preterm and extremely preterm groups. We found no increase in risk of preterm delivery subsequent to biopsy without treatment or ablation. Our study showed an overall significant increase in risk of preterm delivery in twin pregnancies subsequent to LEEP treatment, even after adjustment for several potential risk factors. II.

Normal amniotic pressure throughout gestation.

To characterize amniotic pressure (AP) in pregnancies with normal amniotic fluid volume. Observational study, mainly cross-sectional. Fetal medicine unit within a tertiary referral hospital. Patients undergoing transamniotic invasive procedures in whom amniotic fluid volume was subjectively assessed as normal on ultrasound. Those beyond 16 weeks with a deepest vertical pool on ultrasound less than 3.0 or greater than 8.0 cm were excluded. Overall 194 pregnancies were studied on 232 occasions between 7 and 38 weeks gestation. Manometry readings referenced to the top of the maternal abdomen were obtained via a fluid-filled line from the needle hub and either connected to a pressure transducer (n = 190) or held vertically against a ruler (n = 42). AP in mm Hg, AP corrected for gestational age (z scores), semi-quantitative ultrasonic indices of amniotic fluid volume, clinical variables. AP in singleton pregnancies increased with advancing gestation (P less than 0.001), and the sigmoid-shaped regression curve plateaued in the mid-trimester. AP z scores were not influenced by volume-related phenomena such as twin gestation, the deepest vertical pool, or amniotic fluid index, nor by maternal age, parity, gravidity, fetal sex, or subsequent spontaneous preterm delivery. These findings suggest that AP is not principally determined by intrauterine volume. We speculate that AP, which reflects change in uterine tension as a function of radius, may instead be determined by gestation-specific anatomical and hormonal influences on gravid uterine musculature. A reference range for AP has been constructed for use in amnioinfusion and amnioreduction procedures.