Higher Risk Of sPTB Research Articles

Longitudinal Cervical Length Measurements and Spontaneous Preterm Birth in Singleton and Twin Pregnancies

Changes in cervical length in twin pregnancies exhibit various patterns, but it is unclear whether the mechanism underlying spontaneous preterm birth (sPTB) is consistent. The existence of detailed phenomena in singleton pregnancies is also unclear. To explore the different patterns in cervical length trajectories in singleton and twin pregnancies and to analyze whether the immunological mechanisms of sPTB are consistent among these cervical length patterns. This cohort study recruited pregnant individuals who received antenatal care and delivered at Peking University Third Hospital in Beijing, China, between January 1, 2014, and December 31, 2022. Individuals with singleton and twin pregnancies were included. Cervical length measurements and white blood cell (WBC) indicators. The primary outcome was sPTB. Longitudinal trajectory cluster analysis was used to identify patterns of changes in cervical length in singleton and twin pregnancies. A random-effects model with cubic spline was used to fit and compare the longitudinal trajectory of WBC indicators among early preterm birth, moderate to late preterm birth, and term birth. A total of 43 559 pregnant individuals were included; of these, 41 706 had singleton pregnancies (mean [SD)] maternal age, 33.0 [4.0] years) and 1853 had twin pregnancies (mean [SD] maternal age, 33.3 [3.6] years). Two distinct patterns of cervical length changes were observed in both singleton and twin pregnancies: shortened (21 366 singletons and 546 twins) and stable (20 340 singletons and 1307 twins). In singleton pregnancies, WBC count was associated with early sPTB in individuals with both shortened cervix (odds ratio [OR], 1.35; 95% CI, 1.00-1.82) and stable cervix (OR, 1.64; 95% CI, 1.07-2.50). However, for twin pregnancies, the association of WBC count (OR, 3.13; 95% CI, 1.58-6.18) with the risk of early sPTB was observed only in individuals with a shortened cervix. This study identified 2 distinct cervical length patterns: shortened and stable. These patterns revealed 2 preterm birth mechanisms in twin pregnancies, with the immunopathogenesis of sPTB found only in the shortened cervix pattern; in singleton pregnancies, maternal immune response was associated with a higher risk of sPTB regardless of a shortened or stable cervix.

Differential Effect of Vaginal Microbiota on Spontaneous Preterm Birth among Chinese Pregnant Women.

The effect of vaginal microbiota on spontaneous preterm birth (sPTB) has not been fully addressed, and few studies have explored the associations between vaginal taxa and sPTB in the gestational diabetes mellitus (GDM) and non-GDM groups, respectively. Study Design. To minimize external interference, a total of 41 pregnant women with sPTB and 308 controls (pregnant women without sPTB) from same regain were enrolled in this case-cohort study. Controls were randomly selected at baseline. With the exception of GDM, other characteristics were not significantly different between the two groups. Vaginal swabs were collected at early second trimester. Using 16S amplicon sequencing, the main bioinformatics analysis was performed on the platform of QIIME 2. Vaginal microbiota traits of the sPTB group were compared with controls. Finally, the effects of binary taxa on sPTB in the GDM group and the non-GDM group were analyzed, respectively. The proportion of GDM in the sPTB (19.51%) was higher than the controls (7.47%, P = 0.018). The vaginal microbiota of pregnant women with sPTB exhibited higher alpha diversity metrics (observed features, P = 0.001; Faith's phylogenetic diversity, P = 0.013) and different beta diversity metrics (unweighted UniFrac, P = 0.006; Jaccard's distance, P = 0.004), compared with controls. The presence of Lactobacillus paragasseri/gasseri (aOR: 3.12, 95% CI: 1.24-7.84), Streptococcus (aOR: 3.58, 95% CI: 1.68-7.65), or Proteobacteria (aOR: 3.39, 95% CI: 1.55-7.39) was associated with an increased risk of sPTB in the non-GDM group (P < 0.05). However, the relative abundance of novel L. mulieris (a new species of the L. delbrueckii group) was associated with a decreased risk of sPTB (false discovery rate, 0.10) in all pregnant women. GDM may modify the association of vaginal taxa with sPTB, suggesting that maternal GDM should be considered when using vaginal taxa to identify pregnant women at high risk of sPTB.

Duration of the second stage of labour and risk of subsequent spontaneous preterm birth.

To determine the risk of spontaneous preterm birth (sPTB) associated with the length of second stage of labour in the first term delivery. Retrospective cohort study. University hospital. Women with first two consecutive singleton births and the first birth at term. Those who did not reach the second stage of labour in the first delivery were excluded. Charts from 2007 to 2019 were reviewed. Rate of sPTB (<37weeks of gestation) in the second delivery. Of 13958 women who met study inclusion criteria, 1464 (10.5%) parturients had a prolonged second stage (≥180min) in their first term delivery. The rate of sPTB in the second delivery was similar in those with and without a prolonged second stage in first delivery (2.8% versus 2.8%; adjusted odds ratio [aOR] 1.35, 95% CI 0.96-1.90). After adjustment for mode of delivery, prolonged second stage was also not associated with subsequent sPTB in those who delivered by spontaneous and operative vaginal delivery. Those delivered by second-stage caesarean section in the first delivery had a higher risk of sPTB in the second delivery (25/526, 4.8%; aOR 2.66, 95% CI 1.71-4.12; p<0.001), with a more pronounced risk in those with second-stage caesarean following a prolonged second stage of labour (15/259, 5.8%; aOR 3.40, 95% CI 1.94-5.94; p<0.001). Second-stage duration in a first term vaginal delivery is not associated with subsequent sPTB. The risk of sPTB is increased following second-stage caesarean section, particularly if performed after a prolonged second stage. Second-stage caesarean delivery, particularly after prolonged second stage, increases the risk of preterm birth.

“Does the use of gestation-specific centiles for cervical length change the management of pregnancies at risk of recurrent spontaneous preterm birth?”

IntroductionPreterm birth is the leading cause of neonatal morbidity and mortality. Spontaneous Preterm Birth (sPTB) has many and varied causes but is known to be strongly associated with a short or shortening cervix in the midtrimester of pregnancy. The strongest risk factor for sPTB is a previous sPTB.In women with a history of sPTB, we can offer surveillance and treatments which have been proven to reduce the risk of sPTB, such as cervical cerclage and vaginal progesterone supplementation. Alongside other indications, we currently use 25 mm or shorter as a “trigger threshold” for offering cervical cerclage treatment in the Preterm Birth Prevention Clinic at The National Maternity Hospital. AimTo determine if using gestation-specific centiles instead of a 25 mm cut-off for cervical length changes the antenatal management of women at high risk of sPTB. MethodThis was a retrospective chart review of all women attending the preterm birth clinic over the 2-year period 2018–2020 in a large tertiary referral unit in Dublin, Ireland. Demographic details, obstetric history, preterm birth risk factors and preventative treatments offered were collected and analysed. Cervical lengths were measured with ultrasound using a standardised protocol and all performed or supervised by 2 experienced sonographers. ResultsA total of 200 patients with known risk factors for sPTB attended the Preterm Birth Surveillance Clinic at the National Maternity Hospital during the study period. Of these, 36/200 (18%) went on to deliver again prior to 37 weeks despite attending the clinic +/- receiving interventions & this group are the focus of this paper. The indications for surveillance in this group that had a recurrent sPTB included recurrent second-trimester pregnancy losses/preterm delivery < 34 weeks (26/36 (72%)), cervical trauma (including treatment of CIN) (12/36 (33%)), congenital abnormalities (1/36 (2.8%)), uterine anomaly (1/36 (2.8%)) and placental bleeding (1/36 (2.8%)). There was one smoker in this series. Funnelling was observed in 3/36 cases (8.3%). Of the 36 patients, an additional 15 would have received a cerclage had gestation-specific centiles, i.e., <5th centile, been used and an additional 10/36 (28%) would have been offered progesterone therapy. ConclusionIn those at high risk of preterm birth, the use of gestation-specific centiles for cervical length increases the proportion of patients that would be eligible for cervical cerclage. It is unclear whether this would change clinical outcome.

Midtrimester Cervical Length in Low-Risk Nulliparous Women for the Prediction of Spontaneous Preterm Birth: Should We Consider a New Definition of Short Cervix?

The study aimed to estimate the predictive value of midtrimester cervical length (CL) and the optimal cut-off of CL that should be applied with asymptomatic nulliparous women for the prediction of spontaneous preterm birth (sPTB). This is a prospective cohort study of asymptomatic nulliparous women with a singleton gestation. Participants underwent CL measurement by transvaginal ultrasound between 20 and 24 weeks of gestation. The participants and their health care providers remained blinded to the results of CL measurement. The primary outcomes were sPTB before 35 weeks and sPTB before 37 weeks. Receiver operating characteristics (ROC) curve analyses were performed. Analyses were repeated by using multiples of median (MoM) of CL adjusted for gestational age. Of 796 participants, the mean midtrimester CL was 40 ± 6 mm with a 1st, 5th, and 10th percentile of 25, 29, and 32 mm, respectively. ROC curve analyses suggest that a cut-off of 30 mm was the optimal CL to predict sPTB before 35 weeks (area under the ROC curve [AUC]: 0.70, 95% confidence interval [CI]: 0.56-0.85) and before 37 weeks (AUC: 0.70, 95% CI: 0.59-0.80). Midtrimester CL <30 mm could detect 35% of all sPTB before 35 weeks at a false-positive rate of 5% (relative risk: 9.1, 95% CI: 3.5-23.5, p < 0.001). We observed similar results using a cut-off of CL <0.75 MoM adjusted for gestational age. A midtrimester CL cut-off of 30 mm (instead of 25 mm), or CL less than 0.75 MoM, should be used to identify nulliparous women at high risk of sPTB. · The optimal CL cut-off for the prediction of sPTB is 30 mm in nulliparous women.. · In nulliparous women, a midtrimester CL < 30 mm is highly associated with sPTB before 35 and 37 weeks.. · A midtrimester of CL <30 mm (5th percentile) should define a short cervix in asymptomatic nulliparous women..

Full Dilatation Caesarean Section and the Risk of Preterm Delivery in a Subsequent Pregnancy: A Historical Cohort Study.

Full dilatation caesarean sections (CS) have increased risk of uterine extensions, which leads to cervical trauma that has been associated with an increased risk of spontaneous preterm birth (sPTB) in a subsequent pregnancy. The aim of this study was to determine if CS at full dilatation increased the risk of sPTB in a subsequent pregnancy in our unit. A historical cohort study was performed on women delivered by emergency CS between 2008–2015 (n = 5808) in a university hospital who had a subsequent pregnancy in this time frame (n = 1557). Women were classified into two exposure groups; those who were 6–9 cm and those fully dilated at index CS. The reference group was CS at 0–5 cm dilated. The primary outcome was sPTB < 37 weeks’ gestation. CS at 6–9 cm or fully dilated did not significantly increase the odds of sPTB in a subsequent pregnancy (aOR 1.64, 95% CI: 0.83–3.28, p = 0.158; aOR 1.86, 95% CI: 0.91–3.83; p = 0.090, respectively). However, a short interpregnancy interval of <1 year significantly increased the odds of sPTB in a subsequent pregnancy (aOR 3.10, 95% CI: 1.71–5.61). This study has found a short interpregnancy interval following a CS conferred a higher risk of sPTB than full dilatation CS. This finding highlights postnatal contraception and increased surveillance of women with short interpregnancy interval post CS as possible interventions to reduce sPTB.

Second-trimester transvaginal ultrasound measurement of cervical length for prediction of preterm birth: a blinded prospective multicentre diagnostic accuracy study.

ObjectiveTo estimate the diagnostic performance of sonographic cervical length for the prediction of preterm birth (PTB).DesignProspective observational multicentre study.SettingSeven Swedish ultrasound centres.SampleA cohort of 11 456 asymptomatic women with a singleton pregnancy.MethodsCervical length was measured with transvaginal ultrasound at 18–20 weeks of gestation (C×1) and at 21–23 weeks of gestation (C×2, optional). Staff and participants were blinded to results.Main outcome measuresArea under receiver operating characteristic curve (AUC), sensitivity, specificity, positive and negative predictive values (PPV and NPV), positive and negative likelihood ratios (LR+ and LR−), number of false‐positive results per true‐positive result (FP/TP), number needed to screen to detect one PTB (NNS) and prevalence of ‘short’ cervix.ResultsSpontaneous PTB (sPTB) at <33 weeks of gestation occurred in 56/11 072 (0.5%) women in the C×1 population (89% white) and in 26/6288 (0.4%) in the C×2 population (92% white). The discriminative ability of shortest endocervical length was better the earlier the sPTB occurred and was better at C×2 than at C×1 (AUC to predict sPTB at <33 weeks of gestation 0.76 versus 0.65, difference in AUC 0.11, 95% CI 0.01–0.23). At C×2, the shortest endocervical length of ≤25 mm (prevalence 4.4%) predicted sPTB at <33 weeks of gestation with sensitivity 38.5% (10/26), specificity 95.8% (5998/6262), PPV 3.6% (10/274), NPV 99.7% (5988/6014), LR+ 9.1, LR− 0.64, FP/TP 26 and NNS 629.ConclusionsSecond‐trimester sonographic cervical length can identify women at high risk of sPTB. In a population of mainly white women with a low prevalence of sPTB its diagnostic performance is at best moderate.Tweetable abstractCervical length screening to predict preterm birth in a white low‐risk population has moderate performance.

Adverse perinatal outcomes associated with antiretroviral therapy regimens: systematic review and network meta-analysis

Assess adverse perinatal outcomes associated with antenatal antiretroviral therapy (ART) regimens. Systematic review and network meta-analysis of randomized controlled trials (RCTS). We conducted a systematic literature review by searching PubMed, CINAHL, Global Health, EMBASE, and the Cochrane Central Register of Controlled Trials and four clinical trial databases from 1 January 1980 to 28 April 2018. We included RCTs of antenatal ART regimens in HIV-positive pregnant women, which assessed preterm birth (PTB), spontaneous preterm birth (sPTB), very preterm birth (VPTB), low birthweight (LBW), very low birthweight (VLBW), small-for-gestational-age (SGA), neonatal death (NND), and mother-to-child-transmission. We used random-effects network meta-analysis models to calculate relative risks for treatment comparisons and the hierarchy of treatments. Of 83 260 citations identified, 10 manuscripts were included, assessing 6285 women. Compared with zidovudine (ZDV) monotherapy, we found a higher risk of LBW after exposure to zidovudine/lamivudine/efavirenz (ZDV/3TC/EFV; relative risk 1.61; 95% CI 1.03-2.51), tenofovir disoproxil fumarate/emtricitabine/ritonavir-boosted lopinavir (TDF/FTC/LPV/r; 1.64; 1.18-2.29), or zidovudine/lamivudine/ritonavir-boosted lopinavir (ZDV/3TC/LPV/r; 1.87; 1.58-2.20). TDF/FTC/LPV/r carried an increased risk of VLBW, compared with ZDV monotherapy (5.40; 1.08-27.08). ZDV/3TC/LPV/r posed a higher risk of PTB than ZDV monotherapy (1.43; 1.08-1.91) and a higher risk of sPTB than zidovudine/lamivudine/abacavir (ZDV/3TC/ABC) (1.81; 1.21-2.71). LPV/r-containing regimens also carried the highest risks of VPTB, SGA and NND, although the limited data showed no significant differences. Of the ART regimens assessed in RCTs in pregnancy, LPV/r-containing regimens were associated with the highest risks of adverse perinatal outcomes.

LOOP ELECTROSURGICAL EXCISION PROCEDURE, CERVICAL DYSPLASIA, AND RISK OF PRETERM DELIVERY: A RETROSPECTIVE COHORT STUDY

Objectives To evaluate whether cervical dysplasia with or without loop electrosurgical excision procedure (LEEP) was associated with risk of preterm delivery. Methods This retrospective cohort study linked a provincial perinatal database and a provincial colposcopy database. All women aged ? 45years with a singleton delivery > 20 weeks’ gestation between 1995 and 2012 were included. The exposure groups included women with dysplasia treated with LEEP (Group 1) and women with dysplasia who were not treated (Group 2). The comparison group included women who did not have dysplasia or LEEP (Group 3). The primary outcome was rate of spontaneous preterm birth Results There were 4265 women in Group 1, 3147 women in Group 2, and 63345 unexposed (Group 3) women. Relative to the unexposed women, women in Group 1 were more likely to deliver preterm (aHR 1.22; CI 1.06-1.39), but women in Group 2 were not (aHR 1.01; CI 0.86-1.19). Subgroup analysis showed that untreated high grade dysplasia, but not low grade dysplasia, was not associated with sPTB (aHR 0.67, 95% CI 0.52-0.88). Conclusions Treatment with LEEP was associated with a higher risk of sPTB, and this association was not heterogeneous by grade. High grade dysplasia, but not low grade dysplasia, was associated with a higher risk of sPTB.

Predictors of Cervical Cerclage Success in the Prevention of Spontaneous Preterm Birth [13L

INTRODUCTION: Cerclage is one of the interventions to prevent spontaneous preterm birth (sPTB). This study aimed to identify predictive factors of cerclage success in preventing sPTB. METHODS: Retrospective study of singleton pregnancy at high risk of sPTB in University of Illinois at Chicago between 2013 and 2017. Baseline characteristics, duration of pregnancy, pregnancy outcomes and other predictive factors were analyzed using χ2, student t test, and multiple logistic regression analysis. RESULTS: Of the 310 women identified, 90 (29%) had rescue cerclage, and 65 (21%) had prophylactic cerclage. Most statistically significant predictors of sPTB of rescue cerclage were insertions at 17–20 weeks, aOR 2.26 (95% CI: 1.47–3.50, P&lt;.0001), and at 21–22 weeks, aOR 1.81 (95% CI: 1.15–2.87, P&lt;.0001). Cerclages placed at CL &lt;10 mm was associated with increased likelihood of sPTB, aOR 1.60 (95% CI: 1.10–2.34, P&lt;.0001). Cervical length at 21–25 mm and cerclage at GA &lt;16 weeks were associated with decreased rate of sPTB, aOR 0.40 (95% CI: 0.26–0.61, P&lt;.0001), and aOR 0.26 (95% CI: 0.16–0.40, P&lt;.0001). Except for indomethacin in prophylactic cerclage, cervical dilatation, funneling, presence of sludge, prior sPTB, vaginal infections and use of 17-OHPC, these were not statistically significant in preventing sPTB. CONCLUSION: The success of cerclage in the prevention of sPTB depends on several factors. The most predictive factors were the degree of short cervix and earlier GA at cerclage placement.

Follow-Up of Asymptomatic High-Risk Patients with Normal Cervical Length to Predict Recurrence of Preterm Birth

Background: A midtrimester cervical length (CL) <25 mm is associated with spontaneous preterm birth (sPTB). However, as CL ≥25 mm is not enough to exclude recurrence in high-risk patients, follow-up CL measurement later in pregnancy has been proposed. Objectives: To evaluate whether CL measurement at 26±1 weeks in asymptomatic high-risk patients improves the prediction of sPTB recurrence. Methods: A retrospective cohort of high-risk women because of previous sPTB was analyzed. Patients with a CL ≥25 mm at 20±1 weeks and subsequent CL measurement at 26±1 weeks were included. The exclusion criteria were incomplete follow-up, any treatment before CL assessments, and medically indicated preterm birth. The association and predictive performance of CL at 26±1 weeks for sPTB was studied. Results: Of 131 patients with a CL measurement at 26±1 weeks, 19 and 4.6% presented sPTB before 37 and 34 weeks, respectively. The rate of sPTB before 37 weeks was higher in women with a CL <25 mm (37.5 vs. 16.5%, RR 2.3 [1.07–4.8], p = 0.045), although the detection rate of CL at 26±1 weeks to predict sPTB before 37 weeks was 24% (95% CI 10–46%). The performance did not improve regardless of the selected cutoff. Conclusions: In asymptomatic high-risk patients, CL <25 mm at 26±1 weeks is associated with higher risk of sPTB. However, the prediction of recurrence by CL was low and did not improve, regardless of the selected cutoff.

Quantitative fetal fibronectin to predict spontaneous preterm birth: a review.

Spontaneous preterm birth (sPTB) is the leading cause of neonatal morbidity and mortality globally. Accurate prediction of sPTB would enable targeting of interventions such as admission to hospital, antenatal corticosteroids, magnesium sulphate and in utero transfer as well as guiding prophylactic treatment (e.g., cerclage or progesterone). Measurement of fetal fibronectin concentration in the cervicovaginal fluid is a known predictor of sPTB. Traditionally a positive/negative test (defined by a threshold of 50 ng/ml), recent work has demonstrated improved prediction when used as a quantitative test, whereby the concentration of fetal fibronectin is measured by an automated bedside reader. This review examines the evidence surrounding the use of quantitative fetal fibronectin in asymptomatic women at high risk of sPTB, as well as those with symptoms of threatened sPTB.

PPO.07 Evaluation of the effect of cervical cerclage insertion on quantitative cervicovaginal fetal fibronectin levels, and prediction of spontaneous preterm birth

IntroductionFetal fibronectin (fFN) testing is an established predictor for spontaneous preterm birth (sPTB). A novel bedside fFN analyser allows quantification of fFN (qfFN) concentrations. It is commonly thought that cerclage...

PF.08 Quantitative Fibronectin Can Be Used For Earlier Prediction of Preterm Birth from 18 Weeks, But the Positive Threshold Needs Redefining

IntroductionFetal fibronectin (fFN) is an excellent predictor of spontaneous preterm birth (sPTB) and is used qualitatively (<50 ng/ml negative threshold) from 22 weeks gestation. Its value at earlier gestations using...

The interaction between the maternal BMI and angiogenic gene polymorphisms associates with the risk of spontaneous preterm birth

Obesity is associated with an increased level of inflammation. Interactions between inflammatory and angiogenic pathways are implicated in the major pregnancy disorders. The aim of this study was to investigate whether functional polymorphisms in angiogenesis-regulating genes (VEGFA rs699947, VEGFA rs3025039, KDR rs2071559 and ANGPT1 rs2507800) interact with the maternal BMI to modify the risk of a spontaneous preterm birth (sPTB). We conducted a nested case-control study of 1190 nulliparous Caucasian women (107 sPTBs and 1083 controls). Spontaneous PTB was defined as spontaneous preterm labour or a preterm premature rupture of membranes resulting in a preterm birth at <37 weeks of gestation. DNA was extracted from the peripheral blood and genotyped using the Sequenom MassARRAY system. Among overweight or obese women (BMI ≥25), the VEGFA rs699947 AA genotype was associated with a higher risk of sPTBs [odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.4-4.6, P = 0.001] and a significant interaction between the BMI and the polymorphism was detected (OR = 4.2, 95% CI: 1.7-10.9, P = 0.003). Among women with a BMI <25, ANGPT1 rs2507800 AA genotype was associated with a higher risk of sPTB (OR = 2.3, 95% CI: 1.2-4.4, P= 0.02) and a significant interaction between BMI and the polymorphism was detected (OR = 3.3, 95% CI: 1.1-9.3, P = 0.02). All results remained significant after adjusting for potential confounding factors. The maternal BMI interacts with angiogenesis-regulating gene polymorphisms to modify the risk of sPTBs.