Elastography in predicting preterm delivery in asymptomatic, low-risk women: a prospective observational study

To establish the efficacy of prophylactic nifedipine vs. placebo in reducing spontaneous preterm delivery in asymptomatic women at high risk for preterm delivery. Prospective multicentric randomized double-blind study. Tertiary care centre, University Hospitals of Brescia and Torino, Italy. Eighty-seven singleton pregnancies without uterine contractions and ultrasonographic cervical length of ≤25mm at 24-32weeks, at risk for preterm delivery, with longitudinal follow up in our Preterm Prevention Clinic. Selection was done on the basis of ultrasonographic cervical length; 43 women were randomized to receive placebo and 44 to receive nifedipine. Primary end point: spontaneous preterm delivery <37weeks in nifedipine vs. placebo. delivery <32weeks, maternal side effects, neonatal complications, admissions to the Neonatal Intensive Care Unit and randomization/delivery time in nifedipine vs. placebo. There was no trend towards a lower risk of spontaneous preterm delivery, neither at <37weeks of nifedipine vs. placebo (11.4% vs. 19.0%; p=0.320), or <32weeks (2.3% vs. 2.4%; p=0.973). Nifedipine reduced spontaneous preterm delivery <37weeks (p=0.015) in the multiparous women by stratified analysis for parity. SECONDARY OUTCOMES between the groups did not differ except for a higher percentage of maternal side-effects in the nifedipine group (31.8%) vs. placebo (11.9%) (p<0.05). Subgroup analysis showed a borderline (p=0.047) lower percentage of spontaneous preterm delivery in women with a ultrasonographic cervical length of <20mm in the nifedipine group. Prophylactic nifedipine in asymptomatic women at high risk for preterm delivery had a positive effect on the rate of spontaneous preterm delivery <37weeks in multiparous women.

To validate externally the QUiPP App v.2 algorithms in an independent cohort of high-risk asymptomatic women attending a preterm birth (PTB) surveillance clinic in Ireland. This was a retrospective, single-center, observational study assessing discrimination and calibration of the QUiPP App v.2 at six predetermined clinical timepoints (PTB at < 30, < 34 and < 37 weeks of pregnancy and PTB within 1, 2 and 4 weeks of testing). Discrimination was assessed by estimating the area under the receiver-operating-characteristics curve (AUC) and sensitivity at fixed false-positive rates of 5%, 10% and 20%. Model calibration was assessed to evaluate the concordance between expected and observed outcomes. P-values < 0.05 were considered statistically significant. No adjustments for treatment effects were made. Overall, 762 women with 1660 PTB surveillance clinic visits using the QUiPP App v.2 between 2019 and 2022 were analyzed. The study population included 142 (18.6%) patients who later experienced PTB. The QuiPP App's performance in the prediction of short-term outcomes, such as birth within 1 week (AUC, 0.866 (95% CI, 0.755-0.955)), 2 weeks (AUC, 0.721 (95% CI, 0.569-0.854)) and 4 weeks (AUC, 0.775 (95% CI, 0.699-0.842)), and delivery at < 30 weeks (AUC, 0.747 (95% CI, 0.613-0.865)), was superior to its ability to predict longer-term outcomes (PTB at < 37 weeks: AUC, 0.631 (95% CI, 0.596-0.668)). Calibration was generally good for low-risk results, as the predicted risk in these patients tended to match the observed incidence. However, in women deemed to be at greater risk of PTB, the predicted probability superseded the observed incidence of PTB. The QUiPP App v.2 accurately discriminates women who are at short-term risk of PTB. A 'treatment paradox' may influence calibration in high-risk women. Further research is needed to ascertain if QuiPP treatment thresholds can be safely adjusted in women receiving prophylactic treatment to prevent PTB, and whether this improves the outcome. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objective: To assess the predictive accuracy of serial measurements of cervical length (CL) for preterm birth in asymptomatic women with triplet pregnancy.Methods: A retrospective study of women with triplets who underwent serial sonographic measurements of CL until 28–32 weeks of gestation. The predictive accuracy of CL for preterm birth was determined at 4 periods along gestation: 18–20 weeks (period 1), 21–24 weeks (period 2), 25–27 weeks (period 3) and 28–32 weeks (period 4).Results: A total of 431 measurements of CL from were analyzed. CL decreased in a linear manner across gestation: 40.8 ± 7.1 mm, 36.5 ± 8.4 mm, 29.9 ± 11.4 mm and 25.0 ± 11.8 mm in periods 1, 2, 3 and 4, respectively. The difference in CL between women who did and did not deliver prematurely was small before 25 weeks (periods 1&2) but became more pronounced later in pregnancy (periods 3&4), mainly due to a rapid cervical shortening between periods 2 and 3 (shortening rate −29.0 ± 20.0% vs. −12.6 ± 20.5%, respectively, p = .01). The best predictors of preterm birth were either a single measurement of CL during period 3 or the degree of cervical shortening between periods 2 and 3.Conclusions: Care providers should be aware of the limited predictive value of cervical length before 25 + 0 weeks in triplet pregnancies.

Objective: To determine whether preterm birth in a twin pregnancy increases the risk of subsequent preterm birth (PTB) in a singleton pregnancy and to identify predictors for singleton PTB in women with previous twin PTB.Method: A retrospective cohort study of women with prior twin birth followed by a singleton birth in two tertiary referral centres between 2000 and 2016 was conducted. Rate of PTB in subsequent singleton pregnancy was compared between women who experienced previous preterm versus term twin birth. Analysis was further stratified by gestational age at twin and singleton birth, etiology for PTB and chorionicity in the twin pregnancy.Results: A total of 378 women met the inclusion criteria, of whom 252 (66.7%) experienced PTB in the index twin pregnancy. The overall rate of PTB in the subsequent singleton pregnancy was 11.6% (44/378). Women with prior twin PTB had a higher rate of PTB in the subsequent singleton pregnancy compared with women with prior term twin birth (17.5 versus 6.3%, p = .003, or 3.12, 95%-CI 1.42–6.85), mainly due to a higher rate of late singleton preterm birth (13.1 versus 4.0%, p = .005). Findings of higher odds of PTB in the subsequent singleton pregnancy was limited to women who gave birth before 340/7 weeks in the twin pregnancy and was related to the degree of prematurity (prior twin PTB at 300/7–336/7 weeks: OR 3.09, 95%-CI 1.12–8.51; prior twin PTB at <300/7 weeks: OR 5.8, 95%-CI 2.46–13.68). The association between previous twin PTB and subsequent singleton PTB was limited to women with prior spontaneous twin PTB (OR 3.34, 95%-CI 1.50–7.45).Conclusion: Women with a history of spontaneous PTB in a twin pregnancy are at increased odds of PTB in subsequent singleton pregnancies compared to women with prior term twin birth, and the risk is related to the severity of prematurity in the index twin pregnancy.

Objective: The antenatal features of pregnancies affect the incidence of preterm births. This retrospective study from Trakya University of Northwestern Turkey, describes antenatal factors involved in preterm births at 26-32 weeks of pregnancy and compares with those involved in preterm births at 33-36 weeks.Study Design: The records of preterm births at 26-32 weeks (earlier preterm births, n=419) and at 33-36 weeks (later preterm births, n=158) during the years 2002-2010 were reviewed and the demographic, obstetric and medical features were evaluated retrospectively. The data was expressed as numbers and percentages and analyzed by SPSS 20.0. Results: Iron supplementation [OR 0.27 (0.16-0.45), p=&lt;0.001], short cervix [OR 9.12 (2.09-39.73) p=0.003] and infection [OR 2.6 (1.2-5.6) p=0.014] were important factors in the emergence of earlier preterm births which occurred at the rate of 1.4%.Conclusions: Earlier preterm births at 26-32 weeks of pregnancy, which compose an obstetric issue, are associated with several antenatal risk factors such as nutrition, cervical problems and infections in Northwestern Turkey.

Vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) serve key roles in the regulation of vascular development, revascularization and vasopermeability in the endometrium, decidua and trophoblasts. Furthermore, both VEGF and PlGF are modulators of embryonic vascular development. Thus, the present study aimed to investigate the serum levels of VEGF and PlGF in female patients with early threatened abortion (TA) who experienced preterm delivery. The present case-control study included 130 pregnant patients with or without TA that were admitted to The Maternal and Childcare Hospital of Nantong University from January 2019 to January 2022. Patients were divided into two groups: i) Group A, which included 55 patients diagnosed with TA with slight vaginal bleeding and closed cervical internal os within the first 6-12 weeks of pregnancy; and ii) group B, which included 75 patients with healthy asymptomatic pregnancy. Blood samples were obtained from all patients and VEGF and PlGF levels were examined prior to treatment, and the chi-squared, Student's t-test and two-way ANOVA followed by Bonferroni's post hoc analysis were used to analyze statistical differences between the two patient groups. Results of the present study demonstrated that patients with TA had significantly lower levels of VEGF and PlGF, compared with the controls. In patients with or without TA, the levels of serum PlGF in the preterm delivery group were significantly decreased compared with patients that did not experience preterm delivery. However, there was no significant difference in the levels of VEGF between patients with or without preterm delivery. In addition, lower levels of PlGF, compared with those in patients without TA, may be associated with an increased risk of preterm delivery in patients without early TA.

Background: Pre-term birth (PTB) has been a major problem leading to CNS damage and requires expensive and intensive care.To date, the gold screening tool is cervical length (CL) measurement which has not been shown to be adequate as a single predictor of PTB. The aim of this investigation was to determine the predictive value of cervical consistency index (CCI) in low risk pregnancies. Methods: This was a prospective cross-sectional study performed on pregnant women at 14-28 weeks of gestation. The cervical length (CL) and anteroposterior cervical diameter were measured at rest (AP) and after at least 5 minutes gradual maximum compression (AP’) using the trans-vaginal probe and the CCI was calculated using this formula: CCI = (AP′ /AP)×100. The primary outcome was sPTB before 34+0w & 37+0w. Logistic regression and analysis of ROC curves were performed to evaluate the diagnostic power of CCI compared to CL.The inter-observer & intra-observer agreements were validated by ICC. Results: Among 110 participants with follow-up,11.7% leaded to PTB. Mean CCI for all subjects were 79.13%+/-10.3% that was lower in PTBs(58.2%). Pearson correlation coefficient was found to show a positive correlation between the weeks of pregnancy leading to delivery and the cervical length of women under study (P = 0.0001), and also show a positive correlation between GA in weeks and CCI in women (P = 0.013). According to ROC curve the best cutoff was CCI= 68.82%, which had sensitivity of 68.8% and specificity =70.9% for prediction of PTB comparing with current cutoff CL 0.90 for both. Conclusion: Among low risk women for PTB,CCI shows better diagnostic value than CL. This new variable appears to provide better prediction of sPTB than does CL.

507: Intraamniotic inflammatory response to bacteria in preterm prelabor rupture of membranes pregnancies: analysis of multiple amniotic fluid proteins

Up to 50% of the infants delivered after radical vaginal trachelectomy (RVT) are born prematurely. An effective strategy to reduce this number could be the closure of the cervical os (CCO). Fifteen pregnant patients who had a RVT due to early cervical cancer were included in this prospective case control study. All patients were scheduled for CCO early in the second trimester. CCO was performed in 12 patients. Their data were compared to data from 125 pregnancies after a RVT without CCO. The patients who had CCO were compared to patients without CCO. One patient had an early rupture of the amniotic membranes prior to CCO. Two patients chose not to undergo CCO. In 12 patients CCO was performed without complications. There was no early preterm delivery in the CCO group as compared to a rate of 5% in 125 pregnancies in the non-CCO group. We developed a protocol to reduce the risk of preterm deliveries after a RVT. Digital examinations should be avoided. Vaginal checks for pH can discover ascending infections - the main cause of preterm deliveries after a RVT. Infections should be treated adequately. CCO can further reduce the risk of preterm deliveries after a RVT.

Air pollution from vehicular emissions and other combustion sources is related to cardiovascular and respiratory outcomes. However, few studies have investigated the relationship between air pollution and preterm birth, a primary cause of infant mortality and morbidity. This analysis examined the effect of fine particulate matter (PM(2.5)) and carbon monoxide (CO) on preterm birth in a matched case-control study. PM(2.5) and CO monitoring data from the California Air Resources Board were linked to California birth certificate data for singletons born in 1999-2000. Each birth was mapped to the closest PM monitor within 5 miles of the home address. County-level CO measures were utilised to increase sample size and maintain a representative population. After exclusion of implausible birthweight-gestation combinations, preterm birth was defined as birth occurring between 24 and 36 weeks' gestation. Each of the 10 673 preterm cases was matched to three controls of term (39-44 weeks) gestation with a similar date of last menstrual period. Based on the case's gestational age, CO and PM(2.5) exposures were calculated for total pregnancy, first month of pregnancy, and last 2 weeks of pregnancy. Exposures were divided into quartiles; the lowest quartile was the reference. Because of the matched design, conditional logistic regression was used to adjust for maternal race/ethnicity, age, parity, marital status and education. High total pregnancy PM(2.5) exposure was associated with a small effect on preterm birth, after adjustment for maternal factors (adjusted odds ratio [AOR] = 1.15, [95% CI 1.07, 1.24]). The odds ratio did not change after adjustment for CO. Results were similar for PM(2.5) exposure during the first month of pregnancy (AOR = 1.21, 95% CI [1.12, 1.30]) and the last 2 weeks of pregnancy (AOR = 1.17, 95% CI [1.09, 1.27]). Conversely, CO exposure at any time during pregnancy was not associated with preterm birth (AORs from 0.95 to 1.00). Maternal exposure to PM(2.5), but not CO, is associated with preterm birth. This analysis did not show differences by timing of exposure, although more detailed examination may be needed.

Objectives: To investigate if a cervical length (CL) cutoff of 15 mm is relevant to use in women with threatened preterm labor. Methods: From 2006 to 2009, 146 women with singleton pregnancies were admitted with threatened preterm labor between 23 and 33+6 weeks of gestation at Copenhagen University Hospital. Transvaginal sonographic measurement of CL was carried out on admission. Outcome measures were spontaneous delivery within 48 h, within 7 days and delivery before 34 weeks according to a CL cutoff of 15 mm. Results: CL was <15 mm in 36 women (24.7%) and ≧15 mm in 110 women (75.3%). Spontaneous delivery occurred within 48 h or 7 days of presentation and before 34 weeks in 25, 38.9 and 50.0% of women with CL <15 mm and 3.6, 9.1 and 11.8% of women with CL ≧15 mm, respectively. The 15-mm CL cutoff had a sensitivity, false positive rate and negative predictive value for delivery within 48 h of 69.0, 20.3 and 96.4%, and within 7 days of 58.3, 18.1 and 90.9%. Women with CL <15 mm had odds of delivery within 7 days of 6.4 (95% CI 2.5–16.2). Conclusion: Although a 15-mm CL defines a group of women at high risk of spontaneous preterm delivery, 10 out of 110 women (9.1%) with a CL ≧15 mm deliver within 7 days.

To evaluate salivary progesterone as a predictor of early preterm birth (PTB) and compare it with transvaginal sonographic (TVS) cervical length in asymptomatic high-risk women. Prospective study. Departments of Obstetrics and Gynaecology and Biochemistry at UCMS & GTBH, Delhi, India. Ninety pregnant women. The progesterone concentration in saliva of asymptomatic pregnant women at high risk for preterm delivery was estimated by immunoassay, and cervical length was measured by TVS, at the first antenatal visit at 24-28 weeks of gestation, and then repeated 3-4 weeks later. Early PTB, mean and critical cut-off values of salivary progesterone, and a diagnostic value comparison of salivary progesterone with TVS cervical length. The mean value of salivary progesterone was significantly lower in all women who delivered at <37 weeks of gestation (n = 38), compared with the term group (n = 52; P < 0.001). Salivary progesterone decreased significantly from the first to the second visit, with the maximum decrease observed in women who delivered at <34 weeks of gestation (29.6%, 95% CI 17.8-41.4%, P < 0.002). The single predictive critical cut-off value for salivary progesterone was 2575 pg/ml, below which more than 80% of women delivered prematurely before 34 weeks of gestation, with sensitivity, specificity, and positive and negative predictive values of 83% (95% CI 58.6-96.4%), 86% (95% CI 75.9-93.1%), 60% (95% CI 38.6-78.8%) and 95% (95% CI 87.1-99.0%), respectively. The TVS cervical length decreased significantly (P < 0.001) in the women who delivered prematurely. Low salivary progesterone concentration can be used for predicting early PTB in asymptomatic high-risk women.

Objective Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery. Methods We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks). Results Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity (p = .014) was higher and a history of preterm delivery (p = .0010) was more common in the preterm delivery group than in the term delivery group. Furthermore, the proportion of women diagnosed with adenocarcinoma in situ (AIS) and cervical cancer in the preterm delivery group was higher than that in the term delivery group (p = .0099 and .0004, respectively). In multiple regression models in nulliparous women, cervical cancer or AIS (Odds ratio [OR]: 4.16, 95% CI: 1.26–13.68, p = .019) and a short cervix in the second trimester (OR: 13.41, 95% CI: 3.88–46.42, p < .0001) increased the risk of preterm delivery. Furthermore, a history of preterm delivery (OR: 7.35, 95% CI: 1.55–34.86, p = .012), cervical cancer or AIS (OR: 5.07, 95% CI: 1.24–20.73, p = .024), and a short cervix in the second trimester (OR: 4.29, 95% CI: 1.11–16.62, p = .035) increased the risk of preterm delivery in the multiple regression models in primiparous women. Conclusion Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGES Prior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization. The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.

We investigated the predictive capacity of mid-trimester cervical length (CL) measurement for spontaneous and iatrogenic preterm birth. We performed a prospective observational cohort study in nulliparous women and low-risk multiparous women with a singleton pregnancy between 16(+0) and 21(+6) weeks of gestation. We assessed the prognostic capacity of transvaginally measured mid-trimester CL for spontaneous and iatrogenic preterm birth (<37 weeks) using likelihood ratios (LR) and receiver-operating-characteristic analysis. We calculated numbers needed to screen to prevent one preterm birth assuming different treatment effects. Main outcome measures were preterm birth <32, <34 and <37 weeks. We studied 11,943 women, of whom 666 (5.6%) delivered preterm: 464 (3.9%) spontaneous and 202 (1.7%) iatrogenic. Mean CL was 44.1 mm (SD 7.8 mm). In nulliparous women, the LRs for spontaneous preterm birth varied between 27 (95% CI 7.7-95) for a CL ≤ 20 mm, and 2.0 (95% CI 1.6-2.5) for a CL between 30 and 35 mm. For low-risk multiparous women, these LRs were 37 (95% CI 7.5-182) and 1.5 (95% CI 0.97-2.2), respectively. Using a cut-off for CL ≤ 30 mm, 28 (6.0%) of 464 women with spontaneous preterm birth were identified. The number needed to screen to prevent one case of preterm birth was 618 in nulliparous women and 1417 for low-risk multiparous women (40% treatment effect, cut-off 30 mm). In women at low risk of preterm birth, CL predicts spontaneous preterm birth. However, its isolated use as a screening tool has limited value due to low sensitivity.

Do serial measurements of cervical length improve the prediction of preterm birth in asymptomatic women with twin gestations?