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Background/Objectives: Preterm birth (PTB) remains a significant global health challenge. Previous attempts to predict preterm birth in the first trimester using cervical length have been contradictory. The cervical consistency index (CCI) was introduced to quantify early cervical changes and has shown promise across various clinical scenarios in the mid-trimester, though testing in the first trimester is lacking. This study aims to assess the cervical consistency index performance in predicting preterm birth during the first trimester of pregnancy. Methods: In this prospective cohort study, focused exclusively on research, women with singleton pregnancies, both with and without a history of spontaneous preterm birth (sPTB), were included. The primary outcome was sPTB before 37 weeks, with a secondary outcome of sPTB before 34 weeks. CCI measurements were taken between 11+0 to 13+6 weeks of gestation. Receiver operating characteristic (ROC) curves were generated, and sensitivity and specificity were calculated for the optimal cut-off and for the 5th, 10th, and 15th percentile. Intraobserver and interobserver agreements were assessed using the intraclass correlation coefficient (ICC). Results: Among the 667 patients analyzed, the rates of sPTB before 37 and 34 weeks were 9.2% (61/667) and 1.8% (12/667), respectively. The detection rates (DRs) for CCI predicting PTB before 37 and 34 weeks were 19.7% (12/61) and 33.3% (4/12). Negative predictive values were 91.8% (546/595) and 98.7% (588/596), while the areas under the curve (AUC) for sPTB before 37 and 34 weeks were 0.62 (95% CI: 0.54-0.69) and 0.80 (95% CI: 0.71-0.89), respectively. Of the 61 patients with preterm birth, 13 (21.3%) had a preterm birth history; in this group, the CCI percentile 10th identified 39% (5/13). Intraobserver ICC was 0.862 (95% CI: 0.769-0.920), and interobserver ICC was 0.833 (95% CI: 0.722-0.902). Conclusions: This study suggests that utilizing CCI in the first trimester of pregnancy could serve as a valuable tool for predicting preterm birth before 34 weeks of gestation, demonstrating robust intraobserver and interobserver reliability.

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Introduction: Preterm birth, before 37 weeks of gestation, is the main determinant of neonatal morbidity and mortality and is associated with serious consequences,including compromised quality of life for the affected individual and physical, psychological, and economic costs. Objective: To evaluate the correlation of obstetric history, cervicovaginal infections, and cervical length with preterm birth. A prospective, blind cohort study evaluated 1,370 pregnant women from Ribeirão Preto between 20 and 25 weeks of gestation. Materials and methods: The correlation between obstetric history, cervical length, and gestational age at birth was obtained by calculating the relative risk of the different variables. Results: The distribution of pregnant women according to cervical length (CL) showed a predominance of women with a cervix longer than 2.5 cm (n = 1,308, 95.8%), followed by women with a cervix between 2 and 2.49 cm (n = 42, 3.1%) and < 2 cm (n = 15, 1.1%). Among the 1,370 pregnant women evaluated, 133 had spontaneous preterm birth (< 259 days); 14 (10.5%) preterm births occurred in women under 19 years of age, 105 (79%) in women between 19 and 35 years, and 14 (10.5%) in women older than 35 years. Microbiological analysis showed the growth of Mycoplasma hominis, Ureaplasma urealyticum, and other bacteria in 8, 17, and 16 women with preterm birth, respectively. Among the 133 women with spontaneous preterm birth, CL was < 2.5 cm in 15 women, < 2 cm in 3, < 1.5 cm in 3, and < 1 cm in 2. Conclusion: The identification of pregnant women at high risk for preterm delivery can reduce the incidence of preterm birth. Although no gold standard test exists for the prediction of preterm birth, this study confirms that the measurement of CL is a good individual predictor.

Introducción: El nacimiento pretérmino, antes de las 37 semanas de gestación, es el principal determinante de la morbimortalidad neonatal y se asocia a graves consecuencias,incluyendo el compromiso de la calidad de vida del individuo afectado y costes físicos, psicológicos y económicos. Objetivo: Evaluar la correlación de los antecedentes obstétricos, infecciones cervicovaginales y longitud cervical con el parto prematuro. Estudio de cohorte prospectivo, ciego, evaluando 1.370 gestantes de Ribeirão Preto entre 20 y 25 semanas de gestación. Material y métodos: La correlación entre los antecedentes obstétricos, la longitud cervical y la edad gestacional al nacer se obtuvo calculando el riesgo relativo de las diferentes variables. Resultados: La distribución de las gestantes según la longitud cervical (LC) mostró un predominio de mujeres con cuello uterino mayor de 2,5 cm (n = 1,308, 95.8%), seguidas de mujeres con cuello uterino entre 2 y 2,49 cm (n = 42, 3.1%) y menor de 2 cm (n = 15, 1.1%). De las 1,370 embarazadas evaluadas, 133 tuvieron un parto prematuro espontáneo (< 259 días); 14 (10.5%) partos prematuros se produjeron en mujeres menores de 19 años, 105 (79%) en mujeres de entre 19 y 35 años, y 14 (10.5%) en mujeres mayores de 35 años. Los análisis microbiológicos mostraron la proliferación de Mycoplasma hominis, Ureaplasma urealyticum y otras bacterias en 8, 17 y 16 mujeres con parto prematuro, respectivamente. Entre las 133 mujeres con parto prematuro espontáneo, la CL fue < 2.5 cm en 15 mujeres, < 2 cm en 3, < 1.5 cm en 3 y < 1 cm en 2. Conclusión: La identificación de las gestantes con alto riesgo de parto prematuro puede reducir la incidencia de parto prematuro. Aunque no existe una prueba de referencia para la predicción del parto prematuro, este estudio confirma que la medición de la longitud cervical es una buena predicción individual.

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OBJECTIVE: The aim of this study was to evaluate the maternal and ultrasonographic characteristics of pregnant women who underwent cervical length (CL) measurement by transvaginal ultrasound between 11 and 13 + 6 weeks of gestation and who delivered at term or preterm. METHODS: A retrospective cohort study was carried out between March 2013 and December 2018 by analyzing ultrasound data of singleton pregnant women who underwent CL measurement by transvaginal ultrasound during the first trimester scan. CL was compared between the two groups (full-term and preterm birth [PB]) using Student's t-test. RESULTS: A total of 5097 pregnant women were enrolled, of whom 5061 (99.3%) had term and 36 (0.7%) had PB < 34 weeks. CL measurements did not differ between the term and preterm groups (36.62 vs. 37.83 mm, p = 0.08). Maternal age showed a significant and linear association with CL (r = 0.034, p = 0.012) and CRL (r = 0.086, p < 0.001). Smoking status was associated with shorter CL (36.64 vs. 35.09 mm, p = 0.003). When we analyzed the CL of the pregnant women in the term and preterm groups, according to the gestational age cut-offs for prematurity (28, 30, 32, and 34 weeks), we found that there was no significant difference between the measurements in all groups (p > 0.05). CONCLUSION: We observed no significant differences between CL measurements between 11 and 13 + 6 weeks in pregnant women who had preterm and term deliveries. Gestational age and CRL showed a significant and linear association with CL measurement.

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Objective: To ascertain how screening for preterm birth is performed among obstetricians working in public and private practice in a middle-income country. Methods: Cross-sectional study of 265 obstetrician-gynecologists employed at public and private facilities. An online questionnaire was administered, with items designed to collect data on prematurity screening and prevention practices. Results: The mean age of respondents was 44.5 years; 78.5% were female, and 97.7% had completed a medical residency program. Universal screening (i.e., by ultrasound measurement of cervical length) was carried out by only 11.3% of respondents in public practice; 43% request transvaginal ultrasound if the manual exam is abnormal, and 74.6% request it in pregnant women with risk factors for preterm birth. Conversely, 60.7% of respondents in private practice performed universal screening. This difference in screening practices between public and private practice was highly significant (p < 0.001). Nearly all respondents (90.6%) reported prescribing vaginal progesterone for short cervix. Conclusion: In the setting of this study, universal ultrasound screening to prevent preterm birth was used by just over half of doctors in private practice. In public facilities, screening was even less common. Use of vaginal progesterone in cervical shortening was highly prevalent. There is an unmet need for formal protocols for screening and prevention of preterm birth in middle-income settings.

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Abstract Objective: To ascertain how screening for preterm birth is performed among obstetricians working in public and private practice in a middle-income country. Methods: Cross-sectional study of 265 obstetrician-gynecologists employed at public and private facilities. An online questionnaire was administered, with items designed to collect data on prematurity screening and prevention practices. Results: The mean age of respondents was 44.5 years; 78.5% were female, and 97.7% had completed a medical residency program. Universal screening (i.e., by ultrasound measurement of cervical length) was carried out by only 11.3% of respondents in public practice; 43% request transvaginal ultrasound if the manual exam is abnormal, and 74.6% request it in pregnant women with risk factors for preterm birth. Conversely, 60.7% of respondents in private practice performed universal screening. This difference in screening practices between public and private practice was highly significant (p < 0.001). Nearly all respondents (90.6%) reported prescribing vaginal progesterone for short cervix. Conclusion: In the setting of this study, universal ultrasound screening to prevent preterm birth was used by just over half of doctors in private practice. In public facilities, screening was even less common. Use of vaginal progesterone in cervical shortening was highly prevalent. There is an unmet need for formal protocols for screening and prevention of preterm birth in middle-income settings.

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Preterm birth (PB) is a leading cause of perinatal morbidity and mortality. PB prediction is performed by measuring cervical length, with a detection rate of around 70%. Although it is known that a cytokine-mediated inflammatory process is involved in the pathophysiology of PB, none screening method implemented in clinical practice includes cytokine levels as a predictor variable. Here, we quantified cytokines in cervical-vaginal mucus of pregnant women (18-23.6 weeks of gestation) with high or low risk for PB determined by cervical length, also collecting relevant obstetric information. IL-2, IL-6, IFN-γ, IL-4, and IL-10 were significantly higher in the high-risk group, while IL-1ra was lower. Two different models for PB prediction were created using the Random Forest machine-learning algorithm: a full model with 12 clinical variables and cytokine values and the adjusted model, including the most relevant variables-maternal age, IL-2, and cervical length- (detection rate 66 vs. 87%, false positive rate 12 vs. 3.33%, false negative rate 28 vs. 6.66%, and area under the curve 0.722 vs. 0.875, respectively). The adjusted model that incorporate cytokines showed a detection rate eight points higher than the gold standard calculator, which may allow us to identify the risk PB risk more accurately and implement strategies for preventive interventions.

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Introducción : el tratamiento de la insuficiencia cervical es el cerclaje cervical. Pese a este tratamiento el riesgo de parto prematuro persiste elevado en mujeres con insuficiencia cervical. La mejor forma y utilidad del seguimiento ecográfico de mujeres cercladas es desconocida. El objetivo de esta revisión fue evaluar la capacidad pronóstica de la ecografía transvaginal para predecir riesgo de parto prematuro luego de un cerclaje cervical. Materiales y métodos : realizamos una revisión sistemática de la literatura incluyendo estudios que evaluaran el valor pronóstico de la ecografía transvaginal luego de un cerclaje cervical, para predecir parto prematuro. Resultados : incluimos 14 estudios en la revisión. El parámetro más frecuentemente asociado con parto prematuro fue la longitud cervical posterior al cerclaje, aunque con capacidad predictiva moderada. El punto de corte para definir pacientes en riesgo varió entre 15-28 mm. Conclusión : la longitud cervical disminuida posterior a un cerclaje se asocia con mayor riesgo de parto prematuro. No se ha establecido un valor de corte único ni la utilidad clínica del seguimiento ecográfico de mujeres cercladas.

Introduction : The management of cervical insufficiency involves a cervical cerclage. Despite this treatment, patients with cervical insufficiency remain at high risk of preterm delivery. The best method and utility of ultrasound monitoring for women with cervical cerclage is unknown. The objective of this revision was to evaluate the prognostic performance of ultrasonographic cervical assessment to predict preterm labor after a cervical cerclage. Material and methods : We conducted a systematic literature review, including studies that assessed the prognostic value of transvaginal ultrasound after cervical cerclage in predicting premature birth. Results : We included 14 studies in our review. The most frequently evaluated parameter was cervical length after the cerclage, although with only moderate predictive capacity. The length used to define prognosis varied from 15 to 28 mm. Conclusion : Short cervical length after a cerclage is associated with a higher risk of preterm delivery. A single cutoff value and the clinical utility of ultrasound monitoring for women with cervical cerclage have not been established.

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OBJECTIVE: The objective of this study is to create a new screening for spontaneous preterm birth (sPTB) based on artificial intelligence (AI). METHODS: This study included 524 singleton pregnancies from 18th to 24th-week gestation after transvaginal ultrasound cervical length (CL) analyzes for screening sPTB < 35 weeks. AI model was created based on the stacking-based ensemble learning method (SBELM) by the neural network, gathering CL < 25 mm, multivariate unadjusted logistic regression (LR), and the best AI algorithm. Receiver Operating Characteristics (ROC) curve to predict sPTB < 35 weeks and area under the curve (AUC), sensitivity, specificity, accuracy, predictive positive and negative values were performed to evaluate CL < 25 mm, LR, the best algorithms of AI and SBELM. RESULTS: The most relevant variables presented by LR were cervical funneling, index straight CL/internal angle inside the cervix (≤ 0.200), previous PTB < 37 weeks, previous curettage, no antibiotic treatment during pregnancy, and weight (≤ 58 kg), no smoking, and CL < 30.9 mm. Fixing 10% of false positive rate, CL < 25 mm and SBELM present, respectively: AUC of 0.318 and 0.808; sensitivity of 33.3% and 47,3%; specificity of 91.8 and 92.8%; positive predictive value of 23.1 and 32.7%; negative predictive value of 94.9 and 96.0%. This machine learning presented high statistical significance when compared to CL < 25 mm after T-test (p < .00001). CONCLUSION: AI applied to clinical and ultrasonographic variables could be a viable option for screening of sPTB < 35 weeks, improving the performance of short cervix, with a low false-positive rate.

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BACKGROUND: Preterm birth is a leading cause of infant morbidity and mortality; its multifactorial causes are an obstacle to understanding etiology and pathogenesis. The importance of cytokines and inflammation in its etiology and association with the short cervix is nowadays well-proven. To date, there are no reliable biological or biochemical markers to predict preterm birth; even though the length of the cervix has high specificity, its sensitivity with the cervix below 2.5 cm is low. OBJECTIVE: We study the association of plasma cytokine levels and cervical length in search of predictors of preterm birth. STUDY DESIGN: We evaluated a total of 1400 pregnant women carrying a single fetus between 20 and 25 weeks of gestation, and 1370 of them after childbirth in a nested case-control study of a prenatal cohort. Eligible pregnant women were interviewed and submitted to obstetric morphological and transvaginal ultrasound with cervical length measurement, gynecological examination, and blood collection. Preterm birth occurred in 133 women, 129 included in the study, and a control group randomly selected at a 2:1 ratio. A total of 41 cytokines with a higher probability of being associated with preterm birth or being of significance during labor were determined. RESULTS: Cytokine and cervical length analysis by multivariate analysis of the conditional interference tree revealed that growth-related oncogene values of less than 2293 pg/mL were significantly associated with a cervical length of less than 2.5 cm. CONCLUSIONS: As well as a cervical length shorter than 2.5 cm, growth-related oncogene levels of less than 2293 pg/ml may be associated with an increased risk of PB. Analysis based on the association of biomarkers and of the interaction between cytokines is a promising pathway in search of a predictor of preterm birth.

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BACKGROUND: Short cervical length measured during the second trimester of pregnancy is an important risk factor for spontaneous preterm birth (sPTB). The aim of this study is to identify the association between mid-pregnancy cervical length (CL) and gestational age at birth in asymptomatic singleton pregnant women. METHODS: This is a prospective cohort study involving singleton pregnant women who participated in the screening phase of a Brazilian multicenter randomized controlled trial (P5 trial) between July 2015 and March 2019. Transvaginal ultrasound to measure CL was performed from 18 to 22 + 6 weeks. Women with CL ≤ 30 mm received vaginal progesterone (200 mg/day) until 36 weeks' gestation. For this analysis we considered all women with CL ≤ 30 mm receiving progesterone and a random selection of women with CL > 30 mm, keeping the populational distribution of CL. We obtained prognostic effectiveness data (area under receive operating characteristic curve (AUC), sensitivity and specificity and estimated Kaplan-Meier curves for preterm birth using different CL cutoff points. RESULTS: We report on 3139 women and identified a negative association between cervical length and sPTB. CL ≤ 25 mm was associated with sPTB < 28, sPTB < 34 and sPTB < 37 weeks, whereas a CL 25-30 mm was directly associated with late sPTB. CL by transvaginal ultrasound presented an AUC of 0.82 to predict sPTB < 28 weeks and 0.67 for sPTB < 34 weeks. Almost half of the sPTB occurred in nulliparous women and CL ≤ 30 mm was associated with sPTB at < 37 weeks (OR = 7.84; 95%CI = 5.5-11.1). The number needed to screen to detect one sPTB < 34 weeks in women with CL ≤ 25 mm is 121 and we estimated that 248 screening tests are necessary to prevent one sPTB < 34 weeks using progesterone prophylaxis. CONCLUSIONS: CL measured by transvaginal ultrasound should be used to predict sPTB < 34 weeks. Women with CL ≤ 30 mm are at increased risk for late sPTB.

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Abstract Objective To describe a reference curve for cervical length (CL) in mid-trimester twin gestations using transvaginal ultrasound (TVU) and to investigate whether short CL increases spontaneous preterm birth (sPTB) in asymptomatic twin pregnancies. Methods This was a prospective cohort study performed at 17 outpatient antenatal facilities of Brazil with women at 18 0/7 to 22 6/7 weeks of gestation who participated in a randomized clinical trial screening phase (P5 trial) between July 2015 and March 2019. TVU was performed to provide CL measurement in all screened women. Almost all women with CL ≤ 30 mm received vaginal progesterone 200mg/day and they were also randomized to receive cervical pessary or not. We considered data from the CL distribution among asymptomatic twin pregnancies and analyzed CL and its association with PTB generating receiver operating characteristics (ROC) curves and Kaplan-Meier curves. Results A total of 253 pregnant women with twins were included in the distribution curve. The mean CL was 33.7 mm and median was 35.5mm. The 10th percentile was 17.8mm. We identified a PTB rate of 73.9% (187/253) with 33.6% of sPTB < 37 (85/253) and 15% (38/253) of sPTB < 34 weeks. The best cutoff point to predict sPTB < 37 was 24.15 mm. However, the ROC curve showed a poor performance (0.64). The Kaplan-Meier survival curves identified that only CL values ≤ 20mm were associated to sPTB < 34 weeks. Conclusion A cutoff point of CL ≤ 20 mm can be interesting point to identify short cervix in Brazilian twin pregnancies. However, in Brazilian asymptomatic twin pregnancies, CL does not show a good performance to predict PTB.

Resumo Objetivo Descrever uma curva de referência da medida do colo uterino no Segundo trimestre de gestações gemelares através de ultrassonografia transvaginal (TVU) e investigar a correlação entre a medida do colo uterino (CL) e o parto prematuro espontâneo (sPTB) em pacientes assintomáticas. Métodos Foi realizado uma coorte prospectiva multicêntrica em 17 centros de referência do Brasil com mulheres com gestação gemelar entre 18 0/7 a 22 6/7 semanas de gestação que participaram da primeira fase de um ensaio clínico randomizado (P5 trial) entre Julho/2015 a Março/2019. TVU foi realizada para obter a medida do colo uterino em todas as mulheres. A maioria das mulheres com CL ≤30 mm receberam progesterona por via vaginal 200mg/dia e estas foram randomizadas para receber ou não um pessário cervical. Este estudo considerou dados da medida do colo uterino entre mulheres assintomáticas, desenvolvendo uma curva de referência para gestantes gemelares e sua capacidade de predição do parto prematuro através de curva ROC (receiver operating characteristics) e curvas de sobrevida de Kaplan-Meyer. Resultados O total de 253 gestantes foram incluídos no estudo, A média do CL foi 33.7mm e a mediana 35.5mm. O Percentil 10 do CL foi 17.8mm. A taxa de parto prematuro foi de 73.9% (187/253) com 33.6% de sPTB < 37 (85/253) e 15% (38/253) de sPTB < 34 semanas. O melhor ponto de corte para predizer sPTB < 37 foi 24.15 mm, entretanto a curva ROC demonstrou baixa performance (0.64). A curva de Kaplan-Meier para sPTB identificou que apenas CL ≤ 20 mm estavam associados a sPTB < 34 semanas. Conclusão Colo uterino ≤20 mm pode ser um interessante ponto de corte para identificar colo curto entre gestações gemelares assintomáticas brasileiras. Entretanto, a medida do colo uterino não apresentou boa performance para predizer parto prematuro.

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Introduction: The majority of pregnant women with a short cervix will deliver at term and, thus, may unnecessarily receive advanced monitoring and treatment. It is still necessary to define more accurately which sub-population of women with a short cervix is at elevated risk for early delivery. Objective: To determine if vaginal microbiome composition influenced the rate of spontaneous preterm birth in women with a short cervical length. Methods: In an exploratory, observational prospective study, vaginal secretions were obtained from 591 women at 21­24 week gestation. Vaginal microbiome composition was determined by analyzing the V1­V3 region of the bacterial 16S ribosomal RNA gene. Results: Lactobacillus crispatus was numerically dominant in the vagina in 41.7% of subjects, followed by L. iners in 32% and Gardnerella vaginalis in 12%. In women whose cervix was ≤25mm, the sensitivity to predict an spontaneous preterm birth was 11.8%. However, when L. crispatus was not the dominant vaginal bacterium, this sensitivity increased to 81.8%. Similarly, in women with a cervical length ≤30mm, the sensitivity to predict an spontaneous preterm birth increased from 21.7 to 78.3% when L. crispatus was not the dominant vaginal bacterium.In women with a prior spontaneous preterm birth and a cervix ≤25 or ≤30mm, L. crispatus dominance was also associated with a reduced rate of spontaneous preterm birth in the current pregnancy (p<0.001). Conclusion: In pregnant women with a cervix ≤25mm or ≤30mm, the risk for an spontaneous preterm birth is increased if L. crispatus is not dominant in the vagina.

Introdução: A maioria das mulheres grávidas com colo do útero curto dará à luz a termo e, portanto, pode receber desnecessariamente monitoramento e tratamento avançados. Permanece a necessidade de definir com mais precisão qual subpopulação de mulheres com colo do útero curto está em risco elevado de parto prematuro. Objetivo: Determinar se a composição do microbioma vaginal influenciou a taxa de parto prematuro espontâneo em mulheres com colo curto. Métodos: Em um estudo prospectivo exploratório observacional, os conteúdos vaginais foram obtidos de 591 mulheres com 21­24 semanas de gestação. A composição do microbioma vaginal foi determinada pela análise da região V1­V3 do gene de RNA ribossômico bacteriano 16S. Resultados: Lactobacilluscrispatus foi numericamente dominante na vagina em 41,7% dos indivíduos, seguido por L. iners em 32% e Gardnerella vaginalis em 12%. Em mulheres cujo colo do útero era <25 mm, a sensibilidade para prever uma taxa de parto prematuro espontâneo foi de 11,8%. No entanto, quando L. crispatus não era a bactéria vaginal dominante, essa sensibilidade aumentou para 81,8%. Da mesma forma, em mulheres com comprimento cervical <30 mm, a sensibilidade para prever uma taxa de parto prematuro espontâneo aumentou de 21,7 para 78,3% quando L. crispatus não era a bactéria vaginal dominante. Em mulheres com taxa de parto prematuro espontâneo anterior e colo do útero <25 ou <30 mm, a dominância de L. crispatus também foi associada a uma taxa reduzida de taxa de parto prematuro espontâneo na gravidez atual (p<0,001). Conclusão: Em mulheres grávidas com colo do útero <25 ou <30 mm, o risco de parto prematuro espontâneo é aumentado se L. crispatus não for dominante na vagina.

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OBJECTIVE: There is a lack of consensus about the management of twins with significant cervical length (CL) shortening, especially if CL is above 25 mm. Therefore, it is important to define "abnormal" CL change over time, and to compare the performance of different strategies. The aim of this study was twofold, to describe the performance of the cervical shortening and that of an integrated strategy that includes both the cervical shortening and a fixed CL cutoff <25 mm in any measurement as predictor of spontaneous PTB (sPTB) < 34 weeks in uncomplicated twin pregnancies. MATERIAL AND METHODS: Retrospective cohort study of twins followed in our Twins Clinic at Hospital Italiano de Buenos Aires from 2013 to 2017. Inclusion criteria were dichorionic or monochorionic diamniotic twins with CL measurement between 18 and 33 + 6 weeks with available data of the delivery. Exclusion criteria included any of the following complications: iatrogenic preterm delivery <34 weeks, cerclage, fetal growth restriction, fetal death, structural anomalies, polyhydramnios, twin-twin transfusion syndrome, selective fetal growth restriction, twin anemia-polycythemia sequence, and twin reversed arterial perfusion sequence. Spontaneous preterm birth was defined as spontaneous delivery <34 weeks. Cervical shortening was analyzed in the following periods: 20-24 weeks, 20-28 weeks, 24-28 weeks, 24-32 weeks and 28-32 weeks. Cervical changes were analyzed as velocity of shortening over time (mm/week) and as the ratio of shortening over time (%/week). ROC curves for each period were constructed and two different cutoffs were used to classify changes of the CL as positive or negative screening: a) the shortening of CL associated to the highest value of the Youden Index and b) fixing a 10% false positive rate (FPR). For the second objective, we analyzed an integrated strategy considering a fixed cutoff of 25 mm at any GA and/or a significant shortening. The screening was considered positive if any CL measurement was <25 mm at any GA or there was a shortening of the CL ≥ the cutoff obtained for each period. We report sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio and area under the ROC curve. RESULTS: We included 378 patients and 1417 measurements, 284 (75%) dichorionic and 94 (25%) monochorionic. Between 20 and 28 weeks, with a change in CL cutoff = 1.6 mm/week or 4.1%/week the detection rate was 54.2% (32.8-74.4%) and the specificity 80.5% (75.1-85.1%) and 83.5% (78.5-87.8%) respectively. In the integrated strategy, the detection rate was 65.7% (47.8-80.9%) and the specificity 69 (63.7-74). All the ROC curves of the periods studied showed an AUC < 0.7. In the group of patients that delivered preterm the initial mean CL was shorter than in the term group, 39 (±12) mm vs. 43 (± 7.7) mm (p = .02) and the most important change in CL was at 20-24 weeks both in the velocity and in the ratio of shortening over time. Conversely, patients that delivered at term showed a higher change in CL in the third trimester. CONCLUSION: The performance of all the strategies analyzed as a predictor of sPTB <34 weeks was moderate. The period 20-28 weeks detected half of the patients at risk with a FPR around 10-20% and the integrated strategy increased the sensitivity up to a detection of two thirds of the patients at risk but with a FPR of ∼30%. Future analyses need to explore other strategies to improve the performance and to really identify the patients at higher risk.

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OBJECTIVE: While cervical length (CL) provides an effective screening tool for spontaneous preterm birth in singletons, the performance in twins is still controversial. Our aim was twofold. First, to compare the performance of a single CL measurement at mid-gestation (∼20 weeks) versus serial measurements as a predictor of spontaneous preterm birth < 34 weeks in uncomplicated twin pregnancies. Second, to describe the performance of a single CL at ∼24, ∼28 and ∼32 weeks. MATERIAL AND METHODS: cohort study of twins followed at Hospital Italiano de Buenos Aires from 2013 to 2017. Inclusion criteria were dichorionic or monochorionic diamniotic twins with CL measurement between 18 and 33 + 6 weeks with available data of the delivery. Exclusion criteria included any of the following complications: iatrogenic preterm delivery <34 weeks, cerclage, fetal growth restriction, fetal death, structural anomalies, polyhydramnios, twin-twin transfusion syndrome, selective fetal growth restriction, twin anemia-polycythemia sequence, and twin reversed arterial perfusion sequence. Spontaneous preterm birth was defined as spontaneous delivery < 34 weeks. Two different cutoffs were used to classify CL as short (positive screening) or normal (negative screening): (a) a fixed cutoff of 25 mm at any gestational age (GA). The screening was considered positive if any CL measurement was <25 mm; and (b) a GA adjusted cutoff to a 10% false positive rate (FPR). The 10% FPR for each GA was calculated and the screening was considered positive if any of the CL measurements were below this 10% FPR cutoff. We report sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio and area under the ROC curve. RESULTS: Among 777 twins followed in our Unit, 381 met exclusion criteria and 18 were excluded due to incomplete follow-up. We included 378 patients, 284 (75%) dichorionic and 94 (25%) monochorionic. The performance of one CL at 20 weeks showed a sensitivity ≤ 20% with an area under the ROC curve of 0.58 (95% CI, 0.45-0.70), while the performance of serial measurements showed a sensitivity of 58.8% (95% CI, 40.7-75.4) with an area under the ROC curve of 0.70 (95% CI, 0.61-0.79) (p < .001). The analyses of the performance of a single CL at ∼24, ∼28 and ∼32 weeks showed similar AUC than the serial measurements and, for a FPR = 10%, the performance of one measurement at 24 and 32 weeks showed a sensitivity of 30% (95% CI, 14.7-49.4) and 31.6% (95% CI, (12.6-56.6), while the measurement at 28 weeks showed a sensitivity of 48.3% (95% CI, (29.4-67.5). CONCLUSION: Serial measurements showed a better performance than a single one in mid-gestation. Moreover, among single measurements the CL in mid-gestation showed the poorest performance, while the 28 weeks assessment detected half of the preterm deliveries. However, all the strategies showed modest performances.

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OBJECTIVE: To assess the role of cervical length when predicting vaginal delivery after a previous cesarean section (CS) in women with low Bishop score following the use of a double-balloon catheter for induction of labor (IOL). METHODS: A prospective, longitudinal study was conducted at a large teaching hospital in Santiago to recruit pregnant women at term with a previous CS and Bishop score ≤6 for IOL with a double-balloon catheter. The device was maintained for up to 24 h and the patient continued IOL with oxytocin only if the Bishop score was >6. Demographic and clinical variables were recorded and compared against vaginal delivery as the primary outcome. Multivariate logistic regression analysis was used to compare perinatal demographic and clinical variables in women achieving vaginal delivery versus those having a repeat CS. RESULTS: The final cohort included 40 pregnant women. Women achieving vaginal delivery (n = 17, 42.5%) had statistically significant differences in mean cervical length (24.8 mm versus 33.4 mm, respectively; p = .006), median Bishop score after removing the double-balloon catheter (11 versus 7, respectively; p = .005), and mean interval between double-balloon catheter placement and vaginal delivery or the decision to perform a CS (17.4 h versus 23.6 h, respectively; p = .03). Backward stepwise selection revealed an odds ratio of 0.90 (95% confidence interval = 0.82-0.98) for cervical length and a receiver operating characteristic curve area of 0.73. CONCLUSION: Cervical length, as determined by transvaginal sonography, proved to be effective in predicting vaginal delivery in women with a previous CS and low Bishop score following the use of a double-balloon catheter for IOL.

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El parto prematuro, definido como el parto que ocurre antes de las 37 semanas de gestación, es una condición obstétrica grave que representa el 11% de los embarazos en todo el mundo. Las pruebas predictivas para parto prematuro son importantes, dado el impacto personal, económico y de salud del parto prematuro. Esta revisión explora la utilidad tanto de las pruebas predictivas actuales utilizadas en la práctica clínica (características maternas, longitud cervical y marcadores bioquímicos), así como nuevas pruebas emergentes. Se realizó una búsqueda electrónica en las bases de datos científicas en salud: PUBMED, COCHRANE, SCIELO, revisión de repositorios virtuales de universidades nacionales utilizando los siguientes ítems de búsqueda y sus combinaciones: parto pretérmino, longitud cervical, acortamiento cervical, cervicometría, fibronectina fetal, factores de riesgo, características maternas. Se incluyeron trabajos publicados en inglés y español, desde el año 2006 hasta el año 2020, que respondían al objetivo de la revisión: La utilidad de los diferentes predictores para parto pretérmino. En total se incluyeron 30 artículos en la presente revisión bibliográfica. Existen múltiples criterios científicos sobres las diferentes técnicas actuales para identificar pacientes de riesgo y lograr una prevención adecuada del parto pretérmino. La medición de la longitud cervical por ecografía transvaginal es el método más rentable en mujeres con historia de parto prematuro o síntomas de amenaza de parto prematuro; la evidencia actual permite sostener que también es indispensable realizar cervicometría de rutina a todas las pacientes, aún de bajo riesgo. Existen métodos ecográficos de predicción como la elastografía cervical y el índice de consistencia cervical que son prometedores, pero existen limitaciones en su implementación técnica y se propone que podrían ser una posible alternativa en el futuro, que puede combinarse con la longitud cervical. También, la adición de la medición de la longitud cervical a las pruebas bioquímicas parece mejorar la precisión predictiva(au)

Preterm labor, defined as delivery before 37 weeks of gestation, is a serious obstetric condition that accounts for 11% of pregnancies worldwide. Predictive tests for preterm birth are important, given the personal, economic, and health impact of preterm birth. This review explores the utility of both, the current predictive tests used in clinical practice (maternal characteristics, cervical length and biochemical markers), as well as the new emerging tests. An electronic search was carried out in the scientific health databases: PUBMED, COCHRANE, SCIELO, national universities virtual repositories were also reviewed, using the following search items and their combinations: preterm delivery, cervical length, cervical shortening, cervicometry, fetal fibronectin, risk factors, and maternal characteristics. We included papers in English and Spanish published from 2006 to 2020, which responded to the aim of the review: the utility of predictive test for preterm delivery. A total of 30 articles were included in this review. There are multiple scientific criteria on the different current techniques to identify patients at risk and achieve adequate prevention of preterm birth. Measurement of cervical length by transvaginal ultrasound is the most cost-effective method in women with a history of preterm labor or symptoms of preterm labor; the current evidence allows us to affirm that it is also essential to perform routine cervicometry in all patients, even with low risk. There are promising ultrasound predictive methods such as cervical elastography and cervical consistency index, but there are limitations in their technical implementation, it is proposed that they could be a possible alternative in the future, that can be combined with cervical length measurement. Also, adding cervical length easurement to biochemical tests appears to improve predictive accuracy.(au)

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OBJETIVO: Comparar el índice de consistencia cervical con la longitud cervical en la predicción de parto pretérmino inminente en pacientes sintomáticas. MÉTODO: Estudio prospectivo realizado en mujeres con embarazos únicos entre 24 y 35 semanas, con diagnóstico clínico de amenaza de parto pretérmino, que asistieron al Hospital Central Dr. Urquinaona en Maracaibo, Venezuela. Al momento del diagnóstico, las pacientes fueron evaluadas con ecografía transvaginal para establecer los valores del índice de consistencia cervical y la longitud cervical. La resultante principal fue parto inminente (en los 7 días siguientes a la evaluación). RESULTADOS: Se incluyeron 657 pacientes, de las que 152 presentaron parto pretérmino inminente (grupo A) y 505 fueron consideradas como controles (grupo B). No se encontraron diferencias entre los grupos en cuanto a edad materna, nuliparidad, antecedente de parto pretérmino, antecedente de hábito tabáquico e índice de masa corporal. Las pacientes del grupo A presentaron valores significativamente más bajos del índice de consistencia cervical y de longitud cervical que las del grupo B (p < 0,0001). El índice de consistencia cervical mostró un valor de área bajo la curva de 0,857, mientras que para la longitud cervical este fue de 0,977. La diferencia de la capacidad de discriminación entre las áreas bajo la curva de cada prueba fue significativa (p < 0,0001). CONCLUSIÓN: El índice de consistencia cervical no es superior a la longitud cervical en la predicción de parto pretérmino inminente en pacientes sintomáticas.

OBJECTIVE: To compare the cervical consistency index with the cervical length in predicting imminent preterm delivery in symptomatic patients. METHOD: This prospective study was conducted in women with single pregnancies between 24 and 35 weeks, with a clinical diagnosis of threatened preterm delivery who attended the Central Hospital Dr. Urquinaona, in Maracaibo, Venezuela. At the time of diagnosis, the patients were evaluated using transvaginal ultrasound to establish the values of the cervical consistency index and cervical length. The main result was imminent delivery (in the 7 days following the evaluation). RESULTS: 657 patients were included, 152 women presented imminent preterm delivery (group A) and 505 were considered as controls (group B). No differences were found between the groups concerning maternal age, nulliparity, history of preterm delivery, history of smoking, and body mass index. Group A patients presented significantly lower values of cervical consistency index and cervical length compared to group B patients (p < 0.0001). The cervical consistency index and cervical length showed an area value under the curve of 0.857 and 0.977, respectively. The difference in the ability to discriminate between the areas under the curve of each test was significant (p < 0.0001). CONCLUSIONS: The cervical consistency index is not superior to the cervical length in the prediction of imminent preterm delivery in symptomatic patients.

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OBJECTIVE: To study the association of plasma and vaginal levels of matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9), determined between 20+0 and 25+6 weeks of gestation, with preterm birth and its predictive value. STUDY DESIGN: All 129 cases of preterm birth (cases) and 258 randomly selected term patients (control group) were included in a cohort study with a nested case-control design. Inclusion criteria were living in Ribeirão Preto, Brazil, and gestational age 20+0 to 25+6 at enrollment. Exclusion criteria were multiple fetuses, congenital malformations or chromosome syndromes, and loss to follow-up. Maternal age, parity, smoking, and previous preterm birth were included as covariates. A blood sample and vaginal secretion were obtained for the determination of MMP-2 and MMP-9; the patients were screened for urinary tract infection and bacterial vaginosis, and cervical length was measured by ultrasound. The cut-off values for matrix metalloproteinases were calculated using receiver operating characteristic (ROC) curves for logistic regression analysis (crude and adjusted odds ratios). RESULTS: According to the WHO, in this study, preterm subtypes included 3.8 % extremely preterm, 6.9 % very preterm, and 89.2 % late preterm births. The plasma MMP-9 cut-off was 63.25 ng/mL and the area under the ROC curve was 0.725 (standard error 0.03; 95 % confidence interval, 0.677-0.769). The cut-off for plasma MMP-2 was 239.4 ng/mL and the area under the ROC curve was 0.585 (standard error 0.03, 95 % confidence interval, 0.521-0.649). Crude odds ratios showed an increased risk of preterm birth associated with plasma MMP-2 (odds ratio, 1.75; 95 % confidence interval, 1.14-2.68) and plasma MMP-9 (odds ratio, 3.26, 95 % confidence interval, 2.09-5.07); no association was detected for vaginal MMP-2 or 9. For plasma, adjusted odds ratios were 1.42 (95 % confidence interval, 0.80-2.53) for MMP-2 and 2.71 (95 % confidence interval, 1 .52-4.83) for MMP-9, along with an increased risk in other covariates. CONCLUSION: Elevated plasma MMP-9 levels and decreased MMP-2 levels were positively associated with preterm birth. Plasma MMP-9 level increased nearly three times the preterm risk.

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Abstract Pretermbirth (PTB) is a major obstetric problem associated with high rates of neonatal morbidity and mortality. The prevalence of PTB has not changed in the last decade; thus, the establishment of a screening test and effective treatment are warranted. Transvaginal ultrasoundmeasurement of the cervical length (TUCL) has been proposed as an effective method to screen pregnant women at a higher risk of experiencing PTB. Objective To evaluate the applicability and usefulness of second-trimester TUCL to predict PTB in a cohort of Portuguese pregnant women. Methods Retrospective cross-sectional cohort study including all singleton pregnant women who performed their second-trimester ultrasound (between weeks 18 and 22þ6 days) from January 2013 to October 2017 at Centro Hospitalar Universitário São João. Results Our cohort included 4,481 women. The prevalence of spontaneous PTB was of 4.0%, with 0.7% occurring before the 34th week of gestation. The mean TUCL was of 33.8mm,and percentiles 3, 5 and 10 corresponded toTUCLs of 25.0mm, 27.0mmand 29.0mmrespectively. The multiple logistic regression analysis, including maternal age, previous PTB and cervical surgery showed a significant negative association between TUCL and PTB, with an odds ratio (OR) of 0.92 (95% confidence interval [95%CI]: 0.90-0.95; p<0.001). The use of a TUCL of 20mm is the best cut-off, when compared with the 25-mm cut-off, improving the prediction of risk. Conclusion The present study showed an inverse association between TUCL and PTB, and that the inclusion of other risk factors like maternal age, previous PTB and cervical surgery can improve the screening algorithm. Furthermore, it emphasizes that the TUCL cut-off that defines short cervix can differ according to the population.

Resumo O parto pré-termo (PPT) é uma grande complicação obstétrica que se associa a elevadas taxas de morbimortalidade neonatal. A sua prevalência não tem alterado na última década, sendo esencial determinar uma forma de rastreio e tratamento eficaz. A medição ecográfica transvaginal do comprimento cervical tem sido proposta como um método eficaz de rastreio das grávidas com risco aumentado de PPT. Objetivo Avaliar a aplicabilidade e utilidade da medição ecográfica transvaginal do comprimento cervical na previsão de PPT numa amostra de grávidas portuguesas. Método Estudo de coorte retrospectivo incluindo todas as grávidas com gestação unifetal que realizaram ecografia do 2° trimestre (de 18 a 22semanasþ6 dias) no Centro Hospitalar Universitário de São João entre janeiro de 2013 e outubro de 2017. Resultados A nossa amostra incluiu 4.481 mulheres. A prevalência de PPT espontâneo foi de 4,0%, sendo que 0,7% ocorreu antes das 34 semanas de gestação. A média do comprimento cervical por ecografia transvaginal foi 33,8mm, e os percentis 3, 5 e 10 da amostra corresponderam a comprimentos cervicais de 25,0mm, 27,0mm e 29,0mm, respetivamente. A regressão logística múltipla, que incluiu a idade materna, PPT anterior e antecedentes de conização, demonstrou uma associação estatisticamente significativa entre o comprimento cervical e o risco de PPT, com um risco relativo de 0,92 (intervalo de confiança de 95% [IC95%]: 0.90-0.95; p<0.001). A utilização de um valor de referência de comprimento cervical de 20mm, quando comparado com o valor de referência de 25 mm, melhora a previsão do risco de PPT. Conclusão Este estudo demostra uma associação entre o comprimento cervical avaliado por ecografia tranasvaginal e o risco de PPT, e salienta que a inclusão de outros fatores de risco, como idade materna, PPT anterior e antecedentes de conização podem melhorar o algoritmo de rastreio. Realça ainda que o valor de comprimento cervical utilizado para definir "colo curto" varia de acordo com a população em estudo.

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OBJECTIVE: The objective of this study was to assess the predictive performance of preoperative cervical length (CL) for delivery within 1 week after pleuroamniotic shunting (PAS) in fetuses with severe hydrothorax. METHODS: A prospective cohort of fetuses with severe hydrothorax referred to our fetal surgery center in Querétaro, Mexico from January 2012 to July 2020. Severe fetal hydrothorax was diagnosed as an accumulation of fluid within the fetal pleural space accompanied with severe bilateral lung compression, mediastinal shift, polyhydramnios, and/or hydrops. Transvaginal CL was measured immediately before PAS, and a short cervix was defined as that <25 mm. The interval from fetal intervention to delivery, prevalence of preterm prelabor rupture of membranes (PPROMs), and associations with delivery within the first week after PAS according to a short or a normal CL, were evaluated. RESULTS: Thirty-five pregnancies with severe fetal hydrothorax treated with PAS were evaluated. Median gestational age at PAS was (weeks + days) 31+2 (range, 26+0-36+1). Two (5.7%) and 7 (20.0%) cases delivered within the first 24 h and 1 week after PAS, respectively. Ten (28.6%) women had a short cervix before PAS, while 25 (71.4%) had normal preoperative CL. Women with a short cervix showed lower mean interval between fetal intervention and delivery (2.4 vs. 5.5 weeks, p = 0.01), and higher prevalence of PPROM (50 vs. 12%, p = 0.01), as compared to women with a nonshort cervix. Preoperative short cervix was associated with significantly higher risk of delivery within the first 24 h (20.0 vs. 0%, respectively, p < 0.05) and 1 week after PAS (50.0 vs. 8.0%, respectively, p < 0.01) compared with pregnancies with normal preoperative CL. CONCLUSION: In pregnancies with severe fetal hydrothorax candidates for pleuroamniotic shunt, identification of a short cervix before fetal intervention can predict delivery within 1 week after the surgical procedure.

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