A new model based on artificial intelligence to screening preterm birth.

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.

An enlarged fetal thymus may be the initial response to intrauterine inflammation in pregnant women at risk for preterm birth.

OBJECTIVE: Fetal thymus involvement in prematurity has been studied, and this study aimed to evaluate its relationship with short cervix and amniotic fluid sludge in the second trimester of pregnancy. METHODS: In this prospective cross-sectional study, 79 pregnant women (19+0 to 24+6 weeks) were included, and cervical length and the presence or absence of amniotic fluid sludge were evaluated. In the three-vessel view of the fetal thorax, the thymus was identified, and its perimeter and transverse diameter were measured and transformed to a zeta score based on gestational age. RESULTS: Data from 22 women with short cervix (<25 mm) and 57 patients with normal cervix (≥25 mm) were analyzed. The transverse diameter of the fetal thymus was significantly greater in the short cervix group compared to that of the normal cervix group (z-score 2.708 vs. -0.043, p=0.003). There were no significant differences in the perimeter (z-score -0.039 vs. -0.071, p=0.890) or the transverse diameter (z-score 1.297 vs. -0.004, p=0.091) of the fetal thymus associated with the presence (n=21) or absence of sludge (n=58). CONCLUSION: A short cervix is associated with an increased transverse diameter of the fetal thymus during the second trimester of gestation.

An enlarged fetal thymus may be the initial response to intrauterine inflammation in pregnant women at risk for preterm birth

SUMMARY OBJECTIVE: Fetal thymus involvement in prematurity has been studied, and this study aimed to evaluate its relationship with short cervix and amniotic fluid sludge in the second trimester of pregnancy. METHODS: In this prospective cross-sectional study, 79 pregnant women (19+0 to 24+6 weeks) were included, and cervical length and the presence or absence of amniotic fluid sludge were evaluated. In the three-vessel view of the fetal thorax, the thymus was identified, and its perimeter and transverse diameter were measured and transformed to a zeta score based on gestational age. RESULTS: Data from 22 women with short cervix (<25 mm) and 57 patients with normal cervix (≥25 mm) were analyzed. The transverse diameter of the fetal thymus was significantly greater in the short cervix group compared to that of the normal cervix group (z-score 2.708 vs. −0.043, p=0.003). There were no significant differences in the perimeter (z-score −0.039 vs. −0.071, p=0.890) or the transverse diameter (z-score 1.297 vs. −0.004, p=0.091) of the fetal thymus associated with the presence (n=21) or absence of sludge (n=58). CONCLUSION: A short cervix is associated with an increased transverse diameter of the fetal thymus during the second trimester of gestation.

Lactobacilluscrispatus dominance in the vaginalmicrobiome reduces the occurrence of spontaneouspreterm birth in women with a short cervical length / Dominância de Lactobacillus crispatus no microbioma vaginal reduz a ocorrênciade parto prematuro espontâneo em mulheres com encurtamento do colo uterino

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.

Cervical pessary plus vaginal progesterone in a singleton pregnancy with a short cervix: an experience-based analysis of cervical pessary's efficacy.

BACKGROUND: Several studies were published about cervical pessary, with controversial results. These studies demonstrated that the patient follow-up after pessary insertion is very different between the study centers and the number of pessary insertions per center was often <30 cases. This study aims to determine cervical pessary performance in singleton pregnancies with a short cervix based on a single center learning curve. METHODS: Between 2011 and 2018, 128 singleton pregnancies between 18 and 24 gestational weeks with a short cervix (<25 mm) were referred to our clinic. All cases were treated with progesterone, and when available in our supplies (due to low resources) cervical pessary was also offered. Three groups were created for statistical analysis: Group 1 (n = 33), treated with progesterone-only; Groups 2 and 3, treated with cervical pessary plus progesterone. Group 2 included the first cases (n = 30) of pessary, defined by a learning curve and cumulative sum analysis, while Group 3 included the subsequent 65 cases. The primary outcome was preterm birth (PTB) < 34 gestational weeks. RESULTS: The learning curve was performed with all cases of pessary plus progesterone, and 30 patients were obtained as the number needed for learning, in our study with two operators. The PTB rate < 34 weeks was 27.3, 20, and 4.6% in groups 1, 2, and 3, respectively. There was no significant difference between Group 1 and 2 (OR 1.1; 95% CI 0.066 - 18.45; p = .945). When comparing Groups 1 and 3 there was a significant difference in PTB rates (OR 0.08; CI95% 0.01-0.42; p = .003). Considering Kaplan-Meyer Survival analysis, we can observe that the performance of progesterone alone (Group 1) was similar to Group 2 (progesterone + first 30 cases of pessary) (p = .432), but the performance of Group 3 (progesterone + subsequent 65 cases of pessary) and Group 1 shows a statistically significant difference (p = .011). CONCLUSION: Learning curve and cumulative sum analysis determined that the application and surveillance of at least 30 patients is required to see significant improvements in the primary outcome of PTB < 34 weeks.

Cervical Pessary Plus Progesterone for Twin Pregnancy with Short Cervix Compared to Unselected and Non-Treated Twin Pregnancy: A Historical Equivalence Cohort Study (EPM Twin Pessary Study).

OBJECTIVE: The present study aims to determine if the use of cervical pessary plus progesterone in short-cervix (≤ 25 mm) dichorionic-diamniotic (DC-DA) twin pregnancies is equivalent to the rate of preterm births (PBs) with no intervention in unselected DC-DA twin pregnancies. METHODS: A historical cohort study was performed between 2010 and 2018, including a total of 57 pregnant women with DC-DA twin pregnancies. The women admitted from 2010 to 2012 (n = 32) received no treatment, and were not selected by cervical length (Non-Treated group, NTG), whereas those admitted from 2013 to 2018 (n = 25), were routinely submitted to cervical pessary plus progesterone after the diagnosis of short cervix from the 18th to the 27th weeks of gestation (Pessary-Progesterone group, PPG). The primary outcome analyzed was the rate of PBs before 34 weeks. RESULTS: There were no statistical differences between the NTG and the PPG regarding PB < 34 weeks (18.8% versus 40.0% respectively; p = 0.07) and the mean birthweight of the smallest twin (2,037 ± 425 g versus 2,195 ± 665 g; p = 0.327). The Kaplan-Meyer Survival analysis was performed, and there were no differences between the groups before 31.5 weeks. Logistic regression showed that a previous PB (< 37 weeks) presented an odds ratio (OR) of 15.951 (95% confidence interval [95%CI]: 1.294-196.557; p = 0.031*) for PB < 34 weeks in the PPG. CONCLUSION: In DC-DA twin pregnancies with a short cervix, (which means a higher risk of PB), the treatment with cervical pessary plus progesterone could be considered equivalent in several aspects related to PB in the NTG, despite the big difference between these groups.

OBJETIVO: Este estudo tem como objetivo determinar se o uso de pessário cervical associado a progesterona em gestações de gêmeos dicoriônicos-diamnióticos (DC-DAs) com colo do útero curto (≤ 25 mm) apresenta taxa de parto prematuro (PP) equivalente à de gestações gemelares DC-DA sem nenhuma intervenção/não selecionadas. MéTODOS: Um estudo de coorte histórica foi realizado entre 2010 e 2018, incluindo um total de 57 mulheres grávidas com gestações gemelares DC-DA. As mulheres admitidas de 2010 a 2012 (n = 32) não receberam tratamento, e não foram selecionadas pelo comprimento cervical (grupo Não Tratado, GNT), enquanto as admitidas de 2013 a 2018 (n = 25) receberam pessário cervical rotineiramente associado a progesterona após o diagnóstico de colo curto entre a 18a e a 27ª semanas de gestação (grupo Pessário-Progesterona, GPP). O desfecho primário analisado foi a taxa de PP antes de 34 semanas. RESULTADOS: Não houve diferenças estatísticas entre o GNT e o GPP em relação ao PP < 34 semanas (respectivamente, 18,8% versus 40,0%; p = 0,07) e ao peso médio ao nascer do gêmeo menor (2.037 ± 425 g versus 2.195 ± 665 g; p = 0,327). A análise de Kaplan-Meyer foi realizada, e não houve diferenças entre os grupos antes de 31,5 semanas. A regressão logística demonstrou que o nascimento prematuro anterior (< 37 semanas) apresentou razão de probabilidades (odds ratio, OR) de 15,951 (intervalo de confiança de 95% [IC95%]: 1,294­196,557; p = 0,031*) para o nascimento prematuro < 34 semanas no GPP. CONCLUSãO: Em gêmeos DC-DA com colo uterino curto (o que significa maior risco de nascimento prematuro), o tratamento com pessário cervical associado a progesterona pode ser considerado equivalente em diversos aspectos relacionados à prematuridade no GNT, apesar da grande diferença entre os grupos.

Antibiotic treatment for patients with amniotic fluid "sludge" to prevent spontaneous preterm birth: A historically controlled observational study.

INTRODUCTION: Amniotic fluid "sludge" has been associated with an increased rate of spontaneous preterm delivery before 35 weeks, a higher frequency of clinical and histologic chorioamnionitis in a high-risk population. Only one study evaluating the use of antibiotics in the presence of amniotic fluid "sludge" showed reduced rates of spontaneous preterm birth at <34 weeks. The objective of this study was to evaluate routine antibiotic treatment in the presence of amniotic fluid "sludge" for prevention of preterm delivery. MATERIAL AND METHODS: A historically controlled observational study was performed between October 2010 and January 2015, including a total of 86 pregnant women with singleton pregnancies and the presence of amniotic fluid "sludge" at ultrasound. Women admitted from October 2010 to September 2012 received no treatment with antibiotics, whereas those admitted from October 2012 to January 2015, received routinely clindamycin and first-generation cephalosporin. The groups were compared considering the incidence of spontaneous preterm delivery. The effect of antimicrobials was also compared in the subgroup of women at high risk for spontaneous preterm birth (ie, cervical length ≤25 mm, history of spontaneous preterm birth, previous spontaneous loss in the second trimester, Mullerian malformations or cervical conization). RESULTS: Antibiotic therapy reduced the incidence of spontaneous preterm birth at <34 weeks (13.2% vs 38.5%, P = 0.047) in women at high-risk for preterm birth, with an odds ratio of 0.24 (95% confidence interval [CI] 0.06-0.99). Birthweight was significantly different between the study groups (2961 ± 705 vs. 2554 ± 819 g, respectively; P = 0.028), with no statistical significance for others variables. CONCLUSIONS: This study suggests that antibiotic treatment in high-risk pregnant women with amniotic fluid "sludge" can be effective in the reduction of the frequency of spontaneous preterm delivery and can increase the birthweight.

Amniotic fluid "sludge" is an independent risk factor for preterm delivery.

OBJECTIVE: To determine the prevalence and the clinical significance of amniotic fluid "sludge" (AFS) in asymptomatic patients at low and high risk for spontaneous preterm delivery. METHOD: A prospective cohort study was conducted on 195 singleton pregnancies at low or high risk for preterm birth (PTB) between the 16th and 26th weeks. Cervical length (CL) <25 mm and the presence of AFS were evaluated. The risk for preterm delivery before 28, 32, 35 and 37 weeks were determined according to the presence of AFS, CL < 25 mm and history of high risk for PTB. Stepwise logistic regression was performed to compare variables. RESULTS: AFS was an independent risk factor for PTB < 35 weeks (OR: 3.08, 95% CI: 1.13-8.34, p = 0.027) but not for PTB < 28, 32 and 37 weeks. CL < 25 mm was an independent risk factor for PTB < 28, 32 and 35 but not for PTB < 37 weeks. High risk for PTB was not found as an independent risk factor for PTB. CONCLUSION: AFS is an independent risk factor for PTB before 35 weeks.

Reference range for fetal interventricular septum area by means of four-dimensional ultrasonography using spatiotemporal image correlation.

OBJECTIVE: To determine reference range for fetal interventricular septum area by means of 3-dimensional ultrasonography (3DUS) using the spatiotemporal image correlation (STIC) method. METHODS: A prospective, cross-sectional study was conducted on 328 normal pregnant women between the 18th and 33rd gestational weeks. To obtain the interventricular septum area, a virtual plane was used, with the green line (region of interest) adjacent to the external margin of the septum, which was manually delimited. To evaluate the correlation of the septum area with the gestational age, different regression modes were evaluated. The intraclass correlation coefficient was used to evaluate the interobserver reproducibility. RESULTS: The interventricular septum area showed correlation with the gestational age (r = 0.81). The mean increased from 0.47 ± 0.10 cm² in the 18th week to 2.42 ± 1.13 cm² in the 33rd week of gestation. The mathematical equation that best represented this correlation was provided by linear regression: interventricular septum area = 0.0511 × gestational age (R² = 0.095). The interobserver reproducibility was good, with bias of 0.01 cm², precision of 0.07 cm² and absolute limits of agreement of -0.14 and +0.15 cm². CONCLUSIONS: Reference range for fetal interventricular septum area were determined by means of 3DUS using STIC in the rendering mode and were shown to be reproducible.

Reference ranges of atrioventricular valve areas by means of four-dimensional ultrasonography using spatiotemporal image correlation in the rendering mode.

OBJECTIVE: This study aims to determine reference curves for fetal atrioventricular valve areas by means of three-dimensional ultrasound using the spatiotemporal image correlation (STIC) software. METHODS: This was a cross-sectional prospective study on 328 normal fetuses between the 18th and the 33rd weeks of pregnancy. In order to obtain valve areas, the four heart chambers plane was used with the fetus in a dorsal posterior position. To construct reference ranges, a linear regression model was used, adjusted according to the coefficient of determination (R(2)). To calculate the reproducibility of the tricuspid valve area, the intraclass coefficient correlation (ICC) was used. RESULTS: The mean areas of the tricuspid and mitral valves ranged from 0.19 ± 0.08 and 0.20 ± 0.10 cm(2) in the 18th week to 0.93 ± 0.31 and 1.06 ± 0.39 cm(2) in the 33rd week, respectively. The intra-observer and interobserver reproducibility was excellent with ICC = 0.997 and 0.933, respectively. CONCLUSIONS: Reference curves for fetal atrioventricular valve areas were determined and presented good reproducibility.

Prenatal diagnosis of penoscrotal hypospadia in third trimester by two- and three-dimensional ultrasonography: a case report.

Hypospadia is an abnormal development of the corpus spongiosum, that involves cavernosa urethra, as a result of an inadequate fusion of the urethral folds. The incidence ranges from 0.2 to 4.1 per 1,000 live births. Among the markers of hypospadia, isolated ventral or lateral curvature of the penis associated with shortening are the most important markers and, in severe cases, can result in the classic "tulip sign." The diagnosis of hypospadia is uncommon unless there is a routine of detailed analysis of fetal genitalia morphology. The prenatal diagnosis is of great importance for genetic counseling and allows better planning of postnatal treatment. The three-dimensional ultrasonography (3DUS) in rendering mode enables better comprehension of the pathology by parents, facilitating postnatal planning. We report a case of penoscrotal hypospadia diagnosed at 33 weeks of gestation, suspected due to the absence of testicles in the scrotum and difficulty of penis visualization. We emphasize the findings of 3DUS and its importance in the pathology compression by parents.

Reference intervals for fetal ear length between 19 and 24 weeks of pregnancy on 3-dimensional sonography.

OBJECTIVES: The purpose of this study was to establish reference intervals for fetal ear length using 3-dimensional sonography in the rendering mode. METHODS: A cross-sectional study was conducted on 114 women from 19 weeks to 23 weeks 6 days of normal pregnancy. Fetal ear length measurement was performed in the rendering mode, obtained from 2-dimensional mode reconstruction. To determine the correlation between ear length and gestational age, scatterplots were constructed, and the Pearson correlation coefficient was calculated. Mean, median, SD, maximum, and minimum values and percentiles for each gestational age were calculated. To calculate the intraobserver reproducibility, we used the intraclass correlation coefficient. RESULTS: The mean ear length ± SD increased from 14.43 ± 1.28 mm (range, 12.80-16.50 mm) in the 19th week of pregnancy to 19.72 ± 1.87 mm (range, 17.20-22.40 mm) in the 23rd week. Three-dimensional sonographic ear length measurements were correlated with gestational age, with the best adjustment represented by the following exponential equation: ear length = exp(1.215 × gestational age - 8.692) (R(2) = 0.423). The intraobserver reproducibility was excellent, resulting in an intraclass correlation coefficient of 0.967 (95% confidence interval, 0.939-0.982). CONCLUSIONS: Reference intervals for fetal ear length using 3-dimensional sonography in the rendering mode from 19 weeks to 23 weeks 6 days of pregnancy were determined and proved reproducible.