Evidence of brain injury in fetuses of mothers with preterm labor with intact membranes and preterm prelabor rupture of membranes.

BACKGROUND: Brain injury and poor neurodevelopment have consistently been reported in infants and adults born preterm. These changes occur at least in part prenatally and are associated with intra-amniotic inflammation. The pattern of brain changes has been partially documented by magnetic resonance imaging but not with neurosonography in combination with amniotic fluid brain injury biomarkers. OBJECTIVES: To evaluate the prenatal features of brain remodeling and injury in fetuses from patients with preterm labor with intact membranes or preterm prelabor rupture of membranes and to investigate the potential influence of intra-amniotic inflammation as a mediator of risk. STUDY DESIGN: In this prospective cohort study, fetal brain remodeling and injury was evaluated by neurosonography and amniocentesis in singleton pregnant patients with preterm labor with intact membranes or preterm prelabor rupture of membranes between 24.0-34.0 weeks, with (n=41) and without (n=54) intra-amniotic inflammation. Controls for neurosonography were outpatient pregnant patients without preterm labor or preterm prelabor rupture of membranes matched 2:1 by gestational age at ultrasound. Amniotic fluid controls were patients with an amniocentesis performed for indications other than preterm labor or preterm prelabor rupture of membranes without brain or genetic defects whose amniotic fluid was collected in our biobank for research purposes matched by gestational age at amniocentesis. The group with intra-amniotic inflammation included those with intra-amniotic infection (microbial invasion of the amniotic cavity and intra-amniotic inflammation) and those with sterile inflammation. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture and/or positive 16S ribosomal RNA gene. Inflammation was defined by amniotic fluid interleukin-6 >13.4 ng/ml in preterm labor and >1.43 ng/ml in preterm prelabor rupture of membranes. Neurosonography included the evaluation of brain structure biometric parameters and cortical development. As amniotic fluid brain injury biomarkers we selected neuron-specific enolase, protein S100B and glial fibrillary acidic protein. Data was adjusted for cephalic biometrics, fetal growth centile, fetal sex, non-cephalic presentation and preterm prelabor rupture of membranes at admission. RESULTS: Fetuses from mothers with preterm labor with intact membranes or preterm prelabor rupture of membranes had signs of brain remodeling and injury. First, they had a smaller cerebellum. Thus, in intra-amniotic inflammation, non- intra-amniotic inflammation and control groups, transcerebellar diameter (median (25th; 75th percentile)) was 32.7mm (29.8; 37.6), 35.3mm (31.2;39.6) and 35.0mm (31.3;38.3), respectively (p=0.019); vermian height was 16.9 mm (15.5 ;19.6), 17.2 mm (16.0;18.9) and 17.1mm (15.7;19.0), respectively (p=0.041). Second, they presented a lower corpus callosum area (0.72mm2 (0.59;0. 81), 0.71mm2 (0.63;0.82) and 0.78mm2 (0.71;0. 91), respectively (p=0.006). Third, they showed a delayed cortical maturation (Sylvian fissure depth / biparietal diameter ratio was 0.14 (0.12;0.16), 0.14 (0.13;0.16) and 0.16 (0.15;0.17), respectively (p<0.001), and right parieto-occipital sulci depth ratio was 0.09 (0.07;0.12), 0.11 (0.09;0.14) and 0.11 (0.09;0.14), respectively (p=0.012)). Finally, regarding amniotic fluid brain injury biomarkers, fetuses from mothers with preterm labor with intact membranes or preterm prelabor rupture of membranes, had higher concentrations of neuron-specific enolase (11804.6pg/ml (6213.4;21098.8), 8397.7 pg/ml (3682.1;17398.3) and 2393.7pg/ml (1717.1;3209.3), respectively (p<0.001)); protein S100B (2030.6 pg/ml (993;4883.5), 1070.3pg/ml (365.1-1463.2) and 74.8pg/ml (44.7;93.7), respectively (p<0.001)), and glial fibrillary acidic protein (1.01ng/ml (0.54;3.88), 0.965ng/ml (0.59;2.07) and 0.24mg/ml (0.20;0.28), respectively (p=0.002)). CONCLUSION: Fetuses with preterm labor with intact membranes or preterm prelabor rupture of membranes had prenatal signs of brain remodeling and injury at the time of clinical presentation. These changes were more pronounced in those with intra-amniotic inflammation.

Intra-amniotic infection and/or inflammation is associated with fetal cardiac concentric hypertrophy and diastolic dysfunction in preterm labor and preterm prelabor rupture of membranes.

BACKGROUND: Preterm delivery is associated with cardiovascular remodeling and dysfunction in children and adults. However, it is unknown whether these effects are caused by the neonatal consequences of preterm birth or if these are already present in utero. OBJECTIVE: We evaluated fetal cardiac morphology and function in fetuses of mothers admitted for preterm labor or preterm prelabor rupture of membranes and the association of these changes with the presence of intra-amniotic infection and/or inflammation. STUDY DESIGN: In this prospective cohort study, fetal echocardiography and amniocentesis were performed at admission in singleton pregnant women with preterm labor and/or preterm prelabor rupture of membranes between 24.0 and 34.0 weeks' gestation with (intra-amniotic infection and/or inflammation group, n=41) and without intra-amniotic infection and/or inflammation (non-intra-amniotic infection and/or inflammation, n=54). Controls (n=48) were outpatient pregnant women without preterm labor or preterm prelabor rupture of membranes. Intra-amniotic infection was defined by a positive amniotic fluid culture or positive 16S ribosomal RNA gene. Intra-amniotic inflammation was defined by using the amniotic fluid interleukin-6 cutoff levels previously reported by our group being >1.43 ng/mL in preterm prelabor rupture of membranes and >13.4 ng/mL in preterm labor. Fetal cardiac morphology and function was evaluated using echocardiography, and troponin-I and N-terminal pro-brain natriuretic peptide concentrations were measured in amniotic fluid from women with preterm labor or preterm prelabor rupture of membranes and compared with 20 amniotic fluid Biobank samples obtained for reasons other than preterm labor or preterm prelabor rupture of membranes or cardiac pathology. The data were adjusted for the estimated fetal weight below the 10th percentile and for preterm prelabor rupture of membranes at admission and also for gestational age at amniocentesis when amniotic fluid biomarkers were compared. RESULTS: From 2018 to 2021, 143 fetuses were included; 95 fetuses were from mothers admitted with a diagnosis of preterm labor or preterm prelabor rupture of membranes, and among those, 41 (28.7%) were in the intra-amniotic infection and/or inflammation group and 54 (37.8%) were in the non-intra-amniotic infection and/or inflammation group. A total of 48 (33.6%) fetuses were included in the control group. Fetuses with preterm labor and/or preterm prelabor rupture of membranes had signs of subclinical cardiac concentric hypertrophy (median left wall thickness of 0.93 [interquartile range, 0.72-1.16] in the intra-amniotic infection and/or inflammation group; 0.79 [0.66-0.92] in the non-intra-amniotic infection and/or inflammation group; and 0.69 [0.56-0.83] in controls; P<.001) and diastolic dysfunction (tricuspid A duration 0.23 seconds [0.21-0.25], 0.24 [0.22-0.25], and 0.21 [0.2-0.23]; P=.007). Systolic function was similar among groups. Higher values of amniotic fluid troponin I (1413 pg/mL [927-2334], 1190 [829-1636], and 841 [671-959]; P<.001) and N-terminal pro-brain natriuretic peptide were detected (35.0%, 17%, and 0%; P=.005) in fetuses with preterm labor or preterm prelabor rupture of membranes when compared with the control group. The highest N-terminal pro-brain natriuretic peptide concentrations were found in the intra-amniotic infection and/or inflammation group. CONCLUSION: Fetuses with preterm labor or preterm prelabor rupture of membranes showed signs of cardiac remodeling and subclinical dysfunction, which were more pronounced in those exposed to intra-amniotic infection and/or inflammation. These findings support that the cardiovascular effects observed in children and adults born preterm have, at least in part, a prenatal origin.

Influence of pelvic floor muscle training alone or as part of a general physical activity program during pregnancy on urinary incontinence, episiotomy and third- or fourth-degree perineal tear: Systematic review and meta-analysis of randomized clinical trials.

INTRODUCTION: The complex process of pregnancy and childbirth significantly influences the well-being of both mother and child. Today all pregnant women without medical contraindications are recommended to start or continue regular aerobic and strength training for at least 150 min per week to prevent pregnancy-related diseases and conditions. Urinary incontinence in pregnancy, episiotomy and third- or fourth-degree perineal tear during labor can greatly impact womens' health, quality of life and ability to be physically active. The aim of this study was to examine the efficacy of pelvic floor muscle training (PFMT) during pregnancy in the prevention of urinary incontinence, episiotomy, and third- or fourth-degree perineal tear. MATERIAL AND METHODS: A systematic review and meta-analysis (CRD42022370600) was performed. Only randomized clinical trials published between 2010 and 2023 were included. The following databases were examined: EBSCO (including Academic Search Premier, Education Resources Information Center, MEDLINE, SPORTDiscus and OpenDissertations databases), Clinicaltrials.gov, Web of Science, Scopus, Cochrane Database of Systematic Reviews and Physiotherapy Evidence Database (PEDro). Three meta-analyses to investigate the effect of PFMT exclusively or implemented as a section within a physical activity program during pregnancy on urinary incontinence, episiotomy, and third- or fourth-degree perineal tear were conducted. RESULTS: Thirty studies were analyzed (N = 6691). An effective preventive action of PFMT was found for urinary incontinence (z = 3.46; p < 0.0005; relative risk [RR] = 0.72, 95% confidence interval [CI]: 0.59, 0.87, I2 = 59%) and third- or fourth-degree perineal tear (z = 2.89; p = 0.004; RR = 0.50, 95% CI: 0.31, 0.80, I2 = 48%) but not for episiotomy (z = 0.80; p = 0.42; RR = 0.95, 95% CI: 0.85, 1.07, I2 = 75%). CONCLUSIONS: PFMT during pregnancy proves to be an effective preventive intervention for reducing the risk of urinary incontinence and the occurrence of third- or fourth-degree perineal tears. These findings highlight the importance of incorporating PFMT into antenatal care and training programs to improve maternal well-being and overall childbirth outcomes.

The role of acupuncture in the present approach to labor induction: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the bibliographic references available on the contribution of acupuncture as a strategy to avoid labor induction and the methodology used; and explore the characteristics of the population and the results of the intervention in order to direct the design of future studies. DATA SOURCE: A systematic search for publications between January 2000 and September 2023 of the CENTRAL, PubMed, CINAHL, SCOPUS, ClinicalTrials.gov, and EUDRACT databases was performed. STUDY ELIGIBILITY CRITERIA: We included randomized clinical trials of pregnant women who underwent acupuncture before labor induction with a filiform needle or acupressure, including at least 1 of the following outcomes: spontaneous labor rate, time from procedure to delivery, and cesarean delivery rate. Articles published in English or German language were included. METHODS: Whenever possible, a meta-analysis using RevMan software was performed using a random effects model with the I2 statistic because important heterogeneity in the different acupuncture treatments was expected. When enough data were available, the effect of the participants' characteristics on the results of the interventions were explored using the following subgroups: 1-Age (≥35 vs <35 years), and 2- body mass index (≥30 vs <30 kg/m2). When a meta-analysis was not possible, a narrative synthesis of the results was performed. The quality of the evidence was assessed using GRADE. RESULTS: Seventeen studies including 3262 women fulfilled our inclusion criteria. The meta-analysis showed no statistically significant differences between groups for outcomes (relative risk, 1.00; 95% confidence interval, 0.91-1.10; I2, 11%) comparing acupuncture vs sham acupuncture. However, there was a statistically significant increase in the spontaneous onset of labor rate favoring acupuncture vs no acupuncture (relative risk, 1.12; 95% confidence interval, 1.03-1.23; I2, 25%). Regarding the age analysis, no differences between groups were observed in the spontaneous labor rate and cesarean delivery rate for acupuncture vs sham and acupuncture vs no acupuncture comparisons (difference between groups, P>.05). CONCLUSION: This study suggests that acupuncture may be beneficial in reducing the rate of induction of labor; however, well-designed randomized controlled trials are necessary. Maternal age ≥35 years and a high body mass index were underrepresented, and the findings may not be representative of the current population in our context.

A multivariable prediction model for intra-amniotic infection in patients with preterm labor and intact membranes including a point of care system that measures amniotic fluid MMP-8.

OBJECTIVES: Among patients with preterm labor and intact membranes (PTL), those with intra-amniotic infection (IAI) present the highest risk of adverse perinatal outcomes. Current identification of IAI, based on microbiological cultures and/or polymerase chain reaction amplification of the 16S ribosomal RNA gene, delay diagnosis and, consequently, antenatal management. The aim to of the study was to assess the performance of a multivariable prediction model for diagnosing IAI in patients with PTL below 34.0 weeks using clinical, sonographic and biochemical biomarkers. METHODS: From 2019 to 2022, we prospectively included pregnant patients admitted below 34.0 weeks with diagnosis of PTL and had undergone amniocentesis to rule in/out IAI. The main outcome was IAI, defined by a positive culture and/or 16S ribosomal RNA gene in amniotic fluid. Based on the date of admission, the sample (n=98) was divided into a derivation (2019-2020, n=49) and validation cohort (2021-2022, n=49). Logistic regression models were developed for the outcomes evaluated. As predictive variables we explored ultrasound cervical length measurement at admission, maternal C-reactive protein, gestational age, and amniotic fluid glucose and matrix metalloproteinase-8 (MMP-8) levels. The model was developed in the derivation cohort and applied to the validation cohort and diagnostic performance was evaluated. Clinical management was blinded to the model results. RESULTS: During the study period, we included 98 patients admitted with a diagnosis of PTL. Of these, 10 % had IAI. The final model included MMP-8 and amniotic fluid glucose levels and showed an area under the receiver operating characteristic curve to predict the risk of IAI of 0.961 (95 % confidence interval: 0.860-0.995) with a sensitivity of 75 %, specificity of 93.3 %, positive likelihood ratio (LR) of 11.3 and negative LR of 0.27 in the validation cohort. CONCLUSIONS: In patients with PTL, a multivariable prediction model including amniotic fluid MMP-8 and glucose levels might help in the clinical management of patients undergoing amniocentesis to rule in/out IAI, providing results within a few minutes.

Preterm Prelabour Rupture of Membranes before Viability in Twin Pregnancies: What Can We Expect?

Preterm prelabour rupture of membranes (PPROMs) before viability carries significant perinatal mortality and morbidity. Clinical management and prenatal counselling are a challenge, especially in twin pregnancies, due to scarce evidence on how previable PPROM affects this population. The aim of this study was to describe pregnancy outcomes of twin pregnancies complicated with previable PPROM and evaluate potential prognostic factors that may predict perinatal mortality. A retrospective cohort including dichorionic and monochorionic diamniotic twin pregnancies complicated with PPROM before 24 + 0 weeks of pregnancy was evaluated. Perinatal outcomes of pregnancies managed expectantly were described. Factors predicting perinatal mortality or reaching periviability (defined from 23 + 0 weeks onwards) were evaluated. Of the 45 patients included, 7 (15.6%) spontaneously delivered within the first 24 h after diagnosis. Two patients (5.3%) requested selective termination of the affected twin. In the 36 ongoing pregnancies that opted for expectant management, the overall survival rate was 35/72 (48.6%). There were 25/36 (69.4%) patients who delivered after 23 + 0 weeks of pregnancy. When periviability was achieved, neonatal survival increased up to 35/44 (79.5%). Gestational age at delivery was the only independent risk factor of perinatal mortality. The overall survival rate of twin pregnancies complicated with previable PPROM is poor but similar to singletons. No prognostic factors, apart from achieving periviability, were identified as individual predictors of perinatal mortality.

Maternal educational level and preterm birth: Exploring inequalities in a hospital-based cohort study.

Preterm birth has been related to inequalities in maternal educational level, but the causal mechanism is not entirely known. Some factors associated with preterm birth and low educational level such as chronic medical conditions, pregnancy complications and related-health behaviours could have a mediation role in the pathway. This study aimed to evaluate the association between maternal educational level and preterm birth, analysing the mediation role of these factors. We performed a retrospective cohort study based on hospital electronic records of 10467 deliveries that took place in the Hospital Clínic of Barcelona between 2011 and 2017. Poisson regression was used to obtain crude and adjusted relative risk of preterm birth in women with different educational level and the percentage of change in relative risk was calculated when mediation variables were included in the model. Women with a lower educational level had a higher risk of preterm birth (RR 1.57, 95% CI 1.21, 2.03). The loss of association after the inclusion of body mass index in the model suggests an important mediation role of maternal overweight. Other variables such as smoking, drug use, preeclampsia and genitourinary infections also appear to play a role in the observed inequality between women with different levels of education. Efforts to promote health literacy and to improve preventive interventions, before and during pregnancy, could decrease preterm birth rates and perinatal health inequalities.

Outpatient management of preterm prelabor rupture of membranes before 34 weeks: Maternal and neonatal outcomes.

OBJECTIVE: To evaluate the maternal, fetal, and neonatal outcomes of pregnant women complicated with preterm prelabor rupture of membranes (PPROM) eligible for outpatient care. METHODS: This study included a retrospective cohort of patients with singleton pregnancies with PPROM between 23+0 to 34+0 weeks who remained pregnant after the first 72 h. Outpatient management was considered in women with clinical, ultrasound and analytical stability, and easy access to hospital. Maternal, fetal, and neonatal results were compared between women managed as inpatients versus those managed as outpatients. RESULTS: Women eligible for the outpatient management had a better prognostic profile (no anhydramnios, longer cervical length, less intraamniotic infection, and clinical, ultrasound, and analytical stability) and presented a lower gestational age at admission and longer latency to delivery, resulting in a similar gestational age at delivery as the inpatient group. Postpartum curettage, uterine atony, respiratory distress syndrome, and bronchopulmonary dysplasia were less frequent in the outpatient group. Composite maternal-fetal morbidity and mortality outcomes were similar in both groups, while composite neonatal morbidity and mortality outcomes were significantly lower in the outpatient group. CONCLUSION: Outpatient management may be an option for women presenting stable PPROM before 34 weeks when adequate selection criteria are fulfilled. Differences in perinatal outcomes in the outpatient group compared with the inpatient group are probably attributable to baseline characteristics. Further prospective randomized studies are needed to confirm the benefits of outpatient management in PPROM.

Activity Restriction and Hospitalization in Pregnancy: Can Bed-Rest Exercise Prevent Deconditioning? A Narrative Review.

Evidence suggests that exercise during pregnancy is beneficial to both parent and fetus. However, there are high-risk pregnancy conditions that may warrant hospitalization. In our narrative review, we first describe the clinical implications for activity restriction in pregnancy, the effects of hospitalization, and the impact of bed rest on non-pregnant individuals. We provide examples of a 30 min bed-rest exercise program for hospitalized pregnant patients using the principal of suggested frequency, intensity, time (duration) of activity, and type of activity (FITT) using a resistance tool while in bed. If the individual is able to ambulate, we recommend short walks around the ward. Every minute counts and activity should be incorporated into a program at least 3 times per week, or every day if possible. As in all exercise programs, motivation and accountability are essential. Flexibility in timing of the exercise intervention is important due to the scheduling of medical assessments that may occur throughout the day for these hospitalized patients. Evidence suggests that by improving physical and emotional health through a bed-rest exercise program during a hospitalized pregnancy may help the individual resume demanding daily activity in the postpartum period and improve quality of life once birth has occurred. More research is necessary to improve the health of those individuals who are hospitalized during pregnancy, with follow up and support into the postpartum period.

Noninvasive prediction models of intra-amniotic infection in women with preterm labor.

BACKGROUND: Among women with preterm labor, those with intra-amniotic infection present the highest risk of early delivery and the most adverse outcomes. The identification of intra-amniotic infection requires amniocentesis, perceived as too invasive by women and physicians. Noninvasive methods for identifying intra-amniotic infection and/or early delivery are crucial to focus early efforts on high-risk preterm labor women while avoiding unnecessary interventions in low-risk preterm labor women. OBJECTIVE: This study modeled the best performing models, integrating biochemical data with clinical and ultrasound information to predict a composite outcome of intra-amniotic infection and/or spontaneous delivery within 7 days. STUDY DESIGN: From 2015 to 2020, data from a cohort of women, who underwent amniocentesis to rule in or rule out intra-amniotic infection or inflammation, admitted with a diagnosis of preterm labor at <34 weeks of gestation at the Hospital Clinic and Hospital Sant Joan de Déu, Barcelona, Spain, were used. At admission, transvaginal ultrasound was performed, and maternal blood and vaginal samples were collected. Using high-dimensional biology, vaginal proteins (using multiplex immunoassay), amino acids (using high-performance liquid chromatography), and bacteria (using 16S ribosomal RNA gene amplicon sequencing) were explored to predict the composite outcome. We selected ultrasound, maternal blood, and vaginal predictors that could be tested with rapid diagnostic techniques and developed prediction models employing machine learning that was applied in a validation cohort. RESULTS: A cohort of 288 women with preterm labor at <34 weeks of gestation, of which 103 (35%) had a composite outcome of intra-amniotic infection and/or spontaneous delivery within 7 days, were included in this study. The sample was divided into derivation (n=116) and validation (n=172) cohorts. Of note, 4 prediction models were proposed, including ultrasound transvaginal cervical length, maternal C-reactive protein, vaginal interleukin 6 (using an automated immunoanalyzer), vaginal pH (using a pH meter), vaginal lactic acid (using a reflectometer), and vaginal Lactobacillus genus (using quantitative polymerase chain reaction), with areas under the receiving operating characteristic curve ranging from 82.2% (95% confidence interval, ±3.1%) to 85.2% (95% confidence interval, ±3.1%), sensitivities ranging from 76.1% to 85.9%, and specificities ranging from 75.2% to 85.1%. CONCLUSION: The study results have provided proof of principle of how noninvasive methods suitable for point-of-care systems can select high-risk cases among women with preterm labor and might substantially aid in clinical management and outcomes while improving the use of resources and patient experience.

Impact of Physical Activity Interventions on High-Risk Pregnancies: A Systematic Review and Meta-Analysis.

Pregnant women with absolute contraindications may be advised against physical activity throughout pregnancy. In this context, bed rest elevates the short-term risk of neonatal complications, thereby exacerbating negative long-term effects on childhood development. The aim of the current study was to investigate the impact of various physical activity interventions during bed rest or activity restriction in pregnancy on factors such as birth weight, preterm birth, maternal hypertension, gestational age at delivery, and the incidence of cesarean sections. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was designed. The protocol was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) (CRD42022370875). Nine studies, with a total sample of 3173 women, from six countries on four continents were included. There were significant differences in the relationship between bed rest status and birth weight (Z = 2.64; p = 0.008) (MD = 142.57, 95% CI = 36.56, 248.58, I2 = 0%, Pheterogeneity = 0.45) favourable to active groups. No significant differences were found in other analyzed outcomes. Pregnant women who experience this problem must maintain a minimum of daily activity to alleviate these physiological complications and the medical field must understand the consequences of physical inactivity during pregnancy.

Prediction of Neonatal Respiratory Morbidity Assessed by Quantitative Ultrasound Lung Texture Analysis in Twin Pregnancies.

The objective of this study was to evaluate the performance of quantitative ultrasound of fetal lung texture analysis in predicting neonatal respiratory morbidity (NRM) in twin pregnancies. This was an ambispective study involving consecutive cases. Eligible cases included twin pregnancies between 27.0 and 38.6 weeks of gestation, for which an ultrasound image of the fetal thorax was obtained within 48 h of delivery. Images were analyzed using quantusFLM® version 3.0. The primary outcome of this study was neonatal respiratory morbidity, defined as the occurrence of either transient tachypnea of the newborn or respiratory distress syndrome. The performance of quantusFLM® in predicting NRM was analyzed by matching quantitative ultrasound analysis and clinical outcomes. This study included 166 images. Neonatal respiratory morbidity occurred in 12.7% of cases, and it was predicted by quantusFLM® analysis with an overall sensitivity of 42.9%, specificity of 95.9%, positive predictive value of 60%, and negative predictive value of 92.1%. The accuracy was 89.2%, with a positive likelihood ratio of 10.4, and a negative likelihood ratio of 0.6. The results of this study demonstrate the good prediction capability of NRM in twin pregnancies using a non-invasive lung texture analysis software. The test showed an overall good performance with high specificity, negative predictive value, and accuracy.

Congenital Cytomegalovirus Awareness and Knowledge among Health Professionals and Pregnant Women: An Action towards Prevention.

INTRODUCTION: Cytomegalovirus (CMV) is a major cause of childhood disabilities, and consensus recommendations emphasize the importance of hygienic measures to reduce perinatal infection. Our study aimed to evaluate the level of awareness about CMV among health professionals and pregnant women. METHODS: We submitted a 20-item online survey regarding CMV perinatal infection to all obstetricians and midwives in Catalonia (Spain) and a 7-item lay version of the questionnaire to 700 pregnant women. Levels of knowledge were compared among groups. RESULTS: Of the 1,449 health professionals approached, 338 surveys were answered. 72% of professionals considered CMV a relevant problem. 47% of obstetricians and 28% of midwives (p ≤ 0.001) routinely informed pregnant women, and less than half knew the risk of fetal transmission. We observed significant differences in knowledge between obstetricians and midwives concerning the risks of recurrent infections, risk of transmission, and risk of severe infection (60.7% vs. 45.6%, p = 0.006 and 50.6% vs. 22.5%, p ≤ 0.001); and regarding maternal and neonatal symptoms and newborn sequelae (23% vs. 8.8%, p ≤ 0.001). Of the 700 women approached, we obtained a response rate of 72%. Only 23% had previously heard about CMV, 22% identified transmission routes, and 15% preventive measures. Compared to women without risk factors for CMV infection, women at greater risk had heard more about CMV (mothers of children <3 years: 36% vs. 20%, p < 0.001; occupational exposure: 43% vs. 20%, p ≤ 0.001) and had received more information (mothers of children <3 years: 18% vs. 9.5%, p ≤ 0.001; occupational exposure: 23% vs. 9.3%, p = 0.001). CONCLUSION: Health care professionals have limited knowledge about CMV and may fail to enforce preventive measures. While pregnant women have limited awareness about CMV infection, they recognize the need for information. Health campaigns should be promoted to enhance awareness about this perinatal infection.

Concordance of the risk of neonatal respiratory morbidity assessed by quantitative ultrasound lung texture analysis in fetuses of twin pregnancies.

To evaluate the concordance of the risk of neonatal respiratory morbidity (NRM) assessed by quantitative ultrasound lung texture analysis (QuantusFLM) between twin fetuses of the same pregnancy. Prospective study conducted in twin pregnancies. Fetal ultrasound lung images were obtained at 26.0-38.6 weeks of gestation. Categorical (high or low) and continuous results of the risk of NRM were compared between twins. Fetal ultrasound lung images from 131 pairs (262 images) of twins were included. The images were classified into three gestational age ranges: Group 1 (26.0-29.6 weeks, 78 images, 39 pairs [29.8%]); Group 2 (30.0-33.6 weeks, 98 images, 49 pairs [37.4%]) and Group 3 (34.0-38.6 weeks, 86 images, 43 pairs [32.8%]). Concordance was good in Groups 1 and 3 and moderate in Group 2. In Groups 2 and 3 at least one fetus presented high-risk results in 26.5% and 11.6% of twin pairs, respectively. Only gestational age < 32 weeks, gestational diabetes mellitus, and spontaneous conception were associated with a high risk of NRM in Group 2. There was good concordance of the risk of NRM between twins < 30.0 weeks and > 34.0 weeks. From 30.0 to 33.6 weeks 26.5% of the twin pairs had discordant results, with moderate concordance of the risk of NRM.

Individualized treatment of preterm premature rupture of membranes to prolong the latency period, reduce the rate of preterm birth, and improve neonatal outcomes.

BACKGROUND: Preterm premature rupture of membranes complicates approximately 3% of pregnancies. Currently, in the absence of chorioamnionitis or placental abruption, expectant management, including antenatal steroids for lung maturation and prophylactic antibiotic treatment, is recommended. The benefits of individualized management have not been adequately explored. OBJECTIVE: This study aimed to compare the impact of 2 different management strategies of preterm premature rupture of membranes in 2 tertiary obstetrical centers on latency of >7 days, latency to birth, chorioamnionitis, funisitis, and short-term adverse maternal and neonatal outcomes. STUDY DESIGN: This was a multicenter retrospective study of women with singleton pregnancies with preterm premature rupture of membranes from 23 0/7 to 33 6/7 weeks of gestation between 2014 and 2018 and undelivered within 24 hours after hospital admission managed at Sunnybrook Health Sciences Center, Toronto, Canada (standard management group), and BCNatal (Hospital Clínic of Barcelona and Hospital Sant Joan de Déu Barcelona), Barcelona, Spain (individualized management group), following local protocols. The standard management group received similar management for all patients, which included a standard antibiotic regimen and routine maternal and fetal surveillance, whereas the individualized management group received personalized management on the basis of amniocentesis at hospital admission (if possible), to rule out microbial invasion of the amniotic cavity and targeted treatment. The exclusion criteria were cervical dilatation >2 cm, active labor, contraindications to expectant management (acute chorioamnionitis, placental abruption, or abnormal fetal tracing), and major fetal anomalies. The primary outcome was latency of >7 days, and the secondary outcomes included latency to birth, chorioamnionitis, and short-term adverse maternal and neonatal outcomes. Statistical comparisons between groups were conducted with propensity score weighting. RESULTS: A total of 513 pregnancies with preterm premature rupture of membranes were included in this study: 324 patients received standard management, and 189 patients received individualized management, wherein amniocentesis was performed in 112 cases (59.3%). After propensity score weighting, patients receiving individualized management had a higher latency of >7 days (76.0% vs 41.6%; P<.001) and latency to birth (18.1±14.7 vs 9.7±9.7 days; P<.001). Although a higher rate of clinical chorioamnionitis was suspected in the individualized management group than the standard group (34.5% vs 22.0%; P<.01), there was no difference between the groups in terms of histologic chorioamnionitis (67.2% vs 73.4%; P=.16), funisitis (57.6% vs 58.1%; P=.92), or composite infectious maternal outcomes (9.1% vs 7.9%; P=.64). Prolonged latency in the individualized management group was associated with a significant reduction of preterm birth at <32 weeks of gestation (72.1% vs 90.5%; P<.001), neonatal intensive care unit admission (75.6% vs 83.0%; P=.046), and neonatal respiratory support at 28 days of life (16.1% vs 26.1%; P<.01) compared with that in the standard management group. Moreover, prolonged latency was not associated with neonatal severe morbidity at discharge (survival without severe morbidity, 80.4% vs 73.5%; P=.09). CONCLUSION: Individualized management of preterm premature rupture of membranes may prolong pregnancy and reduce preterm birth at <32 weeks of gestation, the need for neonatal support, and neonatal intensive care unit admissions, without an increase in histologic chorioamnionitis, funisitis, neonatal infection-related morbidity, and short-term adverse maternal and neonatal outcomes.

Intra- and interobserver reproducibility of second trimester ultrasound cervical length measurement in a general population.

OBJECTIVES: To evaluate the reproducibility of ultrasound cervical length (CL) measurement at the second trimester. METHODS: A set of 565 cervical ultrasound images were collected at 19 + 0-24 + 6 weeks' gestation. Two senior maternal-fetal specialists measured CL in each image on three occasions 2 weeks apart. In the interval between the first and following two measures, the clinicians reviewed 20 images together to agree on the criteria for measurement. Measurements were analyzed for intra- and inter-observer disagreement. The robustness of patient classification when CL measure was used with different cutoff thresholds was analyzed. RESULTS: Average intra-observer deviation was 2.8 mm for clinician 1 and 3.7 mm for clinician 2. Inter-observer deviation among the two clinicians was 5.2 and 3.2 mm before and after reviewing measurement criteria together. When cutoffs were used to classify as "short" cervix, disagreement ranged from 22 to 70% depending on operator and threshold used. CONCLUSION: Ultrasound CL measurements by experts showed moderate intra- and inter-observer reproducibility. The use of specific cutoffs to classify patients as high or low risk resulted in wide disagreements. The results stress the importance of training and quality assessments on considering universal screening application of CL measurement.

Latency to delivery in physical examination-indicated cerclage in twins is similar to that in singleton pregnancies.

OBJECTIVE: To compare latency to delivery and perinatal outcomes between twin and singleton pregnancies undergoing physical examination-indicated cerclage. METHODS: Retrospective observational study (2007-2017) of women who underwent physical examination-indicated cerclage at the Hospital Clinic of Barcelona. Primary outcomes were latency from cerclage to delivery and gestational age at delivery. Secondary outcomes included: neonatal morbidity and mortality, preterm prelabor rupture of membranes, clinical chorioamnionitis and cerclage displacement. Wilcoxon-test and χ2 test were used to compare continuous and categorical variables. RESULTS: Sixty women were included (17 twins and 43 singletons). There were no differences in gestational age at cerclage or presence of bulging membranes between groups. Median (25th;75th percentile) gestational age at delivery was 27.1 (24.5;32.3) weeks in the twin group and 27.6 (25.3;35.3) weeks in the singleton group (P = 0.594). There were no statistically significant differences in latency from cervical cerclage to delivery between the two groups (43 days [21;64] vs. 29 days [16;76], respectively; P = 0.938). There were no differences in neonatal mortality (2/26 [7.7%] vs. 1/33 [3.1%]; P = 0.578) or in composite neonatal morbidity (14 [53.9%] vs. 14 [42.4%]; P = 0.283) between groups, respectively. CONCLUSION: These results suggest that physical examination-indicated cerclage placement in twins could prolong latency to delivery similarly to singleton pregnancies.

Assessment of an intervention to optimise antenatal management of women admitted with preterm labour and intact membranes using amniocentesis-based predictive risk models: study protocol for a randomised controlled trial (OPTIM-PTL Study).

INTRODUCTION: The majority of women admitted with threatened preterm labour (PTL) do not delivery prematurely. While those with microbial invasion of the amniotic cavity (MIAC) represent the highest risk group, this is a condition that is not routinely ruled out since it requires amniocentesis. Identification of low-risk or high-risk cases might allow individualisation of care, that is, reducing overtreatment with corticosteroids and shorten hospital stay in low-risk women, while allowing early antibiotic therapy in those with MIAC. Benefits versus risks of amniocentesis-based predictor models of spontaneous delivery within 7 days and/or MIAC have not been evaluated. METHODS AND ANALYSIS: This will be a Spanish randomised, multicentre clinical trial in singleton pregnancies (23.0-34.6 weeks) with PTL, conducted in 13 tertiary centres. The intervention arm will consist in the use of amniocentesis-based predictor models: if low risk, hospital discharge within 24 hours of results with no further medication will be recommended. If high risk, antibiotics will be added to standard management. The control group will be managed according to standard institutional protocols, without performing amniocentesis for this indication. The primary outcome will be total antenatal doses of corticosteroids, and secondary outcomes will be days of maternal stay and the occurrence of clinical chorioamnionitis. A cost analysis will be undertaken. To observe a reduction from 90% to 70% in corticosteroid doses, a reduction in 1 day of hospital stay (SD of 2) and a reduction from 24% to 12% of clinical chorioamnionitis, a total of 340 eligible patients randomised 1 to 1 to each study arm is required (power of 80%, with type I error α=0.05 and two-sided test, considering a dropout rate of 20%). Randomisation will be stratified by gestational age and centre. ETHICS AND DISSEMINATION: Prior to receiving approval from the Ethics Committee (HCB/2020/1356) and the Spanish Agency of Medicines and Medical Devices (AEMPS) (identification number: 2020-005-202-26), the trial was registered in the European Union Drug Regulating Authorities Clinical Trials database (2020-005202-26). AEMPS approved the trial as a low-intervention trial. All participants will be required to provide written informed consent. Findings will be disseminated through workshops, peer-reviewed publications and national/international conferences. PROTOCOL VERSION: V.4 10 May 2021. TRIAL REGISTRATION NUMBERS: NCT04831086 and Eudract number 2020-005202-26.

Mid-trimester prediction of spontaneous preterm birth with automated cervical quantitative ultrasound texture analysis and cervical length: a prospective study.

The objective of this study was to evaluate a novel automated test based on ultrasound cervical texture analysis to predict spontaneous Preterm Birth (sPTB) alone and in combination with Cervical Length (CL). General population singleton pregnancies between 18 + 0 and 24 + 6 weeks' gestation were assessed prospectively at two centers. Cervical ultrasound images were evaluated and the occurrence of sPTB before weeks 37 + 0 and 34 + 0 were recorded. CL was measured on-site. The automated texture analysis test was applied offline to all images. Their performance to predict the occurrence of sPTB before 37 + 0 and 34 + 0 weeks was evaluated separately and in combination on 633 recruited patients. AUC for sPTB prediction before weeks 37 and 34 respectively were as follows: 55.5% and 65.3% for CL, 63.4% and 66.3% for texture analysis, 67.5% and 76.7% when combined. The new test improved detection rates of CL at similar low FPR. Combining the two increased detection rate compared to CL alone from 13.0 to 30.4% for sPTB < 37 and from 14.3 to 42.9% sPTB < 34. Texture analysis of cervical ultrasound improved sPTB detection rate compared to cervical length for similar FPR, and the two combined together increased significantly prediction performance. This results should be confirmed in larger cohorts.

The Predictive Value of the Cervical Consistency Index to Predict Spontaneous Preterm Birth in Asymptomatic Twin Pregnancies at the Second-Trimester Ultrasound Scan: A Prospective Cohort Study.

Novel transvaginal ultrasound (TVU) markers have been proposed to improve spontaneous preterm birth (sPTB) prediction. Preliminary results of the cervical consistency index (CCI), uterocervical angle (UCA), and cervical texture (CTx) have been promising in singletons. However, in twin pregnancies, the results have been inconsistent. In this prospective cohort study of asymptomatic twin pregnancies assessed between 18+0-22+0 weeks, we evaluated TVU derived cervical length (CL), CCI, UCA, and the CTx to predict sPTB < 34+0 weeks. All iatrogenic PTB were excluded. In the final cohort of 63 pregnancies, the sPTB rate < 34+0 was 16.3%. The CCI, UCA, and CTx, including the CL was significantly different in the sPTB < 34+0 weeks group. The best area under the receiver operating characteristic curve (AUC) for sPTB < 34+0 weeks was achieved by the CCI 0.82 (95%CI, 0.72-0.93), followed by the UCA with AUC 0.72 (95%CI, 0.57-0.87). A logistic regression model incorporating parity, chorionicity, CCI, and UCA resulted in an AUC of 0.91 with a sensitivity of 55.3% and specificity of 88.1% for predicting sPTB < 34+0. The CCI performed better than other TVU markers to predict sPTB < 34+0 in twin gestations, and the best diagnostic accuracy was achieved by a combination of parity, chorionicity, CCI, and UCA.