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Objective: To compare the predictive performance of three different mathematical models for first‐trimester screening of pre‐eclampsia (PE), which combine maternal risk factors with mean arterial pressure (MAP), uterine artery pulsatility index (UtA‐PI) and serum placental growth factor (PlGF), and two risk‐scoring systems. Methods: This was a prospective cohort study performed in eight fetal medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with singleton pregnancy and a non‐malformed live fetus attending their routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation were invited to participate in the study. Maternal characteristics and medical history were recorded and measurements of MAP, UtA‐PI, serum PlGF and pregnancy‐associated plasma protein‐A (PAPP‐A) were converted into multiples of the median (MoM). Risks for term PE, preterm PE (< 37 weeks' gestation) and early PE (< 34 weeks' gestation) were calculated according to the FMF competing‐risks model, the Crovetto et al. logistic regression model and the Serra et al. Gaussian model. PE classification was also performed based on the recommendations of the National Institute for Health and Care Excellence (NICE) and the American College of Obstetricians and Gynecologists (ACOG). We estimated detection rates (DR) with their 95% CIs at a fixed 10% screen‐positive rate (SPR), as well as the area under the receiver‐operating‐characteristics curve (AUC) for preterm PE, early PE and all PE for the three mathematical models. For the scoring systems, we calculated DR and SPR. Risk calibration was also assessed. Results: The study population comprised 10 110 singleton pregnancies, including 32 (0.3%) that developed early PE, 72 (0.7%) that developed preterm PE and 230 (2.3%) with any PE. At a fixed 10% SPR, the FMF, Crovetto et al. and Serra et al. models detected 82.7% (95% CI, 69.6–95.8%), 73.8% (95% CI, 58.7–88.9%) and 79.8% (95% CI, 66.1–93.5%) of early PE; 72.7% (95% CI, 62.9–82.6%), 69.2% (95% CI, 58.8–79.6%) and 74.1% (95% CI, 64.2–83.9%) of preterm PE; and 55.1% (95% CI, 48.8–61.4%), 47.1% (95% CI, 40.6–53.5%) and 53.9% (95% CI, 47.4–60.4%) of all PE, respectively. The best correlation between predicted and observed cases was achieved by the FMF model, with an AUC of 0.911 (95% CI, 0.879–0.943), a slope of 0.983 (95% CI, 0.846–1.120) and an intercept of 0.154 (95% CI, –0.091 to 0.397). The NICE criteria identified 46.7% (95% CI, 35.3–58.0%) of preterm PE at 11% SPR and ACOG criteria identified 65.9% (95% CI, 55.4–76.4%) of preterm PE at 33.8% SPR. Conclusions: The best performance of screening for preterm PE is achieved by mathematical models that combine maternal factors with MAP, UtA‐PI and PlGF, as compared to risk‐scoring systems such as those of NICE and ACOG. While all three algorithms show similar results in terms of overall prediction, the FMF model showed the best performance at an individual level. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Effective first‐trimester screening for pre‐eclampsia (PE) can be achieved using a competing‐risks model that combines risk factors from the maternal history with multiples of the median (MoM) values of biomarkers. A new model using artificial intelligence through machine‐learning methods has been shown to achieve similar screening performance without the need for conversion of raw data of biomarkers into MoM. This study aimed to investigate whether this model can be used across populations without specific adaptations. Methods: Previously, a machine‐learning model derived with the use of a fully connected neural network for first‐trimester prediction of early (< 34 weeks), preterm (< 37 weeks) and all PE was developed and tested in a cohort of pregnant women in the UK. The model was based on maternal risk factors and mean arterial blood pressure (MAP), uterine artery pulsatility index (UtA‐PI), placental growth factor (PlGF) and pregnancy‐associated plasma protein‐A (PAPP‐A). In this study, the model was applied to a dataset of 10 110 singleton pregnancies examined in Spain who participated in the first‐trimester PE validation (PREVAL) study, in which first‐trimester screening for PE was carried out using the Fetal Medicine Foundation (FMF) competing‐risks model. The performance of screening was assessed by examining the area under the receiver‐operating‐characteristics curve (AUC) and detection rate (DR) at a 10% screen‐positive rate (SPR). These indices were compared with those derived from the application of the FMF competing‐risks model. The performance of screening was poor if no adjustment was made for the analyzer used to measure PlGF, which was different in the UK and Spain. Therefore, adjustment for the analyzer used was performed using simple linear regression. Results: The DRs at 10% SPR for early, preterm and all PE with the machine‐learning model were 84.4% (95% CI, 67.2–94.7%), 77.8% (95% CI, 66.4–86.7%) and 55.7% (95% CI, 49.0–62.2%), respectively, with the corresponding AUCs of 0.920 (95% CI, 0.864–0.975), 0.913 (95% CI, 0.882–0.944) and 0.846 (95% CI, 0.820–0.872). This performance was achieved with the use of three of the biomarkers (MAP, UtA‐PI and PlGF); inclusion of PAPP‐A did not provide significant improvement in DR. The machine‐learning model had similar performance to that achieved by the FMF competing‐risks model (DR at 10% SPR, 82.7% (95% CI, 69.6–95.8%) for early PE, 72.7% (95% CI, 62.9–82.6%) for preterm PE and 55.1% (95% CI, 48.8–61.4%) for all PE) without requiring specific adaptations to the population. Conclusions: A machine‐learning model for first‐trimester prediction of PE based on a neural network provides effective screening for PE that can be applied in different populations. However, before doing so, it is essential to make adjustments for the analyzer used for biochemical testing. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Epidemiological studies have established that women with pre‐eclampsia (PE) are at increased long‐term cardiovascular risk. Mild cardiac functional changes have been documented during pregnancy in women with PE, but their evolution from presentation to the postpartum period remains poorly defined. The aim of this study was to assess biventricular cardiovascular indices using novel and sensitive two‐dimensional and three‐dimensional (3D) echocardiographic modalities in pregnancy and to track alterations in both risk factors and cardiovascular indices in the postpartum period. Methods: A total of 59 women with PE were examined at 34 (interquartile range, 31–37) weeks' gestation and at 2–3 days, 3 months and 6 months postpartum. During pregnancy, 118 women with a normotensive pregnancy were also recruited as controls. Biventricular ejection fraction and left ventricular mass were measured by 3D echocardiography. Biventricular global longitudinal strain and strain of the left atrium were assessed using speckle‐tracking imaging. Results: In women with PE, compared with controls, there was lower left ventricular diastolic function (left atrial reservoir strain, 44.1% vs 49.2%) and increased left ventricular mass index (148 vs 128 g/m2), but there was no significant difference in right ventricular functional indices. These alterations in cardiac indices were mostly explained by differences in maternal risk factors. In the postpartum period, most cardiac indices improved by 3 months. Multivariable linear mixed‐model analysis demonstrated that this improvement was mostly attributed to reduction in weight and blood pressure. Conclusion: In women with PE, there is postpartum improvement in cardiac functional and structural indices in parallel with improvement in their risk factor profile. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the diagnostic accuracy of the Fetal Medicine Foundation (FMF) competing‐risks model, incorporating maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA‐PI) and placental growth factor (PlGF) (the 'triple test'), for the prediction at 11–13 weeks' gestation of preterm pre‐eclampsia (PE) in a Spanish population. Methods: This was a prospective cohort study performed in eight fetal medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with a singleton pregnancy and a non‐malformed live fetus attending a routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation were invited to participate. Maternal demographic characteristics and medical history were recorded and MAP, UtA‐PI, serum PlGF and pregnancy‐associated plasma protein‐A (PAPP‐A) were measured following standardized protocols. Treatment with aspirin during pregnancy was also recorded. Raw values of biomarkers were converted into multiples of the median (MoM), and audits were performed periodically to provide regular feedback to operators and laboratories. Patient‐specific risks for term and preterm PE were calculated according to the FMF competing‐risks model, blinded to pregnancy outcome. The performance of screening for PE, taking into account aspirin use, was assessed by calculating the area under the receiver‐operating‐characteristics curve (AUC) and detection rate (DR) at a 10% fixed screen‐positive rate (SPR). Risk calibration of the model was assessed. Results: The study population comprised 10 110 singleton pregnancies, including 72 (0.7%) that developed preterm PE. In the preterm PE group, compared to those without PE, median MAP MoM and UtA‐PI MoM were significantly higher, and median serum PlGF MoM and PAPP‐A MoM were significantly lower. In women with PE, the deviation from normal in all biomarkers was inversely related to gestational age at delivery. Screening for preterm PE by a combination of maternal characteristics and medical history with MAP, UtA‐PI and PlGF had a DR, at 10% SPR, of 72.7% (95% CI, 62.9–82.6%). An alternative strategy of replacing PlGF with PAPP‐A in the triple test was associated with poorer screening performance for preterm PE, giving a DR of 66.5% (95% CI, 55.8–77.2%). The calibration plot showed good agreement between predicted risk and observed incidence of preterm PE, with a slope of 0.983 (95% CI, 0.846–1.120) and an intercept of 0.154 (95% CI, −0.091 to 0.397). Conclusions: The FMF model is effective in predicting preterm PE in the Spanish population at 11–13 weeks' gestation. This method of screening is feasible to implement in routine clinical practice, but it should be accompanied by a robust audit and monitoring system, in order to maintain high‐quality screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

This article compares the predictive performance of three different mathematical models for screening pre-eclampsia (PE) in the first trimester of pregnancy. The models combine maternal risk factors with mean arterial pressure (MAP), uterine artery pulsatility index (UtPI), and serum placental growth factor (PlGF). The study, conducted in eight Spanish hospitals, included 10,110 singleton pregnancies. The results showed that all three models had similar overall prediction results and outperformed the scoring systems. However, the FMF model demonstrated the best performance at the individual level. [Extracted from the article]

This article evaluates the accuracy of using fetal biparietal diameter (BPD) at 11-13 weeks for pregnancy dating compared to the measurement of Crown-rump length (CRL). The study was conducted in Spain, UK, Belgium, and Bulgaria and included women with singleton, non-malformed fetus/neonate. The researchers developed a formula for pregnancy dating based on BPD and validated it against commonly used formulas. The results showed that pregnancy dating based on ultrasound measurement of fetal BPD is a reliable alternative to dating based on CRL. [Extracted from the article]

This article, published in the journal Ultrasound in Obstetrics & Gynecology, examines the effectiveness of the cerebro-placental ratio (CPR) in predicting adverse perinatal outcomes in uncomplicated singleton pregnancies attending a 40-42 week appointment. The study analyzed data from 3143 pregnancies and found that maternal age, body mass index, racial origin, parity, and labor induction were significant predictors of adverse perinatal outcomes. However, the addition of the CPR did not improve the predictive performance, and the CPR alone had a low detection rate. Therefore, the study concludes that the CPR is not a reliable predictor of adverse perinatal outcomes in post-term pregnancies. [Extracted from the article]

Objectives: To assess differences in cardiac morphology and function in fetuses of mothers with gestational diabetes mellitus (GDM) compared to controls, and to assess whether, in women with GDM, fetal cardiac changes are accentuated with advancing gestational age.Methods: We studied 112 women with GDM and 224 women with uncomplicated pregnancy at 24-40 weeks' gestation. In all fetuses, a standard four-chamber oblique view was obtained and offline speckle-tracking analysis was performed to measure right and left endocardial global longitudinal strain (GLS) and tricuspid and mitral annular plane systolic excursion. Global sphericity index was also calculated. Echocardiographic parameters were compared between GDM fetuses and controls at two gestational time periods of 24 + 0 to 32 + 0 weeks and 32 + 1 to 40 + 1 weeks.Results: At 24 + 0 to 32 + 0 weeks, we phenotyped 43 fetuses from mothers with GDM and 71 from uncomplicated pregnancies, and, at 32 + 1 to 40 + 1 weeks, we phenotyped 69 fetuses from mothers with GDM and 153 from women with uncomplicated pregnancy. In fetuses of mothers with GDM, compared to controls, right ventricular functional indices were consistently lower both at 24 + 0 to 32 + 0 weeks and at 32 + 1 to 40 + 1 weeks. Right ventricular GLS was reduced in the GDM group at 24 + 0 to 32 + 0 weeks (adjusted mean difference, 0.7%; 95% CI, 0.3-1.1%) and at 32 + 1 to 40 + 1 weeks (adjusted mean difference, 0.9%; 95% CI, 0.6-1.1%). Fetal left ventricular global longitudinal function was similar in GDM pregnancies compared with controls, with the exception of the contractility of the left ventricular basal segment, which was reduced. Global sphericity index was reduced in GDM pregnancies only at 32 + 1 to 40 + 1 weeks (adjusted mean difference, -0.4; 95% CI, -0.7 to 0.1).Conclusions: The offspring of women with GDM are at high risk for development of cardiovascular disease in childhood and early adulthood. Our study demonstrates that GDM is associated with a reduction mainly in fetal right ventricular function, compared to controls, and this response is not exaggerated with increasing gestational age. Further studies are needed to determine whether fetuses with the observed alterations in cardiac function are those at highest risk for subsequent development of cardiovascular disease. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: We have proposed previously that the competing-risks model for prediction of pre-eclampsia (PE) based on maternal characteristics and medical history (prior model), developed in singleton pregnancies, can be extended to risk assessment for twins; in dichorionic (DC) and monochorionic (MC) twin pregnancies with the same characteristics as in singleton pregnancies, the distribution of gestational age at delivery with PE was shifted to the left by 8 and 10 weeks, respectively. However, in a subsequent validation study, we found that, in both the training and validation datasets, the observed incidence of PE was lower than the predicted one and such overestimation of risk was particularly marked for early PE.Objectives: First, to develop a new extension of the competing-risks prior model in screening for PE by maternal demographic characteristics and medical history in twin pregnancies in a training dataset. Second, to examine the predictive performance of this model in screening for PE with delivery < 34 weeks (early PE), < 37 weeks (preterm PE) and at any gestational age (all PE) in twins in a validation dataset. Third, to demonstrate the application of screening in a mixed population of singleton and twin pregnancies.Methods: The data for this study were obtained from two prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation. The training and validation datasets consisted of 2219 and 2999 women, respectively. We used the training dataset to fit a model in which the effect of twins on shifting the distribution of gestational age at delivery with PE in singletons to the left should not be the same for all gestational ages but the shift should depend on the singleton prior mean; the effect increases with increasing prior mean. We examined the predictive performance of the model in the training and validation datasets using the area under the receiver-operating characteristics curve (AUC) and calibration plots. Data on 16 747 singleton pregnancies obtained from the Screening ProgRamme for prE-Eclampsia (SPREE) study were included to examine the performance of screening in a mixed population of singleton and twin pregnancies.Results: Calibration plots and calibration intercept and slope demonstrate superior predictive performance of the new model in the validation dataset. Although the AUC for twin pregnancies is lower than in singleton pregnancies, performance of screening in a mixed population of singleton and twin pregnancies is superior to that in singletons (AUC of 0.790 in a mixed population comprising 2% twins and 98% singletons compared to 0.775 in singletons). For the risk cut-offs likely to be used in practice, all twin pregnancies screen positive using maternal characteristics and medical history.Conclusions: A new competing-risks model in screening for PE by maternal risk factors in twin pregnancy has been developed and, using this model, the predicted risks for early PE, preterm PE and all PE are in relatively good agreement with the observed incidence of the disease. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: This meta-analysis aims to quantitatively summarize current data on various potential risk factors of velamentous cord insertion (VCI). A better understanding of these risk factors could enhance prenatal identification both in settings with routine screening and in those where universal screening for cord insertion anomalies is not yet recommended. Methods: A systematic search was conducted in MEDLINE, Cochrane Library, and Scopus from their inception until 7 February 2024. Eligible studies included observational studies of singleton pregnancies with VCI, identified either prenatally or postnatally, compared with pregnancies with central or eccentric cord insertion. Analyses were performed using DerSimonian and Laird random-effects models, with outcomes reported as risk ratios (RR) or mean differences with 95% confidence intervals (CI). Results: In total, 14 cohort and 4 case-control studies were included, reporting on 952,163 singleton pregnancies. Based on the cohort studies, the overall prevalence of VCI among singleton pregnancies was calculated to be 1.54%. The risk of VCI was significantly higher among pregnancies conceived using assisted reproductive technology (RR, 2.32; 95% CI: 1.77-3.05), nulliparous women (RR, 1.21; 95% CI: 1.15-1.28), women who smoked (RR, 1.14; 95% CI: 1.08-1.19), and pregnancies diagnosed with placenta previa (RR, 3.60; 95% CI: 3.04-4.28). Conclusions: This meta-analysis identified assisted reproductive technology, nulliparity, smoking, and placenta previa as significant risk factors of VCI among singleton pregnancies. These findings could inform screening policies in settings where universal screening for cord insertion is not routinely performed, suggesting a targeted approach for women with these specific risk factors.

Purpose: This study aimed to   investigate hematological and cardiac changes after early (ECC) versus delayed cord clamping (DCC) in preterm infants at 24-34 weeks of gestation., Methods: Ninety-six healthy pregnant women were assigned randomly to the ECC (< 10 s postpartum, n = 49) or DCC (45-60 s postpartum, n = 47). Primary endpoint was evaluation of neonatal hemoglobin, hematocrit and bilirrubin levels within the first 7 days after birth. A postpartum blood test was performed in the mother and a neonatal echocardiography in the first week of life., Results: We found differences in hematological parameters during the first week of life. On admission, the DCC group had higher hemoglobin levels than the ECC group (18.7 ± 3.0 vs. 16.8 ± 2.4, p < 0.0014) and higher hematocrit values (53.9 ± 8.0 vs. 48.8 ± 6.4, p < 0.0011). Around day 7 of life, hemoglobin levels were also higher in the DCC group compared with the ECC group (16.4 ± 3.8 vs 13.9 ± 2.5, p < 0.005), as was the hematocrit (49.3 ± 12.7 vs 41.2 ± 8.4, p < 0.0087). The need of transfusion was lower in the DCC compared to the ECC (8.5% vs 24.5%; OR: 0.29, 95% CI: 0.09-0.97, p < 0.036). The need for phototherapy was also higher in the DCC (80.9% vs 63.3%; OR: 0.23, 95% CI: 0.06-0.84, p < 0.026). No differences in cardiac parameters or maternal blood tests., Conclusion: DCC improved neonatal hematological parameters. No changes in cardiac function were found and maternal blood loss did not increase to require transfusion., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background : In pregnant women, COVID-19 can alter the metabolic environment, cell metabolism, and oxygen supply of trophoblastic cells and, therefore, have a negative influence on essential mechanisms of fetal development. The purpose of this study was to investigate, for the first time, the effects of COVID-19 infection during pregnancy with regard to the bone turnover and endocrine function of several metabolic biomarkers in colostrum and placenta. Methods : One hundred and twenty-four pregnant mothers were recruited from three hospitals between June 2020 and August 2021 and assigned to two groups: Control group and COVID-19 group. Metabolism biomarkers were addressed in placental tissue and colostrum. Results : Lipocalin-2 and resistin levels were higher in the placenta, revealing an underlying pro-inflammatory status in the gestation period for mothers suffering from COVID-19; a decrease in GLP-1 and leptin was also observed in this group. As for adiponectin, resistin, and insulin, their concentrations showed an increase; a decrease in GLP-1, leptin, and PYY was also reported in the colostrum of mothers suffering from COVID-19 compared with the control group. Conclusions : As for bone turnover, placental samples from mothers with COVID-19 showed lower levels of OPG, while DKK-1 increased compared with the control group. Colostrum samples showed higher levels of OPG, SOST, and PTH in the COVID-19 group, a fact that could have noteworthy implications for energy metabolism, fetal skeletal development, and postnatal bone density and mineralization. Further research is needed to explain the pathogenic mechanism of COVID-19 that may affect pregnancy, so as to assess the short-term and long-term outcomes in infants' health.

Preeclampsia (PE) is a multiorgan disorder that complicates around 2-8% of pregnancies and is a major cause of perinatal and maternal morbidity and mortality. PE is a clinical syndrome characterized by hypertension secondary to systemic inflammation, endothelial dysfunction, and syncytiotrophoblast stress leading to hypertension and multiorgan dysfunction. The uterine arteries are the main blood vessels that supply blood to the uterus. They give off branches and plays an important role in maintaining blood supply during pregnancy. The arcuate artery originates from the uterine artery and runs medially through the myometrium. The arcuate arteries divide almost directly into anterior and posterior branches, from which the radial artery leads directly to the uterine cavity during their course. Near the endometrium-myometrium junction, the radial artery generates spiral arteries within the basal layer and functional endometrium. The walls of radial and spiral arteries are rich in smooth muscle, which is lost when trophoblast cells invade and become large-caliber vessels. This physiological transformation of uteroplacental spiral arteries is critical for successful placental implantation and normal placental function. In normal pregnancy, the luminal diameter of the spiral arteries is greatly increased, and the vascular smooth muscle is replaced by trophoblast cells. This process and changes in the spiral arteries are called spiral artery remodeling. In PE, this genetically and immunologically governed process is deficient and therefore there is decreased vascular capacitance and increased resistance in the uteroplacental circulation. Furthermore, this defect in uteroplacental spiral artery remodeling is not only associated with early onset PE, but also with fetal growth restriction, placental abruption, and spontaneous premature rupture of membranes. Doppler ultrasound allows non-invasive assessment of placentation, while the flow impedance decreases as the pregnancy progresses in normal pregnancies, in those destined to develop preeclampsia the impedance is increased., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Objectives: Over the last few years, great interest has arisen in the role of the cerebroplacental ratio (CPR) to identify low-risk pregnancies at higher risk of adverse pregnancy outcomes. This study aimed to assess the predictive capacity of the CPR for adverse perinatal outcomes in all uncomplicated singleton pregnancies attending an appointment at 40-42 weeks. Materials and Methods : This is a retrospective cohort study including all consecutive singleton pregnancies undergoing a routine prenatal care appointment after 40 weeks in three maternity units in Spain and the United Kingdom from January 2017 to December 2019. The primary outcome was adverse perinatal outcomes defined as stillbirth or neonatal death, cesarean section or instrumental delivery due to fetal distress during labor, umbilical arterial cord blood pH < 7.0, umbilical venous cord blood pH < 7.1, Apgar score at 5 min < 7, and admission to the neonatal unit. Logistic mixed models and ROC curve analyses were used to analyze the data. Results: A total of 3143 pregnancies were analyzed, including 537 (17.1%) with an adverse perinatal outcome. Maternal age (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01 to 1.04), body mass index (OR 1.04, 95% CI 1.03 to 1.06), racial origin (OR 2.80, 95% CI 1.90 to 4.12), parity (OR 0.36, 95% CI 0.29 to 0.45), and labor induction (OR 1.79, 95% CI 1.36 to 2.35) were significant predictors of adverse perinatal outcomes with an area under the ROC curve of 0.743 (95% CI 0.720 to 0.766). The addition of the CPR to the previous model did not improve performance. Additionally, the CPR alone achieved a detection rate of only 11.9% (95% CI 9.3 to 15) when using the 10th centile as the screen-positive cutoff. Conclusions: Our data on late-term unselected pregnancies suggest that the CPR is a poor predictor of adverse perinatal outcomes.

Colostrum performs nutritional, anti-inflammatory and anti-infective functions and promotes immune system formation and organ development. The new coronavirus, SARS-CoV-2, has generated concerns about viral transmission through human milk, with a lack of evidence about human milk's protective effects against the infection. This study aimed at analyzing presence of the virus and at identifying the protein expression profile of human colostrum in active and COVID-19-recovered patients. Colostrum samples were collected from women with COVID-19 ( n = 3), women recently recovered from the infection ( n = 4), and non-infected women ( n = 5). The samples were analyzed by means of RT-qPCR to determine presence of the virus and using SWATH-MS for proteomic analysis. Proteomic results were then analyzed using bioinformatic methods. The viral tests were negative for SARS-CoV-2 in the colostrum from COVID-19 patients. The proteomic analysis identified 301 common proteins in all samples analyzed. Nineteen proteins were upregulated and 7 were downregulated in the COVID-19 group versus the control samples, whereas 18 were upregulated and 7 were downregulated when comparing the COVID-19 group to the recovered group. Eleven proteins were biomarkers of active COVID-19 infection. Ten were upregulated: ACTN1, CD36, FAM3B, GPRC5B, IGHA2, IGK, PLTP, RAC1, SDCBP and SERPINF1, and one was downregulated: PSAP. These proteins are mainly related to immunity, inflammatory response and protein transport. In conclusion, the results of this study suggest that colostrum is not a vehicle for mother-to-child SARS-CoV-2 transmission. Moreover, the colostrum's proteome of active and recuperated patients indicate that it could provide immune benefits to infants.

Introduction: Elevated plasma levels of extracellular vesicles have been associated with impaired placentation, angiogenesis imbalance, intravascular inflammation, and endothelial dysfunction in women with preeclampsia, thus suggesting that circulating vesicles may be a good therapeutic target for the treatment of the disease. Recently, statins have been considered a potential treatment for the prevention of preeclampsia because of their pleiotropic effects, including the improvement of endothelial dysfunction and inhibition of inflammatory responses. However, the effects of these drugs on circulating vesicles concentration in women at risk of preeclampsia have not been established. Herein, we aimed to assess the effects of pravastatin on circulating extracellular vesicle generation in women at high risk of term preeclampsia. Methods: In a sample of 68 singleton pregnant women participating in the multicenter, double-blind, placebo-controlled STATIN trial (Nº EducraCT 2016-005206-19 ISRCTN), 35 women received a placebo and 33 women received a 20 mg/day dose of pravastatin for approximately 3 weeks (from 35 to 37 weeks of gestation until delivery). Large extracellular vesicles were characterized and quantified by flow cytometry using annexin V and cell-specific antibodies directed against platelet, endothelial, leukocyte, and syncytiotrophoblast cell surface markers. Results: In women who received the placebo, a significant increase in the plasma levels of large extracellular vesicles from platelets (34%, p < 0.01), leukocytes (33%, p < 0.01), monocytes (60%, p < 0.01), endothelial cells (40%, p < 0.05), and syncytiotrophoblast cells (22%, p < 0.05) were observed. However, treatment with pravastatin significantly reduced the plasma levels of large extracellular vesicles from platelets (42%, p < 0.001), leukocytes (25%, p < 0.001), monocytes (61%, p < 0.001), endothelial cells (69%, p < 0.001), activated endothelial cells (55%, p < 0.001), and syncytiotrophoblast cells (44%, p < 0.001). Discussion: These results indicate that pravastatin reduces the levels of activated cell-derived membrane vesicles from the maternal vasculature, blood, and placental syncytiotrophoblast of women at high risk of term preeclampsia, suggesting that this statin may be beneficial in reducing endothelial dysfunction and pro-inflammatory and pro-coagulatory state characteristics of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Santoyo, Noguera, Avilés, Hernández-Caselles, de Paco-Matallana, Delgado, Cuevas, Llinás and Hernández.)

Introduction: To compare the conventional treatment of gestational diabetes mellitus (GDM) with flexible treatment according to the measurement of fetal abdominal circumference (AC) in daily clinical practice., Research Design and Methods: Two hundred and sixty pregnant women diagnosed with GDM before week 34 were randomly placed in two groups: a control group, treated according to maternal capillary glycemia, and an experimental group, treated according to ultrasound parameters of fetal growth. The glycemic targets in the control group were blood glucose levels when fasting and 1 hour postprandial (<95/140 mg/dL). In the experimental group, glycemic targets depended on the percentile (p) of fetal AC: if AC p <75th, then blood glucose targets when fasting and at 1 hour postprandial were <120/180 mg/dL; and if AC p ≥75th, then the glycemic targets were <80/120 mg/dL. The follow-up of both groups was scheduled according to the GDM protocol of our diabetes and gestation unit., Results: The study was completed by 246 pregnant women, 125 in the control group and 121 in the experimental group. In the experimental group, insulin treatment and neonatal hypoglycemia were significantly lower (p=0.018 and p 0.035, respectively). No differences were observed in large and small infants according to gestational age. However, macrosomic infants were less frequent in the experimental group, although this difference did not reach statistical significance. In terms of gestation complications, the type of delivery and its complications and the rest of the neonatal complications analyzed, no significant differences were observed., Conclusions: The treatment of flexible GDM according to the measurement of fetal AC is safe for the mother and the fetus and almost halves the number of pregnant women who require insulin treatment, without increasing the number of ultrasound checks or medical visits., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Oxidative and inflammatory stress, angiogenic imbalance, and endothelial dysfunction are pathophysiological mechanisms occurring in pre-eclampsia (PE) that may persist over time and predispose women to a higher risk of cardiovascular disease (CVD) in the future. However, there is little evidence on the vascular function of women at risk of PE who have not developed the disease. The main objective of this research is to study factors and biomarkers involved in endothelial dysfunction related to oxidative stress, angiogenic disbalance, and inflammation in women at high risk of term PE who do not develop the disease. An observational, analytical, retrospective, and descriptive study was carried out in a selected sample of 68 high-risk and 57 non-risk of term PE participants in the STATIN study (FFIS/2016/02/ST EUDRACT No: 2016-005206-19). A significant increase in mean arterial pressure (MAP) levels and oxidative stress biomarkers (uric acid, homocysteine, and total serum antioxidant capacity) was found. Biomarkers of inflammation (interleukin-6 and growth differentiation factor 15) and endothelial function (asymmetric dimethylarginine) were significantly elevated in the group at risk of pre-eclampsia. A significative dependence relationship was also established between MAP and interleukin-6 and uric acid. These results suggest that women at high risk of term PE may represent pregnancies with pre-existing maternal risk factors for CVD, manifested by the own cardiovascular overload of pregnancy. A better understanding of maternal cardiovascular function in pregnancy would allow the improved prediction of CVD late in life in women.

COVID-19 has reached pandemic proportions worldwide, with considerable consequences for both health and the economy. In pregnant women, COVID-19 can alter the metabolic environment, iron metabolism, and oxygen supply of trophoblastic cells, and therefore have a negative influence on essential mechanisms of fetal development. The purpose of this study was to investigate, for the first time, the effects of COVID-19 infection during pregnancy with regard to the oxidative/antioxidant status in mothers' serum and placenta, together with placental iron metabolism. Results showed no differences in superoxide dismutase activity and placental antioxidant capacity. However, antioxidant capacity decreased in the serum of infected mothers. Catalase activity decreased in the COVID-19 group, while an increase in 8-hydroxy-2'-deoxyguanosine, hydroperoxides, 15-FT-isoprostanes, and carbonyl groups were recorded in this group. Placental vitamin D, E, and Coenzyme-Q10 also showed to be increased in the COVID-19 group. As for iron-related proteins, an up-regulation of placental DMT1, ferroportin-1, and ferritin expression was recorded in infected women. Due to the potential role of iron metabolism and oxidative stress in placental function and complications, further research is needed to explain the pathogenic mechanism of COVID-19 that may affect pregnancy, so as to assess the short-term and long-term outcomes in mothers' and infants' health.

Background: Effective screening for term preeclampsia is provided by a combination of maternal factors with measurements of mean arterial pressure, serum placental growth factor, and serum soluble fms-like tyrosine kinase-1 at 35 to 37 weeks of gestation, with a detection rate of ≈75% at a screen-positive rate of 10%. However, there is no known intervention to reduce the incidence of the disease., Methods: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1120 women with singleton pregnancies at high risk of term preeclampsia to receive pravastatin at a dose of 20 mg/d or placebo from 35 to 37 weeks of gestation until delivery or 41 weeks. The primary outcome was delivery with preeclampsia at any time after randomization. The analysis was performed according to intention to treat., Results: A total of 29 women withdrew consent during the trial. Preeclampsia occurred in 14.6% (80 of 548) of participants in the pravastatin group and in 13.6% (74 of 543) in the placebo group. Allowing for the effect of risk at the time of screening and participating center, the mixed-effects Cox regression showed no evidence of an effect of pravastatin (hazard ratio for statin/placebo, 1.08 [95% CI, 0.78-1.49]; P =0.65). There was no evidence of interaction between the effect of pravastatin, estimated risk of preeclampsia, pregnancy history, adherence, and aspirin treatment. There was no significant between-group difference in the incidence of any secondary outcomes, including gestational hypertension, stillbirth, abruption, delivery of small for gestational age neonates, neonatal death, or neonatal morbidity. There was no significant between-group difference in the treatment effects on serum placental growth factor and soluble fms-like tyrosine kinase-1 concentrations 1 and 3 weeks after randomization. Adherence was good, with reported intake of ≥80% of the required number of tablets in 89% of participants. There were no significant between-group differences in neonatal adverse outcomes or other adverse events., Conclusions: Pravastatin in women at high risk of term preeclampsia did not reduce the incidence of delivery with preeclampsia. Registration: URL: https://www.isrctn.com; Unique identifier ISRCTN16123934.

Introduction: This study aimed to evaluate the quality of the brain volumes acquired following an evidence-based guideline for the acquisition of brain volumes., Material and Methods: This was a prospective multicenter study. Five centers recruited five cases each, acquiring two volumes per case, at different gestational age ranges. From the collected volumes, 10 operators performed an advanced neurosonography of each case. The evaluable anatomic structures were counted in each volume and expressed as a percentage. The results were compared with those obtained in a previous study where no recommendations had been made for the acquisition of the volumes., Results: Five hundred evaluations were included in the study. In the axial plane, 91.5% of the structures were satisfactorily evaluated, 81.8% in the coronal plane and 89.9% in the sagittal plane. These results were significantly better than those obtained in a previous study where the volumes had been acquired without any guidelines and the percentage of evaluable structures were 80% (P < .001), 67.1% (P < .001) and 55.1% (P < .001) in the axial, coronal and sagittal planes, respectively., Conclusions: The application of an evidence-based guideline for the acquisition of brain volumes improves the quality of these by increasing the number of evaluable structures in the volume., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). Published by John Wiley & Sons Ltd.)

Background: In women with a singleton pregnancy and sonographic short cervix in midgestation, vaginal administration of progesterone reduces the risk of early preterm birth and improves neonatal outcomes without any demonstrable deleterious effects on childhood neurodevelopment. In women with twin pregnancies, the rate of spontaneous early preterm birth is 10 times higher than that in singletons, and in this respect, all twins are at an increased risk of preterm birth. However, 6 trials in unselected twin pregnancies reported that vaginal administration of progesterone from midgestation had no significant effect on the incidence of early preterm birth. Such apparent lack of effectiveness of progesterone in twins may be due to inadequate dosage or treatment that is started too late in pregnancy., Objective: The early vaginal progesterone for the prevention of spontaneous preterm birth in twins, a randomized, placebo-controlled, double-blind trial, was designed to test the hypothesis that among women with twin pregnancies, vaginal progesterone at a dose of 600 mg per day from 11 to 14 until 34 weeks' gestation, as compared with placebo, would result in a significant reduction in the incidence of spontaneous preterm birth between 24 +0 and 33 +6 weeks., Study Design: The trial was conducted at 22 hospitals in England, Spain, Bulgaria, Italy, Belgium, and France. Women were randomly assigned in a 1:1 ratio to receive either progesterone or placebo, and in the random-sequence generation, there was stratification according to the participating center. The primary outcome was spontaneous birth between 24 +0 and 33 +6 weeks' gestation. Statistical analyses were performed on an intention-to-treat basis. Logistic regression analysis was used to determine the significance of difference in the incidence of spontaneous birth between 24 +0 and 33 +6 weeks' gestation between the progesterone and placebo groups, adjusting for the effect of participating center, chorionicity, parity, and method of conception. Prespecified tests of treatment interaction effects with chorionicity, parity, method of conception, compliance, and cervical length at recruitment were performed. A post hoc analysis using mixed-effects Cox regression was used for further exploration of the effect of progesterone on preterm birth., Results: We recruited 1194 women between May 2017 and April 2019; 21 withdrew consent and 4 were lost to follow-up, which left 582 in the progesterone group and 587 in the placebo group. Adherence was good, with reported intake of ≥80% of the required number of capsules in 81.4% of the participants. After excluding births before 24 weeks and indicated deliveries before 34 weeks, spontaneous birth between 24 +0 and 33 +6 weeks occurred in 10.4% (56/541) of participants in the progesterone group and in 8.2% (44/538) in the placebo group (odds ratio in the progesterone group, adjusting for the effect of participating center, chorionicity, parity, and method of conception, 1.35; 95% confidence interval, 0.88-2.05; P=.17). There was no evidence of interaction between the effects of treatment and chorionicity (P=.28), parity (P=.35), method of conception (P=.56), and adherence (P=.34); however, there was weak evidence of an interaction with cervical length (P=.08) suggestive of harm to those with a cervical length of ≥30 mm (odds ratio, 1.61; 95% confidence interval, 1.01-2.59) and potential benefit for those with a cervical length of <30 mm (odds ratio, 0.56; 95% confidence interval, 0.20-1.60). There was no evidence of difference between the 2 treatment groups for stillbirth or neonatal death, neonatal complications, neonatal therapy, and poor fetal growth. In the progesterone group, 1.4% (8/582) of women and 1.9% (22/1164) of fetuses experienced at least 1 serious adverse event; the respective numbers for the placebo group were 1.2% (7/587) and 3.2% (37/1174) (P=.80 and P=.06, respectively). In the post hoc time-to-event analysis, miscarriage or spontaneous preterm birth between randomization and 31 +6 weeks' gestation was reduced in the progesterone group relative to the placebo group (hazard ratio, 0.23; 95% confidence interval, 0.08-0.69)., Conclusion: In women with twin pregnancies, universal treatment with vaginal progesterone did not reduce the incidence of spontaneous birth between 24 +0 and 33 +6 weeks' gestation. Post hoc time-to-event analysis led to the suggestion that progesterone may reduce the risk of spontaneous birth before 32 weeks' gestation in women with a cervical length of <30 mm, and it may increase the risk for those with a cervical length of ≥30 mm., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: Timing of cord clamping and other cord management strategies may improve outcomes at preterm birth. However, it is unclear whether benefits apply to all preterm subgroups. Previous and current trials compare various policies, including time-based or physiology-based deferred cord clamping, and cord milking. Individual participant data (IPD) enable exploration of different strategies within subgroups. Network meta-analysis (NMA) enables comparison and ranking of all available interventions using a combination of direct and indirect comparisons., Objectives: (1) To evaluate the effectiveness of cord management strategies for preterm infants on neonatal mortality and morbidity overall and for different participant characteristics using IPD meta-analysis. (2) To evaluate and rank the effect of different cord management strategies for preterm births on mortality and other key outcomes using NMA., Methods and Analysis: Systematic searches of Medline, Embase, clinical trial registries, and other sources for all ongoing and completed randomised controlled trials comparing cord management strategies at preterm birth (before 37 weeks' gestation) have been completed up to 13 February 2019, but will be updated regularly to include additional trials. IPD will be sought for all trials; aggregate summary data will be included where IPD are unavailable. First, deferred clamping and cord milking will be compared with immediate clamping in pairwise IPD meta-analyses. The primary outcome will be death prior to hospital discharge. Effect differences will be explored for prespecified participant subgroups. Second, all identified cord management strategies will be compared and ranked in an IPD NMA for the primary outcome and the key secondary outcomes. Treatment effect differences by participant characteristics will be identified. Inconsistency and heterogeneity will be explored., Ethics and Dissemination: Ethics approval for this project has been granted by the University of Sydney Human Research Ethics Committee (2018/886). Results will be relevant to clinicians, guideline developers and policy-makers, and will be disseminated via publications, presentations and media releases., Registration Number: Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12619001305112) and International Prospective Register of Systematic Reviews (PROSPERO, CRD42019136640)., Competing Interests: Competing interests: LD, ACK, CDPM, ED, HR, JK, JM, JJ, KF, OA, SH, VS, VD, WE-N and WT-M are Chief Investigators for potentially eligible trials., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)