Cristina Trilla

Introduction: Preeclampsia and fetal growth restriction, which are clinical presentations of placental dysfunction, are frequently associated with angiogenic imbalance during pregnancy and increased long‐term cardiovascular risk. Whether this risk is driven by the pre‐pregnancy risk factors, clinical disease, or by an elevated sFlt‐1/PlGF ratio remains unclear. This study aimed to assess the association between vascular assessments (ophthalmic artery Doppler and carotid intima‐media thickness) 3–6 years postpartum and a history of preeclampsia and fetal growth restriction, and to evaluate if associations were impacted by an angiogenic imbalance during pregnancy. Material and Methods: This was a cross‐sectional study, which included individuals prospectively recruited during their index pregnancy between 2018 and 2021 and re‐evaluated 3–6 years postpartum. Preeclampsia, fetal growth restriction, and sFlt‐1/PlGF values were defined from pregnancy data. Postpartum assessment included ophthalmic artery Doppler and carotid intima‐media thickness performed by a single operator. Multivariable linear regression models assessed associations between placental dysfunction, angiogenic imbalance, and vascular parameters, adjusting for maternal covariates. Results: 354 participants were included, 148 with and 206 without a history of preeclampsia or fetal growth restriction. Both placental dysfunction and angiogenic imbalance during pregnancy were independently associated with a significantly higher ophthalmic artery peak systolic velocity ratio 3–6 years postpartum. Participants with a history of placental dysfunction showed higher values compared to those without [0.75 (0.67–0.81) vs. 0.69 (0.63–0.78), p = 0.03], as did those with an elevated sFlt‐1/PlGF ratio during pregnancy [0.76 (0.66–0.82) vs. 0.70 (0.64–0.78), p = 0.03]. The highest values were observed in women who had experienced both conditions. When preeclampsia and fetal growth restriction were analyzed separately, the association remained significant for preeclampsia, whereas in the fetal growth restriction group, a significant difference was observed only in the right eye. No statistically significant differences were observed in carotid intima‐media thickness. Conclusions: Both a history of angiogenic imbalance and a clinical placental dysfunction presentation (particularly preeclampsia) during pregnancy were associated with increased ophthalmic artery peak systolic velocity ratio 3–6 years postpartum, whereas carotid intima‐media thickness did not differ between the study groups.

Objective: To evaluate the impact of low‐dose aspirin (LDA) on placental size and uterine artery pulsatility index (UtA‐PI) by analyzing longitudinal changes between the first and second trimesters in pregnancies at high risk for early‐onset pre‐eclampsia (PE). Methods: This was a prospective observational cohort study of 631 singleton pregnancies. Women at high risk of early‐onset PE (delivery ≤ 33 + 6 weeks) were identified using maternal factors or a multivariate screening protocol and were prescribed LDA. Placental size was assessed using two‐ and three‐dimensional ultrasonography, and UtA‐PI was measured using transabdominal Doppler, with measurements obtained in the first and second trimesters. Differences in placental measurements and UtA‐PI between high‐risk women receiving LDA and low‐risk untreated women were analyzed. Results: Among the 631 participants, 53 (8.4%) women were prescribed LDA for the prevention of early‐onset PE. Placental size in the first trimester was significantly smaller in the LDA group compared with the untreated group, as exemplified by placental volume (mean ± SD, 68.46 ± 25.19 cm ³ vs 76.31 ± 23.63 cm ³ ; P = 0.022), and this trend persisted into the second trimester. However, no significant differences in placental growth from the first to the second trimester were observed between the groups. UtA‐PI was significantly higher in the LDA group in both trimesters, but a greater decrease in UtA‐PI multiples of the median values between trimesters was noted in these women (mean ± SD, –14.0 ± 0.28% vs –4.5 ± 0.31%; P = 0.021). Perinatal outcomes were similar between the groups, with the exception of a higher rate of Cesarean delivery in the LDA group (38.5% vs 21.1%; P = 0.008). Conclusions: Women at high risk for early‐onset PE have a smaller placenta and higher UtA‐PI in the first and second trimesters. Treatment of high‐risk women with LDA did not affect placental growth but was associated with a greater reduction in UtA‐PI, suggesting a positive effect of LDA on placental perfusion. These findings provide insight into the mechanism of action of LDA in the prevention of PE. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objective: To describe first-trimester maternal, biochemical, biophysical, and ultrasound characteristics in women with recurrent pregnancy loss (RPL) compared to women without RPL. Methods: This was a retrospective cohort study analyzing data from 4440 pregnant women, including 142 women with previous RPL. Maternal and pregnancy characteristics, first-trimester biochemical markers, biophysical assessments, early-onset preeclampsia (EOPE) risk, and perinatal outcomes were compared. Results: Women with RPL were older (37.8 vs. 34.0 years, p < 0.001) and had higher rates of antiphospholipid syndrome (4.9% vs. 0.9%, p < 0.001), other thrombophilias (5.6% vs. 0.8%, p < 0.001), and thyroid disorders (14% vs. 7.5%, p = 0.010) than women without RPL. First-trimester uterine artery pulsatility index (UtA-PI) values, pregnancy-associated plasma protein-A (PAPP-A) levels, mean arterial pressure, and final risk for EOPE were comparable between groups. However, the RPL group had higher rates of very high risk for PE (10.6 vs. 5.1, p = 0.011). Likewise, second-trimester UtA-PI was higher in this group (1.10 vs. 1.01, p = 0.045). Aspirin and low molecular weight heparin prophylaxis were more frequent in women with RPL (23.8% vs. 9.6%, p < 0.001; 14.7% vs. 0.1%, p < 0.001). Regarding perinatal outcomes, we found a higher incidence of second-trimester intrauterine demise in the RPL group (6.4% vs. 1.4%, p = 0.011), with no other differences observed in the remaining outcomes. Conclusions: Women with RPL exhibit distinct maternal characteristics and worse pregnancy outcomes, although first-trimester markers do not seem to significantly differ from findings in women without RPL. These findings underscore the importance of tailored screening and intervention protocols to improve perinatal outcomes in this high-risk population.

Objective: To describe first-trimester maternal, biochemical, biophysical, and ultrasound characteristics in women with recurrent pregnancy loss (RPL) compared to women without RPL. Methods: Retrospective cohort study analyzing data from 4440 pregnant women, including 142 women with previous RPL. Maternal and pregnancy characteristics, first-trimester biochemical markers, biophysical assessments, early-onset preeclampsia (EOPE) risk and perinatal outcomes were compared. Results: Women with RPL were older (37.8 vs. 34.0 years, p < 0.001), had higher rates of antiphospholipid syndrome (4.9% vs. 0.9%, p< 0.001), other thrombophilias (5.6% vs. 0.8%, p < 0.001) and thyroid disorders (14% vs. 7.5%, p=0.010) than women without RPL. Uterine artery pulsatility index (UtA-PI) values, pregnancy-associated plasma protein-A (PAPP-A) levels, mean arterial pressure and final risk for EOPE were comparable between groups. However, RPL group had higher rates of very-high risk for PE (10.6 vs 5.1, p=0.011). Likewise, second-trimester UtA-PI was higher in this group (1.10 vs. 1.01, p=0.045). Aspirin and low molecular weight heparin prophylaxis were more frequent in women with RPL (23.8% vs. 9.6%, p < 0.001; 14.7% vs. 0.1%, p< 0.001). Regarding perinatal outcomes, we found a higher incidence of second trimester intrauterine demise in the RPL group (6.4% vs. 1.4%, p=0.011), with no other differences observed in other outcomes. Conclusions: Women with RPL exhibit distinct maternal characteristics and worse pregnancy outcomes, although first-trimester markers do not seem to significantly differ from findings in women without RPL. These findings underscore the importance of tailored screening and intervention protocols to improve perinatal outcomes in this high-risk population.

Objective: The purpose of this study was to provide gestational age (GA) specific reference ranges for 2-dimensional (2D) placental biometry and 3-dimensional (3D) placental volume between 11 and 14 weeks of gestation. Methods: Placental biometry including 2D and 3D variables was calculated in 1142 first-trimester singleton pregnancies with non-complicated outcome between September 2016 and February 2020. Ultrasound datasets were obtained at the time of the first-trimester ultrasound, and 2D basal plate (BP), chorionic plate (CP), placental thickness (PT), and 3D placental volume (PV) were measured following a standardized methodology. Reference ranges for each variable were calculated according to GA and crown-rump-length (CRL). Results: A total of 1142 uncomplicated pregnancies were considered for analysis. All placental measurements increased significantly between 11 and 14 weeks, especially for PT (39.64%) and PV (64.4%). Reference ranges were constructed for each 2D and 3D first-trimester placental variable using the best-fit regression model for the predicted mean and SD as a function of GA and CRL. Conclusions: Reference ranges of 2D placental biometry and 3D placental volume between 11 and 14 weeks of gestation were constructed, generating reference values. Placental biometry showed a progressive increase during the first trimester. This highlights the importance of using reference range charts according to GA.

Algorithms for first-trimester prediction of pre-eclampsia usually include maternal risk factors, blood pressure, placental growth factor (PlGF), and uterine artery Doppler pulsatility index. However, these models lack sensitivity for the prediction of late-onset pre-eclampsia and other placental complications of pregnancy, such as small for gestational age infants or preterm birth. The aim of this study was to assess the screening performance of PlGF, soluble fms-like tyrosine kinase-1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), uric acid, and high-sensitivity cardiac troponin T (hs-TnT) in the prediction of adverse obstetric outcomes related to placental insufficiency. This retrospective case–control study was based on a cohort of 1390 pregnant women, among which 210 presented pre-eclampsia, small for gestational age infants, or preterm birth. Two hundred and eight women with healthy pregnancies were selected as controls. Serum samples were collected between weeks 9 and 13 of gestation, and maternal serum concentrations of PlGF, sFlt-1, NT-proBNP, uric acid, and hs-TnT were measured. Multivariate regression analysis was used to generate predictive models combining maternal factors with the above-mentioned biomarkers. Women with placental dysfunction had lower median concentrations of PlGF (25.77 vs. 32.00 pg/mL; p < 0.001), sFlt-1 (1212.0 vs. 1363.5 pg/mL; p = 0.001), and NT-proBNP (51.22 vs. 68.71 ng/L; p < 0.001) and higher levels of uric acid (193.66 µmol/L vs. 177.40 µmol/L; p = 0.001). There was no significant difference between groups regarding the sFlt-1/PlGF ratio. Hs-TnT was not detected in 70% of the maternal serums analyzed. Altered biomarker concentrations increased the risk of the analyzed complications both in univariate and multivariate analyses. The addition of PlGF, sFlt-1, and NT-proBNP to maternal variables improved the prediction of pre-eclampsia, small for gestational age infants, and preterm birth (area under the curve: 0.710, 0.697, 0.727, and 0.697 vs. 0.668, respectively). Reclassification improvement was greater in maternal factors plus the PlGF model and maternal factors plus the NT-p roBNP model (net reclassification index, NRI: 42.2% and 53.5%, respectively). PlGF, sFlt-1, NT-proBNP, and uric acid measurements in the first trimester of pregnancy, combined with maternal factors, can improve the prediction of adverse perinatal outcomes related to placental dysfunction. In addition to PlGF, uric acid and NT-proBNP are two promising predictive biomarkers for placental dysfunction in the first trimester of pregnancy.

Background: Vasa previa consists in the presence of extraplacental fetal vessels overlying the cervix. This condition is commonly associated with fatal outcome if prenatally undiagnosed. Two types of vasa previa have been classically described, associated with well-established risk factors. However, a rare third type of vasa previa has also been reported. Case: We present a case of type 3 vasa previa diagnosed in the second trimester, with two fetal vessels overlying the cervix. The placenta was unilobed, not previa, and the cord insertion was marginal. Placental examination after delivery confirmed the prenatal findings. Conclusion: This case suggests that vasa previa can occur in the absence of cord or placental anomalies. A review of vasa previa classification and screening strategies for this condition is needed.

Objectives: Several multivariate algorithms for preeclampsia (PE) screening in the first trimester have been developed over the past few years. These models include maternal factors, mean arterial pressure (MAP), uterine artery Doppler (UtA-PI), and biochemical markers (pregnancy-associated plasma protein-A (PAPP-A) or placental growth factor (PlGF)). Treatment with low-dose aspirin (LDA) has shown a reduction in the incidence of preterm PE in women with a high-risk assessment in the first trimester. An important barrier to the implementation of first-trimester screening is the cost of performing tests for biochemical markers in the whole population. Theoretical contingent strategies suggest that two-stage screening models could also achieve high detection rates for preterm PE with lower costs. However, no data derived from routine care settings are currently available. This study was conducted to validate and assess the performance of a first-trimester contingent screening process using PlGF for PE, with prophylactic LDA, for decreasing the incidence of preterm PE. Methods: This was a two-phase study. In phase one, a contingent screening model for PE was developed using a multivariate validated model and a historical cohort participating in a non-interventional PE screening study (n = 525). First-stage risk assessment included maternal factors, MAP, UtA-PI, and PAPP-A. Several cut-off levels were tested to determine the best screening performance, and three groups were then defined (high-, medium-, and low-risk groups). PlGF was determined in the medium-risk group to calculate the final risk. Phase two included a validation cohort of 847 singleton pregnancies prospectively undergoing first-trimester PE screening using this approach. Women at high risk of PE received prophylactic treatment with 150 mg of LDA. The clinical impact of the model was evaluated by comparing the incidence of early-onset (p = 0.031) after one year of screening implementation. Conclusions: Implementation of contingent screening for PE using PlGF in a routine care setting led to a significant reduction (68.4%) in preterm PE, suggesting that contingent screening can achieve similar results to protocols using PlGF in the whole population. This could have financial benefits, with a similar reduction in the rate of preterm PE.

The outbreak of a pandemic has negative psychological effects. We aimed to determine the impact of the SARS-CoV-2 pandemic during pregnancy and identify the risk factors for maternal well-being. A multicenter, prospective, population-based study was carried out that included women (n = 1320) who were pregnant during the SARS-CoV-2 pandemic in Barcelona (Spain) compared against a pre-pandemic cohort (n = 345). Maternal well-being was assessed using the validated World Health Organization Well-Being Index Questionnaire (WHO-5 Index). Pregnant women attended during the COVID-19 pandemic showed worst WHO-5 well-being scores (median (IQR) of 56 (36–72) for the pandemic cohort vs. 64 (52–76) for the pre-pandemic cohort p < 0.001), with 42.8% of women presenting a poor well-being score vs. 28% for the pre-pandemic cohort (p < 0.001). Presence of a previous psychiatric disorder (OR 7.1; 95% CI 2.6–19, p < 0.001), being in the third trimester of pregnancy (OR 1.7; 95% CI 1.5–2, p < 0.001), or requiring hospital admission for COVID-19 (OR 4.7; 95% CI 1.4–16.7, p = 0.014), significantly contributed to low maternal well-being during the COVID-19 pandemic (multivariate analysis). Being infected by SARS-CoV-2 was not associated with a lower well-being score. We conclude that, during the COVID-19 pandemic, there were higher rates of poor maternal well-being; the infection of SARS-CoV-2 itself did not worsen maternal well-being, but other factors as psychiatric disorders, being in the third trimester of pregnancy or hospital admission for COVID-19 disease did.