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Introduction: This study aims to evaluate the safety of discontinuing aspirin treatment at 24-28 weeks in women at high risk after first-trimester combined screening for preeclampsia (PE) and normal placental growth factor (PlGF) levels at 24-28 weeks of gestation., Material and Methods: This is a post hoc analysis of the StopPRE trial, conducted at nine Spanish maternity hospitals from September 2019 to September 2021. In the StopPRE trial, all high-risk single pregnancies identified during first-trimester screening for PE were treated with 150 mg of daily aspirin. Out of 1604 eligible women with a soluble fms-like tyrosine kinase-1 to PlGF ratio (sFlt-1/PlGF) ≤38 at 24-28 weeks, 968 were randomly assigned in a 1:1 ratio to either continue aspirin until 36 weeks (control group) or discontinue it (intervention group). In this secondary analysis, only women with PlGF ≥100 pg/mL at 24-28 weeks were included. As in the StopPRE trial, the non-inferiority margin was set at a 1.9% difference in preterm PE incidence between the groups., Results: Among the 13 983 screened pregnant women, 1984 (14.2%) were deemed high-risk for preterm PE, of which 397 (20.0%) were ineligible, 636 declined participation, and 32 were excluded. Ultimately, 919 women with PlGF >100 pg/mL were randomized and included in this analysis. Preterm PE occurred in 0.9% of the intervention group (4 out of 465) and 1.5% of the control group (7 out of 454), indicating non-inferiority of aspirin discontinuation. There were no significant differences between the groups in adverse pregnancy outcomes before 37 weeks, at <34 weeks, or ≥37 weeks. Minor antepartum hemorrhage incidence was significantly lower in the intervention group (absolute difference, -5.96; 95% CI, -10.10 to -1.82)., Conclusions: Discontinuation of aspirin treatment at 24-28 weeks in women with PlGF levels ≥100 pg/mL was non-inferior to continuing until 36 weeks for preventing preterm PE. However, these findings should be interpreted with caution, as they originate from a subanalysis of the StopPRE trial., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: To assess whether aspirin treatment can be discontinued in pregnancies with normal uterine artery pulsatility index (≤90th percentile) at 24-28 weeks., Design: Post-hoc analysis of a clinical trial., Setting: Nine maternity hospitals in Spain., Population or Sample: Pregnant individuals at high risk of pre-eclampsia at 11-13 weeks and normal uterine artery Doppler at 24-28 weeks., Methods: All participants received treatment with daily aspirin at a dose of 150 mg. Participants were randomly assigned, in a 1:1 ratio, either to continue aspirin treatment until 36 weeks (control group) or to discontinue aspirin treatment (intervention group), between September 2019 and September 2021. In this secondary analysis, women with a UtAPI >90th percentile at 24-28 weeks were excluded. The non-inferiority margin was set at a difference of 1.9% for the incidence of preterm pre-eclampsia., Main Outcome Measures: Incidence of preterm pre-eclampsia., Results: Of the 1611 eligible women, 139 were excluded for UtAPI >90th percentile or if UtAPI was not available. Finally, 804 were included in this post-hoc analysis. Preterm pre-eclampsia occurred in three of 409 (0.7%) women in the aspirin discontinuation group and five of 395 (1.3%) women in the continuation group (-0.53; 95% CI -1.91 to 0.85), indicating non-inferiority of aspirin discontinuation., Conclusions: Discontinuing aspirin treatment at 24-28 weeks in women with a UtAPI ≤90th percentile was non-inferior to continuing aspirin treatment until 36 weeks for preventing preterm pre-eclampsia., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Introduction: Pre-eclampsia affects 2%-8% of pregnancies and is one of the leading causes of maternal and perinatal morbidity and mortality. First-trimester screening using an algorithm that combines maternal characteristics, mean arterial blood pressure, uterine artery pulsatility index and biomarkers (pregnancy-associated plasma protein-A and placental growth factor) is the method that achieves a greater diagnostic accuracy. It has been shown that daily salicylic acid administration before 16 weeks in women at a high risk for pre-eclampsia can reduce the incidence of preterm pre-eclampsia. However, no previous studies have evaluated the impact of routine first-trimester combined screening for pre-eclampsia with placental growth factor after being implemented in the clinical practice., Material and Methods: This was a multicenter cohort study conducted in eight different maternities across Spain. Participants in the reference group were prospectively recruited between October 2015 and September 2017. Participants in the study group were retrospectively recruited between March 2019 and May 2021. Pre-eclampsia risk was calculated between 11 +0 and 13 +6  weeks using the Gaussian algorithm combining maternal characteristics, mean arterial pressure, uterine arteries pulsatility index, pregnancy-associated plasma protein-A and placental growth factor. Patients with a risk greater than 1/170 were prescribed daily salicylic acid 150 mg until 36 weeks. Patients in the reference group did not receive salicylic acid during gestation., Results: A significant reduction was observed in preterm pre-eclampsia (OR 0.47; 95% CI: 0.30-0.73), early-onset (<34 weeks) pre-eclampsia (OR 0.35; 95% CI: 0.16-0.77), preterm small for gestational age newborn (OR 0.57; 95% CI: 0.40-0.82), spontaneous preterm birth (OR 0.72; 95% CI: 0.57-0.90), and admission to intensive care unit (OR 0.55; 95% CI: 0.37-0.81). A greater treatment adherence resulted in a significant reduction in adverse outcomes., Conclusions: Routine first-trimester screening for pre-eclampsia with placental growth factor leads to a reduction in preterm pre-eclampsia and other pregnancy complications. Aspirin treatment compliance has a great impact on the effectiveness of this screening program., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Importance: Aspirin reduces the incidence of preterm preeclampsia by 62% in pregnant individuals at high risk of preeclampsia. However, aspirin might be associated with an increased risk of peripartum bleeding, which could be mitigated by discontinuing aspirin before term (37 weeks of gestation) and by an accurate selection of individuals at higher risk of preeclampsia in the first trimester of pregnancy., Objective: To determine whether aspirin discontinuation in pregnant individuals with normal soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1:PlGF) ratio between 24 and 28 weeks of gestation was noninferior to aspirin continuation to prevent preterm preeclampsia., Design, Setting, and Participants: Multicenter, open-label, randomized, phase 3, noninferiority trial conducted in 9 maternity hospitals across Spain. Pregnant individuals (n = 968) at high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24 to 28 weeks of gestation were recruited between August 20, 2019, and September 15, 2021; of those, 936 were analyzed (intervention: n = 473; control: n = 463). Follow-up was until delivery for all participants., Interventions: Enrolled patients were randomly assigned in a 1:1 ratio to aspirin discontinuation (intervention group) or aspirin continuation until 36 weeks of gestation (control group)., Main Outcomes and Measures: Noninferiority was met if the higher 95% CI for the difference in preterm preeclampsia incidences between groups was less than 1.9%., Results: Among the 936 participants, the mean (SD) age was 32.4 (5.8) years; 3.4% were Black and 93% were White. The incidence of preterm preeclampsia was 1.48% (7/473) in the intervention group and 1.73% (8/463) in the control group (absolute difference, -0.25% [95% CI, -1.86% to 1.36%]), indicating noninferiority., Conclusions and Relevance: Aspirin discontinuation at 24 to 28 weeks of gestation was noninferior to aspirin continuation for preventing preterm preeclampsia in pregnant individuals at high risk of preeclampsia and a normal sFlt-1:PlGF ratio., Trial Registration: ClinicalTrials.gov Identifier: NCT03741179 and ClinicalTrialsRegister.eu Identifier: 2018-000811-26.

Objective: To evaluate the clinical effectiveness of the routine first-trimester screening for preeclampsia (PE) after being implemented in six Catalan maternities., Methods: Participants in the reference group were recruited prospectively between October 2015 and September 2017. Participants in the study group were recruited retrospectively between November 2018 and May 2019, after implementing the screening program. PE risk was assessed between 11 + 0 and 13 + 6 weeks of gestation using the Gaussian algorithm combining maternal characteristics, mean arterial blood pressure, uterine artery pulsatility index, and maternal serum pregnancy-associated plasma protein-A. Women with a risk ≥1/137 were prescribed daily salicylic acid (150 mg) until 36 weeks of gestation., Results: Preterm PE occurred in 30 of 2641 participants (1.14%) in the reference group, as compared with 18 of 2848 participants (0.63%) in the study group (OR: 0.55; 95% CI, 0.31-0.99; P = 0.045). In the reference group, 37 participants (1.40%) were admitted to ICU, as compared with 23 participants (0.81%) in the study group (OR: 0.57; 95% CI, 0.34-0.96; P = 0.035)., Conclusion: The routine first-trimester PE screening can be implemented in a public healthcare setting, leading to a significant reduction in the incidence of preterm PE and of maternal ICU admission., (© 2022 International Federation of Gynecology and Obstetrics.)

Background: Fetal smallness affects 10% of pregnancies. Small fetuses are at a higher risk of adverse outcomes. Their management using estimated fetal weight and feto-maternal Doppler has a high sensitivity for adverse outcomes; however, more than 60% of fetuses are electively delivered at 37 to 38 weeks. On the other hand, classification using angiogenic factors seems to have a lower false-positive rate. Here, we present a protocol for the Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) trial, which compares the use of angiogenic factors and Doppler to manage small fetuses at term., Objective: The primary objective is to demonstrate that classification based on angiogenic factors is not inferior to estimated fetal weight and Doppler at detecting fetuses at risk of adverse perinatal outcomes., Methods: This is a multicenter, open-label, randomized controlled trial conducted in 20 hospitals across Spain. A total of 1030 singleton pregnancies with an estimated fetal weight ≤10th percentile at 36+0 to 37+6 weeks+days will be recruited and randomly allocated to either the control or the intervention group. In the control group, standard Doppler-based management will be used. In the intervention group, cases with a soluble fms-like tyrosine kinase to placental growth factor ratio ≥38 will be classified as having fetal growth restriction; otherwise, they will be classified as being small for gestational age. In both arms, the fetal growth restriction group will be delivered at ≥37 weeks and the small for gestational age group at ≥40 weeks. We will assess differences between the groups by calculating the relative risk, the absolute difference between incidences, and their 95% CIs., Results: Recruitment for this study started on September 28, 2020. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences in early 2023., Conclusions: The angiogenic factor-based protocol may reduce the number of pregnancies classified as having fetal growth restriction without worsening perinatal outcomes. Moreover, reducing the number of unnecessary labor inductions would reduce costs and the risks derived from possible iatrogenic complications. Additionally, fewer inductions would lower the rate of early-term neonates, thus improving neonatal outcomes and potentially reducing long-term infant morbidities., Trial Registration: ClinicalTrials.gov NCT04502823; https://clinicaltrials.gov/ct2/show/NCT04502823., International Registered Report Identifier (irrid): DERR1-10.2196/37452., (©Pablo Garcia-Manau, Manel Mendoza, Erika Bonacina, Raquel Martin-Alonso, Lourdes Martin, Ana Palacios, Maria Luisa Sanchez, Cristina Lesmes, Ivan Hurtado, Esther Perez, Albert Tubau, Patricia Ibañez, Marina Alcoz, Nuria Valiño, Elena Moreno, Carlota Borrero, Esperanza Garcia, Eva Lopez-Quesada, Sonia Diaz, Jose Roman Broullon, Mireia Teixidor, Carolina Chulilla, Maria M Gil, Monica Lopez, Amparo Candela-Hidalgo, Andrea Salinas-Amoros, Anna Moreno, Francesca Morra, Oscar Vaquerizo, Beatriz Soriano, Marta Fabre, Elena Gomez-Valencia, Ana Cuiña, Nicolas Alayon, Jose Antonio Sainz, Angels Vives, Esther Esteve, Vanesa Ocaña, Miguel Ángel López, Anna Maroto, Elena Carreras. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.10.2022.)

Introduction: The association between preeclampsia and coronavirus disease 2019 (COVID-19) is under study. Previous publications have hypothesized the existence of shared risk factors for both conditions or a deficient trophoblastic invasion as possible explanations for this association. The primary aim of this study was to examine baseline risk factors measured in the first-trimester combined screening for preeclampsia in pregnant women with COVID-19 compared with the general population. A secondary aim of this study was to compare risk factors among patients with mild and severe COVID-19., Material and Methods: This was an observational retrospective study conducted at Vall d'Hebron Hospital Campus (Catalonia, Spain). Study patients were 231 pregnant women undergoing the first-trimester screening for preeclampsia and positive for severe acute respiratory syndrome coronavirus 2 between February 2020 and September 2021. The reference cohort were 13 033 women of the general population from six centers across Catalonia from May 2019 to June 2021. Based on the need for hospitalization, patients were classified in two groups: mild and severe COVID-19. First-trimester screening for preeclampsia included maternal history, mean arterial blood pressure, mean uterine artery pulsatility index (UtAPI), placental growth factor (PlGF), and pregnancy-associated plasma protein-A (PAPP-A)., Results: The proportion of cases at high risk for preeclampsia was significantly higher among the COVID-19 group compared with the general population (19.0% and 13.2%, respectively; p = 0.012). When analyzing risk factors for preeclampsia individually, women with COVID-19 had higher median body mass index (25.2 vs 24.5, p = 0.041), higher UtAPI multiple of the median (MoM) (1.08 vs 1.00, p < 0.001), higher incidence of chronic hypertension (2.8% vs 0.9%, p = 0.015), and there were fewer smokers (5.7% vs 11.6%, p = 0.007). The MoMs of PlGF and PAPP-A did not differ significantly between both groups (0.96 vs 0.97, p = 0.760 and 1.00 vs 1.01, p = 0.432; respectively)., Conclusions: In patients with COVID-19, there was a higher proportion of women at high risk for preeclampsia at the first-trimester screening than in the general population, mainly because of maternal risk factors, rather than placental signs of a deficient trophoblastic invasion., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: To evaluate the possible relationship between preeclampsia and polymorphisms in the main genes involved in folate-homocysteine metabolism., Study Design: Case-control study: 43 patients with preeclampsia and 122 controls without pregnancy complications. Laboratory studies: tHcy and other amino acids, folate and vitamin B(12) and polymorphisms: 677C > T and 1298A > C (MTHFR); 699C > T, 844ins68 and 1080C > T (CBS); 2756A > G (MTR); and 66G > A, IVS1+766G > A and IVS1+754A > C (MTRR)., Results: Plasma tHcy and folate values were significantly higher (P = 0.004 and P = 0.019), while Met/tHcy ratios were lower (P < 0.001) in the patients compared with controls. No association was observed between polymorphisms tested and preeclampsia. In the control group, four such associations were found: the 1298A > C polymorphism (MTHFR) with the ratio Met/tHcy (P = 0.014); the 699C > T polymorphism (CBS) with the ratio tHcy/SigmaAA (P = 0.013); the 2756A > G polymorphism (MTR) with tHcy (P = 0.034); and the IVS1+766G > A polymorphism (MTRR) with hyperhomocysteinemia (P = 0.012)., Conclusion: An association between the polymorphisms analysed and preeclampsia could not be demonstrated.