Introduction: Nowadays, proinflammatory factors are considered to play an important role in the pathophysiology of threatened preterm labor or chorioamnionitis. The aim of this study was to establish the normal reference range for interleukin‐6 (IL‐6) levels in the amniotic fluid and to identify factors which may alter this value.Material and methods: Prospective study in a tertiary‐level center including asymptomatic pregnant women undergoing amniocentesis for genetic studies from October 2016 to September 2019. IL‐6 measurements in amniotic fluid were performed using a fluorescence immunoassay with microfluidic technology (ELLA Proteinsimple, Bio Techne). Maternal history and pregnancy data were also recorded.Results: This study included 140 pregnant women. Of those, women who underwent termination of pregnancy were excluded. Therefore, a total of 98 pregnancies were included in the final statistical analysis. The mean gestational age was 21.86 weeks (range: 15–38.7) at the time of amniocentesis, and 38.6 weeks (range: 30.9–41.4) at delivery. No cases of chorioamnionitis were reported. The log₁₀ IL‐6 values follow a normal distribution (W = 0.990, p = 0.692).The median, and the 5th, 10th, 90th, and 95th percentiles for IL‐6 levels were 573, 105, 130, 1645, and 2260 pg/mL, respectively. The log₁₀ IL‐6 values were not affected by gestational age (p = 0.395), maternal age (p = 0.376), body mass index (p = 0.551), ethnicity (p = 0.467), smoking status (p = 0.933), parity (p = 0.557), method of conception (p = 0.322), or diabetes mellitus (p = 0.381).Conclusions: The log₁₀ IL‐6 values follow a normal distribution. IL‐6 values are independent of gestational age, maternal age, body mass index, ethnicity, smoking status, parity and method of conception. Our study provides a normal reference range for IL‐6 levels in the amniotic fluid that can be used in future studies. We also observed that normal IL‐6 values were higher in the amniotic fluid than in serum.

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.

Introduction: Preterm birth is the leading cause of perinatal mortality worldwide, with prevalence rates showing little reduction. Although mortality rates have decreased, morbidity rates remain concerningly high. In recent years, there has been a surge in studies examining the etiology, risk factors, and management of preterm birth. The use of vaginal probiotics in pregnant women at risk of preterm birth has garnered attention as a potential approach for improving perinatal outcomes and modulating the vaginal microbiota. However, the efficacy of this intervention remains unclear. Therefore, this study explored the impact of vaginal probiotics on perinatal outcomes and vaginal microbiota composition in pregnant women at risk of preterm birth. Materials and Methods: This was a randomized, prospective, longitudinal, double-blind, placebo-controlled, multicentric trial conducted across seven maternities in Spain from October 2017 to August 2022 in pregnant women at risk of preterm birth. Participants were randomly assigned to receive vaginal probiotics containing four lactobacilli strains or a placebo. The primary outcome was to explore a potential correlation between probiotic use among pregnant women at risk of preterm birth and the actual rate of preterm birth before 37 gestational weeks. Secondary outcomes included an evaluation of preterm birth rates, neonatal morbidity, the vaginal microbiota, and changes in the vaginal microbiota after receiving probiotics. Other secondary outcomes were identifying vaginal microbiota patterns associated with preterm birth and exploring potential therapeutic mechanisms involving probiotics. Trial registration: Clinicaltrials.gov, identifier: NCT03689166. Results: A total of 200 participants were included. Of those, birth data were obtained for 181 women. Demographics were similar between both groups. An analysis of perinatal outcomes found no significant differences in preterm birth rates, prematurity rates, gestational weeks at delivery, neonatal complications, time to birth, or latency time to delivery. Microbiota analysis showed no significant differences in vaginal microbiota changes between groups. No serious or unexpected adverse reactions were reported. Conclusions: There were no statistically significant differences for spontaneous preterm birth between pregnant women receiving probiotics and pregnant women receiving the placebo.

Background and Aims: Emerging evidence suggests adverse pregnancy outcomes (APOs) may increase future cardiovascular risk. This study aimed to assess in a Spanish cohort the long-term risk of cardiovascular disease in women with APOs compared to those without such complications. Methods: A retrospective longitudinal cohort study was conducted at Hospital Vall d’Hebron (Barcelona, Spain), including pregnant women delivering between January 2010 and December 2015. Women with pre-existing medical conditions were excluded. APOs included preeclampsia, gestational diabetes, preterm birth, late miscarriage, and stillbirth. Cardiovascular events were defined as acute myocardial infarction or stroke. Both APO and non-APO groups were compared for their risk of cardiovascular events in the years following delivery, using unadjusted and adjusted models. Results: Out of 12,071 pregnant women delivered at Hospital Vall d’Hebron during the study period. 10,734 met the inclusion criteria (8234 in the non-APO group and 2500 in the APO group). The adjusted model revealed a significant association between APOs and cardiovascular events post-delivery (HR 2.5; 95% CI 1.4–4.4). Furthermore, an increased number of APOs (≥2) correlated with a higher risk of post-delivery cardiovascular events (HR 8.6; 95% CI 2.8–26.8). Conclusions: Women with adverse pregnancy outcomes (APOs), particularly those experiencing preeclampsia, preterm birth, and late miscarriage, exhibit an elevated long-term risk of cardiovascular events. Our findings highlight that these associations persist even after adjusting for traditional cardiovascular risk factors, indicating that APOs may independently influence long-term cardiovascular health. This underscores the importance of recognizing pregnancy as a critical window for early cardiovascular health interventions and counseling. Addressing these risks proactively could improve long-term health outcomes for women with a history of APOs.

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.

Background: To evaluate the impact of applying alternative diagnostic criteria for gestational diabetes mellitus (GDM) during the COVID-19 pandemic on GDM prevalence, obstetrical and perinatal outcomes, and costs, as compared to the standard diagnostic method. Methods: A cohort of pregnant individuals undergoing GMD screening with the alternative GDM method, which uses plasma glucose (fasting or non-fasting) and HbA1c, was compared with a cohort of pregnant individuals undergoing the standard GDM screening method. Both cohorts were obtained from six hospitals across Catalonia, Spain, from April 2020 to April 2022. The primary outcome was large for gestational age rate at birth. The secondary outcomes were composite adverse outcomes, including pregnancy complications, delivery complications, and neonatal complications. The cost differences between screening methods were also evaluated. A similar analysis was performed in the subgroup diagnosed with GDM. Results: Data were collected from 1543 pregnant individuals in the standard screening group and 2197 in the alternative screening group. The standard screening group had a higher GDM diagnostic rate than the alternative screening group (10.8% vs. 6.9%, respectively; p < 0.0001). The primary outcome (large for gestational age rate) was similar between groups: 200/1543 (13.0%) vs. 303/2197 (13.8%). The adjusted OR for this outcome was 1.74 (95% CI: 0.74–4.10). An adjusted analysis showed no differences between groups in the composite adverse outcomes for pregnancy complications (OR: 1.11; 95% CI: 0.91–1.36), delivery complications (OR: 0.95; 95% CI: 0.75–1.19), and neonatal complications (OR: 1.28; 95% CI: 0.94–1.75). Among individuals diagnosed with GDM, the large for gestational age rate was similar between groups: 13/166 (7.8%) vs. 15/151 (9.9%). The OR adjusted for this outcome was 1.24 (95% CI: 0.51–3.09). An adjusted analysis showed no differences in the composite adverse outcomes for pregnancy complications (OR: 1.57; 95% CI: 0.84–2.98), delivery complications (OR: 1.21; 95% CI: 0.63–2.35), and neonatal complications (OR: 1.35; 95% CI: 0.61–3.04). The mean cost (which included expenses for consumables, equipment, and personnel) of the alternative screening method was 46.0 euros (22.3 SD), as compared to 85.6 euros (67.5 SD) for the standard screening method. Conclusions: In this Spanish population during the COVID-19 pandemic, GDM prevalence was lower in the alternative screening group than in the standard screening group. After adjusting for GDM risk factors, outcomes related to obstetrics, delivery, and neonatal complications were comparable between both groups. Finally, the alternative screening method was cheaper than the standard screening method.