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 (<34 weeks) and preterm (<37 weeks) PE between groups. Results: Cut-off levels for the contingent screening model were chosen in the first and second stages of screening to achieve a performance with sensitivities of 100% and 80% for early-onset and preterm PE detection, respectively, with a 15% false positive rate. In the development phase, 21.5% (n = 113) of the women had a medium risk of PE and required second-stage screening. In the prospective validation phase, 15.3% (n = 130) of the women required second-stage screening for PlGF, yielding an overall screen-positive rate of 14.9% (n = 126). The incidence of preterm PE was reduced by 68.4% (1.9% vs. 0.6%, 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 most common form of congenital adrenal hyperplasia (CAH) results from a deficiency of the 21-hydroxylase enzyme (21-OHD), presenting with a broad spectrum of clinical phenotypes according to the CYP21A2 gene mutations. Of the 59 patients with suspected CAH, 62.7% presented a positive genetic result. Of them, 78.4% and 18.9% presented with non-classical and classical forms, respectively. An overall phenotype-genotype correlation of 88.9% was observed. Biochemically, 17-hydroxiprogesterone concentrations were significantly higher in genetically confirmed patients. Genetically, 36 patients presented with previously reported pathogenic variants, and one presented a new variant in homozygosis. Among the 74 alleles tested, point mutations were found in 89.2% and large rearrangements were found in the rest. The most prevalent pathogenic variant was p.(Val282Leu). The inclusion of relatives revealed one further case. Interestingly, 87.5% of relatives were carriers of a pathogenic variant, including two siblings initially classified as genetically positive. In addition, the study of male partners with gestational desire identified several carriers of mild mutations. Studying the allelic distribution of the variants also allowed for reclassifying one patient. In conclusion, a genetic approach including Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA) analysis, and allelic distribution of the pathogenic variants represents a beneficial tool for better classifying patients with 21-OHD.

Background/Objectives: Preeclampsia is associated with long-term cardiovascular and metabolic risks. This study aimed to evaluate metabolic and cardiovascular biochemical profiles in women with a history of preeclampsia and angiogenic imbalance during pregnancy. Methods: We conducted a cross-sectional study at Hospital de la Santa Creu i Sant Pau between August 2023 and July 2025. Participants had been prospectively enrolled during pregnancy (2018–2022) and were re-evaluated 3 to 6 years later. Blood and urine samples were collected after a 12-h fast to assess hematological, metabolic, and cardiovascular markers. Angiogenic profiles were determined using sFlt-1/PlGF ratios obtained during pregnancy. Multivariable linear regression models were used to assess associations with a history of PE and angiogenic imbalance, adjusting for relevant confounders. Results: 363 participants were included. 113 (31.1%) had a history of preeclampsia. Women with previous preeclampsia showed slightly higher high-sensitivity troponin T concentrations [4.0 (3.0–6.0) ng/L vs. 3.2 (3.0–5.0) ng/L, p = 0.03]. Women with sFlt-1/PlGF ≥38 exhibited significantly higher urinary protein [0.09 (0.07–0.18) g/L vs. 0.08 (0.07–0.13) g/L, p = 0.01], potassium [4.25 (4.07–4.40) mmol/L vs. 4.19 (4.02–4.37) mmol/L, p = 0.048], and LDH concentrations [168 (150–189) U/L vs. 163 (149–177) U/L, p = 0.046], and lower leukocyte counts [6150 (5348–7055) vs. 6250 (5430–7450) U/mL, p = 0.03]. Conclusions: Women with angiogenic imbalance during pregnancy display subtle alterations in renal and endothelial function markers years after delivery, whereas those with preeclampsia show slightly higher troponin concentrations. These findings, though clinically irrelevant, suggest that pregnancy-related vascular dysfunction may have different long-term manifestations depending on whether the maternal cardiovascular system was sufficiently compromised to develop overt preeclampsia.