(1) This study aimed to evaluate characteristics, perinatal outcomes, and placental pathology of pregnant women with or without SARS-CoV-2 infection in the context of maternal PCR cycle threshold (C_T) values. (2) This was a retrospective case-control study in a third-level health center in Mexico City with universal screening by RT-qPCR. The association of COVID-19 manifestations, preeclampsia, and preterm birth with maternal variables and C_T values were assessed by logistic regression models and decision trees. (3) Accordingly, 828 and 298 women had a negative and positive test, respectively. Of those positive, only 2.6% of them presented mild to moderate symptoms. Clinical characteristics between both groups of women were similar. No associations between C_T values were found for maternal features, such as pre-gestational BMI, age, and symptomatology. A significantly higher percentage of placental fibrinoid was seen with women with low C_Ts (<25; p < 0.01). Regarding perinatal outcomes, preeclampsia was found to be significantly associated with symptomatology but not with risk factors or C_T values (p < 0.01, aOR = 14.72). Moreover, 88.9% of women diagnosed with COVID-19 at <35 gestational weeks and symptomatic developed preeclampsia. (4) The data support strong guidance for pregnancies with SARS-CoV-2 infection, in particular preeclampsia and placental pathology, which need further investigation.

An infectious process into the uterine cavity represents a major endangered condition that compromises the immune privilege of the maternal–fetal unit and increases the risk for preterm birth (PTB) and premature rupture of membranes (PROM). Fetal membranes are active secretors of antimicrobial peptides (AMP), which limit bacterial growth, such as Escherichia coli. Nevertheless, the antibacterial responses displayed by chorioamniotic membranes against a choriodecidual E. coli infection have been briefly studied. The objective of this research was to characterize the profile of synthesis, activity, and spatial distribution of a broad panel of AMPs produced by fetal membranes in response to E. coli choriodecidual infection. Term human chorioamniotic membranes were mounted in a two independent compartment model in which the choriodecidual region was infected with live E. coli (1 × 10⁵ CFU/mL). Amnion and choriodecidual AMP tissue levels and TNF-α and IL-1β secretion were measured by the enzyme-linked immunosorbent assay. The passage of bacterium through fetal membranes and their effect on structural continuity was followed for 24 h. Our results showed that E. coli infection caused a progressive mechanical disruption of the chorioamniotic membranes and an activated inflammatory environment. After the challenge, the amnion quickly (2–4 h) induced production of human beta defensins (HBD)-1, HBD-2, and LL-37. Afterwards (8–24 h), the amnion significantly produced HBD-1, HBD-2, HNP-1-3, S100A7, sPLA2, and elafin, whereas the choriodecidua induced LL-37 synthesis. Therefore, we noticed a temporal- and tissue-specific pattern regulation of the synthesis of AMPs by infected fetal membranes. However, fetal membranes were not able to contain the collagen degradation or the bacterial growth and migration despite the battery of produced AMPs, which deeply increases the risk for PTB and PROM. The mixture of recombinant HBDs at low concentrations resulted in increased bactericidal activity compared to each HBD alone in vitro, encouraging further research to study AMP combinations that may offer synergy to control drug-resistant infections in the perinatal period.

Background: Respiratory syncytial virus (RSV) is a leading cause of hospitalization and mortality in early infancy. Maternal immunization offers a preventive strategy, but uncertainties regarding safety and economic value have limited its implementation. Objectives: To synthesize phase 3 randomized trial evidence on the efficacy and safety of maternal RSV vaccination and to estimate its potential population and economic impact. By integrating a scenario‐based modeling framework derived from pooled meta‐analytic estimates, this review provides high‐certainty, policy‐relevant evidence to guide maternal immunization strategies in diverse settings. Search Strategy: PubMed, MEDLINE, Scopus, and Google Scholar were searched up to April 2025 using predefined terms for RSV vaccination, pregnancy, and randomized controlled trials (RCTs). Selection Criteria: Phase 3 RCTs comparing maternal RSV vaccination with placebo and reporting neonatal or maternal outcomes were included. Non‐randomized studies, monoclonal antibody trials, or reports lacking extractable data were excluded. Data Collection and Analysis: Two reviewers independently screened studies, extracted data, and assessed risk of bias (RoB‐2). Pooled risk ratios (RR) and absolute risk differences were calculated with random‐effects models. Certainty of evidence was graded using Grading of Recommendations Assessment, Development and Evaluation (GRADE). A scenario‐based cost‐effectiveness model was applied to the Mexican birth cohort. Main Results: Four phase 3 RCTs (17 391 women) were included. Maternal RSV vaccination halved the risk of infant RSV infection (risk ratio [RR] 0.47, 95% confidence interval [CI]: 0.29–0.76; number needed to vaccinate [NNV] 85) and reduced severe disease by 64% (RR 0.36, 95% CI: 0.21–0.60; NNV 127). No increased risks were observed for preterm birth, pre‐eclampsia, or stillbirth. Certainty was moderate (any RSV) to high (severe RSV). In Mexico, universal vaccination at list price (US$295 per dose) would prevent approximately 20 769 infections and 228 neonatal deaths annually, though with high costs per case averted. At public‐sector pricing (US$50 per dose), cost‐effectiveness improved substantially. Conclusions: Maternal RSV vaccination is effective, safe, and potentially cost‐justifiable in high‐burden settings, supporting its integration into national immunization programs. PROSPERO registration: CRD420251014636 (March 2025).

Preeclampsia (PE) occurs annually in 8% of pregnancies. Patients without risk factors represent 10% of these. There are currently no first‐trimester biochemical markers that accurately predict PE. An increase in serum 60‐ and 70‐KDa extracellular heat shock proteins (eHsp) has been shown in patients who developed PE at 34 weeks. We sought to determine whether there is a relationship between first‐trimester eHsp and the development of PE. This was a prospective cohort study performed at a third level hospital in Mexico City from 2019 to 2020. eHsp levels were measured during the first‐trimester ultrasound in singleton pregnancies with no comorbidities. First‐trimester eHsp levels and biochemical parameters of organ dysfunction were compared between patients who developed preeclampsia and those who did not. All statistical analyses and model of correlation (r) between eHsp and clinical parameter were performed using bootstrapping R‐software. p‐values <0.05 were considered significant. The final analysis included 41 patients. PE occurred in 11 cases. eHsp‐60 and eHsp−70 were significantly higher at 12 weeks in patients who developed PE (p = 0.001), while eHsp‐27 was significantly lower (p = 0.004). Significant differences in first‐trimester eHsp concentration suggest that these are possible early biomarkers useful for the prediction of PE.

Background: Perinatal research faces significant challenges in understanding placental biology and maternal–fetal interactions due to limited access to human tissues and the lack of reliable models. Emerging technologies, such as liquid biopsy and single-cell analysis, offer novel, non-invasive approaches to investigate these processes. This scoping review explores the current applications of these technologies in placental development and the diagnosis of pregnancy complications, identifying research gaps and providing recommendations for future studies. Methods: This review adhered to PRISMA-ScR guidelines. Studies were selected based on their focus on liquid biopsy or single-cell analysis in perinatal research, particularly related to placental development and pregnancy complications such as preeclampsia, preterm birth, and fetal growth restriction. A systematic search was conducted in PubMed, Scopus, and Web of Science for studies published in the last ten years. Data extraction and thematic synthesis were performed to identify diagnostic applications, monitoring strategies, and biomarker identification. Results: Twelve studies were included, highlighting the transformative potential of liquid biopsy and single-cell analysis in perinatal research. Liquid biopsy technologies, such as cfDNA and cfRNA analysis, provided non-invasive methods for real-time monitoring of placental function and early identification of complications. Extracellular vesicles (EVs) emerged as biomarkers for conditions like preeclampsia. Single-cell RNA sequencing (scRNA-seq) revealed cellular diversity and pathways critical to placental health, offering insights into processes such as vascular remodeling and trophoblast invasion. While promising, challenges such as high costs, technical complexity, and the need for standardization limit their clinical integration. Conclusion: Liquid biopsy and single-cell analysis are revolutionizing perinatal research, offering non-invasive tools to understand and manage complications like preeclampsia. Overcoming challenges in accessibility and standardization will be key to unlocking their potential for personalized care, enabling better outcomes for mothers and children worldwide.

Objective: To develop and internally validate a mechanistic, three‐domain framework for early classification and prediction of pre‐eclampsia (PE) using first‐trimester angiogenic, uteroplacental, and maternal vascular biomarkers. Methods: In a prospective cohort of 1925 singleton pregnancies screened at 11 to 13.6 weeks, placental growth factor (PGF), uterine artery pulsatility index (UtA‐PI), and mean arterial pressure (MAP) were log‐transformed and standardized to gestational age–adjusted multiples of the median. Prespecified percentile thresholds (PGF 95th; MAP >95th) defined domain abnormalities and mechanistic phenotypes. Associations with PE, fetal growth restriction (FGR), and the composite of PE or FGR were assessed using logistic regression. Discrimination (area under the [receiver operating characteristic] curve [AUC]), calibration, and clinical utility were evaluated; bootstrap internal validation was used for optimism correction; and decision‐curve analysis quantified net clinical benefit. Results: PE occurred in 104 of 1925 pregnancies (5.4%). Phenotypes were distributed as normo (81.7%), molecular (7.6%), hemodynamic (3.2%), tensional (5.1%), dual (≥2 domains; 2.1%), and triple (3/3; 0.3%). The risk of PE increased stepwise from 3.9% (normo) to 80.0% (triple) ( P for trend <0.001). The three‐domain model improved discrimination to an AUC of 0.81 (95% confidence interval [CI], 0.77–0.86) versus the clinical model (AUC, 0.68; P < 0.001), achieved good discrimination for isolated FGR (AUC, 0.75 [95% CI, 0.70–0.81]), and provided higher net clinical benefit among 5% to 30% thresholds. In early‐onset PE (n = 14), discrimination was high (AUC, 0.99 [95% CI, 0.98–1.00]); estimates should be interpreted cautiously given the small number of events. Conclusion: A first‐trimester, mechanistic three‐domain framework captures the pathophysiologic continuum of placental insufficiency and supports accurate, clinically meaningful early risk stratification for PE. Findings were internally validated; external validation—particularly for early‐onset PE—is warranted.