Paula Trif

Background and Objectives: The COVID-19 pandemic profoundly disrupted maternal and newborn healthcare worldwide, necessitating rapid reorganization of healthcare services while maintaining essential care. Evidence from Central, Eastern and Southeastern Europe (CESEE) remains fragmented despite the region’s heterogeneous healthcare systems and variable pandemic responses. This scoping review synthesized the available evidence on maternal and newborn healthcare delivery during the COVID-19 pandemic and proposes a Maternal and Newborn Healthcare Resilience Framework (MNRF) to integrate the findings across key domains of healthcare resilience. Materials and Methods: PubMed/MEDLINE, Scopus, and Web of Science Core Collection were searched, with Google Scholar used as a supplementary search source. Eligible publications were published between 1 January 2020 and 31 May 2026. Evidence was synthesized across four predefined MNRF domains: access and continuity of care, healthcare organization and system capacity, quality and family-centered care, and maternal, perinatal, and neonatal outcomes. Results: Twelve publications met the inclusion criteria; several represented analyses derived from shared or partially overlapping datasets, particularly the multinational IMAgiNE EURO project. Across CESEE countries with available evidence, the pandemic disrupted access to antenatal services, accelerated the implementation of telemedicine, and prompted extensive reorganization of maternity and neonatal care. Family-centered practices, including birth companionship, skin-to-skin contact, breastfeeding support, and shared decision-making, were consistently affected. Maternal, perinatal, and neonatal outcomes showed no consistent regional pattern of deterioration in the included evidence; however, data were limited and heterogeneous, and localized increases in stillbirths and changes in neonatal healthcare utilization were reported. Conclusions: The COVID-19 pandemic exposed important vulnerabilities and prompted substantial adaptations in maternal and newborn healthcare delivery in the represented CESEE settings. The MNRF provides a structured, hypothesis-generating conceptual model for organizing these experiences and identifying priorities for preparedness and future research.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide despite substantial advances in screening, surgical techniques, systemic therapies, and multidisciplinary care. The increasing implementation of precision oncology has fundamentally transformed CRC management by enabling molecularly guided therapeutic strategies based on tumor-specific genetic alterations. In recent years, the molecular landscape of CRC has expanded considerably beyond traditional histopathological classification, incorporating a growing number of clinically actionable biomarkers with prognostic, predictive, and therapeutic significance. This review provides a comprehensive and up-to-date overview of the genetic landscape of CRC, focusing on established biomarkers currently integrated into clinical practice, including microsatellite instability/mismatch repair deficiency (MSI/dMMR), KRAS, NRAS, BRAF, HER2, and NTRK alterations. In addition, emerging biomarkers such as tumor mutational burden (TMB), POLE/POLD1 mutations, circulating tumor DNA (ctDNA), DNA damage repair (DDR) alterations, transcriptomic signatures, and artificial intelligence-based molecular prediction models are critically discussed. Particular emphasis is placed on their biological significance, diagnostic methodologies, prognostic and predictive value, and potential role in treatment selection. A structured, database-informed narrative review identified 140 relevant publications, primarily published between January 2020 and June 2026, supplemented by earlier seminal studies and major clinical guidelines. Based on the available evidence, we propose a Clinical Actionability Framework for CRC, categorizing biomarkers into three hierarchical tiers according to their level of clinical validation and therapeutic relevance: established standard-of-care biomarkers, emerging clinical biomarkers, and future precision oncology biomarkers. Collectively, current evidence supports a progressive transition from single-gene testing toward integrated multi-omics precision medicine. Advances in comprehensive genomic profiling, liquid biopsy technologies, transcriptomics, radiogenomics, and artificial intelligence are expected to further refine patient stratification, optimize therapeutic decision-making, and facilitate the development of adaptive precision oncology models. Understanding the evolving genetic landscape of CRC is therefore essential for maximizing treatment efficacy and improving patient outcomes in the era of personalized cancer care.

Background: Maternal influenza during the peripartum period poses a clinically significant risk to newborns, particularly for infants younger than 6 months. This group is especially vulnerable because of immune immaturity and the absence of an approved influenza vaccine for this age group. In light of emerging influenza virus mutations with pandemic potential, current protocols require evaluation with respect to infection prevention. Objective: To map and synthesize the available evidence and recommendations on the management of neonates born to mothers with suspected or confirmed influenza, with particular focus on delivery, skin-to-skin contact, breastfeeding, mother–infant separation, and neonatal antiviral therapy. Sources of Evidence: We performed a scoping review of the literature and professional guidance documents addressing the perinatal and postnatal management of newborns exposed to maternal influenza, using PubMed, Google Scholar, Web of Science, Embase, WHO, and CDC publications. The available evidence was synthesized narratively across the principal domains of clinical care. Conclusions: Current evidence does not support changing the mode of delivery solely because of maternal influenza. When the mother’s clinical condition permits, rooming-in, skin-to-skin contact, and breastfeeding can generally be supported with strict droplet precautions and hand hygiene. These practices provide substantial benefits for bonding, nutrition, and passive immune protection. Temporary separation may be considered in selected cases of severe maternal illness, although consistent evidence of benefit is limited. In neonates with suspected or confirmed influenza, early antiviral treatment should be considered in accordance with current pediatric guidance, whereas routine chemoprophylaxis in infants younger than 3 months remains insufficiently supported by evidence. Overall, recommendations remain heterogeneous, highlighting the need for higher-quality studies and clearer neonatal care pathways.

Background: Preeclampsia is a heterogeneous multisystem disorder characterized by endothelial dysfunction and angiogenic imbalance. While the sFlt-1/PlGF ratio is widely used for diagnostic purposes, its role in defining biological phenotypes of preeclampsia remains insufficiently explored. This study aimed to investigate whether angiogenic imbalance is associated with distinct multisystem phenotypes of preeclampsia and with perinatal outcomes. Methods: We conducted a retrospective cohort study including 320 pregnant women, of whom 68 were diagnosed with preeclampsia. Multisystem phenotypes were defined using laboratory markers reflecting renal, hepatic, and hematologic involvement. The sFlt-1/PlGF ratio was compared across phenotypes. Associations with gestational age at delivery, birth weight, Apgar score, and neonatal intensive care unit (NICU) admission were evaluated. Receiver operating characteristic (ROC) analysis assessed the discriminatory performance of the sFlt-1/PlGF ratio for identifying the renal-dominant phenotype. Results: The mean sFlt-1/PlGF ratio was higher in preeclampsia compared to normotensive pregnancies (58.5 ± 20.3 vs. 34.6 ± 15.9). Within preeclampsia, the renal-dominant phenotype showed the highest ratio (66.0 ± 22.5), followed by hepatic (55.9 ± 18.2) and hematologic phenotypes (52.0 ± 16.8). The renal phenotype was associated with earlier delivery (34.6 weeks), lower birth weight (2196 g), higher NICU admission (10.7%), and lower Apgar scores. The sFlt-1/PlGF ratio demonstrated moderate discrimination for the renal phenotype (AUC = 0.69). Conclusions: Angiogenic imbalance varies across multisystem phenotypes of preeclampsia and is associated with meaningful perinatal differences. The sFlt-1/PlGF ratio may contribute to phenotype-based risk stratification, supporting a move toward precision obstetrics. Prospective studies are needed to validate phenotype-oriented classification models.

Background: Preeclampsia is a major cause of maternal and perinatal morbidity, characterized by placental dysfunction and angiogenic imbalance. The soluble fms-like tyrosine kinase-1-to-placental growth factor (sFlt-1/PlGF) ratio has emerged as a promising biomarker for preeclampsia; however, its prognostic value for maternal and neonatal outcomes remains incompletely defined. Methods: This retrospective cohort study included 320 pregnant women, of whom 68 were diagnosed with preeclampsia, and 252 served as non-preeclamptic controls. Maternal serum sFlt-1 and PlGF levels were measured after 20 weeks of gestation at the time of clinical evaluation for suspected hypertensive disorders of pregnancy. Group comparisons, effect size analysis, receiver operating characteristic (ROC) curve analysis, and multivariable regression models were used to assess diagnostic performance and associations with maternal and neonatal outcomes. Results: The sFlt-1/PlGF ratio was significantly higher in women with preeclampsia compared with non-preeclamptic pregnancies (58.5 ± 17.3 vs. 34.6 ± 19.0; p < 0.001; Cohen’s d = 1.31). ROC analysis demonstrated good discriminative ability for preeclampsia (AUC = 0.81, 95% CI: 0.75–0.87), with a high negative predictive value. Increasing sFlt-1/PlGF values were independently associated with earlier gestational age at delivery, lower birth weight, reduced Apgar (Appearance, Pulse, Grimace, Activity, and Respiration) score, and a higher likelihood of neonatal intensive care unit admission. Conclusions: The sFlt-1/PlGF ratio is a robust biomarker for preeclampsia, providing both diagnostic discrimination and prognostic information regarding maternal and neonatal outcomes. Its integration into clinical practice may support clinical risk awareness when interpreted in the context of standard clinical evaluation and support informed decision-making in pregnancies with suspected or confirmed preeclampsia.

Background and Objectives: Preterm birth and stillbirth are primary adverse pregnancy outcomes. Research during the COVID-19 pandemic revealed reductions in preterm birth in some countries, while stillbirth rates increased or remained unchanged. These findings suggest the presence of preventable risk factors associated with changes in physical activity and lower exposure to community-acquired infections due to lockdown measures, altered social interaction patterns or reduced access to antenatal care. Assessing seasonal variation may offer insights into whether lifestyle changes during the COVID-19 lockdown period influenced preterm birth rates. Materials and Methods: This retrospective cohort study used data from the electronic medical records of Bihor and Sibiu counties. Preterm deliveries (Results: Out of 52,021 newborn infants, 4473 were born preterm. Preterm birth rates remained stable across all three periods (p = 0.13), and no significant seasonal pattern was identified (p = 0.65). In contrast, stillbirth rates increased notably during the strict lockdown period, with the median incidence almost doubling compared to other periods (0.87%, p = 0.05), while remaining unchanged during the rest of the pandemic (p = 0.52). Conclusions: Our study found that preterm birth rates remained unaffected by the pandemic and lockdown periods, while stillbirths increased significantly during the strict lockdown. These findings highlight the importance of maintaining access to timely antenatal care during public health emergencies to prevent adverse perinatal outcomes.

Antiphospholipid syndrome (APS) is an autoimmune disorder associated with thrombotic events and adverse obstetric outcomes, particularly in its obstetric form (OAPS). Affecting approximately 0.5% of the population, APS is a leading contributor to recurrent pregnancy loss (RPL), preeclampsia (PE), and fetal growth restriction ((FGR). Despite advancements in understanding its pathophysiology and management, optimal treatment strategies for APS in pregnancy remain challenging and require systematic evaluation. This review synthesizes current evidence on APS mechanisms, diagnostic criteria, and therapeutic interventions, with a focus on maternal and fetal outcomes in OAPS. A comprehensive search of PubMed, was conducted to identify studies exploring APS pathogenesis, diagnostic standards, and treatment efficacy in obstetric settings. Inclusion criteria prioritized randomized controlled trials, cohort studies, and systematic reviews with a clear focus on APS and pregnancy. The review confirmed that APS current accepted pathogenesis is governed by a “two-hit” model, where antiphospholipid antibodies (aPLs) initiate endothelial damage, culminating in thrombosis and placental insufficiency. Epidemiological analysis underscores the prevalence and severity of APS in obstetric contexts, with lupus anticoagulant (LA) emerging as a significant predictor of adverse outcomes. Evidence supports the use of low-dose aspirin (LDA) and heparin to reduce miscarriage rates, while adjunctive treatments, such as hydroxychloroquine (HCQ), have shown promise in improving live birth rates and reducing preterm delivery in high-risk cases. Emerging therapies, including tumoral necrosis factor (TNF-alpha) inhibitors and nitric oxide modulators, may offer additional benefits in refractory cases. APS remains a critical determinant of adverse pregnancy outcomes, necessitating precise diagnostic criteria and tailored management approaches. This systematic review emphasizes the importance of individualized therapeutic regimens to optimize maternal and fetal health in OAPS and highlights areas for future research, particularly regarding novel pharmacological approaches. Further studies are essential to refine treatment protocols and improve clinical guidelines for managing APS in pregnancy.

Background and Objective: The effects of neonatal hypoglycemia on the developing brain are well known, resulting in poor neurological outcomes. We aimed to perform an updated meta-analysis on neonatal hypoglycemia, the severity of hypoglycemia, and the associated neurodevelopmental outcomes from infancy to adulthood. Methods: A systematic literature search was conducted from inception until March 2024, using the PubMed, CINAHL, Embase, and the CENTRAL databases. Randomized/quasi-randomized trials and observational studies that evaluated at least one of the pre-specified outcomes were included. A random-effects model meta-analysis was performed to yield the pooled OR and its 95% CI for each outcome due to the expected heterogeneity in the studies. The study findings were reported as per the PRISMA guidelines. Neurodevelopmental impairment (NDI), cognitive impairment, and visual-motor or visual impairment were the primary outcomes. Results: A total of 17 studies (19 publications) were included in the final analysis. NDI, as defined by authors, was significantly higher in early- (OR = 1.16; 95% CI = 1.11–1.43) and mid-childhood (OR = 3.67; 95%CI = 1.07–12.2) in infants with neonatal hypoglycemia. ‘Any cognitive impairment’ was significantly more common in infants with neonatal hypoglycemia (OR = 2.12; 95%CI = 1.79–2.52). Visual-motor impairment (OR = 3.33; 95%CI = 1.14–9.72) and executive dysfunction (OR = 1.99; 95%CI = 1.36–2.91) were also more common in the hypoglycemic group. No difference in the incidence of epilepsy, motor impairment, emotional-behavioral problems, or hearing impairment were noted. Certainty of evidence was adjudged as ‘low’ to ‘very low’ for most outcomes. The severity of hypoglycemia was studied at different intervals, with NDI more common with a blood glucose interval between 20 and 34 mg/dL (1.1–1.9 mmol/L). Conclusions: Low-quality evidence from large observational studies finds a significant association with hypoglycemia in the early neonatal period and long-term neurodevelopmental problems. Additional studies with long enough follow-up are paramount to determine the cut-off concentration and to quantify the impact beyond the infancy period.

This meta-analysis assessed short-term outcomes after using human milk-derived fortifiers (HMFs) compared with bovine milk fortifiers (BMFs) in preterm infants fed an exclusive human milk (HM) diet, either mother’s own milk (MOM) or donor human milk (DHM). We searched PubMed, Embase, Google Scholar, CENTRAL and CINHAL between January 2015 and August 2023 for studies reporting outcomes in infants with ≤28 weeks gestation and/or birthweight ≤ 1500 g on an exclusive human milk diet fortified with HMF versus BMF. The primary outcomes were death and NEC (stage ≥ 2). Four studies with a total of 681 infants were included. Mortality was significantly lower in infants fed with an HM-HMFs diet (four studies, 681 infants; RR = 0.50, 95% CI = 0.26–0.94; p = 0.03; I² = 0%), NEC was similar between the two groups (four studies, 681 infants; RR = 0.48, 95% CI = 0.20–1.17; p = 0.11; I²= 39%). BPD was higher in the HM-BMFs group (four studies, 663 infants; RR = 0.83, 95% CI = 0.69–1.000; p = 0.05, I² = 0%), although not statistically significant. No differences were found for sepsis (RR = 0.97, 95% CI = 0.66–1.42; p = 0.96; I² = 26%) or combined ROP (four studies, 671 infants; RR = 0.64, 95% CI = 0.53–1.07; p = 0.28; I² = 69%). An HM-HMFs diet could possibly be associated with decreased mortality with no association with NEC, BPD, sepsis, or ROP. This meta-analysis was limited by the small number of studies included. However, the results should not be refuted for this reason as they provide an impetus for subsequent clinical trials to assess the observed associations.

Background: International studies have reported conflicting data about the effects of COVID-19 pandemic policy measures on maternal and neonatal health. A major impact was reported on stillbirth and prematurity. The published literature suggests that the economic setting influenced the effects of imposed mitigation measures with a more severe effect in low-income countries.Objectives: Our objective is to compare pregnancy outcomes at the only tertiary Maternity Hospital in Bihor County-Romania before and during the COVID-19 pandemic. This study aims to observe and document differences in perinatal outcomes across these periods, without inferring direct causation related to the pandemic or its associated restrictions.Materials and methods: We used data from the registries of Public Health Services Bihor to conduct a retrospective cohort analysis of preterm births and stillbirths during the COVID-19 pandemic in Bihor County, Romania. Pregnancy outcomes were compared between the pandemic period (March 2020–February 2022) to the corresponding historical pre-COVID-19 period (March 2018–February 2020). Maternal socio-demographic variables and neonatal characteristics of these periods were also examined.Results: The COVID-19 pandemic period was associated with an increase in the stillbirth rate (RR: 1.53, 95% CI, 1.05–2.23). Preterm birth was significantly impacted during this period and showed changes when analyzing gestational age (RR: 0.88, 95% CI, 0.79–0.96) or birth weight (RR: 0.91, 95% CI, 0.82–1.00). The main cause of stillbirth was intrauterine asphyxia due to placental causes (67.6%) or cord pathology (12.6%), the most frequently encountered maternal pathology was cardiovascular (28.3%) or infectious (21.7%). Our study revealed no significant changes in terms of maternal and neonatal characteristics during the two-year pandemic period.Conclusions: Lockdown restrictions in Bihor County, Romania were associated with an increase in stillbirths, whilst preterm birth rate decreased. This raises concerns about whether pandemic policy measures may have led to a failure in identifying and offering proper care for pregnant women who were more likely to experience an antepartum loss. Further studies across the globe are needed in order to integrate comparable data that will help develop adequate protocols and policies for protecting maternal and child health during the next pandemic that will follow.