Search Results (94)

Background/Objectives: Despite well-documented chemical and physical hazards in healthcare settings, existing reviews of occupational reproductive risks have largely focused on single-agent risk estimation and have rarely translated occupational hygiene evidence into clinical decision-making frameworks for reproductive counseling and surveillance. This narrative review synthesizes evidence across multiple occupational exposure categories—antineoplastic agents, high-level disinfectants (HLDs), sterilants, and work-organization factors—and proposes an integrated, clinically operational framework for preconception counseling, pregnancy-sensitive risk stratification, exposure-control verification, and reproductive health surveillance among women healthcare workers. Methods: A structured narrative literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and Embase from database inception through January 2025 and updated in March 2026. The review was guided by a Population–Exposure–Comparison–Outcome (PECO) framework and structured using Search–Appraisal–Synthesis–Analysis (SALSA) principles and the Scale for the Assessment of Narrative Review Articles (SANRA). Evidence quality was summarized using a modified hierarchy-of-evidence classification provided as a reader aid. This narrative review employed structured transparency tools but does not claim the methodological status of a systematic review. Quantitative meta-analytic pooling was not performed owing to substantial heterogeneity across study designs, exposure assessment methods, and outcome definitions; findings were synthesized narratively by exposure category. Results: The strongest and most consistent evidence was identified for occupational exposure to antineoplastic agents, which has been associated with spontaneous abortion, stillbirth, congenital abnormalities, impaired fecundability, and selected cancer-related concerns. HLDs and sterilants represent exposure categories warranting precautionary attention, with some evidence suggesting possible adverse effects on fecundability and early pregnancy maintenance; however, findings are considerably more heterogeneous, context-dependent, and reliant on self-reported exposure assessment than those for antineoplastic agents. Broader workplace factors, including shift work, prolonged working hours, physical workload, and mixed exposures, may further contribute to reproductive risk. The synthesis supports task-specific occupational history taking, exposure-control verification, and pregnancy-sensitive risk stratification. Conclusions: This review provides a multi-exposure, clinically operational framework that bridges occupational hygiene evidence with reproductive healthcare delivery, offering practical decision-support tools for clinicians managing women healthcare workers during preconception, pregnancy, and lactation. The framework includes structured occupational history-taking questions, a clinical decision pathway with evidence-tier classification, and a prevention matrix linking exposure sources to workplace controls and clinical actions. Integrating task-specific occupational history taking into routine reproductive care may improve detection of preventable workplace risks and support timely accommodation, while clinicians should calibrate recommendation strength to the underlying evidence quality for each exposure category. Full article

Gestational diabetes mellitus (GDM) is increasingly recognized as a complex pathology rooted in systemic and organelle-level dysfunction, specifically involving chronic low-grade inflammation (CLGI), mitochondrial impairment, and endoplasmic reticulum (ER) stress. Central to this pathophysiology is mitochondrial dysfunction, characterized by reduced respiration, impaired metabolic flexibility, and dysregulated fission/fusion machinery, which fuels a self-perpetuating cycle of reactive oxygen species (ROS) production. Concurrently, chronic ER stress triggered by hyperglycemia and lipotoxicity activates the unfolded protein response (UPR), further amplifying redox imbalance through the Endoplasmic Reticulum Oxidoreductin 1/Protein Disulfide Isomerase (ERO1/PDI) axis and bridging metabolic toxicity to inflammation via c-Jun N-terminal kinase (JNK) and nuclear factor kappa-light-chain–enhancer of activated B cells (NF-κB) signaling. The Advanced Glycation Endproducts (AGEs) and the Receptor for Advanced Glycation Endproducts (RAGE) axis act as a molecular catalyst that sequester antioxidants and drive pro-inflammatory feedback loops. These converging mechanisms culminate in profound placental maladaptation, including structural abnormalities like chorangiosis and functional defects in nutrient transport mediated by hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. This review article provides insight into recent evidence to elucidate the meta-inflammatory environment of GDM, where modest but sustained elevations in biomarkers like Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) disrupt redox homeostasis and impair insulin signaling pathways through the activation of stress-sensitive kinases. By integrating these molecular perspectives, the article underscores the necessity of targeting the systemic inflammatory and oxidative continuum spanning pre-conception to the antenatal period through lifestyle interventions and emerging therapeutic strategies to mitigate GDM risk and improve maternal–fetal outcomes. Full article

Congenital heart disease (CHD) is the most common anatomical malformation occurring in live-born infants and an increasing cause of morbidity and mortality all over the world. Population-based observations have described associations between maternal cardiometabolic disorders and the risk of CHD in offspring. The present article is a narrative review. The aim of this study was to review the epidemiological evidence and clinical observations relating maternal obesity and diabetes mellitus to the risk of CHD in offspring, with particular attention paid to first trimester disturbances of fetal cardiac development and the influence of genetic, epigenetic and environmental factors. Studies have shown that maternal diabetes is a risk factor associated with nearly all subtypes of CHDs in offspring, while obesity and overweight are associated with increased risk for complex defects and outflow tract obstruction and decreased risk for ventricular septal defects. Diabetes and obesity share several phenotypes, which could be transmissible from mother to fetus via the placenta. This means that an increase in maternal glucose could be responsible for the prevalence of CHD in newborns of obese women. On the other hand, maternal diabetes may induce epigenetic modifications in the developing fetus. DNA methylation changes can impact gene expression patterns relevant to heart development. The abovementioned studies are heterogenous, express different opinions and are often difficult to compare. Therefore, the results from these meta-analyses must be interpreted with caution. Optimal diabetes control is responsible for the prevention of oxidative stress in diabetic pregnancies, and a deeper understanding of maternal risk factors holds the potential to improve both prenatal detection of CHDs by identifying at-risk pregnancies and primary prevention of diseases by improving preconception management. Full article

Background/Objectives: Congenital heart defects (CHDs) are associated with disruptions in one-carbon metabolism. In a family-based trio design, we investigated whether plasma concentrations of choline, betaine, and folate are associated with CHD severity. Methods: The study included 72 children with CHD, 69 of their mothers and 64 of the fathers. CHD clinical severity was classified according to the European network of population-based registries for the epidemiological surveillance of congenital anomalies (EUROCAT) system and the German PAN study (Prevalence of Congenital Heart Defects in Newborns). Concentrations of choline, betaine, and folates were quantified in plasma and urine samples from a subgroup of the participants. Results: The children [mean (SD) age 3.1 (3.2) years, 59.7% males] presented with varying CHD severities according to EUROCAT (62.5% severe and 37.5% mild) and PAN classifications (45.8% severe, 30.6% moderate and 23.6% mild). The means (SD) of plasma concentrations of choline were 14.0 (10.0) µmol/L in the children, 9.5 (5.1) µmol/L in the mothers and 10.3 (5.4) µmol/L in the fathers. Plasma choline concentrations < 10 µmol/L were observed in 38 mothers (66.7%) and were associated with having a child with severe CHD [adjusted odds ratio (aOR) 3.7; 95% confidence intervals (95%CIs) = 1.1, 12.2] compared to mothers with choline ≥ 10 µmol/L. Lowered plasma choline concentrations were detected in 27 fathers (62.8%) and were also associated with severe CHD (aOR 7.4; 95%CIs = 1.7, 31.5). Child concentrations of choline, betaine and folate and parents’ concentrations of betaine and folate were not associated with disease severity. Conclusions: Lower plasma choline in the parents detectable several years after conception was related to having a child with severe CHD compared to families of children with higher plasma choline. Maternal and paternal choline metabolism may have a role in modulating CHD severity. Etiological studies aiming at the prevention of congenital anomalies should focus on maternal and paternal risk factors in the preconception and early pregnancy. Full article

Background: Congenital toxoplasmosis remains a significant cause of fetal morbidity worldwide. This case–control study aimed to identify sociodemographic, dietary, and behavioral factors associated with Toxoplasma gondii infection during pregnancy in Italy by comparing infected women with seronegative controls, and to evaluate modifiable risk behaviors and treatment-related outcomes among affected patients. Methods: This case–control study included 201 pregnant women (100 with T. gondii infection and 101 seronegative controls). Participants completed a structured questionnaire on sociodemographic factors, diet, environmental exposures, and preventive behaviors. Clinical data were collected for infected women and analyzed using SPSS v27.0. Results: Sociodemographic and obstetric characteristics did not differ between groups. Infected women were more likely to live in rural areas (p < 0.001), have a lower educational level (p = 0.009), consume unpasteurized dairy products and cured meats (p < 0.05), purchase food from farmers or butchers (p = 0.01), and do not check food preparation practices when eating outside the home. High-risk animal-related behaviors were also more common among cases (p < 0.001). Despite similar baseline awareness, adherence to preventive measures was lower among cases; most infections were diagnosed in the first trimester and treated with spiramycin with good tolerability. Conclusions: Maternal toxoplasmosis is mainly associated with modifiable behavioral and environmental factors, underscoring the need for targeted, preconception counseling to reduce the risk of congenital infection. Full article

Background: Congenital anomalies are influenced by genetic and environmental factors. While interventions including folic acid supplementation have reduced neural tube defects, data on modifiable socio-demographic risk factors remain limited. Aim: This study aimed to assess variation in the prevalence of selected congenital anomalies across the United States according to socio-demographic factors. Methods: A population-based analysis was conducted using CDC-WONDER natality data from 2016 to 2023. Included anomalies were anencephaly, spina bifida, cyanotic heart disease, diaphragmatic hernia, omphalocele, gastroschisis, limb reduction, cleft lip/palate, Down syndrome, chromosomal disorders, and hypospadias. Associations with maternal age, BMI, race, tobacco use, diabetes, and fertility treatments were analyzed. Prevalence rates were calculated per 1000 live births. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated. Joinpoint regression was used to assess annual percent changes (APCs), with p < 0.05 considered significant. Results: Among 3,482,944 singleton live births in 2023, the overall prevalence of the selected congenital anomalies was 3.3 per 1000. Compared to Caucasian mothers, risk was lower in Asian (RR 0.57; 95% CI: 0.52–0.63) and Black (RR 0.81; 95% CI: 0.76–0.85) infants and higher in American Indian/Alaska Native infants. Significant risk factors included pre-pregnancy diabetes (RR 2.41; 95% CI: 2.16–2.69), maternal age > 45 (RR 2.95; 95% CI: 2.36–3.69), and tobacco use (RR 1.78; 95% CI: 1.64–1.94). A significant decline in prevalence was observed from 2016 to 2023 (APC: −0.6%; 95% CI: −1.1 to −0.2; p = 0.006). Conclusions: Significant disparities and modifiable maternal risk factors were associated with the prevalence of selected congenital anomalies in the U.S. from 2016 to 2023. A modest statistically significant decline in overall prevalence was observed during the study period, supporting the importance of continued national surveillance and targeted preconception and prenatal interventions to reduce risk and address inequities. Full article

Down Syndrome (DS) is the most common chromosomal abnormality characterized by neurodevelopmental impairment. Apart from maternal age, its risk factors remain poorly understood. This prospective case-control study aimed to evaluate the role of maternal anti-zona pellucida (ZP) antibodies (Ab) and anti-thyroid-Ab in predicting DS. Correlations of anti-ZP-Ab and anti-thyroid-Ab with maternal age were also assessed. Anti-ZP-Ab were measured after childbirth using ELISA. Anti-thyroid peroxidase (aTPO) and anti-thyroglobulin (aTgII) antibodies were also analysed with the Allelica IM platform. Statistical analyses included receiver operating characteristic curve assessment, expressed as area under the curve (AUC) and linear regression modeling. Between September 2020 and October 2022, 58 women were enrolled. Anti-ZP-Ab levels were significantly higher in women with DS pregnancy with an odds ratio adjusted for maternal age of 71.52 (95% CI: 7.05–725.18) and an excellent predictive performance (AUC = 0.94; 95% CI: 0.88–1.00). For optical density levels > 1, the accuracy was 89.7% (95% CI: 78.2–100.0). No statistically significant differences were observed for aTPO and aTgII. Neither Anti-ZP-Ab nor anti-thyroid antibodies increased with age. These findings suggest that Anti-ZP-Ab are strongly associated with DS risk, suggesting a potential age-independent autoimmune contribution to trisomy 21. Their evaluation may support preconception counseling, especially for women aged > 35 years. Future studies could clarify causality and define the role of maternal autoimmunity in DS etiology. Full article

Background/Objectives: The first 1000 days of life represent a critical window for growth and neurodevelopment, during which nutrition strongly influences brain development and metabolic programming. In phenylketonuria (PKU), dietary management is essential to prevent neurological impairment and later-life risk of non-communicable diseases (NCDs). This review examines current evidence on PKU from pregnancy through complementary feeding, highlighting the impact of nutritional strategies on neurodevelopmental and metabolic outcomes. Methods: This narrative review, following PRISMA guidelines, used a systematic search of PubMed and Scopus with defined PICO questions. Original research, reviews, and guidelines on PKU nutrition during the first 1000 days were included, emphasizing neurological and metabolic outcomes. Results: Articles addressed prenatal and postnatal factors in PKU. Optimised metabolic control in women with PKU is critical to prevent maternal PKU syndrome, reducing risks of miscarriage, congenital heart defects, microcephaly, and neurocognitive impairment. Pre-conception dietary management, frequent blood Phe monitoring, supplementation with Phe-free protein substitutes (PSs), micronutrients, and emerging pharmacological therapies support maternal and foetal health. Following newborn screening, early dietary treatment in infants with PKU maintains plasma Phe within safe ranges, promoting growth and neurodevelopment. Breastfeeding, combined with Phe-free infant PSs, is feasible, and complementary feeding should be introduced carefully. Frequent monitoring and tailored dietary adjustments, including second-stage PSs, support metabolic control, while data on gut microbiota remain limited. Conclusions: Early multidisciplinary interventions are crucial to optimise metabolic and neurodevelopmental outcomes during this window of opportunity. Further research is needed to address remaining gaps and optimise PKU management across the first 1000 days. Full article

Background: With advances in cancer diagnosis and therapy, survival after childhood and young-adult cancers has improved markedly. As survivorship extends, understanding long-term health sequelae, including obstetric outcomes, has become increasingly important. However, the reproductive safety of pregnancy following cancer remains insufficiently characterized. This systematic review and meta-analysis aims to provide a comprehensive evaluation of obstetric outcomes following pregnancy in survivors of childhood and young-adult cancers. Methods: We conducted a systematic review and meta-analysis (PROSPERO: CRD42024573707) of PubMed, Embase, and Cochrane databases to identify controlled studies assessing obstetric complications among female cancer survivors, published between 1 January 2000 and 31 June 2024. Random effects meta-analyses were used to estimate pooled risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity, subgroup analyses, and meta-regression were performed to identify sources of variation. Results: Of 6032 records screened, 16 studies involving 89,123 survivors and 21,569,191 controls were included. Cancer survivorship was associated with higher risks of preeclampsia (RR 1.37, 95% CI 1.17–1.62), gestational diabetes (RR 1.29, 95% CI 1.05–1.59), and miscarriage (RR 1.16, 95% CI 1.01–1.35), but not with anemia in pregnancy (RR 1.16, 95% CI 0.98–1.39) or hypertensive disorders (RR 1.21, 95% CI 0.99–1.49). Cancer type emerged as a potential prognostic factor for preeclampsia. Conclusions: Female cancer survivors are at significantly increased risk of major obstetric complications, underscoring the need for anticipatory preconception counselling and enhanced antenatal surveillance. Future research should delineate cancer- and treatment-specific risks to inform precision reproductive care in this growing survivorship population. Full article

Studies have widely indicated that the composition of maternal nutrition and diets might affect offspring health later in life. Studies on paternal contribution to the offspring’s disease are relatively scarce but are an important subject to the field. Recent research has suggested that paternal factors influenced by nutrition have been implicated in the transgenerational heritage of health and diseases through epigenetic mechanisms. This review aims to explore the current state of knowledge on nutrition-based paternal impacts on gynecological disease through epigenetics, focusing on the transmission of cancer and metabolic diseases from father to female offspring. We will explore the various mechanisms by which epigenetic landmarks, such as DNA methylation, histone modifications, and non-coding RNAs, are passed on through sperm and reprogrammed in the embryo, influencing offspring development and health. We will discuss the impacts of preconception paternal nutrition on two common cancer such as breast cancer and ovarian cancer in female offspring. Additionally, paternal overweight or obesity has been associated with increased risk of obesity in the offspring and compromised metabolic health, which may link to reproductive conditions such as infertility. Understanding the molecular mechanisms underlying non-genetic inheritance is crucial for elucidating the nutrition-mediated developmental origins of health and disease. This review highlights the mechanistic correlation between preconception paternal nutrition and female offspring gynecological health. Furthermore, it emphasizes the need for additional research to establish evidence-based paternal nutrition consultation and guidelines aimed at optimizing reproductive health and pregnancy outcomes in couples planning to conceive. Full article

Background/Objectives: Diabetes mellitus (DM) in pregnancy, including type 1 (T1DM), type 2 (T2DM), and gestational DM (GDM), represents an increasing health burden due to its maternal and fetal complications. Despite the increment in the global prevalence estimates of DM in pregnancy, in Romania, it has not been comprehensively described. This study aimed to analyze the prevalence and dynamics of DM in pregnancy in Romania between 2014 and 2024, using national databases, and to identify prevention strategies for reducing maternal and fetal complications. Methods: Data were obtained from the Romanian National Public Health Institute through two distinct sources: Database 1, consisting of reports from public and medical units associated with the National Health Insurance House and Database 2, based on the reports from general practitioners. Pregnancies complicated by DM were assessed by type, age group, and environmental settlement. Additional data were extracted on pregnancies with insufficient prenatal care and those of socially vulnerable individuals. Results: From 2014 to 2024, the prevalence of DM in pregnancy in Romania was consistently lower than European and global estimates, ranging from 1.01‰ to 3.08‰ in Database 1 and from 0.84‰ to 5.88‰ in Database 2, respectively. GDM accounted for the majority of cases, accounting for 65–88% of reported DM in pregnancy. The highest incidence was observed in the 20–39 years age group, with a growing proportion in women aged ≥40 years. Urban-rural disparities decreased over the decade, with rural cases reaching parity by 2024. Vulnerable populations included adolescents, women with insufficient prenatal care, and those with social risk factors, predominantly from rural areas. Conclusions: Although the reported prevalence of DM in pregnancy in Romania is lower than international figures, the true burden is likely underestimated. GDM remains the leading type of DM in pregnancy, mirroring global trends. Strengthening the reporting system, standardizing diagnostic criteria, and targeting high-risk groups through preconceptional counselling, lifestyle interventions, advanced monitoring technologies, and improving social support through the involved authorities are crucial steps to reduce maternal and fetal morbidity. Full article

Background: Maternal obesity affects 20–25% of pregnancies globally and has been associated with adverse offspring neurodevelopmental outcomes. This umbrella review synthesized evidence on neurodevelopmental pathways linking maternal obesity to offspring cognitive, executive, and behavioral outcomes. Methods: Following PRISMA 2020 guidelines, we systematically searched six databases (PubMed/MEDLINE, Scopus, Web of Science, PsycINFO, EMBASE, CINAHL) for studies published 2008–2024. We included original peer-reviewed studies examining maternal pre-pregnancy obesity (BMI ≥ 30 kg/m²) and offspring neurodevelopmental outcomes using prospective cohort, experimental, neuroimaging, or systematic review designs with validated assessments. Risk of bias was assessed using Newcastle–Ottawa Scale, Cochrane RoB 2.0, and SYRCLE guidelines. Results: Analysis of 78 studies encompassing 650,000+ mother–child pairs from 17 countries revealed significant associations. Study designs included prospective cohorts (59%), animal experiments (22%), systematic reviews/meta-analyses (13%), neuroimaging studies (4%), and randomized trials (3%). Maternal obesity (BMI ≥ 30 kg/m²) was associated with reduced cognitive abilities (IQ differences: −2.5 to −5.8 points), impaired executive function (OR 1.4–2.3), and increased ADHD symptoms (OR 1.4–2.8) and emotional dysregulation (OR 1.5–2.2). Dose–response relationships revealed threshold effects at BMI ≥ 30 kg/m², accelerating at BMI ≥ 35 kg/m². Four primary mechanistic pathways were identified: inflammatory, metabolic, epigenetic, and neurotransmitter alterations. Only 57.7% of studies used prospectively measured pre-pregnancy BMI. Conclusions: Observational and experimental evidence indicates maternal obesity represents a modifiable risk factor for offspring neurodevelopmental impairment. The primarily observational human evidence, supported by mechanistic animal studies, suggests multimodal interventions targeting identified pathways during critical windows (pre-conception through early postnatal period) warrant investigation. Full article

Background/Objectives: Since the first successful birth following assisted reproductive technologies (ART) several decades ago, the global population of ART-conceived children has surpassed 13 million, with over 40,000 born in Kazakhstan. Despite this growth, questions remain about their long-term neurological outcomes, with existing studies reporting inconsistent findings. This study aimed to assess psychomotor development and the prevalence of nervous system pathologies among ART-conceived children in Kazakhstan and to develop a prognostic model for identifying pathological neurodevelopmental conditions. Methods: We studied 252 children (120 conceived via ART and 132 controls) using clinical examination and medical history data. Brain immaturity predictors were identified by univariate and multivariate logistic regression. Results: ART-conceived children exhibited a higher incidence of neurosonographic signs of brain structure immaturity. However, multivariate analysis indicated that ART itself was not an independent risk factor. Instead, perinatal complications—including prematurity, multiple pregnancy, low birth weight, asphyxia, and intrauterine infections—explained the observed differences. The prognostic model highlighted prematurity and preconceptional progesterone therapy as significant predictors. Overall neurological development did not differ significantly between the groups. Conclusions: These findings underscore the importance of early identification of perinatal risk factors and targeted preventive interventions to mitigate adverse neurodevelopmental outcomes in ART-conceived children. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is a common pregnancy complication, and maternal diet before conception may be an important modifiable risk factor. This study aimed to investigate the association between maternal pre-pregnancy energy and macronutrient intake and the risk of GDM. Methods: Data from the BORN2020 cohort in Northern Greece were used. Women were recruited at their first trimester prenatal visit (11–13 weeks of gestation) and provided detailed dietary data via a validated food frequency questionnaire (FFQ), reflecting intake in the six months prior to conception. Weighted Quantile Sum (WQS) regression models were applied to assess the joint effects of food-derived macronutrient mixtures on GDM risk. Analyses were adjusted for parity, maternal age, pre-pregnancy BMI, thyroid disorders, smoking, energy intake, and physical activity. Results: In total, 797 women were included in the analyses. In normal-BMI women, higher pre-pregnancy intake of energy (aOR = 81.16, 95% CI: 4.55–1447.46), total carbohydrates (aOR = 50.66, 95% CI: 3.59–715.04), total fat (aOR = 9.35, 95% CI: 1.17–74.54), and total protein (aOR = 11.06, 95% CI: 1.14–107.09) were significantly associated with increased odds of GDM. The main contributing foods were energy-dense and processed items such as puff pastry, processed meats, potatoes, refined grains, and dairy products. In contrast, dietary fiber, vegetable protein, and animal protein were not significantly associated with GDM risk. Among overweight and obese women, none of the macronutrient or energy mixtures showed significant associations. Conclusions: For women of normal weight, a pre-conception diet high in energy and macronutrients from processed foods is a significant predictor of GDM risk. This association was not found in overweight or obese women, highlighting a critical window for targeted nutritional intervention for normal-weight individuals before pregnancy. Full article

Background: There have been 20.5 million deaths due to cardiovascular diseases (CVDs), including atherosclerotic coronary artery disease (CAD) and stroke, so far in 2025. Atherosclerosis, which begins in newborns, may be influenced by preconception factors and continues to develop in adults, requiring a proper assessment of the burden of atherosclerotic plaque, as it is the direct cause of CAD. This review aims to emphasize the role of a staging system proposed by the Lancet Commission for the quantification of atherosclerotic coronary artery disease (ACAD) with an emphasis on preconception risk factors and protective factors, based on coronary computed tomography angiography (CCTA). Methods: It is suggested that the use of CCTA scanning makes it possible to quantify the atherosclerotic plaque burden into four stages. Results: CCTA enables us to see how much plaque has built up, as well as the type of plaque, but not the biochemistry of the plaque, to determine its vulnerability. However, if the plaque is a non-calcified fatty plaque, it is considered to be a strong predictor of the risk of myocardial infarction (MI), whereas a more stable calcified plaque is known to be protective against MI. There are several risk factors and protective factors which may influence the process of the rupture or vulnerability of the plaque. A randomized trial revealed that, after a median follow-up of 10·0 years, deaths due to CAD or non-fatal MI were less frequent in the CCTA group compared with a control group. Conclusions: Despite a few gaps in knowledge about the value of a staging system of ACAD, the available evidence indicates that it is helpful in decreasing morbidity and mortality with available therapies. Full article