Search Results (260)

Background/Objectives: Fetal growth restriction (FGR), historically termed intrauterine growth restriction (IUGR), is a multifactorial condition in which the fetus fails to reach its genetically determined growth potential, most often due to placental insufficiency. Beyond its link with increased perinatal morbidity and mortality, FGR has been associated with long-term cardiovascular risk through early-life programming. The developing fetal heart is vulnerable to chronic hypoxia and nutrient deprivation, potentially inducing structural and functional alterations with lifelong consequences. This narrative review summarizes and critically appraises experimental and clinical evidence on the impact of FGR on myocardial development and cardiovascular health from fetal life to adulthood. Methods: We conducted a narrative review using a structured literature search of studies published in the last 15 years in PubMed and Scopus, focusing on experimental, imaging, and epidemiological research evaluating cardiac structure, function, and long-term cardiovascular outcomes in FGR. Evidence from fetal and neonatal echocardiography, including Doppler and speckle-tracking techniques, as well as molecular and histological studies, was examined. No statistical meta-analysis was performed. Results: FGR has been associated with reduced cardiomyocyte number, altered myocardial architecture, increased interstitial fibrosis, and persistent ventricular remodeling. Functional studies suggest early impairments in systolic and diastolic performance, with alterations in cardiac energy metabolism and epigenetic regulation. Advanced imaging may enable detection of subclinical cardiac dysfunction in utero and early postnatally. Epidemiological data suggest an increased risk of hypertension, ischemic heart disease, heart failure, and metabolic disorders in adulthood among individuals born growth-restricted. Conclusions: FGR represents an early cardiovascular risk condition. Improved understanding of fetal cardiac programming may help refine risk stratification, surveillance, and preventive strategies to reduce long-term cardiovascular morbidity in individuals born growth-restricted. Full article

Background: Gestational diabetes mellitus (GDM) complicates a significant number of pregnancies and is associated with both short- and long-term risks for the mother and child. Twin pregnancies are inherently high risk, and the coexistence of GDM may amplify these risks. While the effects of GDM in singleton pregnancies have been widely studied, data on its impact in twin gestations remain limited. The aim of this study was to determine differences regarding metabolic characteristics, treatment requirements, and maternal as well as fetal outcomes between twin and singleton pregnancies with GDM to contribute to improved perinatal care. Methods: This retrospective study included obstetric data from 73 twin pregnancies (146 neonates) and 1664 singleton pregnancies with a GDM diagnosis at a tertiary perinatal center in Berlin, Germany, between 2015 and 2022. Baseline characteristics and perinatal outcomes were assessed. Adjusted multiple linear and logistic regression analyses were used for group comparisons. Results: Women with GDM in twin and singleton pregnancies exhibited comparable glucose values in the 75 g oral glucose tolerance test (OGTT) (median fasting: 95 vs. 96 mg/dL; 1 h: 183 vs. 183 mg/dL; 2 h: 144 vs. 139 mg/dL). Despite this, insulin therapy was required significantly less often in twin (5.5%) compared to singleton pregnancies (22.3%) (OR = 0.86; 95% CI: 0.78–0.96). Among insulin-treated women, combined insulin therapy was most common in twins (75%), while singleton mothers most frequently received long-acting insulin alone (61.7%), followed by combined therapy (31.3%) and short-acting insulin alone (7%). Birthweight was significantly lower in twins (β = –0.83 kg; 95% CI: –0.98 to –0.69), and when evaluated using twin-based growth standards, twins were more likely to be classified as having intrauterine growth restriction (IUGR, <3rd percentile) (OR = 3.37; 95% CI: 0.96–9.11), being small for gestational age (SGA, <10th percentile) (OR = 2.50; 95% CI: 1.23–4.76), or having a birthweight below the 30th percentile (OR = 6.11; 95% CI: 3.49–11.12). No large-for-gestational-age (LGA, >90th percentile) neonates were observed in the twin group. Conclusions: GDM manifests differently in twin and singleton pregnancies. Despite similar OGTT values, twin mothers require insulin less frequently. Growth-related complications such as IUGR and SGA are significantly more frequent in twins, likely reflecting the physiological constraints of multiple gestations rather than GDM itself. Conversely, LGA is predominantly a concern in singleton pregnancies. These findings underscore the need for individualized diagnostic criteria and management strategies for GDM in twin pregnancies. Full article

Pre-eclampsia (PE) is a multisystem disorder that affects 5–6% of all pregnancies. Background: PE and intrauterine growth restriction (IUGR) are two major causes of maternal mortality and morbidity. We hypothesize that first-trimester pregnancy-associated plasma protein-A (PAPP-A) levels are useful as a prognostic marker. The aim of our study is to identify the role of PAPP-A and placental thickness in pre-eclampsia screening, as well as its value in IUGR prognosis. Methods: This prospective study was conducted at the Al. Simionescu County Hospital Hunedoara, Romania, Department of Obstetrics and Gynecology, from 12 May to 31 October 2025. A total of 102 patients were included in our study; of these, 28 patients (28.56%) developed pre-eclampsia, and 13 (13.26%) developed IUGR associated with PE. Results: The demographic data showed no differences between groups, except for BMI, smoking habits, and diabetes mellitus. Of the 28 cases of pre-eclampsia, 14.28% had PE detected by 28 weeks, 46.4% had PE associated with IUGR by 33/34 weeks, and 39.32% had PE detected at term/delivery. The highest detection rate was at 33/34 weeks, when the association with IUGR was obvious. For PE with IUGR at 34 weeks, the area under the curve (AUC) was 0.909, with a p-value < 0.001. The PAPP-A cut-off was 0.65 MoM, indicating high sensitivity and specificity for predicting PE. Placental thickness was also assessed, resulting in statistically significant differences between groups. The PAPP-A level shows strong predictive value for PE, especially when associated with placental thickness. Conclusions: This study demonstrates a clear correlation between low PAPP-A in the first trimester of pregnancy, placental thickness in the second trimester, and the subsequent development of pre-eclampsia and its association with IUGR. Full article

Background/Objectives: Circulating inflammatory cytokines and tissue sensitivity are both elevated following heat stress-induced intrauterine growth restriction (IUGR). Cytokines disrupt myoblast function and muscle growth, and thus we hypothesized that suppressing inflammatory tone in IUGR-born lambs by supplementing anti-inflammatory nutraceuticals would improve early postnatal growth. Methods: IUGR lambs produced by maternal heat stress were supplemented daily with 42 mg/kg oral omega-3 polyunsaturated fatty acid (ω-3 PUFA) Ca²⁺ salts or placebo from birth to 28 days of age. Results: By day 28, the 21% lighter bodyweights for IUGR lambs were fully resolved by ω-3 PUFA due to the complete recovery of average daily gain. Subcutaneous fat deposition and visceral organ growth were modestly diminished in IUGR-born lambs, but skeletal muscle mass was more markedly restricted. This coincided with 63% less muscle AdipoR2 but 27% greater circulating adiponectin. ω-3 PUFA reduced or eliminated deficits in subcutaneous fat, visceral organs, and five of the six individual muscles assessed, which corresponded with rescue of myoblast populations and AdipoR2 content. In turn, asymmetric growth restriction was resolved at one month of age. Conclusions: These findings show that targeting heightened inflammatory tone during the neonatal period in IUGR-born offspring can recover early growth in skeletal muscle and other soft tissues. Full article

Background: Intrauterine Growth Restriction (IUGR) is associated with a distinct neonatal metabolic profile, attributable to chronic intrauterine nutritional deprivation and suboptimal placental nutrient exchange. Upon delivery, IUGR neonates typically present with depleted nutrient stores, dysregulated endocrine activity, and a spectrum of micronutrient deficiencies, factors that collectively compromise metabolic homeostasis and significantly influence subsequent health trajectories. Methods: This narrative review systematically synthesizes the current body of evidence from clinical, biochemical, and translational investigations pertaining to the micronutrient status and pivotal endocrine markers in neonates affected by intrauterine growth restriction. The collected findings were integrated to elucidate metabolic adaptation mechanisms, immediate clinical ramifications, and the potential pathways linking neonatal biochemical patterns to long-term metabolic programming. Results: IUGR neonates consistently exhibit reduced cord-blood concentrations of essential micronutrients, including vitamin D, iron (Fe), zinc (Zn), magnesium (Mg), folate (vitamin B9), and cobalamin (vitamin B12), reflecting compromised placental nutrient transfer and limited fetal reserves. Concomitantly, endocrine alterations—most notably reduced insulin (INS) and C-peptide (C-pep) levels—indicate suppressed pancreatic β-cell activity and a prevailing hypoanabolic adaptive state. In parallel, disturbances in mineral metabolism, characterized by lower calcium (Ca) concentrations and increased alkaline phosphatase (ALP) activity, suggest impaired bone mineralization during the critical phase of early postnatal adaptation. Collectively, these biochemical patterns increase vulnerability to early clinical complications such as neonatal hypoglycemia and bone demineralization, disrupt early growth trajectories, and are associated with an elevated long-term risk of insulin resistance and adverse cardiometabolic programming. Conclusions: IUGR neonates consistently demonstrate a synergistic interplay of micronutrient deficiencies and adaptive endocrine responses, profoundly impacting immediate postnatal metabolic stability and predisposing them to long-term health challenges. Therefore, early biochemical screening, followed by tailored nutritional and hormonal interventions, may assist restore metabolic balance, promote growth and decrease long term risk for metabolic diseases. Full article

Background: Prader–Willi syndrome (PWS) is a multisystemic complex imprinting disorder. Prenatal diagnosis of PWS is still a challenge with non-specific ultrasound markers and limitations for diagnosis with non-invasive screening methods. Prenatal suspicion and early postnatal diagnosis are essential for promoting healthy growth and development, preventing complications, and providing healthcare professionals and families with the necessary support and resources for effective management. Presentation: We report two PWS cases caused by maternal uniparental disomy, who presented with IUGR, characterized by reduced fetal abdominal circumference (AC) in the second and early third trimesters, reduced fetal movements, normal Doppler indices and oligohydramnios. They were diagnosed in the early neonatal period with no prenatal suspicion but with similar ultrasound markers of the developing pregnancies, analyzed retrospectively. Aim: This study aims to emphasize the need to raise awareness among specialists about genetic syndromes such as Prader–Willi syndrome, to improve the information provided to couples regarding the limitations of current prenatal screening methods, as well as to ensure that, in cases of prenatal suspicion, appropriate genetic testing can be initiated. A confirmed diagnosis would allow timely and adequate measures to be taken, given the complications of the postnatal period in these patients and their need for specialized care and management. Conclusions: The presence of the aforementioned prenatal characteristics may raise suspicion for PWS. In such cases, invasive diagnostic procedures and methylation testing may be indicated, enabling earlier diagnosis and timely management, which can ultimately improve the quality of life of affected individuals and their families. Full article

Oxidative stress (OS) is a critical regulator of placental development; however, its specific effects on trophoblast biology remain incompletely elucidated. This narrative review synthesizes evidence derived from studies using human placental tissues and trophoblast cell models to delineate how excessive reactive oxygen species (ROS) disrupt molecular and cellular pathways essential for normal placentation. The literature search was restricted to human-based and in vitro investigations. Across these studies, OS was consistently shown to impair mitochondrial function in trophoblasts, resulting in increased mitochondrial ROS generation, loss of mitochondrial membrane potential, and activation of apoptotic signaling cascades. These mitochondrial disturbances were associated with reduced trophoblast proliferation, migration, and invasion, as well as dysregulation of angiogenic balance. Furthermore, several studies reported alterations in mitophagy, involvement of redox-sensitive pathways such as CYP1A1 and KLF9, and the extracellular release of mitochondrial DNA, which was linked to reduced cell viability and increased necrotic cell death. Collectively, the available evidence indicates that OS interferes with key trophoblast-dependent developmental processes, providing mechanistic insight into the pathogenesis of placental dysfunction observed in pregnancy complications such as preeclampsia (PE) and intrauterine growth restriction (IUGR). Elucidation of these pathways may inform the development of targeted therapeutic strategies aimed at preserving placental function and improving adverse pregnancy outcomes. Full article

Background/Objectives: Preeclampsia is a leading cause of maternal and perinatal morbidity worldwide, yet its underlying mechanisms remain unclear. Polyunsaturated fatty acids, particularly docosahexaenoic acid (DHA), are essential for placental development and vascular function, but evidence on their role in preeclampsia is inconsistent. This study aimed to compare serum DHA levels between women with preeclampsia and normotensive pregnant women and to examine their association with disease severity and maternal and perinatal outcomes. Methods: A total of 145 pregnant women aged 18–40 years were enrolled, including 47 with newly diagnosed preeclampsia (PE) and 98 normotensive controls. PE was defined according to the ACOG 2019 criteria. Serum DHA levels were measured using ELISA in fasting blood samples collected at the first visit. Results: Maternal serum DHA levels did not differ significantly between preeclampsia and control groups (p = 0.571); they were similar across control, mild PE, and severe PE groups. DHA showed a negative correlation with neutrophil-to-lymphocyte ratio (r = −0.305) and maternal hospitalization duration (r = −0.334). Independent predictors of PE included nulliparity (OR: 4.43), advanced age (OR: 1.14), elevated BMI (OR: 1.29), and low albumin (OR: 0.77). After adjusting for age and BMI, DHA was an independent negative predictor of IUGR (OR: 0.65). Conclusions: DHA levels: Placental and/or fetal DHA metabolism may be impaired in patients with preeclampsia. Although DHA was not associated with the development of PE, it was a negative predictor of IUGR. DHA reduces the length of maternal hospital stay through its anti-inflammatory effect. Full article

Individuals born after intrauterine growth restriction (IUGR) are at increased risk of long-term cardiovascular complications, including elevated blood pressure, endothelial dysfunction, and arterial stiffness. Endothelial progenitor cells (EPCs), particularly endothelial colony-forming cells (ECFCs), play a critical role in maintaining vascular homeostasis. Previously, Simoncini et al. observed that in a rat model of IUGR, six-month-old males exhibited elevated systolic blood pressure (SBP) and microvascular rarefaction compared with control (CTRL) rats. These vascular alterations were accompanied by reduced numbers and impaired function of bone marrow-derived ECFCs, which were associated with oxidative stress and stress-induced premature senescence (SIPS). In contrast, IUGR females of the same age and from the same litter did not exhibit higher SBP or microvascular rarefaction, raising the question of whether ECFC dysfunction in IUGR female rats can be present without vascular alterations. So, we investigated ECFCs isolated from six-month-old female IUGR offspring (maternal 9% casein diet) and CTRL females (23% casein diet). To complete the vascular assessment, we performed in vivo and in vitro investigations. No alteration in pulse wave velocity (measured by echo-Doppler) was observed; however, IUGR females showed decreased aortic collagen and increased elastin content compared with CTRL. Regarding ECFCs, those from IUGR females maintained their endothelial identity (CD31⁺/CD146⁺ ratio among viable CD45⁻ cells) but exhibited slight alterations in progenitor marker expression (CD34) compared with those of CTRL females. Functionally, IUGR-ECFCs displayed a delayed proliferation phase between 6 and 24 h, while their ability to form capillary-like structures remained unchanged, however their capacity to form capillary-like structures was preserved. Regarding the nitric oxide (NO) pathway, a biologically relevant trend toward reduced NO levels and decreased endothelial nitric oxide synthase expression was observed, whereas oxidative stress and SIPS markers remained unchanged. Overall, these findings indicate that ECFCs from six-month-old female IUGR rats exhibit only minor functional alterations, which may contribute to vascular protection against increase SBP, microvascular rarefaction, and arterial stiffness. Full article

Monogenic diabetes (MD) is a rare and heterogeneous group of disorders caused by genetic variants in genes involved in glucose metabolism. Among many MD genes, the insulin gene (INS) deserves special attention, as its variants are responsible for both permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM), as well as a form of MODY (maturity-onset diabetes of the young)—INS-MODY. The aim of the study was to perform a clinical and molecular analysis of patients focused on the evaluation of INS gene variants identified during molecular testing in patients referred with suspected MD, and to assess the prediction of their impact on protein structure using in silico methods. Between 2017 and 2024, 1043 unrelated probands were tested using targeted next-generation sequencing (tNGS) panels. Three pathogenic or likely pathogenic variants in the INS gene were identified in three unrelated families, indicating that this gene accounts for 0.38% of MD cases. This allowed for the diagnosis of PNDM in two patients with diabetes diagnosed within the first four months of life and INS-MODY in a patient with diabetes since the age of 16. Moreover, in the patient with PNDM and the INS:c.T104C variant, additional disorders were identified in the form of intrauterine growth restriction (IUGR) and neurological disorders. Importantly, two of the identified genetic variants, c.C103G and c.G3C, have not previously been described in the literature. Furthermore, in silico analysis of the variants at the protein level, i.e., investigation of mutations at the 35th residue, indicated that symptom severity correlates with the extent of structural changes in insulin. The results obtained broaden the spectrum of causative variants of the INS gene, but also emphasize the clinical significance of these variants in patients with various forms of diabetes, pointing to the key role of comprehensive genetic testing in enabling accurate diagnosis and targeted treatment of patients. Full article

Background/Objectives: Intrauterine growth restriction (IUGR) is a condition in which a fetus does not reach its normal growth potential and is associated with increased neonatal morbidity. Surveillance relies on cardiotocography, a biophysical ultrasound, and a Doppler assessment, but placental pathology remains insufficiently integrated into clinical evaluations. This study aimed to compare placentas from IUGR and normal pregnancies. Methods: This cohort included 34 pregnancies (16 IUGR, 18 controls) managed at Hunedoara County Hospital (Romania). The ultrasound and Doppler parameters were documented. The placentas were collected after delivery, fixed in formalin, and processed using standard histopathological protocols. The villous morphology and maternal vascular malperfusion features were assessed on H&E sections, focusing on syncytial knots, villous caliber reduction, stromal fibrosis, fibrin deposition, and infarctions. Immunohistochemistry for CD34, cytokeratin 7 (CK7), CD68, vascular endothelial growth factor (VEGF), and Hypoxian inducible factor 1 (HIF-1α)was performed using a semi-quantitative 0–3 scoring system. A statistical analysis was performed using chi-squared testing for categorical variables and t-tests for continuous variables. Results: The ultrasound evaluation showed an estimated fetal weight below the 10th percentile and abnormal Doppler indices in the IUGR group. The histopathology demonstrated a strong association between IUGR and villous abnormalities, including an increased number of syncytial knots, stromal fibrosis, a reduced villous caliber, and placental infarctions. The immunohistochemistry showed a marked overexpression of VEGF and HIF-1α and increased CD68-positive Hofbauer cells in IUGR placentas (p < 0.0001), while CD34 and CK7 displayed preserved strong staining in both groups. Conclusions: Placentas from IUGR pregnancies exhibited advanced maternal vascular malperfusion with consistent hypoxic and inflammatory changes, correlating with Doppler alterations. These findings highlight the diagnostic relevance of placental pathology in pregnancies with IUGR. Full article

Background/Objectives: Fetal growth restriction (FGR), formerly known as intrauterine growth retardation (IUGR), is defined as a fetus’ failure to reach its genetically predetermined growth potential. FGR has also been implicated in the development of autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD), though strong supporting literature has yet to be published. This study aims to review the existing associations between FGR and autism spectrum disorder or attention-deficit hyperactivity disorder as studied in relevant literature, as well as the mechanisms that provide explanation of that association. Methods: We used a combination of the terms ‘Autism spectrum disorder’ OR ‘Attention deficit hyperactivity disorder’ OR ‘neurodevelopmental disorders’ AND ‘intrauterine growth retardation (IUGR)’ OR ‘fetal growth restriction (FGR)’ in an electronic search of PubMed/MEDLINE and Scopus databases. Results: After evaluating the existing literature, we found only a few studies assessed the risk of developing ASD or ADHD in IUGR/FGR children. Neurodevelopmental disorders have generally been linked to very low birth weight, small for gestational age neonates (SGA), prematurity, somatic mutations, and intrauterine caffeine and alcohol exposure. While available evidence supports the notion that IUGR/FGR is related to cognitive impairment and behavioural disorders, the association with ASD or ADHD remains elusive due to the marked variability in the reported outcomes. Few studies have reported a respective higher risk for autism spectrum disorders, yet most of them have failed to identify a statistically significant correlation. Conclusions: While autism spectrum disorders and attention deficiency disorder have been generally associated with FGR children, the existing body of literature offers limited evidence to support this theory. Full article

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are obstetric complications associated with placental dysfunction, which represent a public health problem due to high maternal and fetal morbidity and mortality. Early detection is crucial for timely interventions. Therefore, this study proposes the development of models based on fuzzy cognitive maps (FCM) optimized with metaheuristic algorithms (particle swarm optimization (PSO) and genetic algorithms (GA)) for the prediction of PE and IUGR. The results showed that FCM-PSO applied to the PE dataset achieved excellent performance (accuracy, precision, recall, and F1-Score = 1.0). The FCM-GA model excelled in predicting IUGR with an accuracy and F1-Score of 0.97. Our proposed models outperformed those reported in the literature to predict PE and IUGR. Analysis of the relationships between nodes allowed for the identification of influential variables such as sFlt-1, sFlt-1/PlGF, and uterine Doppler parameters, in accordance with the pathophysiology of placental disorders. FCM optimized with PSO and GA offer a viable clinical alternative as a medical decision support system due to their ability to explore nonlinear relationships and interpretability of variables. In addition, they are suitable for scenarios where low computational resource consumption is required. Full article

During pregnancy, the fetus is entirely dependent on maternal sources of vitamin D, which also regulates placental function. Vitamin D deficiency during pregnancy has been associated with intrauterine growth restriction (IUGR). This study aims to provide a narrative review of the potential influence of vitamin D deficiency on the pathogenesis of IUGR, and the potential benefits of vitamin D supplementation during pregnancy on fetal anthropometry. This review highlights the high prevalence of vitamin D deficiency among pregnant women and newborns worldwide, even in sunny countries. Most studies support that fetal vitamin D levels are directly related to maternal vitamin D levels. There is extensive literature confirming the relation between maternal vitamin D status and fetal growth patterns throughout pregnancy (both early and late). However, there is currently insufficient evidence to establish recommendations on optimal prenatal vitamin D supplementation in women to reduce the risk of IUGR. Full article

High doses of ionizing radiation during prenatal development can cause growth restriction, or a decrease in growth of the developing offspring. This outcome of intrauterine growth restriction (IUGR) can predispose the offspring to lifelong health outcomes, which is referred to as developmental programming. The role of the placenta in radiation-induced IUGR was investigated using a mouse model. Pregnant BALB/cAnNCrl mice were externally irradiated with 1.82 Gy x-ray irradiation on gestational day 14.5. Fetoplacental units were collected on gestational day 18.5, and growth restriction was observed in irradiated offspring. Whole placenta samples from growth restricted and sham-irradiated groups were analyzed via RNA-sequencing analysis. Differential gene expression (DEG) analysis revealed a total of 166 DEGs in the irradiated samples. Validation of these DEG findings were completed using RT-qPCR analysis. Gene ontology (GO) analysis of the DEGs supported the involvement of autoimmune response and dysregulation in retinol (vitamin A) metabolism in the placenta. Upstream prediction analysis identified a number of potential regulators responsible for the DEG profiles including Nppb, Myod1 and genes of the classic complement system (Complement C1q chains C1qa, C1qb, C1qc). Overall, these findings present an overview of the dysregulation in the mouse placenta following an acute, high-dose radiation exposure. Full article