Search Results (174)

Background: The worldwide prevalence of FGR is about 13% and can lead to various adverse perinatal outcomes, including preterm birth, stillbirth, and neonatal mortality. Hypoxia-Inducible Factor-1 (HIF-1) is an important regulator of oxygen homeostasis in humans and is crucial for placental development. The aim of this study is to determine the pattern of HIF-1A expression in placenta, and to correlate its association with preeclampsia, fetal growth restriction and adverse perinatal outcomes. Methods: This study comprised a total of 158 cases with 42 cases of mother having babies with fetal growth restriction (FGR), 39 cases of mother with preeclampsia (PE), 35 cases of mother with preeclampsia and fetal growth restriction and 42 controls. The expression of HIF-1A was evaluated in various placental cell types, including cytotrophoblasts, syncytiotrophoblasts, fetal endothelial cells, maternal endothelial cells, and decidual cells. Results: The expression of HIF-1A in placental decidual cells of mother with FGR (21/42, 50%, p < 0.0001), PE (25/39, 64.1%, p < 0.0001) and PE with FGR (12/35, 34.3%, p < 0.0001) were significantly increased compared to controls (1/42). Intriguingly, HIF-1A expression was significantly reduced in the placental cytotrophoblasts and syncytiotrophoblasts of mother with PE and FGR (2/35, 5.7%) compared to PE alone (11/39, 28.2%) (p = 0.0142). Conclusions: We found that increased HIF-1A expression in the nuclei of decidual cells was observed in the mothers of babies with FGR, both with and without PE. While HIF-1A expression in the cytotrophoblasts and syncytiotrophoblasts was significantly reduced between mothers with PE and mothers with PE and FGR. This suggests HIF-1A expression might play a role in the pathogenesis of FGR. Full article

Pulmonary hemorrhage (PH) is a life-threatening complication predominantly affecting preterm infants, particularly those with very low birth weight (VLBW) and fetal growth restriction (FGR). Typically occurring within the first 72 h of life, PH is characterized by acute respiratory deterioration and significant morbidity and mortality. This review synthesizes current evidence on the multifactorial pathogenesis of PH, highlighting the roles of immature pulmonary vasculature, surfactant-induced hemodynamic shifts, and left ventricular diastolic dysfunction. Key risk factors include respiratory distress syndrome (RDS), hemodynamically significant patent ductus arteriosus (hsPDA), sepsis, coagulopathies, and genetic predispositions. Diagnostic approaches incorporate clinical signs, chest imaging, lung ultrasound, and echocardiography. Management strategies are multifaceted and include ventilatory support—particularly high-frequency oscillatory ventilation (HFOV)—surfactant re-administration, blood product transfusion, and targeted hemostatic agents. Emerging therapies such as recombinant activated factor VII and antifibrinolytics show promise but require further investigation. Preventive measures like antenatal corticosteroids and early indomethacin prophylaxis may reduce incidence, particularly in high-risk populations. Despite advancements in neonatal care, PH remains a major contributor to neonatal mortality and long-term neurodevelopmental impairment. Future research should focus on individualized risk stratification, early diagnostic tools, and optimized treatment protocols to improve outcomes. Multidisciplinary collaboration and innovation are essential to advancing care for this vulnerable population. Full article

Background/Objectives: The application of shear wave elastography (SWE) for the assessment of placental disease is still unproven and there is limited data correlating placental biomechanical properties with aberrations in fetal growth. This study investigated changes in placental shear wave velocity (SWV) in early and late fetal growth restriction (FGR). Methods: We analyzed three study cohorts: Pregnancies with appropriate growth for gestational age (AGA) and those with early (<32 weeks’) and late (>32 weeks’) FGR. Mean SWV at two time points was compared in the following cohorts: all FGR vs. AGA, early FGR vs. late FGR, early FGR vs. AGA, and late FGR vs. AGA. Results: The study comprised 222 women—79 (35.6%) FGR and 143 (64.4%) AGA. Of the FGR pregnancies, 37 (46.8%) were early and 42 (53.2%) were late. On multivariate analysis mean, SWV was not increased in FGR compared to AGA placentae (β 0.21, 95% CI −0.17–0.60, p 0.28). It was also not increased in early FGR compared to late FGR or AGA placentae (β 0.36, 95% CI −0.06–0.77, p 0.09). We observed an effect measure modification by pre-eclampsia, increasing mean SWV to a greater extent in AGA compared to FGR cases. Conclusions: Although previous studies have shown an association between placental SWV and FGR, our study showed no difference between cases and controls. The interaction of pre-eclampsia indicated that SWE may have a greater role in pre-eclampsia than in FGR alone. Further investigation of the influence of increased maternal vascular pressure on placental stiffness would be beneficial. Full article

Gestational chronic hypoxia impacts prenatal development, leading to fetal growth restriction (FGR), defined as the fetus’s failure to reach its genetic growth potential. Postnatal hypoxia in the cerebral tissue can induce a redox imbalance and mitochondrial dysfunction, consequently increasing neuronal death. However, these data cannot necessarily be extrapolated to prenatal hypoxia. In this regard, this study aims to describe the effect of gestational hypoxia on redox balance and apoptosis cell death mechanisms in the prefrontal cortex of guinea pigs. Ten Guinea pig (Cavia porcellus) pregnant dams were utilized in this study; five gestated in normoxia (Nx; three newborn males, and two females) and five gestated under chronic hypobaric hypoxia (Hx; two newborn males, and three females). We monitored the pregnancies by ultrasound examinations from gestational days 20 to 65 (term ~ 70). At birth, pups were euthanized, and the fetal brain was collected for cellular redox measurement, mitochondrial enzyme expression, and apoptosis assay. Gestation under hypoxia induced an imbalance in the expression of anti- and pro-oxidant enzymes, resulting in increased oxidative stress. Additionally, a decrease in cytochrome I and III expression and neuronal density in the neonatal prefrontal cortex was observed. Finally, DNA fragmentation was increased by the TUNEL assay in the brain tissue of newborns gestated under chronic hypoxia. Our findings demonstrate the association of gestational hypoxia with oxidative stress and neuronal death in newborns, which may predispose to neuronal dysfunction in adulthood. Full article

Background: Mitochondria are essential for placental function as they regulate energy metabolism, oxidative balance, and apoptotic signaling. Increasing evidence suggests that placental mitochondrial dysfunction may play a role in the development of many poor perinatal outcomes, including preeclampsia, intrauterine growth restriction (IUGR), premature birth, and stillbirth. Nonetheless, no systematic review has thoroughly investigated this connection across human research. This study aims to consolidate evidence from human research concerning the link between placental mitochondrial dysfunction and negative birth outcomes. Methods: A systematic search of PubMed, Scopus, and Web of Science identified human research examining placental mitochondrial features (e.g., mtDNA copy number, ATP production, oxidative stress indicators) in connection with adverse pregnancy outcomes. Methodological variety resulted in narrative data extraction and synthesis. Results: Twenty-nine studies met the inclusion criteria. Mitochondrial dysfunction was consistently associated with PE, IUGR, FGR, and PTB. The most often observed outcomes included diminished mtDNA copy number, decreased ATP production, elevated reactive oxygen species (ROS), and disrupted mitochondrial dynamics, characterized by increased DRP1 and decreased MFN2. Early-onset preeclampsia and symmetric fetal growth restriction exhibited particularly severe mitochondrial abnormalities, indicating a primary placental origin of the condition. Conclusions: A significant factor contributing to adverse pregnancy outcomes is the dysfunction of placental mitochondria. The analogous molecular signatures across many disorders suggest promising avenues for developing targeted therapies aimed at improving maternal–fetal health and predictive biomarkers. Full article

Background: This study investigates the impact of ovarian endometriosis on pregnancy outcomes. Methods: A retrospective analysis was conducted at Etlik Zübeyde Hanım Women’s Diseases Training and Research Hospital between January 2019 and December 2024, including 1127 pregnant women—170 with ovarian endometriosis and 957 healthy controls. Pregnancies achieved via assisted reproductive techniques were excluded. Statistical analyses were performed using appropriate tests, and a p-value < 0.05 was considered significant. Results: Women with ovarian endometriosis had higher rates of miscarriage (21.8% vs. 7.5%), preterm birth (15.0% vs. 8.8%), and placenta previa (4.7% vs. 0.6%), with adjusted odds ratios (OR) of 3.41, 1.84, and 7.82, respectively. No significant differences were observed in terms of gestational diabetes, hypertensive disorders, fetal growth restriction (FGR), intrahepatic cholestasis of pregnancy (ICP), placental abruption, or preterm premature rupture of membranes (PPROM). Cyst size and bilaterality were not associated with complications. Conclusions: Spontaneously conceiving women with ovarian endometriosis are at increased risk for miscarriage, placenta previa, and preterm birth. Prospective randomized studies are warranted to validate these findings. Full article

Background/Objectives: The relationship between ultrasound parameters and fetal health in the context of intrauterine growth restriction (IUGR) pregnancies constitutes a significant focus of scholarly research. A comprehensive range of Doppler and echocardiographic evaluations, encompassing the umbilical artery, middle cerebral artery, ductus venosus, uterine arteries, cardiac contractility, ventricular filling, and the thickness of the interventricular septum, has been proposed in pathological pregnancies. Methods: The aim of this paper is to present an examination of these metrics and their implications for fetal health within the framework of IUGR pregnancies and to report a case series in which we analyzed the correlation of these factors. The assessment of these ultrasound indicators can help in better management of the cases in order to obtain better fetal outcomes. Results: Our case study presented dynamics corelated to the after-birth evaluation of the neonate, reflecting the importance of complete ultrasound assessment in high-risk cases. Conclusions: Speckle tracking echocardiography has significantly advanced our understanding of cardiac function in IUGR fetuses. As shown in our cases, it can be used to detect early signs of cardiac dysfunction, differentiating between FGR and SGA. Full article

Fetal growth restriction (FGR) is an obstetric condition most frequently caused by placental dysfunction. It is a major cause of perinatal morbidity with limited treatment options, so identifying the underpinning mechanisms is important. Peptidylarginine deiminases (PADs) are calcium-activated enzymes that mediate post-translational citrullination (deimination) of proteins, through conversion of arginine to citrulline. Protein citrullination leads to irreversible changes in protein structure and function and is implicated in many pathobiological processes. Whether placental protein citrullination occurs in FGR is poorly understood. We assessed protein citrullination and PAD isozyme abundance (PAD1, 2, 3, 4 and 6) in human placental samples from pregnancies complicated by early- and late-onset FGR, compared to appropriate-for-gestational-age (AGA) controls. Proteomic mass spectrometry demonstrated that the placental citrullinome profile changed in both early- and late-onset FGR, with 112 and 345 uniquely citrullinated proteins identified in early- and late-onset samples, respectively. Forty-four proteins were citrullinated only in control AGA placentas. The proteins that were uniquely citrullinated in FGR placentas were enriched for gene ontology (GO) terms related to neurological, developmental, immune and metabolic pathways. A greater number of GO and human phenotype pathways were functionally enriched for citrullinated proteins in late- compared with early-onset FGR. Correspondingly, late-onset but not early-onset FGR was associated with significantly increased placental abundance of PAD2 and citrullinated histone H3, determined by Western blotting. PAD3 was downregulated in early-onset FGR while abundance of PAD 1, 4 and 6 was less altered in FGR. Our findings show that placental protein citrullination is altered in FGR placentas, potentially contributing to the pathobiology of placental dysfunction. Full article

Background: COVID-19 is linked to multiple adverse pregnancy outcomes but with inconsistent evidence associating the disease with fetal growth restriction (FGR) and small for gestational age (SGA). There are limited data on the impact of COVID-19 on neonatal growth measurements, specifically microcephaly without SGA or low birth weight. We hypothesize that COVID-19 is associated with smaller neonatal head measurements without increasing the risk of small for gestational age. This relationship may be related to the timing of COVID-19 exposure in pregnancy. Methods: An Institutional Review Board (IRB) approved retrospective cohort study enrolled 140 COVID-19-infected and 136 COVID-19-uninfected patients. Inclusion criteria: (a) singleton birth between 28 April 2020 and 31 December 2022; and (b) maternal COVID-19 infection diagnosed via polymerase chain reaction (PCR). Exclusion criteria: Less than 12 years of maternal age, major fetal anomalies, and fetal loss < 15 weeks. The outcomes were a comparison of newborn growth measurements (length, weight, and head circumference (HC) at birth), Ponderal Index (PI), and development of SGA between SARS-CoV-2-infected and uninfected patients. Maternal and neonatal characteristics were descriptively summarized, and multivariate analyses and linear regression models were performed. Baseline maternal demographics did not differ amongst cohorts. Results: Compared to the uninfected cohort, COVID-19 diagnosed in the third trimester was associated with a lower neonatal HC compared to newborns of uninfected patients (β = −0.38 [0.38 SD lower], 95% CI −0.65 to −0.10, p = 0.024). There was no significant difference among cohorts in birth length, weight, or diagnosis of small for gestational age. Conclusions: We found that COVID-19 infection in the third trimester was associated with a lower neonatal head circumference without associated SGA. The cause underlying this association is unknown. Further research to determine the risk of neurotropic fetal infection by SARS-CoV-2, like ZIKA’s effect on the fetal immune system leading to microcephaly, is urgently needed. Full article

Background: Placental grading remains underutilized in clinical practice despite its potential prognostic value. This study aimed to elucidate the relationship between premature placental calcification (PPC) and relevant perinatal outcomes in a large cohort. Methods: We conducted a retrospective cohort study involving 3088 singleton pregnancies that underwent routine third-trimester ultrasound examinations (30⁺⁰ to 35⁺⁶ gestational weeks) at the Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece, between January 2018 and December 2023. Placental calcification was graded using the Grannum system, categorizing placentas into Grades 0–1 (control), Grade 2, and Grade 3. Primary outcomes assessed were small for gestational age neonates (SGA) and preeclampsia. Secondary outcomes included gestational hypertension, fetal growth restriction (FGR), stillbirth, gestational age at birth, and birthweight centile. Multiple logistic regression was employed to adjust for confounders, i.e., maternal age, BMI, smoking, conception via assisted reproductive technology, and uterine artery pulsatility index. Results: In total, 544 pregnancies (17.6%) had Grade 2 placentas, and 41 pregnancies (1.3%) had Grade 3 placentas. Compared to the control group, Grade 2 placentas were associated with increased odds of SGA (adjusted odds ratio [aOR] 1.80; 95% confidence intervals [CI]: 1.43–2.25) and FGR (aOR 1.81; 95% CI: 1.35–2.42). Grade 3 placentas showed even higher odds of SGA (aOR 3.09; 95% CI: 1.55–6.17) and FGR (aOR 3.26; 95% CI: 1.53–6.95). No significant associations were found between placental grading and preeclampsia or stillbirth. Additionally, PPC was linked to lower birthweight percentiles and earlier gestational age at birth. Conclusions: Premature placental calcification (before 36⁺⁰ weeks), particularly Grade 3, is significantly associated with adverse perinatal outcomes such as SGA and FGR. Incorporating placental grading into routine prenatal care may enhance risk stratification and guide clinical decision making beyond traditional assessment methods. Full article

Placental-derived pregnancy complications encompass a range of disorders that hinder optimal fetal development, significantly impacting maternal and neonatal health outcomes. Key conditions include placental insufficiency, preeclampsia, fetal growth restriction (FGR) or intrauterine growth restriction (IUGR), fetal overgrowth, and gestational diabetes mellitus (GDM), which together contribute to a heightened risk of preterm birth, perinatal mortality, and long-term developmental challenges in affected infants. These complications are particularly notable because they generate approximately 80% of pregnancy disorders and pose significant public health concerns across diverse global contexts. Their management continues to face challenges, including a lack of consensus on diagnostic criteria and varied implementation of care standards. While imaging techniques like magnetic resonance imaging (MRI) and Doppler ultrasound have emerged as critical tools in clinical assessment, disparities in access to such technologies exacerbate existing inequalities in maternal and fetal health outcomes. Maternal and pregnancy care is a broad range of services aimed at promoting the well-being of women throughout the perinatal period. However, access to these services is often limited by economic, geographical, and sociocultural barriers, particularly for marginalized groups and women in low- and middle-income countries (LMICs). The implementation of targeted interventions designed to address specific obstacles faced by disadvantaged populations is a crucial component of bridging the gap in health equity in maternal care. Public health authorities and policymakers strive to develop evidence-based strategies that address the interplay between healthcare access, socioeconomic factors, and effective interventions in order to mitigate the adverse effects of placental-derived pregnancy complications. Continued research and data collection are essential to inform future policies and practices to improve outcomes for mothers and infants. Full article

The vector of modern obstetrics is aimed at finding ways to predict various placenta-associated complications, including those associated with neuronal dysfunction on in fetal growth restriction (FGR). The technology of fetal neuronal exosome (FNE) isolation from the maternal bloodstream opens up unique opportunities for detecting early signs of fetal brain damage. Using this method, FNEs were isolated from the blood of pregnant women with and without early-onset FGR, and the expression of a number of proteins in their composition was assessed (Western blotting). Significant changes in the level of proteins involved in neurogenesis (pro-BDNF (brain-derived neurotrophic factor), pro-NGF (nerve growth factor), TAG1/Contactin2) and presynaptic transmission (Synapsin 1, Synaptophysin) were revealed. The preliminary data on the expression of FNE proteins that perform post-translational modifications—sumoylation (SUMO 1, UBC9) and neddylation (NEDD8, UBC12)—were obtained. A relationship was established between altered protein expression and neonatal outcomes in newborns with growth restriction. Our study opens up new possibilities for non-invasive prenatal monitoring of fetal neurodevelopment disorders and possibilities of their correction in placenta-associated diseases. Full article

Even in the highest inhabited regions of the world, well above 2500 m altitude, women become pregnant and give birth to healthy children. The underlying adaptation to hypobaric hypoxia provides interesting insights into the physio(patho)logy of the human placenta. Although increasing altitude is regularly associated with fetal growth restriction (FGR), oxygen deficiency does not appear to be a direct cause. Rather, placental oxygen consumption is reduced to maintain the oxygen supply to the fetus. This comes at the expense of placental synthesis and transport functions, resulting in inappropriate nutrient supply. The hypoxia-inducible factor (HIF-1α), which modulates the mitochondrial electron transport chain to protect placental tissue from reactive oxygen species, plays a key role here. Reduced oxygen consumption also reflects decreased placental vascularization and perfusion, which is accompanied by an increased risk of maternal pre-eclampsia at high altitude. In native highlanders, the latter seems to be attenuated, partly due to a lower release of HIF-1α. In addition, metabolic peculiarities have been described in indigenous people that enhance glucose availability and thus reduce the extent of FGR. This review attempts to revisit the (albeit incomplete) knowledge in this area to draw the clinical reader’s attention to the crucial role of the placenta in defending the fetus against hypoxia. Full article

The developmental origins of adult disease theory support the concept that undernourished fetuses are at risk of developing metabolic syndrome due to the energy-saving ‘Thrifty Phenotype’. This metabolic plasticity represents an evolutionary adaptation that allows individuals to resist the intense pressure caused by cyclically recurring periods of nutritional deprivation. A comprehensive review was conducted following an extensive literature search in the PubMed/Medline and EMBASE databases concerning reports on fetal/intrauterine growth restriction and its metabolic-related long-term outcomes. We only included articles written in English that were published before 1 July 2024. There are several underlying mechanisms and metabolic and endocrine adjustments shaped by the perinatal environment, and they all contribute to progression towards adult disease. From in utero malnutrition or other insults during the fetal period to fetal programing and postnatal catch-up growth, it is difficult to identify the exact moment when this adaptative phenomenon meant to assure fetal survival and to set children on their own physiological growth curves lose its beneficial effect, establishing the trajectory to obesity, insulin resistance, and other hallmarks of metabolic syndrome. With clinical correspondence to an altered body mass, composition, and eating behaviors, it is evident that the metabolic complications linked to FGR are intricate and arise from disturbances in several pathways and organs, but the underlying processes responsible for the long-term consequences are just starting to be understood. The lack of continuity in perinatal-to-pediatric FGR research sets the challenge of exploring new directions in future scientific opportunities. These will hopefully represent a cornerstone in the management of FGR-related metabolic disorders in children, preventing these disorders from evolving into adult disease. Full article

Background: Fetal growth restriction (FGR) refers to a condition in which a fetus does not reach its genetically predetermined growth potential due to various pathological factors of maternal or fetal origin, with potential long-life consequences, such as elevated blood pressure, type 2 diabetes mellitus, obesity, dyslipidemia, atherosclerosis. Aim: The purpose of our research is to delve into the intricate relationship between economic and social factors and the occurrence of FGR. Methods: We analyzed risk factors previously associated with FGR and aimed to compare them between two cohorts of infants with FGR: a historical cohort of infants born from 2010 to 2012 and a contemporary cohort of infants born from 2020 to 2022. Results: The global incidence of FGR in our study was 5.13%, with non-significant differences between the two time periods: 5.03% in the historical cohort and 5.25% in the contemporary cohort. More mothers of FGR infants receive formal education and are employed in the contemporary group and thus have a more stable income. There was a major decrease in the number of preterm infants with FGR, from 23.9% in the historical cohort to 5.9% in the contemporary cohort (p < 0.001). Compared to the historical cohort, we found significant increases in the incidence of pregnancy-induced hypertension, Cesarean sections, and prenatal follow-up in the contemporary cohort (8.3% vs. 3.8%, p < 0.001; 59.2% vs. 49.9%, p < 0.001; 67.7% vs. 49.6%, p < 0.001, respectively) and we also found significant correlations between prenatal care on one side and maternal smoking, urban residence, higher maternal education, and prematurity on the other. Conclusions: Certain socioeconomic factors show definite improvements over the ten-year timespan, which results in an increase in prenatal care and a decrease in the rate of prematurity. However, the incidence of FGR remains constant over the considered period, meaning that other factors, apart from socioeconomic factors, play a substantial role. Recognizing these risk factors is crucial for developing effective public health strategies aimed at reducing the incidence of FGR and improving maternal and child outcomes. Full article