Stress-Induced Changes in Nucleocytoplasmic Localization of Crucial Factors in Gene Expression Regulation.

This study investigates the toxic effect of harmful materials, unfiltered by the placenta, on neonatal umbilical cord (UC) vessels, focusing on stress-induced adaptations in transcriptional and translational processes. It aims to analyze changes in pathways related to mRNA condensate formation, transcriptional regulation, and DNA damage response under maternal smoking-induced stress. UC vessels from neonates born to smoking (Sm) and nonsmoking mothers (Ctr) were examined. Immunofluorescence staining and confocal microscopy assessed the localization of key markers, including Transcription Complex Subunit 1 (CNOT1) and the largest subunit of RNA polymerase II enzyme (RPB1). Additionally, markers of DNA damage response, such as Poly(ADP-ribose) polymerase-1, were evaluated. In Sm samples, dissolution of CNOT1 granules in UC vessels was observed, potentially aiding stalled translation and enhancing transcription via RPB1 assembly and translocation. Control vessels showed predominant cytoplasmic RPB1 localization. Despite adaptive responses, Sm endothelial cells exhibited significant damage, indicated by markers like Poly(ADP-ribose) polymerase-1. Ex vivo metal treatment on control vessels mirrored Sm sample alterations, emphasizing marker roles in cell survival under toxic exposure. Maternal smoking induces specific molecular adaptations in UC vessels, affecting mRNA condensate formation, transcriptional regulation, and DNA damage response pathways. Understanding these intricate molecular mechanisms could inform interventions to improve neonatal health outcomes and mitigate adverse effects of toxic exposure during pregnancy.

Association between sociodemographic, obstetric, and lifestyle factors among Hungarian pregnant women-A cross-sectional study.

AIM: To learn the association between sociodemographic and obstetric factors and lifestyle characteristics of pregnant women, and to identify factors that can influence pregnant women's health consciousness. METHODS: A cross-sectional, questionnaire-based study was performed among women who gave birth in Szeged in 2014-2015. Data collection was based on a self-administered questionnaire and health documentations. Overall maternal health promoting behavior (MHPB) index was defined by summarizing the scores obtained from diet, physical activity, smoking status, and alcohol consumption. RESULTS: The final analysis included 1548 mothers; 41.3% (n = 602) of the sample had healthy diet, 9.0% (n = 134) were physically active and attended special pregnancy exercise classes, 84.4% (n = 1279) did not drink alcohol, and 93.5% (n = 1447) were nonsmokers. Regarding the MHPB index, 0.8% (n = 11) of the women reached the maximum score (20), while the average was 14.8 (SD = 2.58). Advanced maternal age (p < 0.001), having a spouse or partner (p < 0.001), higher educational level (p < 0.001), planned pregnancy (p < 0.001), and early visit at pregnancy care (p = 0.046) were significantly associated with higher MHPB index. CONCLUSION: The lifestyle of pregnant women can have a great impact on the developing fetus, either in a positive or negative way. In order to evaluate maternal lifestyle, overall health behavior should be considered. Lifestyle of the included women was not satisfactory, an improvement in health consciousness is needed at every social level; however, the differences between the various social classes may suggest the importance of further promotion and improvement of pregnancy planning and pregnancy care among younger and lower educated women.

Molecular Background of Toxic-Substances-Induced Morphological Alterations in the Umbilical Cord Vessels and Fetal Red Blood Cells.

The relationship between smoking and human health has been investigated mostly in adults, despite the fact that the chemicals originating from sustained maternal smoking disrupt the carefully orchestrated regulatory cascades in the developing fetus. In this study, we followed molecular alterations in the umbilical cord (UC) vessels and fetal red blood cells (RBCs), which faithfully reflect the in vivo status of the fetus. We showed evidence for the decreased level of DNA-PKcs-positive nuclei in samples with smoking origin, which is associated with the impaired DNA repair system. Furthermore, we pointed out the altered ratio of MMP-9 metalloproteinase and its endogenous inhibitor TIMP-1, which might be a possible explanation for the morphological abnormalities in the UC vessels. The presented in vivo dataset emphasizes the higher vulnerability of the veins, as the primary target for the toxic materials unfiltered by the placenta. All these events become amplified by the functionally impaired fetal RBC population via a crosstalk mechanism between the vessel endothelium and the circulating RBCs. In our ex vivo approach, we looked for the molecular explanation of metal-exposure-induced alterations, where expressions of the selected genes were upregulated in the control group, while samples with smoking origin showed a lack of response, indicative of prior long-term in utero exposure.

Positive evidence for neonatal imitation: A general response, adaptive engagement.

The study employed four gestural models using frame-by-frame microanalytic methods, and followed how the behaviours unfolded over time. Forty-two human newborns (0-3 days) were examined for their imitation of tongue protrusion, 'head tilt with looking up', three-finger and two-finger gestures. The results showed that all three gesture groups were imitated. Results of the temporal analyses revealed an early and a later, second stage of responses. Later responses were characterized by a suppression of similar, but non-matching movements. Perinatal imitation is not a phenomenon served by a single underlying mechanism; it has at least two different stages. An early phase is followed by voluntary matching behaviour by the neonatal infant.

Change in the Caries Status of Pregnant Women in Southeast Hungary and Its Background.

PURPOSE: To examine the caries status of pregnant women in southeast Hungary and compare the results with a similar study completed in the same region ten years earlier to determine whether any improvement has taken place in the past decade. Another objective was to assess the effects of age, socioeconomic status and number of pregnancies on oral health. MATERIALS AND METHODS: The dental examination of 130 pregnant women was carried out at the Dental Clinic of University of Szeged, Faculty of Dentistry in 2011-2013 (group 1). Caries status was examined according to WHO guidelines. In order to compare demographic and socioeconomic factors with DMF indices, find the decisive influencing factors and compare the results with the results of the previous study (group 2), two-way ANOVA and regression analyses were conducted. RESULTS: The number of highly educated, professional, urban participants included in the present group (group 1) was greater compared with that of group 2. Despite the higher age of the pregnant women in present study, statistically significantly lower DMFT (10.05 vs 12.57, p = 0.008) and DMFS (19.41 vs 26.26, p = 0.001) scores were found than ten years ago. In both studies, the regression analyses showed that women's age was the main contributing factor to caries status. CONCLUSION: The lower DMFT and DMFS values and the participants' willingness to participate in the dental screening in the present study group were probably the result of their higher educational background and that they worked as professionals.

Elevated levels of macromolecular damage are correlated with increased nitric oxide synthase expression in erythrocytes isolated from twin neonates.

Pregnancy is a state associated with an enhanced metabolism and demand for O2 , which may lead to the overproduction of reactive oxygen species (ROS) and hence to oxidative stress. An elevated ROS level may result in delayed development and a low birth weight. The aim of this study was to reveal the consequences of multiple pregnancies on the redox status of neonatal human red blood cells (RBCs) and evaluate the role of endothelial nitric oxide synthase (NOS3) - expressing RBCs in the generation of oxidative stress. The study presents evidence of higher levels of production of hydrogen peroxide, peroxynitrite and nitrate content in the RBCs of twin neonates, clearly reflected by an elevated level of protein and lipid damages. This phenotype appears to be a consequence of multiple pregnancies, regardless of the level of maturity or the birth weight of the twins. Besides the higher level of ROS, there was a general decrease in the expression of genes coding for antioxidants. The first data are presented on NOS3-expressing neonatal human RBCs. The number of RBCs producing NOS3 was more than twice as high in twin neonates compared to singletons, with no correlation to maturity.

Learning to imitate individual finger movements by the human neonate.

Imitation in human neonates, unlike imitation in young infants, is still regarded as controversial. Four studies with 203 newborns are presented to examine the imitation of index finger, two- and three-finger movements in human neonates. Results found differential imitations of all three modelled gestures, a left-handed pattern, and a rapid learning mechanism. The lateralized behavioural pattern suggests the involvement of a right lateralized neural network, and the mechanisms described in this study - (i) the accurate imitation of all aspects of the model's movements, (ii) the rapid learning component, and the (iii) the early sensitive period might fulfil the criteria for filial imprinting.

[Birth marks and neonatal skin disorders. From angel kiss to epidermolysis bullosa]. / Születési jegyek, újszülöttkori borelváltozások. Az angyalcsóktól az epidermolysis bullosáig.

INTRODUCTION: At present there are no exact epidemiologic data on the prevalence of neonatal skin disorders and birth marks in Hungary. AIM: The aim of the authors was to investigate the prevalence of skin disorders in mature healthy neonates after birth. METHOD: The survey was carried out in the Neonatal Care Unit at the Department of Obstetrics and Gynaecology at the University of Szeged between April, 2012 and May, 2013. RESULTS: A total of 2289 newborn infants underwent whole-body screening skin examinations. At least one skin manifestation was found in 63% of the neonates. The major groups of skin disorders were transient benign cutaneous lesions, vascular lesions, pigmented lesions, traumatic, iatrogenic, congenital or acquired disorders with skin injuries, developmental abnormalities and benign skin tumours. The most frequent transient cutaneous lesions were erythema toxicum neonatorum, sebaceous hyperplasia and desquamation. The most common vascular lesions were naevus simplex, haemangioma and haemangioma precursor lesion, while the most frequently observed pigmented lesions were congenital melanocytic naevi and Mongolian spot. CONCLUSIONS: In the vast majority of cases, special treatment was not necessary, but 5.27% of the neonates required local dermatologic therapy, and in 9.2% of neonates follow up was recommended.

A Study of Vitamin D Status and Its Influencing Factors among Pregnant Women in Szeged, Hungary: A Secondary Outcome of a Case-Control Study.

Adequate vitamin D (VD) intake during pregnancy is needed for fetal development and maternal health maintenance. However, while there is no doubt regarding its importance, there is not a unified recommendation regarding adequate intake. The main aim of our study was to measure the VD serum level of studied women, together with its potential influencing factors: demographic (i.e., age, level of education, relationship status and type of residence), conception and pregnancy related factors. Results are based on secondary data analyses of a retrospective case-control study of 100 preterm and 200 term pregnancies, where case and control groups were analyzed together. Data collection was based on a self-administered questionnaire, health documentation, and maternal serum VD laboratory tests. VD intake was evaluated by diet and dietary supplement consumption. According to our results, 68.1% of women took some kind of prenatal vitamin, and only 25.9% of them knew about its VD content. Only 12.1% of included women reached the optimal, 75 nmol/L serum VD level. Higher maternal serum levels were associated with early pregnancy care visits (p = 0.001), assisted reproductive therapy (p = 0.028) and advice from gynecologists (p = 0.049). A correlation was found between VD intake and serum levels (p < 0.001). Despite the compulsory pregnancy counselling in Hungary, health consciousness, VD intake and serum levels remain below the recommendations. The role of healthcare professionals is crucial during pregnancy regarding micronutrients intake and the appropriate supplementation dose.

Molecular Study on Twin Cohort with Discordant Birth Weight.

The increased rate of twinning has pointed out newer challenges in clinical practices related to gestational complications, intrauterine growth restriction, perinatal mortality, and comorbidities. As a twin pregnancy progresses, the increased demand for oxygen supply can easily disrupt the redox homeostasis balance and further impose a greater challenge for the developing fetuses. A substantial birth-weight difference acts as an indicator of a deficit in oxygenation or blood flow to one of the fetuses, which might be related to a low bioavailable nitric oxide level. Therefore, in this study, we focused on networks involved in the adjustment of oxygen supply, like the activation of inducible and endothelial nitric oxide synthase (NOS3) along with free radical and lipid peroxide formation in mature twin pairs with high birth-weight differences. The selected parameters were followed by immunofluorescence staining, fluorescence-activated cell sorting analysis, and biochemical measurements in the umbilical cord vessels and fetal red blood cells. Based on our data set, it is clear that the lower-weight siblings are markedly exposed to persistent intrauterine hypoxic conditions, which are connected to a decreased level in NOS3 activation. Furthermore, the increased level of peroxynitrite aggravates lipid peroxidation and induces morphological and functional damage and loss in redox homeostasis.

Analysis of various factors influencing the development of birthmarks and cutaneous lesions in newborn infants / A születési jegyek és az újszülöttkori borgyógyászati elváltozások kialakulásában szerepet játszó tényezok vizsgálata.

Összefoglaló. Bevezetés: A szakirodalomban számos felmérés született az újszülöttkori borelváltozások elofordulási gyakoriságának vizsgálatára. Az epidemiológiai vizsgálatok eredményei azonban nem mindig adaptálhatók, hiszen jelentos különbségeket találunk az egyes népcsoportok bormanifesztációi között, emellett kevés és ellentmondásos adat áll rendelkezésre arról, hogy milyen tényezok befolyásolják ezen bortünetek kialakulását. Célkituzés: Prospektív kohorszvizsgálatunk fo célkituzése az volt, hogy felmérjük az alapvetoen egészséges, érett újszülöttek borgyógyászati elváltozásainak elofordulási gyakoriságát, illetve megvizsgáljuk az ezen elváltozások kialakulásában szerepet játszó tényezoket. Módszer: Vizsgálatunkat a Szegedi Tudományegyetem Szülészeti és Nogyógyászati Klinikájának Újszülött Osztályán végeztük 2014 áprilisa és 2015 áprilisa között. Az újszülöttek borgyógyászati vizsgálatát követoen az édesanyák 50 kérdést tartalmazó, standardizált kérdoívet töltöttek ki. Az újszülöttekre, illetve a szülés körülményeire vonatkozó adatokat a hivatalos betegdokumentáció adatainak felhasználásával elemeztük. Eredmények: A vizsgálatban összesen 1629, kaukázusi típusú újszülött vett részt. 88,15%-uknál diagnosztizáltunk legalább egyfajta borgyógyászati eltérést. Vizsgálatunkban számos esetben szignifikáns korrelációt találtunk az újszülöttek neme, gestatiós kora és súlya, valamint az újszülöttkori borelváltozások elofordulási gyakorisága között. Emellett a szociodemográfiai tényezok, a szülok fenotípusos jellegzetességei, az édesanya betegségei, gyógyszerszedési szokásai, káros szenvedélyei is hatást gyakorolhatnak a laesiók kialakulására. Következtetés: Az irodalmi adatok áttekintését követoen elmondhatjuk, hogy vizsgálatunk rendkívül átfogó, új adatokat szolgáltat a neonatalis bortünetek elofordulási gyakoriságáról és a kialakulásukban potenciálisan szerepet játszó tényezok kapcsolatáról hazánkban és világviszonylatban is. Orv Hetil. 2022; 163(13): 513-522. INTRODUCTION: Cutaneous lesions are very frequent in neonates. Despite the fact that the incidence of neonatal skin disorders has been reported in several studies, very few reports address the factors that influence the appearance of birthmarks. OBJECTIVE: In this cross-sectional study, we aimed to record cutaneous findings in essentially healthy, term and late preterm neonates, and to use this data to assess the associations between various factors and the appearance of birthmarks. METHOD: The study was conducted on consecutive neonates born between April 2014 and April 2015 at the Department of Obstetrics and Gynecology at the University of Szeged. After the whole-body skin examination, a standardized questionnaire consisting of 50 questions was completed by the mothers. Data relating to the neonatal history of the participating neonates were obtained from the official neonatal medical charts. RESULTS: A total of 1629 Caucasian neonates were included in the study. Of these, 88.15% exhibited at least one skin manifestation. Significant correlations were found between the newborn gender, gestational age and weight and the presence of many skin manifestations. Furthermore, sociodemographic factors, parental phenotypic characteristics, maternal diseases and medicine-taking habits also have impact on the development of certain cutaneous lesions. CONCLUSION: By examining a large number of newborns and by providing detailed analysis of several neonatal, perinatal and parental factors, our study contributes to a deeper understanding of the development of the examined cutaneous lesions. Orv Hetil. 2022; 163(13): 513-522.

Prevalence rates and socioeconomic characteristics of post-partum depression in Hungary.

The rapid socioeconomic transition in post-communist Hungary adversely affected the overall morbidity and mortality rates in the 1990s. Prevalence data on depressive disorders from the region are still scarce, however. This study reports the findings of the first epidemiological survey, using the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Depression Inventory (BDI), on the prevalence of post-partum depression and the associated risk factors in Hungary. A total of 1030 mothers who delivered their babies between May and July 1999 in 16 counties in Hungary were screened for depressive symptoms 3-26 weeks post-partum. The survey found that 10.81% of the sample was above the cut-off score of 13, and the EPDS detected post-partum depressive symptoms with 76% (95% confidence interval (CI)=60.5-87.1) sensitivity and 92% (95% CI=90.5-94.1) specificity. In addition, 24 socio-demographic, socio-psychiatric data and personal and obstetric variables were surveyed. Results of a hierarchical logistic regression analysis showed that depression of the mother during pregnancy was the strongest predictor of depressive symptoms post-partum. Depression before pregnancy, housing conditions, marital relationship status and family history of alcohol problems were also identified as predictors for post-partum depressive symptoms.

Early detection of developmental dysplasia of hip by ultrasound.

OBJECTIVE: To assess the effectiveness of early universal ultrasound (US) screening of developmental dysplasia of the hip (DDH). STUDY DESIGN: A prospective study of universal hip screening of all mature neonates was conducted from 2012 to 2013, at the Department of Obstetrics and Gynaecology, University of Szeged; 1636 newborns (3272 hips) had clinical examinations and hip ultrasound by the Graf method within the1st 3 days of life. Prevalence of DDH, risk factors, sensitivity and specificity of clinical examinations were evaluated. RESULTS: At the 1st US, 70 of the examined 3272 hips (2.14%) were found to be positive. According to Graf categories, the following distribution was observed: type II C, 21 hips (30.0%); D, 24 hips (34.28%); III, 24 hips (34.28%); IV, 1 hip (1.44%). Regarding the risk factors, female gender, breech presentation and positive family history proved to be significant. Interestingly, 28 (50.90%) of the 55 newborns with DDH had neither positive physical signs nor any risk factors, except being female. The physical examination was calculated for sensitivity (20.0%) and specificity (98.34%). CONCLUSIONS: In our 1-year period study, 50.9% of the newborns with DDH had neither any positive physical signs nor any risk factors, except being a female. In contrast, early universal US screening of the hip facilitated to diagnose all cases with hip dysplasia. Hip sonography is an effective mode of prevention in orthopaedics, however further studies are needed to compare the rates of operative procedures in selective versus universal screening models.

Erratum to "Maternal Smoking Highly Affects the Function, Membrane Integrity, and Rheological Properties in Fetal Red Blood Cells".

[This corrects the article DOI: 10.1155/2019/1509798.].

Mature Twin Neonates Exhibit Oxidative Stress via Nitric Oxide Synthase Dysfunctionality: A Prognostic Stress Marker in the Red Blood Cells and Umbilical Cord Vessels.

Intrauterine hypoxic condition increases the generation of reactive oxygen species and fetal oxidative stress. Multiple pregnancy always bears an additional oxidative stress condition with severe complications, such as prematurity, structural abnormalities, delayed development and low birthweight. The umbilical cord (UC) vessels, along with circulating fetal red blood cells (RBCs), highly determine the oxygenation status of fetus and regulate the feto-placental circulation. As UC lacks innervation, the activation of the endothelial nitric oxide synthase (NOS3) is fundamental for proper NO production. Therefore, we aimed to study the NOS3 activation pathways along with damages to macromolecules in the endothelium of UC vessels and RBCs of mature non-discordant twins, in connection to major differences in their birth weight. We provide evidence that, under severe hypoxic conditions such as twin pregnancy, the NOS3-related NO production pathways are altered both in UC vessels and RBCs; moreover, the extent of changes is highly birthweight-specific. Furthermore, macromolecular damages are prominent in the RBCs and arteries compared to the vein, with a similar increase in the Arginase1 level, which is believed to play a role in NOS3 functionality, resulting in endothelial dysfunctionality, which might have relevance to the major etiologies of cardiovascular diseases in later life.

Response of Human Neutrophil Granulocytes to the Hyphae of the Emerging Fungal Pathogen Curvularia lunata.

Curvularia lunata is an ascomycete filamentous fungus causing local and invasive phaeohyphomycoses in both immunocompromised and immunocompetent patients. Neutrophils are crucial participants of the first line host defense against fungal infections. They migrate to the infected site and eliminate the infectious agents by various mechanisms including phagocytoses, oxidative damage, or formation of neutrophil extracellular trap (NET). Neutropenia may be a risk factor for phaeohyphomycoses, and restoration of the neutrophil function can improve the outcome of the infection. In the present study, interaction of primary human neutrophil granulocytes with the hyphae C. lunata was examined and compared to that with the well characterized filamentous fungal pathogen Aspergillus fumigatus. Neutrophils could recognize the serum opsonized hyphae of C. lunata and attach to them. Myeloperoxidase release was also activated by a soluble factor present in the culture supernatant of the fungus. Induction of the oxidative burst was found to depend on serum opsonization of the hyphae. Although extracellular hydrogen peroxide production was induced, the fungus efficiently blocked the oxidative burst by acidifying the reaction environment. This blockage also affected the NET forming ability of the neutrophils.

Endothelial nitric oxide synthase is up-regulated in the umbilical cord in pregnancies complicated with intrauterine growth retardation.

BACKGROUND: NO and NO synthases (NOS) play an important role in the physiology of the fetomaternal blood circulation, although their expression in pathological conditions is unclear. Intrauterine growth retardation (IUGR) is a disorder most probably caused by abnormality of the fetomaternal bloodflow. MATERIALS AND METHODS: The expression of endothelial NOS (ecNOS) from arteria umbilicalis and the nitrite and peroxynitrite level of umbilical blood were determined. Major consequences of peroxynitrite toxicity are lipid peroxidation and glutathione depletion; these parameters were also measured. Finally, superoxide dismutase (SOD) activity was assayed to evaluate the level of superoxide anions. RESULTS: Elevated expression of ecNOS was found to be coupled with significantly lower SOD activity and glutathione level, and increased lipid peroxidation in IUGR neonates. CONCLUSION: The increased NO indices could represent a compensatory effort to improve placental bloodflow, but in IUGR neonates it is coupled with inadequate antioxidant defence, resulting in significant oxidative stress.

Prevention of preterm delivery with periodontal treatment.

OBJECTIVE: To demonstrate the role of periodontal treatment (PT) in the prevention of preterm delivery (PD). METHODS: A comparative prospective study of two groups of pregnant women with threatening PD was carried out at the Department of Obstetrics and Gynaecology of the University of Szeged: group A (n = 39) comprised patients who were merely examined dentally for periodontitis, and group B (n = 44) consisted of patients who received periodontal treatment during pregnancy. RESULTS: Periodontitis was identified in 19 cases (48.7%) in group A and in 18 cases (40.9%) in group B. The mean birth weight of the newborns was significantly higher in group B (3,009.1 g) than in group A (2,580.8 g; p = 0.007). The rate of premature birth was significantly lower in the group who received PT (p = 0.012, odds ratio = 3.5, 95% confidence interval = 1.38-8.86). CONCLUSIONS: The PT of pregnant women can decrease the rate of premature birth and consequently lead to a better neonatal health outcome.

Adverse perinatal outcome in teenage pregnancies: an analysis of a 5-year period in Southeastern Hungary.

OBJECTIVE: To determine the risks of adverse perinatal outcomes of teenage mothers. MATERIAL AND METHODS: A retrospective analysis was performed on teenage mothers (under 20 years of age) who delivered in the period of 2010-2014 at the Department of Obstetrics and Gynecology, University of Szeged (study group). All mothers who delivered in Hungary during the same period were studied as a control group. The following parameters were analyzed: demographic data of the mothers, maternal complications, perinatal outcome and congenital malformations of the newborns. The binominal test, Student's t-test and Poisson's regression were applied using STATA 9.0 (StataCorp, College Station, TX, USA) statistical software (p < .05 was considered to be statistically significant). RESULTS: During this 5-year period, 12,845 births were recorded at the Department, of these 274 (2.1%) were teenage pregnancies with 275 newborns. The offsprings of teenage mothers had significantly lower mean birth weight (3110.2 ± 564.03 g versus 3247 g), higher rate of congenital malformations (8.0 versus 5.0%) and higher admission to neonatal intensive care unit (12.4 versus 8.0%) than the infants in the control group. CONCLUSIONS: Younger maternal age was significantly associated with lower mean birth weight, higher risk of congenital malformations, and increased admission rate to neonatal intensive care unit.

Maternal Smoking Highly Affects the Function, Membrane Integrity, and Rheological Properties in Fetal Red Blood Cells.

An understanding of the basic pathophysiological mechanisms of neonatal diseases necessitates detailed knowledge about the wide range of complications in the circulating fetal RBCs. Recent publications on adult red blood cells (RBCs) provide evidence that RBCs carry an active nitric oxide synthase (NOS3) enzyme and contribute to vascular functioning and integrity via their active nitric oxide synthesis. The aim of this study was to determine the effect of maternal smoking on the phenotypical appearance and functionality of fetal RBCs, based on morphological and molecular studies. We looked for possible links between vascular dysfunction and NOS3 expression and activation and its regulation by arginase (ARG1). Significant morphological and functional differences were found between fetal RBCs isolated from the arterial cord blood of neonates born to nonsmoking (RBC-NS, n = 62) and heavy-smoking (RBC-S, n = 51) mothers. Morphological variations were quantified by Advanced Cell Classifier, microscopy-based intelligent analysis software. To investigate the relevance of the newly suggested "erythrocrine" function in fetal RBCs, we measured the levels of NOS3 and its phosphorylation in parallel with the level of ARG1, as one of the major influencers of NOS3 dimerization, by fluorescence-activated cell sorting. Fetal RBCs, even the "healthy-looking" biconcave-shaped type, exhibited impaired NOS3 activation in the RBC-S population, which was paralleled with elevated ARG1 level, thus suggesting an increased redox burden. Our molecular data indicate that maternal smoking can exert marked effects on the circulating fetal RBCs, which could have a consequence on the outcome of in utero development. We hypothesize that any endothelial dysfunction altering NO production/bioavailability can be sensed by circulating fetal RBCs. Hence, we are putting forward the idea that neonatal RBC could serve as a real-time sensor for not only monitoring RBC-linked anomalies but also predicting the overall status of the vascular microenvironment.