Cord Blood Ischemia-Modified Albumin Levels in Normal and Intrauterine Growth Restricted Pregnancies

Ischemia-modified albumin (IMA) is a sensitive biomarker of cardiac ischemia. Intrauterine growth restriction (IUGR) may imply fetal hypoxia, resulting in blood flow centralization in favour of vital organs (brain, heart, adrenals—“brain sparing effect”). Based on the latter, we hypothesized that cord blood IMA levels should not differ between IUGR and appropriate-for-gestational-age (AGA) full-term pregnancies. IMA was measured in blood samples from doubly-clamped umbilical cords of 110 AGA and 57 asymmetric IUGR pregnancies. No significant differences in IMA levels were documented between AGA and IUGR groups. IMA levels were elevated in cases of elective cesarean section (P = .035), and offspring of multigravidas (P = .021). In conclusion, “brain sparing effect” is possibly responsible for the lack of differences in cord blood IMA levels at term, between IUGR and AGA groups. Furthermore, higher oxidative stress could account for the elevated IMA levels in cases of elective cesarean section, and offspring of multigravidas

Neurotrophin-3 and FLT3 Tyrosine Kinase Receptor in Perinatal Life

Our aim is to determine—in 30 healthy full-term infants and their mothers—circulating levels of neurotrophin-3 (NT-3) (important for antenatal and postnatal brain development and implicated in the immune response) and FLT3 tyrosine kinase receptor (FLT3) (controlling hematopoiesis and found in the nervous tissue), in the fetal and neonatal life. NT-3 levels, in contrast to FLT3 ones, increased significantly on the fourth postnatal day in relation to the low levels found in the mother, fetus, and day 1 neonate (P = .03, respectively). Maternal and umbilical NT3 levels positively correlated with respective FLT3 levels (P = .003 and P = .03). Circulating NT-3 levels increased in early neonatal life, possibly due to exposure to various stimuli soon after birth. FLT3 levels do not seem to behave accordingly, although these two substances probably synergize

Vascular Endothelial Growth Factor and Placenta Growth Factor in Intrauterine Growth-Restricted Fetuses and Neonates

The angiogenic factors vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) are respectively up- and downregulated by hypoxia. We aimed to study circulating levels of the above factors in intrauterine growth restriction (IUGR) and to correlate their levels with the customized centiles of the infants. The study included 25 IUGR and 25 appropriate for gestational age (AGA) full-term, singleton infants and their mothers. Maternal (MS), fetal (UC), and neonatal day 1 (N1) and 4 (N4) blood was examined. MS and N1 PlGF, as well as UC VEGF levels correlated with the customized centiles of the infants (r = 0.39, P = .007, r = 0.34, P = .01, and r = −0.41, P = .004, resp). Furthermore, UC, N1, and N4 VEGF levels were higher in girls (r = 0.36, P = .01, r = 0.33, P = .02, and r = 0.41, P = .005 resp). In conclusion, positive and negative correlations of examined factors with the customized centiles of the infant could rely on placental function and intrauterine oxygen concentrations—both being usually lower in IUGR cases—while higher VEGF levels in girls should possibly be attributed to the stimulating action of estrogens

Circulating Levels of Inflammatory Markers in Intrauterine Growth Restriction

We aimed to investigate possible alterations in circulating levels of the perinatal stress markers high sensitivity (hs)-CRP, PAI-1, and S100B—probably reflecting brain and adipose tissue inflammation—in intrauterine growth-restricted-(IUGR) and appropriate-for-gestational-age-(AGA) pregnancies, given that these groups differ in fat mass and metabolic mechanisms involving aseptic inflammation. Serum hs-CRP, PAI-1, and S100B levels were measured in 40 mothers, and their 20 AGA and 20 IUGR full-term fetuses and neonates on postnatal days 1 and 4. hs-CRP, PAI-1, and S100B levels did not differ at all time points between AGA and IUGR groups. We conclude that the lack of difference in hs-CRP, PAI-1 and S100B levels, between IUGR and AGA fetuses/neonates—despite the lower birth weight, reflecting reduced fat mass in the former—might indicate more intense adipose tissue and nervous system inflammation in IUGRs. However, implication of other inflammation-related mechanisms, common in the IUGR state (e.g. preeclampsia), cannot be excluded

Angiogenic and angiogenic factors in neonates with intrauterine growth restriction

This thesis consists of two parts, the GENERAL and the SPECIFIC The General Part includes the following chapters: I. Intrauterine growth restriction (IUGR) This part refers to the history, definition and epidemiology of IUGR and the clinical importance of distinguishing IUGR from SGA (small for gestational age) neonates. Special emphasis is given in the etiology of IUGR (from the fetus, placenta and mother), the determination of gestational age and the diagnostic methods used to detect IUGR, whether clinical (abdominal palpation, symphysis- fundal height) or imaging procedures (ultrasonographically estimated fetal weight and amniotic fluid volume, three-dimensional ultrasonography, Doppler velocimetry). The importance of customized fetal growth charts and the distinction of symmetric vs. asymmetric IUGR for future prognosis, is highlighted. Finally, this part refers to the treatment and postnatal management, while morbidity, short- and long term consequences and mortality rates are also discussed. II. Angiogenesis The definition and implication of angiogenesis in physiological and pathological conditions and the distinct stages of angiogenetic mechanisms, are analyzed in this chapter. Following that, there is a reference to the angiogenic and the anti-angiogenic factors implicated in angiogenesis and a separate review on: a)VEGF/ PlGF family and their receptors VEGFR-1, sVEGFR-1, VEGFR-2, VEGFR-3, b) angiopoietins Ang-1 and Ang-2 and c) endostatin. III. Fetoplacental circulation and angiogenesis This part refers to the structure and function of the placenta, the impact of oxygen on normal placentation (branching and non- branching angiogenesis) and placental maldevelopment in fetal hypoxia. Finally, emphasis is given in the behavior of angiogenic factors in the presence of IUGR and preeclampsia and other mechanisms of placental pathology in IUGR pregnancies.Η διατριβή αποτελείται από το ΓΕΝΙΚΟ και το ΕΙΔΙΚΟ ΜΕΡΟΣ Το Γενικό μέρος περιλαμβάνει τα κεφάλαια: Ι. Eνδομήτρια Υπολειπόμενη Αύξηση (ΕΥΑ)- Intrauterine growth restriction (IUGR). Γίνεται ιστορική αναδρομή και δίνεται ο ορισμός της ΕΥΑ (και η σημασία της διάκρισης του ΕΥΑ από το small for gestational age-SGA νεογνό), καθώς και επιδημιολογικά δεδομένα. Αναλύεται εκτενώς η αιτιολογία της ΕΥΑ από το έμβρυο, τον πλακούντα και τη μητέρα και δίνονται στοιχεία για τον προσδιορισμό της ηλικίας κύησης. Δίνεται ιδιαίτερη έμφαση στη διάγνωση της ΕΥΑ με κλινικές μεθόδους [ψηλάφηση των κοιλιακών τοιχωμάτων- χειρισμοί Λεοπόλδου, μέτρηση της απόστασης από τον πυθμένα της μήτρας ως την ηβική σύμφυση (symphysis-fundal height, S-F height)], με απεικονιστικές μεθόδους (υπερηχογραφικός προσδιορισμός του εμβρυικού βάρους και του όγκου του αμνιακού υγρού, τρισδιάστατη υπερηχογραφία- 3D, Doppler υπερηχογραφία), και τονίζεται η σημασία των καμπυλών εμβρυικής αύξησης και της διάκρισης της συμμετρικής από την ασύμμετρη ΕΥΑ για την πρόγνωση του εμβρύου. Στη συνέχεια αναφέρονται διάφορες θεραπευτικές μέθοδοι που έχουν κατά καιρούς προταθεί για την αντιμετώπιση της ΕΥΑ, η σημασία της επιλογής του χρόνου τοκετού, η αντιμετώπιση του νεογνού μετά τη γέννηση και η κλινική του εικόνα. Τέλος δίνονται στοιχεία για τη νοσηρότητα και τις επιπλοκές της ΕΥΑ (βραχυ- και μακροπρόθεσμες) και τη σχετιζόμενη με ΕΥΑ θνησιμότητα. ΙΙ. Αγγειογένεση Δίδεται ο ορισμός της αγγειογένεσης και η σημασία της στην ύπαρξη φυσιολογικών και παθολογικών καταστάσεων, ενώ αναλύονται τα βασικά στάδια της αγγειογενετικής διαδικασίας. Ακολούθως, γίνεται αναφορά στους αγγειογενετικούς και αντιαγγειογενετικούς παράγοντες που εμπλέκονται στη διαδικασία της αγγειογένεσης και ανασκοπούνται ξεχωριστά: η οικογένεια του VEGF, PlGF και των υποδοχέων τους VEGFR-1 και sVEGFR-1, VEGFR-2, VEGFR-3, οι αγγειοποιητίνες Ang-1 και Ang-2 και η ενδοστατίνη. ΙΙΙ. Μητροπλακουντιακή κυκλοφορία και αγγειογένεση Στο κεφάλαιο αυτό αναλύεται η δομή και η λειτουργία του πλακούντα, ο ρόλος του οξυγόνου στην ομαλή πλακουντοποίηση (διακλαδιζόμενη και μη διακλαδιζόμενη αγγειογένεση) και οι ανωμαλίες στη μορφολογία και τη λειτουργικότητα του πλακούντα σε εμβρυική υποξία. Τέλος, γίνεται αναφορά στους αγγειογενετικούς παράγοντες σε φυσιολογικές και παθολογικές κυήσεις (προεκλαμψία, ΕΥΑ) και σε άλλους μηχανισμούς πλακουντιακής παθολογίας σε ΕΥΑ κυήσεις

Relationships between maternal novel adipocytokines and bone biomarkers in complicated by gestational hypertensive disorders and normal pregnancies

Objective: To investigate possible associations of the novel adipocytokines resistin, apelin and visfatin (implicated in the complex control of bone biology) with several biochemical determinants of bone turnover in maternal blood from normal pregnancies and pregnancies complicated by gestational hypertensive disorders (preeclampsia or pregnancy-induced hypertension). Methods: Circulating maternal concentrations of resistin, apelin and visfatin were correlated with circulating markers of bone formation [osteocalcin (OC), bone-specific alkaline phosphatase (BALP)] and resorption [osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL) and cross-linked N-telopeptide of type I collagen (NTx)] in full-term pregnancies (20 normal and 20 complicated by gestational hypertensive disorders). Results: In normal pregnancies, no correlation was recorded between maternal concentrations of adipocytokines and the above bone biomarkers. In pregnancies with gestational hypertensive disorders, maternal apelin concentrations negatively correlated with NTx ones (r = -0.489, p = 0.034), while maternal visfatin concentrations positively correlated with OPG ones (r = 0.464, p = 0.039). Conclusions: No associations were found between maternal concentrations of all three studied adipocytokines and respective concentrations of bone biomarkers in normal pregnancies. By contrast, in pregnancies with gestational hypertensive disorders, maternal concentrations of apelin and visfatin correlated with respective concentrations of indices of bone turnover. Further prospective studies are needed to clarify these relationships

Soluble vascular endothelial growth factor receptor-1 in intrauterine growth restricted fetuses and neonates

Background: Angiogenesis, a critical process for growth and development is altered in intrauterine growth restriction (IUGR). Vascular endothelial growth factor (VEGF) and its receptors VEGFR-1, soluble (s) VEGFR-1 and VEGFR-2 represent a regulatory system, essential for both physiological and pathological angiogenesis. Aim: To study the implication of sVEGFR-1-a VEGF antagonist-in IUGR. Study design: Prospective study. Methods: Twenty-five IUGR and 15 appropriate for gestational age (AGA) full-term fetuses and neonates with their mothers were included in the study. Outcome measures: sVEGFR-1 levels were determined by enzyme immunoassay in the serum of: mothers (MS), umbilical cords (UC)-representing fetal state-and neonates on day 1 (N1) and 4 (N4) of life. Results: MS, UC, N1 and N4 sVEGFR-1 levels in IUGR were significantly higher compared to respective AGA cases (p=0.005, p=0.026, p=0.005 and p=0.017, respectively). In IUGR and AGA groups, maternal sVEGFR-1 levels were significantly higher than fetal and neonatal levels (p in all cases < 0.001). The tatter presented in both IUGR and AGA groups a significant decrease from UC to N4 (p in all cases < 0.01). MS, NI and N4 sVEGFR-1 levels negatively correlated with the infants’ customized centiles [(r=-0.489, p=0.001), (r=-0.440, p=0.004), (r=-0.431, p=0.006), respectively]. Conclusions: Higher sVEGFR-1 levels in the IUGR as compared to the AGA group possibly reflect the predominance of antiangiogenic mechanisms present in IUGR. The decrease of sVEGFR-1 levels from UC to N4 may represent ex utero initiation of growth and development and therefore, prevalence of angiogenic mechanisms. (c) 2005 Elsevier Ireland Ltd. All. rights reserved

Breastfeeding in the era of COVID-19. A narrative review

Human milk is the best possible nutrition for infants, as it supplies them with nutrients, bioactive molecules as well as antibodies, which contribute to immune maturation, organ development, and healthy microbial colonisation. Few situations are considered definitive contraindications for breastfeeding. The disastrous Coronavirus Disease-2019 (COVID-19) pandemic raised many health issues, including the safety of breastfeeding for infants born to affected mothers. To date relevant data are limited. This review will make an account of the published data so far, regarding the transmission risk of SARS-CoV-2 via human milk; it will also present the current feeding recommendations, issued by several international boards, though not always in agreement, for infants born to mothers suspected or positive for SARS-CoV-2. In most studies existing so far on women with COVID-19, the virus was not detected in breastmilk. Based on currently available data, it seems that breastfeeding and human milk are not contraindicated for infants born to mothers suspected or confirmed with COVID-19

Adropin concentrations in term pregnancies with normal, restricted and increased fetal growth

Objective: To determine levels of adropin (implicated in insulin resistance and endothelial dysfunction) in intrauterine growth restricted (IUGR), large (LGA) and appropriate for gestational age (AGA) pregnancies.Methods: Cord-blood (UC) adropin and insulin concentrations were measured in 30 IUGR, 30 LGA and 20 AGA full-term infants and their mothers (MS).Results: No significant differences in adropin concentrations were observed between the three groups. In the IUGR group MS adropin was significantly decreased when neonates had higher birth weights [b=-0.003, 95% CI-0.006 to 0.0, p=0.043]. In all groups, MS adropin levels were positively correlated with UC ones (r=0.282, p=0.011) and were significantly increased in female neonates [b=0.977, 95% CI 0.122-1.832, p=0.026]. In the LGA group, MS insulin was negatively correlated with UC adropin (r=-0.362 p=0.049).Conclusions: Increased maternal adropin levels in severe IUGR cases might represent a regulatory feedback mechanism against endothelial placental dysfunction. The positive correlation between maternal and umbilical cord adropin levels implies its transplacental transfer. Increased maternal adropin levels in female neonates could be attributed to interaction of adropin with fetal estrogens through vascular endothelial growth factor (VEGF). The negative correlation between maternal insulin and fetal adropin levels in the LGA group is probably attributed to their respective insulin resistance