Genetic Polymorphisms of Vascular Endothelial Growth Factor in Neonatal Pathologies: A Systematic Search and Narrative Synthesis of the Literature.

(1) Background: Vascular endothelial growth factor (VEGF) is essential in vasculo- and angiogenesis due to its role in endothelial cell proliferation and migration. As a vascular proliferative factor, VEGF is one of the hallmarks of cancer and, in adult populations, the relationship between genetic polymorphism and neoplasm was widely investigated. For the neonatal population, only a few studies attempted to uncover the link between the genetic polymorphism of VEGF and neonatal pathology, especially related to late-onset complications. Our objective is to evaluate the literature surrounding VEGF genetic polymorphisms and the morbidity of the neonatal period. (2) Methods: A systematic search was initially conducted in December 2022. The PubMed platform was used to explore MEDLINE (1946 to 2022) and PubMed Central (2000 to 2022) by applying the search string ((VEGF polymorphism*) and newborn*). (3) Results: The PubMed search yielded 62 documents. A narrative synthesis of the findings was undertaken considering our predetermined subheadings (infants with low birth weight or preterm birth, heart pathologies, lung diseases, eye conditions, cerebral pathologies, and digestive pathologies). (4) Conclusion: The VEGF polymorphisms seem to be associated with neonatal pathology. The involvement of VEGF and VEGF polymorphism has been demonstrated for retinopathy of prematurity.

The Effect of Maternal SARS-CoV-2 Infection on Neonatal Outcome.

(1) Background: Neonates born to SARS-CoV-2 positive mothers are at risk of infection, as well as adverse outcomes due to the infection. The aim of our study was to analyze the impact of maternal SARS-CoV-2 infection on neonatal outcome. (2) Methods: We conducted a prospective, longitudinal study. We collected data on maternal symptomatology upon admission and their correlation with the development of the infant. Through a questionnaire we analyzed the impact on breastfeeding of the separation of the mother from the newborn, as well as the maternal psycho-emotional effect. (3) Results: Ninety infants were enrolled in the study, from one twin pregnancy and the rest singleton pregnancies. Out of the 89 mothers, 34 showed symptoms. Neonates from mothers with anosmia and ageusia had a higher value of WBC and lymphocytes (p = 0.06 and p = 0.04). Breastfeeding was started in 57.3% of mothers after their discharge from hospital and only 41.6% of the whole study group continued at the follow-up visit. Mothers who described a negative experience during hospitalization associated a 2.42 times higher risk of not continuing breastfeeding. (4) Conclusion: None of the infants enrolled in the study had SARS-CoV-2 infection either at birth or within the first two months of life. Breastfeeding was started with more than half newborns after discharge from hospital. The negative experience generated by the separation from their babies influenced breastfeeding.

First Comparative Evaluation of Short-Chain Fatty Acids and Vitamin-K-Dependent Proteins Levels in Mother-Newborn Pairs at Birth.

BACKGROUND: The interplay between vitamin K (vitK) (as carboxylation cofactor, partially produced by the gut microbiota) and short-chain fatty acids (SCFAs), the end-product of fiber fermentation in the gut, has never been assessed in mother-newborn pairs, although newborns are considered vitK deficient and with sterile gut. METHODS: We collected venous blood from 45 healthy mothers with uncomplicated term pregnancies and umbilical cord blood from their newborns at birth. The concentrations of total SCFAs and hepatic/extra-hepatic vitK-dependent proteins (VKDPs), as proxies of vitK status were assayed: undercarboxylated and total matrix Gla protein (ucMGP and tMGP), undercarboxylated osteocalcin (ucOC), undercarboxylated Gla-rich protein (ucGRP), and protein induced by vitK absence II (PIVKA-II). RESULTS: We found significantly higher ucOC (18.6-fold), ucMGP (9.2-fold), and PIVKA-II (5.6-fold) levels in newborns, while tMGP (5.1-fold) and SCFAs (2.4-fold) were higher in mothers, and ucGRP was insignificantly modified. In mother-newborn pairs, only ucGRP (r = 0.746, p < 0.01) and SCFAs (r = 0.428, p = 0.01) levels were correlated. Conclusions: We report for the first time the presence of SCFAs in humans at birth, probably transferred through the placenta to the fetus. The increased circulating undercarboxylated VKDPSs in newborns revealed a higher vitamin K deficiency at the extrahepatic level compared to liver VKDPs.

Survey of transfusion practices in preterm infants in Europe.

BACKGROUND: Preterm infants commonly receive red blood cell (RBC), platelet and fresh frozen plasma (FFP) transfusions. The aim of this Neonatal Transfusion Network survey was to describe current transfusion practices in Europe and to compare our findings to three recent randomised controlled trials to understand how clinical practice relates to the trial data. METHODS: From October to December 2020, we performed an online survey among 597 neonatal intensive care units (NICUs) caring for infants with a gestational age (GA) of <32 weeks in 18 European countries. RESULTS: Responses from 343 NICUs (response rate: 57%) are presented and showed substantial variation in clinical practice. For RBC transfusions, 70% of NICUs transfused at thresholds above the restrictive thresholds tested in the recent trials and 22% below the restrictive thresholds. For platelet transfusions, 57% of NICUs transfused at platelet count thresholds above 25×109/L in non-bleeding infants of GA of <28 weeks, while the 25×109/L threshold was associated with a lower risk of harm in a recent trial. FFP transfusions were administered for coagulopathy without active bleeding in 39% and for hypotension in 25% of NICUs. Transfusion volume, duration and rate varied by factors up to several folds between NICUs. CONCLUSIONS: Transfusion thresholds and aspects of administration vary widely across European NICUs. In general, transfusion thresholds used tend to be more liberal compared with data from recent trials supporting the use of more restrictive thresholds. Further research is needed to identify the barriers and enablers to incorporation of recent trial findings into neonatal transfusion practice.

Association Analysis of the Cerebral Fractional Tissue Oxygen Extraction (cFTOE) and the Cerebral Oxygen Saturation (crSaO2) with Perinatal Factors in Preterm Neonates: A Single Centre Study.

(1) Background: Near-infrared spectroscopy (NIRS) is a non-invasive, easily performed method of monitoring brain oxygenation. The regional cerebral oxygen saturation (crSaO2) and the cerebral fractional tissue oxygen extraction (cFTOE) evaluated by NIRS provide more accurate information on brain oxygenation than the blood oxygen saturation. We investigated the effect of perinatal factors on cerebral oxygenation of preterm newborns. (2) Methods: We conducted a longitudinal study with 48 preterm newborns <34 weeks of gestation who underwent NIRS registration during the first 72 h of life. crSaO2 was measured and cFTOE was calculated foreach patient. (3) Results: One-way ANOVA showed no significant main effect of IVH severity on crSaO2 and cFTOE (p > 0.05); there was a tendency toward statistical significance concerning the difference between the means of crSaO2 (p = 0.083) and cFTOE (p = 0.098). Patients with intraventricular haemorrhage (IVH) had a lower mean of crSaO2 and a higher mean of cFTOE (59.67 ± 10.37% vs. 64.92 ± 10.16% for crSaO2; 0.37 ± 0.11 vs. 0.32 ± 0.11 for cFTOE) compared to those with no IVH. Significantly lower values of crSaO2 and higher values of cFTOE were found in neonates receiving inotropic treatment (p < 0.0001). Episodes of apnoea also proved to influence the cerebral oxygen saturation of the study group (p = 0.0026). No significant association between the maternal hypertension treatment and the cerebral oxygenation of preterms was found. (4) Conclusions: This study showed a decreased cerebral oxygen saturation of preterms with IVH, inotrope support and apnoea episodes.

Association of Parental Factors and Insulin-like Growth Factor 2 Polymorphism with Intrauterine Growth Restriction.

Polymorphism of insulin-like growth factor 2 (IGF2) is known to play a role in cell development. Only the paternal IGF2 copy is active, while the copy inherited from the mother is inactive. This study aimed to explore whether maternal and paternal factors influence IGF2 polymorphism in newborns with intrauterine growth restriction (IUGR) compared to appropriate for gestational age (AGA). A cross-sectional exploratory study was conducted from June 2014 to November 2015 at the Neonatology, Gynecology 1 Clinic, Cluj-Napoca, Romania. The ApaI IGF2 genotypes and allele frequencies were similar in the IUGR and AGA groups (p-value > 0.10). The IUGR babies with a protective IGF2 genetic profile had significantly younger parents (a difference in the median age of 8 years for mothers and 9 years for fathers; p-value < 0.009). The IUGR babies had parents with lower birth weights than AGA babies (mothers' medians: 2800 g vs. 3100 g; fathers' medians: 3000 g vs. 3400 g; p-value < 0.02). In univariable regression analysis, the mother's and father's birth weight proved to be associated with IUGR. The father's birth weight proved to be the only factor significantly associated with IUGR, independent of the mother's birth weight or the presence of a protective IGF2 genetic profile (odd ratio = 0.998 [0.996 to 1.000], p-value = 0.032).

Early Preeclampsia Effect on Preterm Newborns Outcome.

BACKGROUND: An early form of preeclampsia is rare. Abnormal placentation, placental perfusion disorders, and inflammatory cytokine release will have an effect on the fetus and newborn. MATERIAL AND METHODS: The study group consisted of preterm newborns whose mothers had a history of preeclampsia and a gestational age of between 30 weeks and 34 weeks + 6 days. The control group consists of neonates matched for gestational age with the case group, whose mothers had normal blood pressure. The incidence and severity of respiratory distress syndrome (RDS), intraventricular hemorrhage, hypoglycemia, pH gas changes, and hematological parameters were analyzed in the two groups. RESULTS: The study group of preterm neonates had a lower birth weight than the control group (p < 0.001). Most of the deliveries in the group of newborns exposed to preeclampsia were performed by cesarean section. Severe forms of RDS were two times more frequent in the group of newborns exposed to preeclampsia compared to those in the control group. Even though we expected to see a lower incidence, owing to the high number of deliveries by cesarean section, we still observed a higher rate of intraventricular hemorrhage in the preeclampsia group (16 cases in the study group vs. 7 in the control, p = 0.085). Neutropenia and thrombocytopenia were more frequent in preterm newborns exposed to preeclampsia. CONCLUSIONS: The study shows that early preeclampsia increases the risk of complications in preterm neonates. RDS was more frequent in the exposed group than in the control group. The severity of preeclampsia correlates with hematological changes.

Fetal cardiac rhabdomyomas as a sonographic sign of tuberous sclerosis complex - a diagnosis not to be missed. A pictorial essay.

Fetal cardiac rhabdomyomas should trigger the awareness of a potential coexisting tuberous sclerosis complex that can lead to a poor neurological outcome. This condition is not only uncommon but can be easily unrecognized prenatally in the absence of a meticulous neurosonogram and MRI. We emphasize that careful consideration of all prenatal facilities is required to confirm the diagnosis of tuberous sclerosis complex as early as possible during pregnancy.

Diagnostic challenges, management, and outcome of infants born to mothers with COVID 19 during the first wave of the pandemic.

Severe acute respiratory distress syndrome with coronavirus 2 (SARS-CoV-2) infection affected pregnant women during the pandemic. Immunological particularity of this population and the increased need for medical assistance placed this population in a high-risk category for SARS-Cov-2 infection. Owing to high contamination risk and limited studies regarding vertical transmission, the labor and delivery of positive women required particular conditions. Cesarean section probably proved to be the optimal option for delivery of infants to reduce the risk of infection during birth. The aim of the present study was to present the management and outcome of infants born to mothers confirmed with coronavirus disease 2019 (COVID 19) prior to delivery. This is a longitudinal, retrospective study, analyzing demographics, laboratory data and management of neonates born to mothers with diagnosis of SARS-Cov-2 infection. The results showed that 5 neonates were born to SARS-Cov-2-positive mothers, all by Cesarean section and had a negative reverse transcription-quantitative polymerase chain reaction (RT-qPCR) test. None of the women breastfed during the hospital stay. The negative RT-qPCR test allowed us to reduce the hospital stay of infants and care in non-isolated areas. In summary, in the present study, vertical or perinatal transmission of the infection was not present. The testing of the pregnant women, their isolation and delivery in safe conditions for the medical staff were possible, with the latter using adequate protection equipment to limit their infection and the risk for the newborns.

Molecular and Cytogenetic Analysis of Romanian Patients with Differences in Sex Development.

Differences in sex development (DSD) are often correlated with a genetic etiology. This study aimed to assess the etiology of DSD patients following a protocol of genetic testing. MATERIALS AND METHODS: This study prospectively investigated a total of 267 patients with DSD who presented to Clinical Emergency Hospital for Children Cluj-Napoca between January 2012 and December 2019. Each patient was clinically, biochemically, and morphologically evaluated. As a first intervention, the genetic test included karyotype + SRY testing. A high value of 17-hydroxyprogesterone was found in 39 patients, in whom strip assay analysis of the CYP21A2 gene was subsequently performed. A total of 35 patients were evaluated by chromosomal microarray technique, and 22 patients were evaluated by the NGS of a gene panel. RESULTS: The karyotype analysis established the diagnosis in 15% of the patients, most of whom presented with sex chromosome abnormalities. Genetic testing of CYP21A2 established a confirmation of the diagnosis in 44% of patients tested. SNP array analysis was particularly useful in patients with syndromic DSD; 20% of patients tested presented with pathogenic CNVs or uniparental disomy. Gene panel sequencing established the diagnosis in 11 of the 22 tested patients (50%), and the androgen receptor gene was most often involved in these patients. The genes that presented as pathogenic or likely pathogenic variants or variants of uncertain significance were RSPO1, FGFR1, WT1, CHD7, AR, NIPBL, AMHR2, AR, EMX2, CYP17A1, NR0B1, GNRHR, GATA4, and ATM genes. CONCLUSION: An evaluation following a genetic testing protocol that included karyotype and SRY gene testing, CYP21A2 analysis, chromosomal analysis by microarray, and high-throughput sequencing were useful in establishing the diagnosis, with a spectrum of diagnostic yield depending on the technique (between 15 and 50%). Additionally, new genetic variants not previously described in DSD were observed.

Feasibility and clinical utility of a transdiagnostic Internet-delivered rational emotive and behavioral intervention for adolescents with anxiety and depressive disorders.

BACKGROUND: Transdiagnostic interventions delivered for children and adolescents show promising results. In order to increase access to treatment, recent developments in technology have led to alternatives to face-to-face interventions. Transdiagnostic Internet-delivered interventions can be effective for adult anxiety and depressive disorders, but research is more limited regarding the efficacy of such treatments for young populations diagnosed with anxiety and or depressive disorders. OBJECTIVE: This study aims to investigate the feasibility and clinical utility of a transdiagnostic Internet-delivered intervention based on Rational emotive behavior therapy for adolescents diagnosed with anxiety and depressive disorders. METHODS: We tested the preliminary efficacy of a six-week intervention in an open trial, pre-post design. RESULTS: Our results suggest that the intervention is feasible and can be included as a treatment for adolescents with anxiety and depressive disorders, being associated with moderate to large pre-post effect sizes on self-reported anxiety and depressive symptoms, as well as on negative patterns of thinking and knowledge acquisition. Satisfaction with the intervention was high. CONCLUSIONS: Transdiagnostic Internet-delivered interventions for adolescents with anxiety and depressive symptoms are feasible. Future testing of the efficacy of such interventions in randomized controlled trials should be conducted.

Postpartum assessment of fetal inflammatory response syndrome in a preterm population with premature rupture of membranes: A Romanian study.

Fetal inflammatory response syndrome is associated with increased neonatal morbidity and mortality. The aim of the present study was to evaluate the dynamics of the plasmatic value of pro-inflammatory cytokines: tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and neutrophil activating peptide 78 (ENA-78) and the anti-inflammatory cytokine IL-10 in the first and third day of life and the correlation with neonatal morbidities and mortality. The current research was designed as a prospective case control study included 80 neonates hospitalized at the 3rd level Neonatal Intensive Care Unit (NICU), 1st Gynecology Clinic, County Emergency Hospital, Cluj-Napoca, Romania. For each patient, the following parameters were noted: pH at first hour of life, oxygen saturation, fraction of inspired oxygen (FiO2) and duration of premature rupture of the membranes (PROM). Measurements of cytokines were determined from venous blood in the first and third day of life. The values of all cytokines were higher in the newborns from mothers with PROM. The value of IL-6 in the study group was higher compared to the controls during the first day of life and met the highest value in necrotizing enterocolitis (NEC). ENA-78 was higher in the study group (P=0.037) and decreased during the first 3 days of life. The highest value of ENA-78 was found in the neonates with cerebral hemorrhage. IL-10 also had values with a significant difference in the first day of life between both groups (P=0.02). IL-10 had the highest value in sepsis cases. In conclusion, among the inflammatory parameters that were evaluated, the dynamics of ENA-78 and IL-10 were found to influence the neonatal prognosis of newborns with PROM. The decrease in ENA-78 and IL-10 during the third day of life could suggest the evolution towards the ending of the inflammatory process and an increase in the survival rate was noted.

Diagnostic Usefulness of MLPA Techniques for Recurrent Copy Number Variants Detection in Global Developmental Delay/Intellectual Disability.

BACKGROUND: Genetic testing has become a standardized practice in the diagnosis of patients with global developmental delay/intellectual disability (GDD/ID). The aim of this study is to observe the frequency of recurrent copy number variations (CNVs) in patients diagnosed with GDD/ID, using MLPA technique. METHODS: A total of 501 paediatric patients with GDD/ID were analysed using SALSA MLPA probemix P245 Microdeletion Syndromes-1A, and the technical steps were performed according to the MRC Holland MLPA general protocol. RESULTS: Twenty-five of 501 patients (5%) were diagnosed with a microdeletion/microduplication syndrome. Amongst them, 7 of 25 (30%) with clinical suggestion have a confirmed diagnosis, for the other cases the clinical features were not evocative for a specific syndrome. CONCLUSION: This study showed that in cases with a specific clinical diagnosis the MLPA technique could be a useful alternative, less expensive and more efficient to indicate as first intention of a targeted diagnostic test, as it is the case of Williams syndrome, Prader-Willi syndrome or DiGeorge syndrome.

Case Report: Uncommon Association of ITGB4 and KRT10 Gene Mutation in a Case of Epidermolysis Bullosa With Pyloric Atresia and Aplasia Cutis Congenita.

Background: Epidermolysis bullosa is a rare form of genodermatosis produced by different gene mutations. The junctional form of the disease (JEB-PA) can associate pyloric atresia, renal abnormalities, and aplasia cutis congenita. Case Description: A case of a male preterm newborn with suspicion of digestive tube malformation at fetal ultrasound and who was born by cesarian section. At birth, he presented extensive cutaneous aplasia on the lower limbs and bilaterally under ears; outer ear agenesis; nasal septum hypoplasia; micrognathia; multiple blisters on the face, trunk, and limbs; lower limb deformities and absence of toe nails. Pathological examination following a surgical procedure with unfavorable outcome showed pyloric atresia, junctional form of epidermolysis bullosa and aplasia cutis congenita. Homozygous variants in two genes were identified: c.3111+1G>A in ITGB4 (class 5) and c.1498G>T in KRT10 (class 3). Conclusion: The particularity of our case is the novel finding of a coincidental occurrence in the context of consaguinity of two mutations in the ITGB4 and KRT10 genes, and clinical characteristics of epidermolysis bullosa.

Fetal Ovarian Cysts: Prenatal Diagnosis Using Ultrasound and MRI, Management and Postnatal Outcome-Our Centers Experience.

The present study provides our clinical experience regarding the imaging diagnosis, management and postnatal outcome of neonates prenatally suspected of having developed ovarian cysts. This multicenter observational study included patients diagnosed prenatally with fetal ovarian cysts and follow-up in the postnatal period. Descriptive statistics were used to render the information regarding the prenatal imaging aspect of the fetal pelvic masses using ultrasound and/or MRI, prenatal surveillance and postnatal neonate's immediate outcome, indications leading to surgery and pathologic aspect. The inclusion criteria were fulfilled by 21 patients. The mean gestational age at the time of initial diagnosis was 31.28 weeks of gestation (WG). Only five out of 21 cysts regressed completely during pregnancy without postnatal complications. In addition, 11 out of 21 infant's required surgical treatment in the first two weeks after birth, mainly for ovarian torsion. Five out of 21 neonates were referred to postnatal follow-up clinically and by ultrasound, but three out of five cases required emergency surgical treatment for acute complications. Ultrasound plays a major role in the diagnostic of fetal ovarian cyst. From our experience, MRI does not bring supplementary data or change the management. Spontaneous resolution of fetal ovarian cysts is to be expected but the ovarian mass could lead to serious complications, if resolution does not occur in due time.

Fetal cardiovascular alterations in twin-to-twin transfusion syndrome.

Twin-to-twin transfusion syndrome (TTTS) is the consequence of vascular anastomoses of the shared placenta of monochorionic twin pregnancies. Both circulating inter-twin blood flow and vasoactive mediators imbalance cause hypovolemia in the donor and hypervolemia in the recipient fetus. If left untreated, TTTS has a high perinatal mortality rate and adverse long-term outcomes mainly cardiovascular and neurological. The recipient has cardiovascular changes including atrioventricular valve regurgitation, diastolic dysfunction and pulmonary stenosis/atresia. The maladaptive response to vascular changes determines a constant decreased blood flow in the donor that permanently modifies the arterial structure leading to postnatal alterations in the vascular system. Fetoscopic LASER surgery of placental vascular anastomoses may disrupt the underlying pathophysiology and improves cardiovascular function with normalization of systolic and diastolic function within weeks after treatment. The impact of cardiovascular changes is relevant for the safety of the management of a TTTS case. The improvement of the perinatal survival after intrauterine surgery leads to viable infants with the longer-term sequelae. Therefore accurate quantification of cardiovascular involvement is essential for clinicians for pregnancy management but also for patient counseling about the potential treatment options the outcome.

Baseline characteristics of a nationwide cohort of pediatric patients with acute leukemias of Down syndrome.

PURPOSE: Down syndrome (DS) or trisomy 21, brings together some unique aspects from clinical pediatrics. Among the hematological disorders present in DS, by far the most important is the predisposition for developing acute leukemia. Acute myeloid leukemia (AML) of DS has a preleukemic state with the onset in the neonatal period, rarely symptomatic but with the presence of blasts in peripheral blood smear and apparently a spontaneous remission. The unique tumor profile of DS underlines the importance of chromosome 21 in hematopoiesis and it can help understanding leukemogenesis in general. The purpose of this study was to present the very rare cases with DS and transient leukemia and/or acute leukemia that were found in a nationwide survey of Romania, in three centers of pediatric hematology and oncology. METHODS: A nationwide analysis of the very rare cases of transient leukemia of DS are described, involving the three major pediatric hematology centers of Romania: Cluj Napoca, Bucharest and Timisoara. Data analysis was performed using R 3.5.3. Categorical variables were presented as absolute value (percent). Contingency tables were analyzed using the Fisher test. Normality of the distribution was assessed using the Shapiro test and histogram visualization, but also took into consideration the sample size. Non-normally distributed variables were presented as median (quartile 1, quartile 3). Wilcoxon test was used to determine the differences between two non-normally distributed groups. A p value under 0.05 was considered statistically significant. RESULTS: It appears that the more aggressive entity at presentation is represented by CD45 positive leukemia, which is the more frequent of the myeloid lineage and has lower counts at diagnosis. CONCLUSION: We address this manuscript to pediatricians and neonatologists in order to emphasize the importance of diagnosing hematological disorders in children with DS, especially neonates, even if they are asymptomatic.

Association between maternal/newborn genetic variants, placental pathology and spontaneous preterm birth risk: a Romanian population-based study.

Objective: The objective of this study was to determine the association between maternal/newborn single-nucleotide polymorphisms (SNPs) in three candidate genes, placental pathology and the risk of spontaneous preterm birth (SPTB) in a Romanian population.Methods: We performed a prospective case-control study in a tertiary maternity in Romania, including 79 mother-newborn pairs with SPTB and 81 mother-newborn pairs with term delivery. Using real-time Polymerase Chain Reaction (PCR), three SNPs rs8192282 A > G, rs2277698 C > T and rs34003 A > C located on interleukin 6 receptor (IL6R), tissue inhibitor of matrix metalloproteinase-2 (TIMP2) and fibroblast growth factor 1 (FGF1) genes were assessed. The minor allele and genotype frequencies were compared between groups. Multilocus genetic association analyses were performed. From pathology reports, the morphological and histopathological examination of the placentas were extracted.Results: The rs34003 C/C genotype frequency in newborns FGF1 gene was significantly higher in the spontaneous preterm birth (SPTB) group compared to the control group (p = .045). In single-locus analyses, C/C genotype was associated with an increased risk of spontaneous preterm birth (OR = 2.59, 95%CI: 1.02-6.58). Additionally, this homozygote genotype was correlated with the presence of placental pathology, especially with the inflammatory and vascular lesions (p < .01). The prediction model based on rs34003 C/C genotype - placental pathology joint influence had a statistically significant regression coefficient (p < .01, OR = 7.76, 95%CI: 4.03-14.93). Single nucleotide polymorphisms related to IL6R gene in maternal samples and FGF1 gene in newborns were associated with spontaneous preterm delivery in multilocus genetic association analyses (p = .028, OR of 2.375).Conclusions: Our results indicate that rs34003 C/C genotype in newborns FGF1gene is correlated with the occurrence of placental pathological lesions and with an increased SPTB risk. The association of two SNPs in maternal and fetal genes doubled the risk of spontaneous preterm birth in our population.

Antioxidant Capacity of Preterm Neonates Assessed by Hydrogen Donor Value.

Background and objectives: Premature newborns have a number of oxidative stress-inducing disorders. Antioxidant defense is deficient in premature newborns. Hydrogen donors can be used to evaluate the non-enzymatic antioxidant defense. By measuring hydrogen donors, a group of antioxidants can be assessed: tocopherol, ascorbic acid, and glutathione. These represent the most relevant group of non-enzymatic antioxidants. The main aim of this study was to evaluate the non-enzymatic antioxidant defense capacity of premature newborns by measuring hydrogen donors. Materials and Methods: We evaluated the non-enzymatic antioxidant capacity by hydrogen donor measurement in 24 premature newborns with various oxidative stress-inducing disorders and in 14 premature newborns without oxidative stress-inducing conditions. Statistical analysis was performed using the Statistica program (v. 8, StatSoft, Round Rock, TX, USA). Differences between groups were tested with Wilcoxon matched test for quantitative paired data or Mann-Whitney test for quantitative independent data. The Z test for proportions was used to compare qualitative data among subgroups. Results: Hydrogen donors in the study group had a significantly lower value on the first day of life compared to the value of the control group. Also, the hydrogen donor value in the study group was significantly lower on the first day compared to the third day of life (p < 0.05). Neonates with mild respiratory distress (14 cases) had increased hydrogen donor values on their third day of life compared to the first day of life. Conclusions: The antioxidant capacity is influenced by oxidative stress-inducing disorders. Respiratory distress influenced the hydrogen donor value and antioxidant defense. Antioxidant defense gradually improves after birth according to gestational age.

Potential Clinical Predictors of Suspected Early and Late Onset Sepsis (EOS and LOS) in Preterm Newborns: a Single Tertiary Center Retrospective Study.

BACKGROUND: Neonatal sepsis represents one of the common diseases in the neonatal intensive care unit. Here we aim to evaluate the differences between a group of preterm newborns with sepsis and a control group in relation to clinical and laboratory variables. In addition, our goal is to establish potential predictors of early-onset sepsis (EOS) and late-onset sepsis (LOS). METHODS: The study included 113 preterm newborns with sepsis (EOS-63.72%/LOS-36.28%). Laboratory deter-minations included full blood count, CRP, biochemical determinations, blood culture. RESULTS: The most important univariate neonatal predictors were gestational age (p < 0.001), surfactant adminis-tration (p < 0.001), mechanical ventilation (p < 0.001), heart failure (p < 0.001), a history of hypocalcemia (p = 0.037), Apgar score at 1 minute lower than 7 (p = 0.001), birth weight < 1,500 g (p = 0.005), number of hospi-talization days (p = 0.048), and number of weight recovery days < 10 (p < 0.05). The WBC and CRP parameters remained significant univariate predictors of sepsis on day 7 (p = 0.002; OR = 2.01 per 10,000 mm3 increase of WBC, 95% CI: (1.30; 3.09) and p = 0.001; OR = 4.27, 95% CI: (1.85; 9.88), respectively). Logistic regression anal-ysis showed maternal urinary tract infection (OR = 3.05), heart failure (OR = 5.28), the number of hospitalization days (OR = 1.09) and CRP (OR = 3.26) were significant independent risk factors for neonatal sepsis in preterms. The univariate predictors of EOS were gestational age (p = 0.002), birth weight (p = 0.014), 1-minute Apgar score (p = 0.012), maternal urinary tract infection (p = 0.008), surfactant administration (p < 0.001), heart failure (p < 0.001), and CRP level (p < 0.001). Surfactant administration (OR = 6.73) and CRP level (OR = 3.51) represent predictors of EOS in preterms according to the multivariate model. The univariate predictors of LOS were gesta-tional age (p = 0.001), birth weight (p = 0.048), 1-minute Apgar score (p = 0.001), surfactant administration (p < 0.001), hypocalcemia (p = 0.03), heart failure (p = 0.003), CRP level (p < 0.001), mechanical ventilation (p < 0.001), and the number of hospitalization days (p < 0.001). In the multivariate model, the number of hospitali-zation days (OR = 1.11) and heart failure (OR = 5.98) are independent predictors for LOS in preterms. CONCLUSIONS: The study confirms the presence of maternal urinary tract infection, hospitalization days, heart fail-ure, and CRP level as predictors of neonatal sepsis in preterms with differences between EOS and LOS.