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.

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.

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.

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.

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.

Cardiac left heart morphology and function in newborns with intrauterine growth restriction: relevance for long-term assessment.

AIM: To asses the cardiac morphology and functional changes specific for newborns from intrauterine growth restriction (IUGR) pregnancies. MATERIAL AND METHOD: A cohort of IUGR infants were evaluated by serial echocardiographies at delivery and at the first and six months follow-ups. IUGR newborn delivery status was compared to that of newborns in the control group according to gestational age (AGA). RESULTS: Left heart measurements were significantly lower in IUGR newborns compared to AGA babies. Left ventricular size increased at follow-up inthe IUGR group (p<0.05). Systolic dysfunction (the myocardial performance index (MPI)> 0.47) was identified in 40% of the neonates in the IUGR group (16/40), respectively 4.76% in the control group. IUGR neonates had a significantly increased proportion of systolic malfunction (p=0.004). CONCLUSION:  IUGR patients had reduced left ventricle dimensions compared to AGA babies. The MPI stands out as a marker of leftheart function in newborns. Systolic dysfunction was a hallmark of the cardiac adaptation in IUGR neonates.

Serum levels and ApaI polymorphism of insulin-like growth factor 2 on intrauterine growth restriction infants.

PURPOSE: The aim of our study was to evaluate the IGF2 and IGF2R plasmatic level and IGF2-ApaI polymorphism on infants with intrauterine growth restriction (IUGR). MATERIALS AND METHODS: A transversal study was conducted at the Neonatology Ward of the Gynecology Clinic I, Emergency Hospital Cluj-Napoca on neonates with IUGR who were discharged during June 2014 and June 2015. The serum levels of IGF2 and IGF2R were obtained by using ELISA method and IGF2-ApaI polymorphism by taking PCR-RFLP analysis. RESULTS: Forty infants with IUGR and 21 infants of appropriate gestational age (AGA) were evaluated. The serum levels of IGF2 proved higher on the A/G genotype when the IUGR group was compared with AGA (p value = .048). The G allele proved significantly more frequent in both the IUGR and the AGA group compared with the A allele (p < .002). Neither any allele nor any genotype proved a risk factor for IUGR (p value > .3). The A/G genotype proved significantly more frequent on term infants compared with preterm infants (p value = .039). CONCLUSIONS: The infant with IUGR has a higher serum level of IGF2 if has A/G IGF2-ApaI genotype and higher values of IGF2R if it has the A/A genotype.

Neonatal short-term outcomes in infants with intrauterine growth restriction.

OBJECTIVES: To assess the neonatal outcomes in newborns with intrauterine growth restriction (IUGR) in a Romanian population in a 3 level maternity unit. METHODS: A matched case-control design, with one control for each patient was used. The case group comprised neonates with birth weight and birth length below the 10th percentile for the gestational age. Individual matching by gender and age of gestation was used to identify the control group. Both cases and controls were selected from the infants admitted to and discharged from the Neonatal Ward, at the First Gynecology Clinic, of the County Emergency Hospital Cluj-Napoca, Cluj-Napoca, Romania, between January 2012 and June 2014. RESULTS: One hundred and forty-two subjects were included in each group. The cesarean delivery was significantly more frequent in the IUGR group (66.9%) compared with controls (46.5%; p=0.0006). The Apgar score at one minute was ≥ 7 for most infants in both groups (77.9% IUGR group versus 77.5% control group), with no significant differences between the groups. A significantly higher percentage of infants in the IUGR group had hypoglycemia or intraventricular hemorrhage compared with the controls (p < 0.05). Hypoglycemia proved a significant factor for IUGR (odds ratio = 4.763, 95% confidence interval: 1.711-13.255). CONCLUSION: Hypoglycemia and intraventricular hemorrhage characterized the IUGR newborns.

CLINICAL AND ECHOCARDIOGRAPHIC FINDINGS IN NEWBORNS OF DIABETIC MOTHERS.

The aim of the study was to assess the use of echocardiographic measurements in newborns of diabetic mothers. Maternal diabetes is associated with an increased risk of morbidity and mortality in pregnancy and in perinatal period. Thirty-five newborns of diabetic mothers (pre- gestational or gestational diabetes; case group) and thirty-five controls (control group), born between January 2009 and December 2012 in Cluj-Napoca (north-west of Romania), were included in this study. A Logiq e ultrasound with an 8 MHz transducer was used to measure echocardiographic parameters. The interventricular septal thickness in case group was higher as compared with control group (at end systole = 6.61 ± 1.64 mm vs. 5.75 ± 0.95 mm, p = 0.0371; at end diastole = 4.61 ± 1.59 mm vs. 3.42 ± 0.70 mm, p = 0.0001). A risk ratio of 2.333 (0.656, 8.298) was obtained for septal hypertrophy. A higher proportion of septal hypertrophy was identified in the newborns of mothers with gestational diabetes compared to the newborns of pregestational diabetes mothers (p = 0.0058). The mean birth weight was significantly higher in newborns of diabetic mothers (3695.57 ± 738.63) as compared with controls (3276.14 ± 496.51; p = 0.0071). Infants born to mothers with diabetes proved to be at a high risk of septal hypertrophy.

Parental Factors Associated with Intrauterine Growth Restriction.

INTRODUCTION: Linear growth failure is caused by multiple factors including parental factors. OBJECTIVE: The aim of this study was to evaluate parental risk factors for intrauterine growth restriction (IUGR) on a population of Romanian newborn infants in a tertiary level maternity facility for a period of 2.5 years. METHODS: A retrospective matched case-control study was conducted in the Emergency County Hospital of Cluj-Napoca, a university hospital in North-Western Romania. The sample was selected from 4,790 infants admitted to the Neonatal Ward at 1st Gynecology Clinic between January 2012 and June 2014. RESULTS: The age of mothers was significantly lower in the IUGR group compared to controls (p = 0.041). A significantly higher percentage of mothers had hypertension in the IUGR group compared to those in the control group (p<0.05). No other significant differences were identified with regard to the investigated characteristics of mothers between IUGR infants compared to controls (p > 0.13). The age of fathers of infants with IUGR proved significantly lower compared to controls (p = 0.0278).The analysis of infants'comorbidities revealed no significant difference between groups for respiratory distress, hyperbilirubinemia, hypocalcaemia, and heart failure (p > 0.27). Intracranial hemorrhage, necrotizing enterocolitis and hypoglycemia were significantly higher in the IUGR group compared to controls. The logistic regression identified hypertension as a significant risk factor for IUGR (OR = 2.4, 95% Cl [1.3-4.5]). CONCLUSION: Although the age of the mothers and fathers proved significantly lower in the IUGR group compared to controls, only hypertension in the mothers proved significant risk factors for IUGR.