Investigating the Association between Serum and Hematological Biomarkers and Neonatal Sepsis in Newborns with Premature Rupture of Membranes: A Retrospective Study.

(1) Background: Neonatal early-onset sepsis (EOS) is associated with important mortality and morbidity. The aims of this study were to evaluate the association between serum and hematological biomarkers with early onset neonatal sepsis in a cohort of patients with prolonged rupture of membranes (PROM) and to calculate their diagnostic accuracy. (2) Methods: A retrospective cohort study was conducted on 1355 newborns with PROM admitted between January 2017 and March 2020, who were divided into two groups: group A, with PROM ≥ 18 h, and group B, with ROM < 18 h. Both groups were further split into subgroups: proven sepsis, presumed sepsis, and no sepsis. Descriptive statistics, analysis of variance (ANOVA) and a Random Effects Generalized Least Squares (GLS) regression were used to evaluate the data. (3) Results: The statistically significant predictors of neonatal sepsis were the high white blood cell count from the first (p = 0.005) and third day (p = 0.028), and high C-reactive protein (CRP) values from the first day (p = 0.004). Procalcitonin (area under the curve-AUC = 0.78) and CRP (AUC = 0.76) measured on the first day had the best predictive performance for early-onset neonatal sepsis. (4) Conclusions: Our results outline the feasibility of using procalcitonin and CRP measured on the first day taken individually in order to increase the detection rate of early-onset neonatal sepsis, in the absence of positive blood culture.

Hematologic Risk Factors for the Development of Retinopathy of Prematurity-A Retrospective Study.

(1) Background: Retinopathy of prematurity (ROP) can cause severe visual impairment or even blindness. We aimed to assess the hematological risk factors that are associated with different stages of ROP in a cohort of preterm newborns, and to compare the clinical characteristics and therapeutic interventions between groups. (2) Methods: This retrospective study included 149 preterm newborns from a tertiary maternity hospital in Romania between January 2018 and December 2018, who were segregated into: Group 1 (with ROP, n = 59 patients), and Group 2 (without ROP, n = 90 patients). The patients that were affected by ROP were subsequently divided into the following subgroups: Subgroup 1 (Stage 1, n = 21), Subgroup 2 (Stage 2, n = 35), and Subgroup 3 (Stage 3, n = 25). The associations were analyzed using multivariate logistic regression and sensitivity analysis. (3) Results: Platelet mass indexes (PMI) that were determined in the first, seventh, and tenth days of life were significantly associated with Stage 1 ROP. PMI determined in the first day of life was also significantly associated with Stage 2 ROP. The sensitivity and specificity of these parameters were modest, ranging from 44 to 57%, and 59 to 63%. (4) Conclusions: PMI has a modest ability to predict the development of ROP.

A Multicenter Cohort Study Evaluating the Teratogenic Effects of Isotretinoin on Neonates.

(1) Background: Isotretinoin (ISO) is a systemic retinoid known for its teratogenic effects on embryos and fetuses. The aim of this study was to compare the pregnancy outcomes of women who were exposed to isotretinoin with those of women without such exposure from a teratogenic point of view. (2) Methods: A total of 1459 female patients from three clinical hospitals in Poland and Romania, segregated into two groups depending on their ISO exposure, were evaluated between January and December 2019. Medical records were screened to identify the pregnancy outcomes and congenital malformation rates. (3) Results: The congenital malformation rate for the exposed group was 1.2% (four cases), and no specific signs of Accutane embryopathy were identified. Women from the unexposed group were more likely to deliver preterm and through cesarean deliveries and had a higher rate of newborn congenital malformations as compared to women from the exposed group. (4) Conclusions: Even though we could not find a significant association between ISO exposure and teratogenic effects in newborns, effective contraceptive measures are key to preventing unfavorable pregnancy outcomes.

Neonatal Cerebral Sinovenous Thrombosis and the Main Perinatal Risk Factors-A Retrospective Unicentric Study.

(1) Background: Neonatal cerebral sinovenous thrombosis (CSVT) is a rare disorder, associated with long-term neurological sequelae. The aim of this study was to retrospectively evaluate the most commonly encountered perinatal risk factors for this disease in a cohort of newborns from Romania. (2) Methods: The medical records of neonatal CSVT patients treated between January 2017 and December 2021 were descriptively assessed. (3) Results: The study included nine neonates, five males (55.56%) and four females (44.44%), who were born at term. The most commonly presented clinical manifestations were feeding difficulties, lethargy, respiratory distress, loss of consciousness, and seizures. Maternal-inherited thrombophilia, male sex, complicated delivery, perinatal asphyxia, and mechanical ventilation were frequently identified as potential risk factors for developing CSVT. The lesions were more frequently localized in the superior sagittal sinus (n = 7; 77.78%), followed by the transverse (n = 4; 44.44%), sigmoid (n = 2; 22.22%), and cavernous (n = 1; 11.11%) sinuses. Low-molecular-weight heparin was administered to all patients, and two of them died from thrombotic complications. (4) Conclusions: Recognition of potential risk factors and a prompt diagnosis of neonatal CSVT could lead to better patient management and to a reduction of severe complications.

Relevance of Biomarkers Currently in Use or Research for Practical Diagnosis Approach of Neonatal Early-Onset Sepsis.

Neonatal early-onset sepsis (EOS) is defined as an invasive infection that occurs in the first 72 h of life. The incidence of EOS varies from 0.5-2% live births in developed countries, up to 9.8% live births in low resource settings, generating a high mortality rate, especially in extremely low birth weight neonates. Clinical signs are nonspecific, leading to a late diagnosis and high mortality. Currently, there are several markers used for sepsis evaluation, such as hematological indices, acute phase reactants, cytokines, which by themselves do not show acceptable sensitivity and specificity for the diagnosis of EOS in neonates. Newer and more selective markers have surfaced recently, such as presepsin and endocan, but they are currently only in the experimental research stages. This comprehensive review article is based on the role of biomarkers currently in use or in the research phase from a basic, translational, and clinical viewpoint that helps us to improve the quality of neonatal early-onset sepsis diagnosis and management.

Fatal neonatal persistent pulmonary hypertension caused by vegetations of infective endocarditis - case report and review of the literature.

Neonatal infective endocarditis is a rare condition and usually pertains to a specific class of immunologically depressed preterm infants, with a long history of invasive procedures in the Neonatal Intensive Care Unit. We report the case of an aggressive and fatal neonatal infective endocarditis in a full-term infant, who developed massive endocardial vegetations on the tricuspid valve, leading to persistent pulmonary hypertension of the newborn, unresponsive to nitric oxide ventilation. Post-mortem cardiac cultures were positive with Serratia marcescens, an unusual germ for an early-onset infection, which was absent in blood cultures.

Influence of refrigeration or freezing on human milk macronutrients and energy content in early lactation: Results from a tertiary centre survey.

BACKGROUND: Neonates with severe conditions that cannot be breastfed should receive fresh or preserved expressed human milk in addition to parenteral nutrition. OBJECTIVE: To identify the time during lactation when the macronutrients provide maximum energy and evaluate the effect of refrigeration and freezing. METHODS: We analyzed the composition of fresh milk, refrigerated at +4°C and frozen at -20°C, expressed by mothers of 60 preterm and 30 term infants from a level III maternity, in colostrum, transitional, and mature milk. RESULTS: In fresh milk, the protein level constantly decreases during lactation, with a significant difference after 3 weeks of lactation. Preterm milk of day 21 and day 30 had significantly lower protein than term milk (1.27 versus 1.43 g/dL, P=0.015 and 1.13 versus 1.28 g/dL, P=0.001). Refrigeration for 72 hours of term milk decreased protein content less than freezing. Preterm colostrum has significantly less protein after 48 hours of refrigeration or freezing. Preterm milk from day 60 lost carbohydrates if refrigerated 72 hours or frozen for 2 months. Lipids in preterm colostrum decrease after 8 weeks of freezing. Refrigeration for up to 72 hours did not change significantly the energy value of colostrum or transitional milk. Freezing preterm milk more than 2 weeks leads to significant loss of energy. CONCLUSIONS: Milk frozen for more than 2 weeks contains less protein and energy than milk refrigerated for up to 72 hours. In the absence of milk bank access, in common settings, short-term refrigeration is preferable to long-term freezing.

Endocan - a potential diagnostic marker for early onset sepsis in neonates.

INTRODUCTION: Neonatal early onset sepsis assessment is based on the history of pregnancy and delivery and nonspecific clinical signs. None of the biomarkers currently in use for clinical practice has adequate prognostic value, so it is not possible to clearly distinguish neonates with culture-proven sepsis from those with only risk factors or clinical suspicion. Endocan is an endothelial mediator involved in the inflammatory response that is present in low concentrations in the serum of healthy subjects, and in much higher concentrations in patients with SIRS and septic shock. The purpose of this study is to evaluate the utility of serum endocan serum levels as a biomarker for the diagnosis of neonatal early onset sepsis (EOS). METHODOLOGY: Serum endocan concentration was measured in newborns with clinical suspicion of EOS admitted to the Neonatal Intensive Care Unit on day 1, 3 and 7. RESULTS: Serum endocan levels were significantly increased in septic compared to non-septic neonates in the early stages of sepsis (2.43 ± 0.95 vs. 1.77 ± 0.57, p = 0.004), continued to rise up to 72 hours from onset and then decreased by the seventh day under treatment. CONCLUSIONS: These results suggest a potential role for endocan as an early marker for diagnosis and follow-up in neonatal EOS. Studies on a larger number of cases are needed in order to establish the practical utility of this molecule as a diagnostic tool for clinical practice.

Total antioxidant status in fresh and stored human milk from mothers of term and preterm neonates.

BACKGROUND: Antioxidant defense of the body is assured by both endogenous and exogenous factors comprising several enzymes, vitamins, protein components and derivates and oligoelements. Breast milk has been proven to have important and essential antioxidant composition to prevent and protect against diseases in infancy. The objective of this study was to determine the total antioxidant status (TAS) of human milk and to evaluate the differences between premature milk and term milk at different moments of lactation (colostrum, transitional milk and mature milk). A second objective was to evaluate how TAS varies whether the human milk is refrigerated or frozen. METHODS: Pumped human milk samples of the third, seven and 30th day were collected from women who had term deliveries (30 cases) and preterm deliveries (60 cases). Samples were refrigerated (+4 °C) or frozen in domestic conditions (-20 °C) for various durations and TAS was determined using the ABTS® technique with Randox® reagents and compared for the two groups. RESULTS: Higher values were found in term versus preterm fresh milk at 30 days of lactation. A slight reduction in TAS was found after 72 h of refrigeration, while 1 week freezing produced significant decrease of total antioxidants. Freezing for 12 weeks reduced more than 50% of TAS in fresh milk. CONCLUSION: Breastfeeding provides the optimal antioxidant for neonates, regardless of gestational age. Fresh milk has the higher antioxidant power. When it is not available, refrigerated milk for 24 h is better than for 72 h and preferable than frozen milk. Freezing human milk for 3 months in household conditions markedly diminishes TAS.

Early intrauterine development of mixed giant intracranial teratoma in newborn: a case report.

UNLABELLED: Teratoma is one of the most frequent fetal intracranial tumors, but it usually grows very quickly and the fetus is generally a stillborn. Rare cases have slow development or are located in areas that afford immediate surgery after birth with variable chances of survival. Even more rare cases survive days or weeks, but with no chance of surgical treatment and with prolonged palliative care. We present a 34 weeks premature infant, born by C-section with a giant intracranial tumor, whose origin could not be ascertained, occupied almost all-intracranial space and survived 25 days with supportive care. The histological examination established a G3 mixed teratoma, predominantly with immature cells from all three embryonic layers. The cerebellum was normal and infra-mesencephalic structures were present. The infant presented with severe anemia and mild respiratory distress, and was out of neurosurgical therapeutic resources. Antenatal examination was normal until 30 weeks, when fetal ultrasound described a degree of hydrocephalus, but no tumor was individualized. CONCLUSIONS: G3 type complex teratoma, even rare, can be localized at cerebral level and get giant development and growth only in the third trimester of pregnancy, ending with a neonate that has no chance of survival. Such cases cannot benefit of therapeutic interruption of pregnancy and generate serious difficulties for parents and clinicians.

Thapsigargin-induced endoplasmic reticulum stress is not accompanied by mitochondrial membrane potential dissipation in murine pro-B cells.

UNLABELLED: There are almost no data concerning the involvement of endoplasmic reticulum stress (Ca2+ fluxes) in the apoptosis of the pro-B cell type Ba/F3. Thus, we aimed the characterization of thapsigargin-induced effects on Ba/F3 cells in vitro. MATERIAL AND METHOD: For some experiments Ba/F3 cells were treated with 1 microM thapsigargin for 24 hours. To compare, we used as positive control the effects of valinomycin 10 microM. The negative control Ba/F3 cells received no treatment for 24 hours. After that, all batches of Ba/F3 cells were incubated in the presence of 1 mimcroM JC-1 (Sigma-Aldrich) at 37 degrees C for 30 minutes. RESULTS: From the normal Ba/F3 JC-1-control cells (20.000 events gated by flow cytometry) 77.61 +/- 2.90% are associating high and 22.39 = 2.90% lower mitochondrial membrane potential. In the case of thapsigargin, 75.49 +/- 1.78% of the Ba/F3 cells are associating high and 24.51 +/- 1.78% lower mitochondrial membrane potential. CONCLUSIONS: While mitochondrial permeability transition pore (MPTP) opening necessarily correlates with a loss of mitochondrial membrane potential (Psi(mt)), a decrease in Psi(mt) does not necessarily indicate MPTP opening. Also, endoplasmic reticulum stress regulation of high cytosolic calcium levels by thapsigargin may prompt the opening of the MPTP without necessarily triggering irreversible pore activation or subsequent apoptogenic factors in Ba/F3 cells.