Biomarkers and Biochemical Indicators to Evaluate Bone Metabolism in Preterm Neonates.

The purpose of the present study was to evaluate the concentrations of some bone turnover markers in preterm neonates with uncomplicated clinical course in the first month of life. Samples from 13 preterm neonates were collected at three different times: at birth (T0) from umbilical cord blood (UCB); and at 15 (T1) and 30 (T2) days of life from peripheral blood (PB). The concentrations of calcium (Ca), phosphate (P), total alkaline phosphatase (ALP), Collagen Type 1 Amino-terminal Propeptide (PINP), osteocalcin (OC), Collagen Type 1 Carboxyl-Terminal Telopeptide (CTX) and Leptin were assessed. A statistically significant difference for ALP concentration at birth versus T1 and T2 was found. An evident increase in the median concentrations of CTX, OC and PINP from T0 to T2 were observed. A significant difference was also found for Leptin concentration at T0 compared to T1. In preterm infants, in the absence of acute or chronic medical conditions and without risk factors for metabolic bone disease (MBD) of prematurity, there is a significant increase in bone turnover markers during the first month of life. The knowledge of the variations in these markers in the first weeks of life, integrated by the variations in the biochemical indicators of bone metabolism, could help in recognizing any conditions at risk of developing bone diseases.

No differences were observed in the prevention of necrotizing enterocolitis and late-onset sepsis among preterm infants who received either single-species or multi-species probiotics.

BACKGROUND: Probiotic prophylaxis has been suggested to reduce the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in very preterm newborns. However, choosing the optimal probiotic is difficult due to variations in strain-specific effects and interactions facilitated by the use of combination species. AIMS: To compare clinical outcomes of very preterm infants receiving multi or single-species probiotics. STUDY DESIGN: Retrospective, single-center, cohort study. SUBJECTS: Very preterm infants (<32 weeks' gestation) born between 2019 and 2022 at a tertiary perinatal center received either a multi-species (Lactobacillus rhamnosus 45 %, Lactobacillus casei 15 %, Lactobacillus acidophilus 15 %, Bifidobacterium infantis 15 %, Bifidobacterium bifidum 10 %; n = 228) or a single-species (Bifidobacterium breve BR03 and B632; n = 227) probiotic formulation. MAIN OUTCOME MEASURES: NEC, LOS, and mortality. RESULTS: The overall incidence of NEC and LOS was 3.1 % and 13.8 %, respectively. There were no differences between the multi-species and single-species probiotic groups in the rate of NEC (3.5 % vs 2.6 %; p = 0.787), LOS (15.4 % vs 12.3 %; p = 0.416), mortality (0.9 % vs 1.8 %; p = 0.449), or composite outcome (NEC, LOS and/or death; 16.7 % vs 12.8 %; p = 0.290). CONCLUSION: The clinical outcomes of very preterm newborns receiving multi vs. single-species probiotic formulations were similar in our study. In view of the sample size and low baseline rate of NEC in our unit, further trials are warranted to investigate the effects of specific probiotics for prevention of serious neonatal morbidities.

Evaluating the Clinical Risk Index for Babies (CRIB) II Score for Mortality Prediction in Preterm Newborns: A Prospective Observational Study at a Tertiary Care Hospital.

INTRODUCTION: Neonatal mortality is an issue that affects both the developed and developing world. It is very important in the neonatal intensive care unit (NICU) to do the assessment of the severity of neonatal illness, which in turn helps in estimating and preventing mortality in the NICU by improving healthcare control and by rational use of resources. This research was carried out to evaluate how effectively the Clinical Risk Index for Babies (CRIB) II score can predict mortality rates among newborns treated in our NICU.  Methodology: This prospective observational study spanned one year, commencing in October 2021 and concluding in September 2022, within the confines of our NICU. The CRIB II score calculation was performed for included newborns, and the outcomes of the newborns were compared. A receiver operating characteristic (ROC) curve was obtained to ascertain the optimal CRIB II cut-off score for predicting mortality. RESULTS: Within the designated research timeframe, 292 neonates were admitted to the NICU. Forty-four newborns were enrolled in the study. Preterm neonates who died had higher CRIB II scores than those who survived, and their median (IQR) was 6 (1-12) vs. 9.5 (5-14) (p=0.0003). The estimate for the area under the curve was 0.83 (95% CI 0.68-0.92), and the odds ratio of 2.56 suggests neonates with a higher CRIB II score have higher chances of mortality. CONCLUSION: The CRIB II score is very good at predicting mortality in preterm newborns.

Bone Marrow Nucleated Cells and Bone Marrow-Derived CD271+ Mesenchymal Stem Cell in Treatment of Encephalopathy and Drug-Resistant Epilepsy.

The broad spectrum of brain injuries in preterm newborns and the plasticity of the central nervous system prompts us to seek solutions for neurodegeneration to prevent the consequences of prematurity and perinatal problems. The study aimed to evaluate the safety and efficacy of the implantation of autologous bone marrow nucleated cells and bone marrow mesenchymal stem cells in different schemes in patients with hypoxic-ischemic encephalopathy and immunological encephalopathy. Fourteen patients received single implantation of bone marrow nucleated cells administered intrathecally and intravenously, followed by multiple rounds of bone marrow mesenchymal stem cells implanted intrathecally, and five patients were treated only with repeated rounds of bone marrow mesenchymal stem cells. Seizure outcomes improved in most cases, including fewer seizures and status epilepticus and reduced doses of antiepileptic drugs compared to the period before treatment. The neuropsychological improvement was more frequent in patients with hypoxic-ischemic encephalopathy than in the immunological encephalopathy group. Changes in emotional functioning occurred with similar frequency in both groups of patients. In the hypoxic-ischemic encephalopathy group, motor improvement was observed in all patients and the majority in the immunological encephalopathy group. The treatment had manageable toxicity, mainly mild to moderate early-onset adverse events. The treatment was generally safe in the 4-year follow-up period, and the effects of the therapy were maintained after its termination.

Respiratory Support Effects over Time on Regional Lung Ventilation Assessed by Electrical Impedance Tomography in Premature Infants.

Background and objectives: Respiratory distress syndrome (RDS) frequently necessitates respiratory support. While non-invasive methods are typically the preferred approach, mechanical ventilation becomes necessary for patients with insufficient response. Our study aimed to compare two common respiratory support modes, volume-targeted mechanical ventilation and non-invasive ventilation continuous positive airway pressure (CPAP) and high-flow nasal cannula (HFNC), using electrical impedance tomography. Materials and Methods: Infants with very low birth weight and gestational ages of less than 32 weeks were eligible for inclusion in the study. All enrolled infants were beyond the transitional period (>72 h of age). The infants were divided into two groups: infants receiving invasive respiratory support through an endotracheal tube and infants receiving non-invasive respiratory support. We used electrical impedance tomography to assess end-expiratory lung impedance (EELZ), DeltaZ, heterogeneity, and regional ventilation distribution. Patients were evaluated at 0, 30, and 60 min after assuming the supine position to examine potential time-related effects. Results: Our study initially enrolled 97 infants, and the final analysis included a cohort of 72 infants. Ventilated infants exhibited significantly larger EELZ compared to their non-invasive counterparts (p = 0.026). DeltaZ was also greater in the invasive respiratory support group (p < 0.001). Heterogeneity was higher in the non-invasive group and did not change significantly over time. The non-invasive group demonstrated significantly greater ventilation in the dependent lung areas compared to intubated patients (p = 0.005). Regional distribution in the left lung was lower than in the right lung in both groups; however, this difference was significantly more pronounced in intubated patients (p < 0.001). Conclusions: Our study revealed that volume-targeted mechanical ventilation results in higher EELZ and DeltaZ compared to spontaneously breathing infants receiving non-invasive respiratory support. However, lung heterogeneity was lower during mechanical ventilation. Our study also reaffirmed that spontaneous breathing promotes greater involvement of the dependent lung compared to mechanical ventilation.

Colorimetric CO2 Detector to Improve Effective Mask Ventilations in Very Preterm Infants: A Pilot Randomized Controlled Study.

INTRODUCTION: End-tidal CO2 (ETCO2) detector is currently recommended for confirmation of endotracheal tube placement during neonatal resuscitation. Whether it is feasible to use ETCO2 detectors during mask ventilation to reduce risk of bradycardia and desaturations, which are associated with increased risk of death in preterm babies, is unknown. METHODS: This is a pilot randomized controlled trial (NCT04287907) involving newborns 24 + 0/7 to 32 + 0/7 weeks gestation who required mask ventilation at birth. Infants were randomized into groups with or without colorimetric ETCO2 detectors. Combined duration of any bradycardia (<100 bpm) and time below prespecified target oxygen saturation (SpO2) as measured by pulse oximetry were compared. RESULTS: Fifty participants were randomized, 47 with outcomes analysed (2 incomplete data, 1 postnatal diagnosis of trachea-oesophageal fistula). Mean gestational age and birthweight were 28.5 ± 1.9 versus 29.4 ± 1.6 weeks (p = 0.1) and 1,252.7 ± 409.7 g versus 1,334.6 ± 369.1 g (p = 0.5) in the intervention and control arm, respectively. Mean combined duration of bradycardia and desaturation was 276.7 ± 197.7 s (intervention) and 322.7 ± 277.7 s (control) (p = 0.6). Proportion of participants with any bradycardia or desaturation at 5 min were 38.1% (intervention) and 56.5% (control) (p = 0.2). No chest compressions, epinephrine administration, or death occurred in the delivery room. CONCLUSION: This pilot study demonstrates the feasibility of a trial to evaluate colorimetric ETCO2 detectors during mask ventilation of very preterm infants to reduce bradycardia and low SpO2. Further assessment with a larger population will be required to determine if ETCO2 detector usage at resuscitation reduces risk of adverse outcomes, including death and disability, in very preterm infants.

Vivências no processo de aleitamento materno de mães de recém-nascidos prematuros internados em um hospital público do municipio de Guarapuava-PR / Experiences in the breastfeeding process of mothers of preterm newborns admitted to a public hospital in the city of Guarapuava-PR

Objetivo: Descrever os relatos de vivências no processo de amamentação de mães de recém-nascidos prematuros. Método: Estudo qualitativo realizado com mães de recém-nascidos prematuros, internados em uma Unidade de Terapia Intensiva Neonatal, de um hospitalpúblico de Guarapuava-PR, no período de junho a julho de 2018, mediante aplicação de um instrumento com questões fechadas e outro com questões relacionadas à amamentação de prematuros. Foram incluídas no estudo mães que já haviam amamentado seus filhos ao seio ou por meio da ordenha mamária, e excluídas mães com idade inferior a 18 anos ou que apresentavam condições clínicas que as impediam de amamentar, cujos filhos estavam internados em período menor que três dias. Resultados: Participaram do estudo 10 mães de recém-nascidos prematuros, das quais 70% tinham idade gestacional de 32 a 36 semanas, 10% de 28 semanas e 20% de 29 semanas gestacionais. As mães relataram dificuldades em manter a pega e a sucção do leite materno e sentimentos de nervosismo, receberam apoio dos profissionais e familiares no incentivo à amamentação e no cuidado humanizado pela equipe de saúde. Conclusões: Diante do conhecimento das dificuldades encontradas pelas mães na amamentação de prematuros, é possível estabelecer medidas para evitar o desmame precoce, respeitando a autonomia da mãe no cuidado ao bebê.

Objective: To describe the breastfeeding experiences of mothers of preterm newborns. Methods: Qualitative study carried out with mothers of preterm newborns admitted to a Neonatal Intensive Care Unit at a public hospital in Guarapuava-PR, from June to July 2018, using a questionnaire instrument with closed questions and another with questions related to breastfeeding premature babies. The study included mothers who had already breastfed their children, and excluded mothers under the age of 18 or who had medical conditions that prevented them from breastfeeding, and whose children had been hospitalized for less than three days. Results: Ten mothers of preterm newborns took part in the study, 70% of whom had a gestational age of 32 to 36 weeks, 10% 28 weeks and 20% 29 weeks. The mothers reported difficulties in maintaining the latch and sucking breast milk, as well as feelings of nervousness. They received support from professionals and family members in encouraging breastfeeding and humanized care from the health team. Conclusion: With knowledge of the difficulties encountered by mothers in breastfeeding preterm babies, it is possible to establish measures to prevent early weaning, while respecting the mother's autonomy in caring for the baby.

Influence of umbilical cord vitamin D serum levels on the growth of preterm infants.

OBJECTIVE: The aim of this study was to evaluate the influence of serum 25-hydroxyvitamin D [25(OH)D] levels at birth in postnatal growth at discharge and 12 mo of corrected age in preterm infants. METHODS: This prospective cohort included 63 preterm newborns born before 34 gestational weeks evaluated from birth until 12 mo of corrected age. The serum 25(OH)D levels in umbilical cord blood and from their mothers were evaluated at delivery. RESULTS: The mean 25(OH)D levels in preterm newborns were higher than maternal levels (24.8 ± 13.3 ng/mL versus 21 ± 10.2 ng/mL, P < 0.001) and showed a moderate correlation between (r = 0.548; P < 0.001). Considering the body mass index Z-score at 12 mo, 3 (10%), 25 (83%), and 2 (7%) of the preterm infants were thin, had normal body mass index, and were overweight, respectively. The 25(OH)D levels in the umbilical cord did not influence the anthropometric indicators at hospital discharge and 12 mo of corrected age. We observed improvement in all anthropometric indicators assessed over the months, and there was no difference between preterm infants with 25(OH)D levels >20 ng/mL and <20 ng/mL in the umbilical cord. CONCLUSIONS: The results of this study suggested that the 25(OH)D serum levels in the umbilical cord did not influence postnatal growth from birth to the first year of life in preterm infants. There was a direct association between maternal and umbilical cord serum 25(OH)D levels.

Population PK/PD modelling of meropenem in preterm newborns based on therapeutic drug monitoring data.

Background: Preterm neonates rarely participate in clinical trials, this leads to lack of adequate information on pharmacokinetics for most drugs in this population. Meropenem is used in neonates to treat severe infections, and absence of evidence-based rationale for optimal dosing could result in mismanagement. Aim: The objective of the study was to determine the population pharmacokinetic (PK) parameters of meropenem in preterm infants from therapeutic drug monitoring (TDM) data in real clinical settings and to evaluate pharmacodynamics (PD) indices as well as covariates affecting pharmacokinetics. Materials and methods: Demographic, clinical and TDM data of 66 preterm newborns were included in PK/PD analysis. The NPAG program from the Pmetrics was used for modelling based on peak-trough TDM strategy and one-compartment PK model. Totally, 132 samples were assayed by high-performance liquid chromatography. Meropenem empirical dosage regimens (40-120 mg/kg/day) were administered by 1-3-h IV infusion 2-3 times a day. Regression analysis was used to evaluate covariates (gestation age (GA), postnatal age (PNA), postconceptual age (PCA), body weight (BW), creatinine clearance, etc.) influenced on PK parameters. Results: The mean ± SD (median) values for constant rate of elimination (Kel) and volume of distribution (V) of meropenem were estimated as 0.31 ± 0.13 (0.3) 1/h and 1.2 ± 0.4 (1.2) L with interindividual variability (CV) of 42 and 33%, respectively. The median values for total clearance (CL) and elimination half-life (T1/2) were calculated as 0.22 L/h/kg and 2.33 h with CV = 38.0 and 30.9%. Results of the predictive performance demonstrated that the population model by itself gives poor prediction, while the individualized Bayesian posterior models give much improved quality of prediction. The univariate regression analysis revealed that creatinine clearance, BW and PCA influenced significantly T1/2, meropenem V was mostly correlated with BW and PCA. But not all observed PK variability can be explained by these regression models. Conclusion: A model-based approach in conjunction with TDM data could help to personalize meropenem dosage regimen. The estimated population PK model can be used as Bayesian prior information to estimate individual PK parameter values in the preterm newborns and to obtain predictions of desired PK/PD target once the patient's TDM concentration(s) becomes available.

Cortical activation and oxygen perfusion in preterm newborns during kangaroo mother care: A pilot study.

AIM: This study aimed to assess the functional activation of preterm newborns' cerebral cortex during kangaroo mother care. Possible effects of gestational age and previous kangaroo mother care experience were also considered. METHODS: Fifteen preterm newborns were recruited (gestational age: 24-32 weeks). Cortical activation was assessed in frontal, motor and primary somatosensory cortices after 15 and 30 min of kangaroo mother care by multichannel near-infrared spectroscopy (gestational age at assessment: 30-36 weeks). Both oxy- and deoxy-haemoglobin variations were analysed by t-test. Possible effects of gestational age and previous kangaroo mother care experience on cortical activation were studied by regression analysis. RESULTS: After 15 min, bilateral activations (oxy-haemoglobin increase) were observed in frontal, somatosensory and motor cortices. After 30 min, the right motor and primary somatosensory cortices were found activated. Deoxy-haemoglobin increased after 15 min, returning to baseline at 30 min. After 15 min, there was a positive effect of gestational age at the assessment on both haemoglobin concentrations and a negative effect of previous kangaroo mother care on deoxy-haemoglobin increase. CONCLUSION: Motor and somatosensory cortices, particularly on the right side, showed significant activation during kangaroo mother care. Kangaroo mother care seems to benefit activated cortical areas by improving oxygen supply.

Noninvasive Respiratory Support Effects on Sighs in Preterm Infants by Electrical Impedance Tomography.

OBJECTIVE: To evaluate differences regarding sigh frequency between noninvasive respiratory support types and to assess regional ventilation distribution, delta Z, and end-expiratory lung impedance differences before and after sighs. METHODS: Very low-birth-weight infants with gestational ages less than 32 wk were included in the study. Participants were split into two groups: those receiving continuous positive airway pressure and infants receiving high-flow nasal cannula therapy. RESULTS: The study enrolled 30 infants. The high-flow nasal cannula therapy group had more sighs per 10-min period than infants receiving continuous positive airway pressure (p = 0.016). Ventilation distribution was similar in the anterior and right ventilation distribution compartments pre- and post-sigh (46.30% vs. 45.68% and 54.27% vs. 55.26%, respectively). No statistically significant increase in end-expiratory lung impedance or delta Z was observed in global or separate lung regions (p > 0.05). CONCLUSION: The study has demonstrated that sighs are more frequent in infants receiving high-flow nasal cannula respiratory support compared to continuous positive airway pressure. Spontaneously occurring sighs on noninvasive respiratory support due to respiratory distress syndrome (RDS) do not increase end-expiratory lung impedance or alter delta Z, and appear to have limited clinical significance. TRIAL REGISTRATION: Prospectively registered at www. CLINICALTRIALS: gov , reg. No. NCT04542096, reg. date 01/09/2020.

Current Concepts of Corticosteroids Use for the Prevention of Bronchopulmonary Dysplasia.

Despite using antenatal steroids, surfactants and protective ventilation, bronchopulmonary dysplasia (BPD) affects 10-89% of preterm infants. Since lung inflammation is central to the BPD pathogenesis, postnatal systemic corticosteroids could reduce the risk of BPD onset in preterm infants, but short and long-term adverse consequences have been underlined in literature after their use (i.e., hyperglycaemia, hypertension, hypertrophic cardiomyopathy, growth failure, gastrointestinal bleeding, cerebral palsy). Alternative therapeutic strategies such as postponing corticosteroid administration, lowering the cumulative dose, giving pulse rather than continuous doses, or individualizing the dose according to the respiratory condition of the infant have been proposed to avoid their adverse effects. Dexamethasone remains the first-line drug for newborns with severe pulmonary disease beyond the second to the third week of life. Hydrocortisone administration in very preterm infants does not appear to be associated with neurotoxic effects, even if its efficacy in preventing and treating BPD has yet been clearly demonstrated. Alternative methods of corticosteroid administration seem promising. A positive effect on BPD prevention occurs when budesonide is nebulized and intratracheally instilled with a surfactant, but more data are required to establish safety and efficacy in preterm newborns. Additional studies are still needed before the chronic lung disease issue, and its related challenges can be solved.

Clinical factors associated with abnormal general movements of preterm newborns during hospitalization in a neonatal intensive care unit.

INTRODUCTION: There is no clarity about which clinical variables during hospitalization in the Neonatal Intensive Care Unit (NICU) are associated with abnormal General Movements (GMs). OBJECTIVE: To describe the trajectory of GMs of preterm newborns and explore the association between clinical variables and the presence of abnormal GMs during the NICU stay. METHODS: Fifty-eight preterm newborns (33 males), with a mean gestational age at birth of 31,93 week's postmenstrual age, were evaluated using the GMs assessment by Hadders-Algra method. Clinical variables recorded weekly throughout the hospitalization period. The weekly association between clinical variables and the presence of abnormal GMs was tested using the Generalized Estimating Equations (GEE) model. RESULTS: Preterm infants were recorded for up to sixteen weeks and more than half of the infants (56.9 %) had abnormal movements in at least one week during hospitalization. The absence of peri-intraventricular hemorrhage (PIVH) grades I-II and non-invasive ventilatory support and/or oxygen therapy on the day of the evaluation reduced, respectively, by 77.3 % (OR = 0.23; p > 0.0001) and 64.3 % (OR = 0.36; p > 0.0001) the chance of having an abnormal classification. In addition, each day of increased invasive mechanical ventilation increased the chance of having an abnormal classification by 1.11 times (OR = 0.025; p > 0.0001). CONCLUSION: PIVH grades I-II, longer durations of mechanical ventilation and the presence of non-invasive ventilatory support and/or oxygen therapy are associated with abnormal movements during stay in the neonatal period. The data suggest that development outcome of infants having these conditions should be closely monitored.

The prevalence of hypothyroxinemia in premature newborns.

Congenital hypothyroidism diagnosed by TSH assessment in bloodspot screening may be overlooked in preterm newborns due to immaturity of the hypothalamus-pituitary-thyroid axis in them. The purpose of the study was to determine the prevalence and causes of hypothyroxinemia in preterm newborns, determined by TSH and FT4 serum concentration measurement, performed on the 3-5th day of life. We assessed TSH, FT4 and FT3 serum concentration on the 3-5th day of life in preterm children born at our centre within three consecutive years. We assessed the incidence of hypothyroxinemia, and its cause: primary hypothyroidism, secondary hypothyroidism or low FT4 syndrome - with normal TSH concentration, its dependence - among others - on gestational age (GA), birth body weight (BBW) and being SGA. A total of 525 preterm children were examined. FT4 concentration was decreased in 14.9% of preterm newborns. The most frequent cause of hypothyroxinemia was low FT4 syndrome (79.5%). More than 92% cases of hypothyroxinemia occurred in children born before the 32nd week and/or with BBW below 1500 g. Thus, every fourth child in these groups had a reduced FT4 concentration. Neonates with hypothyroxinemia were significantly lighter than those with normal FT4. In older and heavier neonates with hypothyroxinemia, serious congenital defects were observed. Neither IVH nor SGA nor twin pregnancies predispose children to hypothyroxinemia. Among newborns with untreated hypothyroxinemia in whom TSH and FT4 assessment was repeated within 2-5 weeks, a decreased FT4 concentration was confirmed in 56.1% of cases. As hypothyroxinemia affects 25% of newborns born before the 32nd week of gestation and those in whom BBW is less than 1500g, it seems that in this group of children the newborn screening should be extended to measure serum TSH and FT4 concentration between the 3-5th day of life. In older and heavier neonates, additional serum TSH and FT4 assessment should be limited to children with severe congenital abnormalities but not to all SGA or twins. Despite the fact that the most common form of preterm hypothyroxinemia is low FT4 syndrome, it should be emphasized that FT4 remains lowered on subsequent testing in more them 50% of cases.

Changes Overtime in Perinatal Management and Outcomes of Extremely Preterm Infants in One Tertiary Care Romanian Center.

Background and Objectives: Extremely preterm infants were at increased risk of mortality and morbidity. The purpose of this study was to: (1) examine changes over time in perinatal management, mortality, and major neonatal morbidities among infants born at 250-286 weeks' gestational age and cared for at one Romanian tertiary care unit and (2) compare the differences with available international data. Material and Methods: This study consisted of infants born at 250-286 weeks in one tertiary neonatal academic center in Romania during two 4-year periods (2007-2010 and 2015-2018). Major morbidities were defined as any of the following: severe intraventricular hemorrhage (IVH), severe retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and bronchopulmonary dysplasia (BPD). Adjusted logistic regression models examined the association between the mortality and morbidity outcome and the study period. Results: The two cohorts differed with respect to antenatal antibiotics and rates of cesarean birth but had similar exposure to antenatal steroids and newborn referral to the tertiary care center. In logistic regression analyses, infants in the newer compared to the older cohort had a lower incidence of death (OR: 0.19; 95% CI: 0.11-0.35), a lower incidence of IVH (OR: 0.26; 95% CI: 0.15-0.46), and increased incidence of NEC (OR: 19.37; 95% CI: 2.41-155.11). Conclusions: Changes over time included higher use of antenatal antibiotics and cesarean delivery and no change in antenatal steroids administration. Overall mortality was lower in the newer cohort, especially for infants 250-266 weeks' gestation, NEC was higher while BPD and ROP were not different.

Skin-to-skin contact to support preterm infants and reduce NICU-related stress.

OBJECTIVE: Hospitalization in the neonatal intensive care unit (NICU) with numerous painful medical interventions, being separated from parents, leads to the high risk of chronic stress for preterm infants. Today, many NICUs use more appropriate developmental care and pain management, but the early and long-term outcomes of stress in these vulnerable infants require searching for more stress-reducing interventions in neonatal care. The objective of the study was to investigate how skin-to-skin contact (SSC) can influence the biologic stress levels in preterm infants in the NICU by assessing cortisol and oxytocin levels. PARTICIPANTS AND METHODS: The study included 71 preterm infants with gestational age less than 34 + 0/7 weeks who were recruited from level III NICU. The overall design was a baseline-response design. Saliva and urine were collected before (baseline) and after skin-to-skin contact to measure salivary cortisol and urinary oxytocin by enzyme immunoassay method. RESULTS: The infants' baseline hormonal status was represented by the following indicators: the level of salivary cortisol was 0.402 [0.227; 1,271] µg/dl, urinary oxytocin 48.88 [32.97; 88.11] pg/ml. There was a decrease in salivary cortisol levels to 0.157 [0.088; 0.351] µg/dl compared to baseline (p Ë‚ 0.001) with a simultaneous increase of the urinary oxytocin level -73.59 [45.18; 108.8] pg/ml (p = 0.028) in response to SSC. CONCLUSION: Preterm infants in the NICU experience significant stress, characterized by hormonal imbalance: an increased level of the stress hormone cortisol and a decreased level of the anti-stress hormone oxytocin. Skin-to-skin contact helps to ameliorate the hormonal stress in preterm infants by activating the oxytocin release with simultaneous reduction of cortisol secretion.

Dissemination of Gram-positive bacteria to the lung of newborn mice increases local IL-6 and TNFα levels in lethal bacteremia.

Neonatal bacteremia remains the major cause of infectious diseases-related death, especially in preterm newborns. Gram-positive bacteria are the main causative agent of neonatal bacteremia and exhibit a high risk of causing pneumonia and/or meningitis. The pathogenesis of bacteremia in preterm newborn is poorly understood. Current neonatal models of bacterial infection have been used to study the disease mechanisms; however, these studies employed mice of several days of age that could be less comparable to the bacteremia in preterm infants. In this study, we infected intravenously 0-day-old BALB/c mice with different inocula of Staphylococcus aureus, Streptococcus agalactiae or Enterococcus faecalis. We found that the mortality of the newborn mice was inoculum-dependent and also bacterial species-dependent. We observed bacterial burden in the lung, liver, brain, kidney and spleen of the infected animals. The lung was the tissue with the greatest bacterial burden and cellular infiltration in animals infected with the three bacteria evaluated. We found increased production of IL-6 and TNFα in the lung from newborn mice at 3 days post-infection. This neonatal model shows bacterial dissemination to the lung and will be useful for promote a better understanding of the pathophysiology of neonatal pneumonia.

Congenital Hypothyroidism in Preterm Newborns - The Challenges of Diagnostics and Treatment: A Review.

Preterm newborns are forced to adapt to harsh extrauterine conditions and endure numerous adversities despite their incomplete growth and maturity. The inadequate thyroid hormones secretion as well as the impaired regulation of hypothalamus-pituitary-thyroid axis may lead to hypothyroxinemia. Two first weeks after birth are pivotal for brain neurons development, synaptogenesis and gliogenesis. The decreased level of thyroxine regardless of cause may lead to delayed mental development. Congenital hypothyroidism (CH) is a disorder highly prevalent in premature neonates and it originates from maternal factors, perinatal and labor complications, genetic abnormalities, thyroid malformations as well as side effects of medications and therapeutic actions. Because of that, the prevention is not fully attainable. CH manifests clinically in a few distinctive forms: primary, permanent or transient, and secondary. Their etiologies and implications bear little resemblance. Therefore, the exact diagnosis and differentiation between the subtypes of CH are crucial in order to plan an effective treatment. Hypothyroxinemia of prematurity indicates dynamic changes in thyroid hormone levels dependent on neonatal postmenstrual age, which directly affects patient's maintenance and wellbeing. The basis of a successful treatment relies on an early and accurate diagnosis. Neonatal screening is a recommended method of detecting CH in preterm newborns. The preferred approach involves testing serum TSH and fT4 concentrations and assessing their levels according to the cut-off values. The possible benefits also include the evaluation of CH subtype. Nevertheless, the reference range of thyroid hormones varies all around the world and impedes the introduction of universal testing recommendations. Unification of the methodology in neonatal screening would be advantageous for prevention and management of CH. Current guidelines recommend levothyroxine treatment of CH in preterm infants only when the diagnose is confirmed. Moreover, they underline the importance of the re-evaluation among preterm born infants due to the frequency of transient forms of hypothyroidism. However, results from multiple clinical trials are mixed and depend on the newborn's gestational age at birth. Some benefits of treatment are seen especially in the preterm infants born <29 weeks' gestation. The discrepancies among trials and guidelines create an urgent need to conduct more large sample size studies that could provide further analyses and consensus. This review summarizes the current state of knowledge on congenital hypothyroidism in preterm infants. We discuss screening and treatment options and demonstrate present challenges and controversies.