Unveiling the Interplay: Antioxidant Enzyme Polymorphisms and Oxidative Stress in Preterm Neonatal Renal and Hepatic Functions.

AIMS: To explore the relationship between oxidative stress biomarkers and the occurrence of acute kidney injury (AKI) alongside notable liver function disturbances in preterm neonates. BACKGROUND: Given the immaturity of kidneys and incomplete liver development in preterm neonates, oxidative stress poses a considerable threat to their renal and hepatic health. OBJECTIVE: To find out the association between various oxidative stress biomarkers and polymorphisms of antioxidant enzymes with renal and live functions. METHODS: In this cross-sectional study, we gathered umbilical cord blood and peripheral blood samples for assessing oxidative stress biomarkers and identifying single nucleotide polymorphisms (SNPs) in antioxidant enzymes. Utilizing enzyme-linked immunosorbent assay kits, we quantified these oxidative stress biomarkers. Receiver-operating characteristics curve analysis was employed to ascertain the predictive capacity of these biomarkers, denoted by the area-under-the-curve (AUC). RESULTS: Our findings revealed that umbilical cord heat-shock proteins emerged as robust predictors of neonatal AKI (AUC: 0.92; 95% CI: 0.8-1) with a defined cut-off concentration of 1.8 ng/mL. Likewise, umbilical cord 8-hydroxy-2-deoxy guanosine demonstrated significant predictability for liver function alterations (AUC: 0.7; 95% CI: 0.6-0.9) at a cut-off concentration of 2487.6 pg/mL. CONCLUSIONS: We observed significant associations between SNPs in endothelial nitric oxide synthase and catalase with both AKI and impaired liver functions. Prospective studies are warranted to validate these findings, with a particular focus on exploring potential antioxidant interventions aimed at mitigating AKI and liver function abnormalities.

Incidence and Risk Factors of Intraventricular Hemorrhage in Early Preterm Infants: A Cross-Sectional Study.

BACKGROUND: Early preterm infants are susceptible to a serious disorder called intraventricular hemorrhage (IVH), which may cause severe neurological damage. OBJECTIVE: To determine the incidence of IVH in preterm infants at Lady Reading Hospital, Peshawar, Pakistan, and to identify associated risk factors and potential preventive measures. METHODOLOGY: This cross-sectional research examined the prevalence of IVH among early preterm infants and was carried out at Lady Reading Hospital in Peshawar from 1 January 2021 to 31 December 2023. After excluding individuals with congenital defects, insufficient medical records, or non-consent, the research comprised 210 newborns born before 28 weeks of gestation and diagnosed with IVH during the first 72 hours of life. Medical record reviews and in-person observations were used to gather data, with an emphasis on clinical, risk, and demographic characteristics. Using the Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 25.0, Armonk, NY) with a significance threshold of p < 0.05, descriptive techniques were used in the statistical studies to summarize the features and inferential approaches, such as univariate and multivariate logistic regression, to identify IVH risk variables. RESULTS: Among the 210 early preterm newborns studied, the frequency of IVH according to severity was as follows: 79 infants (37.62%) had Grade I, 65 infants (30.95%) had Grade II, 39 infants (18.57%) had Grade III, and 27 infants (12.86%) had Grade IV. Three key demographic findings were that 63 births (30.00%) occurred before 26 weeks of gestation, 87 infants (41.43%) had birth weights of less than 1000 grams, and 111 infants (52.86%) were male. Significant predictors of IVH identified through multivariate logistic regression included birth weight less than 1000 grams (odds ratio (OR) = 3.10, 95% confidence interval (CI): 1.78-5.42, p < 0.01), gestational age less than 26 weeks (OR = 2.68, 95% CI: 1.50-4.76, p < 0.01), Apgar score ≤5 (OR = 4.01, 95% CI: 2.23-7.21, p < 0.01), resuscitation at birth (OR = 2.23, 95% CI: 1.12-4.45, p = 0.02), mechanical ventilation (OR = 3.55, 95% CI: 1.85-6.82, p < 0.01), and sepsis (OR = 2.98, 95% CI: 1.50-5.92, p = 0.02). CONCLUSION: The high incidence of IVH and its association with critical risk factors underscore the need for improved neonatal care practices and targeted interventions in early preterm infants.

Glymphatic System in Preterm Neonates: Developmental Insights Following Birth Asphyxia.

BACKGROUND: Birth asphyxia (BA) and germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) are common clinical events in preterm neonates. However, their effects on the glymphatic system (GS) development in preterm neonates remain arcane. PURPOSE: To evaluate the developmental trajectory of the GS, and to investigate the effects of BA and GMH-IVH on GS function in preterm neonates. STUDY TYPE: Prospective. POPULATION: Two independent datasets, prospectively acquired internal dataset (including 99 preterm neonates, 40 female, mean [standard deviation] gestational age (GA) at birth, 29.95 [2.63] weeks) and the developing Human Connectome Project (dHCP) dataset (including 81 preterm neonates, 29 female, median [interquartile range] GA at birth, 32.71 [4.28] weeks). FIELD STRENGTH/SEQUENCE: 3.0 T MRI and diffusion-weighted spin-echo planar imaging sequence. ASSESSMENT: The diffusion-weighted images were preprocessed in volumetric space using the FMRIB Software Library and diffusion along the perivascular space (DTI-ALPS) index was accessed to evaluate GS function. STATISTICAL TESTS: Two sample t tests, one-way analysis of variance followed by least-significant difference (LSD) post hoc analysis, chi-squared tests, and Pearson's correlation analysis. Significance level: P < 0.05. RESULTS: In prospectively acquired internal dataset, preterm neonates with BA exhibited a significant lower DTI-ALPS index than those without BA (0.98 ± 0.08 vs. 1.08 ± 0.07, T = -5.89); however, GMH-IVH did not exert significant influences on the DTI-ALPS index (P = 0.83 and 0.27). The DTI-ALPS index increased significantly at postmenstrual age ranging from 25 to 34 weeks (r = 0.38) and then plateaued after 34 weeks (P = 0.35), which we also observed in the dHCP dataset. DATA CONCLUSION: BA rather than GMH-IVH serves as the major influencing factor in the development of GS in preterm neonates. Moreover, as GS development follows a nonlinear trajectory, we recommend close monitoring of GS development in preterm neonates with a GA less than 34 weeks. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Comparison of Thermal Stability Between Immersion Bath and Sponge Bath Followed by Kangaroo Mother Care in Stable Preterm in Postnatal Ward.

BACKGROUND: Preterm neonates are at high risk of hypothermia, which can lead to adverse health outcomes. This study aimed to compare the effects of immersion bath followed by Kangaroo Mother Care (KMC) versus sponge bath followed by KMC on the thermal stability of preterm neonates. METHODS: A prospective interventional study was conducted on 76 preterm neonates, with 38 neonates in each group (immersion bath and sponge bath). Axillary temperature was measured before the bath and at various time intervals after the bath (immediately, 15, 30, 45, and 60 minutes). RESULTS: The mean axillary temperature was significantly higher in the immersion bath group compared to the sponge bath group immediately after the bath (97.6°F vs. 96.3°F, p<0.001), at 15 minutes (97.6°F vs. 96.8°F, p<0.001), 30 minutes (97.9°F vs. 97.3°F, p=0.001), and 45 minutes (98.1°F vs. 97.7°F, p=0.002) post-bath. However, the difference was not statistically significant at 60 minutes post-bath (98.2°F vs. 98.0°F, p=0.091). CONCLUSION: Immersion bathing followed by KMC is more effective than sponge bathing followed by KMC in maintaining thermal stability in preterm neonates. Healthcare providers should consider adopting this approach as the preferred bathing method for preterm neonates to promote better health outcomes.

Thyroid Function Test in Preterm Neonates: Normative Data.

Introduction: Initial surge of thyroid-stimulating hormone (TSH) in neonates increases free and total triiodothyronine (T3) and tetraiodothyronine (T4) in 24-36 hours following birth, and the effect then gradually wanes off. As somatic and intellectual development is dependent on normal thyroid function especially in infancy, normative data in these children may be of immense value to diagnose hypothyroidism in this subset of infants. Comprehensive normative values of thyroid function parameters in preterm neonates are scarcely available. The objective of this study was to determine the normative value of thyroid function parameters in preterm neonates. Methods: Preterm neonates (n = 102) born at 34 and 35 weeks of gestation of euthyroid mothers from an iodine-sufficient population were evaluated for T3, T4, free thyroxine (FT4) and TSH during 3-7 days after birth and again after 1 month. The expected date of delivery (EDD) and Ballard score were used to identify the duration of gestation. Results: The mean gestational age was 34.7 ± 0.41 weeks. The mean (± SD) for T3 (ng/dl), T4 (µg/dl), FT4 (ng/ml) and TSH (µIU/ml) on days 3-7 following birth was as follows: 156 ± 44.6, 12.8 ± 3.7, 1.50 ± 0.54 and 7.13 ± 6.04, respectively. Around 4 weeks of age, values changed to 104 ± 38.4, 12.1 ± 4.02, 1.46 ± 0.42 and 3.25 ± 2.85, respectively. All parameters changed significantly around 4 weeks, except FT4. None of the parameters were correlated with gestational age or body weight at birth. Normative values for each parameter in percentiles were generated. Conclusion: This study generated the normative values of the thyroid function test during the first week and after around 4 weeks of life for premature neonates (born at 34-35 weeks).

Variations and National Perspectives on Evaluation and Management of Ventilator-Associated Pneumonia in Neonatal Intensive Care Units: An In-Depth Survey Analysis.

Introduction Infants in the neonatal intensive care unit (NICU) are vulnerable to ventilator-associated pneumonia (VAP), which increases their morbidity and mortality. There is a significant overlap of clinical features of neonatal VAP with other pulmonary pathologies, particularly in preterm infants, which can make the definitive diagnosis and management of VAP challenging. Objective Our study surveyed NICU providers across the United States to understand the perspectives and variations in neonatal VAP diagnostic and management practices. Methods The REDCap survey was distributed to the actively practicing members of the Section on Neonatal-Perinatal Medicine (SoNPM) of the American Academy of Pediatrics (AAP). We used descriptive statistics to analyze the data from the respondents. Results Of 254 respondents, the majority (86.6%, 220) were neonatologists and had a relatively even geographical distribution. Most (75.9%, 193) stated that they would perform a gram stain and respiratory culture as part of a sepsis workup irrespective of the patient's duration on invasive mechanical ventilation (IMV); 224 (88.2%) of providers preferred the endotracheal aspiration (ETA) technique to collect specimens. In cases where a positive respiratory culture was present, VAP (52.4%, 133) was the predominantly assigned diagnosis, followed by pneumonia (27.2%, 69) and ventilator-associated tracheitis (VAT) (9.8%, 25). Respondents reported a prescription of intravenous gentamicin (70%, 178) and vancomycin (41%, 105) as the initial empiric antibiotic drugs, pending final respiratory culture results. Most respondents (55.5%, 141) opted for seven days of antibiotics duration to treat VAP. The reported intra-departmental variation among colleagues in acquiring respiratory cultures and prescribing antibiotics for VAP was 48.8% (124) and 37.4% (95), respectively, with slightly more than half (53.5%, 136) of providers reporting having VAP prevention guidelines in their units. Conclusion The survey study revealed inconsistencies in the investigation, diagnostic nomenclature, choice of antibiotic, and treatment duration for neonatal VAP. Consequently, there is a pressing need for further research to establish a clear definition and evidence-based criteria for VAP.

Cerebral oxygenation during immediate fetal-to-neonatal transition and fidgety movements between six to 20 weeks of corrected age: An ancillary study to the COSGOD III trial.

Fidgety movements provide early information about a potential development of cerebral palsy in preterm neonates. The aim was to assess differences in the combined outcome of mortality and fidgety movements defined as normal or pathological in very preterm neonates according to the group allocation in the randomised-controlled multicentre COSGOD III trial. Preterm neonates of two centres participating in the COSGOD III trial, whose fidgety movements were assessed as normal or pathological at six to 20 weeks of corrected age, were analysed. In the COSGOD III trial cerebral oxygen saturation (crSO2) was measured by near-infrared spectroscopy (NIRS) during postnatal transition and guided resuscitation in preterm neonates randomised to the NIRS-group, whereby medical support was according routine, as it was also in the control group. Fidgety movements were classified in normal or abnormal/absent at six to 20 weeks of corrected age. Mortality and fidgety movements of preterm neonates allocated to the NIRS-group were compared to the control-group. Normal outcome was defined as survival with normal fidgety movements. One-hundred-seventy-one preterm neonates were included (NIRS-group n = 82; control-group n = 89) with a median gestational age of 29.4 (27.4-30.4) and 28.7 (26.7-31.0) weeks in the NIRS-group and the control-group, respectively. There were no differences in the combined outcome between the two groups: 90.2% of the neonates in the NIRS-group and 89.9% in the control-group survived with normal outcome (relative risk [95% CI]; 0.96 [0.31-2.62]).Conclusions: In the present cohort of preterm neonates, monitoring of crSO2 and dedicated interventions in addition to routine care during transition period after birth did not show an impact on mortality and fidgety movements defined as normal or pathological at six to 20 weeks corrected age. What is Known • Fidgety movements display early spontaneous motoric pattern and may provide early information about a potential development of cerebral palsy in preterm neonates.  What is New  â€¢ This retrospective observational study of the randomised-controlled multicentre COSGOD III trial is the first study investigating the potential influence of cerebral oxygenation guided resuscitation during postnatal transition period on combined outcome of mortality and fidgety movements up to 20 weeks of corrected age in very preterm neonates. • This study adds to the growing interest of assessing cerebral oxygenation, that monitoring of cerebral oxygen saturation and dedicated interventions during postnatal transition period according to the COSGOD III trial has no significant influence on mortality and fidgety movements defined as normal or pathological in very preterm neonates.

Investigating transmission patterns among preterm neonates during an outbreak of necrotizing enterocolitis related to Clostridium butyricum using whole-genome sequencing.

BACKGROUND: Necrotizing enterocolitis is the most severe life-threatening acquired gastrointestinal disorder among preterm neonates. We describe here an outbreak of Clostridium butyricum-related necrotizing enterocolitis in preterm neonates that occurred in three different neonatal centres, in southeast France. METHODS: We defined a confirmed case of C. butyricum-related necrotizing enterocolitis in preterm neonates by the presence of clinical signs according to modified Bell criteria and C. butyricum identified from stool samples using real-time polymerase chain reaction or culture. A phylogenetic analysis of the isolated strains by whole-genome sequencing was also performed. RESULTS: Between 5th and 27th January 2022, we identified 10 confirmed cases of C. butyricum-related necrotizing enterocolitis, including five from Neonatal Centre 1, four from Neonatal Centre 2, and one from Neonatal Centre 3. The attack rate of necrotizing enterocolitis in Neonatal Centre 1 was 7.1% (5/70). The positivity rate of C. butyricum detected from stool samples was higher during the outbreak period (37/276; 13.4%) than outside this period (7/369; 1.9%), while systematic screening was maintained (P<0.001). Phylogenetic analysis showed a clonality between strains inside four clusters. Two clusters included neonates hospitalized in different neonatal centres, suggesting the transmission of C. butyricum strains during the transfer of neonates between neonatal centres. CONCLUSIONS: This outbreak of C. butyricum-related necrotizing enterocolitis confirms a cross-transmission between preterm neonates, including twin or triplet siblings, and involving necrotizing enterocolitis cases together with asymptomatic carriers. After three months of follow-up, no further cases were identified following the implementation of contact precautions with sporicidal agents.

Time to adequate weight gain and predictors among low-birth-weight preterm neonates at Neonatal Intensive Care Unit of hospitals in Bahir-Dar.

Weight gain in low birth-weight babies remains a challenge to the management of the neonatal period in low and middle-income countries like Ethiopia. Therefore, this study aimed to determine the time to adequate weight gain and its predictors among low-birth-weight preterm neonates admitted to neonatal intensive care unit of public hospitals in Bahir Dar City. An institution-based retrospective follow-up study was conducted from March 4 to April 3, 2023, using three years of data. About 344 low-birth-weight preterm babies were recruited and followed up until 28 days of age. Model goodness-of-fit was checked by Cox Snell residuals test. The Cox-Proportional Hazards Model was used to assess predictors of weight gain with a statistically significant level of P-value < 0.05. The median weight gain time was 15 days with an overall incidence density rate of 6.3 per 100 person-day of observation (95% CI 0.055, 0.071). Absence of medical problems of mothers (AHR: 1.63, 95% CI 1.015, 4.614), spontaneous vaginal mode of delivery (AHR: 1.53, 95% CI 1.028, 2.593), and long duration of labor (AHR: 3.18, 95% CI 1.579, 6.413) were significant predictors. The time of adequate weight gain was long. Early detection and management of significant predictors is recommended.

The effect of preterm birth on thalamic development based on shape and structural covariance analysis.

Acting as a central hub in regulating brain functions, the thalamus plays a pivotal role in controlling high-order brain functions. Considering the impact of preterm birth on infant brain development, traditional studies focused on the overall development of thalamus other than its subregions. In this study, we compared the volumetric growth and shape development of the thalamic hemispheres between the infants born preterm and full-term (Left volume: P = 0.027, Left normalized volume: P < 0.0001; Right volume: P = 0.070, Right normalized volume: P < 0.0001). The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus exhibit higher vulnerability to alterations induced by preterm birth. The structural covariance (SC) between the thickness of thalamus and insula in preterm infants (Left: corrected P = 0.0091, Right: corrected P = 0.0119) showed significant increase as compared to full-term controls. Current findings suggest that preterm birth affects the development of the thalamus and has differential effects on its subregions. The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus are more susceptible to the impacts of preterm birth.

Kangaroo Mother Care in Term and Late Preterm Neonates: A Systematic Review.

This systematic review aims to investigate the efficacy of kangaroo mother care (KMC) in term and late-preterm babies. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, seven studies were analyzed, which covered a wide range of outcomes, from the post-vaccination serum bilirubin level and pain during the vaccination to the prevention of hypothermia and long-term neurodevelopmental outcomes. Results point out that KMC might come with some advantages such as the reduction of neonatal bilirubin levels, a painless and quicker vaccination process, and better prevention of hypothermia. Moreover, initial and lengthy KMC also plays a possible role in the better long-term brain development of low-birth-weight neonates. Furthermore, the limitation of smaller numbers of studies and variability in results remains to be solved. The next step is working to build stronger evidence and creating proper conditions for the implementation of KMC in future healthcare.

Lung ultrasound in early prediction of bronchopulmonary dysplasia in pre-term babies.

PURPOSE: Bronchopulmonary dysplasia (BPD) is a respiratory morbidity related to prematurity. Early prediction of BPD allows the selection of patients who would benefit from new therapies. Lung ultrasound (LUS) is a non-invasive diagnostic tool that has proven to be reliable for many neonatal diseases recently. The study aimed to detect the role of LUS in predicting BPD at days 7 and 14 of life in preterm babies. METHODS: This was a prospective cohort study that included 95 preterm babies ≤ 34 weeks. Lung ultrasounds were performed on days 7 and 14 of life. RESULTS: The mean gestational age of the studied neonates was 30.25 ± 2.21 weeks. The mean birth weight was 1347.66 ± 432.14 gm. Patients who developed BPD had statistically significantly higher LUS scores on both days 7 and 14 of life. At first examination, a LUS score > 8 showed a sensitivity of 83.33% and a specificity of 60.87%, whereas at follow-up, a LUS score > 8 showed a sensitivity of 76.39% and a specificity of 82.61%. The multivariate logistic regression analysis shows that the most important factors associated with BPD were gestational age ≤ 30 weeks, LUS score at first examination > 8, platelets ≤ 245 × 109/L, segment neutrophils ≤ 42%, and CRP > 5 mg/l. CONCLUSIONS: The LUS score predicts BPD at 7 and 14 days of life. LUS scores increased with increasing BPD severity. LUS score > 8 was an independent factor in the prediction of BPD.

A Case of an Extremely Preterm Infant with Intussusception Triggered by Acquired Cytomegalovirus Infection.

Intussusception is a common cause of intestinal obstruction in infants aged 6-18 months. However, intussusception in preterm neonates (IPN) is an exceedingly rare disorder. The etiology of IPN remains unclear, but common prenatal injuries, such as those causing intestinal hypoxia/hypoperfusion, dysmotility, and strictures, have been proposed as possible contributing factors. Diagnosis is often delayed because the symptoms closely resemble those of necrotizing enterocolitis (NEC). Given the divergent treatments for IPN and NEC, establishing an early and accurate diagnosis is crucial. IPN is predominantly located in the small intestine (91.6%), and ultrasonography proves useful in its diagnosis. We present a case of a very preterm infant who developed intussusception triggered by acquired cytomegalovirus (aCMV) infection, necessitating surgical treatment. The cause of intussusception in this case was diagnosed as aCMV enteritis because no organic lesions were observed in the advanced part of the intussusception. The presence of CMV was confirmed by CMV-DNA-PCR examination of the resected intestinal tract. Intestinal edema and decreased intestinal peristalsis due to aCMV enteritis are likely the primary causes of the intussusception.

Fecal microbiota and volatile metabolome pattern alterations precede late-onset meningitis in preterm neonates.

OBJECTIVE: The fecal microbiota and metabolome are hypothesized to be altered before late-onset neonatal meningitis (LOM), in analogy to late-onset sepsis (LOS). The present study aimed to identify fecal microbiota composition and volatile metabolomics preceding LOM. METHODS: Cases and gestational age-matched controls were selected from a prospective, longitudinal preterm cohort study (born <30 weeks' gestation) at nine neonatal intensive care units. The microbial composition (16S rRNA sequencing) and volatile metabolome (gas chromatography-ion mobility spectrometry (GC-IMS) and GC-time-of-flight-mass spectrometry (GC-TOF-MS)), were analyzed in fecal samples 1-10 days pre-LOM. RESULTS: Of 1397 included infants, 21 were diagnosed with LOM (1.5%), and 19 with concomitant LOS (90%). Random Forest classification and MaAsLin2 analysis found similar microbiota features contribute to the discrimination of fecal pre-LOM samples versus controls. A Random Forest model based on six microbiota features accurately predicts LOM 1-3 days before diagnosis with an area under the curve (AUC) of 0.88 (n=147). Pattern recognition analysis by GC-IMS revealed an AUC of 0.70-0.76 (P<0.05) in the three days pre-LOM (n=92). No single discriminative metabolites were identified by GC-TOF-MS (n=66). CONCLUSION: Infants with LOM could be accurately discriminated from controls based on preclinical microbiota composition, while alterations in the volatile metabolome were moderately associated with preclinical LOM.

Inadequate weight gain and factors influencing it among preterm neonates in neonatal intensive care units in the Amhara region, Ethiopia, in 2022.

Background: Adequate weight gain is crucial for the health and development of preterm neonates admitted to neonatal intensive care units (NICUs). Understanding the factors influencing weight gain in this vulnerable population is essential for improving outcomes. This study aimed to assess the weight gain status and associated factors among preterm neonates admitted to NICUs in specialized hospitals in the Amhara region of Ethiopia. Methods: A cross-sectional study design involving 363 preterm neonates admitted to NICUs in specialized hospitals within the Amhara region was used. Data were collected using structured questionnaires and the Kobo Tool Box. Daily weight measurements were recorded for three consecutive days. Descriptive statistics, logistic regression analysis, and graphical presentations were utilized for data analysis and presentation. Results: The study revealed that a significant proportion (80.8%) of preterm neonates experienced poor weight gain during their NICU stay. The factors significantly associated with poor weight gain were older maternal age, delayed initiation of enteral feeding, lack of kangaroo mother care (KMC), and inadequate antenatal care visits. Conclusion: Addressing the identified factors, such as providing adequate support during the antenatal period, promoting a timely initiation of enteral feeding, and encouraging KMC practices, is crucial for improving weight gain outcomes in preterm neonates. The findings highlight the importance of a comprehensive approach to neonatal care targeting both maternal and neonatal factors. Policymakers and healthcare providers should prioritize interventions aimed at optimizing weight gain in preterm neonates to improve these neonates' overall well-being and long-term outcomes.

Effects of extremely preterm birth on cytokine and chemokine responses induced by T-cell activation during infancy.

Objectives: Extremely preterm (EPT; gestational week < 28 + 0, < 1000 g) neonates are vulnerable to infections and necrotising enterocolitis, important contributors to mortality and morbidity. However, knowledge regarding their immune maturation remains limited. We here investigated the longitudinal development of functional T-cell capacity in EPT infants. Methods: Peripheral blood mononuclear cells were isolated at 14th and 28th day (D) and at gestational week 36 + 0 (Gw36) from EPT infants, participated in a randomised, double-blind, placebo-controlled study of Lactobacillus reuteri DSM 17938 probiotic supplementation. Blood collected from 25 full-term (FT) infants at D14 was used as control. The secretion of immune mediators was determined through comprehensive Luminex panels after stimulation with human T-cell activator CD3/CD28 beads. Results: The levels of many mediators were low in EPT infants at D14, whereas the secretion of several chemokines was higher in EPT than in FT infants. Furthermore, Th2:Th1 cytokine ratios were higher in EPT than in FT infants. Progressively elevated secretion of, for example, IFN-γ, TNF and IL-17A in EPT infants was observed from D14 to D28 and then at Gw36. Elevated levels were observed for many proinflammatory mediators at D28. Probiotic supplementation or perinatal factors (e.g. clinical chorioamnionitis, preeclampsia and delivery mode) did not influence the cytokine and chemokine responses. Conclusions: Immune mediators induced by T-cell activation in EPT infants were mainly reduced at D14 and Th2 skewed compared to those in FT infants, but mostly recovered at Gw36, indicating immune maturation. Increased proinflammatory responses at D28 may be related to the heightened risk of severe immune-associated complications seen in EPT infants.

Association of Caffeine Daily Dose With Respiratory Outcomes in Preterm Neonates: A Retrospective Cohort Study.

Apnea and poor respiratory drive increase the risk of extubation failure (EF) and prolonged invasive mechanical ventilation (IMV) in preterm neonates (pre-nates) with respiratory distress. Caffeine citrate (CC) is often prescribed for pre-nates in doses of 5-10 mg/kg in 24 h. This study aimed to evaluate the most effective dosage regimen (5 mg/kg/day vs >5-10 mg/kg/day) to prevent apnea and EF with minimal caffeine-associated potential side effects (CC-APSEs) in pre-nates. This one-year retrospective cohort study included all the eligible neonates admitted to NICU and received CC-therapy till 28 days of life (DOL) or discharge. Based on CC-daily dose formed LD-caffeine-group (5 mg/kg/day) and HD-caffeine-group (>5-10 mg/kg/day). Antenatal, prenatal, and postnatal characteristics, CC-regimen, comorbidities, and CC-APSEs were compared between the groups. Predictors of apnea and EF were analyzed through logistic regression. There were 181 and 72 neonates in the LD and HD-caffeine-groups respectively. In HD-caffeine-group daily CC-dose was 7 to 7.5 mg/kg/day in 93% of neonates and >7.5 to 10 mg/kg/day in only 7%. Significantly fewer neonates experienced apnea and EF in the HD-caffeine-group till 28DOL or discharge. This difference was even greater in the subgroup of ≤28 weeks GA (15.6% vs 40.0%; P < .01). In HD-caffeine-group the incidence of severe/moderate-BPD was significantly lower and the frequency of CC-APSEs was higher. Multivariate analysis showed that; the smaller the GA higher the risk of apnea (AOR = 0.510, 95% CI 0.483-0.999) and EF (AOR = 0.787, 95% CI 0.411-0.997). The HD-caffeine was inversely associated with developing apnea (AOR = 0.244, 95% CI 0.053-0.291) and EF (AOR = 0.103, 95% CI 0.098-2.976). IMV-duration before extubation (AOR = 2.229, 95% CI 1.672-2.498) and severe/moderate-BPD (AOR = 2.410, 95%CI 1.104-2.952) had a high risk of EF. Initiating early HD-caffeine may prevent apnea and extubation failure in preterm neonates. Optimization of caffeine initiation time and dosages can be a safe and feasible approach to decrease the burden of neonatal respiratory morbidities.

Umbilical Cord Blood as an Alternative to Neonatal Blood for Complete Blood Count: A Comparison Study.

OBJECTIVE: To assess concordance between umbilical cord blood (UCB) and neonatal blood (NB) laboratory test results at birth. STUDY DESIGN: This retrospective study considered very preterm neonates (<32 weeks' gestational age) admitted to a tertiary neonatal intensive care unit from 2012 to 2023. Inclusion criteria required neonates with a complete blood count measured in both UCB and NB drawn within 2 hours after birth. Median hemoglobin (Hb) and hematocrit (Hct) concentrations were compared between UCB (venous samples) and NB (venous, arterial, or capillary samples). RESULTS: A total of 432 neonates with paired UCB and NB values were included in the study. Hb concentration in UCB was 14.7 g/dL (IQR 13.5-16.1 g/dL) compared with 14.8 g/dL (IQR 12.6-19.3 g/dL) in venous NB samples, 13.9 g/dL (IQR 12.9-15.3 g/dL) in arterial NB and 18.7 g/dL (IQR 16.6-20.8 g/dL) in capillary NB. The regression equation showed a correction factor of 1.08 for converting Hb values from UCB to venous NB. Median Hct concentration in UCB was 0.45 L/L (IQR: 0.41-0.49 L/L) compared with 0.48 L/L (IQR 0.43-0.54 L/L) in venous NB, 0.42 L/L (IQR 0.38-0.45 L/L) in arterial NB and 0.57 L/L, (IQR 0.51-0.63 L/L) in capillary NB. CONCLUSIONS: Hb and Hct concentrations measured in UCB are similar to those measured in venous blood in very preterm infants and are valid alternatives for NB tests at birth. Hb and Hct concentrations in arterial and capillary NB are respectively lower and higher compared with UCB measurements.

Factors Associated With Failure of Non-invasive Ventilation in Preterm Neonates Requiring Initial Respiratory Support.

BACKGROUND: Non-invasive ventilation (NIV) modalities minimize the requirement for invasive mechanical ventilation (IMV) in preterm neonates, therefore improving neonatal outcomes, as IMV is linked to increased complications. However, NIV has demonstrated an elevated likelihood of failure, for which various studies have been done, but very little research is available addressing the factors that are responsible for NIV failure in resource-limited areas of developing nations. Understanding the underlying factors and their association with NIV failure in very and moderately preterm neonates at a tertiary care hospital would be important in devising targeted strategies to increase NIV success and newborn outcomes. OBJECTIVE: To compare the following factors in neonates of 28-34 weeks gestational age with or without failure of NIV: fraction of inspired oxygen (FiO2) at the time of initiating NIV, time at surfactant administration, respiratory distress syndrome presence, antenatal steroid use, time taken for post-surfactant administration stabilization, gestational age, development of bronchopulmonary dysplasia, and average weight gained or lost. STUDY DESIGN AND PARTICIPANTS: This was a longitudinal observational study. One hundred two preterm neonates with a gestational age of 28-34 weeks in the neonatal intensive care unit (NICU) requiring NIV support within 24 hours of admission. METHODS: Eligible newborns were re-evaluated at 72 hours after commencing NIV. Outcome was evaluated as success (no NIV or NIV with positive end-expiratory pressure (PEEP)<8 cm H2O and FiO2<0.7) or failure (NIV with PEEP≥8 cm H2O or FiO2≥0.7, intubation, or death). It was compared with regard to many parameters. RESULTS:  About 40 (39%) study participants reported NIV failure within 72 hours of initiating NIV. In the NIV failure group, male babies constituted 75% (P = 0.027), the median gestational age (IQR) was 29 (29-31) weeks (P = 0.015), the median birth weight (IQR) was 1088 (960-1293.5) grams (P = 0.003), and the median weight gain or loss (IQR) was a loss of 21 (-70.5 to 11.75) grams (P<0.001). Vaginal birth comprised 67.5% of the NIV failure group, showing greater failure rates than births out of lower segment cesarean section (LSCS) (P = 0.003) Conclusion: NIV failure showed a significant association with lesser gestational age, male sex, lower birth weight, vaginal method of delivery, and lesser weight gain during hospital stay.

When will the Glomerular Filtration Rate in Former Preterm Neonates Catch up with Their Term Peers?

AIMS: Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs. METHODS: We combined published inulin clearance values and serum creatinine (Scr) concentrations in (pre)term born individuals throughout childhood. Inulin clearance was assumed to be equal to GFR, and Scr to reflect creatinine synthesis rate/GFR. We developed a GFR function consisting of GFRbirth (GFR at birth), and an Emax model dependent on PNA (with GFRmax, PNA50 (PNA at which half of GFR max is reached) and Hill coefficient). The final GFR model was applied to predict gentamicin, tobramycin and vancomycin concentrations. RESULT: In the GFR model, GFRbirth varied with birthweight linearly while in the PNA-based Emax equation, GA was the best covariate for PNA50, and current weight for GFRmax. The final model showed that for a child born at 26 weeks GA, absolute GFR is 18%, 63%, 80%, 92% and 96% of the GFR of a child born at 40 weeks GA at 1 month, 6 months, 1 year, 3 years and 12 years, respectively. PopPK models with the GFR maturation equations predicted concentrations of renally cleared antibiotics across (pre)term-born neonates until 18 years well. CONCLUSIONS: GFR of preterm individuals catches up with term peers at around three years of age, implying reduced dosages of renally cleared drugs should be considered below this age.