Neonatal Drug Formularies—A Global Scope

Objective. Human umbilical cord blood (hUCB) is rich in stem cells. The CD45+/CD34+ coexpression in hUCB is a marker of hemopoietic progenitor cells. The objective of this study is to compare the coexpression of hUCB CD45+/CD34+ cells in preterm (PT) and full-term (FT) neonates.Methods. We studied the coexpression of hUCB CD45+/CD34+ cells in PT and FT neonates. The study included 25 PT (29–36 weeks gestation) and 25 FT (37–41) neonates delivered at Ain Shams University, Maternity Hospital. Absolute mononuclear layer cord blood CD45+/CD34+ cell count were measured by flow cytometry. Morbidity was assessed for 12 of the studied 25 PT infants, using Morbidity Assessment Index for Newborns score.Results. The absolute CD45+/CD34+ count did not differ between PT and FT infants: Z = −0.485, p = 0.63. There was no correlation between absolute cell count and GA (r = 0.013, p = 0.9) for all 50 neonates. Mode of delivery did not affect the absolute count in the PT infants: Z = –0.6, p = 0.57. There was no correlation between the degree of morbidity and absolute cell count in PT neonates; r = 0.13, p = 0.69.Conclusion. The absolute cell count is not affected by gestational age and did not relate to morbidity scores in the studied PT infants. Further, wide-scale work will be needed to study CD45+/CD34+ count in hUCB in sick PT neonates.

For quick detection of neonatal early-onset bacterial infection (EOBI) pro-inflammatory cytokines like Interleukin-6 (IL-6) and Interleukin-8 (IL-8) in combiantion with C-reactive Protein (CRP) have been used. Automated determination of immature myeloid information (IMI) seems to be an additional useful tool in the diagnosis of NBI. To compare the diagnostic value of IMI, I/T-Ratio, plasma IL-6 and IL-8 levels and CRP in term and preterm neonates at time of clinical suspicion of EOBI. 31 preterm and 123 term neonates with clinical and serological signs of EOBI were analysed. 91 preterm and 159 term neonates with risk factors but without proven EOBI served as non-infected controls. Neonates with EOBI showed significantly elevated IMI levels at time of first clinical suspicion of EOBI (Preterm: 1 028/µL (38-8 759) vs. 289/µL (6-3 126); Term: 1 268/µL (48-14 035) vs. 856/µL (19-5 735); p<0.05 respectively). I/T-Ratio, IL-6, IL-8 and CRP values were significantly higher in preterm and term neonates with EOBI (p<0.05). Sensitivity of IMI at a cut-off level of 650/µL was 84.2% [95%-CI: 74.0-91.6%] in preterm and 65.4% [95%-CI: 56.8-73.3%] in term infants. Specificity was 66.7% [95%-CI: 47.1-82.7%] and 53.9% [95%-CI: 43.8-63.7%], respectively. Combination of different infection parameters improved sensitivity up to 93.5% and specificity up to 98.9%. The diagnostic value of IMI in diagnosing EOBI in preterm and term neonates is not comparable to IL-6, IL-8 and CRP. Combination of IMI-Channel with IL-6, IL-8 or CRP improves their sensitivity, specificity and predictive value.

Term and preterm neonates have very few circulating Tfh-like cells (cTfh), and no circulating Tfr-like cells. Neonatal cTfh are CXCR5lo PD-1lo CD45RAhi , suggestive of a naive, possibly recently activated phenotype. CXCL13 is high at birth, but decreases rapidly in the first weeks of life. Overall, signs of GC activity in human neonates are weak, even in those born prematurely or after sepsis.

Audiovisual integration (AVI) is linked to the development of several cognitive abilities, rendering it a vehicle to better understand and anticipate a wide range of sequelae associated with preterm (PT) birth. In the present study, we aimed to complement the scarce literature on PT birth and AVI early in life, by investigating neonatal brain networks encompassing areas reported in the infant AVI literature. We used data from the Developing Human Connectome Project (http://www.developingconnectome.org/) to build two localized and one whole-brain connectomes from functional and structural connectivity data. Using graph analysis on a multiplex structural–functional brain network, we investigated the association between prematurity and (1) the edges present in functional and structural networks, (2) the integration and segregation properties of functional and structural networks, and (3) the inter-layer assortativity. We found substantial differences between PT and full-term (FT) neonates in the edges of the structural network at the whole-brain level and in one localized connectome. Across parcellation schemes, associations between prematurity and network efficiency were different, but similar inter-layer metrics were observed. In an exploratory analysis, we further showed lower functional connectivity strength in PT neonates. These findings are discussed in the light of perinatal brain developmental trajectories and deepen our understanding atypical AVI abilities in PT infants. More generally, the present work contributes to our understanding of whole-brain network development by investigating functional–structural coupling from a network neuroscience perspective.

Introduction: Neonatal renal function is a critical determinant of early health outcomes, especially in preterm neonates whose nephrogenesis may be incomplete at birth. Acute kidney injury (AKI) contributes significantly to neonatal morbidity and mortality worldwide, yet remains underdiagnosed, particularly in resource-limited settings like Bangladesh. Aim of the Study: The study aimed to conduct a comparative analysis of renal function status in term versus preterm neonates to evaluate implications for clinical care. Methods: This hospital-based comparative cross-sectional study was conducted at Dhaka Shishu Hospital, Bangladesh over a period of six months, from May to November 2024. Fifty neonates (25 term ≥37 weeks and 25 preterm &lt;37 weeks) were enrolled consecutively. Serum creatinine, urea, sodium, potassium, calcium, and phosphorus were measured at 24 hours and 7 days of life. AKI was defined according to modified neonatal KDIGO criteria. Statistical analysis included t-tests, chi-square tests, and logistic regression; p&lt;0.05 was considered significant. Results: Among the 50 neonates studied, preterm neonates had significantly lower birth weights (1.78±0.35 kg) than term neonates (2.77±0.41 kg; p&lt;0.001). Cesarean section was the predominant mode of delivery overall (80.0%), more common in preterms (88.0%) than terms (72.0%; p=0.028) Cesarean delivery was the predominant mode overall (80.0%), being more common in preterm (88.0%) than term neonates (72.0%; p=0.028). Male neonates predominated in both groups, though not statistically significant. Preterm neonates had higher serum creatinine at 24 hours (0.82±0.31 vs. 0.68±0.24 mg/dL; p=0.041) and 7 days (0.71±0.28 vs. 0.52±0.19 mg/dL; p=0.003). Blood urea at 7 days was also elevated in preterms (31.2±14.7 vs. 22.8±9.4 mg/dL; p=0.014). Reduced urine output was more common in preterms at 24 hours (40.0% vs. 12.0%; p=0.008) and 7 days (24.0% vs. 4.0%; p=0.023). AKI prevalence was significantly higher in preterms (48.0%) than in term neonates (16.0%; p=0.013). Preterm birth was an independent predictor of AKI (adjusted OR=4.12; p=0.038). Conclusion: Preterm neonates demonstrated significantly higher rates of AKI and impaired renal function compared to term neonates, underscoring the need for routine renal function monitoring and early intervention in this high-risk population.

Background: Bronchopulmonary dysplasia (BPD) continues to be an important problem in neonates especially premature infants despite improved facilities of care, monitoring and treatment. Pulmonary hypertension (PH) is a major complicating factor and key cause of mortality in this population. Altered vascular and alveolar growth particularly in canalicular and early saccular stages of lung development following mechanical ventilation and oxygen therapy result in arrest of the lung development leading to BPD with PH. Early recognition of PH in infants with these risk factors is important for optimal management. We tested the hypothesis that asymmetric dimethylarginine, would be greater in infants with bronchopulmonary dysplasia associated pulmonary hypertension than in infants with BPD alone. The Aim: The aim of the current study was to measure the Asymmetric dimethylarginine (ADMA) levels, arginine levels & the plasma arginine-to-ADMA ratio in newborn infants with broncho-pulmonary dysplasia, to evaluate echocardiographic parameters among neonates with bronchopulmonary dysplasia, to correlate between plasma ADMA & arginine-to-ADMA ratio and echocardiographic (ECHO) parameters in those patients and to compare full term & preterm neonates with bronchopulmonary dysplasia as regard to plasma ADMA level. Methods: A case-control study was carried out of ninety (90) newborns selected from those admitted to Neonatal Intensive Care Unit at Maternity & Children Hospital and Alzhraa University hospital during the period from October 2015 to March 2018. Neonates were divided into 2 groups: Patient with BPD with PH (cases group): It included 45 neonates with BPD & PH, 35 preterm neonates and 10 full term neonates. Patient with BPD only (Control group): It included 45 neonates with BPD without PH. These 45 neonates were divided as 22 preterm neonates and 23 full term neonates. Laboratory work was done in Alzhraa University hospital. Asymmetric dimethylarginine (ADMA) levels & arginine levels were measured using competitive enzyme linked immune-assay (ELISA). Results: Patients with both BPD and PH had greater plasma levels of ADMA than patients with BPD alone (P value 0.000). ADMA level > 186 ng/dl can predict development of PH in patient with BPD with sensitivity 100% and specify 100%. Preterm neonates with BPD had greater level of ADMA than full term neonates (P value 0.002). There was no statically significance difference between level of ADMA if withdrawn before or after 28 days of age (range of age at time of sampling in our study was 23 - 40 days) (P value 0.878), even ADMA level increased above the cut point early in the disease before we screened some cases by ECHO. There was no statically significance difference between level of arginine in cases and control groups with P value 0.530. The plasma arginine-to-ADMA ratio was lower in cases than in controls suggesting a greater likelihood of inhibition of nitric oxide production in patients with both BPD and PH than in patients with BPD alone (P value 0.000). ADMA level can predict severity of pulmonary hypertension in patient with BPD, as it was positively correlated with the grade of pulmonary hypertension (P value 0.006). ADMA level is higher in neonates with BPD and PH who died than those who survived; it can predict death in neonates with BPD &PH at cut off point > 643 ng/dl. Conclusion: ADMA increased in newborn infants with BPD, who developed PH. ADMA may have diagnostic and prognostic values. ADMA level was higher in preterm neonates than full term neonates and its level was correlated positively with severity of PH. ADMA levels were significant higher in infants with BPD with PH who died later than those who survived. There was no statically significance difference between levels of ADMA, whether it was drawn before or after 28 days of age (range 23 - 40 days). Echocardiographic screening and ADMA measurement could help in prevention of PH, diagnosis and early treatment of newborn infants suffering from BPD.

A Phase II/III, Multicenter, Safety, Efficacy, and Pharmacokinetic Study of Dexmedetomidine in Preterm and Term Neonates

The net impact of clinical seizures on outcome characteristics in infants with neonatal encephalopathies at 12 months of age

The normal length of penis in preterm and term neonates is different among different nations, and is affected by various factors. The present study aimed to determine stretched penile length (SPL) values and cutoff level of micropenis in term and preterm Iranian neonates, for the first time. All male neonates born in two general hospitals of Tehran (Akbarabadi, and Rasoul hospitals), center of Iran, with gestational age of 28-42 weeks were included and their SPL and penile circumference (PC) were examined on the first 3 days after birth by the same physician. Birth weight (BW), and height, gestational age, type of delivery, mother's age, twin/multiple pregnancy, drug, and medical history of mother during pregnancy were recorded and cutoff levels of two variables were calculated based on the collected variables for different gestational ages. Among a total of 587 neonates, 203 neonates were born term and 384 preterm. Mean ± SD of neonates' BW were 2,682.51 ± 739.30 (850-4800) gr. Mean ± SD of their SPL was 22.48 ± 3.34 mm; 25.92 ± 1.54 mm in term and 20.66 ± 2.50 mm in preterm infants (P = 0.001). Mean ± SD of PC was 6.71 ± 1.31 mm; 8.14 ± 0.48 in term and 5.96 ± 0.92 in preterm infants (P = 0.001). SPL and PC were significantly correlated with type of delivery, number of parity, gestational age, BW, and crown-heel length, head circumference (P < 0.001). This study suggested that SPL in male neonates was 22.48 mm and PC was 6.71 mm, both correlated with gestational age and BW. Due to the ethnical variety of this cutoff points and lack of an appropriate study in Iran, these cutoff points can be used by all physicians as a reference for Iranian newborns (term and preterm), in order to prevent misdiagnosis of micropenis and genital disorders.

Objective. To investigate the outcome of preterm and term neonates born to mothers with malignant diseases diagnosed during pregnancy.Methods. A retrospective analysis with a matched-paired control group in a third level obstetric department and third level neonatal department of the University Hospital Frankfurt. Patients were preterm and term neonates from mothers with oncologic diseases diagnosed during pregnancy and matched-paired preterm and term neonates from healthy mothers.Measurements and results. Nineteen preterm and three term (1 × twins) neonates from 21 mothers with oncologic diseases and matched-paired neonates from 21 healthy mothers were included. With the exception of one case, pregnancy was terminated because of the necessity for maternal oncological treatment. Children from mothers with malignant diseases had a significantly lower birth weight and a tendency towards a higher incidence of high-grade respiratory distress syndrome. No significant differences concerning Apgar scores, red blood cell (RBC), white blood cell (WBC), and platelet (PLT) counts postpartum, and duration of hospital days between the two groups of neonates were observed.Conclusion. Direct perinatal outcome of preterm or term neonates from mothers with malignant diseases diagnosed during ongoing intact pregnancy does not differ from the outcome of a comparable group of neonates from healthy mothers. This might be in contrast to the long-term outcome of this special patient group. In our study we could find no elevated mortality in neonates where pregnancy was terminated because of the need for maternal chemotherapeutic therapy.

The response of the adaptive immune system is usually less intense in premature neonates than term neonates. The primary objective of this study was to determine whether immunological parameters vary between preterm (PT) neonates (≥32 weeks of gestational age) and very preterm (VPT) neonates (<32 weeks of gestational age). A cross-sectional study was designed to prospectively follow PT and VPT neonates at risk of developing sepsis. Plasma concentrations of IFN-γ, TNF-α, IL-6, IL-4, and IL-10 were detected using flow cytometry. C-reactive protein (C-RP) and the complex SC5b-9 were detected in the plasma using commercial kits. A total of 83 patients were included. The laboratory results and clinical histories showed that 26 patients had sepsis; 14 were VPT, and 12 were PT. The levels of C-RP, SC5b-9 (innate immune response mediators), and IL-10 or IL-4 (anti-inflammatory cytokines) were elevated during sepsis in both groups. IFN-γ, TNF-α, and IL-6 (proinflammatory cytokines) were differentially elevated only in PT neonates. The VPT neonates with sepsis presented increases in C-RP, SC5b-9, and anti-inflammatory cytokines but not in proinflammatory cytokines, whereas PT neonates showed increases in all studied mediators of inflammation.

Background and Objectives: Clitoromegaly is an important parameter in the evaluation of ambiguous genitalia in neonates, but the normative data for clitoral size in newborns have racial/ethnic differences. The present study aimed to determine clitoral length (CL) and clitoral width (CW) values and establish cutoff measurement to define clitoromegaly in both term and preterm Iranian neonates for the first time.Methods: A total number of 580 female newborn infants delivered at 28–42 weeks of gestation were enrolled in the study, and their CL and CW were measured on the first 72 h of birth. Data about birth weight (BW), body length (BL), and head circumference (HC) of newborns; mothers' age; and gestational age (GA) were recorded, too. Results were presented as mean ± standard deviation (SD) for quantitative variables and were summarized by frequency (percentage) for categorical variables. Backward stepwise regression analysis was used for prediction of CL and CW.Results: Among 580 Iranian female newborns studied, 187 were term neonates and the other 393 newborns were preterm. Mean ± SD values of CL were 6.11 ± 0.39 mm in term infants and 5.45 ± 0.64 mm in preterm infants (P < 0.001). Mean ± SD values of CW were 4.22 ± 0.43 in term infants and 3.68 ± 0.53 in preterm infants (P < 0.001). Regression analysis showed that CL was correlated with GA considered by last menstrual period, BL, BW, and HC; and CW was associated with GA, BL, and BW.Conclusion: This study suggests normative values (mean + 1, 2, and 3 SD) of CL and CW according to GA, which can be used as a reference for Middle East's newborns, especially Iranian newborn babies.

Seizures in Preterm Neonates: A Multicenter Observational Cohort Study

Clinical value of a set of neuropeptides in term and preterm neonates with seizures: Brain derived neurotrophic factor, galanin and neuropeptide Y

Background: Cerebral oxygenation monitored non-invasively by near-infrared spectroscopy (NIRS) is of increasing interest in neonatal care. Cerebral oxygenation is determined by cerebral oxygen delivery and cerebral oxygen consumption. Oxygen delivery as well as oxygen consumption might be influenced by metabolic parameters like blood glucose and lactate.Objective: The aim of the present systematic qualitative review is therefore to identify and summarize all studies, which describe cerebral oxygenation measured with NIRS and blood glucose and/or blood lactate levels in neonates.Data sources: A systematic search of Ovid Embase and PubMed was performed. Search terms included near-infrared spectroscopy, fractional tissue oxygen extraction, cerebral tissue oxygen saturation, regional cerebral tissue oxygen saturation, oxygenation, term, and preterm neonates, cesarean delivery, transition, after-birth, newborn, vaginal delivery, cesarean delivery, baby, neonatal transition, metabolism, lactate, glucose, and blood glucose level.Study selection/data synthesis: Studies analyzing cerebral oxygenation and blood glucose and/or blood lactate levels in neonates were included. Animal studies, duplicates, or studies in non-English language were excluded.Results: Twenty-five studies were identified that describe blood glucose and/or blood lactate levels as primary or secondary outcome parameters with additional measured cerebral oxygenation by NIRS in neonates. Twelve studies were included with blood glucose measurements: four described an association between blood glucose levels and cerebral oxygenation, two show no association, and six do not report on possible associations. Eighteen studies were included with lactate measurements: one describe an association between lactate levels and cerebral oxygenation, while three show no association and 14 do not report on possible associations.Discussion: The influence of blood glucose and blood lactate levels on the cerebral oxygenation in neonates is still controversial. However, there seems to be an association between cerebral oxygenation and the metabolic parameter blood glucose and lactate, which need further investigation.