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Neonatal Morbidity: Current Advances, New Perspectives and Future Challenges

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A special issue of Children (ISSN 2227-9067). This special issue belongs to the section "Pediatric Neonatology".

Deadline for manuscript submissions: closed (5 January 2025) | Viewed by 14568

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Special Issue Editors

Prof. Dr. Katerina Lykeridou

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Guest Editor

Department of Midwifery, School of Health and Care Sciences, University of West Attica, Athens, Greece
Interests: midwifery care; high-risk intrapartum care; intrapartum-related complications; emergencies in the perinatal period; special populations

Dr. Dimitra Metallinou

E-Mail Website
Guest Editor Assistant

Department of Midwifery, University of West Attica, 12243 Athens, Greece
Interests: midwifery care; perinatal care; neonatal care; infectious diseases; neonatal intensive care; critically-ill neonates; neonatal brain injury; biomarkers

Special Issue Information

Dear Colleagues,

Although significant advances have been achieved in perinatology and intensive neonatal care, rates of neonatal morbidity and adverse sequelae remain high, underlining the need for interdisciplinary cooperation to improve neonatal health outcomes. Scientific fields and technologies related to the measurement of biological molecules are rapidly evolving, and offer ever-expanding information for a comprehensive understanding of the neonatal biological system, thus contributing to the early identification of neonates at high risk of developing complications and life-threatening diseases. This knowledge could assist clinicians and neonatal intensive care unit (NICU) staff to plan individualized interventions which will either prevent or optimize neonatal outcomes.

Systematic antenatal care, the diagnosis and treatment of maternal infections, the detection of perinatal risk factors and focused neonatal care are key aspects of both reducing neonatal morbidity and improving neonatal prognosis. Intrapartum- and prematurity-related complications are closely related to neonatal morbidity, highlighting the necessity of skilled obstetricians and midwives, evidence-based and up-to-date guidelines, effective prevention methods and high-quality healthcare facilities. A number of protective actions are now at the center of early intervention programs in the NICU, and their goal is to sustain preterm neonates’ development by empowering their potentialities. It is now evident that the environment and the sensory stimuli, predominantly during the perinatal period, have an impact on neonate development. Parents do not simply facilitate environmental stimuli, but are part of the environment itself, changing their interaction according to the neonate’s needs, reactions, and requests and impacting on its socio-emotional development. Lastly, an imperative goal for healthcare professionals to consider is the reduction of the economic, social and, above all, family burden resulting from neonatal morbidity.

This Special Issue of Children is an update on current advances pertaining to the prevention, prevalence, risk factors, diagnosis, etiology, pathophysiology, treatment, as well as short- and long-term neurodevelopmental outcomes of several neonatal critical conditions. We also encourage submissions that investigate and demonstrate new perspectives and discuss future challenges regarding neonatal morbidity. Finally, this Special Issue aims to highlight the pivotal role of the interdisciplinary team in the neonatal period, raise awareness of novel biomarkers and effective pharmacological and non-pharmacological therapies, and enhance the understanding of family dynamics in special populations such as high-risk and critically-ill neonates. We invite researchers and colleagues to submit original research articles, reviews and case reports that address relevant topics.

We wish for a pleasant collaboration and look forward to receiving your contributions.

Prof. Dr. Katerina Lykeridou
Guest Editor

Dr. Dimitra Metallinou
Guest Editor Assistant

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Published Papers (8 papers)

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8 pages, 497 KiB

Open AccessArticle

Diagnostic Value of Umbilical Cord Blood Interleukin-6 Level in Premature Infants with Early-Onset Sepsis

by Jinfang Yuan, Yufeng Wu, Yahui Zhang, Lin Zeng, Jiansuo Zhou, Meihua Piao, Xiaomei Tong, Yuan Wei, Liyan Cui and Tongyan Han

Children 2025, 12(3), 301; https://doi.org/10.3390/children12030301 - 27 Feb 2025

Viewed by 318

Abstract

Objective: Early-onset sepsis (EOS) is a serious, grave, and frequently fatal condition in premature infants. This study aimed to assess the diagnostic value of interleukin-6 (IL-6) levels in umbilical cord blood for identifying EOS in preterm infants. Methods: This prospective cohort study was conducted on preterm infants between May 2019 and April 2021. Based on the diagnostic criteria for EOS, the participants were divided into EOS and non-EOS groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of cord blood IL-6 levels for EOS. Results: The levels of IL-6 were significantly higher in the EOS group (n = 10) compared to the non-EOS group (n = 178) [617.5 pg/mL (323.3, 1579.8) vs. 49.7 pg/mL (15.8, 142.8), respectively; p = 0.000]. ROC curve analysis demonstrated that a cutoff value of 250.5 pg/mL for cord blood IL-6 yielded a sensitivity of 90%, specificity of 82%, and area under the curve of 0.876, with a confidence interval of 0.753–0.999, indicating its high accuracy as a diagnostic marker for EOS among preterm infants (p < 0.001). Conclusions: The detection of IL-6 in the umbilical cord blood offers convenience and exhibits significant diagnostic potential for EOS in preterm infants, thereby providing valuable support for clinical decision-making. Full article

(This article belongs to the Special Issue Neonatal Morbidity: Current Advances, New Perspectives and Future Challenges)

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15 pages, 687 KiB

Open AccessArticle

A Survey on the Organization and Operation of Level II/III Neonatal Intensive Care Units in Greece: A Comparison Between 2004 and 2022

by Kosmas Sarafidis, Nicoletta Iacovidou, Eleftheria Hatzidaki, Ilias Chatziioannidis and Gabriel Dimitriou

Children 2025, 12(1), 85; https://doi.org/10.3390/children12010085 - 13 Jan 2025

Viewed by 668

Abstract

Background/Objectives: Limited data exist on the organization and operation of Level II/III Neonatal Intensive Care Units (NICUs) in Greece; this retrospective cross-sectional survey explored their structure and functioning in 2004 and 2022. Methods: A structured questionnaire was utilized, along with demographic and perinatal data obtained from the Hellenic Statistical Authority. Results: Between 2004 and 2022, live births decreased by 28%, while the prematurity rate rose from 6.96% to 11.87% (p < 0.001). Significant regional differences were observed in the number of NICUs (p = 0.033), live births (p < 0.001), and NICUs per 10,000 live births (p = 0.025). In this survey, data from 20 Level III NICUs in 2004 and 22 NICUs (one Level II) in 2022 were analyzed. NICU admissions increased by 16.1% (p = 0.389), while the rate of admitted neonates/1000 live births increased from 13.5 to 21.8 (p < 0.001). In 2022, premature infants constituted 40.2% of NICU admissions. The number of board-certified neonatologists increased by 21.8% between 2004 and 2022 (p = 0.795), along with a rise in the ratio of neonatologists per 10,000 live births (from 14.8 to 25, respectively, p < 0.001). Conversely, there was a significant 17.2% reduction in the nursing staff by 2022 (p = 0.034). The number of available NICU beds also increased during the study period. The ratio of ventilators to intensive care beds significantly improved (p < 0.001). In 2022, new treatment modalities, like therapeutic hypothermia, were introduced, and most NICUs reported offering long-term follow-up programs. Conclusions: This survey highlights significant advancements in Level II/III NICU infrastructure and care capabilities, while emphasizing demographic changes and a critical shortage of neonatal nursing staff. These factors should be carefully considered by health authorities in the development of future neonatal care strategic planning in the country. Full article

(This article belongs to the Special Issue Neonatal Morbidity: Current Advances, New Perspectives and Future Challenges)

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18 pages, 671 KiB

Open AccessArticle

High-Potency Prenatal Cannabis Exposure and Birth Outcome Measures

by Natalia M. Kleinhans, Allegra J. Johnson, Sarah F. Larsen, Sara K. Berkelhamer, Mary E. Larimer and Stephen R. Dager

Children 2024, 11(12), 1436; https://doi.org/10.3390/children11121436 - 26 Nov 2024

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Abstract

Background/Objectives: Pregnant women have limited information on the impact of prenatal cannabis exposure (PCE) alone. Our aim was to determine if PCE, without alcohol, tobacco, or illicit drug use, is associated with altered birth outcome measures in obstetrically low-risk women. Methods: In this observational cohort study, pregnant women were recruited between 2019 and 2022 from communities in Washington and Oregon, USA, and enrolled following their first trimester. PCE eligibility required a minimum of three days/week of cannabis use during the first trimester with no required minimum use thereafter. For all participants, illicit drug, nicotine, or alcohol use was exclusionary throughout pregnancy and monitored via urine toxicology at multiple time points. Cannabis use was quantified into delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) mg/day using product weight and potency. Outcome measures included gestational age, weight, length, head circumference, and Apgar scores. Results: Study participants included 37 people in the PCE cohort and 35 controls. Average cannabis use for the PCE cohort was 198.0 mg of THC (SD = 221.2 mg)/day and 3.5 mg of CBD (SD = 4.3)/day. PCE newborns weighed less (38th vs. 52nd percentile, p = 0.04) and were shorter (40th vs. 55th percentile, p = 0.03) for their gestational age than controls. Female PCE newborns had smaller head circumference for gestational age (28th percentile; SD = 23), compared to male PCE newborns (55th percentile; SD = 32; p = 0.02). Conclusions: PCE is associated with reduced birth weight and shorter length for gestational age. The effect of PCE on brain growth may be sexually dimorphic. Future PCE studies should include sex as a biological variable and longitudinally evaluate long-term developmental and physiological outcomes. Full article

(This article belongs to the Special Issue Neonatal Morbidity: Current Advances, New Perspectives and Future Challenges)

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14 pages, 1027 KiB

Open AccessArticle

Predictive Value of Inflammatory Markers NLR, PLR, APRI, SII, and Liver Function Tests in Systemic Inflammatory Response Syndrome Detection in Full-Term Newborns

by Manuela Pantea, Daniela Iacob, Mirabela Dima, Mihaela Prodan, Oana Belei, Rodica Anamaria Negrean and Adrian Cosmin Ilie

Children 2024, 11(5), 593; https://doi.org/10.3390/children11050593 - 14 May 2024

Cited by 2 | Viewed by 2066

Abstract

Systemic Inflammatory Response Syndrome (SIRS) is associated with significant morbidity and mortality in full-term newborns. This study aimed to evaluate the predictive value of the Neutrophil-to-Lymphocyte Ratio (NLR), Derived Neutrophil-to-Lymphocyte Ratio (dNLR), Platelet-to-Lymphocyte Ratio (PLR), Neutrophil, Lymphocyte, and Platelet Ratio (NLPR), AST-to-Platelet Ratio Index (APRI), and Systemic Immune–Inflammation Index (SII) in identifying the risk for SIRS development in full-term newborns. Conducted between January 2023 and January 2024, this observational cohort study compared full-term newborns diagnosed with SIRS with newborns without SIRS, measuring the inflammatory markers within the first day of life and three days post-birth. The study included 229 newborns, 81 with SIRS and 148 controls without SIRS. Statistically significant differences were observed in NLR (3.81 vs. 2.20, p < 0.0001), PLR (68.12 vs. 52.30, p < 0.0001), and liver enzymes (AST 40.96 U/L vs. 31.58 U/L, ALT 34.66 U/L vs. 22.46 U/L, both p < 0.0001) between the groups. The NLPR demonstrated substantial diagnostic value, with a sensitivity of 78.36% and specificity of 83.52% at 72 h (p < 0.0001). Regression analysis highlighted that the NLPR and SII were strongly predictive of SIRS, with the NLPR showing over three-times higher SIRS risk (HR 3.29, p < 0.0001) and SII indicating nearly 3.5 times the risk (HR 3.47, p < 0.0001). The NLPR, APRI, and SII showed similar prediction values to CRP levels measured on the first and third days of life (HR 3.16). Inflammatory markers like NLR, PLR, and systemic indices such as NLPR and SII, alongside liver function tests, are significant predictors of SIRS in full-term newborns. These findings support the integration of these markers into routine neonatal care, allowing for early identification and potentially improved management of newborns at risk for SIRS, thereby enhancing clinical outcomes. Full article

(This article belongs to the Special Issue Neonatal Morbidity: Current Advances, New Perspectives and Future Challenges)

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12 pages, 1391 KiB

Open AccessArticle

Intermittent High-Dose Vitamin D3 Administration in Neonates with Multiple Comorbidities and Vitamin D Insufficiency

by Catalin Cirstoveanu, Iulia Ionita, Carmina Georgescu, Carmen Heriseanu, Corina Maria Vasile and Mihaela Bizubac

Children 2024, 11(3), 328; https://doi.org/10.3390/children11030328 - 9 Mar 2024

Cited by 2 | Viewed by 2308

Abstract

Background: Neonates have an increased risk of vitamin D insufficiency due to the inadequate supplementation of mothers and infants after birth. Insufficiency of vitamin D is frequently detected in critically ill patients and is associated with disease severity and mortality. There is yet to be a consensus on the appropriate regimen of vitamin D3 supplementation in high-risk infants. Aim: The main objectives of this study were to determine the prevalence of vitamin D insufficiency in neonates with severe comorbidities and to evaluate whether high-dose vitamin D3 oral administration leads to normal plasmatic concentrations without side effects. Methods: The current study was a randomized, prospective trial of 150 patients admitted to the Neonatal Intensive Care Unit (NICU) at Maria Sklodowska Curie Emergency Children’s Hospital in Bucharest. Patients were divided into three subgroups based on the chronological order of their admission date. Each subgroup received a different pharmaceutical product of vitamin D3. We administered a dosage of 10,000 IU/kg of vitamin D3 orally in three steps, as follows: at admission, one week after admission, and one month from the first administration, targeting a serum 25-hydroxyvitamin D concentration of at least 40 ng/mL. Results: Most neonates (68%) achieved an optimum vitamin D level after one month, even though only 15% of patients had an optimum concentration at admission. After the first high dose of vitamin D3, there was a 27% increase in the mean vitamin D plasmatic level compared to admission levels. However, after one month, the concentrations decreased in all subgroups due to the gap of three weeks between the last two administrations. Conclusions: An intermittent, weekly high-dose vitamin D3 oral administration leads to a steadier increase and normalization of vitamin D concentration in most critically ill neonates. However, high-dose vitamin D3 administered orally after three weeks decreases vitamin D levels in this high-risk population. Full article

(This article belongs to the Special Issue Neonatal Morbidity: Current Advances, New Perspectives and Future Challenges)

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12 pages, 20294 KiB

Open AccessArticle

The Molecular and Histopathological Assessment of Inflammatory Status in Very and Extremely Premature Infants: A Prospective Study

by Claudia Ioana Borțea, Ileana Enatescu, Manuela Pantea, Mirabela Dima, Emil Radu Iacob, Catalin Dumitru, Alin Popescu, Florina Stoica, Rodica Elena Heredea and Daniela Iacob

Children 2023, 10(2), 352; https://doi.org/10.3390/children10020352 - 10 Feb 2023

Cited by 1 | Viewed by 1812

Abstract

Prematurity comes with a varying range of complications, implying a high prevalence of complications and mortality and depending on the severity of prematurity and the sustained inflammation among these infants, which recently sparked an important scientific interest. The primary objective of this prospective study was to establish the degree of inflammation in very (VPIs) and extremely preterm infants (EPIs) in association with the histology findings of the umbilical cord (UC), while the secondary objective was to study the inflammatory markers in the neonates’ blood as predictors of fetal inflammatory response (FIR). A total of thirty neonates were analyzed, ten of them being born extremely premature (<28 weeks of gestation) and twenty very premature (28–32 weeks of gestation). The EPIs had considerably higher levels of IL-6 at birth than VPIs (638.2 pg/mL vs. 151.1 pg/mL). The CRP levels at delivery did not vary substantially across groups; however, after days, the EPIs had significantly higher CRP levels (11.0 mg/dL vs. 7.2 mg/dL). In contrast, the LDH was considerably higher in the extremely preterm infants at birth and four days after birth. Surprisingly, the proportions of infants with pathologically increased inflammatory markers did not differ between the EPIs and VPIs. The LDH increased considerably in both groups, although the CRP levels increased exclusively among the VPIs. The stage of inflammation in the UC did not vary substantially between the EPIs and VPIs. The majority of infants were identified with Stage 0 UC inflammation (40% in EPI vs. 55% in VPIs). There was a substantial correlation link between gestational age and newborn weight and a significant inverse correlation among gestational age and IL-6 and LDH levels. There was a strong negative association between weight and IL-6 (rho = −0.349) and LDH (rho = −0.261). The stage of the UC inflammation demonstrated a statistically significant direct connection with IL-6 (rho = 0.461) and LDH (rho = 0.293), but none with the CRP. Further studies involving a bigger population size of preterm newborns are required to validate the findings and analyze more inflammatory markers, while prediction models on inflammatory markers that are measured expectantly, before the onset of preterm labor, need to be created. Full article

(This article belongs to the Special Issue Neonatal Morbidity: Current Advances, New Perspectives and Future Challenges)

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27 pages, 803 KiB

Open AccessSystematic Review

Evaluating Educational Patterns and Methods in Infant Sleep Care: Trends, Effectiveness, and Impact in Home Settings—A Systematic Review

by Maria Aggelou, Dimitra Metallinou, Maria Dagla, Victoria Vivilaki and Antigoni Sarantaki

Children 2024, 11(11), 1337; https://doi.org/10.3390/children11111337 - 31 Oct 2024

Viewed by 2127

Abstract

Background: Sleep care is crucial for the health and development of infants, with proper sleep patterns reducing the risk of sudden infant death syndrome (SIDS) and other sleep-related incidents. Educational interventions targeting caregivers are essential in promoting safe sleep practices. Methods: This systematic review adhered to PRISMA guidelines, searching databases such as PubMed, MEDLINE, Scopus, and the Cochrane Library. Inclusion criteria focused on studies involving home-based interventions for infants aged 0–12 months, including parental education and behavioral interventions. Exclusion criteria included studies in clinical settings and non-peer-reviewed articles. Data extraction and synthesis were performed by two independent reviewers, using a narrative approach to categorize interventions and outcomes. Results: Twenty-three studies met the inclusion criteria. Key findings indicate that home-based educational interventions, including hospital-based programs, home visits, and mobile health technologies, significantly improve parental knowledge and adherence to safe sleep practices. These interventions also enhance parental satisfaction and contribute positively to infant health outcomes. Conclusions: Educational interventions have demonstrated effectiveness in promoting safe sleep practices among caregivers, particularly in home settings. These interventions, including hospital-based programs, home visits, and digital tools, improve parental knowledge, adherence to guidelines, and overall satisfaction. The impact is evident in the reduction of unsafe sleep behaviors and enhanced infant health outcomes. However, variability in the intervention methods and delivery, cultural contexts, and geographic focus suggest a need for more tailored, long-term, and comprehensive studies. Future research should standardize outcome measures and assess the sustained impact of these educational strategies on infant sleep patterns and caregiver practices over time. This will provide deeper insights into the trends and long-term effectiveness of educational patterns and methods in diverse home environments. Full article

(This article belongs to the Special Issue Neonatal Morbidity: Current Advances, New Perspectives and Future Challenges)

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8 pages, 1732 KiB

Open AccessCase Report

Autosomal Dominant Hypocalcemia Type 1 and Neonatal Focal Seizures

by Raluca Ioana Teleanu, Marlene Alexandra Sarman, Diana Anamaria Epure, Margarita Matei, Ioana Roşca and Eugenia Roza

Children 2023, 10(6), 1011; https://doi.org/10.3390/children10061011 - 3 Jun 2023

Cited by 1 | Viewed by 2680

Abstract

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism that is characterized by gain-of-function mutations in the CASR gene, which provides instructions for producing the protein called calcium-sensing receptor (CaSR). Hypocalcemia in the neonatal period has a wide differential diagnosis. We present the case of a female newborn with genetic hypoparathyroidism (L125P mutation of CASR gene), hypocalcemia, and neonatal seizures due to the potential correlation between refractory neonatal seizures and ADH1. Neonatal seizures were previously described in patients with ADH1 but not in association with the L125P mutation of the CASR gene. Prompt diagnosis and management by a multidisciplinary and an appropriate therapeutic approach can prevent neurological and renal complications. Full article

(This article belongs to the Special Issue Neonatal Morbidity: Current Advances, New Perspectives and Future Challenges)

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