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Clinical Diagnosis and Management of Neonatal Diseases

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Pediatrics".

Deadline for manuscript submissions: 20 December 2025 | Viewed by 6677

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Special Issue Editors

Dr. Ayala Gover

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Guest Editor

1. Neonatal Intensive Care Unit, Bnai-Zion Medical Center, Haifa 31048, Israel
2. The Ruth & Bruce Rappaport Faculty of Medicine, Technion, Haifa 32000, Israel
Interests: neonatology; neonatal intensive care; neonatal hemodynamics; point of care ultrasound

Prof. Dr. Arieh Riskin

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Special Issue Information

Dear Colleagues,

As the field of neonatology continues to evolve, we invite researchers to submit their original manuscripts to our Special Issue dedicated to the diagnosis and management of neonatal diseases. We welcome high-quality studies across a range of topics, including but not limited to neonatal care, preterm birth, neonatal respiratory and cardiovascular management, neurodevelopmental outcomes, and point-of-care ultrasound for neonatal conditions. Our goal is to highlight research that can inform clinical practice and improve outcomes for the most vulnerable patients. In this Special Issue, we encourage clinical research that provides new insights into the diagnosis, treatment, and care of neonates, with an emphasis on improving long-term health and development. Submissions will undergo a rigorous peer-review process. We warmly welcome researchers to contribute their work to this issue and look forward to receiving your innovative and impactful submissions.

Dr. Ayala Gover
Prof. Dr. Arieh Riskin
Guest Editors

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Keywords

newborn
preterm
neonatal intensive care
low birth weight
point-of-care ultrasound
neonatal monitoring

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Published Papers (9 papers)

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Research

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10 pages, 748 KiB

Open AccessArticle

Sedation and Analgesia for Intubation, LISA, and INSURE Procedures in Israeli NICUs: Caregivers’ Practices and Perspectives

by Rasha Zoabi Safadi, Ayala Gover, Naama Tal Shahar, Irit Shoris, Arina Toropine, Adir Iofe, David Bader, Morya Shnaider and Arieh Riskin

J. Clin. Med. 2025, 14(16), 5865; https://doi.org/10.3390/jcm14165865 - 19 Aug 2025

Viewed by 177

Abstract

Background/Objectives: Early pain exposure in newborns is linked to negative short- and long-term outcomes. Preterm infants often require endotracheal intubation for mechanical ventilation or brief laryngoscopy for surfactant administration via Less Invasive Surfactant Administration (LISA) or Intubation–Surfactant–Extubation (INSURE). While premedication before intubation is well-studied, data regarding premedication for LISA/INSURE are limited. We aimed to explore premedication practices for intubation and LISA/INSURE procedures across Neonatal Intensive Care Units (NICUs) in Israel. Methods: An anonymous online questionnaire comprising 27 questions about premedication practices was distributed to neonatal caregivers in Israel. The questions addressed the use of premedication before intubation or LISA/INSURE, the existence of written protocols, pharmacological agents employed, and caregiver satisfaction with the medications used. Results: Questionnaires were collected between January and July 2023, yielding 69 responses from 20 NICUs. Almost all respondents (95.7%) routinely use premedication before intubation, but only 65.7% use it for LISA/INSURE. For non-emergency intubations, extremely low-birth-weight (ELBW) infants received premedication less often than the general neonatal population (75.4% vs. 95.7%, respectively). Most caregivers (91.2%) did not report increased procedure failure associated with premedication during LISA/INSURE. The vast majority of Israeli caregivers do not include muscle relaxants in their premedication regimen for intubation. Dual therapy regimens yielded higher satisfaction rates than monotherapy. Higher complication rates, particularly respiratory depression, were observed with Fentanyl, especially when used as monotherapy. Conclusions: Significant variations exist in premedication practices among caregivers across Israeli NICUs. Premedication is commonly administered for intubation but is considerably less frequent for LISA/INSURE, despite these procedures also being painful. ELBW infants received less premedication. Notably, muscle relaxants are infrequently used for premedication by Israeli NICU caregivers. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Management of Neonatal Diseases)

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14 pages, 693 KiB

Open AccessArticle

Short-Term Clinical and Biochemical Outcomes of Infants Born After 34 Weeks of Gestation with Mild-to-Moderate Cord Blood Acidosis—A Retrospective Study

by Ayala Gover, Arieh Riskin, Livnat Sharkansky, Rawan Hijazi, Ranin Ghannam and Hussein Zaitoon

J. Clin. Med. 2025, 14(16), 5720; https://doi.org/10.3390/jcm14165720 - 13 Aug 2025

Viewed by 353

Abstract

Background/Objectives: Umbilical cord pH is used as a predictor of risk for poor neurologic outcome in high-risk newborns. While data on neonates with severe acidemia show a strong association with birth asphyxia and long-term adverse outcomes, the significance of mild-to-moderate acidemia is less clear. This study aimed to investigate short-term outcomes of late preterm and term infants born with mild-to-moderate cord blood acidosis and to compare the predictive ability of pH and base excess. Methods: This was a retrospective cohort study, including term and late preterm (≥34 weeks) neonates with mild–moderate umbilical cord blood acidosis, defined as pH 7.0–7.2 or base excess between −12 and −16. Data including demographic, clinical, and laboratory measures were extracted. The cohort population was stratified based on the level of acidosis, mild or moderate, with separate analyses performed by definitions of pH and BE. Mild acidosis was defined as cord blood pH 7.13–7.20 and base excess > −12 and moderate acidosis was defined as cord blood pH 7.00–7.12 or base excess between −12 and −16. Results: The study included 337 newborns. Most had mild acidosis, but 90 infants had BE of −12 to −16 and 86 infants had pH 7.00–7.12. Rate of NICU admission was 12.8% (43/337), rising up to 27% among newborns with moderate acidosis. The leading cause for admission was respiratory distress, and there were no cases of moderate–severe HIE. Renal and hepatic dysfunction were more common in moderate compared to mild acidosis; however, most lab abnormalities were mild and transient. Using ROC curves, BE ≤ −12 was found to be a better predictor for renal and liver involvement than pH ≤ 7.12. Conclusions: Moderate acidosis in cord blood was associated with an increased incidence of short-term neonatal morbidities, NICU admissions and renal or liver dysfunction compared to mild cord blood acidemia. BE correlated with abnormal values better than pH. Infants with cord gas BE levels ≤ −12 may benefit from closer clinical monitoring and assessment of renal and liver function. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Management of Neonatal Diseases)

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9 pages, 195 KiB

Open AccessArticle

Persistent Pulmonary Hypertension of the Newborn in Very Low Birth Weight Infants: Risk Factors and Clinical Outcomes from a Matched Case–Control Study

by Anucha Thatrimontrichai, Pattima Pakhathirathien, Manapat Praditaukrit, Gunlawadee Maneenil, Supaporn Dissaneevate, Ploypailin Jantarawongpisal and Jenjira Saechan

J. Clin. Med. 2025, 14(13), 4759; https://doi.org/10.3390/jcm14134759 - 4 Jul 2025

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Abstract

Background/Objectives: To identify the risk factors and clinical outcomes of persistent pulmonary hypertension of the newborn (PPHN) in very low birth weight (VLBW) infants in a resource-limited setting. Methods: We conducted a 1:4 matched case–control study in a Thai neonatal unit between 2014 and 2023. Neonates born at a gestational age (GA) < 32 weeks and with a birth weight (BW) < 1500 g were included. Neonates who died in the delivery room or had major congenital anomalies were excluded. Matching was based on GA, BW, year of birth, and endotracheal intubation at birth. Conditional logistic regression analysis was performed. Results: Over the 10-year study period, the incidence of PPHN among VLBW neonates was 4.6% (31/667). After matching, there were 31 cases and 124 controls. In univariable analysis, PPHN was significantly associated with lower 1 min and 5 min Apgar scores; however, no significant association remained in multivariable analysis. PPHN was significantly associated with composite adverse outcomes—including mortality and major morbidities (adjusted odds ratio [aOR] = 7.51, 95% confidence interval [CI]: 2.41–23.40), mortality alone (aOR = 2.88, 95% CI: 1.06–7.63), major morbidities (aOR = 2.99; 95% CI: 1.29–6.95), and severe neurological injury (aOR = 4.44, 95% CI: 1.56–12.59). Daily hospital costs were also higher in PPHN cases, with an average increase of 97.1 USD. Conclusions: In VLBW infants, PPHN was associated with a lower Apgar score and surfactant administration. PPHN was significantly linked to adverse outcomes, particularly mortality, major morbidities, and severe neurological injury. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Management of Neonatal Diseases)

11 pages, 440 KiB

Open AccessArticle

Mortality Risk Factors and Survival Outcomes in Infants with Persistent Pulmonary Hypertension of the Newborn

by Kokaew Chuaikaew, Gunlawadee Maneenil, Anucha Thatrimontrichai, Supaporn Dissaneevate and Manapat Praditaukrit

J. Clin. Med. 2025, 14(13), 4502; https://doi.org/10.3390/jcm14134502 - 25 Jun 2025

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Background/Objectives: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by increased pulmonary vascular resistance, resulting in severe hypoxemia. This study determined the factors associated with increased risk of mortality and survival rate in infants with PPHN. Methods: This retrospective study was conducted between 2010 and 2023. The risk factors for mortality were assessed by Cox’s proportional hazard models, and the Kaplan–Meier survival curve was used to analyze the survival rates. Results: This study included 233 neonates with PPHN. Gestational age (GA) less than 28 weeks (adjusted hazard ratio [AHR] = 5.46, 95% confidence interval [CI]: 2.25–13.24, p < 0.001), Small for gestational age (SGA) (AHR = 2.93, 95% confidence interval [CI]: 1.24–6.92, p = 0.026), acute kidney injury (AKI) (AHR = 2.48, 95% CI: 1.27–4.84, p = 0.01), pneumothorax (AHR = 3.03, 95% confidence interval [CI]: 1.48–6.21, p = 0.003), vasoactive-inotropic score (VIS) at 24 h of age (AHR = 1.0026, 95% confidence interval [CI]: 1.0004–1.005, p = 0.026), and score for neonatal acute physiology II (SNAP-II) ≥ 43 (AHR = 4.03, 95% CI: 1.66–9.77, p = 0.005) were associated with an increased risk of mortality. The overall survival rate was 82.4%; it rose from 63.8% to 87.1% after inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) were introduced (p < 0.001). The cumulative survival rates at the end of the 30 days were 62.1% (95% CI: 49.0–78.7) in the Pre-iNO era and 87.5% (95% CI: 82.7–92.6) in the Post-iNO/ECMO era, respectively (p < 0.001). Conclusions: GA less than 28 weeks, SGA, AKI, pneumothorax, high VIS and SNAP-II scores were associated with mortality in infants with PPHN. The improvement in the survival rate was related to the provision of advanced care, including iNO and ECMO therapy. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Management of Neonatal Diseases)

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13 pages, 236 KiB

Open AccessArticle

Changes in the Incidence and Severity of NEC over the Last Decade: A Single-Center Study

by Noa Ofek Shlomai, Meshy Tayeb, Rawan Abu Omar and Smadar Eventov Friedman

J. Clin. Med. 2025, 14(10), 3551; https://doi.org/10.3390/jcm14103551 - 19 May 2025

Cited by 1 | Viewed by 723

Abstract

Background: Necrotizing enterocolitis is the leading gastrointestinal cause of morbidity and mortality in neonatal intensive care units. Despite advancements in neonatal care, the incidence of NEC remains unchanged. This study evaluated trends in NEC incidence and severity over the past decade and identified associated risk factors in our NICU population. Methods: This was a retrospective cohort study comparing the prevalence and severity of NEC among VLBW infants born before 32 weeks of gestation across the following two periods: 2012–2016 and 2017–2021. Clinical data were extracted from medical records, with NEC diagnosis and grading based on the modified Bell’s criteria. Results: A total of 299 infants were included. Those born in the later period were significantly more preterm and had lower birth weights. While the overall NEC incidence increased in the later cohort, the rate of surgical NEC was lower. Logistic regression identified hemodynamic instability requiring pressor support, late-onset sepsis, and earlier gestational age as significant risk factors for NEC. Conclusions: Although the incidence of NEC was higher in the later cohort, its severity was lower compared to the earlier cohort. These findings suggest that advancements in neonatal care and feeding protocols may contribute to improved outcomes. Early NEC stages may represent alternative intestinal or systemic conditions warranting further research for better diagnosis. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Management of Neonatal Diseases)

14 pages, 922 KiB

Open AccessArticle

Postural Analysis in Ventral and Dorsal Decubitus Babies Using Deep Learning Techniques: A Protocol Study

by Sara Velázquez-Iglesias, Vidal Moreno-Rodilla, Belén Curto-Diego, Fátima Pérez-Robledo, Rocío Llamas-Ramos, Jose Ignacio Calvo-Arenillas and Inés Llamas-Ramos

J. Clin. Med. 2025, 14(9), 3096; https://doi.org/10.3390/jcm14093096 - 30 Apr 2025

Viewed by 568

Abstract

Background: The analysis of posture in the early stages of motor development has always been a subject of research and study. With the evolution of new technologies, the need arises to implement evaluation tools that allow an objective and effective assessment of postural control, which is intrinsically linked to motor development. Objectives: The objective was to analyze posture in babies from 0 to 6 months in ventral and dorsal decubitus using artificial intelligence to determine objective parameters of postural assessment. Methods: The study is an observational and cross-sectional study. The babies will be studied following a systematic kinesiological assessment, and the images of the babies will be taken, both in ventral and dorsal decubitus, on a glass platform, to analyze their posture by means of deep learning techniques. Results: Many authors have investigated posture in newborns. However, there is no method for assessing motor and postural development to determine the support area of typically developing babies. Artificial intelligence is postulated as an effective tool to objectively analyze the posture of babies and detect possible delays. Using deep learning techniques as a predictive tool, the support areas of each baby will be defined according to their age. Conclusions: Early detection of motor or postural developmental delays in babies to optimize effective treatment is of great importance. Artificial intelligence can help manage the complexity and growing volume of data in healthcare by knowing the correct postural control at each stage of a baby’s early months, while reducing the workload of healthcare professionals by facilitating decision-making. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Management of Neonatal Diseases)

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11 pages, 957 KiB

Open AccessArticle

The Effect on Extubation of Early vs. Late Definitive Closure of the Patent Ductus Arteriosus in Premature Infants: A Target Trial Emulation Using Electronic Health Records

by Zhou Du, Craig R. Wheeler, Michael Farias, Diego Porras, Philip T. Levy and Arin L. Madenci

J. Clin. Med. 2025, 14(6), 2072; https://doi.org/10.3390/jcm14062072 - 18 Mar 2025

Viewed by 742

Abstract

Background/Objectives: Premature infants are often referred for the definitive procedural closure of the patent ductus arteriosus (PDA) with the failure of, or contraindication to, pharmacotherapy and the inability to wean respiratory support. However, once this need is identified, the importance of expedited closure is unclear. The objective of this study was to compare the effect of the timing of definitive closure (i.e., surgical ligation or device occlusion) on early respiratory outcomes in premature infants. Method: We first specify a hypothetical randomized trial (the “target trial”) that would estimate the effect on extubation of early (0–4 days from referral) vs. late (5–14 days from referral) definitive PDA closure. We then emulate this target trial using a single-institution registry of premature infants (born <30 weeks or with a birth weight < 1500 g) who underwent the definitive closure of PDA between January 2014 and October 2023. Results: We identify 131 eligible infants. At the end of the follow-up, 70 and 38 infants were adherent to early and late PDA closure strategies, respectively. The cumulative incidence of extubation in the early group was higher than that in the late group until day 40 (maximum risk difference: 22 percentage points at day 13; 95% CI: −11 to 56). Outcomes were similar at the end of the 45-day follow-up period (risk difference: −1 percentage point; 95% CI: −46 to 42). Conclusions: The need for mechanical ventilation was equivalent between early and late PDA closure strategies at the end of a 45-day follow-up period although infants in the early intervention group were extubated sooner. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Management of Neonatal Diseases)

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Review

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13 pages, 1351 KiB

Open AccessReview

Ascites and Enterocolitis in a Preterm Infant with Acquired CMV Infection: A Case Study and Review of the Literature

by Keren Nathan, Ellen Bamberger, Daniel Dubin, Morya Shneider, Narmin Shehade Smair and Rasha Zoabi Safadi

J. Clin. Med. 2025, 14(16), 5854; https://doi.org/10.3390/jcm14165854 - 19 Aug 2025

Viewed by 185

Abstract

Postnatal cytomegalovirus (pCMV) infection is typically asymptomatic in term infants but poses significant risks to very preterm and very low birth weight (VLBW) infants. The primary mode of transmission of pCMV is breast milk from seropositive mothers. Here, we present the case of a 29-week preterm female who contracted pCMV and began to manifest symptoms at day of life (DOL) 50. She developed respiratory compromise, massive ascites, and was extremely ill. The patient was managed with ganciclovir (GCV), intravenous immunoglobulins (IVIG), and percutaneous drainage of the ascites. She gradually improved and was discharged after a 5-month neonatal intensive care unit (NICU) stay. After presenting the case, we review the clinical manifestations of pCMV, and particularly its less well-recognized gastrointestinal manifestations, including ascites. We then outline guidelines for treatment and prevention. Clinicians should consider pCMV in VLBW and extremely premature infants presenting with thrombocytopenia, colitis, or ascites, especially in the second and third months of life. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Management of Neonatal Diseases)

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17 pages, 296 KiB

Open AccessReview

Oxygen Saturation Targeting in the Neonatal Intensive Care Unit

by Faeq Almudares, Bheru Gandhi, Jonathan Davies, Xanthi Couroucli, Natalie Villafranco, Nidhy Paulose Varghese, Milenka Cuevas Guaman, Charleta Guillory and Binoy Shivanna

J. Clin. Med. 2025, 14(11), 3975; https://doi.org/10.3390/jcm14113975 - 4 Jun 2025

Viewed by 1785

Abstract

Oxygen (O₂) is vital for cellular development, function, proliferation, and repair, underscoring its critical role in organogenesis. Both hypoxia (reduced tissue O₂) and hyperoxia (excess tissue O₂), when prolonged, can trigger inflammation and oxidative stress, contributing to acute and long-term cardiopulmonary and neurodevelopmental morbidity. In sick neonates, immature defense mechanisms and coexisting morbidities demand nuanced and sometimes opposing strategies for O₂ saturation targets and therapeutic titration. Most current neonatal O₂ targeting guidelines are based on animal models or small clinical studies, resulting in recommendations with limited evidence. This narrative review aims to provide an updated overview of the physiological roles of O₂ in development, its delivery and consumption, approaches to O₂ saturation monitoring, and therapeutic targeting in neonates under both normal and pathological conditions. We also highlight key knowledge gaps and propose directions for future research on neonatal O₂ saturation targeting. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Management of Neonatal Diseases)

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