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Oscillatory Blood Pressure Values in Newborn Infants: Observational Data Over Gestational Ages.

Hillman NH, Williams HL, Petersen RY

Neonatology · 2025 · PMID 39496234 · Publisher ↗

INTRODUCTION: Normative blood pressure (BP) values on preterm infants exist but are based on small cohorts of infants. Utilizing electronic medical records (EMR), we can explore earlier gestational ages (GA) and follow t... INTRODUCTION: Normative blood pressure (BP) values on preterm infants exist but are based on small cohorts of infants. Utilizing electronic medical records (EMR), we can explore earlier gestational ages (GA) and follow their progression to 40 weeks corrected gestational age (CGA). METHODS: A retrospective cohort study of infants within the SSM Health System from July 1, 2013 through June 30, 2023. Infants born at >22 0/7 weeks but <41 weeks GA were included if any BP measurements existed (n = 29,323 infants, 1.4 million BPs). Data were extracted electronically from EMR using Microsoft SQL. Systolic BP (SBP), mean arterial pressures (MAP), and diastolic BP (DBP) were determined for each week of life from birth and percentile ranges (1st to 99th) for infants alive at CGA, and BP patterns for GA determined. RESULTS: Percentiles for SBP, DBP, and MAP are provided. There is a rapid increase in BP at all gestations during the first 2 weeks, thus BP values are higher at any CGA in infants born at an earlier GA than infants born at that GA. For MAP values between the 5th and 10th percentile, the GA is appropriate for first week and then use CGA + 5 mm Hg. After the first week, 2.8 X CGA is between 90 and 95 percentile for SBP. CONCLUSIONS: The BP is dependent on the GA at birth and the CGA when it is measured. SBP, MAP, and DBP all increase rapidly in the 2 weeks of life prior to a gradual increase over time.

Optimal Strategies for Screening Common Birth Defects in Children of Low- and Middle-Income Countries: A Systematic Review.

Zaki U, Qazi SH, Shamim U … +3 more , Fatima S, Das JK, Bhutta ZA

Neonatology · 2025 · PMID 39462499 · Full text

INTRODUCTION: Congenital anomalies are one of the major causes of the global burden of diseases, and low- and middle-income countries (LMICs) are disproportionately affected. This review assesses the prenatal and postnat... INTRODUCTION: Congenital anomalies are one of the major causes of the global burden of diseases, and low- and middle-income countries (LMICs) are disproportionately affected. This review assesses the prenatal and postnatal screening methods and compares the prevalence of major congenital anomalies in LMICs. METHODOLOGY: We conducted a systematic search in MEDLINE/PubMed, CINAHL, Cochrane databases of systematic reviews, clinical trials.gov for relevant studies using Medical Subject Headings and keywords. We categorized the studies into different systems and screening methods depending on the time the tests were conducted (prenatal or postnatal). The studies were then subjected to detailed descriptive analysis. RESULTS: A total of 59 studies were selected for analysis; these focused on screening methods for congenital anomalies and compared their prevalence with regards to different systems. The most common screening techniques both prenatal and postnatal included antenatal ultrasound, fetal echocardiography, pulse oximetry, and clinical examination. The most common congenital abnormalities involved the central nervous system (neural tube defects) and musculoskeletal (clubfoot), followed by gastrointestinal (omphalocele and gastroschisis) and cardiovascular (structural heart defect). Overall, different systems had varying prevalences of different birth defects, ranging from 0.28 to 8.5%. In contrast, the prevalence of musculoskeletal system disorders varied from 1.01% to 3.96%, in the cardiovascular system from 0.57% to 10.4%, and in the urogenital group from 0.83% to 5.9%. CONCLUSION: The review highlights the lack of screening programs and studies, especially in the primary and secondary care settings in LMICs, and limited studies do indicate a high burden of various congenital anomalies. There is a need for guidelines and programs in global maternal and child health programs to include timely screening and management of common birth defects in LMICs. INTRODUCTION: Congenital anomalies are one of the major causes of the global burden of diseases, and low- and middle-income countries (LMICs) are disproportionately affected. This review assesses the prenatal and postnatal screening methods and compares the prevalence of major congenital anomalies in LMICs. METHODOLOGY: We conducted a systematic search in MEDLINE/PubMed, CINAHL, Cochrane databases of systematic reviews, clinical trials.gov for relevant studies using Medical Subject Headings and keywords. We categorized the studies into different systems and screening methods depending on the time the tests were conducted (prenatal or postnatal). The studies were then subjected to detailed descriptive analysis. RESULTS: A total of 59 studies were selected for analysis; these focused on screening methods for congenital anomalies and compared their prevalence with regards to different systems. The most common screening techniques both prenatal and postnatal included antenatal ultrasound, fetal echocardiography, pulse oximetry, and clinical examination. The most common congenital abnormalities involved the central nervous system (neural tube defects) and musculoskeletal (clubfoot), followed by gastrointestinal (omphalocele and gastroschisis) and cardiovascular (structural heart defect). Overall, different systems had varying prevalences of different birth defects, ranging from 0.28 to 8.5%. In contrast, the prevalence of musculoskeletal system disorders varied from 1.01% to 3.96%, in the cardiovascular system from 0.57% to 10.4%, and in the urogenital group from 0.83% to 5.9%. CONCLUSION: The review highlights the lack of screening programs and studies, especially in the primary and secondary care settings in LMICs, and limited studies do indicate a high burden of various congenital anomalies. There is a need for guidelines and programs in global maternal and child health programs to include timely screening and management of common birth defects in LMICs.

Fifteen Years of Neonatal Therapeutic Hypothermia: Clinical Trends Show Unchanged Post-Rewarming Outcomes despite Reduction in Hypoxic-Ischemic Encephalopathy Severity.

van Oldenmark BO, van Steenis A, de Vries LS … +2 more , Groenendaal F, Steggerda SJ

Neonatology · 2025 · PMID 39437752 · Publisher ↗

INTRODUCTION: Hypoxic-ischemic encephalopathy (HIE) affects 1-2 per 1,000 births and is associated with mortality and long-term neurodevelopmental challenges. At present, therapeutic hypothermia (TH) is the only neuropro... INTRODUCTION: Hypoxic-ischemic encephalopathy (HIE) affects 1-2 per 1,000 births and is associated with mortality and long-term neurodevelopmental challenges. At present, therapeutic hypothermia (TH) is the only neuroprotective intervention for these infants. This study examines whether HIE severity, clinical management during TH, and post-rewarming outcomes have changed since its introduction 15 years ago. METHODS: Neonatal characteristics, HIE severity, management during TH, and post-rewarming MRI of all infants with HIE undergoing TH between 2008 and 2023 were compared across three five-year epochs. Linear regression was used to estimate annual changes over time. RESULTS: In total, 252 infants underwent TH. Median gestational age (39.5 weeks), birth weight (3,376 g), and time to start TH (4.25 h) remained stable over time. Apgar score at 5 min (p = 0.031) and lowest pH <1 h postpartum (p = 0.020) increased over time. Thompson score at 1-3 h decreased across epochs (p = 0.046). There was an increase in percentage with normal-mild aEEG background patterns on admission (p = 0.041) and a decrease in aEEG-confirmed seizures (p < 0.001) and antiseizure medication (p < 0.001). Inotropic support decreased (p = 0.007), and use of invasive mechanical ventilation decreased over the last 5 years. Mortality (28.6%) and post-rewarming composite adverse outcome (i.e., neonatal mortality and/or adverse MRI score) (37.9%) remained unchanged. Number of infants seen at 2-year follow-up increased (p < 0.001). CONCLUSION: Over the last 15 years, we treated more infants with milder HIE, as indicated by lower Thompson and milder aEEG scores, and the need for invasive cardiorespiratory support declined. However, there were no improvements in composite adverse outcome (mortality and/or adverse MRI score).

Neurodevelopmental Changes and Postnatal Growth in the First 3 Years of Extremely Preterm Infants.

Matsunaga Y, Inoue H, Miyauchi Y … +6 more , Watabe T, Yasuoka K, Sawano T, Ochiai M, Sakai Y, Ohga S

Neonatology · 2025 · PMID 39389049 · Publisher ↗

INTRODUCTION: Infants born extremely preterm are at high risk for neurodevelopmental problems. However, their neurodevelopment exhibits a variety of trajectories. This study aimed to investigate the association between c... INTRODUCTION: Infants born extremely preterm are at high risk for neurodevelopmental problems. However, their neurodevelopment exhibits a variety of trajectories. This study aimed to investigate the association between changes in neurodevelopmental outcomes and clinical characteristics among extremely preterm infants. METHODS: This is a retrospective study of surviving children born at gestational age 22-28 weeks in Kyushu University Hospital between 2010 and 2020. We collected perinatal and post-discharge data and investigated the association between clinical characteristics and changes in developmental quotient (DQ) scores between 1.5 and 3 years of corrected age. RESULTS: Out of the 179 eligible extremely preterm infants, 115 (64%) underwent neurological evaluations at 1.5 and 3 years of corrected age. Among them, 33 (29%) showed improvement in their DQ scores (+10 or more), 62 (54%) showed no change (-9 to +9), and 20 (17%) showed a decline (-10 or less). Gestational age, birth weight, and perinatal complications during the NICU stay did not affect individual changes in DQ scores. Multivariable analysis revealed that greater growth in height until age 3 years was a significant predictor of increasing DQ scores, while male sex and having siblings had a negative effect on changes in the DQ scores. CONCLUSION: We first demonstrate clinical data conceptualizing that growth in height, sex, and sibling status, rather than perinatal complications, are biologically linked with favorable or unfavorable neurodevelopmental changes of extremely preterm infants during the first 3 years of life.

Erratum.

Neonatology · 2025 · PMID 39378857 · Publisher ↗

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"Flux in the Belly:" A History of Infantile Gastroenteritis.

Obladen M

Neonatology · 2025 · PMID 39321761 · Publisher ↗

BACKGROUND: Although a major cause of infant mortality for centuries, little research was done on the causes of infants' diarrhea. Artificial feeding, teething, and summer heat were believed to cause the severe disease t... BACKGROUND: Although a major cause of infant mortality for centuries, little research was done on the causes of infants' diarrhea. Artificial feeding, teething, and summer heat were believed to cause the severe disease that spared breastfed infants. SUMMARY: Since antiquity, infants' digestive disorders were termed dyspepsia, flux of the belly, diarrhea, gastroenteritis, watery gripes, the runs, dysentery, or cholera, without definitions. Alois Bednar discerned 3 grades (dyspepsia, diarrhea, and cholera) of the same disease. Infants' neurologic symptoms were interpreted as alimentary toxicosis. Chronic diarrhea caused emaciation and dehydration. In 1950, Laurence Finberg found diarrhea with hypernatremia causing cerebral damage. Seasonal influence was known since Hippocrates. Baudelocque recommended obtaining infant milk fresh from the cow because it decomposes in the summer heat. In the cities, summer diarrhea caused a third of total infant mortality. Physicians debated whether heat acted directly on the infant or spoiled the food. The discovery of microorganisms in the 1860s revolutionized medical understanding. However, influential researchers such as Adalbert Czerny classified nutritional disturbances by assumed pathogenesis ("ex alimentation, ex infection, ex constitution"), but denied the possibility of bacterial infection via milk. Heating baby food, practiced for centuries, was introduced in Denmark, Sweden, and France, whereas in Britain and Germany, professional and public debate on pasteurization persisted. KEY MESSAGES: It took half a century to implement effective hygienic measures once the bacterial origin became known. Foodborne infection was rejected, and the prejudice that raw milk possesses essential "living" properties, adopted by influential scientists, contributed to delaying pasteurization.

No Short-Term Effect of Low-Dose Nicotine on Inflammation after Global Hypoxia in Newborn Piglets.

Volstad KB, Pripp AH, Ludviksen JA … +4 more , Stiris T, Saugstad OD, Mollnes TE, Andresen JH

Neonatology · 2025 · PMID 39317175 · Full text

INTRODUCTION: Perinatal asphyxia initiates cytokine release and complement activation with risk of brain damage. We assessed the effect of nicotine on innate immunity and hypothesized that nicotine infusion in a newborn... INTRODUCTION: Perinatal asphyxia initiates cytokine release and complement activation with risk of brain damage. We assessed the effect of nicotine on innate immunity and hypothesized that nicotine infusion in a newborn piglet model of asphyxia would decrease the immune response and be neuroprotective. METHODS: Newborn piglets (n = 41) were randomized to one of three groups after hypoxia: two groups receiving nicotine, (1) 18 µg/kg/h (n = 17), (2) 46 µg/kg/h (n = 15), and (3) control group receiving saline (n = 9). C3a, IL-6, TNF, and IL-10 were measured in plasma and IL-6 and IL-8 in microdialysis fluid from cerebral periventricular white matter, using immuno-assays. RESULTS: Plasma C3a and IL-6 increased significantly from start to end hypoxia (mean 4.4 ± 0.55 to 5.6 ± 0.71 ng/mL and 1.66 ± 1.04 to 2.68 ± 0.71 pg/mL, respectively), while IL-10 and TNF increased significantly after 4 h (mean 1.4 ± 1.08 to 2.9 ± 1.87 and 3.3 ± 0.67 to 4.0 ± 0.58 pg/mL, respectively) (p < 0.001 for all). IL-6 increased significantly (p < 0.001) in microdialysis samples from end hypoxia to end experiment (mean 0.65 ± 0.88 to 2.78 ± 1.84 ng/mL). No significant differences were observed between the nicotine groups and the control group neither in plasma nor in microdialysis samples. CONCLUSION: Hypoxia leads to rapid release of cytokines in plasma and cerebral microdialysis fluid, and complement activation measured on C3a. However, low-dose nicotine administration did not affect the immune response. INTRODUCTION: Perinatal asphyxia initiates cytokine release and complement activation with risk of brain damage. We assessed the effect of nicotine on innate immunity and hypothesized that nicotine infusion in a newborn piglet model of asphyxia would decrease the immune response and be neuroprotective. METHODS: Newborn piglets (n = 41) were randomized to one of three groups after hypoxia: two groups receiving nicotine, (1) 18 µg/kg/h (n = 17), (2) 46 µg/kg/h (n = 15), and (3) control group receiving saline (n = 9). C3a, IL-6, TNF, and IL-10 were measured in plasma and IL-6 and IL-8 in microdialysis fluid from cerebral periventricular white matter, using immuno-assays. RESULTS: Plasma C3a and IL-6 increased significantly from start to end hypoxia (mean 4.4 ± 0.55 to 5.6 ± 0.71 ng/mL and 1.66 ± 1.04 to 2.68 ± 0.71 pg/mL, respectively), while IL-10 and TNF increased significantly after 4 h (mean 1.4 ± 1.08 to 2.9 ± 1.87 and 3.3 ± 0.67 to 4.0 ± 0.58 pg/mL, respectively) (p < 0.001 for all). IL-6 increased significantly (p < 0.001) in microdialysis samples from end hypoxia to end experiment (mean 0.65 ± 0.88 to 2.78 ± 1.84 ng/mL). No significant differences were observed between the nicotine groups and the control group neither in plasma nor in microdialysis samples. CONCLUSION: Hypoxia leads to rapid release of cytokines in plasma and cerebral microdialysis fluid, and complement activation measured on C3a. However, low-dose nicotine administration did not affect the immune response.

Delivery Room Handling of the Newborn: Filling the Gaps.

Saugstad OD, Kapadia V, Vento M

Neonatology · 2024 · PMID 39308394 · Full text

BACKGROUND: Newborn resuscitation algorithms have since the turn of the century been more evidence-based. In this review, we discuss the development of American Heart Association (AHA) and the International Liaison Commi... BACKGROUND: Newborn resuscitation algorithms have since the turn of the century been more evidence-based. In this review, we discuss the development of American Heart Association (AHA) and the International Liaison Committee on Resuscitation (ILCOR)'s algorithm for newborn resuscitation from 1992-2024. We have also aimed to identify the remaining gaps in non-evidenced practice. SUMMARY: Of the 22 procedures reviewed in the 2020 ILCOR recommendations, the evidence was either low, very low, or non-existing. The strength of recommendation is weak or non-existing for most topics discussed. Several knowledge gaps are also summarized. The special challenge for low- and middle-income countries (LMIC) is discussed. KEY MESSAGES: Newborn resuscitation is still not evidence-based, although great progress has been achieved the recent years. We have identified several knowledge gaps which should be prioritized in future research. The challenge of obtaining evidence-based knowledge from LMIC should be focused on in future research.

Association between Congenital Anomalies and Late-Onset Bacterial Infections in Neonates Admitted to Neonatal Intensive Care Units in Australia and New Zealand: A Population-Based Cohort Study.

Chughtai AA, Spotswood N, Strunk T … +6 more , Parmar T, Schindler T, Popat H, Chow SSW, Lui K, Australian and New Zealand Neonatal Network

Neonatology · 2025 · PMID 39299217 · Full text

INTRODUCTION: Compromised neonatal intensive care unit neonates are at risk of acquiring late-onset infections (late-onset sepsis [LOS]). Neonates born with congenital anomalies (CAs) could have an additional LOS risk. M... INTRODUCTION: Compromised neonatal intensive care unit neonates are at risk of acquiring late-onset infections (late-onset sepsis [LOS]). Neonates born with congenital anomalies (CAs) could have an additional LOS risk. METHODS: Utilising the population-based Australian and New Zealand Neonatal Network data from 2007 to 2017, bacterial LOS rates were determined in very preterm (VPT, <32 week), moderately preterm (MPT, 32-36 weeks), and term (FT, 37-41 weeks) neonates with or without CA. Stratified by major surgery, the association between CA and bacterial LOS was evaluated. RESULTS: Of 102,808 neonates, 37.7%, 32.8%, and 29.6% were born VPT, MPT, and FT, respectively. Among these, 3.4% VPT, 7.5% MPT, and 16.2% FT neonates had CA. VPT neonates had the highest LOS rate (11.1%), compared to MPT (1.8%) and FT (1.8%) neonates. LOS rates were higher in CA neonates than those without (8.2% versus 5.1% adjusted relative risk [aRR] 1.67, 95% confidence interval [CI]: 1.45-1.92). Neonates with surgery had a higher LOS rate (14.2%) than neonates without surgery (4.4%, p < 0.001). Among the neonates without surgery, CA neonates had consistently higher LOS rates than those without CA (VPT 14.3% vs. 9.6% [aRR 1.32, 95% CI: 1.11-1.57]; MPT 4% vs. 0.9% [aRR 4.45, 95% CI: 3.23-6.14]; and FT 2% vs. 0.7% [aRR 2.87, 95% CI: 1.97-4.18]). For the neonates with surgery, CAs were not associated with additional LOS risks. CONCLUSION: Overall, we reported higher rates of LOS in neonates with CA compared to those without CA. Regardless of gestation, CA was associated with an increased LOS risk among non-surgical neonates. Optimisation of infection prevention strategies for CA neonates should be explored. Future studies are needed to evaluate if the infection risk is caused by CA or associated complications. INTRODUCTION: Compromised neonatal intensive care unit neonates are at risk of acquiring late-onset infections (late-onset sepsis [LOS]). Neonates born with congenital anomalies (CAs) could have an additional LOS risk. METHODS: Utilising the population-based Australian and New Zealand Neonatal Network data from 2007 to 2017, bacterial LOS rates were determined in very preterm (VPT, <32 week), moderately preterm (MPT, 32-36 weeks), and term (FT, 37-41 weeks) neonates with or without CA. Stratified by major surgery, the association between CA and bacterial LOS was evaluated. RESULTS: Of 102,808 neonates, 37.7%, 32.8%, and 29.6% were born VPT, MPT, and FT, respectively. Among these, 3.4% VPT, 7.5% MPT, and 16.2% FT neonates had CA. VPT neonates had the highest LOS rate (11.1%), compared to MPT (1.8%) and FT (1.8%) neonates. LOS rates were higher in CA neonates than those without (8.2% versus 5.1% adjusted relative risk [aRR] 1.67, 95% confidence interval [CI]: 1.45-1.92). Neonates with surgery had a higher LOS rate (14.2%) than neonates without surgery (4.4%, p < 0.001). Among the neonates without surgery, CA neonates had consistently higher LOS rates than those without CA (VPT 14.3% vs. 9.6% [aRR 1.32, 95% CI: 1.11-1.57]; MPT 4% vs. 0.9% [aRR 4.45, 95% CI: 3.23-6.14]; and FT 2% vs. 0.7% [aRR 2.87, 95% CI: 1.97-4.18]). For the neonates with surgery, CAs were not associated with additional LOS risks. CONCLUSION: Overall, we reported higher rates of LOS in neonates with CA compared to those without CA. Regardless of gestation, CA was associated with an increased LOS risk among non-surgical neonates. Optimisation of infection prevention strategies for CA neonates should be explored. Future studies are needed to evaluate if the infection risk is caused by CA or associated complications.

Neonatal Linear Immunoglobulin A Bullous Dermatosis: A Critical Case Recovering after Prompt Recognition, Intensive Management, and Breastfeeding Interruption - A Case Report.

Papasavva D, Dosso L, Morren MA … +7 more , Fontao L, Bruschi L, Gorostidi F, Ferry T, Guenova E, Fischer Fumeaux CJ, Joye S

Neonatology · 2025 · PMID 39278203 · Full text

INTRODUCTION: Neonatal linear immunoglobulin A (IgA) bullous dermatosis (NLABD) is a rare, life-threatening, mucocutaneous bullous disorder. The pathogenesis and optimal treatment remain poorly defined and raise critical... INTRODUCTION: Neonatal linear immunoglobulin A (IgA) bullous dermatosis (NLABD) is a rare, life-threatening, mucocutaneous bullous disorder. The pathogenesis and optimal treatment remain poorly defined and raise critical clinical challenges. CASE PRESENTATION: We present a case of a full-term female infant with severe cutaneous and respiratory symptoms due to NLABD. Diagnosis was confirmed by immunofluorescence on the infant's skin biopsy, while IgAs directed against the basement membrane of the skin and mucosa were identified in the mother's milk. The infant fully recovered after nearly 8 weeks of intensive multidisciplinary care, including non-invasive ventilation, nutritional support, wound care, systemic corticoid treatment, and breastfeeding discontinuation. CONCLUSION: This case underscores the importance of timely adequate diagnosis and management of this rare and serious condition. Moreover, it adds novel evidence documenting the presence of pathogenic IgAs in breastmilk. INTRODUCTION: Neonatal linear immunoglobulin A (IgA) bullous dermatosis (NLABD) is a rare, life-threatening, mucocutaneous bullous disorder. The pathogenesis and optimal treatment remain poorly defined and raise critical clinical challenges. CASE PRESENTATION: We present a case of a full-term female infant with severe cutaneous and respiratory symptoms due to NLABD. Diagnosis was confirmed by immunofluorescence on the infant's skin biopsy, while IgAs directed against the basement membrane of the skin and mucosa were identified in the mother's milk. The infant fully recovered after nearly 8 weeks of intensive multidisciplinary care, including non-invasive ventilation, nutritional support, wound care, systemic corticoid treatment, and breastfeeding discontinuation. CONCLUSION: This case underscores the importance of timely adequate diagnosis and management of this rare and serious condition. Moreover, it adds novel evidence documenting the presence of pathogenic IgAs in breastmilk.

Less Invasive Surfactant Administration for Preterm Infants - State of the Art.

Härtel C, Kribs A, Göpel W … +2 more , Dargaville P, Herting E

Neonatology · 2024 · PMID 39226881 · Full text

BACKGROUND: Less invasive surfactant administration (LISA) has become the preferred method of surfactant administration for spontaneously breathing babies on continuous positive airway pressure (CPAP). SUMMARY: The devel... BACKGROUND: Less invasive surfactant administration (LISA) has become the preferred method of surfactant administration for spontaneously breathing babies on continuous positive airway pressure (CPAP). SUMMARY: The development of LISA followed the need to combine CPAP and surfactant replacement as mainstay treatment options for respiratory distress syndrome, thereby avoided exposure to positive pressure ventilation. KEY MESSAGES: This review summarises the current knowns and unknowns of LISA including the physiological concept, its relevance for short-term and long-term outcomes and the challenges for practical implementation of LISA as part of a less invasive respiratory care bundle. Further, we provide an update of the evidence on alternatives to LISA, for example, nebulised surfactant administration, pharyngeal deposition of surfactant and delivery via supraglottic airway.

Physiological-Based Cord Clamping: When the Baby Is Ready for Clamping.

Te Pas AB, Knol R, Lopriore E … +2 more , van den Akker TH, Hooper SB

Neonatology · 2024 · PMID 39197438 · Full text

BACKGROUND: The timing of cord clamping has become a focal point for neonatal caregivers due to the promising outcomes associated with delayed cord clamping, which is a simple and cost-effective method to enhance the sur... BACKGROUND: The timing of cord clamping has become a focal point for neonatal caregivers due to the promising outcomes associated with delayed cord clamping, which is a simple and cost-effective method to enhance the survival and well-being of preterm infants. While initially the rationale behind delaying clamping was to facilitate increased placental transfusion, research has unveiled additional hemodynamic benefits. SUMMARY: Experimental studies have demonstrated improved circulatory transition when clamping is postponed until the lungs are adequately aerated. This suggests that infants requiring assistance during the transition phase may benefit from stabilization while still attached to the cord. The Aeration, Breathing, and then Clamping (ABC) project aimed to translate these experimental findings into clinical practice. KEY MESSAGE: In this review, we will discuss the insights gained and lessons learned from the project's implementation.

Inborn Errors of Immunity in Early Childhood: Essential Insights for the Neonatologist.

Dirks J, Wölfl M, Speer CP … +2 more , Härtel C, Morbach H

Neonatology · 2024 · PMID 39182489 · Publisher ↗

BACKGROUND: Inborn errors of immunity (IEI), formerly referred to as primary immunodeficiencies, manifest with a wide range of symptoms such as increased susceptibility to infections, immune dysregulation, and autoinflam... BACKGROUND: Inborn errors of immunity (IEI), formerly referred to as primary immunodeficiencies, manifest with a wide range of symptoms such as increased susceptibility to infections, immune dysregulation, and autoinflammation. Although most cases manifest in childhood, onset during the neonatal period is rare but potentially critical. SUMMARY: In this review, we discuss the diverse clinical presentations of IEI and the specific challenges they pose to neonatologists. Rather than detailing every molecular defect, we focus on common clinical scenarios in neonates and young infants, providing practical diagnostic strategies to ensure timely and effective therapeutic interventions. KEY MESSAGES: Clinical presentations of IEI in neonates may include delayed separation of the umbilical cord, skin rashes such as eczema and erythroderma, and recurrent episodes of inflammation. We also highlight immunological emergencies that require urgent medical attention, such as hyperinflammatory activity mimicking acute neonatal liver failure, sometimes seen in hemophagocytic lymphohistiocytosis. We also discuss appropriate medical action in the case of a positive newborn screening for severe T-cell defects. Early medical intervention in such circumstances may significantly improve outcomes.

Non-Invasive Ventilatory Support in Preterm Neonates in the Delivery Room and the Neonatal Intensive Care Unit: A Short Narrative Review of What We Know in 2024.

Roehr CC, Farley HJ, Mahmoud RA … +1 more , Ojha S

Neonatology · 2024 · PMID 39173610 · Full text

BACKGROUND: Guidelines recommend non-invasive ventilatory (NIV) support as first-line respiratory support mode in preterm infants as NIV is superior to intubation and mechanical ventilation in preventing death or broncho... BACKGROUND: Guidelines recommend non-invasive ventilatory (NIV) support as first-line respiratory support mode in preterm infants as NIV is superior to intubation and mechanical ventilation in preventing death or bronchopulmonary dysplasia. However, with an ever-expanding variety of NIV modes available, there is much debate about which NIV modality should ideally be used, how, and when. The aims of this work were to summarise the evidence on different NIV modalities for both primary and secondary respiratory support: nCPAP, nasal high-flow therapy (nHFT), and nasal intermittent positive airway pressure ventilation (nIPPV), bi-level positive airway pressure (BiPAP), nasal high-frequency oscillatory ventilation (nHFOV), and nasally applied, non-invasive neurally adjusted ventilatory assist (NIV-NAVA) modes, with particular focus on their use in preterm infants. SUMMARY: This is a narrative review with reference to published guidelines by European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update. nCPAP is currently the most commonly used primary and secondary NIV modality for premature infants. However, there is increasing evidence on the superiority of nIPPV over nCPAP. No beneficial effect was found for BiPAP over nCPAP. For the use of nHFT, nHFOV, and NIV-NAVA, more studies are needed to establish their place in neonatal respiratory care. KEY MESSAGES: The superiority of nIPPV over nCPAP needs to be confirmed by contemporaneous trials comparing nCPAP to nIPPV at comparable mean airway pressures. Future trials should study NIV modalities in preterm infants with comparable respiratory pathology and indications, at comparable pressure settings and with different modes of synchronisation. Importantly, future trials should not exclude infants of the smallest gestational ages.

Neonatal Adverse Outcomes among Hospital Livebirths in Canada: A National Retrospective Study.

Nelson CRM, Ray JG, Auger N … +6 more , Moore AM, Little J, Murphy PA, Van den Hof M, Shah PS, Canadian Perinatal Surveillance System, Public Health Agency of Canada

Neonatology · 2025 · PMID 39173602 · Full text

INTRODUCTION: In Canada, newborn morbidity far surpasses mortality. The neonatal adverse outcome indicator (NAOI) summarizes neonatal morbidity, but Canadian trend data are lacking. METHODS: This Canada-wide retrospectiv... INTRODUCTION: In Canada, newborn morbidity far surpasses mortality. The neonatal adverse outcome indicator (NAOI) summarizes neonatal morbidity, but Canadian trend data are lacking. METHODS: This Canada-wide retrospective cross-sectional study included hospital livebirths between 24 and 42 weeks' gestation, from 2013 to 2022. Data were obtained from the Canadian Institute of Health Information's Discharge Abstract Database, excluding Quebec. The NAOI included 15 newborn complications (e.g., birth trauma, intraventricular hemorrhage, or respiratory failure) and seven interventions (e.g., resuscitation by intubation and/or chest compressions), adapted from Australia's NAOI. Rates of NAOI were calculated by gestational age. Unadjusted rate ratios (RR) and 95% confidence interval (CI) were calculated for neonatal mortality, neonatal intensive care unit (NICU) admission, and extended hospital stay, each in relation to the number of NAOI components present (0, 1, 2, 3, 4, or ≥5). RESULTS: Among 2,821,671 newborns, the NAOI rate was 7.6%. NAOI increased from 7.3% in 2013 to 8.0% in 2022 (p < 0.01). NAOI prevalence was highest in the most preterm infants. Compared to no NAOI, RRs (95% CI) for mortality were 8.5 (7.6-9.5) with 1, 118.1 (108.4-128.4) with 3, and 395.3 (367.2-425.0) with ≥5 NAOI components. Respective RRs for NICU admission were 6.7 (6.6-6.7), 11.2 (10.9-11.3), and 11.9 (11.6-12.2), and RR for extended hospital stay were 6.6 (6.4-6.7), 12.2 (11.7-12.7), and 26.4 (25.2-27.5). International comparison suggested that Canada had a higher prevalence of NAOI. CONCLUSION: The Canadian NAOI captures neonatal morbidity using hospitalization data and is associated with neonatal mortality, NICU admission, and extended hospital stay. Newborn morbidity may be on the rise in recent years. INTRODUCTION: In Canada, newborn morbidity far surpasses mortality. The neonatal adverse outcome indicator (NAOI) summarizes neonatal morbidity, but Canadian trend data are lacking. METHODS: This Canada-wide retrospective cross-sectional study included hospital livebirths between 24 and 42 weeks' gestation, from 2013 to 2022. Data were obtained from the Canadian Institute of Health Information's Discharge Abstract Database, excluding Quebec. The NAOI included 15 newborn complications (e.g., birth trauma, intraventricular hemorrhage, or respiratory failure) and seven interventions (e.g., resuscitation by intubation and/or chest compressions), adapted from Australia's NAOI. Rates of NAOI were calculated by gestational age. Unadjusted rate ratios (RR) and 95% confidence interval (CI) were calculated for neonatal mortality, neonatal intensive care unit (NICU) admission, and extended hospital stay, each in relation to the number of NAOI components present (0, 1, 2, 3, 4, or ≥5). RESULTS: Among 2,821,671 newborns, the NAOI rate was 7.6%. NAOI increased from 7.3% in 2013 to 8.0% in 2022 (p < 0.01). NAOI prevalence was highest in the most preterm infants. Compared to no NAOI, RRs (95% CI) for mortality were 8.5 (7.6-9.5) with 1, 118.1 (108.4-128.4) with 3, and 395.3 (367.2-425.0) with ≥5 NAOI components. Respective RRs for NICU admission were 6.7 (6.6-6.7), 11.2 (10.9-11.3), and 11.9 (11.6-12.2), and RR for extended hospital stay were 6.6 (6.4-6.7), 12.2 (11.7-12.7), and 26.4 (25.2-27.5). International comparison suggested that Canada had a higher prevalence of NAOI. CONCLUSION: The Canadian NAOI captures neonatal morbidity using hospitalization data and is associated with neonatal mortality, NICU admission, and extended hospital stay. Newborn morbidity may be on the rise in recent years.

Lack of Blinding May Affect Objective Outcomes in Trials on Neonatal Ventilation.

Bruschettini M, Schmölzer GM, Lai NM … +3 more , Mitra S, Davis PG, Soll RF

Neonatology · 2024 · PMID 39154644 · Publisher ↗

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Diagnostic Utility of Preserved Dried Umbilical Cord Polymerase Chain Reaction in Intrauterine Herpes Simplex Virus Infection: A Case Report and Literature Review.

Tsuda Y, Matsushige T, Inoue H … +6 more , Hoshide M, Hamano H, Hasegawa K, Moriuchi M, Moriuchi H, Hasegawa S

Neonatology · 2025 · PMID 39137732 · Publisher ↗

INTRODUCTION: Intrauterine herpes simplex virus (HSV) infection is uncommon and challenging to diagnose, requiring detection of HSV in skin lesions within 48 h post-birth. CASE PRESENTATION: A preterm female infant prese... INTRODUCTION: Intrauterine herpes simplex virus (HSV) infection is uncommon and challenging to diagnose, requiring detection of HSV in skin lesions within 48 h post-birth. CASE PRESENTATION: A preterm female infant presented with the typical triad of blisters, microcephaly, and chorioretinitis, but the initial diagnostic approach was elusive due to negative results for TORCH pathogens from vesicles/serum. Referred at 7 months for developmental delay and epilepsy, her brain imaging showed calcification and cortical dysplasia. Polymerase chain reaction (PCR) of her preserved dried umbilical cord detected HSV-2 DNA, diagnosing intrauterine HSV infection. HSV-2 was later found in relapsed blisters at 8 months but not in cerebrospinal fluid or brain tissue. A literature review identified 104 congenital/intrauterine HSV cases; 28.8% presented the typical triad, and 50% were diagnosed using specimens collected 48 h post-birth. CONCLUSION: This case marks the first retrospective diagnosis of intrauterine HSV infection via PCR on preserved umbilical cord, underscoring its diagnostic value.

Peripheral Vein Cannulation in Neonates: Is Skin Transillumination the Way Forward?

Pillai A, Sidaraddi S, Ghawade AP … +1 more , Moralwar P

Neonatology · 2025 · PMID 39134003 · Publisher ↗

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Intermediate vs. High Oxygen Saturation Targets in Preterm Infants: A National Cohort Study.

Taylor RS, Singh B, Mukerji A … +7 more , Dorling J, Alvaro R, Lodha A, El-Naggar W, Yoon EW, Shah PS, Canadian Neonatal Network Investigators

Neonatology · 2025 · PMID 39102804 · Full text

INTRODUCTION: Optimal oxygen saturation targets remain unknown for extremely preterm infants. METHODS: Cohort analysis of eligible preterm infants born <29 weeks' gestation admitted between 2011 and 2018 to centers submi... INTRODUCTION: Optimal oxygen saturation targets remain unknown for extremely preterm infants. METHODS: Cohort analysis of eligible preterm infants born <29 weeks' gestation admitted between 2011 and 2018 to centers submitting data to the Canadian Neonatal Network (CNN) database. Site questionnaires to determine saturation targets, alarm settings, and date of change, allowed assignation of centers to intermediate (88-93%) or high (90-95%) saturation targets. A 6-month washout period was applied to sites which switched targets during the study period. Our primary outcome was survival free of major morbidity. Secondary outcomes were death, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity, and evidence of brain injury during admission. Generalized estimating equations were applied to compensate for demographic differences and site practices. RESULTS: There were 2,739 infants in the high (mean gestational age [GA] 26 ± 1.6 weeks) and 6,813 infants in the intermediate (mean GA 26.2 ± 1.6 weeks) saturation target group. Survival without morbidity was higher in the intermediate target group (adjusted odds ratio [aOR] 1.59; 95% CI: 1.04, 2.45). There was no difference in mortality between groups (aOR 0.81; 95% CI: 0.59, 1.11), in NEC, treated retinopathy, or brain injury. On subgroup analysis, restricting data to sites which switched targets during the study, intermediate saturation targets were associated with lower rates of BPD (aOR 0.45; 95% CI: 0.28, 0.72). CONCLUSION: For neonates <29 weeks' gestation, intermediate saturation target was associated with higher odds of survival without major morbidity compared to higher oxygen saturation target. INTRODUCTION: Optimal oxygen saturation targets remain unknown for extremely preterm infants. METHODS: Cohort analysis of eligible preterm infants born <29 weeks' gestation admitted between 2011 and 2018 to centers submitting data to the Canadian Neonatal Network (CNN) database. Site questionnaires to determine saturation targets, alarm settings, and date of change, allowed assignation of centers to intermediate (88-93%) or high (90-95%) saturation targets. A 6-month washout period was applied to sites which switched targets during the study period. Our primary outcome was survival free of major morbidity. Secondary outcomes were death, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity, and evidence of brain injury during admission. Generalized estimating equations were applied to compensate for demographic differences and site practices. RESULTS: There were 2,739 infants in the high (mean gestational age [GA] 26 ± 1.6 weeks) and 6,813 infants in the intermediate (mean GA 26.2 ± 1.6 weeks) saturation target group. Survival without morbidity was higher in the intermediate target group (adjusted odds ratio [aOR] 1.59; 95% CI: 1.04, 2.45). There was no difference in mortality between groups (aOR 0.81; 95% CI: 0.59, 1.11), in NEC, treated retinopathy, or brain injury. On subgroup analysis, restricting data to sites which switched targets during the study, intermediate saturation targets were associated with lower rates of BPD (aOR 0.45; 95% CI: 0.28, 0.72). CONCLUSION: For neonates <29 weeks' gestation, intermediate saturation target was associated with higher odds of survival without major morbidity compared to higher oxygen saturation target.

Aspects on Oxygenation in Preterm Infants before, Immediately after Birth, and Beyond.

Sotiropoulos JX, Saugstad OD, Oei JL

Neonatology · 2024 · PMID 39089224 · Full text

BACKGROUND: Oxygen is crucial for life but too little (hypoxia) or too much (hyperoxia) may be fatal or cause lifelong morbidity. SUMMARY: In this review, we discuss the challenges of balancing oxygen control in preterm... BACKGROUND: Oxygen is crucial for life but too little (hypoxia) or too much (hyperoxia) may be fatal or cause lifelong morbidity. SUMMARY: In this review, we discuss the challenges of balancing oxygen control in preterm infants during fetal development, the first few minutes after birth, in the neonatal intensive care unit and after hospital discharge, where intensive care monitoring and response to dangerous oxygen levels is more often than not, out of reach with current technologies and services. KEY MESSAGES: Appropriate oxygenation is critically important even from before birth, but at no time is the need to strike a balance more important than during the first few minutes after birth, when body physiology is changing at its most rapid pace. Preterm infants, in particular, have a poor control of oxygen balance. Underdeveloped organs, especially of the lungs, require supplemental oxygen to prevent hypoxia. However, they are also at risk of hyperoxia due to immature antioxidant defenses. Existing evidence demonstrate considerable challenges that need to be overcome before we can ensure safe treatment of preterm infants with one of the most commonly used drugs in newborn care, oxygen.
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