Recognizing the future leaders of neonatology is fundamental to safeguarding tomorrow's driving force in innovation. This collection will showcase the high-quality work of internationally recognized researchers in the early stages of their careers. We aim to highlight research by leading scientists of the future across the entire breadth of neonatology, and present advances in theory, experiment and methodology with applications to compelling problems. All Rising Star researchers will be suggested by established Editors within our board in recognition of their influence on the future directions in their respective fields. While future innovations in neonatology are yet to be discovered, this Research Topic will give us a hint at whom to follow.

Leiden University

Kobe University

Clinical Department of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz

University of Alberta

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Frontiers in Pediatrics

Neonatology

Rising Stars in Neonatology: 2023

Editorial on the Research Topic <a href="https://www.frontiersin.org/research-topics/56028/rising-stars-in-neonatology-2023">Rising stars in neonatology: 2023</a>It is acknowledged that medicine as it is being practiced today is an applied science. This is substantiated by all the scientific progress over the last decades and the subsequent progress in clinical practice (<a href="#B1">1</a>). Nonetheless, this does not derogate the need for further diligently planned and executed empirical studies—studies that are relevant, cost-efficient, and ethically sound—as these have the potential not only to inform and impact clinical practice but also to improve outcomes for newborn infants and their families (<a href="#B2">2</a>). Scientific evidence forms the basis of recommendations for essential interventions in neonatology, for example, neonatal resuscitation after birth (<a href="#B3">3</a>) or the management of respiratory distress syndrome (<a href="#B4">4</a>). However, to provide sound treatment recommendations, we need scientific evidence that has focused on appropriate (clinical) outcomes. The development of a core outcome set for neonatal research should further support scientists' outcome selection, ensuring that studies are targeting the issues most relevant to providers and their patients (<a href="#B5">5</a>).Driven by advances in several scientific fields including genetics and advanced imaging, there have been increasing opportunities for research in neonatal-perinatal medicine (<a href="#B6">6</a>). Consequently, clinical studies in the field of neonatology are as multifaceted as ever (<a href="#B7">7</a>). This scientific plurality is also represented by the articles in this Research Topic, which is aimed at showcasing the high-quality work of internationally recognized researchers in the early stages of their careers. The first two studies in this Research Topic have used scientific advantages, one in genetics and advanced laboratory analytics and the other in non-invasive patient monitoring, for their respective investigations:<a href="https://doi.org/10.3389/fped.2023.1225294">Vidinopoulos et al.</a> (Front Pediatr 2023) studied the effects of 24 h of mechanical ventilation on inflammation in the brainstem respiratory centers of preterm fetal sheep. They found increased systemic interleukin levels in comparison to the control group of non-ventilated sheep but only moderate inflammatory effects—and similar mRNA expression levels of inflammation, injury, cell death, and prostaglandin synthesis—within the brainstem respiratory centers of the ventilated sheep.In their post hoc analysis of data from previous observational studies, <a href="https://doi.org/10.3389/fped.2023.1276769">Wolfsberger et al.</a> (Front Pediatr 2023) targeted fractional tissue oxygen extraction, i.e., relative oxygen extraction from the arterial to the venous compartment, in peripheral muscle tissue, as calculated from the tissue oxygenation index measured by near-infrared spectroscopy. Based on data from 240 stable term and late preterm neonates, they were able to provide reference values of peripheral fractional tissue oxygen extraction for the first 24 h after birth, which remained stable when comparing four 6-h periods.Evaluating the quality of medical care is often the first step to identifying areas for improvement. <a href="https://doi.org/10.3389/fped.2024.1366363">Wudu et al.</a> (Front Pediatr 2024) prospectively studied 306 neonates admitted to neonatal intensive care units in Northeast Ethiopia due to sepsis, focusing on mortality and predictors of time to death. While the mortality rate was alarmingly high, the identified modulating factors such as tachypnea, thrombocytopenia, and use of continuous positive airway pressure could serve as catalysts for improving care practices and patient survival.Finally, as part of our family-centered approach, especially in neonatology and all of pediatrics, we must as clinical researchers always bear in mind how important it is to actively work together with parents while planning and doing research (<a href="#B8">8</a>). <a href="https://doi.org/10.3389/fped.2023.1324948">Tippmann et al.</a> (Front Pediatr 2024) investigated parental perceptions of informed consent procedures for neonatal research, with their results emphasizing the importance of gaining parental approval of study participation, but also showing that the timing of consent obtainment—before or after birth—was of less importance to parents.While pre-clinical and clinical studies are important first steps, improving the quality of neonatal care requires active dissemination, implementation in guidelines and policies, and, ultimately, adoption in practice (<a href="#B9">9</a>). Therefore, while we hope that this research collection is informative and worth reading, we hope even more that these studies will help inform further research as well as clinical practice to come one step closer to our joint goal of improving the health and quality of life of our patients.LM: Conceptualization, Writing &#x2013; original draft, Writing &#x2013; review &amp; editing. JD: Writing &#x2013; review &amp; editing. KF: Writing &#x2013; review &amp; editing.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Editorial: Rising stars in neonatology: 2023

BackgroundIn impoverished nations like Ethiopia, neonatal sepsis contributes significantly to neonatal mortality. Despite variations in the specific timing of death and predictors of neonatal mortality associated with sepsis across different settings, there's limited documented information in the Neonatal Intensive Care Units of northeastern Ethiopia. Consequently, the aim of this study was to determine time to death and its predictors among neonates with sepsis admitted to Neonatal Intensive Care Units in comprehensive specialized hospitals in northeastern Ethiopia</sec>MethodsA prospective cohort study conducted at the institution level involved 306 neonates diagnosed with sepsis. Data collection utilized face-to-face interviews and chart reviews. Subsequently, the data were inputted into Epi-data version 4.6 and later analyzed using STATA version 17. The median time to death was determined, and both the Kaplan-Meier curve and log-rank test were applied. Furthermore, a Cox proportional hazard regression model was utilized to identify predictors of neonatal mortality associated with sepsis.</sec>ResultThe cumulative incidence of mortality among neonates admitted with sepsis was 34% (95% CI: 28.9%–39.5%). The neonatal mortality rate stood at 51 (95% CI: 42.1, 62) per 1,000 neonates admitted to the intensive care units with sepsis over a total of 1,854 person-days of observation. Additionally, the median time to death was 13 days (IQR = 5–23 days). Tachypnea [AHR 6.2 (95% CI: 1.5–9.7)], respiratory distress syndrome [AHR 2.1 (95% CI: 1.3–3.5)], lethargy [AHR 1.8 (95% CI: 1.2–2.6)], preterm birth [AHR 1.8 (95% CI: 1.2–2.7)], continuous positive airway pressure use [AHR 2.1 (95% CI: 1.3–3.4)], home delivery [AHR 2.63 (95% CI: 1.1–6.4)], Subgalea hemorrhage [AHR 1.8 (95% CI: 1.1–3.9)], and low platelet count [AHR 5.9 (95% CI: 2.3–8.6)] were found to be predictors of time to death in neonates with sepsis.</sec>ConclusionThe study revealed an alarmingly high neonatal mortality rate among septic neonates, underscoring the urgency for intervention. Enhancing the quality of care in neonatal intensive care units, bolstering infection prevention during procedures such as continuous positive airway pressure, exercising caution with locally made accessories, and reinforcing a culture of institutional delivery are critical in curbing neonatal sepsis-related mortalities.</sec>

Background: In impoverished nations like Ethiopia, neonatal sepsis contributes significantly to neonatal mortality. Despite variations in the specific timing of death and predictors of neonatal mortality associated with sepsis across different settings, there's limited documented information in the Neonatal Intensive Care Units of northeastern Ethiopia. Consequently, the aim of this study was to determine time to death and its predictors among neonates with sepsis admitted to Neonatal Intensive Care Units in comprehensive specialized hospitals in northeastern EthiopiaMethods: A prospective cohort study conducted at the institution level involved 306 neonates diagnosed with sepsis. Data collection utilized face-to-face interviews and chart reviews. Subsequently, the data were inputted into Epi-data version 4.6 and later analyzed using STATA version 17. The median time to death was determined, and both the Kaplan-Meier curve and log-rank test were applied. Furthermore, a Cox proportional hazard regression model was utilized to identify predictors of neonatal mortality associated with sepsis.Result: The cumulative incidence of mortality among neonates admitted with sepsis was 34% (95% CI: 28.9%–39.5%). The neonatal mortality rate stood at 51 (95% CI: 42.1, 62) per 1,000 neonates admitted to the intensive care units with sepsis over a total of 1,854 person-days of observation. Additionally, the median time to death was 13 days (IQR = 5–23 days). Tachypnea [AHR 6.2 (95% CI: 1.5–9.7)], respiratory distress syndrome [AHR 2.1 (95% CI: 1.3–3.5)], lethargy [AHR 1.8 (95% CI: 1.2–2.6)], preterm birth [AHR 1.8 (95% CI: 1.2–2.7)], continuous positive airway pressure use [AHR 2.1 (95% CI: 1.3–3.4)], home delivery [AHR 2.63 (95% CI: 1.1–6.4)], Subgalea hemorrhage [AHR 1.8 (95% CI: 1.1–3.9)], and low platelet count [AHR 5.9 (95% CI: 2.3–8.6)] were found to be predictors of time to death in neonates with sepsis.Conclusion: The study revealed an alarmingly high neonatal mortality rate among septic neonates, underscoring the urgency for intervention. Enhancing the quality of care in neonatal intensive care units, bolstering infection prevention during procedures such as continuous positive airway pressure, exercising caution with locally made accessories, and reinforcing a culture of institutional delivery are critical in curbing neonatal sepsis-related mortalities.

Time to death and its predictors among neonates admitted with sepsis in neonatal intensive care unit at comprehensive specialized hospitals in Northeast Ethiopia

Background and objectiveObtaining informed consent in neonatal emergency research is challenging. The aim of this study was to assess parental perceptions of informed consent following participation in a clinical trial in neonatal emergency care.</sec>MethodsThis was a supplementary analysis of a randomised controlled trial comparing video and direct laryngoscopy for neonatal endotracheal intubation in the delivery room and neonatal intensive care unit. After obtaining informed consent for the clinical trial, parents were asked to answer a series of self-administered questions about their perceptions of clinical trial participation and the consent process. Informed consent had been given either before birth, after birth but before inclusion in the trial, or after inclusion in the trial.</sec>ResultsWe received responses from 33 mothers and 27 fathers (n = 60) of the 63 preterm and term infants who participated in the study. Fifty-three (89.8%, n = 59) parents agreed that infants should participate in clinical trials, and 51 (85%, n = 60) parents agreed that parents should be asked for informed consent. Fifty-three (89.8%, n = 59) parents felt that their infant's participation in this particular trial would be beneficial. Fifty-two (86.7%, n = 60) parents felt that the informed consent process was satisfactory. One parent (100%, n = 1) approached before birth, 23 parents (82.1%, n = 28) approached after birth but before enrolment and 26 (83.9%, n = 31) parents approached after enrolment were satisfied with the timing of the consent process. Eight (13.3%, n = 60) parents felt some pressure to provide informed consent. Of these, two (25%) were approached before enrolment and six (75%) were approached after enrolment.</sec>ConclusionParents valued their infant's participation in an emergency neonatal clinical trial and considered it important to be asked for consent. In this study, it seemed less important whether consent was obtained before or after the intervention. Future studies may need to investigate which form of consent is most acceptable to parents for the individual study in question.</sec>

Background and objective: Obtaining informed consent in neonatal emergency research is challenging. The aim of this study was to assess parental perceptions of informed consent following participation in a clinical trial in neonatal emergency care.Methods: This was a supplementary analysis of a randomised controlled trial comparing video and direct laryngoscopy for neonatal endotracheal intubation in the delivery room and neonatal intensive care unit. After obtaining informed consent for the clinical trial, parents were asked to answer a series of self-administered questions about their perceptions of clinical trial participation and the consent process. Informed consent had been given either before birth, after birth but before inclusion in the trial, or after inclusion in the trial.Results: We received responses from 33 mothers and 27 fathers (n = 60) of the 63 preterm and term infants who participated in the study. Fifty-three (89.8%, n = 59) parents agreed that infants should participate in clinical trials, and 51 (85%, n = 60) parents agreed that parents should be asked for informed consent. Fifty-three (89.8%, n = 59) parents felt that their infant's participation in this particular trial would be beneficial. Fifty-two (86.7%, n = 60) parents felt that the informed consent process was satisfactory. One parent (100%, n = 1) approached before birth, 23 parents (82.1%, n = 28) approached after birth but before enrolment and 26 (83.9%, n = 31) parents approached after enrolment were satisfied with the timing of the consent process. Eight (13.3%, n = 60) parents felt some pressure to provide informed consent. Of these, two (25%) were approached before enrolment and six (75%) were approached after enrolment.Conclusion: Parents valued their infant's participation in an emergency neonatal clinical trial and considered it important to be asked for consent. In this study, it seemed less important whether consent was obtained before or after the intervention. Future studies may need to investigate which form of consent is most acceptable to parents for the individual study in question.

Parental perceptions of informed consent in a study of tracheal intubations in neonatal intensive care

BackgroundPeripheral muscle fractional tissue oxygen extraction (pFTOE) represents the relative extraction of oxygen from the arterial to venous compartment, providing information about dynamic changes of oxygen delivery and oxygen consumption. The aim of the present study was to establish reference values of pFTOE during the first 24 h after birth in stable term and late preterm neonates.</sec>MethodsThe present study is a post-hoc analysis of secondary outcome parameters of prospective observational studies. Only stable neonates without infection, asphyxia and any medical support were eligible for our analysis to obtain normal values. For measurements of peripheral muscle tissue oxygenation index (pTOI) during the first 24 h after birth in term and preterm neonates, the NIRO200/NIRO200NX was used. Arterial oxygen saturation (SpO2) was obtained by pulse oximetry. pFTOE was calculated out of pTOI and SpO2: pFTOE = (SpO2-pTOI)/SpO2. Measurements of neonates were stratified into four groups according to their respective measurement time point (6 h periods) after birth. Term and preterm neonates were analyzed separately. Mean values of measurements during the first time period (0–6 h after birth) were compared to measurements of the following time periods (second = 7–12 h, third = 13–18 h, fourth = 19–24 h after birth).</sec>ResultsTwo-hundred-fourty neonates (55 term and 185 late preterm neonates) had at least one peripheral muscle NIRS measurements within the first 24 h after birth. Mean gestational age and birth weight were 39.4 ± 1.1 weeks and 3360 (2860–3680)g in term neonates and 34.0 ± 1.4 weeks and 2060 (1750–2350)g in preterm neonates, respectively. In term neonates pFTOE was 0.264 (0.229–0.300), 0.228 (0.192–0.264), 0.237 (0.200–0.274) and 0.220 (0.186–0.254) in the first, second, third and fourth time period. In preterm neonates pFTOE was 0.229 (0.213–0.246), 0.225 (0.209–0.240), 0.226 (0.210–0.242) and 0.238 (0.222–0.255) in the first, second, third and fourth time period. pFTOE did not show any significant changes between the time periods, neither in term nor in preterm neonates.</sec>ConclusionWe provide reference values of pFTOE for stable term and late preterm neonates within the first 24 h after birth, which were stable when comparing four 6-h periods. These normal values are of great need for interpreting pFTOE in scientific context as well as for potential future clinical applications.</sec>

Background: Peripheral muscle fractional tissue oxygen extraction (pFTOE) represents the relative extraction of oxygen from the arterial to venous compartment, providing information about dynamic changes of oxygen delivery and oxygen consumption. The aim of the present study was to establish reference values of pFTOE during the first 24 h after birth in stable term and late preterm neonates.Methods: The present study is a post-hoc analysis of secondary outcome parameters of prospective observational studies. Only stable neonates without infection, asphyxia and any medical support were eligible for our analysis to obtain normal values. For measurements of peripheral muscle tissue oxygenation index (pTOI) during the first 24 h after birth in term and preterm neonates, the NIRO200/NIRO200NX was used. Arterial oxygen saturation (SpO2) was obtained by pulse oximetry. pFTOE was calculated out of pTOI and SpO2: pFTOE = (SpO2-pTOI)/SpO2. Measurements of neonates were stratified into four groups according to their respective measurement time point (6 h periods) after birth. Term and preterm neonates were analyzed separately. Mean values of measurements during the first time period (0–6 h after birth) were compared to measurements of the following time periods (second = 7–12 h, third = 13–18 h, fourth = 19–24 h after birth).Results: Two-hundred-fourty neonates (55 term and 185 late preterm neonates) had at least one peripheral muscle NIRS measurements within the first 24 h after birth. Mean gestational age and birth weight were 39.4 ± 1.1 weeks and 3360 (2860–3680)g in term neonates and 34.0 ± 1.4 weeks and 2060 (1750–2350)g in preterm neonates, respectively. In term neonates pFTOE was 0.264 (0.229–0.300), 0.228 (0.192–0.264), 0.237 (0.200–0.274) and 0.220 (0.186–0.254) in the first, second, third and fourth time period. In preterm neonates pFTOE was 0.229 (0.213–0.246), 0.225 (0.209–0.240), 0.226 (0.210–0.242) and 0.238 (0.222–0.255) in the first, second, third and fourth time period. pFTOE did not show any significant changes between the time periods, neither in term nor in preterm neonates.Conclusion: We provide reference values of pFTOE for stable term and late preterm neonates within the first 24 h after birth, which were stable when comparing four 6-h periods. These normal values are of great need for interpreting pFTOE in scientific context as well as for potential future clinical applications.

Peripheral muscle fractional tissue oxygen extraction in stable term and preterm neonates during the first 24 h after birth

BackgroundPreterm infants have immature respiratory drive and often require prolonged periods of mechanical ventilation. Prolonged mechanical ventilation induces systemic inflammation resulting in ventilation-induced brain injury, however its effect on brainstem respiratory centers is unknown. We aimed to determine the effects of 24 h of mechanical ventilation on inflammation and injury in brainstem respiratory centres of preterm fetal sheep.</sec>MethodsPreterm fetal sheep at 110 ± 1 days (d) gestation were instrumented to provide mechanical ventilation in utero. At 112 ± 1 d gestation, fetuses received either mechanical ventilation (VENT; n = 7; 3 ml/kg) for 24 h, or no ventilation (CONT; n = 6). At post-mortem, fetal brainstems were collected for assessment of mRNA and histological markers of inflammation and injury.</sec>ResultsIn utero ventilation (IUV) did not alter any blood-gas parameters. IUV significantly increased systemic IL-6 and IL-8 concentrations over the 24 h period compared to CONT. The number of ameboid microglia within the nucleus tractus solitarius and the raphe nucleus increased in VENT fetuses (p < 0.05 for both vs. control). The % area fraction of GFAP + staining was not significantly higher within the preBötzinger complex (p = 0.067) and retrotrapezoid nucleus and parafacial respiratory group (p = 0.057) in VENT fetuses compared to CONT. Numbers of caspase-3 and TUNEL-positive cells were similar between groups. Gene expression (mRNA) levels of inflammation, injury, cell death and prostaglandin synthesis within the brainstem were similar between groups.</sec>ConclusionMechanical ventilation induces a systemic inflammatory response with only moderate inflammatory effects within the brainstem respiratory centres of preterm fetal sheep.</sec>

Background: Preterm infants have immature respiratory drive and often require prolonged periods of mechanical ventilation. Prolonged mechanical ventilation induces systemic inflammation resulting in ventilation-induced brain injury, however its effect on brainstem respiratory centers is unknown. We aimed to determine the effects of 24 h of mechanical ventilation on inflammation and injury in brainstem respiratory centres of preterm fetal sheep.Methods: Preterm fetal sheep at 110 ± 1 days (d) gestation were instrumented to provide mechanical ventilation in utero. At 112 ± 1 d gestation, fetuses received either mechanical ventilation (VENT; n = 7; 3 ml/kg) for 24 h, or no ventilation (CONT; n = 6). At post-mortem, fetal brainstems were collected for assessment of mRNA and histological markers of inflammation and injury.Results: In utero ventilation (IUV) did not alter any blood-gas parameters. IUV significantly increased systemic IL-6 and IL-8 concentrations over the 24 h period compared to CONT. The number of ameboid microglia within the nucleus tractus solitarius and the raphe nucleus increased in VENT fetuses (p &lt; 0.05 for both vs. control). The % area fraction of GFAP + staining was not significantly higher within the preBötzinger complex (p = 0.067) and retrotrapezoid nucleus and parafacial respiratory group (p = 0.057) in VENT fetuses compared to CONT. Numbers of caspase-3 and TUNEL-positive cells were similar between groups. Gene expression (mRNA) levels of inflammation, injury, cell death and prostaglandin synthesis within the brainstem were similar between groups.Conclusion: Mechanical ventilation induces a systemic inflammatory response with only moderate inflammatory effects within the brainstem respiratory centres of preterm fetal sheep.