Neonatal Therapeutic Intervention Research Articles

RENAL DYSFUNCTION IN PRETERM INFANTS WITH PERINATAL PATHOLOGY: RISK FACTORS, SENSITIVITY AND SPECIFICITY OF LABORATORY MARKERS OF DAMAGE

RENAL DYSFUNCTION IN PRETERM INFANTS WITH PERINATAL PATHOLOGY: RISK FACTORS, SENSITIVITY AND SPECIFICITY OF LABORATORY MARKERS OF DAMAGE

PREDICTIVE FACTORS AND CLINICAL AND PARACLINICAL FEATURES OF URINARY TRACT DYSFUNCTION IN PRETERM INFANTS

PREDICTIVE FACTORS AND CLINICAL AND PARACLINICAL FEATURES OF URINARY TRACT DYSFUNCTION IN PRETERM INFANTS

Concept and considerations of a medical device: the active noise cancelling incubator.

An increasingly 24/7 connected and urbanised world has created a silent pandemic of noise-induced hearing loss. Ensuring survival to children born (extremely) preterm is crucial. The incubator is a closed medical device, modifying the internal climate, and thus providing an environment for the child, as safe, warm, and comfortable as possible. While sound outside the incubator is managed and has decreased over the years, managing the noise inside the incubator is still a challenge. Using active noise cancelling in an incubator will eliminate unwanted sounds (i.e., from the respirator and heating) inside the incubator, and by adding sophisticated algorithms, normal human speech, neonatal intensive care unit music-based therapeutic interventions, and natural sounds will be sustained for the child in the pod. Applying different methods such as active noise cancelling, motion capture, sonological engineering. and sophisticated machine learning algorithms will be implemented in the development of the incubator. A controlled and active sound environment in and around the incubator can in turn promote the wellbeing, neural development, and speech development of the child and minimise distress caused by unwanted noises. While developing the hardware and software pose individual challenges, it is about the system design and aspects contributing to it. On the one hand, it is crucial to measure the auditory range and frequencies in the incubator, as well as the predictable sounds that will have to be played back into the environment. On the other, there are many technical issues that have to be addressed when it comes to algorithms, datasets, delay, microphone technology, transducers, convergence, tracking, impulse control and noise rejection, noise mitigation stability, detection, polarity, and performance. Solving a complex problem like this, however, requires a de-disciplinary approach, where each discipline will realise its own shortcomings and boundaries, and in turn will allow for innovations and new avenues. Technical developments used for building the active noise cancellation-incubator have the potential to contribute to improved care solutions for patients, both infants and adults.Code available at: 10.3389/fped.2023.1187815.

Administration of selective brain hypothermia using a simple cooling device in neonatal rats

BackgroundThe interruption of oxygen and blood supply to the newborn brain around the time of birth is a risk factor for hypoxic-ischemic encephalopathy and may lead to infant mortality or lifelong neurological impairments. Currently, therapeutic hypothermia, the cooling of the infant's head or entire body, is the only treatment to curb the extent of brain damage. New methodIn this study, we designed a focal brain cooling device that circulates cooled water at a steady state temperature of 19 ± 1 °C through a coil of tubing fitted onto the neonatal rat's head. We tested its ability to selectively decrease brain temperature and offer neuroprotection in a neonatal rat model of hypoxic-ischemic brain injury. ResultsOur method cooled the brain to 30–33 °C in conscious pups, while keeping the core body temperature approximately 3.2 °C warmer. Furthermore, the application of the cooling device to the neonatal rat model demonstrated a reduction in brain volume loss compared to pups maintained at normothermia and achieved a level of brain tissue protection the same as that of whole-body cooling. Comparison with existing methodsPrevailing methods of selective brain hypothermia are designed for adult animal models rather than for immature animals such as the rat as a conventional model of developmental brain pathology. Contrary to existing methods, our method of cooling does not require surgical manipulation or anaesthesia. ConclusionOur simple, economical, and effective method of selective brain cooling is a useful tool for rodent studies in neonatal brain injury and adaptive therapeutic interventions.

Associations between Early Thyroid-Stimulating Hormone Levels and Morbidities in Extremely Preterm Neonates

Introduction: High-end cutoffs of thyroid-stimulating hormone (TSH) have been emphasized for hypothyroidism therapy in extremely preterm infants, but the significance of low TSH levels remains unknown. This study hypothesized that the spectrum of TSH levels by newborn screening after birth signifies specific morbidities in extremely preterm neonates. Methods: The multicenter population cohort analyzed 434 extremely preterm neonates receiving TSH screening at 24–96 h of age in 2008–2019. Neonates were categorized by blood TSH levels into group 1: TSH <0.5 µU/mL, group 2: 0.5 ≤ TSH <2 µU/mL, group 3: 2 ≤ TSH <4 µU/mL, and group 4: TSH ≥4 µU/mL. Neonatal morbidities were categorized using the modified Neonatal Therapeutic Intervention Scoring System. Results: The four groups differed in gestational age, birth weight, and the postnatal age at blood sampling so did the proportions of mechanical ventilation usage (p = 0.01), hypoxic respiratory failure (p = 0.005), high-grade intraventricular hemorrhage (p = 0.007), and periventricular leukomalacia (p = 0.048). Group 1 had higher severity scores for respiratory distress syndrome (RDS; effect size 0.39 [95% confidence interval [CI]: 0.18–0.59]) and brain injury (0.36 [0.15–0.57]) than group 2, which remained significant after adjusting for gestational age, birth weight, dopamine usage, and the postnatal age at TSH screening (RDS: mean + 0.45 points [95% CI: 0.11–0.79]; brain injury: +0.32 [0.11–0.54]). Conclusions: Low TSH levels in extremely preterm neonates are associated with severe RDS and brain injuries. Studies recruiting more neonates with complete thyroid function data are necessary to understand central-peripheral interactions of the hypothalamic-pituitary-thyroid axis.

Antenatal risk factors for retinopathy of premature

This literature review presents the antenatal risk factors for the development of retinopathy of prematurity (ROP). Despite advances in antenatal and neonatal therapeutic interventions, screening, and follow-up, ROP remains a potentially vision-threatening retinopathy that requires careful monitoring and timely intervention to prevent the progression of adverse visual impairment or blindness. ROP is a multifactorial disease. The main risk factors are low gestational age and low birth weight. Recent experimental and clinical data support the hypothesis that multiple antenatal factors are involved in the etiology and progression of ROP. These factors include the age of the mother, maternal diseases, pregnancy-associated maternal pathologies, use of drugs to correct these conditions, and inflammatory process. Their roles are ambiguous and often contradictory. The physiology of the mother and placenta can significantly influence the risk of ROP development in preterm infants. The placenta connects the mothers body and the fetus, and it functions in the exchange of nutrients and oxygen between the mother and the fetus. Therefore, any pathological changes in the mothers body entail changes in the placenta, which this directly affects the fetus. A sudden loss of placental support is detrimental to the development of infants in the immediate postnatal period. Thus, these factors should be taken into account when assessing the risk of ROP development to predict and prevent poor vision in children.

A purely solid-state based method for bilirubin levels determination in plasma.

In the past half-century, the advent of solid-state electronics, i.e., microcontrollers, transistors, photodiodes, light-emitting diodes and more, has led to the improvement of the tools we, as a human race, need and use in our daily lives. Solid-state electronics has specifically contributed significantly to the field of biomedical engineering and has allowed various round-the-clock point-of-care testing applications. These include handheld, wearable, and implantable sensors and devices for accelerated interventions. Furthermore, miniaturization has accelerated the implementation of low-cost and energy-efficient systems with increased performance. In this paper, we have used optical techniques along with the benefits of solid-state electronics to measure bilirubin concentration in plasma with concentrations projected from healthy individuals to hyperbilirubinemia (0 - 30 mg/dL). Traditionally, full-range spectrophotometry is the gold standard optical method and provides the most accurate results but suffers from instrument complexity. Thus, this paper proposes and investigates the measurement of bilirubin by using a dual-wavelength approach combined with photodegradation kinetics. By tracking the changes in the spectral characteristics of bilirubin for 10 minutes (~3 J/cm2), a new model was built to measure bilirubin concentrations and distinguish between low vs high and risky vs non-risky levels. Results show a high positive correlation between the optical responses and concentration (R-square > 0.93) with an average accuracy of ~1.4 mg/dL. On top of that, the technique's viability for point-of-care testing of bilirubin levels was studied using a system-on-chip optical module. Thus, this could help suggest neonatal therapeutic interventions, including enteral feeding, phototherapy, and blood transfusion.

A New Quantitative Triage System for Hospitalized Neonates to Assist with Decisions of Hospital Evacuation Priorities.

Hospitalized neonates are vulnerable to natural and man-made disasters because of their persistent requirement for medical resources and may need to be evacuated to safe locations when electricity and medical gas supply become unreliable. In Japan, a triage system for hospitalized neonates, or the Simple Triage and Rapid Treatment for Neonates, Revised (START-Neo-R), has been used to determine whether neonates are in suitable conditions for transportation. However, this scale is not useful to determine the evacuation order of neonates because a considerable number of evacuees are classified into the same categories. To solve this problem, a novel triage system, Neonatal Extrication Triage (NEXT) was developed. This study tested the validity and reproducibility of both triages and compared them with a standardized prognostic scoring system for hospitalized neonates, the Neonatal Therapeutic Intervention Scoring System (NTISS). In this retrospective observational study, physicians and nurses independently assessed each neonate hospitalized at a tertiary neonatal intensive care unit (NICU) twice weekly using NEXT and START-Neo-R. The NEXT system comprises six questionnaires regarding medical resources required during transition and transportation, providing composite scores on a 12-point scale. The START-Neo-R classified neonates into five levels based on the severity of disease and dependence on medical care. Inter-rater reliability of both systems was assessed using Cohen's kappa coefficient, whereas the criterion validity with NTISS was assessed using Spearman's correlation coefficient. Overall, 162 neonates were assessed for 49 days, resulting in triage data for 1,079 accumulated patients. Both NEXT scores and START-Neo-R ranks were well-dispersed across different levels without excessive accumulation in specific categories. Inter-rater reliability of NEXT (kappa coefficient, 0.973; 95% confidence interval, 0.969-0.976) and START-Neo-R (kappa coefficient, 0.952; 95% confidence interval, 0.946-0.957) between physicians and nurses was sufficiently high. The correlation coefficient of NEXT and START-Neo-R scores with NTISS scores were 0.889 (P <.001) and 0.850 (P <.001), respectively. Both START-Neo-R and NEXT had good reproducibility and correlation with the severity of neonates indicated by NTISS. With its well-dispersed scores across different levels, the NEXT system might be a powerful tool to determine the priority of evacuation objectively.

LABORATORY DIAGNOSTIC CRITERIA OF RENAL IMPAIRMENT IN PREMATURE NEWBORNS WITH SEVERE PERINATAL PATHOLOGY

Introduction: Critically ill neonates are at high risk of developing renal impairment (RI), including acute kidney injury (AKI), which is associated with short- and long-term pathological outcomes and increased mortality. The incidence of acute kidney injury varied by gestational age (GA) group.&#x0D; Aim: Identify laboratory diagnostic criteria of RI in premature newborns (PNs) with different GA who had severe heterogeneous perinatal pathology.&#x0D; Methods: The study was a prospective cohort of patients admitted electively to the III level Neonatal Intensive Care Unit at the Clinical Maternity Hospital 2 (Chernivtsi, Ukraine) between December 2015 and January 2018. One hundred sixty three PNs were treated at the hospital, from which a total of 68 patients were recruited into the study. Inclusion criteria: the GA is more than 24 weeks and less than 37 weeks; birth body weight is more than 500 g and less than 2500 g; presence of clinical signs of severe perinatal pathology. The severity of the perinatal pathology was classified on the basis of the neonatal Therapeutic Intervention Scoring System. The PNs were divided into three groups according to the GA: Group I consisted of 25 newborns born at the GA of 24-31 weeks, Group II – 25 newborns born at the GA 32-33 weeks, Group III – 18 newborns were born in a GA of 34-36 weeks.&#x0D; The levels of sodium, potassium, calcium and chlorine, alanine aminopeptidase, and aspartate aminopeptidase were measured in serum. The levels of creatinine and urea were measured in serum and urine. The concentration of total protein, albumin, α1-microglobulin, and β2-microglobulin was measured in urine.&#x0D; Findings and results: All PNs had signs of severe perinatal pathology and a neonatal Therapeutic Intervention Scoring System score of 10 or higher during the early neonatal period. There was no statistically significant difference in most serum biochemical parameters between groups of the study, excluding the level of serum chlorine. Our results demonstrated no significant difference in levels of urinary total protein and albumin between groups of the study, but showed a progressive increase the level of urinary creatinine and urea with increasing GA. The maximum level of urinary β2-microglobulin was found in “Late-Preterm” newborns who were born at 34-36 weeks, the minimal level of urinary α1-microglobulin was detected in patients with GA 32-33 weeks.&#x0D; Conclusions: Our results demonstrated that most PNs with severe perinatal pathology have some aspects of impaired tubular and glomerular functions. This is evidenced by changes in urinary new biomarkers. We found direct correlations between GA and serum creatinine (r=0.31, p&lt;0.05), urinary creatinine (r=0.40, p&lt;0.05), urinary α1-microglobulin (r=0.37, p&lt;0.05), and urinary β2-microglobulin (r=0.51, p&lt;0.05). Longer longitudinal cohort studies on PNs are required to determine the prognostic and diagnostic criteria of RI in these patients.

Neonatal Therapeutic Intervention Scoring System (NTISS) in Rural Country: Mortality and Length of Stay (LOS) Predictive Score in Preterm Infant

Background: Preterm infants need comprehensive management due to high risk of mortality and morbidity. Proper treatment in NICU can decrease the mortality risk in them, but some of them may take long time before they can go home. Neonatal Therapeutic Intervention Scoring System (NTISS) hopefully can be a predictive score for the mortality and Length of stay (LOS) of a preterm infant, yet, it’s use is still very limited in Indonesia. The authors aim to analyze NTISS to predict mortality and length of stay of preterm infants in Indonesia. Method: This retrospective study conducted in March 2017 and collected medical record data of preterm infants treated in NICU from July 2016 - March 2017. The inclusion criteria were infants with gestational age &lt;37 weeks, treated at NICU&gt; 24 hours and complete medical record data. NTISS total scores are collected after 24 hours at the NICU. Results: A total of 108 infants met the inclusion criteria. The ratio of NTISS scores had an area under the curve (area under curve / AUC) of 0.879 (95% CI 0.259-0.913) with cutoff at 20.2. it had 91.3% and 74.1% in sensitivity and specificity respectively; 48.8% and 96.9% in positive and negative predictive value respectively; positive likelihood ratio 3.52; negative likelihood ratio 0.12; and 77% inaccuracy. There was no correlation between NTISS scores and length of stay (p = 0.084). Conclusion: NTISS can be used to predict the mortality of preterm infants.

Early Gut Microbiota Changes in Preterm Infants with Bronchopulmonary Dysplasia: A Pilot Case-Control Study.

Bronchopulmonary dysplasia (BPD) is a complex chronic lung disease that primarily affects premature or critically ill infants. This pilot study investigated early changes in gut microbiota composition in BPD patients and explored the potential risk factors associated with these changes. Preterm infants admitted to our neonatal intensive care unit with a gestational age of 26 to 32 weeks were prospectively surveyed and eligible for stool collection on days 7 and 28 of postnatal age between February 2016 and June 2017. A 16S rRNA sequencing approach was applied to compare the gut microbiota composition between the BPD group and controls. Multiple linear regression analysis was used to identify the predictor variables. Eight subjects in the BPD group and 10 subjects in the preterm group were analyzed during the observation period. Actinobacteria, Proteobacteria, Bacteroidetes, and Firmicutes were the four dominant bacteria phyla of intestinal microflora. A significantly lower diversity of gut microbiota was observed in the BPD group compared with the preterm group on day 28 (number of observed operational taxonomic units, p = 0.034; abundance-based coverage estimator, p = 0.022; Shannon index, p = 0.028). Multiple linear regression analysis revealed that high Neonatal Therapeutic Intervention Scoring System score (≧19) at 24 hours was statistically significant in predicting the proportion of aerobic with facultative anaerobic bacteria on day 28 (p = 0.002). Infants with BPD are prone to develop gut dysbiosis in early life. A higher severity of illness and treatment intensity may indicate a higher risk of disrupting an anaerobic environment in the gut during the first month of life. · BPD patients are prone to develop gut dysbiosis.. · Lower diversity of gut microbiota.. · Higher risk of disrupting anaerobic environment..

Providing clarity around ethical discussion: development of a neonatal intervention score.

To develop a Neonatal Intervention Score (NIS) to describe the clinical trajectory of a neonate throughout their neonatal intensive care unit (NICU) admission. The NIS was developed by modifying the Neonatal Therapeutic Intervention Scoring System (NTISS) to reflect illness severity, dependency on life-sustaining interventions and overall life trajectory on a longitudinal basis, rather than illness burden. Validity for longitudinal use within the NICU was tested by calculating the score for 99 preterm babies born less than 28weeks at predetermined time points throughout their admission to tertiary level care at two institutions. A total of 1333 NISs were analysed, ranging from 0 to 32.5 (mean 9.77, SD 5.4). Internal consistency (Cronbach alpha) reached 0.8. NIS moderately correlated to both SNAPPE-II and SNAP-II (Spearman's rho=0.47, p=<0.001) within the first 24hours. The NIS is a useful and reliable descriptive tool of relative illness severity and degree of medical interventions throughout a baby's admission. Integrating a longitudinal description of medical dependency of a patient may assist both clinical and ethical decision-making and empirical research by providing an objective account of a baby's clinical trajectory. Establishment of validity within individual institutions is required.

Identificação da gravidade e do uso de intervenções em recém-nascidos com asfixia perinatal

Objetivo: identificar a gravidade e o uso de intervenções em recém-nascidos com asfixia perinatal. Métodos: estudo documental, realizado com 48 prontuários de recém-nascidos com asfixia perinatal em Unidade de Terapia Intensiva Neonatal, baseado no sistema de escore para intervenção terapêutica neonatal. Dados analisados por meio de estatística descritiva e inferencial. Resultados: os recém-nascidos avaliados apresentaram complicações como infecção neonatal presumida (63,2%), insuficiência respiratória (59,1%), sepse (38,7%) e convulsão (39,7%). Durante a internação, 35,4% foram a óbito. As intervenções mais utilizadas foram transporte e sinais vitais (100,0%), ambiente termorregulado (97,9%), ventilação mecânica invasiva (91,6%), antibióticos (77,0%), intubação (75,0%), flebotomia (72,9%) e cateter venoso central (68,7%). Conclusão: a média de pontuação do escore Neonatal Therapeutic Intervention Scoring System foi de 19,9, sendo verificadas médias estatisticamente diferentes entre as categorias das variáveis Duração da internação, Desfecho clínico e Escolaridade da mãe.

Collaboration in Regulatory Science to Facilitate Therapeutic Development for Neonates.

Historically, neonatal therapeutic interventions were derived from adult therapeutics, and tragedies resulting from this approach have demonstrated differences in the pathophysiologic and developmental processes between neonates and older patients. Over the past 3 decades, researchers and collaborative research networks have made progress in the systematic evaluation of neonatal therapies, yet most neonatal therapeutic products have been incompletely assessed for safety and efficacy, and remain unlabeled and unapproved. This work describes the legislative initiatives that have stimulated an increase in pediatric and neonatal studies. It highlights examples of successful neonatal drug studies that have resulted in informative neonatal labeling changes, as well as studies that have produced incomplete information. Strategies that support the design of successful studies, including targeting specific subpopulations, modeling and simulation to inform dose selection, innovative design strategies, biomarkers, and endpoints are discussed. Multi-stakeholder consortia such as the International Neonatal Consortium (INC), are working to improve the tools needed for the development of neonatal therapies. These research tools may be used by trial networks to inform consistent and efficient multicenter studies. More data are needed to support safe and effective use of drugs in neonates, and to obtain these data, a thorough understanding of pathophysiology, drug disposition, biomarkers, and clinically-meaningful endpoints is required. This information will be derived from clinical trials, registries, real-world evidence, and the medical literature. Collaboration of consortia and the development of research networks are essential to achieving these goals.

Zonulin: A Potential Marker of Intestine Injury in Newborns.

Introduction Zonulin (ZO), a new diagnostic biomarker of intestinal permeability, was tested in newborns presenting symptoms of infection and/or inflammation of the gut or being at risk of intestinal pathology. Material and Methods Serum ZO was assessed in 81 newborns diagnosed with sepsis, necrotizing enterocolitis (NEC), rotavirus infection, and gastroschisis, also in extremely low gestational age babies, and in controls (healthy newborns). ZO concentration was compared to C-reactive protein (CRP) and procalcitonin (PCT) values, leucocyte and platelet count, basic demographic data, and the value of the Neonatal Therapeutic Intervention Scoring System (NTISS). Results Median values of ZO were markedly higher in groups with rotavirus infection and gastroschisis (36.0 (1-3Q: 26.0–43.2) and 20.3 (1-3Q: 17.7–28.2) ng/ml, resp.) versus controls (3.5 (1-3Q: 2.7–4.8) ng/ml). Its concentration in the NEC group was twice as high as in controls but did not reach statistical significance. ZO levels were not related to NTISS, CRP, and PCT. Conclusions Zonulin is a promising biomarker of intestinal condition, markedly elevated in rotavirus infections. Its role in defining the severity of necrotizing enterocolitis and the risk for perforation is not well described and needs further evaluation. An increase in zonulin may not be parallel to the release of inflammatory markers, and low CRP should not exclude an injury to neonatal intestine.

Factors limiting usefulness of serum and urinary NGAL as a marker of acute kidney injury in preterm newborns

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is postulated to be a highly sensitive and specific marker of acute kidney injury (AKI). The aim of this study was to assess the factors affecting serum and urine total NGAL in preterm newborns, limiting the role of this new potential marker of AKI. Methods: Serum and urinary total NGAL concentrations were determined in 57 preterm infants admitted to the Neonatal Intensive Care Unit in the following points of time: first week of life, between 8 and 14 days of life, and after the fourth week of life. Patients’ clinical conditions were evaluated based on NTISS (Neonatal Therapeutic Intervention Scoring System). Two gestational age subgroups were distinguished: ≤29 and 30 to 35 weeks of gestation. We sought correlation between total NGAL values and gestational age, birth weight, Apgar score and severity of clinical condition, with particular interest in inflammatory status. Results: Serum and urinary total NGAL concentration correlated with inflammatory markers, such as CRP and procalcitonin, as well as with NTISS values. Birth weight and gestational age influence urinary NGAL (uNGAL) values in the first two weeks of life. In AKI (N = 8) patients uNGAL values were significantly higher than in non-AKI newborns. Conclusions: We conclude that inflammatory status and prematurity limits the specificity of total NGAL measurement as a marker of AKI.

PO-0634 Factors Limiting Usefulness Of Serum And Urinary Ngal As A Marker Of Acute Kidney Injury In Preterm Newborns

<h3>Background and aims</h3> Neutrophile gelatinase-associated lipocaline (NGAL) is postulated to be a highly sensitive and specific marker of acute kidney injury (AKI). The aim of this study was to assess the factors affecting serum and urine total NGAL in preterm newborns, limiting the role of this new potential marker of AKI. <h3>Methods</h3> Serum and urinary total NGAL concentrations were determined in 57 admitted to the Neonatal Intensive Care Unit preterm infants in the following points of time: first week of life, between 8 and 14 day of life, and after the fourth week of life. Patients’ clinical condition was evaluated based on NTISS (Neonatal Therapeutic Intervention Scoring System). Two gestational age subgroups were distinguished: &lt;30 and 30 to 35 weeks of gestation. We seek correlation between total NGAL values and gestational age, birth weight, Apgar score and severity of clinical condition with particular interest in inflammatory status. <h3>Results</h3> Serum and urinary total NGAL concentration correlated with inflammatory markers, such as CRP and procalcitonin as well as with NTISS values. Birth weight and gestational age influence uNGAL values in the first two weeks of life. In AKI (N=8) patients uNGAL values were significantly higher than in non-AKI newborns. <h3>Conclusions</h3> We conclude that inflammatory status and prematurity limits the specificity of total NGAL measurement as the marker of AKI. <h3>Acknowledgement</h3> This study was supported by the grant from Medical University of Silesia (KNW–1–057/P/2/0).

Predictive Power of Serial Neonatal Therapeutic Intervention Scoring System Scores for Short-term Mortality in Very-low-birth-weight Infants

The Neonatal Therapeutic Intervention Scoring System (NTISS) is used to indicate disease severity for neonates who need intensive care. We examined the ability of serial NTISS scores to predict mortality in very-low-birth-weight preterm infants. We reviewed the medical records of all preterm infants that had a birth weight of <1500g and were admitted to a neonatal intensive care unit from 2007 to 2011. We calculated the NTISS scores at 24 hours, 48 hours, and 72 hours after admission, and assessed the predictive power for mortality using receiver-operating characteristic curve and area under the curve analysis. We also constructed a predictive model with gestational age, birth weight, and NTISS scores to predict mortality in these very-low-birth-weight infants. In total, 172 infants were enrolled into this study. Eighteen (10.5%) infants died in the first 7 days after birth. The area under the curve of the NTISS score was 0.913 at 24 hours, 0.955 at 48 hours, and 0.958 at 72 hours. However, there was no significant difference in the overall average NTISS scores between 48 hours and 72 hours. The NTISS score at 48 hours was a better predictor of mortality than that at 24 hours after admission. Combining gestational age, birth weight, and NTISS score at 48 hours, birth weight was found to contribute little to the predictive power of mortality. The model with gestational age and NTISS score at 48 hours had a better predictive power than the NTISS score alone (area under the curve=0.99). The NTISS score at 48 hours seemed to be effective to predict mortality in preterm infants whose birth weight was less than 1500g. In addition, gestational age played a more important role in predicting mortality than birth weight.

The validity of the variable “NICU admission” as an outcome measure for neonatal morbidity: a retrospective study

To determine whether "neonatal intensive care unit (NICU) admission" is a valid surrogate outcome measure to assess neonatal condition in clinical studies. Retrospective study. Tertiary hospital in the Netherlands. Neonates admitted to NICU during a 10-year period. Inclusion was restricted to singletons born beyond 37weeks of gestation, and admitted to NICU in the first 24h for delivery-related morbidity. Patient characteristics and admission data were compared for four groups based on the line of care during delivery, i.e. home birth (Ia), midwife-led hospital delivery (Ib), secondary care (II), tertiary care (III). Percentage of neonates/infants that died during NICU admission, diagnosis on admission, treatment received and a Neonatal Therapeutic Intervention Score System (NTISS). We studied 776 newborns (Ia 52, Ib 25, II 160, III 512, 27 unknown). The mortality rate differed significantly (Ia 15%, Ib 12%, II 22%, III 1%, p<0.01), as did the NTISS morbidity scores at admission [Ia 12.0 (6.0-23.0), Ib 8.5 (6.3-10.0), II 21.0 (15.0-30.0), III 6.0 (4.0-9.0); p<0.01], diagnosis at admission, received treatment and the duration of admission. The severity of neonatal illness after 37weeks of gestation differed depending on the line of care in which they were born, with neonates born in secondary care consistently having the highest morbidity, and those born in tertiary care having the lowest. NICU admission should not be used as an outcome measure for neonatal morbidity, specifically not when comparing different birth settings.

Serum and Urinary NGAL in Septic Newborns

Neutrophil gelatinase-associated lipocalin (NGAL) is postulated to be a potentially new and highly specific/sensitive marker of acute kidney injury (AKI). The aim of this study was to assess the impact of inflammation on serum and urine NGAL in newborns that were treated due to infection. We determined serum and urine NGAL concentrations in 73 infants (51 with sepsis; 22 with severe sepsis) admitted to the Intensive Care Unit in the first month of life, for three consecutive days during the course of treatment for infection. 29 neonates without infection served as the control group. Septic patients, in particular, severe sepsis patients, had increased serum and urinary NGAL levels in the three subsequent days of observation. Five septic patients who developed AKI had elevated serum and urinary NGAL values to a similar extent as septic neonates without AKI. A strong correlation was found between the concentration of serum and urinary NGAL and inflammatory markers, such as CRP and procalcitonin. Serum and urinary NGAL levels were also significantly associated with NTISS (neonatal therapeutic intervention scoring system) values. We conclude that increased serum and urinary NGAL values are not solely a marker of AKI, and more accurately reflect the severity of inflammatory status.