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BACKGROUND: To evaluate the impact of implementation of 2019 European respiratory distress syndrome (RDS) guidelines on the incidence of bronchopulmonary dysplasia (BPD). METHOD: We retrospectively collected the clinical data of very preterm infants (VPIs) born before 32 gestational weeks from January 1st 2018 to December 31st 2021. VPIs were divided into group A and group B according to their birth date which was before or at/after January 1st 2020, when the 2019 European RDS guidelines were introduced. BPD is considered as primary outcome. We statistically analyzed all the data, and we compared the general characteristics, ventilation support, medication, nutrition and the outcomes between the two groups. RESULTS: A total of 593 VPIs were enrolled, including 380 cases in group A and 213 cases in group B. There were no statistic differences regarding to gender ratio, gestational age, birth weight and delivery mode between the two groups. Compared with group A, group B showed higher rate of antenatal corticosteroid therapy (75.1% vs. 65.5%). The improvement of ventilation management in these latter patients included lower rate of invasive ventilation (40.4% vs. 50.0%), higher rate of volume guarantee (69.8% vs. 15.3%), higher positive end expiratory pressure (PEEP) [6 (5, 6) vs. 5 (5, 5) cmH2O] and higher rate of synchronized nasal intermittent positive pressure ventilation (sNIPPV) (36.2% vs. 5.6%). Compared with group A, group B received higher initial dose of pulmonary surfactant [200 (160, 200) vs. 170 (130, 200) mg/Kg], shorter antibiotic exposure time [13 (7, 23) vs. 17 (9, 33) days], more breast milk (86.4% vs. 70.3%) and earlier medication for hemodynamically significant patent ductus arteriosus (hsPDA) treatment [3 (3, 4) vs. 8 (4, 11) days] (p < 0.05). As the primary outcome, the incidence of BPD was significantly decreased (16.9% vs. 24.2%) (p < 0.05), along with lower extrauterine growth retardation (EUGR) rate (39.0% vs. 59.7%), while there were no statistic differences regarding to other secondary outcomes, including mortality, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), retinopathy of preterm (ROP) and necrotizing enterocolitis (NEC). However, in the subgroups of infants less than 28 gestational weeks or infants less than 1,000 g, the incidence of BPD was not significantly decreased (p > 0.05). CONCLUSIONS: After implementation of 2019 European RDS guidelines, the overall incidence of BPD was significantly decreased in VPIs. Continuous quality improvement is still needed in order to decrease the incidence of BPD in smaller infants who are less than 28 gestational weeks or less than 1,000 g.

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Fortified human milk is the first choice for preterm infants. Although individualized fortification is recommended, the optimal method for this population remains uncertain. We conducted a comparative study assessing the growth effects of adjusted (AF) and targeted fortification (TF) in extremely low birth weight (ELBW) infants. This single-center, randomized, controlled clinical trial was conducted at a tertiary neonatal unit in Spain. Eligible participants were premature infants with a birthweight of <1000 g exclusively fed with human milk. A total of 38 patients were enrolled, 15 of them randomized to AF group and 23 to TF group. AF was based on blood urea nitrogen (BUN) concentration and TF on human milk analysis. The primary outcome was weight gain velocity (g/kg/day). No significant differences were found in weight gain velocity at 28 days, at 36 weeks of postmenstrual age, at discharge, nor during the intervention. Protein intake was significantly higher in the AF group (5.02 g/kg/day vs. 4.48 g/kg/day, p = 0.001). No differences were found in the lipid, carbohydrate, and energy intake; in the weight z score change between the different time points; nor in the length and head circumference growth. Both AF and TF are comparable methods of fortification and provide the appropriate growth rate in ELBW infants.

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BACKGROUND: The incidence of vitamin D deficiency among pregnant women remains high and is associated with vitamin D deficiency in infants. In normally breastfed infants, Bifidobacteriaceae and Lactobacillaceae are known to help in maintaining immunotolerance and prevent infection. Vitamin D in the gastrointestinal tract plays a role in determining the composition and function of intestinal bacteria. Preterm infants are vulnerable to intestinal dysbiosis and sepsis due to bacterial translocation. This study aimed to determine the association between vitamin D levels and intestinal dysbiosis. METHODS: It was a cohort study conducted in the Neonatal Unit, Cipto Mangunkusumo Hospital, Tertiary hospital in Indonesia, from November 2019 to January 2021. The inclusion criteria in this study were preterm infants with a gestational age of less than 32 weeks or a birth weight of less than 1500 g. Total 25-hydroxyvitamin D (25(OH)D) levels were collected from the umbilical cords of very preterm or very low birth weight infants. A fecal examination was performed on the seventh day of life to assess intestinal bacteria using real-time PCR for four bacterial genera: Bifidobacteriaceae, Lactobacillaceae, Enterobacteriaceae, and Clostridiaceae. RESULTS: A total of 43 infants were included in this study. Among the subjects, 53.4% had vitamin D deficiency. There was no association identified between vitamin D deficiency and intestinal dysbiosis (RR 0.67; 95% CI (0.15-2.82), p-value = 0.531). However, the ratio of Lactobacillacecae to Enterobacteriaceae was lower in those with vitamin D deficiency. CONCLUSION: Vitamin D deficiency was not associated with dysbiosis in preterm infants. However, this study found that the ratio of Lactobacillaceae to Enterobacteriaceae in those with vitamin D deficiency was lower than in those without vitamin D deficiency. Further research is warranted to confirm this finding.

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Background: Prematurity presents a significant life crisis for families, often exceeding their expectations. Fathers of premature infants face the burden of multiple caregiving roles and undergo psychological changes. When confronted with such crises, individuals often engage in self-evaluation and may experience positive transformations. This study aims to employ a qualitative research methodology to explore the experiences of fathers of preterm infants. Materials and methods: A phenomenological approach design will be utilized, drawing upon semi-structured in-depth interviews informed by existing literature. Thematic analysis will be employed, adhering to the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. In-depth individual interviews, lasting 40-60 minutes, will be conducted with fathers of preterm infants to understand their experiences. The thematic analysis process will facilitate a comprehensive understanding of the factors contributing to post-traumatic growth among these fathers. This methodology provides a structured approach to investigating the experiences and influences on post-traumatic growth in fathers of preterm infants. Results: This study will highlight changes in post-traumatic growth among fathers of preterm infants. Discussion: Research on the post-traumatic growth (PTG) of fathers of preterm infants is crucial to understanding the unique challenges and psychological transformations they experience. This study aims to explore the factors contributing to PTG in these fathers and how cultural contexts in China influence this process. By elucidating these aspects, the findings can inform targeted interventions and support systems tailored to the needs of fathers of preterm infants. The results may also contribute to developing guidelines and policies to promote psychological well-being and resilience among this population in the healthcare system. Ethics and dissemination: This study adheres to the International Ethical Guidelines for Biomedical Research and the Declaration of Helsinki. Approval has been obtained from the People's Hospital of Deyang Human Research Ethics Committee (No: 2019-04-150-K01). The research follows the principles of open science, and the findings will be published while ensuring participants' confidentiality.

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BACKGROUND: This study aims to evaluate the impact of a home-based, post-discharge early intervention (EI) program on reducing parental stress levels in families with preterm infants born between 28+ 0 and 31+ 6 weeks gestational age. METHODS: A randomized controlled trial was conducted, with families randomly allocated to either the EI or standard care (SC) group. A term reference group was also recruited for comparison. The Parental Stress Index-Short Form was used to assess parental stress levels, yielding a total stress score and three subdomain scores. Assessment was performed at baseline, at the 60-day mark of the study, and when the infants reached six corrected months of age. Parents in the reference group were assessed only at six months of corrected age for infants. The intervention comprised three sections: intellectual, physical, and social training, which was administered to the infants in the EI group immediately after discharge and to those in the SC group after 60 days of enrollment. RESULTS: Seventy-three families were enrolled in this study, with 37 allocated to the EI group, and 36 to the SC group. Prior to intervention, higher stress levels were reported by mothers in both groups than fathers, with no difference observed between the EI and SC groups. Re-assessment performed at 60 days of the study showed that mothers and fathers in the EI group had significantly lower total stress score than those in the SC group (82.00 ± 5.64 vs. 94.26 ± 7.99, p < 0.001; 80.74 ± 7.14 vs. 89.94 ± 9.17, p < 0.001, respectively), which was predominantly due to the lower scores in parental distress and parental-child dysfunction interaction subdomains in the EI group (both had p < 0.001). Mothers in the EI group exhibited a more pronounced reduction in total stress score after intervention when compared to fathers (13.15 ± 4.68 vs. 8.26 ± 4.03, p < 0.001). At six months of infant age, the total stress score and subdomain scores of parents in the EI and SC groups were similar, but significantly higher than those of the reference group. CONCLUSION: The home-based, post-discharge EI program demonstrated significant effectiveness in reducing parental stress levels among the parents of very preterm infants. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (registration number: CTR1900028330). Registration date: December 19, 2019.

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BACKGROUND: Premature infants have less physiologic reserve and often delayed vaccination compared to full-term infants. The birth dose of hepatitis B vaccine (HepB-BD) is an essential measure to achieve the goal of "zero infections" of hepatitis B virus in all newborns. However, there are few investigations of hepatitis B vaccination of preterm infants, leading to uncertainty of coverage and insufficient knowledge of factors influencing timely vaccination of this important population. METHODS: We obtained hepatitis B vaccine (HepB) vaccination histories of premature infants born during 2019-2021 in three provinces from the respective provincial immunization information systems. Extracted data included date of birth, sex, region, and dates of HepB administration. We conducted descriptive analyses that included basic characteristics of the study subjects, HepB-BD administration, and full-series HepB vaccination. Factors potentially influencing HepB-BD and full series vaccination were analyzed by logistic regression. RESULTS: There were 1623 premature infants included in the analytic data set. Overall HepB-BD coverage was 71.41%; coverage among premature infants born to mothers with unknown hepatitis B surface antigen (HBsAg) status was 69.57%; coverage was higher at county-level-and-above hospitals (72.02%) than hospitals below county level (61.11%). Full-series HepB coverage was 94.15%; full-series coverage among preterm infants weighing less than 2000 g at birth was 76.92%. Logistic regression showed that the HepB-BD vaccination rate was positively associated with being born to an HBsAg-positive mother and being preterm with high birth weight. Regression analysis for factors influencing full-series HepB coverage showed that being born prematurely was positively associated with full-series coverage and being premature with a very low birth weight was negatively associated with full-series coverage. CONCLUSIONS: HepB-BD coverage levels in three provinces of China were less than the target of 90%, especially among premature infants born to mothers with unknown HBsAg status and at hospitals below the county level. Screening of pregnant women should be a universal normal standard. Hepatitis B vaccination training should be strengthened in hospitals to improve the HepB-BD vaccination rate of premature infants and to effectively prevent mother-to-child transmission of hepatitis B virus.

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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.

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AIM: Concerns exist regarding potential adverse neurodevelopmental outcomes associated with paracetamol exposure during pregnancy and early infancy. This review evaluates the evidence for the impact of paracetamol use for patent ductus arteriosus (PDA) treatment on neurodevelopmental outcomes in preterm infants. METHODS: A literature search was performed via Medline, Ovid Embase and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. The search details are below: ('Infant, Newborn' [MeSH] OR 'neonate*' [Title/Abstract]) AND ('Paracetamol' [MeSH] OR 'Acetaminophen' [Title/Abstract]) AND ('Ductus Arteriosus, Patent/drug therapy' [MeSH] OR 'patent ductus arteriosus' [Title/Abstract]) AND ('Neurodevelopmental Disorders' [MeSH] OR 'neurodevelopment*' [Title/Abstract] OR 'Child Development' [MeSH] OR 'Developmental Disabilities' [MeSH]). All studies were critically appraised and synthesised. RESULTS: Seven studies reported neurodevelopmental outcomes after paracetamol use for PDA treatment in preterm infants <32 weeks gestation. The studies varied in dosage, route, and duration of paracetamol administration and in the methods used to assess neurodevelopmental outcomes. None of the studies revealed different outcomes between paracetamol-exposed preterm infants and controls. CONCLUSION: Current low-to-moderate quality evidence suggests no association between paracetamol used for PDA treatment and adverse neurodevelopmental outcomes in preterm infants. Future well-powered studies with standardised neurodevelopmental assessments are warranted to strengthen the current evidence base.

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OBJECTIVE: This study aimed to prove the effectiveness of physiological flexion swaddling and oromotor interventions in terms of the duration needed to achieve the oral feeding ability of preterm infants in the NICU. METHODS: A randomized clinical trial in five Neonatal intensive care units (NICU) was performed involving 70 preterm infants born at 28-34 weeks gestational age. Participants were allocated to 1) the experimental group (n = 39) received physiological flexion swaddling and oromotor interventions, and 2) the control group (n = 31) received conventional swaddling and oromotor interventions. Mann-Whitney U analysis was used to determine the effectiveness of each group according to the duration needed to achieve oral feeding ability, while Kaplan-Meier survival analysis was applied to compare the duration of both groups. RESULTS: The experimental group had a significantly shorter duration in achieving oral feeding ability [4 (1-15) vs. 7 (2-22) days; p = 0.02]. The Kaplan-Meier survival curve analysis showed that infants in the experimental group achieved full oral feeding ability earlier than those in the control group (15 vs. 22 days). CONCLUSIONS: Physiological flexion swaddling and oromotor interventions have been proven to be effective in shortening the number of days needed to achieve the oral feeding ability of preterm infants in the NICU.

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Germinal matrix-intraventricular hemorrhage (GM-IVH) is a detrimental neurological complication that occurs in preterm infants, especially in babies born before 32 weeks of gestation and in those with a very low birth weight. GM-IVH is defined as a rupture of the immature and fragile capillaries located in the subependymal germinal matrix zone of the preterm infant brain, and it can lead to detrimental neurological sequelae such as posthemorrhagic hydrocephalus (PHH), cerebral palsy, and other cognitive impairments. PHH following GM-IVH is difficult to treat in the clinic, and no levelone strategies have been recommended to pediatric neurosurgeons. Several cellular and molecular mechanisms of PHH following GM-IVH have been studied in animal models, but no effective pharmacological strategies have been used in the clinic. Thus, a comprehensive understanding of molecular mechanisms, potential pharmacological strategies, and surgical management of PHH is urgently needed. The present review presents a synopsis of the pathogenesis, diagnosis, and cellular and molecular mechanisms of PHH following GM-IVH and explores pharmacological strategies and surgical management.

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AIM: We investigated the associations between motor performance and IQ at 5 years of age and school difficulties and grade point averages (GPAs) at 18 years of age. Additionally, the accuracy of preschool IQ in predicting school difficulties was examined. METHODS: A nationwide follow-up study of children born in 1994-1995 who were <28 weeks of gestation or had a birthweight <1000 g. The Danish personal identification number was used to merge data from a national cohort study with population-based registries. Logistic regression analyses examined the associations between motor performance/IQ and school difficulties. Linear regression analyses and the area under the receiver operator curve (AUC) were used to examine the relationship between IQ and GPAs. RESULTS: The study population comprised 248 children, 37% were classified with school difficulties. Motor performance and IQ were associated with school difficulties. The odds of having school difficulties increased as IQ decreased, and the same pattern was observed for GPAs. IQ predicted school difficulties, with an AUC of 0.80 (confidence interval: 0.74-0.86). CONCLUSION: Preschool motor performance and IQ were associated with school difficulties. Additionally, IQ was linked to GPAs. As a screening tool, the predictive ability of preschool IQ for academic difficulties was moderate/high in this cohort.

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Peripherally inserted central catheters (PICCs) play a critical role in neonatal intensive care units (NICUs), facilitating treatment in premature and critically ill neonates. However, achieving optimal PICC placement can present challenges, requiring meticulous monitoring and adjustment. Here, we describe the case of a 52-day-old, 1.9 kg preterm infant in the NICU requiring a central venous catheter for antibiotics and antifungals. Despite initial insertion into the basilic vein of the right forearm, imaging revealed the catheter's deviation into the right internal jugular vein. Leveraging the influence of arm position on catheter tip depth, external manipulation of the infant's right arm successfully repositioned the catheter tip into the superior vena cava (SVC). This case highlights the significant impact of arm positioning on PICC placement and underscores the efficacy of external extremity manipulation as a simple, non-invasive technique to adjust catheter position. Such innovative strategies offer promising alternatives to invasive interventions, emphasizing the importance of dynamic monitoring and adjustment techniques in neonatal PICC management.

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BACKGROUND: Preterm birth contributes to adverse mental health outcomes of parents dealing with a premature neonate. The main objective of this study is to determine whether music therapy (MT) songwriting during the infants' stay in the neonatal intensive care unit (NICU) is superior to standard care in reducing the risk of postpartum depression in high-risk parents of preterm children throughout the hospital treatment. The secondary objectives include assessment of effectiveness of MT in other aspects of mental health (anxiety level, perceived stress, mental wellbeing, coping, resilience). Furthermore, this trial will evaluate the medical and social factors that may be associated with the effects of MT songwriting. PARTICIPANTS AND PROCEDURE: The study design is a sequential mixed method study with a dominant status QUAN to qual. The quantitative trial was designed as a parallel, multicenter, pragmatic, randomized controlled trial. The qualitative study is a descriptive phenomenological study that seeks to understand the lived experiences of participants exposed to songwriting. Participants are parents of premature infants hospitalized in NICU (106 families) in 5 hospitals, in Colombia and Poland. Intervention: 3 MT songwriting sessions per week across 3 weeks. Primary outcome: the risk of postnatal depression; secondary outcomes: anxiety level, mental wellbeing, resilience, stress, coping. RESULTS: The results will be analyzed quantitatively and qualitatively. CONCLUSIONS: This study will provide a report on the effectiveness of MT songwriting on mental health in at-risk parents of preterm infants.

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BACKGROUND: Several population pharmacokinetic (PopPK) models of caffeine in preterm infants have been published, but the extrapolation of these models to facilitate model-informed precision dosing (MIPD) in clinical practice is uncertain. This study aimed to comprehensively evaluate their predictive performance using an external, independent dataset. METHODS: Data used for external evaluation were based on an independent cohort of preterm infants. Currently available PopPK models for caffeine in preterm infants were identified and re-established. Prediction- and simulation-based diagnostics were used to assess model predictability. The influence of prior information was assessed using Bayesian forecasting. RESULTS: 120 plasma samples from 76 preterm infants were included in the evaluation dataset. Twelve PopPK models of caffeine in preterm infants were re-established based on our previously published study. Although two models showed superior predictive performance, none of the 12 PopPK models met all the clinical acceptance criteria of these external evaluation items. Besides, the external predictive performances of most models were unsatisfactory in prediction- and simulation-based diagnostics. Nevertheless, the application of Bayesian forecasting significantly improved the predictive performance, even with only one prior observation. CONCLUSIONS: Two models that included the most covariates had the best predictive performance across all external assessments. Inclusion of different covariates, heterogeneity of preterm infant characteristics, and different study designs influenced predictive performance. Thorough evaluation is needed before these PopPK models can be implemented in clinical practice. The implementation of MIPD for caffeine in preterm infants could benefit from the combination of PopPK models and Bayesian forecasting as a helpful tool.

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Introduction: Human cytomegalovirus (HCMV) is the most common viral infection seen in newborns. The major route of transmission for acquired human cytomegalovirus infection is breast milk from mothers who are HCMV seropositive to the infants. Thus, a rapid, economical, and simple method to perform HCMV test in breast milk is crucial and necessary for preventing acquired HCMV infection, especially in underdeveloped regions with limited laboratory resources. Methods: In this study, an effective technique for the detection of HCMV was constructed by combining multienzyme isothermal rapid amplification (MIRA) and lateral flow chromatography strip (LFD). Primers for the conserved HCMV sequence UL83 were utilized for MIRA-LFD testing. Results: Our results showed that the entire MIRA reaction could be completed in 12 minutes at 37°C, and LFD outcomes could be observed visibly after 10 minutes. The detection sensitivity of this method reached 50 copy/µl. Samples of breast milk were examined to compare MIRA-LFD and conventional qPCR. The accuracy of MIRA-LFD was 100%. Discussion: The straightforward, rapid, economic features of the test can provide the significant advantages for the prevention of breast milk-acquired cytomegalovirus infection, particularly in resource-limited locations with high seroprevalence of cytomegalovirus.

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Bronchopulmonary dysplasia (BPD) is a common morbidity affecting preterm infants and is associated with substantial long-term disabilities. The pathogenesis of BPD is multifactorial, and the clinical phenotype is variable. Extensive research has improved the current understanding of the factors contributing to BPD pathogenesis. However, effectively preventing and managing BPD remains a challenge. This review aims to provide an overview of the current evidence regarding the prevention of BPD in preterm infants, offering practical insights for clinicians.

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AIM: To assess the effect of ventricular decompression on cerebral oxygenation in preterm neonates with intraventricular haemorrhage (IVH) and posthemorrhagic ventricular dilatation (PHVD) using near-infrared spectroscopy (NIRS). METHODS: Fifty-three preterm neonates born <34 weeks' gestation between 2013 and 2023 with IVH and subsequent PHVD were prospectively included. Regional cerebral oxygen saturation (rScO2) as well as fractional cerebral tissue oxygen extraction (cFTOE) were analysed 2 weeks before and after ventricular decompression. RESULTS: Ventricular decompression was performed at 18 ± 6 days of life. Patients with repeated lumbar punctures prior to ventricular drainage showed consistently higher rScO2 and lower cFTOE levels 2 weeks before and after intervention compared to those without. Patients who underwent direct ventricular drainage showed an immediate increase in rScO2 levels on the day of the procedure. In patients who underwent prior lumbar punctures, ventricular decompression did not yield additional acute effects on cerebral oxygenation. CONCLUSION: Patients who underwent repeated lumbar punctures preceding ventricular drainage consistently maintained higher rScO2 and lower cFTOE levels during the study period. In these patients, ventricular decompression did not further affect cerebral oxygenation, as they already demonstrated improved cerebral hemodynamics, whereas an immediate improvement was observed in those without prior lumbar punctures.

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Lung function has never been assessed during kangaroo mother care (KMC) in preterm infants. We measured lung (rSO2L) and cerebral (rSO2C) oxygenation by near-infrared spectroscopy (NIRS) in infants born at less than 32 weeks of gestation or weighing ≤ 1500 g during KMC. rSO2L, rSO2C, and pulmonary (FOEL) and cerebral (FOEC) tissue oxygen extraction fraction were measured in 20 preterm infants before, during, and after a 2-h period of KMC at a mean postnatal age of 36 ± 21 days of life. We found that rSO2L, rSO2C, FOEL, and FOEC did not change in our patients. After 120 min of KMC, rSO2L was lower (71.3 ± 1.4 vs. 76.7 ± 4.6%; P = 0.012) in infants with BPD (n = 6; 30%) than in infants without BPD (n = 14 = 60%), while FOEL was higher (0.26 ± 0.02 vs. 0.20 ± 0.05; P = 0.012).Conclusion: Cerebral and lung oxygenation did not change in preterm infants during KMC. A transient decrease in lung oxygenation was offset by the increase in oxygen extraction, but these changes were clinically insignificant. These results confirm the safety of KMC in preterm infants who are in stable clinical conditions. What is Known • Kangaroo mother care (KMC) is widely used to improve the care of preterm newborns since it improves their outcome. • KMC is safe as patients' vital parameters, are not negatively affected, but lung function has never been directly assessed. What is New • Cerebral and lung oxygenation measured by near-infrared spectroscopy did not change during KMC. • A transient decrease in lung oxygenation compensated for by the increase in oxygen extraction occurred only in infants with BPD, but these changes were clinically insignificant.

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Objective: To examine whether variation of regional cerebral oxygen saturation (rScO2) within three days after delivery predicts development of brain injury (intraventricular/cerebellar hemorrhage or white matter injury) in preterm infants. Study design: A prospective study of neonates <32 weeks gestational age with normal cranial ultrasound admitted between 2018 and 2022. All received rScO2 monitoring with near-infrared spectroscopy at admission up to 72 h of life. To assess brain injury a magnetic resonance imaging was performed at term-equivalent age. We assessed the association between rScO2 variability (short-term average real variability, rScO2ARV, and standard deviation, rScO2SD), mean rScO2 (rScO2MEAN), and percentage of time rScO2 spent below 60% (rScO2TIME<60%) during the first 72 h of life and brain injury. Results: The median [IQR] time from birth to brain imaging was 68 [59-79] days. Of 81 neonates, 49 had some form of brain injury. Compared to neonates without injury, in those with injury rScO2ARV was higher during the first 24 h (P = 0.026); rScO2SD was higher at 24 and 72 h (P = 0.029 and P = 0.030, respectively), rScO2MEAN was lower at 48 h (P = 0.042), and rScO2TIME<60% was longer at 24, 48, and 72 h (P = 0.050, P = 0.041, and P = 0.009, respectively). Similar results were observed in multivariable logistic regression. Although not all results were statistically significant, increased rScO2 variability (rScO2ARV and rScO2SD) and lower mean values of rScO2 were associated with increased likelihood of brain injury. Conclusions: In preterm infants increased aberration of rScO2 in early postdelivery period was associated with an increased likelihood of brain injury diagnosis at term-equivalent age.

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BACKGROUND: Considerable interindividual variability for the pharmacokinetics of caffeine in preterm infants has been demonstrated, emphasizing the importance of personalized dosing. This study aimed to develop and apply a repository of currently published population pharmacokinetic (PopPK) models of caffeine in preterm infants to facilitate model-informed precision dosing (MIPD). RESEARCH DESIGN AND METHODS: Literature search was conducted using PubMed, Embase, Scopus, and Web of Science databases. Relevant publications were screened, and their quality was assessed. PopPK models were reestablished to develop the model repository. Covariate effects were evaluated and the concentration-time profiles were simulated. An online simulation and calculation tool was developed as an instance. RESULTS: Twelve PopPK models were finally included in the repository. Preterm infants' age and body size, especially the postnatal age and current weight, were identified as the most clinically critical covariates. Simulated blood concentration-time profiles across these models were comparable. Caffeine citrate-dose regimen should be adjusted according to the age and body size of preterm infants. The developed online tool can be used to facilitate clinical decision-making. CONCLUSIONS: The first developed repository of PopPK models for caffeine in preterm infants has a wide range of potential applications in the MIPD of caffeine.