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

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.

Physiology during sleep in preterm infants: Implications for increased risk for the sudden infant death syndrome.

Approximately 15 million babies are born preterm (<37 weeks of completed gestation) worldwide annually. Although neonatal and perinatal medicine have contributed to the increased survival rate of preterm newborn infants, premature infants are at increased risk of mortality in the first years of life. Infants born preterm are at four times the risk of Sudden Infant Death Syndrome (SIDS) compared to infants born at term. SIDS is believed to be multifactorial in origin. The Triple Risk hypothesis has been proposed to explain this. The model suggests that when a vulnerable infant, such as one born preterm, is at a critical but unstable developmental period in homeostatic control, death may occur if exposed to an exogenous stressor, such as being placed prone for sleep. The highest risk period is at ages 2-4 months, with 90 % of deaths occurring before 6 months. The final pathway to SIDS is widely believed to involve some combination of immature cardiorespiratory control and a failure of arousal from sleep. This review will focus on the physiological factors which increase the risk for SIDS in preterm infants and how these factors may be identified and potentially lead to effective preventative strategies.

High threshold of total developmental quotient at 3 years for follow-up in extremely preterm infants.

AIM: To investigate the relationship between the developmental quotient (DQ) at age 3 years and the need for educational support at school age in extremely preterm infants. METHODS: A total of 176 infants with a gestational age of <28 weeks were analyzed. The total DQ and subscales were evaluated using the Kyoto Scale of Psychological Development (KSPD) test. Neurodevelopment at age 3 years was stratified using total DQ in a conventional (DQ < 70 as developmental delay, DQ 70- <85 as subnormal, DQ ≥85 as normal) and a modified way (subdividing normal into DQ 85- <93 as low-normal and DQ ≥93 as high-normal). The prevalence of future educational support was compared for each stratum. Additionally, subscales were compared between those with and without educational support in each total DQ stratum. RESULTS: In conventional stratification, the prevalence of educational support was 32 (63 %) for developmental delay, 14 (24 %) for subnormal, and 10 (15 %) for normal. In modified stratification, the prevalence was 8 (26 %) for low-normal and 2 (5 %) for high-normal. While there was no significant difference in the odds of educational support between the normal and subnormal, the low-normal had significantly higher odds compared to the high-normal (OR 6.00; 95 % CI, 1.16-30.95, p = 0.03). Among the low-normal stratum, the language-social subscale was significantly lower in those with educational support. CONCLUSION: Setting high thresholds for total DQ and evaluating detailed subscales at age 3 years may be useful for developmental follow-up in extremely preterm infants.

Predictors of Direct Breastfeeding in Preterm Infants.

Objective: Rates of mother's own milk (MOM) provision in the neonatal intensive care unit (NICU) vary widely, despite acceptance as the gold standard for nutrition in preterm infants. Direct breastfeeding (DBF) supports long-term provision of MOM, but factors that support DBF in preterm infants are unknown. The purpose of this study was to identify factors that predict DBF at oral feeding initiation and at NICU discharge. Methods: This was a retrospective cohort study of preterm infants born at ≤ 32 weeks who were receiving MOM at 32 weeks corrected gestational age (cohort 1) and at discharge to home (cohort 2). The primary outcomes were rates of DBF at oral feeding initiation (cohort 1) and at hospital discharge (cohort 2). We examined bivariate associations between infant characteristics, maternal sociodemographic factors, and hospital practices (e.g., lactation visit timing and frequency) with DBF outcomes and then built logistic regression models to determine the adjusted odds ratio and 95% confidence interval ([adjusted odds ratio [aOR] [95%CI]) for independent predictors of the DBF outcomes. Results: Sixty-four percent of eligible infants initiated DBF, and 51% were DBF at discharge. Sociodemographic, NICU, and lactation support factors were associated with both outcomes. Post hoc analysis showed that similar factors also influenced lactation support provision. Conclusions: Lactation support, NICU and sociodemographic variables influence DBF initiation and DBF at discharge. Interventions that optimize efficient use of available lactation support, address bias, and provide ample opportunity for DBF practice could improve rates.

Improving accuracy of outcome prediction for infants born extremely preterm using a digital tool: Translating 'NIC-PREDICT' into clinical practice, the first steps.

BACKGROUND: Many clinicians overestimate mortality and disability rates in infants born extremely preterm. We developed a digital tool ('NIC-PREDICT') that predicts infant mortality and survival with and without major disability in infants born 23-27 weeks' gestation. AIMS: To determine if clinicians could use NIC-PREDICT accurately, and if their perceptions of infant outcomes improved after its release in 2021. MATERIALS AND METHODS: Midwives, nurses, obstetricians, neonatologists and paediatricians working in tertiary and non-tertiary hospitals in Victoria were asked to use NIC-PREDICT to estimate three mutually exclusive outcomes: (i) mortality; (ii) survival free of major disability; and (iii) survival with major disability for six different scenarios where a liveborn infant was offered survival-focused care after birth. The proportions who completed the survey (responded to all six scenarios) and the proportions able to provide 100% accurate results for all scenarios were determined. Estimates of the three outcomes were compared with true rates. RESULTS: A total of 85 clinicians responded: 70 (82%) completed the survey, with an overall accuracy of 76%. Overall, predictions of mortality were accurate (mean difference from true value 0.7% (95% confidence interval (CI) -0.7, 2.1) P = 0.33), as were predictions of survival without major disability (mean difference - 0.7 (95% CI -3.0, 1.7) P = 0.58). However, survival with major disability was overestimated by 4.9% ((95% CI 1.7, 8.0) P = 0.003). CONCLUSIONS: Most perinatal clinicians who responded used NIC-PREDICT correctly to estimate expected outcomes in infants born extremely preterm who are offered intensive care. Undue pessimism about survival with major disability remains an ongoing concern.

A Volume-Adjustable Artificial Womb for Extremely Preterm Infants.

More than 13 million children are born preterm annually. Prematurity-related mortality accounts for 0.9 million deaths worldwide. The majority of those affected are Extremely Preterm Infants (gestational age less than 28 weeks). Immaturity causes organ failure and specific morbidities like germinal matrix hemorrhage, bronchopulmonary dysplasia, and necrotizing enterocolitis. Artificial womb and placenta technologies address these issues. As a bridge-to-life technology, they provide a liquid environment to allow organ maturation under more physiological conditions. The proposed artificial womb can adapt to fetal growth. Volume adjustment is achieved by removing fluid from the interspace between an inner and outer chamber. Results of the in vitro tests showed a temperature constancy of 36.8°C ± 0.3°C without pressure loss over 7 days. The volume of the inner sac was variable between 3.6 and 7.0 L. We designed a filtration and disinfection system for this particular purpose. This system has proven strong disinfection capabilities, effective filtering of metabolic waste, and the ability to avoid phospholipid washout. The presented artificial womb has sufficient volume variability to adapt to the physiologic growth of an extremely preterm neonate over a 4-week period. We regard this as an important step in the development of this bridge-to-life technology.

The association between serum 25-hydroxyvitamin D levels and retinopathy of prematurity in preterm infants.

Objective: This study aimed to investigate the correlation between serum 25-hydroxyvitamin D (25(OH)D) levels and retinopathy of prematurity (ROP) in premature infants one month after birth. Methods: Preterm infants (gestational age <32 weeks) admitted to the Affiliated Hospital of Qingdao University from 2017 to 2022 were divided into ROP and non-ROP groups based on ROP occurrence any stage. Serum 25(OH)D levels and clinical data were compared between the two groups at 1 month after birth, and the relationship between vitamin D levels and ROP was analyzed. Results: Among the 217 premature infants included, 55 (25.35%) were in the ROP group, and 162 (74.65%) were in the non-ROP group. The ROP group had lower gestational age and birth weight, longer invasive ventilation (IV), non-invasive ventilation (NIV), and oxygen therapy times compared to the non-ROP group. Apgar scores, cesarean delivery, and antenatal steroids ratios were lower in the ROP group, while sepsis and pulmonary surfactant utilization ratios were higher (all p < 0.05). Significant differences in serum 25-(OH)D levels were observed among children in the non-ROP group (14.20 ± 5.07 ng/ml), ROP treated group (7.891 ± 1.878 ng/ml), and untreated group (12.168 ± 4.354 ng/ml) (p < 0.001). Multivariate regression analysis identified antenatal steroids as protective factors and lower birth weight, serum 25-(OH)D levels, long-term invasive mechanical ventilation, and sepsis as independent risk factors for ROP in premature infants. Conclusion: Vitamin D, lower birth weight, long-term invasive mechanical ventilation, and sepsis were associated with incidence of ROP in preterm infants. Vitamin D was associated with the severity of ROP, emphasizing the importance of prudent vitamin D supplementation and regular monitoring of serum 25-(OH)D levels.

[Interpretation of the 2023 "Guidelines for parenteral nutrition in preterm infants: the American Society for Parenteral and Enteral Nutrition"]. / ã€Šç¾Žå›½è‚ å¤–è‚ å† è¥å »å­¦ä¼šæ—©äº§å„¿è‚ å¤–è¥å »æŒ‡å—ï¼ˆ2023）》解读.

The "Guidelines for parenteral nutrition in preterm infants: the American Society for parenteral and enteral nutrition" were developed by the American Society for Parenteral and Enteral Nutrition and published in the Journal of Parenteral and Enteral Nutrition in September 2023. The guidelines provide recommendations on 12 key clinical questions regarding parenteral nutrition (PN) for preterm infants. In comparison to similar guidelines, this set offers more detailed perspectives on PN for preterm infants. It presents evidence-based recommendations for the commencement time, nutrient dosage, and composition of PN, considering primary outcomes such as growth and development, as well as secondary outcomes like sepsis, retinopathy of prematurity, parenteral nutrition-related liver disease, and jaundice. This article aims to interpret the guidelines to provide a reference for colleagues in the field.

[Clinical characteristics of Ureaplasma urealyticum infection and colonization in extremely preterm infants]. / è¶ æ—©äº§å„¿è§£è„²è„²åŽŸä½“æ„ŸæŸ“åŠå®šæ¤çŠ¶æ€çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the clinical characteristics of Ureaplasma urealyticum (UU) infection and colonization in extremely preterm infants and its impact on the incidence of bronchopulmonary dysplasia (BPD). METHODS: A retrospective analysis was conducted on 258 extremely preterm infants who were admitted to the Department of Neonatology, Shenzhen Maternity and Child Healthcare Hospital, from September 2018 to September 2022. According to the results of UU nucleic acid testing and the evaluation criteria for UU infection and colonization, the subjects were divided into three groups: UU-negative group (155 infants), UU infection group (70 infants), and UU colonization group (33 infants). The three groups were compared in terms of general information and primary and secondary clinical outcomes. RESULTS: Compared with the UU-negative group, the UU infection group had significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay (P<0.05), while there were no significant differences in the incidence rates of BPD and moderate/severe BPD between the UU colonization group and the UU-negative group (P>0.05). CONCLUSIONS: The impact of UU on the incidence of BPD in extremely preterm infants is associated with the pathogenic state of UU (i.e., infection or colonization), and there are significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay in extremely preterm infants with UU infection. UU colonization is not associated with the incidence of BPD and moderate/severe BPD in extremely preterm infants.

[The association between preterm birth and hypertension]. / æ—©äº§ä¸Žé«˜è¡€åŽ‹çš„å ³ç³».

In recent years, the number of premature births worldwide has been increasing, and their long-term prognoses, particularly the cardiovascular outcomes of preterm individuals in adulthood, have become a growing concern. Adults who were born prematurely are at a higher risk for cardiovascular diseases, which may be related to changes in cardiovascular structure, renal structure alterations, changes in body composition, and overactivation of the hypothalamic-pituitary-adrenal axis. To improve the outcomes for preterm individuals, long-term follow-up monitoring and effective prevention and treatment measures are necessary. This article aims to review the relevant literature, summarize the risks and mechanisms of hypertension during childhood and adulthood in those born prematurely, and enhance awareness and understanding of the risk of hypertension in adults who were born prematurely.

Assessment of neural function recovery in premature infants at high risk of brain injury using amplitude integrated electroencephalography and GMs scales.

Preterm infants are a high-risk group for brain injury, and it is important to evaluate the neurological recovery of preterm infants. Therefore, this paper evaluates the neurological recovery in preterm infants at high risk of brain injury by amplitude-integrated EEG and GMs scale. The study collected basic information on preterm infants and performed amplitude integrated EEG examination and GMs scale evaluation. Amplitude integrated EEG examination attaches electrodes using multielectrode arrays onto specific areas of the premature head to record brain wave activity to monitor electrical activity in the preterm brain in real time and amplify and process through the signals received by the electrodes to obtain more detailed EEG data. The GMs scale evaluates the developmental and functional status of the child and allows an objective assessment of the development and recovery of neurological function by observing their performance in motor, language, cognition, and social interaction. Analysis of the data by statistical processing. The results showed that early brain injury was evident in high-risk infants. Amplitude integrated EEG parameters can have some predictive value for brain injury. There were also differences in GMs scale assessment between brain injury and non-brain injury. Amplitude integrated EEG combined with GMs scale has certain value in predicting brain injury and can provide an important basis for early intervention in children with preterm brain injury and help to improve their neurodevelopmental outcome.

Combining artificial intelligence and conventional statistics to predict bronchopulmonary dysplasia in very preterm infants using routinely collected clinical variables.

BACKGROUND: Prematurity is the strongest predictor of bronchopulmonary dysplasia (BPD). Most previous studies investigated additional risk factors by conventional statistics, while the few studies applying artificial intelligence, and specifically machine learning (ML), for this purpose were mainly targeted to the predictive ability of specific interventions. This study aimed to apply ML to identify, among routinely collected data, variables predictive of BPD, and to compare these variables with those identified through conventional statistics. METHODS: Very preterm infants were recruited; antenatal, perinatal, and postnatal clinical data were collected. A BPD prediction model was built using conventional statistics, and nine supervised ML algorithms were applied for the same purpose: the results of the best-performing model were described and compared with those of conventional statistics. RESULTS: Both conventional statistics and ML identified the degree of immaturity (low gestational age and/or birth weight), need for mechanical ventilation, and absent or reversed end diastolic flow (AREDF) in the umbilical arteries as risk factors for BPD. Each of the two approaches also identified additional potentially predictive clinical variables. CONCLUSION: ML algorithms might be useful to integrate conventional statistics in identifying novel risk factors, in addition to prematurity, for the development of BPD in very preterm infants. Specifically, the identification of AREDF status as an independent risk factor for BPD by both conventional statistics and ML highlights the opportunity to include detailed antenatal information in clinical predictive models for neonatal diseases.

Parental views on prospective consent: Experience from a pilot randomised trial recruiting extremely preterm infants during the perinatal period.

AIM: To explore parental perceptions of the consenting process and understanding of the study in a pilot randomised controlled trial wherein extremely premature infants (<29 weeks' gestation) were recruited either antenatally or by 4 h of life. METHODS: We prospectively surveyed parents who had consented, declined consent or were eligible infants in the Positioning Preterm Infants for Neuroprotection study, a low-risk intervention study in the first 72 h of life. Structured interview questions explored the process and acceptability of the consenting approach by the parents and their knowledge of the study. Additional comments made by the parents were transcribed verbatim. RESULTS: Sixty-two parents participated in the surveys; of those, 41 had provided their consent, 8 declined consent and 13 were parents of missed eligible infants. Overall, most parents reported they understood the study well before providing their consent and approaching them for consenting did not create a burden for them. A verbal explanation of the study by the study team, especially by the medical practitioners, was viewed as beneficial. Where consent was obtained in the birthing unit (imminent births and within 4 h of birthing), it was suggested that the 4-h period for obtaining post-natal consent may be too short. A deferred consent with a follow-up opportunity for obtaining informed consent could be a suitable alternative. CONCLUSION: Parents found the consenting process acceptable and indicated they had sufficient understanding of the study to provide an informed consent. Deferred consent should be explored for future, low-risk intervention studies as an alternative to prospective consent where extremely preterm infants need to be recruited in the immediate neonatal period.

Parents' and healthcare providers' perceptions, experiences, knowledge of, and attitudes toward kangaroo care of preterm babies in hospital settings: Mixed-methods systematic review.

BACKGROUND: Kangaroo care is an effective intervention to increase survival and improve the health and development of preterm infants. Despite this, implementation of kangaroo care globally remains low. The objectives of this review were to: (a) synthesize evidence on parents' and healthcare practitioners' perceptions, experiences, knowledge of, and attitudes toward kangaroo care of preterm babies in hospital settings; and (b) establish parents' satisfaction with kangaroo care. METHODS: Studies of any design were included if they focused on parents' or healthcare practitioners' perceptions, experiences, knowledge of, and attitudes to kangaroo care of preterm babies, or reported parents' satisfaction, and were conducted in hospital settings. The search of seven electronic databases, African Journals Online, World Health Organization regional databases, and a gray literature search was conducted in April/May 2020, and updated in January 2024. Study selection was undertaken by two independent reviewers. Quality assessment using the Mixed Method Appraisal Tool and data extraction were completed by one reviewer with a 10% check by a second reviewer. Data were synthesized narratively using a parallel results convergent integrated design. RESULTS: Thirty-seven studies, 19 quantitative, 16 qualitative, and 2 mixed methods, were included. The findings suggested that while healthcare practitioners generally demonstrated knowledge about kangaroo care, there was a notable minority with insufficient understanding among those who received training. Parents' knowledge, particularly among fathers, was limited. Both healthcare practitioners and parents appeared to have positive attitudes to kangaroo care. Little is known about parental satisfaction with kangaroo care. CONCLUSIONS: Most healthcare practitioners were knowledgeable about kangaroo care, but parents had limited knowledge. This review findings suggest a need to enhance parental knowledge of kangaroo care before neonatal unit admission, and training is needed for HCPs to implement kangaroo care consistently.

Exclusive breastfeeding and length of hospital stay in premature infants at a Brazilian reference center for kangaroo mother care

Abstract Objective: To evaluate exclusive breastfeeding at discharge and hospital length-of-stay in pre-term infants undergoing or not the Kangaroo-Mother Care Method (KMC). Methods: A retrospective cohort study was conducted including preterm infants < 1800 g admitted to the neonatal unit of a KMC reference center. The infants were grouped into the KMC group and the non-KMC group. Multiple logistic and Poisson regressions were performed to evaluate the association between the KMC and two outcomes, exclusive breastfeeding at discharge, and hospital length-of-stay, adjusted for potential confounders. Results: 115 mother-infant dyads were included, 78 in the KMC group and 37 in the non-KMC group. In the bivariate analysis, the KMC group had a lower prevalence of maternal adverse conditions (6% vs. 32%, p < 0.001), a higher number of prenatal visits (median 6 vs. 3.5, p < 0.001), higher gestational ages (median 32 vs. 31 weeks, p < 0.05), higher birth weights (median 1530 vs. 1365 g, p < 0.01), a lower prevalence of necrotizing enterocolitis (3.8% vs. 16.2%, p < 0.05), parenteral nutrition (50% vs. 73%, p < 0.05), and deep vascular access (49.7% vs. 78.4%, p < 0.01), a higher prevalence of exclusive breastfeeding (65% vs. 8%, p < 0.001) and a shorter length of hospital stay (median 28 vs. 42 days, p < 0.001). In the multiple regression analysis, the KMC group was 23 times more likely to be exclusively breastfed at discharge (OR = 23.1; 95% CI = 4,85-109,93) and had a 19% reduction in the hospital length-of-stay (IDR = 0.81; 95% CI = 0.76-0.86) compared to the non-KMC group. Conclusions: The KMC is associated with better short-term neonatal outcomes and should be encouraged in all Brazilian maternity hospitals.

Clinical phenotype of pulmonary vascular disease requiring treatment in extremely preterm infants.

BACKGROUND: Pulmonary vascular disease (PVD) and pulmonary hypertension (PH) is a significant disorder affecting prognosis of extremely preterm infants. However, there is still a lack of a consensus on the definition and optimal treatments of PH, and there is also a lack of research comparing these conditions with persistent pulmonary hypertension of newborn (PPHN), early PH, and late PH. To investigate PH in extremely preterm infants, this study compared the baseline characteristics, short-term outcomes, and treatment duration, categorized by the timing of requiring PH treatment. METHODS: This study retrospectively analyzed extremely preterm infants admitted to a single tertiary center. Between 2018 and 2022, infants with clinical or echocardiographic diagnosis of PH who required treatment were divided into three groups based on the timing of treatment initiation: initial 3 days (extremely early-period), from day 4 to day 27 (early-period), and after day 28 (late-period). The study compared the outcomes, including mortality rates, bronchopulmonary dysplasia (BPD) severity, PH treatment duration, and oxygen therapy duration, among the three groups. RESULTS: Among the 157 infants, 67 (42.7%) were treated for PH during their stay. Of these, 39 (57.3%) were treatment in extremely early, 21 (31.3%) in early, and seven (11.4%) in late periods. No significant differences were observed in maternal factors, neonatal factors, or morbidity between the three groups. However, infants who received extremely early-period treatment had a higher mortality rate, but shorter duration of noninvasive respiratory support, oxygen therapy, and PH medication use. On the other hand, the late-period treatment group received longer durations of respiratory support and treatment. CONCLUSIONS: This study revealed differences in mortality rates, respiratory outcomes, and treatment duration between the three groups, suggesting varying pathophysiologies over time in extremely preterm infants.

Narrative Review on Echocardiographic Evaluation of Patent Ductus Arteriosus in Preterm Infants.

Persistent Patent Ductus Arteriosus (PDA) is prevalent among extremely preterm infants, with its occurrence inversely related to gestational age. A persistent PDA correlates with increased mortality and morbidities such as intraventricular hemorrhage, pulmonary hemorrhage, chronic lung disease, bronchopulmonary dysplasia, and necrotizing enterocolitis as observed clinically. Conversely, numerous randomized controlled trials have failed to demonstrate significant benefits from PDA treatment. One contributing factor to these conflicting findings is that PDA affects each individual differently depending on the cardiovascular decompensation and its hemodynamic impact. PDA management should be based on the hemodynamic significance, rather than just the presence or size of PDA. This comprehensive narrative review paper describes echocardiographic parameters that allow a better understanding of the hemodynamic impact of PDA. A newer modality, like lung ultrasound, is also described here as an adjunct to assess the PDA impact on the lungs from pulmonary overcirculation.

16S rDNA Sequencing for Bacterial Identification in Preterm Infants with Suspected Early-Onset Neonatal Sepsis.

BACKGROUND: The high prevalence of suspected early-onset neonatal sepsis among preterm infants leads to immediate antibiotic administration upon admission. Notably, most blood cultures for suspected early-onset neonatal sepsis do not yield a causative pathogen. This study aimed to assess polymerase chain reaction (PCR) targeting the variable region V4 of the 16S ribosomal gene (16S rDNA) and Sanger sequencing for bacterial identification in preterm infants with suspected early-onset neonatal sepsis. METHODS: Therefore, this prospective study was conducted. Preterm infants with suspected early-onset neonatal sepsis were included in this study. The three groups were formed based on the risk of infection and clinical sepsis. Blood samples were collected upon admission to the neonatal unit for culture and molecular analysis. PCR amplification and subsequent Sanger sequencing of the V4 region of the 16S rDNA were performed. RESULTS: Twenty-eight patients were included in this study. Blood cultures were negative in 100% of the patients. Amplification and sequencing of the V4 region identified bacterial genera in 19 patients across distinct groups. The predominant taxonomically identified genus was Pseudomonas. CONCLUSIONS: Amplifying the 16S rDNA variable region through PCR and subsequent Sanger sequencing in preterm neonates with suspected early-onset neonatal sepsis can enhance the identification of microbial species that cause infection, especially in negative cultures.

The evolution of nutritional care in preterm infants with a focus on the extreme preterm infant.

The evolution of nutritional care in preterm infants, particularly those classified as extremely preterm, has undergone significant advancements in recent years. These infants, born at less than 28 weeks of gestation, face unique challenges related to their elevated nutrient requirements, underdeveloped organ systems and minimal reserves, posing a need for timely and specialised nutritional strategies. Historically, the nutritional management of preterm infants focussed on short-term goals to promote survival. In recent years, the focus has shifted to the quality of nutrient provision to optimise neurodevelopment and longer-term health outcomes. This review highlights the shift from a generalised nutritional approach to a robust, evidence-based approach for preterm infants, acknowledging the intricate interplay between nutrition, holistic care and developmental outcomes. As neonatal care continues to evolve, ongoing research will refine nutritional interventions, optimise growth and enhance the long-term health outcomes of these vulnerable infants.

Randomized Controlled Trial of Enteral Vitamin D Supplementation (ViDES) in Infants <28 Weeks Gestational Age or <1000 Grams Birth Weight: Study Protocol.

Background: Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear. Methods: Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants <28 weeks gestation or <1000 grams birth weight at a large academic center in the United States.Infants are stratified by birth weight and randomized within 96 hours after birth to either routine supplementation (400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the first 28 days after birth.We hypothesize that the higher and early vitamin D dose (800 IU/d with early feeding) compared to placebo plus routine dose (400 IU/d with established feeding) will substantially increase total 25-hydroxyvitamin D3 levels measured as state-of-art at one month, reduce respiratory support at 36 weeks' postmenstrual age (on an ordinal scale predictive of later adverse outcomes) and improve or at least not worsen other important secondary outcomes. The infants in the study will follow up at 22-26 months' corrected age (~2 years) with blinded certified examiners to evaluate neurodevelopmental outcomes.The sample size of a minimum of 180 infants provides >90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability. Discussion: Our study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterminfants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results. Trial registration: ClinicalTrials.gov registered on July 14, 2022 (NCT05459298).