Neurodevelopment In Preterm Infants Research Articles

The neonatal gut microbiota: A role in the encephalopathy of prematurity.

Preterm birth correlates with brain dysmaturation and neurocognitive impairment. The gut microbiome associates with behavioral outcomes in typical development, but its relationship with neurodevelopment in preterm infants is unknown. We characterize fecal microbiome in a cohort of 147 neonates enriched for very preterm birth using 16S-based and shotgun metagenomic sequencing. Delivery mode strongly correlates with the preterm microbiome shortly after birth. Low birth gestational age, infant sex assigned at birth, and antibiotics associate with microbiome composition at neonatal intensive care unit discharge. We integrate these data with term-equivalent structural and diffusion brain MRI. Bacterial community composition associates with MRI features of encephalopathy of prematurity. Particularly, abundances of Escherichia coli and Klebsiella spp. correlate with microstructural parameters in deep and cortical gray matter. Metagenome functional capacity analyses suggest that these bacteria may interact with brain microstructure via tryptophan and propionate metabolism. This study indicates that the gut microbiome associates with brain development following preterm birth.

Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial

(JAMA. 2024;331(7):582–591. doi: 10.1001/jama.2023.27693) A large, nationwide, randomized clinical trial examining how donor milk and preterm infant formula affect neurodevelopment in premature infants has found that outcomes in both groups were similar. The double-blinded trial was conducted with 483 participants at 15 academic medical centers in the United States that are part of a National Institute of Child Health Neonatal Research Network. Previous studies have shown that preterm infants fed with maternal milk while hospitalized have better neurodevelopment outcomes.

Affective Touch in Preterm Infant Development: Neurobiological Mechanisms and Implications for Child-Caregiver Attachment and Neonatal Care.

Affective touch is crucial in infant development, particularly in regulating emotional, cognitive, and physiological processes. Preterm infants are often deprived of essential tactile stimulation owing to their early exposure to the external environment, which may affect long-term developmental outcomes. This review aimed to examine the neurobiological mechanisms of affective touch and highlight effective interventions, such as skin-to-skin contact (SSC) and kangaroo care (KC), to promote development in preterm infants. This review summarizes recent studies in the literature on affective touch, the role of C-tactile fibers, and the effects of tactile interventions in neonatal care. Studies were selected based on their relevance to the care and development of preterm infants, with a focus on physiological and neurodevelopmental outcomes. Key interventions, including SSC and massage therapy, are discussed in relation to their effectiveness in the neonatal intensive care unit (NICU). The results suggest that affective touch, mainly through activation of tactile C-fibers, improves caregiver-infant bonding, reduces stress responses, and supports neurodevelopment in preterm infants. Interventions such as SSC and KC have also been shown to improve physiological regulation in these infants, including heart rate, breathing, and temperature control while promoting emotional regulation and cognitive development. Affective touch is a key component of early development, particularly in preterm infants admitted to the NICU. Integrating tactile interventions such as SSC and KC into neonatal care practices may significantly improve long-term developmental outcomes. Future research should explore the epigenetic mechanisms underlying affective touch and further refine tactile interventions to optimize neonatal care.

Investigation of the catch-up status and termination for corrected age of neurodevelopment in premature infants of different gestational ages.

Corrected age entails determining the age of premature infants by adjusting their gestational age to 40 weeks. Research on corrected age in relation to neurodevelopment is limited, both domestically and internationally, resulting in a lack of consensus and recommendations regarding the appropriate termination of the neurodevelopmental corrected age. This study aimed to assess the neurodevelopmental catch-up status of premature infants with varying gestational ages and to identify appropriate termination criteria for the corrected age of neurodevelopment. The study included 1,579 premature infants without high-risk factors and 8,441 full-term infants receiving care at the child health clinics of the Second Affiliated Hospital of Army Medical University, Chongqing Health Center for Women and Children, and Maternal and Child Health Care Hospital of Wanzhou District, Chongqing between January 1, 2018, and March 1, 2023. Infants were grouped based on gestational age into early, middle, and late premature infants, as well as full-term infants. Over a 48-month period, the developmental quotient (DQ) of each functional area on the Gesell Developmental Scale was compared across groups. There were no statistically significant differences in DQ of all functional areas between late premature infants and full-term infants at 36 months of age (all P>0.05). In contrast, some developmental functional areas in middle- and early-premature infants and full-term infants exhibited significant differences at 36 months of age; however, by 48 months of age, these differences were no longer significant (all P>0.05). The DQ of all functional areas in the late, middle, and early premature infant groups demonstrated a catch-up trend from 6 to 48 months of chronological age (all P<0.05). The termination age for neurodevelopmental correction in premature infants may continue beyond 36 months of age, with longer correction time required for those born at younger gestational ages.

Preeclampsia and Future Implications on Growth and Body Composition in Preterm Infants.

Preeclampsia is associated with intrauterine growth restriction (IUGR), which can lead to impaired postnatal growth and neurodevelopment in preterm infants. Preeclampsia can also occur without IUGR and its impact on postnatal nutrition, growth, and body composition remains not fully investigated to the best of our knowledge. This study included infants born before 37 weeks of gestation who underwent air displacement plethysmography to measure body composition (fat-free mass [FFM] and fat mass [FM]) at term-equivalent age. We compared infants born to mothers with preeclampsia and IUGR (PE-IUGR group) and preeclampsia without IUGR (PE-non-IUGR group) to those born to mothers without preeclampsia (control group). In total, 291 infants were enrolled (control: n = 227; PE-non-IUGR: n = 43; PE-IUGR: n = 21). FFM was significantly lower in the PE-IUGR (mean differences -231 g (IQR: (-373, -88); p < 0.001)) and PE-non-IUGR groups (mean differences -260 g (IQR: (-372, -149); p < 0.001)) in comparison to the control group. FM was not significantly different between the three groups. This study indicates that infants of preeclamptic mothers, even without IUGR, had significantly lower FFM at term-equivalent age compared to the control group. Further research is necessary to determine if these variations can be modified.

Early parental vocal contact in neonatal units: rationale and clinical guidelines for implementation.

This paper aims to present clear and evidence-based proposals for the integration of Early Parental Vocal Contact into the clinical practices of neonatal units. In the first part, we present a comprehensive rationale exploring the ontogenesis of voice perception in both term and preterm newborns that establishes a foundational understanding. This knowledge serves as a crucial starting point for developing evidence-based auditory and multisensory interventions aimed at fostering the developmental trajectory of preterm infants. Drawing insights from neuroscience and brain development, our proposals underscore the significance of tailoring auditory environments within neonatal settings. Special attention is given to the unique needs of preterm infants, factoring in their gestational age and maturation levels. In the second part clinical guidelines for implementation are provided and healthcare professionals are supported to assist parents in modulating their vocal interactions, aligning them with the infant's responses. Furthermore, we provide practical suggestions for engaging in discussions with parents about the content, duration, and frequency of vocal interventions. Finally, we delve into the potential roles of caregivers, parents, and health professionals within this enriched parental vocal interactional environment. Our perspective is firmly grounded in an infant and family-centered developmental care philosophy, aiming to enhance the overall well-being and the neurodevelopment of preterm infants in neonatal units.

Sleep state-dependent development of resting-state functional connectivity during the preterm period.

The brains of preterm infants exhibit altered functional connectivity (FC) networks, but the potential variation in sleep states and the impact of breathing patterns on FC networks are unclear. This study explores the evolution of resting-state FC from preterm to term, focusing on breathing patterns and distinguishing between active sleep (AS) and quiet sleep (QS). We recruited 63 preterm infants and 44 healthy-term infants and performed simultaneous electroencephalography and functional near-infrared spectroscopy. FC was calculated using oxy- and deoxyhemoglobin signals across eight channels. First, FC was compared between periodic breathing (PB) and non-PB segments. Then sleep state-dependent FC development was explored. FC was compared between AS and QS segments and between preterm infants at term and term-born infants in each sleep state. Finally, associations between FC at term, clinical characteristics, and neurodevelopmental outcomes in late infancy were assessed in preterm infants. In total, 148 records from preterm infants and 44 from term-born infants were analyzed. PB inflated FC values. After excluding PB segments, FC was found to be elevated during AS compared to QS, particularly in connections involving occipital regions. Preterm infants had significantly higher FC in both sleep states compared to term-born infants. Furthermore, stronger FC in specific connections during AS at term was associated with unfavorable neurodevelopment in preterm infants. Sleep states play a critical role in FC development and preterm infants show observable changes in FC.

Head growth trajectories as a window into neurodevelopment in preterm infants

Head growth trajectories as a window into neurodevelopment in preterm infants

The effects of different positions on neurodevelopment in preterm infants admitted in neonatal intensive care units: a systematic review protocol

Introduction Preterm birth poses significant challenges to infant health, with neurodevelopmental outcomes often affected. In the Neonatal Intensive Care Unit (NICU), positioning strategies are commonly employed with the aim of mitigating adverse effects and promoting neurodevelopment in preterm infants. However, the evidence regarding the impact of different positions on neurodevelopmental outcomes remains heterogeneous and inconclusive. Objective The aim of this systematic review is to evaluate the effects of different positioning strategies on neurodevelopmental outcomes in preterm infants admitted to Neonatal Intensive Care Units (NICUs). Methods A comprehensive search will be conducted in electronic databases including PubMed, MEDLINE, EMBASE, and Cochrane Library. To comply with the established guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, the systematic review will be conducted to identify relevant studies published up to the date of the search. This systematic review protocol has been registered in PROSPERO to ensure thorough and transparent reporting of the search process, synthesis of findings, and analysis methods. Discussion In the context of preterm infants admitted to Neonatal Intensive Care Units (NICUs), the discussion surrounding the effects of different positions on neurodevelopmental outcomes is multifaceted and warrants careful consideration. Variations in study methodologies, including sample sizes, outcome measures, and follow-up durations, underscore the need for standardized approaches to facilitate comparison and synthesis of findings. The heterogeneity in reported outcomes, ranging from cognitive and motor development to sensory processing, highlights the complexity of neurodevelopmental assessment in this population and emphasizes the importance of comprehensive evaluation frameworks. Through rigorous synthesis and analysis of existing literature, our protocol aims to contribute meaningful insights that can drive future research agendas and enhance neurodevelopmental outcomes for this vulnerable population. Systematic Review Registration number CRD42023492163

Size and Location of Preterm Brain Injury and Associations With Neurodevelopmental Outcomes.

We examined associations of white matter injury (WMI) and periventricular hemorrhagic infarction (PVHI) volume and location with 18-month neurodevelopment in very preterm infants. A total of 254 infants born <32 weeks' gestational age were prospectively recruited across 3 tertiary neonatal intensive care units (NICUs). Infants underwent early-life (median 33.1 weeks) and/or term-equivalent-age (median 41.9 weeks) MRI. WMI and PVHI were manually segmented for quantification in 92 infants. Highest maternal education level was included as a marker of socioeconomic status and was defined as group 1 = primary/secondary school; group 2 = undergraduate degree; and group 3 = postgraduate degree. Eighteen-month neurodevelopmental assessments were completed with Bayley Scales of Infant and Toddler Development, Third Edition. Adverse outcomes were defined as a score of less than 85 points. Multivariable linear regression models were used to examine associations of brain injury (WMI and PVHI) volume with neurodevelopmental outcomes. Voxel-wise lesion symptom maps were developed to assess relationships between brain injury location and neurodevelopmental outcomes. Greater brain injury volume was associated with lower 18-month Motor scores (β = -5.7, 95% CI -9.2 to -2.2, p = 0.002) while higher maternal education level was significantly associated with higher Cognitive scores (group 3 compared 1: β = 14.5, 95% CI -2.1 to 26.9, p = 0.03). In voxel-wise lesion symptom maps, brain injury involving the central and parietal white matter was associated with an increased risk of poorer motor outcomes. We found that brain injury volume and location were significant predictors of motor, but not cognitive outcomes, suggesting that different pathways may mediate outcomes across domains of neurodevelopment in preterm infants. Specifically, assessing lesion size and location may allow for more accurate identification of infants with brain injury at highest risk of poorer motor outcomes. These data also highlight the importance of socioeconomic status in cognitive outcomes, even in preterm infants with brain injury.

Human Breast Milk Exosomal miRNAs are Influenced by Premature Delivery and Affect Neurodevelopment.

This study investigates the exosomal microRNA (miRNA) profiles of term and preterm breast milk, including the most abundant and differentially expressed (DE) miRNAs, and their impact on neurodevelopment in infants. Mature milk is collected from the mothers of term and preterm infants. Using high-throughput sequencing and subsequent data analysis, exosomal miRNA profiles of term and preterm human breast milk (HBM) are acquired and it is found that the let-7 and miR-148 families are the most abundant miRNAs. Additionally, 23 upregulated and 15 downregulated miRNAs are identified. MiR-3168 is the most upregulated miRNA in preterm HBM exosome, exhibiting targeting activity toward multiple genes involved in the SMAD and MAPK signaling pathways and playing a crucial role in early neurodevelopment. Additionally, the effects of miR-3168 on neurodevelopment is confirmed and it is determined that it is an essential factor in the differentiation of neural stem cells (NSCs). This study demonstrates that miRNA expression in breast milk exosomes can be influenced by preterm delivery, thereby potentially impacting neurodevelopment in preterm infants.

Exploration of the impact of dysbiosis in the gut microbiota on microbial composition in children’s neurodevelopment

Objective To investigate the impact of gut microbiota dysbiosis on neurodevelopment in children. Methods This study included 338 children aged 0-3 years admitted to our hospital from January to December 2022, The children were divided into a normal neurodevelopment group (169 cases) and a poor neurodevelopment group (169 cases). Basic personal information and clinical data were collected through a detailed questionnaire, and the microbial composition in fecal samples was analyzed using 16S rRNA gene sequencing. Results Children in the poor neurodevelopment group showed a significant decrease in gut microbiota diversity compared to those in the normal neurodevelopment group (Shannon index, p < 0.05). The abundance of Bifidobacterium and Veillonella genera significantly decreased (p < 0.05), while the abundance of Streptococcus genus increased significantly (p < 0.05). Conclusion There is an association between gut microbiota dysbiosis and poor neurodevelopment in children. The increased abundance of Streptococcus genus and decreased abundance of Bifidobacterium and Veillonella genera in the gut microbiota may be potential risk factors for poor neurodevelopment in preterm infants. Future research should further explore the potential beneficial effects of gut microbiota modulation on neurodevelopment in children.

Insulin-like growth factor-1 and insulin-like growth factor binding protein-3 as early predictors of growth, body composition, and neurodevelopment in preterm infants.

To investigate the relationship between insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3) and long-term growth, body composition, and neurodevelopment in preterm infants. Prospective data were collected from ≤32 weeks gestational age infant cohort (N = 50). IGF-1 and IGFBP-3 concentrations were measured at 1 week (early) and 35 weeks (late) post-menstrual age (PMA). Growth, body composition, and neurodevelopment outcomes were measured at 4 and 12 months PMA. Relationships were measured by linear regression analysis. Early IGFBP-3 concentration was positively associated with neurodevelopment at 12 months PMA. Early IGF-1 concentration was positively associated with weight at 4 months PMA, head circumference at 12 months PMA, and body mass index at 12 months PMA. Late IGFBP-3 concentration was positively associated with weight at 4 months PMA. Further investigation of these associations may lead to novel biomarkers and/or treatments to optimize health outcomes in preterm infants.

Pain Exposure and Brain Connectivity in Preterm Infants

Early-life exposure to painful procedures has been associated with altered brain maturation and neurodevelopmental outcomes in preterm infants, although sex-specific differences are largely unknown. To examine sex-specific associations among early-life pain exposure, alterations in neonatal structural connectivity, and 18-month neurodevelopment in preterm infants. This prospective cohort study recruited 193 very preterm infants from April 1, 2015, to April 1, 2019, across 2 tertiary neonatal intensive care units in Toronto, Canada. Structural connectivity data were available for 150 infants; neurodevelopmental outcomes were available for 123 infants. Data were analyzed from January 1, 2022, to December 31, 2023. Pain was quantified in the initial weeks after birth as the total number of invasive procedures. Infants underwent early-life and/or term-equivalent-age magnetic resonance imaging with diffusion tensor imaging to quantify structural connectivity using graph theory measures and regional connection strength. Eighteen-month neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition. Stratifying by sex, generalized estimating equations were used to assess whether pain exposure modified the maturation of structural connectivity using an interaction term (early-life pain exposure × postmenstrual age [PMA] at scan). Generalized estimating equations were used to assess associations between structural connectivity and neurodevelopmental outcomes, adjusting for extreme prematurity and maternal education. A total of 150 infants (80 [53%] male; median [IQR] gestational age at birth, 27.1 [25.4-29.0] weeks) with structural connectivity data were analyzed. Sex-specific associations were found between early-life pain and neonatal brain connectivity in female infants only, with greater early-life pain exposure associated with slower maturation in global efficiency (pain × PMA at scan interaction P = .002) and local efficiency (pain × PMA at scan interaction P = .005). In the full cohort, greater pain exposure was associated with lower global efficiency (coefficient, -0.46; 95% CI, -0.78, to -0.15; P = .004) and local efficiency (coefficient, -0.57; 95% CI, -1.04 to -0.10; P = .02) and regional connection strength. Local efficiency (coefficient, 0.003; 95% CI, 0.001-0.004; P = .005) and regional connection strength in the striatum were associated with cognitive outcomes. In this cohort study of very preterm infants, greater exposure to early-life pain was associated with altered maturation of neonatal structural connectivity, particularly in female infants. Alterations in structural connectivity were associated with neurodevelopmental outcomes, with potential regional specificities.

The association of cumulative vasoactive drugs and neurodevelopmental outcomes in preterm Infants

To assess the effect of cardiovascular medications on the neurodevelopment of preterm infants, as measured by calculated cumulative time of vasoactive-inotropic score (VISct). A retrospective study was conducted on preterm infants who developed significant hypotension defined as a mean BP more than 2SDs below the mean for GA and received treatment with duration > 6 hours for each hypotensive episode, we calculated the vasoactive inotropic score (VIS) and cumulative exposure to cardiovascular medications over time (VISct). The composite Bayley III was reported from the high-risk follow-up clinic for the surviving infants between 18 to 21 months corrected age. VISct was significantly higher in infants with abnormal neurodevelopment. Cognitive Bayley was the most affected component with median (IQR) VISct 882.5(249,2047) versus 309(143,471) (p-value 0.012), followed by language function with VISct 786(261,1563.5), versus 343(106.75,473.75) (p-value 0.016) when those with Bayley III <85 were compared with those with normal Bayley IIIs. High VISct scores may have negative effect on cognitive and language neurodevelopmental outcomes.

Pain/Stress, Mitochondrial Dysfunction, and Neurodevelopment in Preterm Infants

Introduction: Preterm infants experience tremendous early life pain/stress during their neonatal intensive care unit (NICU) hospitalization, which impacts their neurodevelopmental outcomes. Mitochondrial function/dysfunction may interface between perinatal stress events and neurodevelopment. Nevertheless, the specific proteins or pathways linking mitochondrial functions to pain-induced neurodevelopmental outcomes in infants remain unidentified. Our study aims to investigate the associations among pain/stress, proteins associated with mitochondrial function/dysfunction, and neurobehavioral responses in preterm infants. Methods: We conducted a prospective cohort study, enrolling 33 preterm infants between September 2017 and July 2022 at two affiliated NICUs located in Hartford and Farmington, CT. NICU Network Neurobehavioral Scale (NNNS) datasets were evaluated to explore potential association with neurobehavioral outcomes. The daily pain/stress experienced by infant’s during their NICU stay was documented. At 36–38 weeks post-menstrual age (PMA), neurobehavioral outcomes were evaluated using the NNNS and buccal swabs were collected for further analysis. Mass spectrometry-based proteomics was conducted on epithelial cells obtained from buccal swabs to evaluate protein expression level. Lasso statistical methods were conducted to study the association between protein abundance and infants’ NNNS summary scores. Multiple linear regression and Gene Ontology (GO) enrichment analyses were performed to examine how clinical characteristics and neurodevelopmental outcomes may be associated with protein levels and underlying molecular pathways. Results: During NICU hospitalization, preterm premature rupture of membrane (PPROM) was negatively associated with neurobehavioral outcomes. The protein functions including leptin receptor binding activity, glutathione disulfide oxidoreductase activity and response to oxidative stress, lipid metabolism, and phosphate and proton transmembrane transporter activity were negatively associated with neurobehavioral outcomes; in contrast, cytoskeletal regulation, epithelial barrier, and protection function were found to be associated with the optimal neurodevelopmental outcomes. In addition, mitochondrial function-associated proteins including SPRR2A, PAIP1, S100A3, MT-CO2, PiC, GLRX, PHB2, and BNIPL-2 demonstrated positive association with favorable neurodevelopmental outcomes, while proteins of ABLIM1, UNC45A, keratins, MUC1, and CYB5B showed positive association with adverse neurodevelopmental outcomes. Conclusion: Mitochondrial function-related proteins were observed to be associated with early life pain/stress and neurodevelopmental outcomes in infants. Large-scale studies with longitudinal datasets are warranted. Buccal proteins could be used to predict potential neurobehavioral outcomes.

Effects of two-stage preterm formulas on growth, nutritional biomarkers, and neurodevelopment in preterm infants.

Formula-fed preterm infants require nutrient-enriched formulas with optimized protein levels to support growth and neurodevelopment. The purpose of this study was to evaluate the safety, tolerability, and effectiveness of a new liquid two-staged formula system designed to provide tailored nutrition during hospital stay and after discharge. Male and female very-low-birth-weight preterm infants (birth weight ≤1,500 g; gestational age ≤32 weeks) were recruited from three neonatal units in Poland and Slovakia in a prospective, open-label, interventional study. Stage 1 formula providing 3.6 g intact protein/100 kcal was consumed from enrollment until reaching 1,800 g, followed by a post-discharge (PD) Stage 2 formula with 2.8 g/100 kcal protein, which was consumed for 30 days. Weight gain velocity (WGV in g/kg/day) between the first day of achieving full enteral feeding (FEF D1 rate of 150 ml/kg/day and cessation of parenteral feeding) and day reaching 1,800 g was compared to the minimally required WGV (15 g/kg/day) for non-inferiority (primary endpoint), and to the Fenton median growth rate for superiority (17.3 g/kg/day), adjusting for sex, gestational age, site, visit, and WGV. Changes in z-scores, feeding tolerance, nutritional biomarker status, and safety were also assessed from FEF D1 to 30 days PD. In an observational follow-up at 2 years of age, neurodevelopment was evaluated using the Bayley Scales of Infant and Toddler Development (BSID-III). Adjusted weight gain velocity (95% CI) between the first day of full enteral feeding and day reaching 1,800 g in per protocol (PP, N = 18) was 23.0 (20.1-25.9) g/kg/day; lower limit of the 95% CIs exceeded the non-inferiority margin (15 g/kg/day, p < 0.001) and the superiority margin (17.3 g/kg/day, p < 0.001). Mean stool frequency ranged from 2.5 to 3.3 stools per day. The two-stage formula supported adequate growth patterns throughout the study and nutritional biomarkers of protein and mineral status were within normal ranges. At 24 months corrected age, the mean ± SD of the BSID cognitive scale was 97.3 ± 13.9 in PP, with all infants achieving a score >70. None of the adverse events reported were related to the study formulas. The two-stage preterm formulas supported postnatal weight gain, adequate growth, cognitive development within normal ranges, and a safe profile of protein and bone biomarkers. Clinicaltrials.gov registration, NCT03728764, NCT04962035.

A meta-analysis of adverse effects of retinopathy of prematurity on neurodevelopment in preterm infants.

Retinopathy of prematurity (ROP) increases with the survival of late preterm infants, but its relationship with neurodevelopmental outcomes in preterm infants remains controversial. To investigate the relationship between ROP and its severity and adverse neurodevelopmental outcomes in preterm infants. We conducted a meta-analysis. All relevant literature before November 2022 were retrieved from PubMed, Embase, Cochrane Library Web of Science, CNKI, CBM, Wan fang Data, and VIP Database. According to the inclusion criteria and exclusion criteria, eligible literature were included to conduct clinical trial quality assessment, and the Newcastle-Ottawa scale was used to evaluate the quality of evidence. Meta-analysis was performed using RevMan5.3. Data extraction, quality assessment, and meta-analysis were performed independently by 2 people. Mean difference or standardized mean difference of motor, language and cognitive scores (Bayley III or Bayley II) were used as effect sizes for continuous data analysis, all of which were represented by 95% CI. For heterogeneity (I2 ≥ 50% or P < .10), a random effects model was used, otherwise a fixed effects model was used. A total of 6 literature were included. The results of the ROP group for motor (comprehensive motor, proportional motor, and fine motor), language and cognitive scores were -5.57 (95%CI, -1.43 to 0.04), -0.95 (95%CI, 1.4-0.50), -1.34 (95% CI, 1.77-0.92), -1.75 (95% CI, 2.26-1.24) and -5.56 (95% CI, 9.56-1.57). Additionally, the results of severe ROP group for motor (comprehensive motor, proportional motor, fine motor), language and cognitive scores were -8.32 (95%CI, -8.91 to 7.74), -1.10 (95%CI, -1.83 to -0.36), -1.08 (95%CI, -1.75 to -0.41), -7.03 (95%CI, -7.71 to 6.35), and -7.96 (95%CI, -8.5 to -7.42). The Bayley Scale scores of the ROP group were lower than those of the not ROP group, and the scores of the severe ROP were significantly lower than those of the not severe ROP group. These findings suggest that ROP can indeed delay motor, language and cognitive, especially in severe cases.

The Influence of Early Nutrition on Neurodevelopmental Outcomes in Preterm Infants

Premature infants, given their limited reserves, heightened energy requirements, and susceptibility to nutritional deficits, require specialized care. Aim: To examine the complex interplay between nutrition and neurodevelopment in premature infants, underscoring the critical need for tailored nutritional approaches to support optimal brain growth and function. Data sources: PubMed and MeSH and keywords: preterm, early nutrition, macronutrients, micronutrients, human milk, human milk oligosaccharides, probiotics AND neurodevelopment or neurodevelopment outcomes. Recent articles were selected according to the authors’ judgment of their relevance. Specific nutrients, including macro (amino acids, glucose, and lipids) and micronutrients, play an important role in promoting neurodevelopment. Early and aggressive nutrition has shown promise, as has recognizing glucose as the primary energy source for the developing brain. Long-chain polyunsaturated fatty acids, such as DHA, contribute to brain maturation, while the benefits of human milk, human milk oligosaccharides, and probiotics on neurodevelopment via the gut-brain axis are explored. This intricate interplay between the gut microbiota and the central nervous system highlights human milk oligosaccharides’ role in early brain maturation. Conclusions: Individualized nutritional approaches and comprehensive nutrient strategies are paramount to enhancing neurodevelopment in premature infants, underscoring human milk’s potential as the gold standard of nutrition for preterm infants.

Trends in Outcomes of Major Intracerebral Haemorrhage in a National Cohort of Very Preterm Born Infants in Switzerland.

Major brain lesions, such as grade 3 intraventricular haemorrhage (G3-IVH) and periventricular haemorrhagic infarction (PVHI) are among the main predictors for poor neurodevelopment in preterm infants. In the last decades advancements in neonatal care have led to a general decrease in adverse outcomes. To assess trends of mortality and neurodevelopmental impairment (NDI) in a recent Swiss cohort of very preterm infants with grade 3 intraventricular haemorrhage (G3-IVH) and periventricular haemorrhagic infarction (PVHI). In this retrospective population-based cohort study, rates of mortality, and NDI at 2 years corrected age were reported in infants born at 24-29 weeks gestational age (GA) in Switzerland in 2002-2014, with G3-IVH and/or PVHI. Out of 4956 eligible infants, 462 (9%) developed G3-IVH (n = 172) or PVHI (n = 290). The average mortality rates for the two pathologies were 33% (56/172) and 60% (175/290), respectively. In 2002-2014, no change in rates of mortality (G3-IVH, p = 0.845; PVHI, p = 0.386) or NDI in survivors (G3-IVH, p = 0.756; PVHI, p = 0.588) were observed, while mean GA decreased (G3-IVH, p = 0.020; PVHI, p = 0.004). Multivariable regression analysis showed a strong association of G3-IVH and PVHI for both mortality and NDI. Death occurred after withdrawal of care in 81% of cases. In 2002-2014, rates of mortality and NDI in very preterm born infants with major brain lesions did not change. The significant decrease in mean GA and changing hospital policies over this time span may factor into the interpretation of these results.