Neurodevelopmental Outcome In Preterm Infants Research Articles

Early postnatal nutrition and renal consequences in preterm infants.

Perinatal nutritional factors may lead to decreased nephron endowment, decreased kidney function, and long-term development of chronic kidney disease and non-communicable diseases. At the same time, optimal postnatal nutrition and catch-up growth are associated with better neurodevelopmental outcomes in preterm infants. Therefore, nutritional management of preterm infants is a major challenge for neonatologists. In this context, the Section of Nutrition, Gastroenterology and Metabolism reviewed the current knowledge on nutritional issues related to kidney function. This narrative review discusses the clinical impact of early postnatal nutrition on long-term kidney function. In preterm infants, data are largely lacking to determine the extent to which early nutrition contributes to nephrogenesis and nephron endowment. However, some nutritional principles may help clinicians better protect the developing kidney in preterm infants. IMPACT: Clinical data show that preterm infants are an emerging population at high risk for chronic kidney disease. Both undernutrition and overnutrition can alter long-term kidney function. In preterm infants, data are largely lacking to determine the extent to which early postnatal nutrition contributes to nephrogenesis, nephron endowment and increased risk for chronic kidney disease. Some nutritional principles may help clinicians better protect the developing kidney in preterm infants: avoiding extrauterine growth restriction; providing adequate protein and caloric intakes; limiting exposure to high and prolonged hyperglycaemia; avoiding micronutrient deficiencies and maintaining acid-base and electrolyte balance.

Associations between gut microbiota and adverse neurodevelopmental outcomes in preterm infants: a two-sample Mendelian randomization study.

Gut microbiota are associated with adverse neurodevelopmental outcomes in preterm infants; however, the precise causal relationship remains unclear. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to comprehensively study the relationship between gut microbiota and adverse neurodevelopmental outcomes in preterm infants and identify specific causal bacteria that may be associated with the occurrence and development of adverse neurodevelopmental outcomes in preterm infants. The genome-wide association analysis (GWAS) of the MiBioGen biogroup was used as the exposure data. The GWAS of six common adverse neurodevelopmental outcomes in premature infants from the FinnGen consortium R9 was used as the outcome data. Genetic variations, namely, single nucleotide polymorphisms (SNPs) below the locus-wide significance level (1 × 10-5) and genome-wide statistical significance threshold (5 × 10-8) were selected as instrumental variables (IVs). MR studies use inverse variance weighting (IVW) as the main method. To supplement this, we also applied three additional MR methods: MR-Egger, weighted median, and weighted mode. In addition, the Cochrane's Q test, MR-Egger intercept test, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out methods were used for sensitivity analysis. Our study shows a causal relationship between specific gut microbiota and neurodevelopmental outcomes in preterm infants. These findings provide new insights into the mechanism by which gut microbiota may mediate adverse neurodevelopmental outcomes in preterm infants.

Association of epidural analgesia in labor with neurodevelopmental outcomes in premature infants born at

To explore associations between epidural administration to mothers in labor with neurodevelopmental outcomes at 3 years corrected age in preterm infants born <29 weeks gestational age. Infants born <29 weeks gestational age between 2006 and 2012 were included. Our primary outcome was a composite of death or neurodevelopmental impairment at 3 years corrected age. Infants were divided into those whose mothers did or did not receive epidural analgesia in labor. Univariable and multivariable regression was used for analysis. There were 548 infants in the no epidural analgesia group and 121 in the epidural analgesia group. The adjusted odds ratio (95%CI) of neurodevelopmental impairment or death in the epidural group was 1.25 (0.82-1.93). Propensity score-matched results were 1.32 (0.79-2.22). Preterm infants born <29 weeks gestational age to mothers who received epidural analgesia during labor were not associated with poor neurodevelopmental outcomes at 3 years corrected age.

Effect of Placental Transfusion on Long-Term Neurodevelopmental Outcomes in Premature Infants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BackgroundThe pathophysiology and the potential risks of placental transfusion (PT) differ substantially in preterm infants, necessitating specific studies in this population. This study aimed to evaluate the safety and efficacy of PT in preterm infants from the perspective of long-term neurodevelopmental outcomes. MethodsWe conducted a systematic literature search using placental transfusion, preterm infant, and its synonyms as search terms. Cochrane Central Register of Controlled Trials, Medline, and Embase were searched until March 07, 2023. Two reviewers independently identified, extracted relevant randomized controlled trials, and appraised the risk of bias. The extracted studies were included in the meta-analysis of long-term neurodevelopmental clinical outcomes using fixed-effects models. ResultsA total of 5612 articles were identified, and seven randomized controlled trials involving 2551 infants were included in our meta-analysis. Compared with immediate cord clamping (ICC), PT may not impact adverse neurodevelopment events. No clear evidence was found of a difference in the risk of neurodevelopmental impairment (risk ratio [RR]: 0.89, 95% confidence interval [CI]: 0.76 to 1.03, P = 0.13, I2 = 0). PT was not associated with the incidence of cerebral palsy (RR: 1.23, 95% CI: 0.59 to 2.57, P = 0.79, I2 = 0). Analyses showed no differences between the two interventions in cognitive, language, and motor domains of neurodevelopment. ConclusionsFrom the perspective of long-term neurodevelopment, PT at preterm birth may be as safe as ICC. Future studies should focus on standardized, high-quality clinical trials and individual participant data to optimize cord management strategies for preterm infants after birth.

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.

Postnatal acetaminophen exposure and neurodevelopmental outcomes at 18-21 months corrected gestational age in preterm infants

Studies have reported prenatal acetaminophen exposure is associated with abnormal neurodevelopment. There is limited and conflicting data on neurodevelopmental outcomes following postnatal acetaminophen exposure. Our objective was to investigate the neurodevelopmental outcomes of preterm infants < 29 weeks gestation postnatally exposed to acetaminophen. Retrospective cohort study of infants born between 2008 and 2017 at a tertiary care perinatal center. Exclusion criteria included chromosomal disorders, major congenital abnormalities, and congenital infections. The primary outcome was a composite score of <85 on the cognitive, language, or motor components of the Bayley Scales of Infant and Toddler Development, 3rd edition, assessed at 18 to 21 months corrected gestational age. Multivariate logistic regression was used to assess confounders. Of the 945 infants included in the study, 120 were in the acetaminophen group. There was no difference in any of Bayley-III cognitive, language or motor composite scores of < 85 between the two groups for postnatal acetaminophen exposure, adjusted odds ratios (aORs) 1.03, 95% CI 0.60-1.78, or days of acetaminophen use, aORs 1.10, 95% CI 0.93-1.29. There was no difference in neurodevelopmental outcome between the acetaminophen exposed and non-exposed groups. Our results need validation in larger cohorts. Animal research and cohort studies have suggested that prenatal acetaminophen exposure may be associated with an elevated risk of neurobehavioral abnormalities. However, there is limited and conflicting research on the impact of postnatal acetaminophen on neurodevelopment. The results of this study suggest that postnatal acetaminophen does not negatively impact neurodevelopment at 18 to 21 months in preterm infants born at <29 weeks gestational age. While these results need validation in larger and more longitudinal studies, this study provides reassurance for the use of postnatal acetaminophen in extremely preterm infants.

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.

Clinical and neurodevelopmental outcomes in premature infants exposed to intravenous fish- and soybean oil-based lipid emulsions.

The optimal composition of lipid emulsions in parenteral nutrition (PN) for premature infants remains controversial. This study examined the effects of a combination of soybean oil-based (SoyLE) and fish oil-based (FishLE) lipid emulsions compared to FishLE as monotherapy on the lipid and fatty acid profiles and clinical outcomes of premature infants requiring prolonged PN. 42 premature infants received FishLE+SoyLE or FishLE. Serum concentrations of lipoproteins and 29 fatty acids (FA) were measured at baseline, 4, and 8 weeks of PN and growth and neurodevelopmental outcomes were measured at 3, 6, 12, 18, and 24 months of life. Lipid profiles were similar between groups. Plasma concentrations of ω-6 fatty acids tended to decrease over time in both groups. Concentrations of most ω-3 fatty acids, in particular docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid, were significantly increased over time in the FishLE+SoyLE group whereas they did not change in the FishLE alone group. However, serum concentrations of almost all fatty acids were similar between groups at the end of the study period. No differences in growth parameters including weight, height, fronto-occipital circumference (FOC), body mass index (BMI) were observed up to two years of age. Similarly, there were no differences in neurodevelopmental test scores at 6, 12, 18, and 24 months of age. No substantial differences in lipid profiles and short clinical outcomes were found in infants exposed to FishLE+SoyLE when compared to FishLE.

The miRNA transcriptome of cerebrospinal fluid in preterm infants reveals the signaling pathways that promote reactive gliosis following cerebral hemorrhage.

Germinal Matrix-Intraventricular Haemorrhage (GM-IVH) is one of the most common neurological complications in preterm infants, which can lead to accumulation of cerebrospinal fluid (CSF) and is a major cause of severe neurodevelopmental impairment in preterm infants. However, the pathophysiological mechanisms triggered by GM-IVH are poorly understood. Analyzing the CSF that accumulates following IVH may allow the molecular signaling and intracellular communication that contributes to pathogenesis to be elucidated. Growing evidence suggests that miRs, due to their key role in gene expression, have a significant utility as new therapeutics and biomarkers. The levels of 2,083 microRNAs (miRs) in 15 CSF samples from 10 infants with IVH were measured using miRNA whole transcriptome sequencing. Gene ontology (GO) and miR family analysis were used to uncover dysregulated signalling which were then validated in vitro in human foetal neural progenitor cells treated with IVH-CSF. Five hundred eighty-seven miRs were differentially expressed in the CSF extracted at least 2 months after injury, compared to CSF extracted within the first month of injury. GO uncovered key pathways targeted by differentially expressed miRs including the MAPK cascade and the JAK/STAT pathway. Astrogliosis is known to occur in preterm infants, and we hypothesized that this could be due to abnormal CSF-miR signaling resulting in dysregulation of the JAK/STAT pathway - a key controller of astrocyte differentiation. We then confirmed that treatment with IVH-CSF promotes astrocyte differentiation from human fetal NPCs and that this effect could be prevented by JAK/STAT inhibition. Taken together, our results provide novel insights into the CSF/NPCs crosstalk following perinatal brain injury and reveal novel targets to improve neurodevelopmental outcomes in preterm infants.

The differential associative relationship between early risk factors, neonatal morbidities and early neurodevelopmental outcome in preterm infants

BackgroundVery preterm infants of <29 weeks' gestation are at high risk for adverse neurodevelopment due to multiple risk factors in the early stages of life. There is little information regarding the associative effects of risk factors in early life, neonatal morbidities and subsequent neurodevelopmental outcomes. AimsInvestigate the association of early neurodevelopmental outcomes, neonatal complications and the risk factors in the early hours of life in a cohort of preterm infants <29 weeks' gestational age. MethodsWe enrolled all surviving preterm neonates born at gestation <29 weeks between January 2015 and June 2021 in the University of Hong Kong–Shenzhen Hospital. Demographic and clinical characteristics were collected from a database of the neonatal intensive care unit. Neurodevelopmental outcomes of the survivors were evaluated using the Ages and Stages Questionnaire (ASQ-3) which were measured at the adjusted age of 12 to 18 months. The multivariate linear regression model was used to determine correlation presented as β coefficient (β) with 95 % confidence intervals (CI). ResultsIn this cohort of 56 survivors <29 weeks' gestation, urine output within the first 12 h of life and Apgar score at 5 min were positively associated with different domains of ASQ-3 score, however male sex and highest fraction of inspired oxygen (FiO2) in the first 12 h of life were negatively related with at least one of neurocognitive domains of ASQ-3 at adjusted age of 12 to 18 months. During hospitalization, in addition to the frequency of packed red cell transfusions, the development of severe necrotizing enterocolitis was inversely associated with both neuromotor and neurocognitive skills (gross motor domain: β = −16.93, CI: −32.04, −1.82; fine motor domain: β = −16.42, CI: −28.82, −4.02; problem solving domain: β = −13.14, CI: −24.45, −1.83; all P < 0.05), whereas severe intraventricular hemorrhage had adverse effects on gross motor only (β = −13.04, CI: −24.42, −1.65; P = 0.03). Bronchopulmonary dysplasia and retinopathy of prematurity were not related with ASQ-3. ConclusionsIn this small cohort study of very preterm neonates born at <29 weeks' gestation, risk factors in the early hours of life and neonatal morbidities during hospitalization had differential associative relationships with ASQ-3 at 12–18 months adjusted age. This information may be important for parental counseling and management including early diagnosis and intervention.

GSDMD gene knockout alleviates hyperoxia-induced hippocampal brain injury in neonatal mice

BackgroundNeonatal hyperoxia exposure is associated with brain injury and poor neurodevelopment outcomes in preterm infants. Our previous studies in neonatal rodent models have shown that hyperoxia stimulates the brain’s inflammasome pathway, leading to the activation of gasdermin D (GSDMD), a key executor of pyroptotic inflammatory cell death. Moreover, we found pharmacological inhibition of caspase-1, which blocks GSDMD activation, attenuates hyperoxia-induced brain injury in neonatal mice. We hypothesized that GSDMD plays a pathogenic role in hyperoxia-induced neonatal brain injury and that GSDMD gene knockout (KO) will alleviate hyperoxia-induced brain injury.MethodsNewborn GSDMD knockout mice and their wildtype (WT) littermates were randomized within 24 h after birth to be exposed to room air or hyperoxia (85% O2) from postnatal days 1 to 14. Hippocampal brain inflammatory injury was assessed in brain sections by immunohistology for allograft inflammatory factor 1 (AIF1) and CD68, markers of microglial activation. Cell proliferation was evaluated by Ki-67 staining, and cell death was determined by TUNEL assay. RNA sequencing of the hippocampus was performed to identify the transcriptional effects of hyperoxia and GSDMD-KO, and qRT-PCR was performed to confirm some of the significantly regulated genes.ResultsHyperoxia-exposed WT mice had increased microglia consistent with activation, which was associated with decreased cell proliferation and increased cell death in the hippocampal area. Conversely, hyperoxia-exposed GSDMD-KO mice exhibited considerable resistance to hyperoxia as O2 exposure did not increase AIF1 + , CD68 + , or TUNEL + cell numbers or decrease cell proliferation. Hyperoxia exposure differentially regulated 258 genes in WT and only 16 in GSDMD-KO mice compared to room air-exposed WT and GSDMD-KO, respectively. Gene set enrichment analysis showed that in the WT brain, hyperoxia differentially regulated genes associated with neuronal and vascular development and differentiation, axonogenesis, glial cell differentiation, hypoxia-induced factor 1 pathway, and neuronal growth factor pathways. These changes were prevented by GSDMD-KO.ConclusionsGSDMD-KO alleviates hyperoxia-induced inflammatory injury, cell survival and death, and alterations of transcriptional gene expression of pathways involved in neuronal growth, development, and differentiation in the hippocampus of neonatal mice. This suggests that GSDMD plays a pathogenic role in preterm brain injury, and targeting GSDMD may be beneficial in preventing and treating brain injury and poor neurodevelopmental outcomes in preterm infants.

The Effect of Postnatal Cytomegalovirus Infection on (Micro)structural Cerebral Development in Very Preterm Infants at Term-Equivalent Age

Introduction: There are some data indicating a negative impact of postnatal cytomegalovirus (CMV) infection on long-term neurodevelopmental outcome of preterm infants. So far, there is only little knowledge about a cerebral imaging correlate of these neurodevelopmental alterations induced by postnatal CMV infection in preterm infants. The aim of the current study was to investigate the effect of postnatal CMV infection on the incidence of brain injury and on microstructural brain maturation in very preterm infants at term-equivalent age. Methods: Infants <32 gestational weeks (02/2011–11/2018) received cerebral MRI including axial diffusion-weighted images at term-equivalent age. All infants were screened for CMV infection using urine/saliva samples, and infection was regarded as acquired postnatal if a sample became positive >5 postnatal days. We compared brain injury as well as fractional anisotropy and apparent diffusion coefficient in 14 defined cerebral regions between infants with and without postnatal CMV infection. Results: 401 infants were eligible, of whom 18 (4.5%) infants had a postnatal CMV infection. There were no significant differences in rates of brain injury or in microstructural brain development between both groups. This applied equally to the subgroup of infants <28 gestational weeks. Conclusion: Although infants with postnatal CMV infection were born more immature and more frequently suffered from complications related to immaturity, we neither observed a higher rate of preterm brain injury nor disadvantageous alterations in microstructural brain maturation at term-equivalent age.

Neurodevelopmental Outcome of Preterm Infants with Hypothyroidism

Background: Hypothyroidism is one of the most common causes of preventable intellectual disability and is common in preterm infants. Some studies have reported that developmental delay is still high in these patients despite appropriate treatment. Objectives: This study aimed to investigate the short-term neurodevelopmental outcome of preterm infants with thyroid dysfunction. Methods: This cohort study included 50 preterm infants with thyroid dysfunction requiring levothyroxine treatment (case group) and 50 age- and sex-matched healthy preterm infants with normal thyroid tests (control group). The patients were followed, and Ages and Stages Questionnaires (ASQ) (including five domains) were filled out at 6 and 12 months to evaluate the short-term neurodevelopmental outcome. Results: There was no statistically significant difference in gestational age, sex, and birth weight between the two groups (P-values = 0.648, 0.756, and 0.866, respectively). A total number of 4 (8%) and 7 (14%) of the case group and 1 (2.85%) and 2 (5.71%) of the control group had a possible neurodevelopmental delay based on the low score in at least one domain of ASQ at 6 and 12 months of age (P-values = 0.321 and 0.222, respectively). Treated hypothyroidism was not significantly associated with higher impaired neurodevelopmental outcomes (P-value = 0.236, Odd Ratio: 2.686, 95% CI: 0.523 - 13.787). Conclusions: In this study, the risk of neurodevelopmental impairment in preterm infants with hypothyroidism was similar to that of healthy preterm infants. Thus, these findings may confirm the adequacy of levothyroxine replacement therapy in preventing neurodevelopmental delay.

Melatonin as a Therapy for Preterm Brain Injury: What Is the Evidence?

Despite significant improvements in survival following preterm birth in recent years, the neurodevelopmental burden of prematurity, with its long-term cognitive and behavioral consequences, remains a significant challenge in neonatology. Neuroprotective treatment options to improve neurodevelopmental outcomes in preterm infants are therefore urgently needed. Alleviating inflammatory and oxidative stress (OS), melatonin might modify important triggers of preterm brain injury, a complex combination of destructive and developmental abnormalities termed encephalopathy of prematurity (EoP). Preliminary data also suggests that melatonin has a direct neurotrophic impact, emphasizing its therapeutic potential with a favorable safety profile in the preterm setting. The current review outlines the most important pathomechanisms underlying preterm brain injury and correlates them with melatonin's neuroprotective potential, while underlining significant pharmacokinetic/pharmacodynamic uncertainties that need to be addressed in future studies.

Development and validation of a prediction model for evaluating extubation readiness in preterm infants

Successful early extubation has advantages not only in terms of short-term respiratory morbidities and survival but also in terms of long-term neurodevelopmental outcomes in preterm infants. However, no consensus exists regarding the optimal protocol or guidelines for extubation readiness in preterm infants. Therefore, the decision to extubate preterm infants was almost entirely at the attending physician's discretion. We identified robust and quantitative predictors of success or failure of the first planned extubation attempt before 36 weeks of post-menstrual age in preterm infants (<32 weeks gestational age) and developed a prediction model for evaluating extubation readiness using these predictors. Extubation success was defined as the absence of reintubation within 72 h after extubation. This observational cohort study used data from preterm infants admitted to the neonatal intensive care unit of Seoul National University Bundang Hospital in South Korea between July 2003 and June 2019 to identify predictors and develop and test a predictive model for extubation readiness. Data from preterm infants included in the Medical Informative Medicine for Intensive Care (MIMIC-III) database between 2001 and 2008 were used for external validation. From a machine learning model using predictors such as demographics, periodic vital signs, ventilator settings, and respiratory indices, the area under the receiver operating characteristic curve and average precision of our model were 0.805 (95% confidence interval [CI], 0.802–0.809) and 0.917, respectively in the internal validation and 0.715 (95% CI, 0.713–0.717) and 0.838, respectively in the external validation. Our prediction model (NExt-Predictor) demonstrated high performance in assessing extubation readiness in both internal and external validations.

Clinical characteristics and long-term neurodevelopmental outcomes of leukomalacia in preterm infants and term infants: a cohort study

BackgroundLeukomalacia is a serious form of neonatal brain injury that often leads to neurodevelopmental impairment, and studies on neonatal leukomalacia and its long-term outcomes are lacking. The aim of this study was to analyze the clinical manifestations, imaging features, and long-term neurodevelopmental outcomes in preterm infants and term infants with leukomalacia.MethodsNewborns diagnosed with leukomalacia by head magnetic resonance imaging (MRI) and who were admitted to intensive care units from January 2015 to June 2020 were enrolled. All infants were followed up to June 2022 (2–7 years old), and their neurodevelopmental outcomes were evaluated. The clinical data and long- term outcomes of preterm infants and term infants was analyzed by Chi-square tests.ResultsA total of 218 surviving infants with leukomalacia including 114 preterm infants and 104 term infants completed the follow-up. The major typesof leukomalacia on MRI were periventricular leukomalacia in the preterm group and subcortical cystic leukomalacia in the term group, respectively (χ2 = 55.166; p < 0.001). When followed up to 2–7 years old, the incidence of neurodevelopmental impairment in the preterm group and term group was not significantly different (χ2 = 0.917; p = 0.338). However, the incidence of cerebral palsy (CP) in the preterm group was significantly higher (χ2 = 4.896; p = 0.027), while the incidence of intellectual disability (ID) (χ2 = 9.445; p = 0.002), epilepsy (EP) (χ2 = 23.049; p < 0.001), and CP combined with ID andEP (χ2 = 4.122; p = 0.042) was significantly lower than that in the term group.ConclusionsPeriventricular leukomalacia mainly occurred in preterm infants while subcortical cystic leukomalacia was commonly seen in term infants. Although the long-term neurodevelopmental outcomes of leukomalacia were both poor, preterm infants were more prone to CP, while term infants were more prone to ID, EP, and the combination of CP with ID and EP.

Diagnostic performance of synthetic relaxometry for predicting neurodevelopmental outcomes in premature infants: a feasibility study.

To investigate the predictability of synthetic relaxometry for neurodevelopmental outcomes in premature infants and to evaluate whether a combination of relaxation times with clinical variables or qualitative MRI abnormalities improves the predictive performance. This retrospective study included 33 premature infants scanned with synthetic MRI near or at term equivalent age. Based on neurodevelopmental assessments at 18-24 months of corrected age, infants were classified into two groups (no/mild disability [n= 23] vs. moderate/severe disability [n= 10]). Clinical and MRI characteristics associated with moderate/severe disability were explored, and combined models incorporating independent predictors were established. Ultimately, the predictability of relaxation times, clinical variables, MRI findings, and a combination of the two were evaluated and compared. The models were internally validated using bootstrap resampling. Prolonged T1-frontal/parietal and T2-parietal periventricular white matter (PVWM), moderate-to-severe white matter abnormality, and bronchopulmonary dysplasia were significantly associated with moderate/severe disability. The overall predictive performance of each T1-frontal/-parietal PVWM model was comparable to that of individual MRI finding and clinical models (AUC = 0.71 and 0.76 vs. 0.73 vs. 0.83, respectively; p >0.27). The combination of clinical variables and T1-parietal PVWM achieved an AUC of 0.94, sensitivity of 90%, and specificity of 91.3%, outperforming the clinical model alone (p= 0.049). The combination of MRI finding and T1-frontal PVWM yielded AUC of 0.86, marginally outperforming the MRI finding model (p= 0.09). Bootstrap resampling showed that the models were valid. It is feasible to predict adverse outcomes in premature infants by using early synthetic relaxometry. Combining relaxation time with clinical variables or MRI finding improved prediction. Synthetic relaxometry performed during the neonatal period may serve as a biomarker for predicting adverse neurodevelopmental outcomes in premature infants. • Synthetic relaxometry based on T1 relaxation time of parietal periventricular white matter showed acceptable performance in predicting adverse outcome with an AUC of 0.76 and an accuracy of 78.8%. • The combination of relaxation time with clinical variables and/or structural MRI abnormalities improved predictive performance of adverse outcomes. • Synthetic relaxometry performed during the neonatal period helps predict adverse neurodevelopmental outcome in premature infants.

Neurodevelopmental Outcomes of Preterm Infants Born

This study aimed to determine neurodevelopmental outcomes of preterm infants born at <29 weeks' gestational age (GA) with bronchopulmonary dysplasia and pulmonary hypertension (BPD-PH) at 18 to 24 months' corrected age (CA). In this retrospective cohort study, preterm infants born at <29 weeks' GA between January 2016 and December 2019, admitted to level 3 neonatal intensive care units, who developed BPD and were evaluated at 18 to 24 months' CA in the neonatal follow-up clinics were included. We compared demographic characteristics and neurodevelopmental outcomes between the two groups: Group I: BPD with PH and Group II: BPD with no PH, using univariate and multivariate regression models. The primary outcome was a composite of death or neurodevelopmental impairment (NDI). NDI was defined as any Bayley-III score < 85 on one or more of the cognitive, motor, or language composite scores. Of 366 eligible infants, 116 (Group I [BPD-PH] =7, Group II [BPD with no PH] = 109) were lost to follow-up. Of the remaining 250 infants, 51 in Group I and 199 in Group II were followed at 18 to 24 months' CA. Group I and Group II had median (interquartile range [IQR]) birthweights of 705 (325) and 815 g (317; p = 0.003) and median GAs (IQR) were 25 (2) and 26 weeks (2; p = 0.015) respectively. Infants in the BPD-PH group (Group I) were more likely to have mortality or NDI (adjusted odds ratio: 3.82; bootstrap 95% confidence interval; 1.44-40.87). BPD-PH in infants born at <29 weeks' GA is associated with increased odds of the composite outcome of death or NDI at 18 to 24 months' CA. · Long-term neurodevelopmental follow-up of preterm infants born <29 weeks' GA.. · Association of neurodevelopmental outcomes with BPD-associated PH.. · Need for longitudinal follow-up of children with BPD-associated PH..

Predicting neurodevelopmental outcomes in preterm infants: A comprehensive evaluation of neonatal and maternal risk factors

ObjectiveThis retrospective cohort study aimed to evaluate neurodevelopmental outcomes of preterm infants (≤ 34 weeks gestational age) in the NICU. MethodsThis retrospective cohort study included 89 preterm infants admitted to the NICU of Ghaem hospital, Mashhad, between 2016 and 2020. Data on neonatal and maternal factors were collected. By recalling the mentioned infants in 2021, the neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development. Data analysis included descriptive statistics, non-parametric tests, and binary logistic regression conducted with SPSS V.26 and R program software. ResultsThe sample comprised 48.3 % males with a mean gestational age of 32.10 weeks. Bayley Scale analysis revealed significant associations of Intrauterine Growth Restriction, Pneumothorax, and Bronchopulmonary Dysplasia with impairments in all domains. Diabetes in Pregnancy, Surfactant use, and Necrotizing Enterocolitis were also significantly linked to various impairments. Lower Apgar scores, gestational age, birth weight, and extended hospitalization and oxygen therapy durations correlated with several domain impairments. Logistic regression showed hospitalization duration impacted the coarse motor domain (OR = 0.92, p = 0.019), oxygen therapy duration influenced cognitive, perceptual, and fine motor domains. ConclusionThis study underscores the importance of considering neonatal and maternal factors when assessing developmental outcomes in preterm infant. Long hospital stays and increase duration of oxygen therapy associated with negative developmental outcomes in different domains of Bayley scales.Early identification of these risk factors and targeted interventions may improve long-term outcomes for preterm children.

The association of maternal overweight on long-term neurodevelopmental outcomes in premature infants (< 29 weeks) at 18-24 months corrected age.

To determine the association of maternal pre-pregnancy body mass index (BMI) and neurodevelopmental impairment (NDI) at 18-24 months corrected age (CA) in infants born < 29 weeks gestation. Infants born between 2005 and 2015 at < 29 weeks gestation were included. BMI was categorized into BMI1 [18.5-24.9 kg/m2], BMI2 [25-29.9 kg/m2], BMI3 [ ≥ 30 kg/m2]. Primary outcome was death or NDI (Bayley-III scores < 85, cerebral palsy, hearing or visual impairment). Univariate and multivariate analysis were used. There were 315 infants in BMI1, 235 in BMI2, and 147 in BMI3 groups. Adjusted odds ratio (aOR) of death or NDI in BMI2 vs. BMI1 and BMI3 vs BMI1 groups were 1.33 (95% CI 0.86-2.06) and 0.76 (95% CI 0.47-1.22). Adjusted odds ratio of Bayley-III language composite < 85 was 2.06 (95% CI 1.28-3.32). Pre-pregnancy BMI was not associated with death or NDI in extremely preterm infants. Infants born to overweight mothers had higher odds of low language scores.