Neurodevelopmental Outcome In Preterm Infants Research Articles

Using heart rate variability to predict neurological outcomes in preterm infants: a scoping review.

Infants born preterm are at higher risk of neurological complications, including intraventricular haemorrhage and white matter injury. After discharge, these infants may experience adverse neurodevelopmental outcomes and exhibit lower educational attainment. Early detection of brain injury and accurate prediction of neurodevelopmental impairment would allow early intervention and support. Heart rate variability (HRV) describes the variation of time intervals between each subsequent heartbeat. HRV is controlled by the autonomic nervous system, which may be affected by hypoxia and compromised blood flow. While HRV has primarily been investigated in neonatal sepsis, the association between HRV, brain injury and neurodevelopmental outcomes in preterm infants is less established. The present scoping review examines the utility of HRV monitoring for predicting short-term and long-term neurological outcomes in preterm infants. Following systematic search of Medline, Embase, Web of Science and the Cochrane Library, 15 studies were included. Nine studies examined the relationship between HRV and brain injury, with all but two showed an association. Eight studies examined the relationship between HRV and long-term outcomes and all eight found an association. This scoping review suggests that decreased HRV in the neonatal period is associated with short- and long-term neurodevelopmental outcomes in preterm infants. IMPACT: Changes in heart rate variability correlate with the occurrence of intraventricular haemorrhage in preterm infants. A decrease in heart rate variability may precede the development of intraventricular haemorrhage. Alterations in heart rate variability correlate with long-term neurodevelopmental outcomes. Significant variability exists in metrics used in assessing heart rate variability.

Neurodevelopmental outcomes following paracetamol use for treatment of patent ductus arteriosus: A review.

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

Machine Learning for the Identification of Key Predictors to Bayley Outcomes: A Preterm Cohort Study.

The aim of this study was to understand how neurological development of preterm infants can be predicted at earlier stages and explore the possibility of applying personalized approaches. Our study included a cohort of 64 preterm infants, between 24 and 34 weeks of gestation. Linear and nonlinear models were used to evaluate feature predictability to Bayley outcomes at the corrected age of 2 years. The outcomes were classified into motor, language, cognitive, and socio-emotional categories. Pediatricians' opinions about the predictability of the same features were compared with machine learning. According to our linear analysis sepsis, brain MRI findings and Apgar score at 5th minute were predictive for cognitive, Amiel-Tison neurological assessment at 12 months of corrected age for motor, while sepsis was predictive for socio-emotional outcome. None of the features were predictive for language outcome. Based on the machine learning analysis, sepsis was the key predictor for cognitive and motor outcome. For language outcome, gestational age, duration of hospitalization, and Apgar score at 5th minute were predictive, while for socio-emotional, gestational age, sepsis, and duration of hospitalization were predictive. Pediatricians' opinions were that cardiopulmonary resuscitation is the key predictor for cognitive, motor, and socio-emotional, but gestational age for language outcome. The application of machine learning in predicting neurodevelopmental outcomes of preterm infants represents a significant advancement in neonatal care. The integration of machine learning models with clinical workflows requires ongoing education and collaboration between data scientists and healthcare professionals to ensure the models' practical applicability and interpretability.

Early neurodevelopmental outcomes of preterm infants with intraventricular haemorrhage and periventricular leukomalacia.

Intraventricular haemorrhage (IVH) and periventricular leukomalacia (PVL) in preterm infants are associated with an increased risk of long-term neurodevelopmental impairments (NDI) and cerebral palsy (CP). However, little is known about their impact on early neurodevelopmental outcomes despite increasing evidence highlighting the feasibility and importance of early NDI/CP diagnosis. We aimed to determine the early neurodevelopmental outcomes of preterm infants with IVH and PVL. This was a retrospective single-centre cohort study of preterm infants born at <29 weeks gestation or <1000 g birth weight who attended an Early Neurodevelopment Clinic at 3 to 4 months of corrected age. Primary outcomes of early NDI and CP/high-risk CP diagnoses based on Prechtl's General Movements Assessment and the Hammersmith Infant Neurological Examination were compared between infants without IVH and infants with mild IVH (grades I-II), severe IVH (grades III-IV), and severe brain injury (SBI; severe IVH or cystic PVL). Of 313 infants, 52.1% (n = 163), 41.2% (n = 129), 6.7% (n = 21) and 8.6% (n = 27) had no IVH, mild IVH, severe IVH and SBI, respectively. The adjusted odds of early CP/high-risk CP diagnosis were significantly higher in infants with severe IVH (aOR 6.07, 95% CI 1.50-24.50) and SBI (aOR 15.28, 95% CI 3.70-63), but not in those with mild IVH (aOR 1.24, 95% CI 0.49-3.10). However, the adjusted odds of any early NDI were similar across groups. Preterm infants with severe IVH and SBI are at increased risk of early CP/high-risk of CP diagnosis at 3 to 4 months of corrected age.

Comparison of CRIB-II with SNAPPE-II as a Predictor of Mortality and Neurodevelopmental Outcome at 12 Months of Age for Newborns ≤32 Weeks of Gestational Age

Premature births before 32 weeks of gestation pose a significant challenge in perinatal healthcare. The global incidence of premature births is on the rise. To ensure appropriate care and resource allocation, assessing the severity of neonatal illnesses is crucial. In this context, the study assessed CRIB-II and SNAPPE-II, two widely used scoring systems for newborn illness severity. These systems consider both perinatal and postnatal variables, providing comprehensive assessments. This prospective observational study conducted in an Eastern Indian tertiary care children’s hospital between February 2021 and August 2022 aimed to evaluate and compare the predictive capabilities of two scoring systems, CRIB-II and SNAPPE-II, for in-hospital mortality and long-term neurodevelopmental outcomes in preterm infants born before 32 weeks of gestational age. Results showed that both CRIB-II (AUC of 0.862, 95% CI: 0.745-0.939) and SNAPPE-II (AUC of 0.919 95%, CI: 0.816-0.975) demonstrated similar predictive abilities for neonatal mortality (difference: 0.057, 95% CI: -−0.044 to 0.16, P value .268). However, when it came to predicting long-term neurodevelopmental outcomes at 12 months of corrected gestational age, SNAPPE-II maintained significance, while CRIB-II did not. The discrepancy in their performance over time emphasizes the complexity of predicting long-term outcomes in very preterm infants. To conclude, this study suggests that CRIB-II and SNAPPE-II are comparable in predicting neonatal mortality. Given their similarity, CRIB-II may be preferred for its practicality in high-capacity NICUs. However, further research is needed to assess these systems’ utility in comparing later neurodevelopmental outcomes and to explore the impact of new factors on their predictive accuracy.

Optimal presence: enhancing parent integration to maximize neurodevelopmental outcomes in preterm infants.

Preterm birth disrupts the natural progression of events in the parent-infant relationship and bestows many of the typical parent responsibilities to the clinical care team. In turn, the neonatal intensive care environment (NICU) introduces obstacles to parents that would not otherwise be encountered and forces parents to adapt to this artificial environment as they seek to bond with and care for their newborn. Facilitating parent presence at the bedside and incorporating them into the care of their preterm infant is critical for lessening the immediate burden to both the parent and offspring while also ensuring the best possible outcome for preterm infants. In this review, we explore the impact that parents exert on the neurodevelopmental outcome of preterm infants and identify several barriers and facilitators to parent presence.

The Predictive Value of Amplitude-Integrated Electroencephalography for the Neurodevelopmental Outcomes of Preterm Newborns at 12 Months Corrected Age.

In clinical practice, it is crucial to identify diagnostic methods that can forecast the neurodevelopmental outcomes of very preterm neonates. Our study aimed to assess the predictive significance of amplitude-integrated electroencephalography (aEEG) for the neurodevelopmental outcomes of preterm infants at 12 months corrected age and to establish the cut-off score that could indicate potential neurodevelopmental impairments. Preterm neonates born before 32 weeks of gestational age between June 2020 and July 2022 were included in a prospective manner. Amplitude-integrated electroencephalography recordings were conducted at five age intervals (days 1-3; first, second, third and fourth weeks). Recordings were analyzed using the Burdjalov scoring system. The neurodevelopment assessment with Bayley Scales of Infant Development-Second Edition was carried out at 12 months corrected age. A total of 140 newborns were included in the study. Neurodevelopment was assessed in 108 infants at 12 months corrected age. Higher total aEEG Burdjalov scores were observed in groups with normal cognitive and motor development. The most sensitive and specific score for prediction of cognitive impairment in 12 months corrected age was an aEEG evaluation of 5.5 according to Burdjalov score within the first three days. The most sensitive and specific score for prediction of motor impairment was 8.5 within the first week. According to our research there is currently not enough data to accurately foresee the development of newborns at 12 months corrected age according to early aEEG test results. However, conducting a research with bigger sample size and repeated evaluations at a later age might increase the prognostic value of aEEG. In this study cut-off scores of aEEG performed early in life to predict later neurodevelopment outcomes were determined.

Parent-Guided Developmental Intervention for Infants With Very Low Birth Weight

Early interventions improve neurodevelopmental outcomes after preterm birth, but few studies of early intervention have focused on preterm infants whose families reside in low- or middle-income countries (LMICs). To evaluate whether parent-guided early intervention improves the neurodevelopmental outcomes of preterm infants in an LMIC. This randomized clinical trial was performed at a high-risk obstetric referral hospital in Brazil, with outcome evaluations by examiners masked to randomization group. Eligibility criteria were (1) birth at the study hospital, (2) residence within 40 km of the birth hospital, and (3) gestational age of less than 32 weeks or birth weight of less than 1500 g. Of 138 enrolled infants, 19 died after randomization and 19 withdrew from the study; all other enrollees (50 per randomization group) were evaluated for the primary outcome. Data were collected from January 1, 2016, to May 31, 2022, and analyzed from June 10 to July 31, 2022. On postnatal day 7, infants were randomized to usual care, consisting of support for lactation, kangaroo care, and routine developmental therapies, or to a parent-guided enhanced developmental intervention, consisting of usual care plus infant massage and enhanced visual stimulation, auditory stimulation, social interactions, and support for motor development, instructed by developmental therapists. The primary outcome was the Bayley Scales of Infant and Toddler Development-Third Edition score at 18 months of age adjusted for prematurity. Among the 100 infants included in the analysis, mean (SD) gestational age was 28.4 (2.2) weeks, and 57 (57%) were male. The mean (SD) gestational age for the intervention group was 28.3 (2.3) weeks; for the usual care group, 28.5 (2.2) weeks. Female infants accounted for 21 infants (42%) of the intervention group and 22 (44%) of the usual care group; male infants, 29 (58%) and 28 (56%), respectively. The enhanced developmental intervention group had higher cognitive scores at 18 months of corrected age (mean [SD], 101.8 [11.9] vs 97.3 [13.5]; mean difference, 4.5 [95% CI, 0.1-8.9]). In this randomized clinical trial of a parent-guided developmental intervention for early cognitive function of very preterm or very low birth weight infants implemented in an LMIC, the intervention improved very preterm infants' neurodevelopmental outcomes at 18 months of adjusted age. Parent-guided early intervention can improve neurodevelopmental outcome of very preterm infants born in LMICs. ClinicalTrials.gov Identifier: NCT02835612.

Prediction of post-hemorrhagic ventricular dilatation trajectory using a growth mixture model in preterm infants.

Early intervention for post-hemorrhagic ventricular dilatation (PHVD), guided by ventricular size measurements from cranial ultrasound (cUS), is associated with improved neurodevelopmental outcomes in preterm infants but benefits must be balanced against intervention risks. Anterior horn width (AHW) and ventricular index (VI) were measured from cUS for preterm infants (<29 weeks) with intraventricular hemorrhage admitted from 2010-2018. PHVD was defined as AHW > 6 mm or VI >97th percentile for postmenstrual age. Individual ventricular size trajectories were plotted, and a growth mixture model (GMM) used to identify latent trajectory classes and compare these to predetermined outcome of neurosurgical intervention. Measurements were obtained from 1543 cUS in 249 infants, of whom 39 had PHVD without and 17 PHVD with neurosurgical intervention based on signs of raised intracranial pressure. The GMM predicted trajectory identified: 93.3% of infants without PHVD, 88.2% and 30.8% of infants with PHVD with and without intervention using AHW; 100% of infants without PHVD, 52.9% and 59.0% of infants with PHVD with and without intervention using VI. The AHW GMM identified a significant proportion of infants with severe PHVD. Model refinement offers a promising approach for identifying differences in PHVD trajectory at an early stage to guide management. It is difficult to distinguish the trajectory of PHVD in the early stage of development, in particular PHVD that spontaneously arrests from slowly progressive PHVD which eventually requires intervention. We report the first modeling-based evaluation of PHVD trajectory for the prediction of short-term outcome of PHVD progression and neurosurgical intervention. With additional clinical validation and optimization to increase accuracy, predictive modeling has the potential to identify important differences in PHVD trajectory at an early stage in the clinical course, allowing for more individualized data-driven risk-benefit assessments to guide decisions on early intervention.

Has the COVID-19 pandemic negatively impacted children's development? An assessment of the neurodevelopment of premature babies born during the pandemic.

Pandemics, such as COVID-19, have the potential to adversely affect children's development due to a variety of negative factors at the level of children, families, and services. In this study the effect of the pandemic on the cognitive, language and motor development of premature babies who are among the most vulnerable group, were evaluated. The study included 236 premature infants who were followed at Hacettepe University Department of Developmental Pediatrics. The Bayley-Third Edition Developmental Assessment (Bayley III) was used to evaluate the neurodevelopment of 152 premature infants from the pre-pandemic group and 84 from the post-pandemic group at the corrected age of 18-24 months. The perinatal and sociodemographic risks were also evaluated. No difference in Bayley III scores (cognitive, language, and motor) was found between the pre- and post-pandemic groups. Furthermore, the multivariate covariance analysis displayed that regardless of the pandemic, infants with higher maternal education consistently scored higher in the cognitive, language, and motor domains; and the motor area scores of infants with moderate perinatal risk were also significantly higher than infants with high perinatal risk. It is crucial to monitor the development of vulnerable children who encounter developmental risks, such as premature babies. Fortunately, no significant effect was encountered during the COVID-19 pandemic. However, this does not underweigh the need for close supervision in extraordinary circumstances. Additionally, it should be noted that severe postnatal comorbidities, perinatal risks, and social factors, such as maternal education level, interact to influence the neurodevelopmental outcomes of preterm infants.

Impact of COVID-19 pandemic on neurodevelopmental outcomes of premature infants: a retrospective national cohort study

ObjectiveTo compare the neurodevelopmental outcomes of preterm infants before and during the COVID-19 pandemic.DesignPremature infants born in 2018 were assigned to the pre-pandemic group, while those born in 2019 were...

Brain health in preterm infants: importance of early-life pain and analgesia exposure.

"Everyday" exposures in the neonatal period, such as pain, may impact brain health in preterm infants. Specifically, greater exposure to painful procedures in the initial weeks after birth have been related to abnormalities in brain maturation and growth and poorer neurodevelopmental outcomes in preterm infants. Despite an increasing focus on the importance of treating pain in preterm infants, there is a lack of consensus of optimal approaches to managing pain in this population. This may be due to recent findings suggesting that commonly used analgesic and sedative medications in preterm infants may also have adverse effects of brain maturation and neurodevelopmental outcomes. This review provides an overview of potential impacts of pain and analgesia exposure on preterm brain health while highlighting research areas in need of additional investigations for the development of optimal pain management strategies in this population.

Postnatal Growth Assessment and Prediction of Neurodevelopment and Long-Term Growth in Very Low Birth Weight Infants: A Nationwide Cohort Study in Korea.

Background/Objectives: Extrauterine growth restriction (EUGR) is associated with high mortality and an increased incidence of poor neurodevelopmental outcomes in preterm infants. In this study, we aimed to compare the Intergrowth-21ST (IG-21ST) and Fenton charts in predicting long-term neurodevelopmental and anthropometric outcomes of very low birth weight (VLBW) infants. Methods: Data were collected from 2649 VLBW infants registered in the Korean Neonatal Network born between 240/7 and 316/7 weeks of gestational age from January 2013 to December 2017. Follow-up assessments were conducted at 18-24 months of age, corrected for prematurity. Multiple logistic regression analysis was performed to evaluate the association between EUGR and long-term outcomes. Results: Among the 2649 VLBW infants, 60.0% (1606/2649) and 36.9% (977/2649) were diagnosed as having EUGR defined by the Fenton chart (EUGRF) and by the IG-21ST chart (EUGRIG), respectively. The EUGRIG group exhibited a higher proportion of infants with cerebral palsy, neurodevelopmental impairment (NDI), and growth failure. In multiple logistic regression analysis, adjusted for risk factors for long-term outcome, the EUGRIG group showed higher risk of cerebral palsy (adjusted odds ratio [aOR], 1.66; 95% confidence interval [CI], 1.04-2.65), NDI (aOR, 2.09; 95% CI, 1.71-2.55), and growth failure (aOR, 1.57; 95% CI, 1.16-2.13). Infants with EUGRF tended to develop NDI (aOR, 1.29; 95%CI, 1.03-1.63) and experience growth failure (aOR, 2.44; 95% CI, 1.77-3.40). Conclusions: The IG-21ST chart demonstrated a more effective prediction of long-term neurodevelopmental outcomes, whereas the Fenton chart may be more suitable for predicting growth failure at 18-24 months.

The effect of oral motor intervention with different initiation times to improve feeding outcomes in preterm infants: protocol for a single-blind, randomized controlled trial

BackgroundPremature infants commonly encounter difficulties with oral feeding, a complication that extends hospital stays, affects infants’ quality of life, and imposes substantial burdens on families and society. Enhancing preterm infants’ oral feeding skills and facilitating their transition from parenteral or nasal feeding to full oral feeding pose challenges for neonatal intensive care unit (NICU) healthcare professionals. Research indicates that oral motor interventions (OMIs) can enhance preterm infants’ oral feeding capabilities and expedite the transition from feeding initiation to full oral feeding. Nonetheless, the most suitable timing for commencing these interventions remains uncertain.MethodsThis is a single-blind, randomized controlled trial. Preterm with a gestational age between 29+0 to 34+6 weeks will be eligible for the study. These infants will be randomized and allocated to one of two groups, both of which will receive the OMIs. The intervention commences once the infant begins milk intake during the early OMIs. Additionally, in the late OMIs group, the intervention will initiate 48 h after discontinuing nasal continuous positive airway pressure.DiscussionOMIs encompass non-nutritive sucking and artificial oral stimulation techniques. These techniques target the lips, jaw, muscles, or tongue of premature infants, aiming to facilitate the shift from tube feeding to oral feeding. The primary objective is to determine the ideal intervention timing that fosters the development of oral feeding skills and ensures a seamless transition from parenteral or nasal feeding to full oral feeding among preterm infants. Furthermore, this study might yield insights into the long-term effects of OMIs on the growth and neurodevelopmental outcomes of preterm infants. Such insights could bear substantial significance for the quality of survival among preterm infants and the societal burden imposed by preterm birth.Trial registrationchictr.org.cn ChiCTR2300076721. Registered on October 17, 2023.

Neurodevelopmental outcome in preterm infants with intraventricular hemorrhages: the potential of quantitative brainstem MRI.

This retrospective study aimed to identify quantitative magnetic resonance imaging markers in the brainstem of preterm neonates with intraventricular hemorrhages. It delves into the intricate associations between quantitative brainstem magnetic resonance imaging metrics and neurodevelopmental outcomes in preterm infants with intraventricular hemorrhage, aiming to elucidate potential relationships and their clinical implications. Neuroimaging was performed on preterm neonates with intraventricular hemorrhage using a multi-dynamic multi-echo sequence to determine T1 relaxation time, T2 relaxation time, and proton density in specific brainstem regions. Neonatal outcome scores were collected using the Bayley Scales of Infant and Toddler Development. Statistical analysis aimed to explore potential correlations between magnetic resonance imaging metrics and neurodevelopmental outcomes. Sixty preterm neonates (mean gestational age at birth 26.26 ± 2.69wk; n = 24 [40%] females) were included. The T2 relaxation time of the midbrain exhibited significant positive correlations with cognitive (r = 0.538, P < 0.0001, Pearson's correlation), motor (r = 0.530, P < 0.0001), and language (r = 0.449, P = 0.0008) composite scores at 1 yr of age. Quantitative magnetic resonance imaging can provide valuable insights into neurodevelopmental outcomes after intraventricular hemorrhage, potentially aiding in identifying at-risk neonates. Multi-dynamic multi-echo sequence sequences hold promise as an adjunct to conventional sequences, enhancing the sensitivity of neonatal magnetic resonance neuroimaging and supporting clinical decision-making for these vulnerable patients.

Predicting 2-year neurodevelopmental outcomes in preterm infants using multimodal structural brain magnetic resonance imaging with local connectivity

The neurodevelopmental outcomes of preterm infants can be stratified based on the level of prematurity. We explored brain structural networks in extremely preterm (EP; < 28 weeks of gestation) and very-to-late (V-LP; ≥ 28 and < 37 weeks of gestation) preterm infants at term-equivalent age to predict 2-year neurodevelopmental outcomes. Using MRI and diffusion MRI on 62 EP and 131 V-LP infants, we built a multimodal feature set for volumetric and structural network analysis. We employed linear and nonlinear machine learning models to predict the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) scores, assessing predictive accuracy and feature importance. Our findings revealed that models incorporating local connectivity features demonstrated high predictive performance for BSID-III subsets in preterm infants. Specifically, for cognitive scores in preterm (variance explained, 17%) and V-LP infants (variance explained, 17%), and for motor scores in EP infants (variance explained, 15%), models with local connectivity features outperformed others. Additionally, a model using only local connectivity features effectively predicted language scores in preterm infants (variance explained, 15%). This study underscores the value of multimodal feature sets, particularly local connectivity, in predicting neurodevelopmental outcomes, highlighting the utility of machine learning in understanding microstructural changes and their implications for early intervention.

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

Severe Bronchopulmonary Dysplasia Adversely Affects Brain Growth in Preterm Infants

Introduction: Bronchopulmonary dysplasia (BPD) is associated with neurodevelopmental outcomes of preterm infants, but its effect on brain growth in preterm infants after the neonatal period is unknown. This study aimed to evaluate the effect of severe BPD on brain growth of preterm infants from term to 18 months of corrected age (CA). Methods: Sixty-three preterm infants (42 with severe BPD and 21 without severe BPD) who underwent magnetic resonance imaging at term equivalent age (TEA) and 18 months of CA were studied by using the Infant Brain Extraction and Analysis Toolbox (iBEAT). We measured segmented brain volumes and compared brain volume and brain growth velocity between the severe BPD group and the non-severe BPD group. Results: There was no significant difference in brain volumes at TEA between the groups. However, the brain volumes of the total brain and cerebral white matter in the severe BPD group were significantly smaller than those in the non-severe BPD group at 18 months of CA. The brain growth velocities from TEA to 18 months of CA in the total brain, cerebral cortex, and cerebral white matter in the severe BPD group were lower than those in the non-severe BPD group. Conclusion: Brain growth in preterm infants with severe BPD from TEA age to 18 months of CA is less than that in preterm infants without severe BPD.

Variability in Definitions and Criteria of Extrauterine Growth Restriction and Its Association with Neurodevelopmental Outcomes in Preterm Infants: A Narrative Review.

Extrauterine growth restriction (EUGR) has been used in the literature and clinical practice to describe inadequate growth in preterm infants. Significant variability is seen in the criteria for EUGR, with no standard definition reached to date. Moreover, no consensus on the optimal timing for assessment or the ideal growth monitoring tool has been achieved, and an ongoing debate persists on the appropriate terminology to express poor postnatal growth. To ensure an adequate understanding of growth and early intervention in preterm infants at higher risk, it is critical to relate the diagnostic criteria of EUGR to the ability to predict adverse outcomes, such as neurodevelopmental outcomes. This narrative review was conducted to present evidence that evaluates neurodevelopmental outcomes in preterm infants with EUGR, comparing separately the different definitions of this concept by weight (cross-sectional, longitudinal and "true" EUGR). In this article, we highlight the challenges of comparing various published studies on the subject, even when subclassifying by the definition of EUGR, due to the significant variability on the criteria used for each definition and for the evaluation of neurodevelopmental outcomes in different papers. This heterogeneity compromises the obtention of a single firm conclusion on the relation between different definitions of EUGR and adverse neurodevelopmental outcomes.

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.