Risk Of Adverse Neurodevelopmental Outcomes Research Articles

Long-Term Pulmonary and Neurodevelopmental Outcomes of Meconium Aspiration Syndrome Affected Infants: A Retrospective National Population-Based Study in Taiwan

Introduction: Meconium aspiration syndrome (MAS) may cause severe pulmonary and neurologic injuries in affected infants after birth, leading to long-term adverse pulmonary or neurodevelopmental outcomes. Methods: This retrospective population-based cohort study enrolled 1,554,069 mother-child pairs between 2004 and 2014. A total of 8,049 infants were in the MAS-affected group, whereas 1,546,020 were in the healthy control group. Children were followed up for at least 3 years. According to respiratory support, MAS was classified as mild, moderate, and severe. With the healthy control group as the reference, the associations between MAS severity and adverse pulmonary outcomes (hospital admission, intensive care unit (ICU) admission, length of hospital stay, or invasive ventilator support during admission related to pulmonary problem) or adverse neurodevelopmental outcomes (cerebral palsy, needs for rehabilitation, visual impairment, or hearing impairment) were accessed. Results: MAS-affected infants had a higher risk of hospital and ICU admission and longer length of hospital stay, regardless of severity. Infants with severe MAS had a higher risk of invasive ventilator support during re-admission (odds ratio: 17.50, 95% confidence interval [CI]: 7.70–39.75, p < 0.001). Moderate (hazard ratio [HR]: 1.66, 95% CI: 1.30–2.13, p < 0.001) and severe (HR: 4.94, 95% CI: 4.94–7.11, p < 0.001) MAS groups had a higher risk of adverse neurodevelopmental outcome, and the statistical significance remained remarkable in severe MAS group after adjusting for covariates (adjusted HR: 2.28, 95% CI: 1.54–3.38, p < 0.001) Conclusions: Adverse pulmonary or neurodevelopmental outcomes could occur in MAS-affected infants at birth. Close monitoring and follow-up of MAS-affected infants are warranted.

Controlled Antenatal Thyroid Screening Study III: Effects of gestational thyroid status on adolescent brain morphology.

Children born to mothers with gestational hypo- or hyperthyroidism may have increased risk of adverse neurodevelopmental outcomes. However, the effects of maternal thyroid status on offspring brain development are unclear. To establish whether adolescent brain morphology is affected by suboptimal gestational thyroid function (SGTF). The Controlled Antenatal Thyroid Screening (CATS) study randomized mothers with SGTF to levothyroxine or no supplementation from ∼12 weeks' gestation. At age 9, children born to mothers who were over-treated with levothyroxine had a higher risk of conduct and hyperactivity traits. For the current CATS III study, children underwent neuroimaging studies, including T1-weighted structural magnetic resonance imaging (MRI). A total of 85 children aged 11-16 years had usable T1-weighted MRI data (exposed to untreated SGTF (n=21), normal GTF (n=24), or treated SGTF (optimally-treated (n=21), over-treated (n=20)). Primary outcome: to examine the association of SGTF and its treatment with global brain volumes. Secondary and exploratory outcomes: to investigate the association of maternal TSH and free T4 levels with global and subregional brain volumes. Results were adjusted for age, sex and pubertal scores. There were no significant differences in global brain volumetric measures between groups, including total gray matter volume (p=0.373). Weak positive correlations were found between maternal TSH, but not FT4, levels and several brain volumes, but these did not survive testing for multiple comparisons. We found no evidence that SGTF was associated with differences in adolescent brain morphology, and no impact of levothyroxine supplementation.

The search for blood biomarkers that indicate risk of adverse neurodevelopmental outcomes in fetal growth restriction.

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369242, Identifier CRD42022369242.

Evaluation of white matter microstructural alterations in premature infants with necrotizing enterocolitis.

Preterm infants with necrotizing enterocolitis (NEC) are at high risk of adverse neurodevelopmental outcomes. The aim of this study was to explore the value of diffusion tensor imaging (DTI) combined with serum C-reactive protein (CRP) and procalcitonin (PCT) in evaluating alterations of white matter (WM) microstructure in preterm infants with NEC. A retrospective cross-sectional study was conducted in which all participants were consecutively enrolled at The Third Affiliated Hospital of Zhengzhou University from June 2017 and October 2021. Data from 30 preterm infants with NEC [mean gestational age at birth 31.41±1.15 weeks; mean age at magnetic resonance imaging (MRI) 37.53±3.08 weeks] and 40 healthy preterm infants with no NEC were recorded (mean gestational age at birth 32.27±2.09 weeks; mean age at MRI 37.15±3.23 weeks). WM was used to obtain the fractional anisotropy (FA) and mean diffusivity (MD) values of the regions of interest (ROIs). Additionally, serum levels of CRP and PCT were determined. Spearman correlation analysis was performed between the WM-derived parameters, CRP level, and the PCT serum index. Preterm infants with NEC had reduced FA values and elevated MD values in WM regions [posterior limbs of the internal capsule (PLIC), lentiform nucleus (LN), frontal white matter (FWM)] compared to the control group (P<0.05). Additionally, the FA of the PLIC was negatively correlated with serum CRP (r=-0.846; P<0.05) and PCT (r=-0.843; P<0.05). Meanwhile, the MD of PLIC was positively correlated with serum CRP (r=0.743; P<0.05) and PCT (r=0.743; P<0.05, respectively). The area under the curve (AUC) of FA and MD combined with CRP and PCT in the diagnosis of WM microstructure alterations with NEC was 0.968, representing a considerable improvement in predicted efficacy over single indicators, including FA [AUC: 0.938; 95% confidence interval (CI): 0.840-0.950], MD (AUC: 0.807; 95% CI: 0.722-0.838), CRP (AUC: 0.867; 95% CI: 0.822-0.889), and PCT (AUC: 0.706; 95% CI: 0.701-0.758). WM can noninvasively and quantitatively assess the WM microstructure alterations in preterm infants with NEC. WM combined with serum CRP and PCT demonstrated superior performance in detecting and evaluating WM microstructure alterations in preterm infants with NEC.

Prospective assessment of early developmental markers and their association with neuropsychological impairment

Children who experience adversities in the pre-perinatal period are at increased risk of developing impairment later in life, despite the absence of overt brain and neurological abnormalities. However, many of these children exhibit sequelae several years after a period of normal appearance. As a result, the need for reliable developmental assessments for the early detection of infants at high risk of adverse neurodevelopmental outcomes has emerged. The Griffiths Mental Developmental Scales have a promising but poorly explored prognostic ability. This longitudinal study evaluated the predictive power of the Griffiths Mental Developmental Scales at 12 and 24 months on the cognitive and neuropsychological profile at 6 years of age in a sample of 70 children with a history of prematurity or perinatal asphyxia but without brain and neurological abnormalities. We found that the Griffiths Mental Developmental Scales at 24 months had good predictive ability on the intelligence quotient at 6 years and the capacity to predict some neuropsychological performances. On the other hand, the Griffiths Mental Developmental Scale at 12 months was not associated with the performance at 6 years or 24 months. Conclusion: Data on brain development converge to indicate that the first two years of age represent a critical stage of development, particularly for children experiencing mild pre-perinatal adversities who are thought to exhibit white matter dysmaturity. For this reason, this age is crucial for identifying which children are at major risk, leaving enough time to intervene before overt deficits become apparent. Brain development in the first 2 years could explain the limited reliability of early neurodevelopmental testing.What is Known:• Pre-perinatal adversities increase the risk of developing neurodevelopmental disorders.• The predictive ability of the Griffith scale is poorly explored in low-grade conditions.What is New:• The predictive ability of the Griffith scale has been investigated in low-risk children.• A complete neuropsychological profile could offer a more accurate prediction than the intellectual quotient.

Functional measures on PEDI are associated with BSID-3 scales at 2 years, following neonatal surgery

BackgroundNeonates requiring early surgical intervention for major non-cardiac congenital anomalies are at high risk of adverse neurodevelopmental outcomes. Early recognition of potential neuro-developmental delay is critical to facilitate access to early childhood intervention services and therefore maximise the functional capabilities of these children. AimsThis study aims to compare Bayley's Scales of Infant and Toddler Development (BSID-3) and the Paediatric Evaluation of Disability Inventory (PEDI) as early screening tools in predicting neuro-developmental disability across multiple domains. In addition, it looks at determining which pre, peri and post-operative risk factors lend themselves to more adverse outcomes. Study designRetrospective cohort study. SubjectsNeonates requiring surgical intervention at the Royal Children's Hospital from 2012 to 2018 who subsequently underwent neurodevelopmental assessment at 2 years of age. Outcome measuresThe main outcome was the relationship between performance on the PEDI compared with the BSID-3, in 2-year-olds following neonatal surgery. ResultsParent -reported functional measures across all domains on PEDI strongly related to the more formal measures of cognition, language, and motor development assessed on BSID-3 (p < 0.05). ConclusionsThe questionnaire-based PEDI tool could be considered a reliable replacement to the formal Bayley (BSID-3) scale in low-risk infants and provide a more accessible means of assessment where there are deficiencies in availability of suitably trained clinicians or limited resource centres.

Impact of Prenatal Acetaminophen Exposure for Hippocampal Development Disorder on Mice.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used as analgesic agents. They have been detected in various environmental matrices. The degradation of environmental contaminants and the long-term adverse effects have become a major public concern. Prenatal exposure to acetaminophen can cause damage to the developing hippocampus. However, the molecular mechanisms behind hippocampal damage following prenatal acetaminophen exposure (PAcE) remain unclear. The present study shows an increased risk of adverse neurodevelopmental outcomes in offspring following exposure to acetaminophen during pregnancy on mice. The results revealed that different doses, timings, and duration of exposure to acetaminophen during pregnancy were associated with dose-dependent changes in the hippocampus of the offspring. Furthermore, exposure to high doses, multiple-treatment courses, and late pregnancy induced pathological changes, such as wrinkling and vacuolation, inhibited hippocampal proliferation and increased apoptosis. In addition, PAcE significantly decreased the expression of genes related to synaptic development in fetal hippocampal neurons and hippocampal astrocyte and microglia were also damaged to varying degrees. The significant reduction either in SOX2, an essential gene in regulating neural progenitor cell proliferation, and reduction of genes related to the SOX2/Notch pathway may suggest that the role of SOX2/Notch pathway in impaired hippocampal development in the offspring due to PAcE. In general, PAcE at high doses, multiple-treatment courses, and mid- and late gestation were associated with neurodevelopmental toxicity to the offspring.

Growth and risk of adverse neuro-developmental outcome in newborns with congenital heart disease: A single-centre retrospective study

BackgroundMortality in infants with CHD is decreasing and focus has shifted to improving long-term outcomes. Growth and neurodevelopmental outcomes are important long-term endpoints for both clinicians and parents. ObjectiveTo evaluate growth and determine the impact of growth on neurodevelopmental outcomes at one year of age in infants who had an operative or therapeutic catheter procedure for CHD in neonatal period. MethodsThis was a single-centre retrospective cohort study of infants born at term gestation with CHD. Demographic details, measurements of growth, and scores of Bayley Scales of Infant and Toddler Assessment (third edition), were collected. Enrolled study participants were categorised in subgroups based on the procedures required prior to one-year assessment. Regression analysis was performed to explore predictive ability of anthropometric measurements on mean scores of developmental assessment. ResultsA total of 184 infants were included in the study. Mean z-scores for weight and head circumference at birth were age-appropriate. Mean scores for various developmental domains ranged from borderline to normal except for infants with single ventricular physiology who had gross motor delay concomitant with growth failure. In this group, z-score of weight at one-year-assessment predicted mean score of cognition (p-value 0.02), fine motor (p-value 0.03) and gross motor nearly (p-value 0.06). ConclusionsInfants born at term gestation, with CHD, without genetic diagnosis had normal fetal growth. Postnatal growth restriction and developmental delay was most marked in infants with single ventricle physiology, suggesting careful nutritional and developmental monitoring.

Prenatal Predictors of Neurobehavioral Outcome in Children with Fetal Growth Restriction at 6 Years of Age: A Retrospective Cohort Study

(1) Background: Fetal growth restriction (FGR) increases the risk of adverse neurodevelopmental outcomes, especially in preterm newborns. This study aims to describe the behavioral results of FGR at 6 years of age and to demonstrate the relationship of certain predictive factors with this development. (2) Methods: This retrospective cohort study included 70 children born in 2015 at the University Hospital Carlos Haya, Málaga, Spain who had been exposed to FGR during pregnancy; neonatal and infant data were recorded retrospectively. Children were assessed prospectively at 6 years of age by means of a strengths and difficulties questionnaire (SDQ) to study behavioral outcomes. (3) Results: We demonstrated that there are higher behavioral disability rates in children exposed to FGR during pregnancy and, in particular, high rates of hyperactivity or conduct problems. We also proved a negative relationship between the birth weight percentile and the total behavioral scale score, along with a positive correlation between hyperactivity and the emotional and behavioral scales. Learning difficulties were more frequent in early-onset FGR than in late-onset FGR. (4) Conclusions: Our study of behavioral development has demonstrated higher behavioral disability rates in children with FGR at 6 years of age; specifically, high rates of hyperactivity or conduct problems. At the same time, we have proved a negative relationship between the birth weight percentile and the total behavioral scale score.

Maternal Prenatal Risk Phenotypes and Neurobehavioral Outcomes among Infants Born Very Preterm

To assess whether prenatal risk phenotypes are associated with neurobehavioral impairment for childrenborn <30weeks of gestation at discharge from the neonatal intensive care unit (NICU) and at 24-month follow-up. We studied infants from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) study, a multisite investigation of infants born <30weeks of gestation. There were 704 newborns enrolled in the NOVI study; of these, 679 (96%) had neonatal neurobehavioral data and 556 (79%) had 24-month follow-up data. Maternal prenatal phenotypes (physical and psychological risk groups) were characterized from 24 physical and psychological health risk factors. Neurobehavior was assessed at NICU discharge using the NICU Network Neurobehavioral Scales and at 2-year follow-up using the Bayley Scales of Infant and Toddler Development and the Child Behavior Checklist. Children born to mothers in the psychological risk group were at increased risk for dysregulated neonatal neurobehavior (OR,2.04; 95% CI,1.08-3.87) at NICU discharge, and for severe motor delay (OR,3.80; 95% CI,1.48-9.75), and clinically significant externalizing problems (OR,2.54; 95% CI,1.15-5.56) at age 24months, compared with children born to mothers in the low-risk group. Children born to mothers in the physical risk group were more likely to have severe motor delay (OR,2.70; 95% CI,1.07-6.85) compared with the low-risk group. High-risk maternal prenatal phenotypes were associated with neurobehavioral impairment for children born very preterm. This information could identify newborns at risk for adverse neurodevelopmental outcomes.

In-hospital growth and long-term neurodevelopmental outcomes of very low birth weight infants.

Very low birth weight infants (VLBW) are at risk for adverse growth and neurodevelopmental outcomes. We aimed to evaluate the association between growth during Neonatal Intensive Care Unit (NICU) stay and long-term neurodevelopmental outcomes in a cohort of preterm VLBW newborns. We conducted a longitudinal observational study in the Follow-up Service of our Clinic from January 2014 to April 2017. All preterm VLBW infants born at our hospital and enrolled in our follow-up program were considered eligible for the study. The neurodevelopmental assessment was performed using the Griffiths Mental Development Scales at 12 and 24 months corrected age. Study population included 172 subjects (47.1% males) with a mean gestational age of 29 weeks and a mean birth weight of 1,117 g. A unitarian Δz-score increase in head circumference from birth to discharge was associated with a 1.6-point increase in General Quotient at 24 months corrected age. An association with subscales C and D was also found. Likewise, an increase in length Δz-score was associated with better 24-month subscale C scores although not reaching statistical significance. No relationship with the outcome at 24 months was found for weight gain. Growth during NICU stay appears to be related to a more favorable neurodevelopmental outcome at 24 months corrected age, especially in the hearing and language domain (subscale C). The longitudinal evaluation of auxological parameters during hospitalization can contribute to the identification of subjects at risk for adverse neurodevelopmental outcomes in the first years of life.

Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes: Design, Recruitment, and Technical Challenges of a Multicenter, Observational Neuroimaging Study.

Patients with hypoplastic left heart syndrome who have been palliated with the Fontan procedure are at risk for adverse neurodevelopmental outcomes, lower quality of life, and reduced employability. We describe the methods (including quality assurance and quality control protocols) and challenges of a multi-center observational ancillary study, SVRIII (Single Ventricle Reconstruction Trial) Brain Connectome. Our original goal was to obtain advanced neuroimaging (Diffusion Tensor Imaging and Resting-BOLD) in 140 SVR III participants and 100 healthy controls for brain connectome analyses. Linear regression and mediation statistical methods will be used to analyze associations of brain connectome measures with neurocognitive measures and clinical risk factors. Initial recruitment challenges occurred that were related to difficulties with: (1) coordinating brain MRI for participants already undergoing extensive testing in the parent study, and (2) recruiting healthy control subjects. The COVID-19 pandemic negatively affected enrollment late in the study. Enrollment challenges were addressed by: (1) adding additional study sites, (2) increasing the frequency of meetings with site coordinators, and (3) developing additional healthy control recruitment strategies, including using research registries and advertising the study to community-based groups. Technical challenges that emerged early in the study were related to the acquisition, harmonization, and transfer of neuroimages. These hurdles were successfully overcome with protocol modifications and frequent site visits that involved human and synthetic phantoms.

Systemic postnatal corticosteroid use for the prevention of bronchopulmonary dysplasia and its relationship to early neurodevelopment in extremely preterm infants

BackgroundSystemic postnatal corticosteroid use in extremely preterm infants poses a risk of adverse neurodevelopmental outcomes. This study explores their use beyond seven days of age with early neurodevelopmental assessments during the fidgety period (9–20 weeks postterm age).MethodsThis retrospective single-center cohort study included inborn extremely preterm infants from 1 January 2014 to 31 December 2018. Outborn infants, those with congenital or genetic abnormalities, and those who received postnatal corticosteroids for nonrespiratory reasons were excluded. The cohort was dichotomized based on the status of corticosteroid receipt. Early neurodevelopmental outcomes were reported using Prechtl’s General Movements Assessment.ResultsOf the 282 infants, 67 (23.75%) received corticosteroids. Of these, 34 (50.75%) received them for dependency on invasive ventilation (intermittent positive-pressure ventilation), and the remainder received them for dependency on non-invasive ventilation continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP). Abnormal or absent fidgety movements were observed in 13% of infants (7/54) who received corticosteroids compared to 2% of infants (3/146) who did not. An increased odds for an abnormal general movements assessment from corticosteroid use after adjusting for gestational age [adjusted odds ratio (aOR) = 5.5, 95% confidence interval (CI) = 1.14–26.56] was observed. The motor optimality scores differed between the two groups [corticosteroid group: 25.5 (23–26) versus no-corticosteroid group: 26 (24–28); z = − 2.02]. A motor optimality score < 20 was observed in 14.8% of infants (8/54) in the corticosteroid group compared to 2% of infants (3/146) in the noncorticosteroid group. This difference was significant after adjustment for gestational age (aOR 5.96, 95% CI 1.28–27.74).ConclusionsAbnormal early neurodevelopment was observed in infants who received systemic postnatal corticosteroids. The relationship between these findings and other factors influencing early neurodevelopment needs further exploration.

The Long-Term Outcome and Rehabilitative Approach of Intraventricular Hemorrhage at Preterm Birth.

Technological advances in neonatology led to the improvement of the survival rate in preterm babies with very low birth weights. However, intraventricular hemorrhage (IVH) has been one of the major complications of prematurity. IVH is relevant to neurodevelopmental disorders, such as cerebral palsy, language and cognitive impairments, and neurosensory and psychiatric problems, especially when combined with brain parenchymal injuries. Additionally, severe IVH requiring shunt insertion is associated with a higher risk of adverse neurodevelopmental outcomes. Multidisciplinary and longitudinal rehabilitation should be provided for these children based on the patients' life cycles. During the infantile period, it is essential to detect high-risk infants based on neuromotor examinations and provide early intervention as soon as possible. As babies grow up, close monitoring of language and cognitive development is needed. Moreover, providing continuous rehabilitation with task-specific and intensive repetitive training could improve functional outcomes in children with mild-to-moderate disabilities. After school age, maintaining the level of physical activity and managing complications are also needed.

The vascular phenotype of BPD: new basic science insights-new precision medicine approaches.

Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth. Up to 1/3 of children with BPD develop pulmonary hypertension (PH). PH increases mortality, the risk of adverse neurodevelopmental outcome and lacks effective treatment. Current vasodilator therapies address symptoms, but not the underlying arrested vascular development. Recent insights into placental biology and novel technological advances enabling the study of normal and impaired lung development at the single cell level support the concept of a vascular phenotype of BPD. Dysregulation of growth factor pathways results in depletion and dysfunction of putative distal pulmonary endothelial progenitor cells including Cap1, Cap2, and endothelial colony-forming cells (ECFCs), a subset of vascular progenitor cells with self-renewal and de novo angiogenic capacity. Preclinical data demonstrate effectiveness of ECFCs and ECFC-derived particles including extracellular vesicles (EVs) in promoting lung vascular growth and reversing PH, but the mechanism is unknown. The lack of engraftment suggests a paracrine mode of action mediated by EVs that contain miRNA. Aberrant miRNA signaling contributes to arrested pulmonary vascular development, hence using EV- and miRNA-based therapies is a promising strategy to prevent the development of BPD-PH. More needs to be learned about disrupted pathways, timing of intervention, and mode of delivery. IMPACT: Single-cell RNA sequencing studies provide new in-depth view of developmental endothelial depletion underlying BPD-PH. Aberrant miRNA expression is a major cause of arrested pulmonary development. EV- and miRNA-based therapies are very promising therapeutic strategies to improve prognosis in BPD-PH.

Late (≥ 7 days) inhaled corticosteroids to reduce bronchopulmonary dysplasia in preterm infants.

Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks' postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation may be an effective and safe alternative. To assess the benefits and harms of inhaled corticosteroids versus placebo, initiated between seven days of postnatal life and 36 weeks' postmenstrual age, to preterm infants at risk of developing bronchopulmonary dysplasia. We searched CENTRAL, MEDLINE, Embase, CINAHL, and three trials registries to August 2022. We searched conference proceedings and the reference lists of retrieved articles for additional studies. We included randomised controlled trials (RCTs) comparing inhaled corticosteroids to placebo, started between seven days' postnatal age (PNA) and 36 weeks' PMA, in infants at risk of BPD. We excluded trials investigating systemic corticosteroids versus inhaled corticosteroids. We collected data on participant characteristics, trial methodology, and inhalation regimens. The primary outcomes were mortality, BPD, or both at 36 weeks' PMA. Secondary outcomes included short-term respiratory outcomes (mortality or BPD at 28 days' PNA, failure to extubate, total days of mechanical ventilation and oxygen use, and need for systemic corticosteroids) and adverse effects. We contacted the trial authors to verify the validity of extracted data and to request missing data. We analysed all data using Review Manager 5. Where possible, we reported the results of meta-analyses using risk ratios (RRs) and risk differences (RDs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, along with their 95% confidence intervals (CIs). We analysed ventilated and non-ventilated participants separately. We used the GRADE approach to assess the certainty of the evidence. We included seven trials involving 218 preterm infants in this review. We identified no new eligible studies in this update. The evidence is very uncertain regarding whether inhaled corticosteroids affects the combined outcome of mortality or BPD at 36 weeks' PMA (RR 1.10, 95% CI 0.74 to 1.63; RD 0.07, 95% CI -0.21 to 0.34; 1 study, 30 infants; very low-certainty) or its separate components: mortality (RR 3.00, 95% CI 0.35 to 25.78; RD 0.07, 95% CI -0.08 to 0.21; 3 studies, 61 infants; very low-certainty) and BPD (RR 1.00, 95% CI 0.59 to 1.70; RD 0.00, 95% CI -0.31 to 0.31; 1 study, 30 infants; very low-certainty) at 36 weeks' PMA. Inhaled corticosteroids may reduce the need for systemic corticosteroids, but the evidence is very uncertain (RR 0.51, 95% CI 0.26 to 1.00; RD -0.22, 95% CI -0.42 to -0.02; number needed to treat for an additional beneficial outcome 5, 95% CI 2 to 115; 4 studies, 74 infants; very low-certainty). There was a paucity of data on short-term and long-term adverse effects. Despite a low risk of bias in the individual studies, we considered the certainty of the evidence for all comparisons discussed above to be very low, because the studies had few participants, there was substantial clinical heterogeneity between studies, and only three studies reported the primary outcome of this review. Based on the available evidence, we do not know if inhaled corticosteroids initiated from seven days of life in preterm infants at risk of developing BPD reduces mortality or BPD at 36 weeks' PMA. There is a need for larger randomised placebo-controlled trials to establish the benefits and harms of inhaled corticosteroids.

Analysis of Neurodevelopment in Children Born Extremely Preterm Treated With Acid Suppressants Before Age 2 Years

Children born preterm are at increased risk of adverse neurodevelopmental outcomes and may be particularly vulnerable to the effects of gastric acid suppression during infancy. To assess whether early acid suppressant use in infants born extremely preterm is associated with poorer neurodevelopmental outcomes. The Extremely Low Gestational Age Newborn study was a multicenter, longitudinal cohort study of infants born before 28 weeks' gestational age between March 22, 2002, and August 31, 2004. The current analyses were performed from September 12, 2020, through September 22, 2022. Of the 1506 infants enrolled, 284 died before discharge and 22 died before 24 months of age. An additional 2 died before age 10 years, leaving 1198 (79.5%) eligible for a visit. Of these, 889 (74%) participated in the visit at age 10. At age 10 years, the association of early-life acid suppressant use with neurocognitive, neurodevelopmental, and psychiatric symptomatology was assessed. Acid suppressant use before 24 months of age was determined from medical records and from questionnaires administered to mothers. Neurodevelopmental assessments at age 10 years included the School-Age Differential Ability Scales-II, the Developmental Neuropsychological Assessment-II, the Autism Diagnostic Observation Schedule-2, the Social Responsiveness Scale-2, and the Child Symptom Inventory-4 for attention-deficit/hyperactivity disorder (ADHD), depression, and anxiety. Of the 889 participants assessed at age 10 years (mean [SD] age, 9.97 [0.67] years; mean [SD] gestational age at birth, 26.1 [1.3] weeks; 455 [51.2%] male), 368 (41.4%) had received acid suppressants by 24 months of age. Associations were observed between acid suppressant use and decreased full-scale IQ z score (adjusted β, -0.29; 95% CI, -0.45 to -0.12), verbal IQ z score (adjusted β, -0.34; 95% CI, -0.52 to -0.15), nonverbal IQ z score (adjusted β, -0.22; 95% CI to -0.39 to -0.05), working memory z score (adjusted β, -0.26; 95% CI to -0.45, -0.08), autism spectrum disorder (adjusted relative risk, 1.84; 95% CI, 1.15-2.95), and epilepsy (adjusted relative risk, 2.07; 95% CI, 1.31 to 3.35). Results were robust to multiple sensitivity analyses. Use of acid suppressants was not associated with inhibitory control, ADHD, anxiety, or depression. The results of this cohort study suggest that early-life use of acid suppressants in extremely preterm infants may be associated with poorer neurodevelopmental outcomes and add to evidence indicating caution in use of these agents.

The General Movements Motor Optimality Score in High-Risk Infants: A Systematic Scoping Review.

The aim of this systematic scoping review was to explore the use of the motor optimality score in the fidgety movement period in clinical practice, and to investigate evidence for the motor optimality score in predicting neurodevelopmental outcomes. Thirty-seven studies, with 3662 infants, were included. Studies were conceptualized and charted into 4 categories based on the motor optimality score: prediction, outcome measure, descriptive, or psychometric properties. The most represented populations were preterm or low-birth-weight infants (16 studies), infants with cerebral palsy or neurological concerns (5 studies), and healthy or term-born infants (4 studies). The motor optimality score has the potential to add value to existing tools used to predict risk of adverse neurodevelopmental outcomes. Further research is needed regarding the reliability and validity of the motor optimality score to support increased use of this tool in clinical practice. What this adds to the evidence : The motor optimality score has potential to improve the prediction of adverse neurodevelopmental outcomes. Further research on validity and reliability of the motor optimality score is needed; however, a revised version, the motor optimality score-R (with accompanying manual) will likely contribute to more consistency in the reporting of the motor optimality score in future.

Impact of Differing Language Background Exposures on Bayley-III Language Assessment in a National Cohort of Children Born Less than 29 Weeks' Gestation.

Preterm infants are at risk for adverse neurodevelopmental outcomes, especially language delay. Preterm infants < 29 weeks’ gestational age, cared for in Canadian Neonatal Follow-Up Network affiliated hospitals, were assessed between 18 to 21 months corrected age using the Bayley-III. Bayley-III Language Composite Scores were compared using univariate and multivariate analyses for children in three primary language groups: English, French and other. 6146 children were included. The primary language at home was English, French or another language for 3708 children (60%), 1312 children (21%) and 1126 children (18%), respectively, and overall, 44% were exposed to two or more languages at home. Univariate analysis showed that primary language was associated with lower Bayley-III Language scores; however, multivariate analyses demonstrated that neither primary language nor language of administration were significantly associated with lower language scores when adjusted for gestational age, other developmental delays and sociodemographic factors, but multiple language exposure was. Sociodemographic and other factors are more important in determining language development than primary language at home. Further studies are needed to examine the association between exposure to multiple languages and lower Bayley-III language scores in preterm infants.

Verification of the ability of the new MRI classification system to predict neurodevelopmental outcome in very low-birth-weight infants

BackgroundVery low-birth-weight infants (VLBWI) are at high risk for adverse neurodevelopmental outcomes. A new, feasible and practical classification system for white matter injury has been reported by Martinez-Biarge et al. Therefore, we investigated the relationship between white matter injury and neurodevelopmental outcomes using this system. Materials and methodsWe enrolled a consecutive series of VLBWI birth weights <1500 g between 2012 and 2015. Two radiologists evaluated the brain MRI obtained in the VLBWI at term-equivalent age. MRI findings were classified into six Grades (Grade 0, Ia, Ib, II, III, IV). The frequency of abnormalities in each Grade was examined. The neurodevelopmental outcome of the VLBWI was assessed at two years or older, and we investigated the presence of cerebral palsy (CP) and intellectual disability (ID), and other serious outcomes. We also calculated the simple kappa value before the raters were matched. ResultsAmong 167 VLBWI, 131 met the eligibility criteria. 114 was Grade 0 (87%), 11 was Grade I (8.4%), 3 was Grade II (2.3%), 1 was Grade III (0.8%), and 2 was Grade IV (1.5%). The frequency of any abnormalities of intelligence in Grade 0 was 24%. The frequency of CP in Grade I was 18%. All Grade III and Grade IV cases had mild CP and an ID. The simple kappa value was 0.95. ConclusionThe prognostic value of the MRI scoring tool was limited. However, all Grade III and Grade IV cases had mild CP and ID. The results demonstrated an excellent inter-rater correlation.