Risk Of Neurodevelopmental Delay Research Articles

Perinatal and neurodevelopmental outcomes of fetal isolated ventriculomegaly: a systematic review and meta-analysis.

Isolated fetal ventriculomegaly can have a range of consequences, ranging from mild neurodevelopmental delay to perinatal death; the extent of these consequences often depend on the severity of ventriculomegaly. This systematic review and meta-analysis aims to investigate the impact of the degree of ventricular dilatation on the risk of neurodevelopmental delay and adverse perinatal outcomes in fetuses diagnosed with isolated fetal ventriculomegaly from gestational week 15 onwards. PubMed, Embase, Scopus and the Cochrane Library were searched electronically to identify studies investigating the prognosis of mild and/or severe isolated fetal ventriculomegaly. Articles were included if they reported neurodevelopmental or perinatal outcomes in fetuses prenatally diagnosed with isolated fetal ventriculomegaly from week 15 of gestation and onwards. Studies were excluded if they reported on non-isolated ventriculomegaly (IVM), failed to specify the degree of ventriculomegaly, were non-English papers, animal studies or published outside of the 21-year period of interest. Study quality was assessed by two independent reviewers using a modified version of the Newcastle-Ottawa Quality Assessment Scale. Ventriculomegaly was defined as either mild or severe when ventricular diameter measured as 10-15 or >15 mm, respectively. Meta-analyses were conducted for adverse neurodevelopmental outcome, intrauterine fetal demise and infant mortality. Following the removal of duplicates, the search yielded 2,452 citations, of which 23 studies were included and 8 were eligible for meta-analysis. There were 767 and 347 cases of mild and severe isolated fetal ventriculomegaly, respectively. Adverse outcomes were consistently reported at a higher rate in severe cases than mild. The relative risks of adverse neurodevelopmental outcome, intrauterine fetal demise and infant mortality were 4.24 [95% confidence interval (CI): 2.46-7.30], 4.46 (95% CI: 1.64-12.11) and 6.02 (95% CI: 1.73-21.00), respectively, upon comparison of mild versus severe cases of isolated fetal ventriculomegaly. The likelihood of adverse neurodevelopmental and perinatal outcomes, including intrauterine and infant mortality, is increased in severe isolated fetal ventriculomegaly compared to mild isolated fetal ventriculomegaly.

Quantitative Magnetic Resonance Imaging for Neurodevelopmental Outcome Prediction in Neonates Born Extremely Premature—An Exploratory Study

PurposeNeonates born at < 28 weeks of gestation are at risk for neurodevelopmental delay. The aim of this study was to identify quantitative MR-based metrics for the prediction of neurodevelopmental outcomes in extremely preterm neonates.MethodsT1-/T2-relaxation times (T1R/T2R), ADC, and fractional anisotropy (FA) of the left/right posterior limb of the internal capsule (PLIC) and the brainstem were determined at term-equivalent ages in a sample of extremely preterm infants (n = 33). Scores for cognitive, language, and motor outcomes were collected at one year corrected-age. Pearson’s correlation analyses detected relationships between quantitative measures and outcome data. Stepwise regression procedures identified imaging metrics to estimate neurodevelopmental outcomes.ResultsCognitive outcomes correlated significantly with T2R (r = 0.412; p = 0.017) and ADC (r = −0.401; p = 0.021) (medulla oblongata). Furthermore, there were significant correlations between motor outcomes and T1R (pontine tegmentum (r = 0.346; p = 0.049), midbrain (r = 0.415; p = 0.016), right PLIC (r = 0.513; p = 0.002), and left PLIC (r = 0.504; p = 0.003)); T2R (right PLIC (r = 0.405; p = 0.019)); ADC (medulla oblongata (r = −0.408; p = 0.018) and pontine tegmentum (r = −0.414; p = 0.017)); and FA (pontine tegmentum (r = −0.352; p = 0.045)).T2R/ADC (medulla oblongata) (cognitive outcomes (R2 = 0.296; p = 0.037)) and T1R (right PLIC)/ADC (medulla oblongata) (motor outcomes (R2 = 0.405; p = 0.009)) revealed predictive potential for neurodevelopmental outcomes.ConclusionThere are relationships between relaxometry‑/DTI-based metrics determined by neuroimaging near term and neurodevelopmental outcomes collected at one year of age. Both modalities bear prognostic potential for the prediction of cognitive and motor outcomes. Thus, quantitative MRI at term-equivalent ages represents a promising approach with which to estimate neurologic development in extremely preterm infants.

Time-motion observations to characterize the developmental environment in a paediatric post-acute care hospital.

Chronically hospitalized children are at risk for neurodevelopmental delay, compounded by restricted social interactions, movement and environmental stimulation. We measured patients' movements and interactions to characterize developmentally relevant aspects of our inpatient environment and identify opportunities for developmental enrichment. As part of a quality improvement initiative to inform neurodevelopmental programming for children with medical complexity at our paediatric post-acute care specialty hospital, we conducted >232 hours of time-motion observations. Trained observers followed 0- to 5-year-old inpatients from 7am to 7pm on weekdays, categorizing observations within five domains: Where, With, Position, State and Environment. Observations were collected continuously utilizing REDCap on iPads. A change in any domain initiated a new observation. Patients were median 1year and 8months of age (range 2months to 3years 9months) with a median length of hospitalization of 514 days (range 66-1298). In total, 2636 unique observations (or median 134 observations per patient-day [range 95-210]) were collected. Patients left their rooms up to 4 times per day for median 1h and 34 min (range 41 min to 4h:30 min). Patients spent 4h:6min (2h:57 min to 6h:30 min) interacting with someone and 3h:51 min (57 min to 6h:36 min) out of bed each day. Patients were simultaneously out of their beds, interacting with someone and awake for 2h:21 min (51 min to 4h:19 min) each day. Despite a care model prioritizing time out of bed and social interaction, time-motion observations indicate patients spent many of their waking hours in bed and alone. Quantifying our inpatients developmental opportunities will inform neurodevelopmental programming initiatives.

Infant Saliva Microbiome Activity Modulates Nutritional Impacts on Neurodevelopment.

Neurodevelopment is influenced by complex interactions between environmental factors, including social determinants of health (SDOH), nutrition, and even the microbiome. This longitudinal cohort study of 142 infants tested the hypothesis that microbial activity modulates the effects of nutrition on neurodevelopment. Salivary microbiome activity was measured at 6 months using RNA sequencing. Infant nutrition was assessed longitudinally with the Infant Feeding Practices survey. The primary outcome was presence/absence of neurodevelopmental delay (NDD) at 18 months on the Survey of Wellbeing in Young Children. A logistic regression model employing two microbial factors, one nutritional factor, and two SDOH accounted for 33.3% of the variance between neurodevelopmental groups (p < 0.001, AIC = 77.7). NDD was associated with Hispanic ethnicity (OR 18.1, 2.36-139.3; p = 0.003), no fish consumption (OR 10.6, 2.0-54.1; p = 0.003), and increased Candidatus Gracilibacteria activity (OR 1.43, 1.00-2.07; p = 0.007). Home built after 1977 (OR 0.02, 0.001-0.53; p = 0.004) and Chlorobi activity (OR 0.76, 0.62-0.93, p = 0.001) were associated with reduced risk of NDD. Microbial alpha diversity modulated the effect of fish consumption on NDD (X2 = 5.7, p = 0.017). These data suggest the benefits of fish consumption for neurodevelopment may be mediated by microbial diversity. Confirmation in a larger, randomized trial is required.

Implementation of the Cardiac Inpatient Neurodevelopmental Care Optimization (CINCO) programme: an interdisciplinary, generalisable approach to inpatient neurodevelopmental care.

Children with CHD are at risk for neurodevelopmental delays, and length of hospitalisation is a predictor of poorer long-term outcomes. Multiple aspects of hospitalisation impact neurodevelopment, including sleep interruptions, limited holding, and reduced developmental stimulation. We aimed to address modifiable factors by creating and implementing an interdisciplinary inpatient neurodevelopmental care programme in our Heart Institute. In this quality improvement study, we developed an empirically supported approach to neurodevelopmental care across the continuum of hospitalisation for patients with CHD using three plan-do-study-act cycles. With input from multi-level stakeholders including parents/caregivers, we co-designed interventions that comprised the Cardiac Inpatient Neurodevelopmental Care Optimization (CINCO) programme. These included medical/nursing orders for developmental care practices, developmental kits for patients, bedside developmental plans, caregiver education and support, developmental care rounds, and a specialised volunteer programme. We obtained data from the electronic health record for patients aged 0-2 years admitted for at least 7 days to track implementation. There were 619 admissions in 18 months. Utilisation of CINCO interventions increased over time, particularly for the medical/nursing orders and caregiver handouts. The volunteer programme launch was delayed but grew rapidly and within six months, provided over 500 hours of developmental interaction with patients. We created and implemented a low-cost programme that systematised and expanded upon existing neurodevelopmental care practices in the cardiac inpatient units. Feasibility was demonstrated through increasing implementation rates over time. Key takeaways include the importance of multi-level stakeholder buy-in and embedding processes in existing clinical workflows.

Prevalence of neurodevelopmental delays in infants with perinatal HIV infection in comparison with HIV exposure in rural South Africa.

Assessing neurodevelopmental functioning in early infancy is essential as this is a critical period for infant development. Infants born to mothers with HIV are at a greater risk of developmental delays than those born to mothers without HIV. In this study, we analyzed differences in early neurodevelopmental functioning for infants with HIV exposure versus HIV infection to inform infant screening and early intervention. Participants were recruited from community health centers in Mpumalanga Province, South Africa. Prenatally, mothers completed baseline demographic assessment at 8 to 24-week gestation periods. Infant neurodevelopment was assessed using the Bayley Infant Neurodevelopmental Screener (BINS) 12 months postnatally. Five areas of development were assessed: cognition, receptive communication, expressive communication, fine motor ability, and gross motor ability. Postnatal infant assessment using the BINS revealed that infants were at risk for neurodevelopmental delays across all domains assessed. Notably, infants exposed to HIV, regardless of HIV status, were 'at emerging risk' or 'at clear risk' for cognitive (43.5%), receptive communication (38.2%), expressive communication (53.1%), fine motor (49.9%), and gross motor delays (55.6%). Differences were noted by HIV status in the cognition domain, such that HIV-exposed infants were more likely to be at emerging or clear risk than HIV-infected infants. There was a different trend with gross motor delays, such that HIV-infected infants were at a greater risk for motor delays than HIV-exposed, uninfected infants. Screening tools for this vulnerable population provide valuable early life assessment to determine infant needs for intervention and treatment planning. Such interventions may mitigate the impact of HIV status on neurodevelopmental health generally and cognition.

Impact of time to full enteral feeding on long-term neurodevelopment without mediating by postnatal growth failure in very-low-birth-weight-infants

This study aimed to determine if time to achieve full enteral feeding (TFF) directly impacted long-term neurodevelopmental delay (NDD) and whether long-term postnatal growth failure (PGF) was a mediator of this association in very-low-birth-weight (VLBW) infants. Using prospectively collected cohort data from the Korean Neonatal Network, we included eligible VLBW infants who achieved TFF at least once and classified enrolled infants into four groups using exposure severity (P1 to P4 as TFF < 16, 16–30, 31–45, and > 45 postnatal days, respectively). After adjusting for confounding variables, survival without NDD was significantly decreased in P4 infants compared with that in P2 infants. P1 infants had a lower risk of weight and height PGF than P2 infants; however, P4 infants had higher risks of height and head circumference PGF than P2 infants. Weight and height PGF were significantly associated with an increased risk of NDD. In mediation analysis, early and delayed TFF revealed direct positive and negative impacts, respectively, on the risk of NDD without mediation by PGF. TFF impacted survival without NDD, and PGF did not mediate this association in VLBW infants. Additionally, these results can be translated into evidence-based quality improvement practice.

High Burden of Neurodevelopmental Delay among Children Born to Women with Obstructed Labour in Eastern Uganda: A Cohort Study.

Over 250 million infants in low and middle-income countries do not fulfill their neurodevelopment potential. In this study, we assessed the incidence and risk factors for neurodevelopmental delay (NDD) among children born following obstructed labor in Eastern Uganda. Between October 2021 and April 2022, we conducted a cohort study of 155 children (aged 25 to 44 months), born at term and assessed their neurodevelopment using the Malawi Developmental Assessment Tool. We assessed the gross motor, fine motor, language and social domains of neurodevelopment. The incidence of neurodevelopmental delay by 25 to 44 months was 67.7% (105/155) (95% CI: 59.8-75.0). Children belonging to the poorest wealth quintile had 83% higher risk of NDD compared to children belonging to the richest quintile (ARR (Adjusted Risk Ratio): 1.83; 95% CI (Confidence Interval): [1.13, 2.94]). Children fed the recommended meal diversity had 25% lower risk of neurodevelopmental delay compared to children who did not (ARR: 0.75; 95% CI: [0.60, 0.94]). Children who were exclusively breastfed for the first 6 months had 27% lower risk of neurodevelopmental delay compared to children who were not (ARR: 0.73; 95% CI: [0.56, 0.96]). We recommend that infants born following obstructed labor undergo neurodevelopmental delay screening.

Brain development is altered in rabbit fetuses with congenital diaphragmatic hernia.

Children with congenital diaphragmatic hernia (CDH) are at risk for neurodevelopmental delay. Some changes are already present prenatally. Herein,we further examined how the brain develops in fetal rabbits with surgically created DH. Two fetuses underwent surgical DH creation on day 23 (term=d31). DH pups and littermate controls were harvested at term. Ten DH pups and 11 controls underwent transcardial perfusion for brain fixation and measurement of brain volume, brain folding, neuron and synaptic density, pre-oligodendrocyte count, proliferation, and vascularization. Twelve other DH and 11 controls had echocardiographic assessment of cardiac output and aortic and cerebral blood flow, magnetic resonance imaging (9.4T) for cerebral volumetry, and molecular assessment of vascularization markers. DH pups had lower lung-to-body weight ratio (1.3±0.3 vs. 2.4±0.3%; p<0.0001) and lower heart-to-body weight ratio (0.007±0.001 vs. 0.009±0.001; p=0.0006) but comparable body weight and brain-to-body weight ratio. DH pups had a lower left ventricular ejection fraction, aortic and cerebral blood flow (39±8 vs. 54±15mm/beat; p=0.03) as compared to controls but similar left cardiac ventricular morphology. Fetal DH-brains were similar in volume but the cerebellum was less folded (perimeter/surface area: 25.5±1.5 vs. 26.8±1.2; p=0.049). Furthermore, DH brains had a thinner cortex (143±9 vs. 156±13μm; p=0.02). Neuron densities in the white matter were higher in DH fetuses (124±18 vs. 104±14; p=0.01) with comparable proliferation rates. Pre-oligodendrocyte count was lower, coinciding with the lower endothelial cell count. Rabbits with DH had altered brain development compared to controls prenatally, indicating that brain development is already altered prenatally in CDH.

Primary Hereditary Haemochromatosis and Pregnancy

Background. Haemochromatosis is a rare autosomal genetic disease that can cause multiple organ failure. In the past, this condition was not considered to affect pregnancy. The objectives of this study are to update the management of haemochromatosis in general as there are new treatments being investigated other than phlebotomy and to summarise the effects of the condition on pregnancy and vice versa. Methods. The initial search was in Ovid Medline® from 2002 to 2013. Review articles for haemochromatosis and case reports of its related complications in pregnancy were found. None of the reviews addressed pregnancy in detail. A second search in PubMed from 2014 to 2016 included studies regarding haemochromatosis and pregnancy and iron metabolism association with other metals and biomarkers, defining the mechanism of foetomaternal risks in maternal haemochromatosis. A third search at PubMed from 2017 to 2022 using key words haemochromatosis and pregnancy was done to look at the new data. Results. The results are qualitative indicating that even in the absence of abnormal iron parameters, haemochromatosis increases the risk of foetomaternal complications due to genetic predisposition, necessitating antenatal monitoring. Newer medications targeting the pathophysiology of the disease to eliminate it are being developed. The coabsorption of lead with iron causes increased risk of maternal preeclampsia, gestational hypertension, foetal congenital abnormalities, and growth problems. There is risk of neurodevelopmental delays, large for gestational age and childhood leukaemia in babies whose mothers and themselves have mutations for haemochromatosis. Conclusion. Previously, women with haemochromatosis were thought to have no higher risk of complications than the general population. However, there is evidence of foetomaternal complications. As a result, pregnancy with haemochromatosis necessitates additional monitoring for both mother and baby.

Infant Saliva Levels of microRNA miR-151a-3p Are Associated with Risk for Neurodevelopmental Delay.

Prompt recognition of neurodevelopmental delay is critical for optimizing developmental trajectories. Currently, this is achieved with caregiver questionnaires whose sensitivity and specificity can be limited by socioeconomic and cultural factors. This prospective study of 121 term infants tested the hypothesis that microRNA measurement could aid early recognition of infants at risk for neurodevelopmental delay. Levels of four salivary microRNAs implicated in childhood autism (miR-125a-5p, miR-148a-5p, miR-151a-3p, miR-28-3p) were measured at 6 months of age, and compared between infants who displayed risk for neurodevelopmental delay at 18 months (n = 20) and peers with typical development (n = 101), based on clinical evaluation aided by the Survey of Wellbeing in Young Children (SWYC). Accuracy of microRNAs for predicting neurodevelopmental concerns at 18 months was compared to the clinical standard (9-month SWYC). Infants with neurodevelopmental concerns at 18 months displayed higher levels of miR-125a-5p (d = 0.30, p = 0.018, adj p = 0.049), miR-151a-3p (d = 0.30, p = 0.017, adj p = 0.048), and miR-28-3p (d = 0.31, p = 0.014, adj p = 0.048). Levels of miR-151a-3p were associated with an 18-month SWYC score (R = -0.19, p = 0.021) and probability of neurodevelopmental delay at 18 months (OR = 1.91, 95% CI, 1.14-3.19). Salivary levels of miR-151a-3p enhanced predictive accuracy for future neurodevelopmental delay (p = 0.010, X2 = 6.71, AUC = 0.71) compared to the 9-month SWYC score alone (OR = 0.56, 95% CI, 0.20-1.58, AUC = 0.567). This pilot study provides evidence that miR-151a-3p may aid the identification of infants at risk for neurodevelopmental delay. External validation of these findings is necessary.

Growth and Neurodevelopmental Outcomes of Very Low Birth Weight Infants upto Six Months of Age at a Tertiary Level NICU in Central India: A Prospective Cohort Study

Introduction: The long-term outcomes of Very Low Birth Weight (VLBW) infants are influenced by prematurity, as well as the occurrence of various short-term morbidities, such as Respiratory Distress Syndrome (RDS), sepsis, Necrotising Enterocolitis (NEC), Patent Ductus Arteriosus (PDA), Intraventricular Haemorrhage (IVH), Periventricular Leukomalacia (PVL), Retinopathy Of Prematurity (ROP), and Chronic Lung Disease (CLD). It has been estimated that approximately half of all VLBW infants develop cognitive and behavioural deficits in the future. Therefore, studying VLBW infants and providing longitudinal follow-up after their hospital discharge is increasingly important. This helps in the early diagnosis of neurodevelopmental abnormalities and enables timely intervention for a better quality of life in the future. Aim: To assess the growth and neurodevelopmental outcomes of VLBW infants discharged from the NICU until six months of age. Materials and Methods: A prospective cohort study was conducted in the Neonatal In tensive Crae Unit (NICU) at NSCB Medical College, Jabalpur, Madhya Pradesh, India. The duration of the study was one year and six months, from March 2018 to September 2019. A total of 40 VLBW infants were enrolled and followed-up for six months. The infants were divided into two groups: Group 1 (&lt;32 weeks) and group 2 (&gt;32 weeks). Physical parameters such as weight, length, and head circumference were recorded on admission and at one, three and six months of corrected gestational age. Developmental assessment was performed using the Denver Developmental Screening Test-II (DDST-II) method. The association of risk factors with neurodevelopmental outcomes was also assessed. Data were analysed using Statistical Package for Social Sciences (SPSS) version 20.0, and the Chi-square test, Fisher’s-exact test, and Student’s t-test were used. A p-value less than 0.05 was considered significant. Results: Among the 40 subjects, 12 (30%) were &lt;32 weeks, and 28 (70%) were ≥32 weeks. Overall, parameters were higher in infants ≥32 weeks. Weight and head circumference gain velocity were greater in infants ≥32 weeks during the first three months of life (p&lt;0.05). From three to six months, &lt;32 weeks infants showed a significant increase (p&lt;0.001) in weight and head circumference gain velocity. The length gain velocity in both groups was comparable since birth, and &lt;32 weeks VLBW infants demonstrated good catch-up growth, which was statistically significant (p&lt;0.05). At six months of corrected age, 16 (40%) infants out of the total 40 infants had abnormal neurodevelopmental outcomes. A total of 7 (58.33%) of the &lt;32 weeks VLBW infants and 9 (32.14%) of the ≥32 weeks VLBW infants had Neurodevelopmental Delay (NDD). Hypoglycaemia, shock, hyaline membrane disease, and mechanical ventilation were significantly associated with an increased risk of NDD. Conclusion: The incidence of NDD was significantly higher in infants with lower gestational age, lower birth weight and the presence of associated factors such as hyaline membrane disease, hypoglycaemia, shock, ventilation, and hyperbilirubinaemia. Improved perinatal care, early assessment of development using appropriate tools, and early intervention are necessary to improve the outcomes of these infants.

Abstract 10403: Residual Lesion Severity is Associated With Adverse Neurodevelopmental Outcomes in Young Children With Congenital Heart Disease

Introduction: There are few modifiable risk factors for adverse neurodevelopmental (ND) outcomes in congenital heart disease. We assessed the Residual Lesion Score (RLS), a quality improvement metric that assesses residual lesion severity following congenital heart surgery (CHS), as a predictor of ND delay. Hypothesis: We hypothesized that RLS would be independently associated with ND outcomes. Methods: This was a single center, retrospective review of patients who underwent CHS from 01/2011-12/2019 and received post-discharge ND evaluation between the ages of 12 and 42 months using the Bayley Scales of Infant Development, 3 rd ed. (BSID-3). RLS was assigned at discharge per previously published criteria: Class 1, no residua; Class 2, minor residua; Class 3, major residua or in-hospital unplanned reintervention. Associations between RLS and BSID-3 scores (at the first ND evaluation) were evaluated using linear regression, adjusting for baseline patient risk, the Childhood Opportunity Index, and maternal education level. Linear mixed effects models assessed trends in ND outcomes over time. Results: Of 477 patients with mean age at ND testing of 21.2 ± 6.1 months, 282 (59.1%), 132 (27.7%), and 63 (13.2%) patients had RLS 1, 2, and 3 lesions, respectively. Table 1A shows BSID-3 outcomes by RLS. On multivariable analysis, Class 3 patients had significantly lower cognitive, receptive and expressive communication, and fine and gross motor scaled scores, compared to Class 1 patients, with the largest difference observed in the cognitive domain ( Table 1B ). In a subset of 191 patients with more than one ND evaluation, Class 3 patients made fewer gains in skills from the first to the last evaluation in the cognitive and language domains, compared to Class 1 patients (both p&lt;0.05). Conclusions: Patients with major residua (RLS 3) are at increased risk for ND delay, warranting closer ND follow-up and greater developmental support for cognitive, communication, and motor skills.

Metabolomic and exposomic biomarkers of risk of future neurodevelopmental delay in human milk

BackgroundThe chemical composition of human milk has long-lasting effects on brain development. We examined the prognostic value of the human milk metabolome and exposome in children with the risk of neurodevelopmental delay (NDD).MethodsThis retrospective cohort study included 82 mother–infant pairs (40 male and 42 female infants). A total of 59 milk samples were from mothers with typically developing children and 23 samples were from mothers of children at risk. Milk samples were collected before 9 months of age (4.6 ± 2.5 months, mean ± SD). Neurocognitive development was assessed by maternal report at 14.2 ± 3.1 months using the Ages and Stages Questionnaires-2.ResultsMetabolome and exposome profiling identified 453 metabolites and 61 environmental chemicals in milk. Machine learning tools identified changes in deoxysphingolipids, phospholipids, glycosphingolipids, plasmalogens, and acylcarnitines in the milk of mothers with children at risk for future delay. A predictive classifier had a diagnostic accuracy of 0.81 (95% CI: 0.66–0.96) for females and 0.79 (95% CI: 0.62–0.94) for males.ConclusionsOnce validated in larger studies, the chemical analysis of human milk might be added as an option in well-baby checks to help identify children at risk of NDD before the first symptoms appear.ImpactMaternal milk for infants sampled before 9 months of age contained sex-specific differences in deoxysphingolipids, sphingomyelins, plasmalogens, phospholipids, and acylcarnitines that predicted the risk of neurodevelopmental delay at 14.2 months of age.Once validated, this early biosignature in human milk might be incorporated into well-baby checks and help to identify infants at risk so early interventions might be instituted before the first symptoms appear.

Association between the ratio of placental weight to birthweight and the risk of neurodevelopmental delay in 3-year-Olds: The Japan environment and Children's study

IntroductionThe ratio of placental weight to birthweight (PW/BW ratio) is well known as a simple indicator of the prenatal intrauterine environment and placental functioning. We assessed the impact of PW/BW ratio on the risk of neurodevelopmental delay in 3-year-olds. MethodsWe used data of 71 205 mother–child pairs enrolled in the Japan Environment and Children's Study. Low PW/BW ratio was defined as a PW/BW ratio below the 10th percentile of the study population, high PW/BW ratio was defined as above the 90th percentile, and normal PW/BW ratio was defined as between the low and high PW/BW ratio. Neurodevelopment was assessed using the Japanese translation of the Ages and Stages Questionnaires, third edition. Associations between PW/BW ratio and risk of developmental delay were examined using multivariable models. ResultsCompared with boys in the normal PW/BW group, boys in the high PW/BW group had higher risk for developmental delays in all domains except fine motor skills (communication: adjusted risk ratio [aRR], 1.17; 95% confidence interval [CI], 1.04–1.33; gross motor skills: aRR, 1.28; 95% CI, 1.13–1.46; problem solving: aRR, 1.20; 95% CI, 1.09–1.31; personal–social: aRR, 1.26; 95% CI, 1.10–1.43), and boys in the low PW/BW group also had higher risk for developmental delays in some domains. For girls, there was almost no association between PW/BW ratio and developmental delay. DiscussionAn unbalanced PW/BW ratio, especially high PW/BW ratio, might indicate intrauterine suboptimality, which affects child neurodevelopment in a sex-specific manner.

Umbilical cord serum elementomics of 52 trace elements and early childhood neurodevelopment: Evidence from a prospective birth cohort in rural Bangladesh.

Prenatal exposures to neurotoxic metals and trace elements are associated with early childhood neurodevelopmental outcomes. However, consequences of simultaneous exposure to mixtures of elements remain unclear. To examine individual and joint effects of prenatal trace element exposure on early childhood neurodevelopment. Using a well-established Bangladesh prospective birth cohort (2008-2011), we measured concentrations of 52 trace elements in umbilical cord serum of 569 mother-infant pairs using inductively coupled plasma mass spectrometry. Neurodevelopment was evaluated at 20-40months of age using Bayley Scales of Infant and Toddler Development, Third Edition. Stability elastic net (ENET) was used to screen elements individually associated with the outcome; candidate exposures were combined by weighted linear combination to form a risk score representing their mixture effect on early childhood neurodevelopment. Stability ENET identified 15 trace elements associated with cognitive composite score and 14 associated with motor composite score, which were linearly combined to form the element risk score (ERS). Children with higher ERScognitive had lower probability of cognitive developmental delay (ORhighest vs lowest: 0.21; 95%CI: 0.10, 0.40; P<0.001; Ptrend<0.001). Children with ERSmotor in the top quintile had a significantly lower risk of motor developmental delay (OR: 0.16; 95%CI: 0.09, 0.31; P<0.001; Ptrend<0.001) versus the lowest quintile. In Bayesian kernel machine regression analyses, lithium [conditional posterior inclusion probability (cPIP)=0.68], aluminum (cPIP=0.83) and iron (cPIP=1.00) contributed most to the lower cognitive composite score; zinc (cPIP=1.00), silver (cPIP=0.81), and antimony (cPIP=0.65) mainly contributed to the change of motor composite score. Co-exposure to lithium/aluminum/iron or zinc/silver/antimony appears to impact children's neurodevelopment. ERS score reflecting maternal exposure could indicate children's risk of neurodevelopmental delay, warranting further studies to explore the underlying mechanism.

Risk stratification helps identify congenital diaphragmatic hernia (CDH) infants in need of formal neurodevelopmental assessment: Observations from a structured, interdisciplinary long-term follow-up clinic

Background/Purpose: Neurodevelopmental delay (NDD) affects congenital diaphragmatic hernia (CDH) infants. Initial assessment by experienced developmental pediatricians, supported by Bayley-3 tests, is a viable pathway for NDD identification and surveillance. We risk stratified CDH infants to observe differences in incidence and type of NDD based on disease severity. Methods: Patients from a CDH long-term follow-up database started in 2012 were reviewed (REB#2019–4583). Risk stratification into low, moderate, and high-risk cohorts was performed using the CDH Study Group Mortality Prediction Score. Patients requiring ECLS, supplemental oxygen at 30 days and patch repair were also considered high-risk (i.e. usual clinical criteria). Post-discharge NDD assessments by developmental pediatricians and occupational therapists (Bayley-3) were analyzed for all patients >18months. NDD incidence and type per risk group was determined using descriptive statistics. Results: Of 102 CDH patients included for study, 26% (27/102) had NDD. Risk stratification identified 2(2%), 7(7%), and 18(18%) patients with NDD in the low, moderate and high-risk groups, respectively. Language delay (2 low; 6 moderate; 10 high) was the most prevalent. Three patients had both expressive and receptive language delay. Motor deficits were observed almost exclusively in the high-risk group. Conclusion: Based on our experience, NDD affects one-quarter of CDH infants. Risk stratification helped identify infants at increased risk of NDD. While language delays predominated across all risk groups, multiple deficits occurred in higher risk cohorts. These patients should receive structured NDD assessment as part of an optimal interdisciplinary CDH care pathway.

Early life exposure to indoor air pollutants and the risk of neurodevelopmental delays: The Japan Environment and Children's Study.

Air pollution has been associated with childhood neurodevelopment. However, the role of indoor air pollution, especially volatile organic compounds (VOCs), on childhood neurodevelopment has been poorly explored to date. We investigated the association between indoor air pollutants and childhood neurodevelopment in 5,017 randomly selected children from the Japan Environment and Children's Study. When the participants reached 1.5 and 3years of age, they were followed up with home visits and neurodevelopmental tests using the Ages and Stages Questionnaire (ASQ). At both ages, we collected indoor air samples for 1week and measured 13 indoor air pollutants: particulate matter with an aerodynamic diameter of≤2.5μm, ozone, nitrogen dioxide, sulfur dioxide, and nine VOCs. The associations between air pollutants and ASQ scores were estimated using linear mixed effects models and weighted quantile sum regressions (WQS) at each age separately. Stratified analysis by sex was conducted. Exposure to m,p-xylene at the age of 3 was associated with lower communication, fine motor, and overall ASQ scores (coefficients: -0.18 [99% confidence intervals (CI): -0.35, -0.02], -0.23 [99%CI: -0.43, -0.03], and-0.72 [99%CI: -1.41, -0.04] per 1µg/m3 increase, respectively). Exposure to o-xylene at the age of 3 was associated with lower communication, gross motor, fine motor, and overall ASQ scores (coefficients: -0.48 [99%CI: -0.90, -0.07], -0.45 [99%CI: -0.78, -0.13], -0.65 [99%CI: -1.14, -0.16], and-2.15 [99%CI: -3.83, -0.47] per 1µg/m3 increase, respectively). The WQS index was associated with lower gross motor ASQ scores at the age of 3 (coefficient: -0.27 [95%CI: -0.51, -0.03] for one-unit WQS index increases), which was attributed to benzene (33.96%), toluene (26.02%), o-xylene (13.62%), and ethylbenzene (9.83%). Stratified analysis showed similar results. Although further investigations are required, our results suggest an association of neurodevelopmental delays with indoor low-level exposure to m,p-xylene and o-xylene in early life.

Impact of Cardiac Neurodevelopmental Evaluation for Children with Congenital Heart Disease

ABSTRACT Children with congenital heart disease (CHD) are at increased risk for neurodevelopmental delays. This study of school-aged children with single ventricle CHD compared access to services for those who did and did not complete an evaluation. Children completing an evaluation had more academic services, including an Individualized Education Plan (66% vs 34%,P = .017), small group academic instruction (54% vs 20%,P = .01), any instructional supports (77% vs 44%,P = .008). A barrier to not completing the evaluation was lack of knowledge about the Cardiac Neurodevelopmental Program (82%). The neurodevelopmental evaluation is an impactful tool that can increase access to school services in vulnerable CHD patients.

Early aEEG can predict neurodevelopmental outcomes at 12 to 18\u2009month of age in VLBWI with necrotizing enterocolitis: a cohort study

BackgroundStudies have shown that neurological damage is common in necrotizing enterocolitis (NEC) survivors. The purpose of the study was to investigate the predictive value of amplitude-integrated electroencephalogram (aEEG) for neurodevelopmental outcomes in preterm infants with NEC.MethodsInfants with NEC were selected, and the control group was selected based on 1:1–2 pairing by gestational age. We performed single-channel (P3–P4) aEEG in the two groups. The Burdjalov scores were compared between the two groups. Cranial magnetic resonance imaging (MRI) was performed several months after birth. The neurological outcomes at 12 to 18 months of age were compared with the Gesell Developmental Schedules (GDS). The predictive value of aEEG scores for neurodevelopmental delay was calculated.ResultsThere was good consistency between the two groups regarding general conditions. In the 1st aEEG examination, the patients in NEC group had lower Co (1.0 (0.0, 2.0) vs. 2.0 (2.0, 2.0), P = 0.001), Cy (1.0 (0.0, 2.0) vs. 3.0 (3.0, 4.0), P < 0.001), LB (1.0 (0.0, 2.0) vs. 2.0 (2.0, 2.0), P < 0.001), B (1.0 (1.0, 2.0) vs. 3.0 (3.0, 3.5), P < 0.001) and T (3.0 (2.0, 8.0) vs. 10.0 (10.0, 11.5), P < 0.001), than the control group. Cranial MRI in NEC group revealed a widened interparenchymal space with decreased myelination. The abnormality rate of cranial MRI in the NEC group was higher than that in the control group (P = 0.001). The GDS assessment indicated that NEC children had inferior performance and lower mean scores than the control group in the subdomains of gross motor (71 (SD = 6.41) vs. 92 (SD = 11.37), P < 0.001), fine motor (67 (SD = 9.34) vs. 96 (SD = 13.69), adaptive behavior (76 (SD = 9.85) vs. 95 (SD = 14.38), P = 0.001), language (68 (SD = 12.65) vs. 95 (SD = 11.41), P < 0.001), personal-social responses (80 (SD = 15.15) vs. 93(SD = 14.75), P = 0.037) and in overall DQ (72 (SD = 8.66) vs. 95 (SD = 11.07), P < 0.001). The logistic binary regression analysis revealed that the NEC patients had a significantly greater risk of neurodevelopmental delay than the control group (aOR = 27.00, 95% CI = 2.561–284.696, P = 0.006). Confirmed by Spearman’s rank correlation analysis, neurodevelopmental outcomes were significantly predicted by the 1st aEEG Burdjalov score (r = 0.603, P = 0.001). An abnormal 1st Burdjalov score has predictive value for neurodevelopmental delay with high specificity (84.62%) and positive predictive value (80.00%).ConclusionsChildren with NEC are more likely to develop neurodevelopmental delay. There is high specificity and PPV of early aEEG in predicting neurodevelopmental delay.