Risk Of Neurodevelopmental Deficits Research Articles

Association between chest-to-head circumference ratio at birth and childhood neurodevelopment: the Japan Environment and Children's Study.

Children born growth-restricted are well recognized to be at an increased risk of poor neurodevelopmental outcomes. This prospective study examined the influence of chest-to-head circumference ratio at birth on neurodevelopment in the first three years among children enrolled in the Japan Environment and Children's Study. We analyzed information of 84,311 children (43,217 boys, 41,094 girls). Children were divided into low, normal, and high chest-to-head circumference ratio groups. Neurodevelopment was assessed every six months (from 6 months to 3 years) using the Ages and Stages Questionnaire (Japanese translation), with delays defined as scores below 2 standard deviations from the mean. Additionally, we evaluated the contributions of chest and head circumference to the observed association. Linear mixed-effect regression revealed increased risk of delays in communication, gross motor, fine motor, problem-solving, and personal-social skills in the low-ratio group compared to the normal-ratio group. Adjusted risk ratios were in the range of 1.14 - 1.39 in boys and 1.16 - 1.37 in girls, with no such increase observed in the high-ratio group. The heightened risk in the low-ratio group was likely associated with a relatively narrow chest rather than a large head. The area under the ROC curves in predicting any developmental delay at three years for newborn measurements ranged from 0.513 to 0.526 in boys and 0.509 to 0.531 in girls. These findings suggest that a low chest-to-head circumference ratio may indicate children who are at risk for neurodevelopmental deficits. However, the ability to predict poor neurodevelopmental outcomes at three years of age is limited.

Long-term outcomes of visual motor integration and motor development children with retinopathy of prematurity.

Premature infants have a risk of neurodevelopmental deficits. Little is known, however, about how retinopathy of prematurity (ROP) affects visual motor integration (VMI), which is necessary for both fine motor skills and further school abilities. Due to the systemic escape of bevacizumab in the treatment of ROP, concerns regarding the long-term neurodevelopmental effect of the drug have arisen. The aim is to evaluate VMI and motor development long-term outcomes after intravitreal bevacizumab (IVB) injection and laser treatment for ROP. Two groups of premature children were included: Bevacizumab group - 16 premature children who received IVB treatment and laser group - 23 premature children who underwent laser photocoagulation treatment in this single center cross-sectional study. At 2-6 years of age, VMI (Beery-Buktenica Developmental Test), motor development (Peabody Developmental Motor Scales-2), visual acuity, and refractive status were assessed. The incidence of abnormal visual function was significantly higher in bevacizumab group than in laser group (p = 0.022). The incidence of abnormal VMI skill was significantly higher in bevacizumab group than in laser group (p = 0.024). Incidences of abnormal gross, fine, and total motor skills were significantly higher in bevacizumab group compared to laser group (p < 0.05). Premature children who received bevacizumab for ROP demonstrated significantly lower VMI and motor development features than those with laser treatment at preschool age. Although our results suggest the relevance of bevacizumab injection in impaired VMI and motor development outcomes, general level of sickness rather than treatment might be the cause of delayed motor development.

Impact of Retinopathy of Prematurity on Visual Motor Integration

Background: Preterm infants are at risk for neurodevelopmental deficits. An association between retinopathy of prematurity (ROP) and impaired cognitive outcome has already been described. However, less is known about the impact of ROP on visual motor integration (VMI), which is a prerequisite not only for fine motor abilities but also for further school skills. Therefore, the aim of this study was to retrospectively investigate the impact of ROP on VMI at preschool age. Methods: The study was conducted at the Medical University of Vienna, including patients born between January 2009 and December 2014 with a gestational age of less than 30 weeks and/or a birth weight of less than 1,500 g. VMI was determined by Beery-Buktenica Developmental Test of Visual Motor Integration (Beery VMI) at the age of 5 years. Results: Out of 1,365 patients, 353 met inclusion criteria for this study. Two hundred sixteen of them had no ROP, while 137 had ROP (stage 1: n = 23, stage 2: n = 74, stage 3: n = 40). Mean value of the Beery VMI score was significantly lower in the ROP group compared to the No-ROP group (90 ± 16 vs. 99 ± 14; p < 0.01). By correcting for other important medical conditions, ROP still had a significant impact on Beery VMI score (p < 0.01). Particularly, lower scores were found for stage 2 (p < 0.01) and stage 3 (p < 0.01). Conclusion: Beery VMI scores were significantly lower in preterm infants with ROP stage 2 and 3 than in infants without ROP. This study shows the negative impact of ROP on VMI skills at preschool age, even after adjustment for key demographic and medical characteristics.

Congenital heart disease in school-aged children: Cognition, education, and participation in leisure activities

BackgroundChildren with congenital heart disease (CHD) are at risk for neurodevelopmental deficits. This study aimed to investigate the impact of cognitive deficits on educational outcome and participation in leisure activities.MethodsA prospective cohort of 134 children with CHD who underwent cardiopulmonary bypass surgery (CPB) was examined at 10 years of age. IQ was assessed with the WISC-IV and executive functions with the BRIEF (parent- and teacher-report). Parents reported on type and level of education and educational support, and leisure activity participation. Ordinal regression analyses assessed the association between cognitive deficits and educational outcome and participation.ResultsTotal IQ (P = 0.023), working memory (P < 0.001), processing speed (P = 0.008), and teacher-reported metacognition (P = 0.022) were lower than norms. Regular school was attended by 82.4% of children with CHD compared to 97% of the general Swiss population (P < 0.001). Seventy-five percent of children participated in leisure activities. Lower total IQ and teacher-rated global executive functions were associated with more educational support and lower IQ was associated with less participation.ConclusionAs school-aged children with CHD experience cognitive deficits, follow-up is required to provide optimal support with regard to educational outcome and participation in leisure activities.ImpactContemporary cohorts of children with congenital heart disease undergoing cardiopulmonary bypass surgery remain at increased risk for cognitive deficits.Cognitive deficits affect educational outcome and leisure activities.These findings underline the importance of early detection of cognitive deficits and recommend support with respect to cognitive functioning.

Utilisation of early intervention services in infants with congenital heart disease following open-heart surgery.

To examine the use of early intervention services in infants with CHD after open-heart surgery and identify factors associated with receipt of services. Surveys were administered to caregivers of infants who underwent open-heart surgery before 1 year of age at a single institution between July, 2017 and July, 2018. Information regarding the infant's use of early intervention services and the caregiver's experience with the programme was obtained. Clinical data were retrieved from the medical record review. Logistic regression identified factors associated with receipt of services. The study included 158 eligible infants. Ninety-eight caregivers (62%) completed the surveys. Of those surveyed, 53.1% of infants were currently or previously enrolled in early intervention services. Infants most frequently received physical therapy (76.9%). The majority of caregivers found services to be moderately/very helpful (92.3%) and sufficient for their child (76.9%). In the univariate analysis, single-ventricle disease, known syndrome/genetic abnormality, extracardiac anomaly, and longer intensive care and hospital length of stay were associated with receipt of services. Single-ventricle disease (p = 0.004) and known syndrome/genetic abnormality (p < 0.0001) remained independently associated with receipt of services in the multivariable analysis. Amongst infants at risk for neurodevelopmental deficits, approximately half received services after open-heart surgery. Caregivers expressed satisfaction with the programme. While infants with single-ventricle disease and a known syndrome/genetic abnormality were more likely to receive early intervention services, many at-risk infants with CHD failed to receive services. Further research is needed to identify barriers to early intervention services and promote developmental outcomes.

Community initiated kangaroo mother care and early child development in low birth weight infants in India-a randomized controlled trial

BackgroundIn a randomized controlled trial (RCT) with 8402 stable low birthweight (LBW) infants, majority being late preterm or term small for gestational age, community-initiated KMC (ciKMC) showed a significant improvement in survival. However, the effect of ciKMC on neurodevelopment is unclear. This is important to elucidate as children born with low birth weight are at high risk of neurodevelopmental deficits. In the first 552 stable LBW infants enrolled in the above trial, we evaluated the effect of ciKMC on neurodevelopmental outcomes during infancy.MethodThis RCT was conducted among 552 stable LBW infants, majorly late preterm or term small for gestational age infants without any problems at birth and weighing 1500–2250 g at birth. The intervention comprised of promotion of skin-to-skin contact and exclusive breastfeeding by trained intervention delivery team through home visits. The intervention group mother-infant-dyads were supported to practice ciKMC till day 28 after birth or until the baby wriggled-out. All infants in the intervention and control groups received Home Based Post Natal Care (HBPNC) visits by government health workers. Cognitive, language, motor and socio-emotional outcomes were assessed at infant-ages 6- and 12-months using Bayley Scale of Infant Development (BSID-III). Other outcomes measured were infant temperament, maternal depression, maternal sense of competence, mother-infant bonding and home-environment. We performed post-hoc equivalence testing using two one-sided tests of equivalence (TOST) to provide evidence that ciKMC does not do harm in terms of neurodevelopment.ResultsIn the intervention arm, the median (IQR) time to initiate ciKMC was 48 (48 to 72) hours after birth. The mean (SD) duration of skin-to-skin-contact was 27.9 (3.9) days with a mean (SD) of 8.7 (3.5) hours per day. We did not find significant effect of ciKMC on any of the child developmental outcomes during infancy. The TOST analysis demonstrated that composite scores for cognitive, language and motor domains at 12 months among the study arms were statistically equivalent.ConclusionOur study was unable to capture any effect of ciKMC on neurodevelopment during infancy in this sample of stable late preterm or term small for gestational age infants. Long term follow-up may provide meaningful insights.Trial registrationThe trial is registered at clinicaltrials.gov NCT02631343 dated February 17, 2016; Retrospectively registered.

Prevalence of Sensorineural Hearing Loss in Children with Palliated or Repaired Congenital Heart Disease.

BackgroundChildren with congenital heart disease (CHD) are at increased risk of neurodevelopmental deficits, and the presence of sensorineural hearing loss (SNHL) may further lead to poor language skills acquisition and speech delays. Prevalence of SNHL in the general pediatric population is estimated to be 0.2% at birth to 0.35% during adolescence. Very few studies have attempted to estimate SNHL prevalence in children who have undergone congenital heart surgery.MethodsThis retrospective study aimed to estimate SNHL prevalence in children who underwent congenital heart surgery in our institution and were followed up in our high-risk pediatric cardiology clinics for four years from 2009 to 2013. Data were collected on demographics, preoperative variables, surgical variables, and post-operative variables.ResultsSNHL prevalence in asymptomatic, palliated/repaired CHD patients followed in our high-risk clinics and undergoing routine surveillance was 11.6% (20 of 172 patients with hearing impairment). SNHL prevalence was not statistically higher in single-ventricle patients (17.2%) compared to biventricular patients (14.7%). Inotropic score in the first 24 hours of postoperative period (p=0.05), lowest arterial PaO2 (p=0.003), duration of Lasix drip (p=0), and bolus dose in days (p=0.03) were all found to be statistically significant in the hearing-impaired group. However, using logistic regression, we identified no statistically significant predictors for hearing loss.ConclusionThe results suggest the need for routine audiology screening of all patients with complex CHD, especially those who have undergone neonatal cardiac repair/palliation at less than one year of age, irrespective of risk factors.

Efficacy of docosahexaenoic acid-enriched formula to enhance maternal and fetal blood docosahexaenoic acid levels: Randomized double-blinded placebo-controlled trial of pregnant women with gestational diabetes mellitus

Gestational diabetes mellitus (GDM) compromises the level of docosahexaenoic acid (DHA) in phospholipids of maternal and fetal red blood cells and fetal plasma. This is of some concern because of the importance of DHA for fetal neuro-visual development. We have investigated whether this abnormality could be rectified by supplementation with DHA-enriched formula. Women with GDM (n=138) recruited from Newham University Hospital, London received two capsules of DHA-enriched formula (active-group) or high oleic acid sunflower seed oil (placebo-group) from diagnosis until delivery. Maternal (baseline and delivery) and fetal (cord blood) red blood cell and plasma phospholipid fatty acid composition, and neonatal anthropometry were assessed. One hundred and fourteen women (58 active, 56 placebo) completed the trial. The active-group compared with the placebo-group had significantly enhanced level of DHA in plasma phosphatidylcholine (4.5% vs 3.8%, P=0.011), red blood cell phosphatidylcholine (2.7% vs 2.2%, P=0.022) and phosphatidylethoanolamine (9.5% vs 7.6%, P=0.002). There was no difference in cord plasma and red blood cell phospholipid DHA between the two groups. The neonates of the two groups of women had comparable anthropometric measurements at birth. Daily supplementation of 600mg DHA enhances maternal but not fetal DHA status in pregnancy complicated by GDM. The inefficacy of the supplement to improve fetal status suggests that the transfer of DHA across the placenta maybe impaired in women with the condition. Regardless of the mechanisms responsible for the impairment of the transfer, the finding has implications for the management of neonates of women with GDM because they are born with a reduced level of DHA and the condition is thought to be associated with a risk of neuro-developmental deficits. We suggest that babies of women with GDM, particularly those not suckling, similar to the babies born prematurely require formula milk fortified with a higher level of DHA.

Neurodevelopmental profile of children of a high-risk neonatal program: A follow-up study from Saudi Arabia

Introduction: Preterm infants are at increased risk for neurodevelopmental deficits. These deficits may be alleviated with early intervention. There has been no study to assess neurodevelopment of high risk neonates in Saudi Arabia. Objective: To assess the neurodevelopmental features of preterm (≤29 weeks or ≤1.25 kg) infants who were admitted over a two-year period following birth at a tertiary care neonatal intensive care unit (NICU). Methods: This study used a pool of standardized psychometric scales: Vineland Adaptive Behavior Scales, Bayley Scales of Infant Development, and Stanford-Binet Intelligence Test. Follow-up assessments were applied to examine 168 infants at 18 months; 96 of them were re-evaluated at 3 years. Results: Major neurodevelopmental abnormalities were present in 26 (15.50%) and 11 (11.46%) children, at 18 months and 3 years, respectively. The two scales: Bayley vs. Vineland at 18 months, and the two scales: Stanford-Binet vs. Vineland at 3 years were correlated significantly: χ 2 (1, N = 168) = 58.07, P < 0.001; and χ 2 (1, N = 96) = 49.45, P < 0.001, respectively. Nevertheless, Bayley scale and Stanford-Binet test were more likely to detect neurodevelopmental impairment among children at 18 months and 3 years, respectively. Conclusions: Infants born at the NICU at King Fahd Medical Center (KFMC), have rates of neurodevelopmental outcomes that are similar to those reported in other studies. This study confirms the need for early developmental screening to detect preterm infants with special needs. Neurodevelopmental outcomes for the cohort managed at KFMC were similar to previously published data on preterm infants elsewhere.

Neurochemical changes in the developing rat hippocampus during prolonged hypoglycemia

Hypoglycemia is common during development and is associated with the risk of neurodevelopmental deficits in human infants. The effects of hypoglycemia on the developing hippocampus are poorly understood. The sequential changes in energy substrates, amino acids and phosphocreatine were measured from the hippocampus during 180 min of insulin-induced hypoglycemia (blood glucose < 2.5 mmol/L) in 14-day-old rats using in vivo(1)H NMR spectroscopy. Hypoglycemia resulted in neuroglycopenia (brain glucose < 0.5 micromol/g). However, the phosphocreatine/creatine (PCr/Cr) ratio was maintained in the physiological range until approximately 150 min of hypoglycemia, indicating that energy supply was sufficient to meet the energy demands. Lactate concentration decreased soon after the onset of neuroglycopenia. Beyond 60 min, glutamine and glutamate became the major energy substrates. A precipitous decrease in the PCr/Cr ratio, indicative of impending energy failure occurred only after significant depletion of these amino acids. Once glutamate and glutamine were significantly exhausted, aspartate became the final energy source. N-acetylaspartate concentration remained unaltered, suggesting preservation of neuronal/mitochondrial integrity during hypoglycemia. Correction of hypoglycemia normalized the PCr/Cr ratio and partially restored the amino acids to pre-hypoglycemia levels. Compensatory neurochemical changes maintain energy homeostasis during prolonged hypoglycemia in the developing hippocampus.

Ventricular haemorrhages and hypoxic-ischaemic lesions in preterm infants: neurodevelopmental outcome at 3 1/2 years.

The association of cerebral ultrasound images and developmental outcome at age 3 1/2 years was studied in 50 preterm infants (mean gestational age 31 weeks, mean birthweight 1450 g). 25 children had normal neonatal scans and 25 had abnormal neonatal scans; 11 without and 14 with ventricular dilatation. At one year a repeat scan was done and neurodevelopmental outcome was assessed. Follow-up results at 3 1/2 years stress the importance of long-term follow-up: at one year four of the 50 children had developmental deficits, at 3 1/2 years 13 had such deficits. At 3 1/2 years the risk of neurodevelopmental deficits was extremely high for children with persistent haemorrhagic and/or atrophic ventricular dilatation. There was significant over-representation of children with developmental deficits in the group with abnormal scans, both neonatally and at one year. The incidence of cerebral palsy was high in the group with large haemorrhages extending into the parenchyma and/or periventricular leucomalacia. In the group with periventricular leucomalacia there was also a greater risk of mental retardation with severe behavioural problems. Follow-up at a later age than 3 1/2 years will be necessary to determine the effects on the motor, intellectual and emotional development of these children.