Risk Factor For Neurodevelopmental Impairment Research Articles

Risk Factors for Neurodevelopmental Impairment at 2- and 5-Years Corrected Age in Preterm Infants with Established Bronchopulmonary Dysplasia

Introduction: The objective of this study was to identify risk factors for neurodevelopmental impairment (NDI) at 2- and 5-years corrected age (CA) in a cohort of preterm infants with established bronchopulmonary dysplasia (BPD). Methods: This single-center retrospective cohort study included infants born between 2009 and 2016 at a gestational age (GA) <30 weeks with moderate or severe BPD at 36 weeks’ postmenstrual age. Perinatal characteristics, (social) demographics, and comorbidities were collected from the electronic patient records. Odds ratios for NDI were calculated with univariate and multivariate logistic regression analyses adjusting for potential confounders. Results: Of the 602 eligible infants, 123 infants were diagnosed with BPD. NDI was present in 30.3% and 56.1% at 2- and 5-years CA, respectively. The only independent risk factors associated with NDI in the multivariate analyses were birthweight (adjusted odds ratio [aOR] 0.74, 95% CI 0.57–0.95; aOR 0.70, 95% CI 0.54–0.91, respectively), small for GA (SGA) (aOR 3.25, 95% CI 1.09–9.61; aOR 5.44, 95% CI 1.62–18.2, respectively) at both time points, and male gender at 5-years CA (OR 2.49, 95% CI 1.11–5.57). Conclusion: Birthweight and SGA are independent risk factors for NDI at 2- and 5-years CA and male gender at 5-years CA in preterm infants with BPD. In contrast, well-known other risk factors for NDI in the general population of preterm infants, such as GA, maternal education, and neonatal comorbidities were not independently associated with NDI.

Neurodevelopmental Outcome at Two Years for Preterm Infants With Intraventricular Hemorrhage: A Case-Control Study

BackgroundHigh-grade intraventricular hemorrhage (IVH), including grade III and grade IV IVH, is known to impact neurodevelopmental outcome of preterm infants, but prognosis remains difficult to establish due to confounding factors and significant variations in the reported outcomes. The aim of this study was to compare the neurodevelopmental outcome of preterm infants with or without severe IVH. MethodsA retrospective case-control study was conducted including preterm infants with gestational age <32 weeks hospitalized between 2009 and 2017 in a level III neonatal intensive care unit. This study included 73 cases with high-grade IVH and 73 controls who were matched to cases, based on the same gestational age, birth weight, sex, and year of birth. The neurodevelopmental outcome was compared at two years of age corrected for prematurity between cases and controls. Neurodevelopmental impairment was defined as cerebral palsy, hearing deficiency, visual impairment, or developmental delay. Multivariate analysis was used to identify whether high-grade IVH was an independent risk factor for neurodevelopmental impairment. ResultsIn univariate analysis, high-grade IVH was associated with death or poor neurodevelopmental outcome at two years of age corrected for prematurity (odds ratio [OR], 16.3; 95% confidence interval [CI], 5.93 to 57.8; P < 0.001), and this association remained significant after adjusting for confounding factors including neonatal infection and bronchopulmonary dysplasia in multivariate analysis (OR, 8.71; 95% CI, 2.48 to 38.09; P = 0.002). ConclusionsThis study highlights the impact of high-grade IVH as an independent risk factor of poor neurodevelopmental outcomes in very preterm infants and suggests that early interventions could improve the prognosis of these infants.

Identification of risk factors in pre-term infants with abnormal general movements

This study aimed to investigate the relationship between prenatal, perinatal, and postnatal risk factors for neurodevelopmental impairment (NDI) with the outcomes of General Movement (GM) Assessment (GMA) in pre-term infants at 3-5 months of age. We sought to identify the risk factors associated with the predictors of psychomotor development in pre-term newborns, such as normal fidgety movements (FMs), absent FMs, or abnormal FMs, assessed during the fidgety period of motor development. The SYNAGIS program (prophylactic of Respiratory Syncytial Virus Infection) was used to identify risk factors for the development of neuromotor deficits in 164 pre-term infants who were at high risk of developing these deficits. Based on the GMA, all participants were divided into three groups of infants who presented: (1) normal FMs; (2) absent FMs; and (3) abnormal FMs. The results of the current study suggest that abnormal GMs not only indicate commonly known factors like birth asphyxia (BA), respiratory distress syndrome (RDS), periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH) grades 3-4, but also predict the development of motor impairments. In the present study, several specific risk factors including bronchopulmonary dysplasia (BPD), infertility treatments, maternal acute viral/bacterial infections during pregnancy, and elevated bilirubin levels were identified as attributes of an atypical fidgety movement pattern. Additional clinical data, such as risk factors for NDI associated with early predictors of psychomotor development in pre-term newborns, i.e., absent or abnormal FMs, may be helpful in predicting neurological outcomes in pre-term infants with developmental concerns in the 1st month of life.

Dextro-Transposition of Great Arteries and Neurodevelopmental Outcomes: A Review of the Literature.

Background: Arterial switch operation (ASO) is the gold-standard surgical approach for dextro-transposition of the great arteries (D-TGA). It is performed during the neonatal period and has almost diminished the previously high mortality rate (from 90% if left untreated to <0.5%). Despite the impressively high survival rates, the surgical procedure itself—along with the chronic post-operative complications and the perinatal impaired cerebral oxygen delivery—introduces multiple and cumulative risk factors for neurodevelopmental impairment. Method: This study is a review of English articles, using PUBMED and applying the following search terms, “transposition of the great arteries”, “neurodevelopment”, “autism”, “cerebral palsy”, and “attention-deficit hyperactivity disorder”. Data were extracted by two authors. Results: Even though general IQ is mainly found within the normal range, D-TGA children and adolescents display reduced performance in the assignments of executive functions, fine motor functions, attention, working memory, visual–spatial skills, and higher-order language skills. Moreover, D-TGA survivors may eventually struggle with inferior academic achievements and psychiatric disorders such as depression, anxiety, and ADHD. Conclusions: The existing literature concerning the neurodevelopment of D-TGA patients suggests impairment occurring during their lifespan. These findings underline the importance of close developmental surveillance so that D-TGA patients can better reach their full potential.

Small for Gestational Age is an Independent Risk Factor for Neurodevelopmental Impairment

Background: There is a deficit of publications regarding the impact of small for gestational age (SGA) on later neurodevelopment of premature infants and existing results are conflicting. Objectives: The aim of the present study was multifaceted neurodevelopmental assessment of children born prematurely, with particular assessment of SGA as an independent risk factor for impairment in prematurely born children. Methods: Eighty-nine children born with very low birth weight were evaluated at the age of 50 months. Anthropometric measurements and several psychomotor tests (WeeFIM-Functional Independence Measure scale, Leiter Test-Non-Verbal Psychometric Evaluation, DTVP-2-Developmental test of Visual Perception, CAST-Childhood Autism Spectrum test, EAS-C-temperament questionnaire and TSD-children vocabulary test) were performed in each child. Results: SGA appears to be a risk factor for low self-reliance (mean WeeFIM score 89 ± 20 points vs 99 ± 15; P = 0.034), decreased non-verbal intelligence (Leiter score 87 ± 18 points vs 100 ± 18 points; P = 0.022) and low visual perception (Frostig test 81 ± 17 points vs 93 ± 17 points; P = 0.035). Moreover, the incidence of autism spectrum disorders was significantly higher in the SGA group (21% vs 2.8%; P = 0.029). There were no differences in frequency of cerebral palsy diagnosis, vocabulary test results and temper tests scores between SGA and AGA groups. Conclusions: Birth weight small for gestational age seems to be an additional, independent risk factor of neurodevelopmental delay in prematurely born children.

High risk of long-term neurodevelopmental impairment in donor twins with spontaneous twin anemia-polycythemia sequence.

To evaluate the long-term neurodevelopmental and behavioral outcomes in surviving infants of pregnancies with spontaneous twin anemia-polycythemia sequence (TAPS), to compare outcome between donors and recipients, and to investigate potential risk factors for neurodevelopmental impairment (NDI). This was a retrospective study of a consecutive cohort of spontaneous-TAPS survivors delivered between 2005 and 2017 at the Leiden University Medical Center, The Netherlands. Neurological, motor, cognitive and behavioral development were assessed at a median age of 4 years. The primary outcome was NDI, which was a composite outcome of cerebral palsy, deafness, blindness and motor and/or cognitive delay. NDI was subdivided into two grades of severity: mild-to-moderate and severe NDI. Outcome was compared between surviving donor and recipient twins. Logistic regression analysis was used to assess risk factors for NDI. Forty-nine twin pregnancies complicated by spontaneous TAPS were eligible for inclusion. The perinatal survival rate was 83% (81/98) of twins. Neurodevelopmental assessment was performed in 91% (74/81) of surviving twins. NDI occurred in 30% (22/74) of TAPS survivors, and was found more often in donors (44%; 15/34) than in recipients (18%; 7/40) (odds ratio (OR), 4.1; 95% CI, 1.8-9.1; P = 0.001). Severe NDI was detected in 9% (7/74) of survivors and was higher in donors compared with recipients (18% (6/34) vs 3% (1/40)), although the difference did not reach statistical significance; P = 0.056). Donors demonstrated lower cognitive scores compared with recipients (P = 0.011). Bilateral deafness was identified in 15% (5/34) of donors compared with 0% (0/40) of recipients (P = 0.056). Parental concern regarding development was reported more often for donor than for recipient twins (P = 0.001). On multivariate analysis, independent risk factors for NDI were gestational age at delivery (OR, 0.7; 95% CI, 0.5-0.9; P = 0.003) and severe anemia (OR, 6.4; 95% CI, 2.4-17.0; P < 0.001). Surviving donor twins of pregnancies complicated by spontaneous TAPS have four-fold higher odds of NDI compared with recipient cotwins, are at increased risk of cognitive delay and have a high rate of deafness. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Spontaneous movements in the first four months of life: An accelerometric study in moderate and late preterm infants.

Moderate preterm infants (MPI) and late preterm infants (LPI) account for the majority of children born preterm. Up to 5% of MPI and LPI are estimated to manifest neurodevelopmental impairments. However, information about normal early motor development in these patients is lacking. To find characteristic patterns for motor development in the first four months of life among MPI and LPI without risk factors for developmental impairment by using accelerometry of spontaneous movements. Prospective and observational study. Twenty-three MPI and LPI (9 female, 14 male) without known risk factors for neurodevelopmental impairment were included in this study. Spontaneous movements were measured by accelerometry at the time of hospital discharge (mean: 36.6wks postmenstrual age (PMA)) and at the corrected age of three months (mean: 53.0wks PMA). Motor development was described by analyzing 36 parameters calculated from the acceleration signal. Normal neurodevelopmental outcome was confirmed by Bayley Scales of Infant Development at the corrected age of two years. Statistically significant differences (p < 0.05) between the two measurements could be shown in 26 out of the 36 parameters. Striking changes in motor development were an increase in acceleration and variability of the spontaneous movements, the main criterion for analyzing spontaneous movements. Furthermore, the regularity of spontaneous movements increased significantly. Characteristic patterns of normal motor development in MPI and LPI can be identified and provide a basis for future investigations aiming at the early detection of abnormal motor development for this specific patient group.

HIGH SYSTEMIC BLOOD PRESSURE IN PRETERM INFANTS WITH BRONCHOPULMONARY DYSPLASIA AND LONG-TERM OUTCOMES

Abstract BACKGROUND Bronchopulmonary dysplasia (BPD) is a known risk factor for neurodevelopmental impairment in preterm infants. BPD is also associated with an increased incidence of high systemic blood pressure (HBP). However, it is not known if a diagnosis of HBP in BPD patients relates to later neurodevelopmental outcomes. OBJECTIVES We aimed to determine the incidence of neonatal HBP diagnosis in a cohort of preterm infants born &lt;29 weeks of gestational age (GA) with BPD. The secondary objective was to assess if a concomitant diagnosis of BPD and HBP influences neurodevelopmental outcomes at 18 months. DESIGN/METHODS We performed a single center retrospective study using data from medical charts. All infants born &lt;29 weeks GA admitted to our level-IV neonatal intensive care unit between January 2010 and December 2012 diagnosed with BPD at 36 weeks of corrected GA were included. Patients transferred before 36 weeks of corrected GA, that died before 18 months or had congenital anomalies were excluded. Patients were classified in the HBP group if HBP was a documented diagnosis in the chart. The control group was the remaining patients with BPD at 36 weeks corrected GA but without HBP. Severe neurodevelopmental impairment at 18 months was defined as either any Bailey-III score &lt;70, cerebral palsy or severe hearing or visual impairment. Descriptive statistics for prenatal and postnatal patients’ characteristics were analyzed. Logistic regression was performed for factors associated with long-term disability. Level of significance was determined as a p value &lt;0.05. RESULTS During the study period, 337 preterm infants &lt;29 weeks of GA were identified and after exclusions, 98 newborns met the criteria of BPD at 36 weeks corrected GA. Mean GA and mean birth weight were 26.7 ± 1.7 weeks and 882 ± 199 g respectively. The majority were males (57%) and received antenatal steroids (87.8%). We identified twenty-five newborns (25.5%) with a diagnosis of HBP. Demographic data was similar between the 2 groups. 56% of the HBP group received a post-natal course of steroids, compared to 36% for the control group (p 0.07). The neurodevelopmental outcome at 18 months was similar between the two groups (p 0.54) and was not influenced by the presence of a HBP diagnosis after regression analysis (p 0.8). CONCLUSION The diagnosis of HBP was frequent in our cohort of preterm infants born &lt;29 weeks GA with BPD but did not seem to be related to long-term neurodevelopmental outcomes.

Reduction of brain volumes after neonatal cardiopulmonary bypass surgery in single-ventricle congenital heart disease before Fontan completion.

BackgroundLittle is known about the relationship between brain volumes and neurodevelopmental outcome at 2 years of age in children with single-ventricle congenital heart disease (CHD). We hypothesized that reduced brain volumes may be associated with adverse neurodevelopmental outcome.MethodsVolumetric segmentation of cerebral magnetic resonance imaging (MRI) scans was carried out in 44 patients without genetic comorbidities and in 8 controls. Neurodevelopmental outcome was assessed with the Bayley-III scales.ResultsGray matter (GM), deep GM, white matter (WM), and cerebrospinal fluid (CSF) volumes were 611±59, 43±4.5, 277±30, and 16.4 ml, respectively (interquartile range (IQR) 13.1, 23.3 ml). Children undergoing neonatal cardiopulmonary bypass surgery showed smaller deep GM (P=0.005) and WM (P=0.021) volumes. Brain volumes were smaller in patients compared with controls (GM: P=0.017, deep GM: P=0.012, and WM: P=0.015), whereas CSF volumes were greater (P=0.014). Of all intracranial volumes, only CSF volume was associated with neurodevelopmental outcome, accounting for 21% (P=0.011) of variability in the cognitive composite score when combined with common risk factors in a multivariable analysis.ConclusionIncreased CSF volume represents a significant risk factor for neurodevelopmental impairment in children with single-ventricle CHD. Later assessments are warranted to determine the prognostic role of intracranial volumes for long-term outcome.

Neonatal cerebral lesions predict 2-year neurodevelopmental impairment in children treated with laser surgery for twin–twin transfusion syndrome

Objective: The objective of this study is to assess whether postnatally detected cerebral abnormalities are predictive of neurodevelopmental impairment (NDI) in survivors of twin–twin transfusion syndrome (TTTS) that underwent laser surgery. Materials and methods: Ninety-nine children treated for TTTS had neurodevelopmental assessment at age 2-years (±6 weeks). ‘High-risk survivors’ had cerebral imaging in the neonatal period. ‘High-risk survivors’ were defined as (1) delivered at <32 weeks; or (2) cerebral imaging clinically indicated. NDI was a composite outcome of: Battelle Developmental Inventory 2nd edition (BDI-2) score <70, cerebral palsy, blindness, and/or deafness. Multilevel logistic regression with robust standard errors was used to evaluate associations between cerebral lesions and NDI. Results: Fifty-six children were ‘high-risk survivors’ and had neonatal cerebral imaging. Ten twins (18%) had at least one cerebral lesion, including grade 1–2 intraventricular hemorrhage (8), cystic periventricular leukomalacia (2), ventriculomegaly (1), and bilateral subependymal cyst (1). The risk of NDI in the ‘high-risk survivors’ was 7% (4/56) compared with 0% (0/43) in the remaining group. Among ‘high-risk survivors’, cerebral lesions were a significant risk factor for NDI (OR = 19.28, p < .001). Conclusions: Among ‘high-risk survivors’ of TTTS treated with laser surgery, cerebral lesions identified on neonatal imaging were associated with NDI at 2-years.

Neuro-developmental outcome in single-ventricle patients: is the Norwood procedure a risk factor?

Complex neonatal surgery is considered a risk factor for neuro-developmental impairment in single-ventricle patients. Neuro-developmental outcome was compared between preschool-aged Fontan patients who underwent a Norwood procedure and single-ventricle patients not requiring neonatal surgery with cardiopulmonary bypass. Verbal, performance and full-scale intelligence quotient (IQ) were evaluated with the Wechsler Preschool and Primary Scale of Intelligence. Cognitive functions were assessed with the German 'Kognitiver Entwicklungstest für das Kindergartenalter' (KET-KID). Risk factors for impaired neuro-development were evaluated. Neuro-developmental assessment was completed in 95 patients (Norwood: n = 69; non-Norwood: n = 26). Median (interquartile range) IQ and KET-KID scores were in the normal range. Except for verbal KET-KID, scores did not differ between Norwood and non-Norwood patients (verbal IQ: 98 (86-105) vs 93 (85-102), P = 0.312; performance IQ: 91 (86-100) vs 96 (86-100), P = 0.932; full-scale IQ: 93 (86-101) vs 89 (84-98), P = 0.314; KET-KID verbal: 48 (17-72) vs 25 (2-54), P = 0.020; KET-KID non-verbal: 33 (18-62) vs 45 (15-54), P = 0.771; KET-KID global: 42 (14-65) vs 28 (6-63), P = 0.208). Full-scale IQ was below average (<85 points) in 14 (20%) Norwood and 9 (35%) non-Norwood cases (P = 0.181). Global KET-KID was below average (<16th percentile) in 19 (28%) and 10 (38%) patients (P = 0.326). Smaller head circumference z-score and complications before neonatal surgery were independently associated with lower scores. Neuro-developmental outcome of preschool-aged Fontan patients was in the normal range. The Norwood procedure was not a risk factor for neuro-developmental impairment. Preoperative condition and patient-related factors were more important determinants than variables related to surgical palliation.

FKBP5 genotype and early life stress exposure predict neurobehavioral outcomes for preterm infants.

This study evaluated the relationship between stressful early life neonatal intensive care unit (NICU) experiences, genetic variation of a stress response-associated gene (FKBP5), and neurobehavioral outcomes. The impact of genetic variation and stress experience on neurobehavioral outcomes was examined for 41 preterm infants. Statistical analyses explored the main effects of FKBP5 genotype and NICU stress experience, as well as their interaction on infant neurobehavioral development prior to discharge. Statistical analyses demonstrated a relationship between both FKPB5 genotype and stress related to NICU care that were independently associated with neurobehavioral outcomes; indicating a main effect of genotype and a main effect of stress on neurodevelopment. Additionally, we found an interaction between the minor allele genotype and NICU stress potentially associated with less favorable developmental progress at discharge. Evidence of genetic and environmental risk factors for neurodevelopmental impairment suggests the need for improved evidence-based practice initiatives to protect those most vulnerable to the combination of genetic susceptibility to stress and medical fragility.

Neonatal Seizures: Frequency, Clinical Forms, Aetiology and Outcome in Tropical Practice

Background: Seizures are common cause of paediatric admissions in poor resource countries and a risk factor for neurodevelopmental impairment. This study aimed to determine the frequency, clinical forms, aetiology and outcome of seizures in relation to rectal temperature in newborn. Patients and Methods: The study was located in paediatric department of our University Hospital. This prospective research had assessed consecutive admitted newborns aged 0-28 days with incident seizure during a period from January to December, 2013. Newborns with epilepsy and non-incident admission seizure were excluded. Results: Seizures were observed in 344/4836 (7.1%). The sample included 192 males and 152 females. The seizures frequency in newborn 0-21 days was 95.9% and was 52.6% in neonates < 1day. The focal seizures were reported in 68% follow by generalized tonic-clonic in 24.4%. Status epilepticus was observed in 7.6%. Seizures had occurred in a context of hypothermia in 77.9%, normal temperature, 14.2% and hyperthermia in 7.8%. The hypothermia and normal temperature seizures were more common in newborn < one week and hyperthermia was noted in older. The associated pathologies in the context of hyperthermia were neonatal infections (17.4%) and falciparum malaria (22.7%) respectively in one week newborn and older. Perinatal ischaemic/hypoxic (35.5%), falciparum malaria (13.6%) and respiratory tract infections and gastroenteritis (11.8%) were the main diseases associated with seizures in the context of hypothermia and normal temperature. The aetiologies were marked by neonatal brain injuries and perinatal asphyxia. Sixteen neonates with seizures were died giving a direct mortality rate of 4.7%. Eight (2.3%) surviving newborns had heavy neurodevelopmental deficits at discharge. Conclusion: The neonate seizures are an indicative of infection with or without fever. The causes of newborn convulsions must be prevented through a wide available public health programs.

Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study

To determine the incidence and risk factors for neurodevelopmental impairment (NDI) in children with hemolytic disease of the fetus/newborn treated with intrauterine transfusion (IUT). Neurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests, including the Bayley Scales of Infant Development, the Wechsler Preschool and Primary Scale of Intelligence, and the Wechsler Intelligence Scale for Children, according to the children's age. Primary outcome was the incidence of neurodevelopmental impairment defined as at least one of the following: cerebral palsy, severe developmental delay, bilateral deafness, and/or blindness. A total of 291 children were evaluated at a median age of 8.2 years (range, 2-17 years). Cerebral palsy was detected in 6 (2.1%) children, severe developmental delay in 9 (3.1%) children, and bilateral deafness in 3 (1.0%) children. The overall incidence of neurodevelopmental impairment was 4.8% (14/291). In a multivariate regression analysis including only preoperative risk factors, severe hydrops was independently associated with neurodevelopmental impairment (odds ratio, 11.2; 95% confidence interval, 1.7-92.7). Incidence of neurodevelopmental impairment in children treated with intrauterine transfusion for fetal alloimmune anemia is low (4.8%). Prevention of fetal hydrops, the strongest preoperative predictor for impaired neurodevelopment, by timely detection, referral and treatment may improve long-term outcome.

Outcome of extremely low birth weight survivors at school age: the influence of perinatal parameters on neurodevelopment

Extremely low birth weight (ELBW) is associated with impaired neurodevelopmental outcome in infancy. Information on the long-term cognitive and neurological consequences of ELBW is scarce. We aimed to identify the perinatal and neonatal factors of ELBW infants associated with adverse cognitive and neurological outcome at school age. A regional cohort of 135 ELBW infants born between 1993 and 1998 was prospectively evaluated at 3, 6, 12, and 18 months postmenstrual age and at yearly intervals up to age 10 years. The comprehensive follow-up programme for high-risk infants included neurological examinations and psychometric evaluations. According to the overall results of these tests, children were classified as either being normal or having minor or major impairment. At a mean age of 8.4 (SD: 1.6) years, 43% of children had survived without any impairment. Minor impairment was diagnosed in 39% and major impairment in 18% of assessed children. The proportion of disabled school children rose with decreasing gestational age. The following neonatal complications were significant risk factors for developing major or minor impairment at school age: an increase in head circumference < 6 mm per week (OR 4.0, 95% CI: 1.1-14.8), parenteral nutrition > or = 6 weeks (OR 2.5, 95% CI: 1.1-6.0), and mechanical ventilation > 14 days (OR 2.3, 95% CI: 1.0-5.1). High-grade intraventricular haemorrhage (IVH) and/or PVL (OR 13.3, 95% CI: 4.0-44.9), neonatal seizures (OR 5.2, 95% CI: 1.2-22.4) and bowel perforation, and/or necrotizing enterocolitis (OR 4.4, 95% CI: 1.1-17.0) were significant risk factors for developing major impairment. In spite of the relatively large proportion of normal children, ELBW remains an important risk factor for neurodevelopmental impairment at school age. Thus, measures to prevent complications such as necrotizing enterocolitis, cerebral haemorrhage, and undernutrition remain important goals for neonatal intensive care.