Bayley Scales Of Infant Development-II Research Articles

Maintenance of the synergistic effects of cord blood cells and erythropoietin combination therapy after additional cord blood infusion in children with cerebral palsy: 1-year open-label extension study of randomized placebo-controlled trial

BackgroundThis 1-year open-label extension study aimed to identify the persistent synergistic effects of allogeneic umbilical cord blood (UCB) cells and erythropoietin (EPO) in children with cerebral palsy (CP) for up to 2 years.MethodsThis open-label extension study followed children with CP who were enrolled in the previous randomized, double blind, placebo-controlled trial. The following groups from the first trial were maintained: (A) UCB + EPO, (B) UCB, (C) EPO, and (D) only placebo, and all the participants had continued active rehabilitation. This extended study started 3 months after termination of the first trial, which had a 1-year follow-up duration. All subjects received single additional UCB intravenous infusion at the extension baseline regardless of their initial allocation. Outcome measures were the gross motor performance measure (GMPM), gross motor function measure-66 (GMFM-66), and Bayley scales of infant development-II (BSID-II), which were followed at 3, 6, and 12 months after the extension baseline. Changes in the outcome scores from the baseline values of the previous trial and this study were analysed.ResultsSixty-nine children (4.29 ± 1.28 years, M:F = 34:35) were included in this study. Each group showed improvements in the outcome measures at 12 months after additional UCB infusion compared to the baseline scores, except for GMFM and GMPM in Group C which were elevated at 3 and 6 months post-therapy. Total subject analyses did not show significant differences in the outcome measures between the four different groups at 3, 6 and 12 months after additional UCB therapy. However, patients with severe dysfunction, whose GMFCS levels were IV and V, revealed a larger improvement of the GMPM score in Group A than in Group D (Ps < 0.05) from the baseline value of the previous trial. The changes in BSID-II mental scale scores were positively correlated with the number of administered total nucleated cells per unit body weight during this one-year extension study period (r = 0.536, P = 0.001).ConclusionsThese results suggest that when administering UCB to treat patients with CP, combination therapy with EPO is more effective, and the effect might last as long as 2 years, especially in patients with severe impairments.Trial registration: CHA Bundang Medical Center IRB, No. 2015–06-093, approved on July 29, 2015, (https://www.e-irb.com:3443/devlpg/nlpgS200.jsp), ClinicalTrials.gov, NCT03130816, retrospectively registered on April 27, 2017 (https://clinicaltrials.gov/ct2/show/NCT03130816?term=NCT03130816&draw=2&rank=1).

Breastfeeding and neurodevelopment in infants with prenatal alcohol exposure.

Few studies have evaluated the differential benefits of breastfeeding on infant neurodevelopment at varying levels of prenatal alcohol exposure (PAE). This study examined whether the association between breastfeeding and neurodevelopment is modified by prenatal drinking pattern. The study included 385 infants from Ukraine born to women prospectively enrolled in a cohort study during pregnancy. Neurodevelopment was assessed at six and 12 months using the Bayley Scales of Infant Development II (BSID-II) Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI). Linear regression modeling with interaction terms and stratification by PAE group was used to determine the relationship between breastfeeding, PAE, and neurodevelopment. A significant interaction between PAE and breastfeeding was observed for the MDI and PDI at six and 12 months. Infants with high PAE who were breastfed at least four months had BSID-II scores 14 or more points higher compared to those never breastfed. Counterintuitively, those with moderate PAE had poorer performance on the BSID-II at 12 months when breastfed longer. There was a significant joint effect of PAE and breastfeeding on infant neurodevelopment at six and 12 months. Breastfeeding may provide distinct benefits to infants exposed to high levels of PAE. We found a positive effect of breastfeeding on infant neurodevelopment among infants with prenatal alcohol exposure (PAE), particularly those exposed to higher levels during gestation. This study is one of the first to evaluate whether breastfeeding mitigates harm caused by PAE. Breastfeeding may provide distinct benefits to infants with higher levels of PAE.

Outcome of partial agenesis of corpus callosum

The diagnosis of corpus callosum anomalies by prenatal ultrasound has improved over the last decade due to improved imaging techniques, scanning skills and the routine implementation of transvaginal neurosonography. Our aim was to investigate all cases of incomplete agenesis of the corpus callosum and to report the sonographic characteristics, the associated anomalies and the perinatal outcome. We performed a retrospective analysis from January 2007 to December 2017 of corpus callosum anomalies, either referred for second opinion or derived from the prenatal ultrasound screening program in a single tertiary referral center. Cases with complete agenesis were excluded from analysis. Standardized investigation included detailed fetal ultrasound including neurosonogram, fetal karyotyping (standard karyotype or array CGH) and fetal MRI. Pregnancy outcome was collected and pathological investigation in case of termination of pregnancy or fetal/neonatal loss was compared with prenatal findings. The pregnancy and fetal/neonatal outcome are reported. The neurological assessment was conducted by a pediatric neurologist using Bayley scales of infant development-II and standardized Child development Inventory investigation when Bayley investigation was unavailable. Corpus callosum anomalies were diagnosed in 148 cases during the study period, 62 (41.9%) of which were excluded due to complete agenesis, remaining 86 fetuses with partial agenesis (58.1). In 20 cases partial agenesis (23.2%) was isolated whereas 66 (76.7%) presented with different malformations in which 29 cases (43.9 %) were only CNS lesions, 21 cases (31.8 %) were non CNS lesions and in 16 cases (24.3%) a combination of CNS and non CNS lesions was found. The mean gestational age at diagnosis for isolated and non-isolated cases was comparable: 24.29 (SD 5.05) and 24.71 (SD 5.35) weeks respectively. Of the 86 pregnancies with partial agenesis, 46 patients opted for termination of pregnancy .Neurological follow-up was available for 35 children. The overall neurological outcome was normal in 21/35 children (60%); 3/35 (8.6%) showed mild, and 6/35 (17.1%) moderate impairment. The remaining 5/35 (14.3%) had a severe impairment. The median duration of follow-up for the isolated form was 45.6 months (range 36-52 months) and 73.3 months (range 2-138 months) for non-isolated form. Partial corpus callosum agenesis should be accurately investigated by neurosonography and fetal MRI to describe its morphology and associated anomalies. Genetic anomalies are frequently present in non-isolated cases. Efforts must be taken to improve ultrasound diagnosis of partial agenesis and confirmation of its isolated nature in order to enhance parental counseling. Although children with prenatal diagnosis of isolated agenesis have favorable prognosis later in life in 60%, they have often mild to severe disabilities including speech disorders at school age and behavior and motor deficit disorders that can emerge at a later age.

Associations between serum taurine concentrations in mothers and neonates and the children’s anthropometrics and early neurodevelopment: Results from the Seychelles Child Development Study, Nutrition Cohort 2

BackgroundHigh concentrations of taurine are present in the developing human brain and maternal breast milk. Taurine is thought to influence fetal growth and brain development based on experimental rodent studies. As fish is an important dietary source of taurine, we investigated associations between taurine concentrations and child outcomes in a high fish consuming population. ObjectiveTo examine associations between maternal and cord serum taurine concentrations and birth anthropometric measures and cognitive development in children at 20 months of age. MethodsPregnant women were recruited between 2008 and 2011 as part of Nutrition Cohort 2 (NC2) of the Seychelles Child Development Study (SCDS). Maternal taurine serum concentrations were measured at 28 week’s gestation and in cord serum. Child weight, length and head circumference were measured at birth and neurodevelopment was assessed using Bayley Scales of Infant Development II (BSID-II) at 20 months of age. Associations between taurine status, birth measures and neurodevelopmental outcomes were examined (n = 300) using regression models and adjusted for relevant covariates. ResultsMean (SD) maternal and cord taurine concentrations were 124.9 (39.2) µmol/L (range 28.2–253.9 µmol/L) and 187.6 (60.0) µmol/L (range 55.0–417.4 µmol/L) respectively. We found no associations between maternal taurine concentrations and child anthropometric and neurodevelopmental measures (weight β = −0.001, SE=0.001; length β = −0.006, SE=0.006; head circumference β = −0.002, SE=0.002; MDI β = −0.005, SE=0.015; PDI β = −0.004, SE=0.016; all P > 0.05), or between cord taurine concentrations and outcomes (weight β = −0.001, SE<0.000; length β = −0.001, SE=0.004; head circumference β < 0.000, SE=0.002; MDI β = 0.004, SE=0.010; PDI β = −0.015, SE=0.012; all P > 0.05). ConclusionThe Seychellois population have high maternal and cord taurine concentrations owing to their high fish intake and may be considered taurine replete compared to individuals who consume a Westernised diet. This high taurine status may explain why there were no significant associations between maternal and cord taurine concentrations and outcomes after adjusting for covariates.

Safety and Efficacy of Allogeneic Umbilical Cord Blood Therapy for Global Development Delay and Intellectual Disability.

Most pediatric patients with global developmental delay (GDD) or intellectual disability (ID) have disrupted development. Since allogeneic umbilical cord blood (UCB) may exert neurotrophic effects, a prospective clinical trial was conducted to assess the efficacy and safety of UCB therapy for GDD and ID. A total of 13 children (ages 23-149 months) with GDD and ID were enrolled and followed up for 12 months. Under criteria of histocompatibility and cell number, allogeneic UCB units were selected and infused once intravenously, and adverse events were monitored. The Bayley Scale of Infant Development-II (BSID-II) was used as primary outcome measurement tool, and evaluations for various functional abilities were also implemented. Safety assessment did not reveal significant adverse effects. Functional improvements in mental and motor developments along with daily living activities and languages were observed at 12 months postintervention compared with the baseline abilities (P < 0.05). Furthermore, mental developmental quotient derived from BSID-II mental scale revealed significantly facilitated improvement during the first 3 months (P < 0.05). In the survey conducted 80.7 ± 13.0 months after UCB infusion to assess satisfaction and long-term safety, no long-term adverse effects were reported, and 70% of the guardians reported satisfaction with the UCB infusion. Long-term changes in two patients who were regularly followed up beyond the study completion were noticeable. One case observed for 4 years showed dramatic improvement until 12 months after UCB therapy, whereas she showed insignificant improvement beyond 12 months after the therapy. Another case showed alleviation of autism with findings of anti-inflammatory response in his peripheral blood after UCB infusion. This clinical study provides support for further applications of UCB as a therapeutic avenue for children with GDD or ID owing to its safety and partial efficacy. Due to patient heterogeneity, further studies focusing on specific clinical manifestations and etiologies are required. Registered at www.clinicaltrials.gov (NCT01769716).

Alcohol-related dysmorphic features as predictors of neurodevelopmental delay in infants and preschool-aged children: Results from a birth cohort in Ukraine.

Cardinal and non-cardinal dysmorphic features are associated with prenatal alcohol exposure (PAE); however, their association with neurodevelopment is less clear. The objective of this study was to determine whether alcohol-related dysmorphic features predict neurodevelopmental delay in infants and toddlers. We analyzed a prospective pregnancy cohort in western Ukraine enrolled between 2008 and 2014. A dysmorphology examination comprising body size and three cardinal and 14 non-cardinal dysmorphic features was performed at approximately 6 to 12 months of age. PAE was self-reported and operationalized as absolute ounces of alcohol per day around the time of conception. Neurodevelopment was assessed at 6 to 12 months with the Bayley Scales of Infant Development-II (BSID-II), and at 3.5 to 4.5 years of age with the Differential Ability Scales-II, the Child Behavior Checklist, and multiple measures that were used to create an executive functioning factor score. We performed logistic regression to predict children's neurodevelopment from dysmorphic features, growth measures, sex, and PAE. From an analytic sample of 582 unique children, 566 had BSID-II scores in infancy, and 289 completed the preschool battery. Models with all cardinal and non-cardinal dysmorphic features, growth measures, sex, and PAE performed better than models with subsets of those inputs. In general, models had poor performance classifying delays in infancy (area under the curve (AUC) <0.7) and acceptable performance on preschool-aged outcomes (AUC ~0.75). When the sample was limited to children with moderate-to-high PAE, predictive ability improved on preschool-aged outcomes (AUC 0.76 to 0.89). Sensitivity was relatively low for all models (12% to 63%), although other metrics of performance were higher. Predictive analysis based on dysmorphic features and measures of growth performed modestly in this sample. As these features are more reliably measured than neurodevelopment at an earlier age, the inclusion of dysmorphic features and measures of growth in predictive models should be further explored and validated in different settings and populations.

Sex-specific associations between prenatal exposure to phthalates and neurocognitive development in Taiwanese children: Application of environmental mixture methods to small study sample

BACKGROUND AND AIM: Few studies have examined the sex-specific effect of phthalates as a mixture by applying multiple mixture methods to a small study sample. This study, therefore, examined sex-specific associations of prenatal exposure to urinary phthalates with neurocognitive development in Taiwanese children aged two to three years old. METHODS: The study included 127 children who were followed up at the ages two-three years in the Taiwanese Maternal and Infant Cohort Study. The Mental Development Index (MDI) and Psychomotor Development Index (MDI) were measured in children using the Bayley Scales of Infant Development-II (BSID-II). The monomethyl phthalate, monoethyl phthalate, mono-butyl phthalate (MBP), mono-benzyl phthalate, mono-2-ethylhexyl phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate, mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) were measured in urine samples collected from mothers during pregnancy. Multivariable linear regression (MLR), Weighted Quantile Sum (WQS) regression, quantile g-computation (qgcom), Bayesian Kernel Machine Regression (BKMR), the Super Learner with g-computation were applied and compared to examine the sex-specific effects of the phthalate mixture on MDI and PDI. RESULTS: The mediation MDI and PDI were 94.0 and 99.0, respectively. The spearman correlation ranged between -0.01 and 0.74. None of these methods could detect any sex-specific associations between phthalates and MDI. Results suggest that WQS and qgcomp were able to detect inverse associations between phthalates and PDI with a stronger effect in boys. BKMR and Super Learner with g-computation were unable to detect any precise associations of phthalates with PDI. However, mixture methods detected mixtures&amp;#x27; negative directionality and linear dose-response effects on neurocognitive development. MBP, MEHP, and MEOHP dominated these associations with PDI. CONCLUSIONS: Mixture methods outperformed MLR. However, flexible approaches like BKMR and Super Learner with g-computation may perform better with larger samples. Therefore, the study recommends using multiple mixtures methods for getting comprehensive results from mixture studies. KEYWORDS: Mixture; Neurodevelopment; WQS; BKMR; G-computation

Factors associated with neurodevelopmental impairment in preterm infants with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a common and serious complication in preterm infants with very low birth weight and is known to lead to poor neurodevelopmental outcomes. This study aimed to identify factors associated with neurodevelopmental impairment (NDI) in patients with moderate to severe BPD. A total of 83 preterm infants born between 24- and 29-weeks' gestation who were admitted to the neonatal intensive care unit and developed moderate/severe BPD between 2013 and 2017 were retrospectively evaluated. Developmental assessment was performed at 18 to 24 months of corrected age using the Bayley Scales of Infant Development II (BSID-II). Patients with NDI (n=41) and without NDI (n=42) were compared. BSID-II Mental Development Index and Psychomotor Development Index scores were 87±11 and 83±8 in the non-NDI group and 57±12 and 52±8 in the NDI group, respectively (p<0.001). The NDI group had significantly lower birth weight (847±174 vs. 1012±192 g) and gestational age (26.1±1.3 and 27.6±1.6 weeks) compared to the non-NDI group (p<0.001). Intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, exposure to steroids, duration of respiratory support, and length of hospital stay were significantly higher in the NDI group (p<0.001). Many of the conditions in this study were found to be associated with poor neurodevelopmental outcomes in patients with BPD, such as prolonged respiratory support, prolonged hospitalization, intraventricular hemorrhage, retinopathy, and steroid therapy, can be avoided or prevented with strict protocols and prevention strategies. Appropriate management of comorbid risk factors may help prevent poor neurodevelopmental outcomes.

Mortality and Long-Term Outcome of Neonates with Congenital Heart Disease and Acute Perinatal Stroke: A Population-Based Case-Control Study

Objective: Neonates with congenital heart disease (CHD) and perinatal stroke have high mortality and survivors are at risk for poor long-term neurodevelopmental outcome. The aim of this study was to assess the risk factors and outcome of neonates with both CHD and MRI-confirmed perinatal stroke (Study Group) and compare those to the risk factors and outcome of infants matched for CHD without stroke (Control-1) and of infants matched for MRI-confirmed stroke without CHD (Control-2). Methods: We conducted a population-based case-control study enrolling 28 term neonates with CHD and MRI-confirmed acute perinatal stroke born between 2007–2017 in the Central-Hungarian Region. Each of the control groups included 56 infants. The Bayley Scales of Infant Development-II, the Brunet-Lézine test and the Binet Intelligence scales-V were used for neurodevelopmental follow-up at a median age of 61 months. Results: Mortality was highest in the Study Group (25% compared to 5% and 2%, respectively, p = 0.001). Adverse neurodevelopmental outcome was prevalent in the Study (53%) and Control-2 Groups (52%, p = 0.03). Significantly different parameters among the three groups included Apgar scores, mode of delivery, gestational age at birth, cardiac interventions and twin pregnancy. In a multivariable regression analysis adjusted for clinically relevant parameters, patients in the Study Group had significantly higher odds for mortality compared to patients in the Control-1 Group (OR: 6.5 95% CI: 1.1–39.4). Conclusions: Neonates with perinatal stroke and CHD are at a higher risk for dying compared to neonates with CHD without stroke. In addition, the stroke-associated direct insult to the brain likely plays an important role in the development of neurodevelopmental morbidity in these patients.

The Effect of Size and Asymmetry at Birth on Brain Injury and Neurodevelopmental Outcomes in Congenital Heart Disease

Poor and asymmetric fetal growth have been associated with neonatal brain injury (BI) and worse neurodevelopmental outcomes (NDO) in the growth-restricted population due to placental insufficiency. We tested the hypothesis that postnatal markers of fetal growth (birthweight (BW), head circumference (HC), and head to body symmetry) are associated with preoperative white matter injury (WMI) and NDO in infants with single ventricle physiology (SVP) and d-transposition of great arteries (TGA). 173 term newborns (106 TGA; 67 SVP) at two sites had pre-operative brain MRI to assess for WMI and measures of microstructural brain development. NDO was assessed at 30 months with the Bayley Scale of Infant Development-II (n = 69). We tested the association between growth parameters at birth with the primary outcome of WMI on the pre-operative brain MRI. Secondary outcomes included measures of NDO. Newborns with TGA were more likely to have growth asymmetry with smaller heads relative to weight while SVP newborns were symmetrically small. There was no association between BW, HC or asymmetry and WMI on preoperative brain MRI or with measures of microstructural brain development. Similarly, growth parameters at birth were not associated with NDO at 30 months. In a multivariable model only cardiac lesion and site were associated with NDO. Unlike other high-risk infant populations, postnatal markers of fetal growth including head to body asymmetry that is common in TGA is not associated with brain injury or NDO. Lesion type appears to play a more important role in NDO in CHD.

Extremely low birth weight infant surviving left congenital diaphragmatic hernia: a case report

In this study, we present the case of a 900 g, male infant born at 27+5 weeks, who was placed on high frequency oscillatory ventilation (HFOV) until repair of a left congenital diaphragmatic hernia (CDH) at 39 days of life (DOL). To date, this is the smallest infant with repair of the left CDH reported in the literature. After birth, he passed the cardiopulmonary stabilization phase and successfully underwent delayed surgery; in the process, he received ventilator assistance through HFOV. He weighed 1,660 gm at the time of surgery. We performed the thoracoscopic primary closure of the diaphragmatic defect. He was extubated on post-operation day (POD) 7 and discharged from hospital on POD 36 with 0.1 L/min supplemental oxygen via nasal cannula. He is being followed for growth and development and there has been no recurrence at the surgical site at 24 months of corrected age. In this case, high mean airway pressure (MAP) was required based on the patient’s weight to achieve adequate recruitment of the left lung, and the patient was diagnosed with mental developmental delay on Bayley Scales of Infant Development-II. Thus, we suggest that the postnatal course and long-term outcomes for extremely low birth weight (ELBW) and preterm infants with left CDH is different from that for full-term babies. Therefore, future research should focus on preterm infants with left CDH.

The role of early-onset-sepsis in the neurodevelopment of very low birth weight infants

AimsThe study investigated a putative association between early-onset-sepsis (EOS) and poor neurodevelopmental outcomes at 2 years corrected age in very low birth weight infants.MethodsThis was a single-center cohort study on infants weighing less than 1500 g with a gestational age below 35 weeks at birth born between 2008 and 2011. Neurodevelopmental outcomes were assessed at follow-up with the Bayley Scales of Infant Development-II. EOS was defined as either culture-proven EOS or clinical EOS using blood culture, CrP levels, and clinical symptoms and treatment. Neurodevelopmental impairment (NDI) was defined as one or more of the following: Mental Developmental Index (MDI) and/or Psychomotor Developmental Index (PDI) scores lower than 70; presence of cerebral palsy.ResultsOf 405 eligible newborns in the study period 166 were included. Two had culture-proven and 29 clinical EOS. Median MDI scores in patients with EOS were 96 (IQR: 86–106) and in the control group 94 (84–106, p = 0.77). PDI scores in patients with EOS were 96 (86–106) and in the control group 99,5 (92–103, p = 0.03). Of infected patients 7/31 (24%) showed NDI as defined, whereas only 11/135 (8%) showed NDI in the control group (OR 3.3, p = 0.03). Multiple regression analyses identified chorioamnionitis and poor CRIB-Scores as individual risk factors for MDI or PDI values < 70.ConclusionIn our study, EOS among VLBW-infants significantly impaired the neurodevelopment at 2 years corrected age. As shown in previous reports infection continues to be a problem and strategies for a reduction need further improvement.

The role of brain territorial involvement and infection/inflammation in the long-term outcome of neonates with arterial ischemic stroke: A population-based cohort study

BackgroundNeonatal arterial ischemic stroke (NAIS) carries the risk of significant long-term neurodevelopmental burden on survivors. AimsTo assess the long-term neurodevelopmental outcome of term neonates diagnosed with NAIS and investigate the associations among brain territorial involvement on MRI, clinical risk factors and neurodevelopmental outcomes. Study designPopulation-based cohort study. SubjectsSeventy-nine term neonates with NAIS confirmed by MRI born between 2007 and 2017. Outcome measuresLong-term neurodevelopmental outcome assessed using the Bayley Scales of Infant Development-II, the Brunet-Lézine test and the Binet Intelligence scales-V. ResultsFollow-up was available in 70 (89%) of the subjects enrolled, at a median age of 60 months [IQR: 35–84]. Normal neurodevelopmental outcome was found in 43% of the patients. In a multivariable model, infants with main MCA stroke had an increased risk for overall adverse outcome (OR: 9.1, 95% CI: 1.7–48.0) and a particularly high risk for cerebral palsy (OR: 55.9, 95% CI: 7.8–399.2). The involvement of the corticospinal tract without extensive stroke also increased the risk for cerebral palsy/fine motor impairment (OR: 13.5, 95% CI: 2.4–76.3). Multiple strokes were associated with epilepsy (OR: 9.5, 95% CI: 1.0–88.9) and behavioral problems (OR: 4.4, 95% CI: 1.1–17.5) and inflammation/infection was associated with cerebral palsy (OR: 9.8, 95% CI: 1.4–66.9), cognitive impairment (OR: 9.2, 95% CI: 1.8–47.8) and epilepsy (OR: 10.3, 95% CI: 1.6–67.9). ConclusionsMain MCA stroke, involvement of the corticospinal tract, multiple strokes and inflammation/infection were independent predictors of adverse outcome, suggesting that the interplay of stroke territorial involvement and clinical risk factors influence the outcome of NAIS.

Risk Factors of Growth Retardation and Developmental Deficits in Very Preterm Infants in a German Tertiary Neonatal Unit.

Over the last two decades, improvements in perinatology have led to increased survival rates of preterm infants. A large number of studies and meta-analyses have investigated of preterm infants and/or the influence of developmental care. However, the combined influence of the most frequent risk factors and developmental care on the long-term somatic, motor, and cognitive outcome of preterm infants remains unclear. This retrospective, single-center cohort study includes 256 children treated in a tertiary neonatal intensive care unit in Rostock, Germany, between 2008 and 2013. Follow-up examinations (somatic, psychomotor, and mental development) were performed at (corrected) 24 months using Bayley Scales of Infant Development II (BSID-II). Developmental care was carried out according to the legal framework and national guidelines (physiotherapy and/or early education). Bronchopulmonary dysplasia (BPD) and an exclusive formula feeding showed a 2.8–4.6-fold higher risk (95% Confidence Interval: Mental Developmental Index 1.73–7.58; Psychomotor Developmental Index 1.44–14.54; body length 1.20–6.41) for developmental deficits (mental and psychomotor developmental index; body length). Developmental care after discharge according to national guidelines did not prevent this. Since this is a retrospective pilot study, no recommendations can be made based on this analysis. Therefore, future research should evaluate whether standard developmental care should be extended by tailored measures depending on individual risk factors.

Is Developmental Screening Enough in High-Risk Populations?

In this issue of Pediatrics, Sananes et al1 leverage the Pediatric Heart Network Single Ventricle Reconstruction Trial to describe developmental and behavioral concerns in a cohort of children with hypoplastic left heart syndrome and related single right ventricle conditions. The Pediatric Heart Network recognized the importance of conducting developmental screening as recommended by the American Academy of Pediatrics (AAP)2,3 in this population at high risk for neurodevelopmental concerns.The researchers evaluate how well a diagnostic developmental evaluation at 14 months of age, with the Bayley Scales of Infant Development-II,4 and developmental screening at 3, 4, and 5 years of age, with the Ages & Stages Questionnaire (ASQ),5 predicted the outcome of “developmental functioning” as measured by the Adaptive Score on the Behavior Assessment System for Children-2 (BASC-2)6 at 6 years of age.There were some correlations between early developmental evaluations and later outcomes at age 6 years, such as a “failure” (scoring 2 SDs below the mean) on the Psychomotor Developmental Index of the Bayley Scales of Infant Development-II at age 14 months having a relatively good sensitivity (0.79) to identify lower adaptive skills at 6 years of age. In general, however, researchers in this study found that scores on the Bayley Scales of Infant Development-II at 14 months had a low positive predictive value for the BASC-2 Adaptive Scores at age 6 years. Some domains of the ASQ, including the personal-social, problem-solving, and communication scales, were correlated with 6-year-old BASC-2 Adaptive Scores, with “fail” ratings for problem-solving and personal-social domains at age 4 to 5 years having PPVs ranging from 75 to 93. Additionally, rates of parent-reported behavior problems on the BASC-2 were significantly higher at age 6 than at younger ages.It is helpful to understand specific domains and tasks that assessment tools measure. The BASC-2 is a broad-based behavioral rating scale and measures different constructs than the Bayley Scales of Infant Development-II and ASQ and differs from other measures of adaptive functioning.A signature developmental profile described in children with congenital heart disease (CHD) involves a “low severity, high prevalence” pattern of deficits.7 Thus, children may have mild deficits across numerous domains of development and behavior that subsequently culminate in impairments in day-to-day functioning. More subtle challenges in attention regulation and executive functioning are common in children with CHD and may not present functional impact until school-age. These concepts underscore the importance of in depth, multidisciplinary diagnostic evaluations at critical time points in development as recommended in the AAP-approved American Heart Association scientific statement on neurodevelopmental evaluation and treatment7 and guidelines for incorporating formal neurodevelopmental follow-up programs into cardiac care.8 Targeted neurodevelopmental evaluations should be conducted in addition to ongoing AAP-recommended developmental screening and surveillance for all children.2,3In this study, it was reassuring that more than three-quarters of children who passed the ASQ screening at younger ages subsequently scored within the average range on BASC-2 at age 6 years. Authors of this study raise important issues about developmental screening, surveillance, and evaluation in children with CHD as well as other high-risk pediatric populations, including those with conditions and risk factors associated with neurologic injury and developmental delay or disability). These issues include the following:The work of Sananes et al1 has implications for pediatric and surgical specialties. Implementing developmental screening within populations known to be at high risk can serve as a touchpoint to discuss developmental implications of chronic diseases as well as offer hope and support. When children have been diagnosed with developmental delays or are known to be at risk for delays, a proactive developmental support approach is important. A blended approach including developmental surveillance, screening, and diagnostic evaluations is logical. Unlike with many medical conditions, a named diagnosis is not required for a child to access and benefit from developmental interventions such as physical, occupational, and speech-language therapy and Part C Early Intervention programming.

Maternal Cadmium Exposure and Neurobehavior in Children up to Age 8 Years: The HOME Study

Background: It is unclear whether cadmium (Cd) exposure during fetal brain development is associated with child neurobehavior. This study examined the potential associations between Cd exposure during pregnancy and neurobehavior among children. Methods: We used data from 276 children in the Health Outcomes and Measures of the Environment (HOME) Study, a well-established prospective pregnancy and birth cohort. We measured maternal urinary Cd concentrations at 26 weeks of gestation. For cognitive function, we assessed Mental Development Index (MDI) and Full-Scale Intelligence Quotient (FSIQ) using the Bayley Scales of Infant Development-II, the Wechsler Preschool and Primary Scales of Intelligence-III, or the Wechsler Intelligence Scales for Children-IV at ages 1, 2, 3, 5, and 8 years. We assessed child behaviors using the Behavior Assessment System for Children-2 at ages 2, 3, 4, 5, and 8 years, yielding four composite measures: Externalizing Problems, Internalizing Problems, Behavioral Symptoms Index, and Adaptive Skills. We used linear mixed models with covariate adjustment to estimate the associations between maternal urinary Cd concentrations and child neurobehavior. Results: We categorized study participants into three groups based on maternal urinary Cd concentrations (Group 1: &lt; limit of detection (LOD), Group 2: 0.06-0.22 μg/g creatinine, Group 3: &gt;0.22-1.73 μg/g creatinine). In linear mixed models adjusting for maternal and child characteristics, maternal urinary Cd levels were not significantly associated with cognitive function at ages 1, 2, 3, 5, and 8 years or with behavioral composite measures at 2, 3, 4, 5, and 8 years. Conclusions: No significant associations were observed between maternal urinary Cd and cognitive or behavioral measures in children at 1 to 8 years of age in this study.

Household interventions for secondary prevention of domestic lead exposure in children.

Lead exposure is a serious health hazard, especially for children. It is associated with physical, cognitive and neurobehavioural impairment in children. There are many potential sources of lead in the environment, therefore trials have tested many household interventions to prevent or reduce lead exposure. This is an update of a previously published review. To assess the effects of household interventions intended to prevent or reduce further lead exposure in children on improvements in cognitive and neurobehavioural development, reductions in blood lead levels and reductions in household dust lead levels. In March 2020, we updated our searches of CENTRAL, MEDLINE, Embase, 10 other databases and ClinicalTrials.gov. We also searched Google Scholar, checked the reference lists of relevant studies and contacted experts to identify unpublished studies. Randomised controlled trials (RCTs) and quasi-RCTs of household educational or environmental interventions, or combinations of interventions to prevent lead exposure in children (from birth to 18 years of age), where investigators reported at least one standardised outcome measure. Two authors independently reviewed all eligible studies for inclusion, assessed risk of bias and extracted data. We contacted trialists to obtain missing information. We assessed the certainty of the evidence using the GRADE approach. We included 17 studies (three new to this update), involving 3282 children: 16 RCTs (involving 3204 children) and one quasi-RCT (involving 78 children). Children in all studies were under six years of age. Fifteen studies took place in urban areas of North America, one in Australia and one in China. Most studies were in areas with low socioeconomic status. Girls and boys were equally represented in those studies reporting this information. The duration of the intervention ranged from three months to 24 months in 15 studies, while two studies performed interventions on a single occasion. Follow-up periods ranged from three months to eight years. Three RCTs were at low risk of bias in all assessed domains. The other 14 studies were at unclear or high risk of bias; for example, we considered two RCTs and one quasi-RCT at high risk of selection bias and six RCTs at high risk of attrition bias. National or international research grants or governments funded 15 studies, while the other two did not report their funding sources. Education interventions versus no intervention None of the included studies in this comparison assessed effects on cognitive or neurobehavioural outcomes, or adverse events. All studies reported data on blood lead level outcomes. Educational interventions showed there was probably no evidence of a difference in reducing blood lead levels (continuous: mean difference (MD) -0.03, 95% confidence interval (CI) -0.13 to 0.07; I² = 0%; 5 studies, 815 participants; moderate-certainty evidence; log-transformed data), or in reducing floor dust levels (MD -0.07, 95% CI -0.37 to 0.24; I² = 0%; 2 studies, 318 participants; moderate-certainty evidence). Environmental interventions versus no intervention Dust control: one study in this comparison reported data on cognitive and neurobehavioural outcomes, and on adverse events in children. The study showed numerically there may be better neurobehavioural outcomes in children of the intervention group. However, differences were small and the CI included both a beneficial and non-beneficial effect of the environmental intervention (e.g. mental development (Bayley Scales of Infant Development-II): MD 0.1, 95% CI -2.1 to 2.4; 1 study, 302 participants; low-certainty evidence). The same study did not observe any adverse events related to the intervention during the eight-year follow-up, but observed two children with adverse events in the control group (1 study, 355 participants; very low-certainty evidence). Meta-analysis also found no evidence of effectiveness on blood lead levels (continuous: MD -0.02, 95% CI -0.09 to 0.06; I² = 0%; 4 studies, 565 participants; moderate-certainty evidence; log-transformed data). We could not pool the data regarding floor dust levels, but studies reported that there may be no evidence of a difference between the groups (very low-certainty evidence). Soil abatement: the two studies assessing this environmental intervention only reported on the outcome of 'blood lead level'. One study showed a small effect on blood lead level reduction, while the other study showed no effect. Therefore, we deem the current evidence insufficient to draw conclusions about the effectiveness of soil abatement (very low-certainty evidence). Combination of educational and environmental interventions versus standard education Studies in this comparison only reported on blood lead levels and dust lead levels. We could not pool the studies in a meta-analysis due to substantial differences between the studies. Since the studies reported inconsistent results, the evidence is currently insufficient to clarify whether a combination of interventions reduces blood lead levels and floor dust levels (very low-certainty evidence). Based on available evidence, household educational interventions and environmental interventions (namely dust control measures) show no evidence of a difference in reducing blood lead levels in children as a population health measure. The evidence of the effects of environmental interventions on cognitive and neurobehavioural outcomes and adverse events is uncertain too. Further trials are required to establish the most effective intervention for reducing or even preventing further lead exposure. Key elements of these trials should include strategies to reduce multiple sources of lead exposure simultaneously using empirical dust clearance levels. It is also necessary for trials to be carried out in low- and middle-income countries and in differing socioeconomic groups in high-income countries.

General anesthesia for cesarean delivery and childhood neurodevelopmental and perinatal outcomes: a secondary analysis of a randomized controlled trial

BackgroundIn 2016, the U.S. Food and Drug Administration expressed concern that neurodevelopment may be negatively affected by anesthesia or sedation exposure in pregnancy or before three years of age. We examined the association between general anesthesia at the time of cesarean delivery and early childhood neurodevelopment. MethodsA secondary analysis of a multicenter randomized controlled trial assessing magnesium for prevention of cerebral palsy in infants at risk for preterm delivery. Exposure was general compared to neuraxial anesthesia. The primary outcome was motor or mental delay at two years of age, assessed by Bayley Scales of Infant Development II (BSIDII). Secondary outcomes included BSIDII subdomains and perinatal outcomes. Multivariable logistic regression models were performed to control for confounders. ResultsOf 557 women undergoing cesarean delivery, 119 (21%) received general anesthesia. There were no differences in the primary composite outcome of developmental delay (aOR 0.93, 95% CI 0.61 to 1.43) or the BSIDII subdomains of mild, moderate, or severe mental delay, or mild or moderate motor delay. Severe motor delay was more common among infants exposed to general anesthesia (aOR 1.98, 95% CI 1.06 to 3.69). Infants exposed to general anesthesia had longer neonatal intensive care stays (51 vs 37 days, P=0.010). ConclusionsGeneral anesthesia for cesarean delivery was not associated with overall neurodevelopmental delay at two years of age, except for greater odds of severe motor delay. Future studies should evaluate this finding, as well as the impact on neurodevelopment of longer or multiple anesthetic exposures across all gestational ages.

Maternal cadmium exposure and neurobehavior in children: The HOME study

BackgroundIt is unclear whether cadmium (Cd) exposure during fetal brain development is associated with child neurobehavior. ObjectiveTo examine the potential associations between Cd exposure during pregnancy and neurobehavior among children. MethodsWe used data from 276 children in the Health Outcomes and Measures of the Environment (HOME) Study, a well-established prospective pregnancy and birth cohort. We measured maternal urinary Cd concentrations at 26 weeks of gestation. For cognitive function, we assessed Mental Development Index (MDI) and Full-Scale Intelligence Quotient (FSIQ) using the Bayley Scales of Infant Development-II, the Wechsler Preschool and Primary Scales of Intelligence-III, or the Wechsler Intelligence Scales for Children-IV at ages 1, 2, 3, 5, and 8 years. We assessed child behaviors using the Behavior Assessment System for Children-2 at ages 2, 3, 4, 5, and 8 years, yielding four composite measures: Externalizing Problems, Internalizing Problems, Behavioral Symptoms Index, and Adaptive Skills. We used linear mixed models with covariate adjustment to estimate the associations between maternal urinary Cd concentrations and child neurobehavior. ResultsWe categorized study participants into three groups based on maternal urinary Cd concentrations (Group 1: < limit of detection (LOD), Group 2: 0.06-0.22 μg/g creatinine, Group 3: ＞0.22 μg/g creatinine). In linear mixed models adjusting for maternal and child characteristics, maternal urinary Cd levels were not significantly associated with cognitive function at ages 1, 2, 3, 5, and 8 years or with behavioral composite measures at 2, 3, 4, 5, and 8 years. ConclusionsNo significant associations were observed between maternal urinary Cd and cognitive or behavioral measures in children at 1–8 years of age in this study.

Neurodevelopmental effect of intracranial hemorrhage observed in hypoxic ischemic brain injury in hypothermia-treated asphyxiated neonates - an MRI study

BackgroundIdentification of early signs of hypoxic ischemic encephalopathy (HIE) with magnetic resonance imaging (MRI) has proven of prognostic significance. Yet, the importance of intracranial hemorrhage (ICH), being present concomitantly had not been investigated yet, despite the known influence of hypothermia on hemostasis. We aimed to determine whether presence of ICH on MRI alongside the signs of HIE have an impact on prognosis in neonates with the clinical diagnosis of HIE.MethodsA retrospective study of consecutively sampled 108 asphyxiated term infants admitted to a tertiary neonatal intensive care unit (between 2007 and 2016), treated with whole body hypothermia and having brain MRI within 1 week of life was conducted. Presence or absence of HIE signs on MRI (basal ganglia-thalamus, watershed pattern and total brain injury) and on MR spectroscopy (lactate peak with decreased normal metabolites measured by Lac/NAA ratio) and/or of the five major types of ICH were recorded. Neurodevelopmental outcome was measured with Bayley Scales of Infant Development-II (BSID-II) test. Death or abnormal neurodevelopment (BSID-II score < 85) was defined as poor outcome in Chi-square test. Multivariate logistic regression analysis was performed on survivors.ResultsMRI and MR-spectroscopy (MRS) signs of HIE were present in 72% (n = 78). 36% (n = 39) of neonates had ICH, being mainly small in size. Chi-square test showed a relationship between neurodevelopmental outcome and initial MRI. Unadjusted logistic regression showed that neonates presenting MRI and MRS signs of HIE have 6.23 times higher odds for delayed mental development (OR = 6.2292; CI95% = [1.2642; 30.6934], p = 0.0246), than infants without imaging alterations; with no ICH effect on outcome. Adjustment for clinical and imaging parameters did not change the pattern of results, i.e. HIE remained an independent risk factor for delayed neurodevelopment (OR = 6.2496; CI95% = [1.2018; 32.4983], p = 0.0294), while ICH remained to have no significant effect.ConclusionHIE related MRI abnormalities proved to be important prognostic factors of poor outcome in cooled asphyxiated infants when present, suggesting that early MRI with MRS is beneficial for prognostication. Interestingly, ICHs present in about one third of all cases had no significant effect on neurodevelopmental outcome, despite the known hemostasis altering effects of hypothermia.