Bayley Scales Of Infant Development Research Articles

The effects of early rehabilitation in high-risk infants with brain injury: a systematic review and meta-analysis.

BackgroundA meta-analysis was conducted to examine the effects of early rehabilitation on the incidence of sequelae and associated disabilities in high-risk infants with brain injury.MethodsEnglish and Chinese medical databases including PubMed, Web of Science and Embase, China National Knowledge Infrastructure (CNKI) and Wanfang database, were search from 2005 to 2020 for relevant studies related to rehabilitation in high-risk children with brain injury. Patients who received basic treatment combined with early rehabilitation after brain injury formed the treatment group, and infants who only received basic treatment were considered the control group. The data were statistically analyzed using Stata16.0 analysis software.ResultsA total of 13 studies were included, involving 1,930 patients. Meta-analysis showed that the effective rate of early rehabilitation in the treatment of high-risk children with brain injury was significantly higher than that of the control group without early rehabilitation [odds ratio (OR) =4.98; 95% confidence interval (CI): 3.66 to 6.79]. Early rehabilitation also significantly improved patient adaptability [standardized mean difference (SMD) =0.632; 95% CI: 0.496 to 0.769], gross motor skills (SMD =0.971; 95% CI: 0.705 to 1.236), fine motor skills (SMD =0.904; 95% CI: 0.670 to 1.138), language skills (SMD =0.757; 95% CI: 0.483 to 1.030), and personal-social scores (SMD =0.786; 95% CI: 0.648 to 0.925) compared to patients in the control group. The mental development index (MDI) score (SMD =1.194; 95% CI: 0.839 to 1.549) and the psychomotor development index (PDI) score (SMD =0.973; 95% CI: 0.661 to 1.286) were significantly higher in the treatment group compared to the control group.DiscussionEarly rehabilitation therapy can improve the neuromotor and intellectual development in high-risk infants with brain injury.

Application Analysis of Accompanying Nursing Mode Combined with Health Education in Hyperbaric Oxygen Therapy for Infants with Hypoxic Ischemic Encephalopathy

To study application effect of accompanying nursing mode and health education on infants with hypoxic ischemic encephalopathy (HIE) treated with hyperbaric oxygen therapy (HBOT) via pure oxygen chamber. 124 cases of HIE infants treated with pure oxygen chamberHBOT admitted to our department (December 2018-December 2019) were chosen as the research samples, and split into experimental group and control group according to the order of admission, with 62 cases in each group. The control group received routine nursing while and the experimental group received accompanying nursing mode combined with health education to compare the mental development index (MDI), psychomotor development index (PDI), height, weight, neurological sequelae, efficacy and family members’ satisfaction with HBOT between the two groups. After nursing, MDI and PDI in experimental group were obviously higher compared with control group (P<0.001);After nursing, the height and weight indexes in experimental group were obviously higher compared with control group (P<0.05);After nursing, the total incidence of neurological sequelae in experimental group (3.2%) was obviously lower compared with control group (P<0.05);After nursing, the total number of effective infants in experimental group was obviously higher compared with control group (P<0.05);After nursing, the number of family members satisfied with HBOT in experimental group was obviously higher compared with control group (P<0.05).The accompanying nursing mode combined with health education can greatly improve clinical indicators of HIE infants treated with pure oxygen chamber HBOT, promote their physical and mental development, and then improve the satisfaction of the family members with pure oxygen chamber HBOT, which should be promoted and applied in clinical practice as a high-quality nursing mode.

Efficiency Evaluation of Neuroprotection for Therapeutic Hypothermia to Neonatal Hypoxic-Ischemic Encephalopathy.

Background: To evaluate the safety and neurological outcomes of therapeutic hypothermia to neonatal hypoxic-ischemic encephalopathy (HIE).Materials and Methods: Medical records of 61 neonates with moderate to severe HIE were retrospectively enrolled and divided into a therapeutic hypothermia group (n = 36) and conventional therapy group (n = 25).Results: No significant difference in the incidence of severe adverse events was found between the two groups. Minimum and maximum voltages of amplitude-integrated electroencephalography (aEEG) recording results showed statistically significant differences in therapeutic hypothermia group after 72 h. The neonatal behavioral neurological assessment (NBNA) on the 28th day after birth and Bayley Scales of Infant Development, second edition (BSID II) scores at 18 months old were significant higher in the therapeutic hypothermia group than the conventional therapy group.Conclusion: Therapeutic hypothermia for neonates with moderate to severe HIE improved the development of the nervous system in 0–18-month-old infants and showed a predominant role in reducing death and major neuron development-associated disabilities.

Cost-effectiveness and economic returns of group-based parenting interventions to promote early childhood development: Results from a randomized controlled trial in rural Kenya.

BackgroundEarly childhood development (ECD) programs can help address disadvantages for the 43% of children under 5 in low- and middle-income countries (LMICs) experiencing compromised development. However, very few studies from LMIC settings include information on their program’s cost-effectiveness or potential returns to investment. We estimated the cost-effectiveness, benefit–cost ratios (BCRs), and returns on investment (ROIs) for 2 effective group-based delivery models of an ECD parenting intervention that utilized Kenya’s network of local community health volunteers (CHVs).Methods and findingsBetween October 1 and November 12, 2018, 1,152 mothers with children aged 6 to 24 months were surveyed from 60 villages in rural western Kenya. After baseline, villages were randomly assigned to one of 3 intervention arms: a group-only delivery model with 16 fortnightly sessions, a mixed-delivery model combining 12 group sessions with 4 home visits, and a control group. At endline (August 5 to October 31, 2019), 1,070 children were retained and assessed for primary outcomes including cognitive and receptive language development (with the Bayley Scales of Infant Development, Third Edition) and socioemotional development (with the Wolke scale). Children in the 2 intervention arms showed better developmental outcomes than children in the control arm, although the group-only delivery model generally had larger effects on children. Total program costs included provider’s implementation costs collected during the intervention period using financial reports from the local nongovernmental organization (NGO) implementer, as well as societal costs such as opportunity costs to mothers and delivery agents. We combined program impacts with these total costs to estimate incremental cost-effectiveness ratios (ICERs), as well as BCRs and the program’s ROI for the government based on predictions of future lifetime wages and societal costs. Total costs per child were US$140 in the group-only arm and US$145 in the mixed-delivery arm. Because of higher intention-to-treat (ITT) impacts at marginally lower costs, the group-only model was the most cost-effective across all child outcomes. Focusing on child cognition in this arm, we estimated an ICER of a 0.37 standard deviation (SD) improvement in cognition per US$100 invested, a BCR of 15.5, and an ROI of 127%. A limitation of our study is that our estimated BCR and ROI necessarily make assumptions about the discount rate, income tax rates, and predictions of intervention impacts on future wages and schooling. We examine the sensitivity of our results to these assumptions.ConclusionsTo the best of our knowledge, this study is the first economic evaluation of an effective ECD parenting intervention targeted to young children in sub-Saharan Africa (SSA) and the first to adopt a societal perspective in calculating cost-effectiveness that accounts for opportunity costs to delivery agents and program participants. Our cost-effectiveness and benefit–cost estimates are higher than most of the limited number of prior studies from LMIC settings providing information about costs. Our results represent a strong case for scaling similar interventions in impoverished rural settings, and, under reasonable assumptions about the future, demonstrate that the private and social returns of such investments are likely to largely outweigh their costs.Trial registrationThis trial is registered at ClinicalTrials.gov, NCT03548558, June 7, 2018. American Economic Association RCT Registry trial AEARCTR-0002913.

Changes in cortical hemodynamics with the emergence of skilled motor ability in infants: An fNIRS study

The brain activity changes during infancy that underpin the emergence of functional motor skills, such as reaching and stepping, are not well understood. The current study used functional near-infrared spectroscopy (fNIRS) to examine the hemodynamic response across the frontal, mid-coronal plane (sensorimotor cortex) and external occipital protuberance (cerebellar cortex) regions of typically developing infants (5 to 13 months) during reach-to-grasp or supported treadmill stepping behaviour. Motor ability was assessed using the third edition of the Motor Subscale of the Bayley Scales of Infant Development (BSID-III). Infants with enhanced motor ability demonstrated greater oxy-hemoglobin (HbO) concentration in the contralateral anterior mid-coronal and frontal-dorsal areas during right-handed reach-to-grasp. During bilateral reaching behavior, infants with enhanced motor ability showed greater HbO increases in right frontal-dorsal regions and lower HbO increases in left anterior mid-coronal areas. In contrast, infants' motor ability was associated with changes in de-oxyhemoglobin (HbR) concentration in the ipsilateral anterior mid-coronal, contralateral frontal and left external occipital protuberance regions during left-handed reaching behavior. These relationships between upper limb hemodynamics and infant motor ability are consistent with increased lateralization and cognitive-motor coupling as motor skills emerge. During stepping behavior, infants with enhanced motor ability demonstrated smaller increases in HbR concentration in the bilateral external occipital protuberance region consistent with an emerging efficiency as cruising and independent stepping behavior is still nascent. Together, the current results identify several distinct neural markers of functional motor ability during infancy that may be relevant to diagnostic testing and rehabilitation of developmental movement disorders.

Multi-organ dysfunction scoring in neonatal encephalopathy (MODE Score) and neurodevelopmental outcomes.

Neonatal encephalopathy (NE) is associated with an increased risk of multi-organ injury. The lack of standardised definitions for multi-organ dysfunction in NE hinders accurate quantification of these complications. A simple multi-organ dysfunction in neonatal encephalopathy scoring (MODE) system was created to include the cardiovascular, respiratory, gastrointestinal, haematological and neurological systems with a maximum score of 15. The MODE score was then compared with the grade of NE, Bayley Scales of Infant Development (Bayley-III) at 2years of age and mortality. The Bayley score was used as it gave an objective score making it easier to compare the MODE score. Bayley score of <90 and/or abnormal MRI as an adverse outcome. Infants with perinatal asphyxia (PA:n=85) were prospectively enrolled (PA only n=9; NE I=23; NE II=42; NE III=11). Infants with higher MODE scores were significantly more likely to have moderate/severe NE (NE II/III: median scores (IQR) 7(5-10) versus mild NE 2 (1-3); p-value<0.001) The MODE score was highly predictive of mortality (AUC 0.96, p-value=0.002). Infants who had an abnormal neurological examination at discharge or abnormal Bayley-III scores had significantly higher MODE scores (p-value=0.001). Quantifying multi-organ injury is important to plan optimal early management and long-term follow-up. Additional use of clinical biomarkers may be useful as surrogate endpoints in future clinical trials and link to multi-organ longer-term developmental follow-up.

Long-term safety and clinical outcomes of intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A

IntroductionCurrently, there is no effective therapy for mucopolysaccharidosis IIIA (MPS IIIA). Intravenously-administered enzyme replacement therapies, while effective in other forms of MPS without neurological involvement, have not been successful in patients with MPS IIIA, as they are unable to cross the blood-brain barrier to improve neurological symptoms. We evaluated the long-term safety, tolerability, and clinical outcomes of recombinant human heparan-N-sulfatase (rhHNS) administered intrathecally (IT) in children with MPS IIIA in a phase 1/2 extension study. MethodsPatients aged ≥3 years with MPS IIIA who had previously completed a phase 1/2 study and received ≥5 of the 6 planned rhHNS infusions via IT administration, were eligible for inclusion. Patients who received 10 mg in the phase 1/2 study had their dose increased to 45 mg. Patients who were treated with 45 mg or 90 mg rhHNS IT in the phase 1/2 study remained on this monthly dose in the extension study. rhHNS was administered via an intrathecal drug delivery device (IDDD). Primary endpoints included the type and severity of adverse events, presence of anti-rhHNS antibodies in the CSF and serum, and changes in laboratory values. Secondary endpoints included standardized neurocognitive assessments and brain magnetic resonance imaging. ResultsIn the extension study, 12 patients with a mean (SD) age of 9.6 (7.3) years continued treatment with rhHNS IT for a median of 264.4 weeks. Ten of 12 patients completed the extension study. rhHNS IT was generally well-tolerated. All patients experienced at least one treatment-emergent adverse event (TEAE), most being mild or moderate in severity. No serious adverse events (SAEs) were considered related to the study drug, and no deaths occurred. Most SAEs were related to malfunctions of the IDDD. Declines from baseline in Bayley Scales of Infant Development, Third Edition or Kaufman Assessment Battery for Children, Second Edition, Nonverbal Index developmental quotient scores were evident at all rhHNS dosing groups: −17.97%, −18.99%, and −12.12% in the 10/45, 45, and 90 mg groups, respectively, at Month 54. ConclusionsOverall, rhHNS IT was well tolerated in the extension study. However, rhHNS IT was unable to slow the neurocognitive decline of patients with MPS IIIA. This study was subsequently terminated early because pre-specified efficacy criteria were not met, and the study did not yield clinical proof of concept. (Clinicaltrials.gov Identifier NCT01299727).

Consequences of using chronological age versus corrected age when testing cognitive and motor development in infancy and intelligence quotient at school age for children born preterm.

BackgroundChildren born preterm (<37 weeks’ gestation) have an increased risk of poor neurodevelopment, including lower intelligence quotient (IQ) scores compared with their term-born counterparts.ObjectiveTo explore the differences in psychometric scores for cognition and motor skills when they are age-standardized according to chronological age instead of corrected age for children born preterm.MethodsWe assessed = 554 children born <33 weeks’ gestation with the Bayley Scales of Infant Development, 2nd edition (mental and motor scores) at 18 months and the Weschler Abbreviated Scale of Intelligence (IQ score) at seven years of age. Scores were standardized according to chronological age and corrected age and differences between mean chronological and corrected scores were compared, along with the proportion of children whose scores could be classified as impaired.ResultsWhen scores were standardized according to chronological age instead of corrected age there was a large significant difference of 17.3 points on the mental scale (79.5 vs. 96.8, respectively) and 11.8 points on the motor scale (84.8 vs. 96.6, respectively) at 18 months. By seven years, the difference in IQ scores remained, although of a smaller magnitude at 1.9 points between mean chronological and corrected age scoring (97.2 vs. 99.1, respectively).ConclusionConsistent with previous literature, outcome assessments for preterm infants consistently differed according to use of chronological or corrected age to standardized scores. Cognitive scores were impacted more severely than motor scores, and differences were more substantial in early childhood than later in childhood. For clinical purposes, correction for preterm birth is only likely to have an impact during early childhood, however assessments for research purposes should continue to correct into childhood to account for the persistent bias due to preterm birth.

Brain growth after surgical treatment for infant postinfectious hydrocephalus in Sub-Saharan Africa: 2-year results of a randomized trial.

Hydrocephalus in infants, particularly that with a postinfectious etiology, is a major public health burden in Sub-Saharan Africa. The authors of this study aimed to determine whether surgical treatment of infant postinfectious hydrocephalus in Uganda results in sustained, long-term brain growth and improved cognitive outcome. The authors performed a trial at a single center in Mbale, Uganda, involving infants (age < 180 days old) with postinfectious hydrocephalus randomized to endoscopic third ventriculostomy plus choroid plexus cauterization (ETV+CPC; n = 51) or ventriculoperitoneal shunt (VPS; n = 49). After 2 years, they assessed developmental outcome with the Bayley Scales of Infant Development, Third Edition (BSID-III), and brain volume (raw and normalized for age and sex) with CT scans. Eighty-nine infants were assessed for 2-year outcome. There were no significant differences between the two surgical treatment arms in terms of BSID-III cognitive score (p = 0.17) or brain volume (p = 0.36), so they were analyzed together. Raw brain volumes increased between baseline and 2 years (p < 0.001), but this increase occurred almost exclusively in the 1st year (p < 0.001). The fraction of patients with a normal brain volume increased from 15.2% at baseline to 50.0% at 1 year but then declined to 17.8% at 2 years. Substantial normalized brain volume loss was seen in 21.3% patients between baseline and year 2 and in 76.7% between years 1 and 2. The extent of brain growth in the 1st year was not associated with the extent of brain volume changes in the 2nd year. There were significant positive correlations between 2-year brain volume and all BSID-III scores and BSID-III changes from baseline. In Sub-Saharan Africa, even after successful surgical treatment of infant postinfectious hydrocephalus, early posttreatment brain growth stagnates in the 2nd year. While the reasons for this finding are unclear, it further emphasizes the importance of primary infection prevention and mitigation strategies along with optimizing the child's environment to maximize brain growth potential.

Hybrid type 1 effectiveness/implementation trial of the international Guide for Monitoring Child Development: protocol for a cluster-randomised controlled trial

IntroductionMore than 40% of children under 5 years of age in low-income and middle-income countries are at risk of not reaching their developmental potential. The international Guide for Monitoring Child...

Neonatal stroke: Clinical characteristics and neurodevelopmental outcomes

Neonatal stroke can potentially result in significant neurological sequelae in affected infants. Studies on neurodevelopmental outcomes and the need for rehabilitation therapies in the first two years are limited. We aimed to describe the clinical characteristics, diagnostic evaluation, and neurodevelopmental outcomes of a cohort of infants with neonatal stroke. A retrospective cohort study of infants with neonatal stroke, from 2011 to 2020. Maternal and infant characteristics were described. Placental pathology, echocardiogram results, and prothrombotic evaluations were reported. The neurodevelopmental outcomes using Bayley scale of infant development (BSID III), rates of epilepsy and cerebral palsy, and the need for rehabilitation therapies at two years were described. During the study period, 55 infants had neonatal stroke. Majority (93%) were term or late preterm infants. Maternal chorioamnionitis and perinatal HIE were diagnosed in about a third of the infants. Most (66%) of the infants presented with seizures. On brain MRI, the lesions were unilateral in 76% and arterial in origin in 86% of the infants. Meconium exposure (42%), intrauterine inflammation/infection (37%) and fetal vascular malperfusion (16%) were seen on placental histopathology. At two-year BSID III assessment, median (min, max) composite cognitive, language, and motor scores were 100 (55-145), 97 (47-124), and 100 (46-141), respectively. Among this cohort, epilepsy (27%), cerebral palsy (16%) and the need for rehabilitation therapies (physical -24%, occupational -18%, speech -21%) were reported at two years. Neonatal stroke presented commonly in term or late preterm infants with seizures. It was unilateral and arterial in origin in most infants. Maternal chorioamnionitis and perinatal HIE were the most commonly associated conditions at birth. About one-fifth of the infants had mild or severe developmental delays at two years. Epilepsy, cerebral palsy, and need for rehabilitation therapies were noted in a significant proportion of infants at two years.

Neurodevelopmental Outcome of Children with Congenital Heart Disease: A Cohort Study from Infancy to Preschool Age

To characterize the neuropsychological outcome of children with congenital heart disease (CHD) at age 5years; the stability of cognitive and language abilities across childhood; and to identify early neurodevelopmental markers of neuropsychological outcomes in these children. Five-year-old children (n=55) with complex CHD were assessed using standardized and comprehensive neuropsychological measures. Stability of language and cognitive performance was assessed by comparing standardized scores between ages 1, 2, and 5years old. Association between 5-year-old skills and scores obtained in early childhood was studied to identify potential early markers of preschool performance. Receiver operating characteristic curves were used to evaluate the classification accuracy of Bayley Scales of Infant Development, Third Edition scales in identifying later impairments. At age 5years, our cohort obtained scores significantly below the norms on most developmental domains, with 35% to 65% of participants showing impaired short-term/working memory, attention, and preacademic skills. Developmental patterns measured between ages 1 and 5years were different for cognitive and language domains, with a decline with age for cognitive functioning and stable results for expressive language. The Bayley Scales of Infant Development, Third Edition language scores at age 2years provided a good predictive value in identifying children with impaired language at age 5years. In our cohort, we found a high prevalence of impairments affecting higher-order cognitive domains. Although language difficulties can be detected as early as 2years of age, other neuropsychological impairments, such as attention and pre-academic skills, only appear later during development, which reinforces the need for long-term monitoring and systematic assessment before school entry.

Association between Term Equivalent Brain Magnetic Resonance Imaging and 2-Year Outcomes in Extremely Preterm Infants: A Report from the Preterm Erythropoietin Neuroprotection Trial Cohort

To compare the term equivalent brain magnetic resonance imaging (MRI) findings between erythropoietin (Epo) treated and placebo control groups in infants 240/7-276/7weeks of gestational age and to assess the associations between MRI findings and neurodevelopmental outcomes at 2years corrected age. The association between brain abnormality scores and Bayley Scales of Infant Development, Third Edition at 2years corrected age was explored in a subset of infants enrolled in the Preterm Erythropoietin Neuroprotection Trial. Potential risk factors for neurodevelopmental outcomes such as treatment assignment, recruitment site, gestational age, inpatient complications, and treatments were examined using generalized estimating equation models. One hundred ten infants were assigned to Epo and 110 to placebo groups. 27% of MRI scans were rated as normal, and 60%, 10%, and 2% were rated as having mild, moderate, or severe abnormality. Brain abnormality scores did not significantly differ between the treatment groups. Factors that increased the risk of higher brain injury scores included intubation; bronchopulmonary dysplasia; retinopathy of prematurity; opioid, benzodiazepine, or antibiotic treatment >7days; and periventricular leukomalacia or severe intraventricular hemorrhage diagnosed on cranial ultrasound. Increased global brain abnormality and white matter injury scores at term equivalent were associated with reductions in cognitive, motor, and language abilities at 2years of corrected age. Evidence of brain injury on brain MRIs obtained at term equivalent correlated with adverse neurodevelopmental outcomes as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition at 2years corrected age. Early Epo treatment had no effect on the MRI brain injury scores compared with the placebo group.

Effect of Anodal Transcranial Direct Current Stimulation Combined With Cognitive Training for Improving Cognition and Language Among Children With Cerebral Palsy With Cognitive Impairment: A Pilot, Randomized, Controlled, Double-Blind, and Clinical Trial.

About 30–45% of cerebral palsy (CP) patients have cognitive impairment. Previous studies showed the evidence that transcranial direct current stimulation (tDCS) may have some benefits in attention-deficit/hyperactivity disorder, autism spectrum disorder, and motor development in CP. The aim of this study is to evaluate the effect of tDCS on cognition, language, and activities of daily living (ADL) among children with CP with cognitive impairment. It was a pilot, randomized, controlled, double-blind, clinical trial in a tertiary pediatric hospital, and 13 children with CP and a cognitive age under 42 months were enrolled. tDCS group (n = 8) had active tDCS and cognitive training (20 min/session, total 20 sessions, for 12 weeks) and sham group (n = 5) had sham tDCS and cognitive training. Primary outcome was the Bayley Scales of Infant Development II (BSID II). Secondary outcomes were the Pediatric Evaluation of Disability Inventory (PEDI), the Laboratory Temperament Assessment Battery (Lab-TAB), the Early Childhood Behavior Questionnaire (ECBQ), the Korean version of MacArthur–Bates Communicative Development Inventories (M-B CDI-K), the Sequenced Language Scale for Infants (SELSI) and the Preschool Receptive-Expressive Language Scale (PRES). After intervention, the tDCS group showed significant improvements in all measurements (p < 0.05) except the M-B CDI-K (grammar), whereas the sham group only showed significant improvements in the Lab-TAB (manipulation domain), the ECBQ (attentional shifting), and the M-B CDI-K (comprehension). The between-group differences in the degree of post-intervention improvement were not statistically significant. The degree of improvement was associated with better baseline cognitive function and younger age (p < 0.05). There were no major adverse events after tDCS. The combined application of tDCS and cognitive training was feasible and associated with improvements in cognitive function, ADL, and language among children with CP with cognitive impairment. However, considering that it is a pilot study, further larger-scale systematic investigation is needed.Clinical Trial Registration: The trial was registered in the Clinical Research Information Service database, identifier: KCT0003023.

Mediation effect of air pollution and temperature on the association between greenness and infant’s neurodevelopment: to identify critical windows

BACKGROUND AND AIM: Green spaces can have a beneficial effect on health, but little is known about how they affect the neurodevelopment of infants. We investigated to identify mediation effect of TRAPs and temperature mixtures between greenness and infant’s neurodevelopment during windows of susceptibility. METHODS: 418 mother-infant pairs from the mothers and children environmental health (MOCEH) study were analyzed. Daily TRAPs concentrations including PM10 and NO2 were estimated by land-use regression and daily temperature levels obtained from the Korea Meteorological Administration were averaged over each period from pregnancy to 24 months of age. Infant’s neurodevelopment was evaluated based on mental development index (MDI) and physical development index (PDI) at 6 months, 12 months, and 24 months of age assessed by the Korean Bayley Scale of Infant Development II. Bayesian kernel machine regression was used to estimate the mixture index of TRAPs and temperature on infant’s MDI and PDI. Then, causal mediation approach was used to estimate the mediation effect of the mixture index on the association between greenness and infant’s MDI and PDI after adjusting for potential confounders. RESULTS:The total effect of greenness during the entire pregnancy and 6 months from birth on MDI at 6-month-old infants was 1.25 [95% confidence interval: 0.39, 2.39] and 1.09 (0.12, 2.09), respectively. And the indirect effect of the mixture index of TRAPs and temperature during the entire pregnancy and 6 months from birth was each 0.59 (0.19, 1.00) and 0.53(0.04, 1.09). Further, the total effect and the indirect effect of greenness during the entire pregnancy on PDI at 6-month-old infants was 1.45 (0.40, 2.72) and 0.47 (0.12, 0.99). No significant association was observed in other periods. CONCLUSIONS:Our finding suggested that the residential green space has a beneficial effect on infant’s neurodevelopment by reducing overall effect of TRAPs and temperature during pregnancy and early childhood. KEYWORDS: Neurodevelopmental outcomes, Green space, Multi-pollutant, Causal inference

In-utero exposure to indoor air pollution or tobacco smoke and cognitive development in a South African birth cohort study

BACKGROUND AND AIM: There is increasing evidence indicating that air pollution exposure is associated with neuronal damage. Since pregnancy is a critical window of vulnerability, air pollution exposure during this period could have adverse effects on neurodevelopment. This study aims 1) to analyze associations of prenatal exposure to indoor air pollution (particulate matter with diameters ≤10μm, PM10) and tobacco smoke on neurodevelopment and 2) to determine if these associations are mediated by deviations of epigenetic gestational age from chronological gestational age (ΔGA). METHODS: Data of 734 children from the South African Drakenstein Child Health Study were analyzed. Antenatal PM10 exposure was measured using devices placed in the families’ homes. Maternal smoking during pregnancy was determined by maternal urine cotinine measures. Bayley Scales of Infant Development were used to measure cognition, language, motor, and adaptive behavior development at two years of age. Overall composite scores were calculated as the average of the four sub-scores. Linear regression models adjusted for maternal age, gestational age, sex of child, ancestry, birth weight/length, and socioeconomic status were used to explore associations. A mediation analysis was conducted to analyze if the associations were mediated by ΔGA using DNA methylation measurements from cord blood. RESULTS:An increase of one interquartile range in PM10 (54.40μg/m3) was significantly associated with lower cognition sub-scores (β-estimate [95%-confidence interval]: -0.01 [-0.22, 0.00]). Maternal smoking was significantly associated with lower overall composite scores (-1.84 [-3.52, -0.16]) and lower adaptive behavior sub-scores (-3.39 [-5.63, -1.14]). Other scores were not associated with PM10 or smoking. Associations were not significantly mediated by ΔGA (e.g., for PM10 and cognition, proportion mediated [95%-confidence interval]: 1% [-18, -20%]). CONCLUSIONS:We found an association of prenatal exposure to indoor air pollution (PM10) and tobacco smoke on neurodevelopment at 2 years of age. Further research is needed to understand underlying biological mediators. KEYWORDS: Air pollution, Particulate matter, Neurodevelopmental outcomes, Environmental epidemiology, Epigenomics

Association between prenatal air pollutant exposure and child development in a follow-up birth cohort study

BACKGROUND AND AIM: Air pollutant exposure adversely associates with infant development. This study aimed to investigate the effect of prenatal air pollutant exposure on children development. METHODS: Mother–infant pairs in two birth-cohort studies were recruited from five hospitals from 2001 to 2005. Children’s mental and psychomotor development was measured by the Bayley Scales of Infant Development in children aged 2 years. Hourly concentrations of five air pollutants (i.e. NO2, CO, O3, SO2, and PM10) within 1 year before childbirth were obtained from 76 air quality monitoring stations cross Taiwan. We used weighted K-nearest neighbor method (k=3) to estimate the personalized air pollution exposure and transformed the concentration of the five air pollutants into Individual Air Quality Index (IAQI) values. Multiple variable regression was used to assess the association between prenatal air pollutant exposure and Bayley score in 2-year-old children. RESULTS:Overall, 286 mother-infant pairs completed all measurements. The geometrical mean of mental development index (MDI) score and psychomotor development index (PDI) score were 95.2 and 99.3, respectively. After adjusted for recruited cohort, parental education, gestational week, and child's sex, monthly average of prenatal air pollutants' IAQI different of CO, NO2, and PM10 were negatively associated with PDI score. Per unit increasing of the monthly average different of CO, NO2, and PM10 IAQI were associated with 10.30 (95% confidence interval, CI = 4.40-16.56), 2.58 (95% CI = 0.96-4.21), and 0.63 (95% CI = 0.06-1.19) decrease of PDI score in children, respectively. CONCLUSIONS:Prenatal exposure to CO, NO2, and PM10 and their concatenation changes with time may affect children’s development at age 2 years. KEYWORDS: air pollution, neurodevelopmental outcomes, children's environmental health, birth cohort

Long-Term Outcome after Asphyxia and Therapeutic Hypothermia in Late Preterm Infants: A Pilot Study.

Therapeutic hypothermia (THT) is the recommended treatment for neuroprotection in (near) term newborns that experience perinatal asphyxia with hypoxic-ischemic encephalopathy. The benefit of THT in preterm newborns is unknown. This pilot study aims to investigate long-term outcomes of late preterm asphyctic infants with and without THT compared to term infants. The single-center, retrospective analysis examined medical charts of infants with perinatal asphyxia born between 2008 and 2015. Long-term outcome was assessed using the Bayley Scales of Infant Development 2 at the age of (corrected) 24 months. Term (n = 31) and preterm (n = 8) infants with THT showed no differences regarding their long-term outcomes of psychomotor development (Psychomotor Developmental Index 101 ± 16 vs. 105 ± 11, p = 0.570), whereas preterm infants had a better mental outcome (Mental Developmental Index 105 ± 13 vs. 93 ± 18, p = 0.048). Preterm infants with and without (n = 69) THT showed a similar mental and psychomotor development (Mental Developmental Index 105 ± 13 vs. 96 ± 20, p = 0.527; Psychomotor Developmental Index 105 ± 11 vs. 105 ± 15, p = 0.927). The study highlights the importance of studying THT in asphyctic preterm infants. However, this study shows limitations and should not be used as a basis for decision-making in the clinical context. Results of a multicenter trial of THT for preterm infants (ID No.: CN-01540535) have to be awaited.

Relationship Between Maternal Economic Vulnerability and Childhood Neurodevelopment at 2 and 5 Years of Life.

To assess the relationship between economic vulnerability during pregnancy and childhood neurodevelopment. This is a secondary analysis of two parallel multicenter, randomized, controlled trials of administration of levothyroxine to pregnant individuals with subclinical hypothyroidism or hypothyroxinemia in the United States. All participants who delivered a live, nonanomalous neonate and completed the WPPSI-III (Weschler Preschool & Primary Scale of Intelligence) at 5 years of life and the Bayley-III (Bayley Scales of Infant Development) test at 2 years were included. The primary outcome is WPPSI-III score. Secondary outcome included Bayley-III subtest scores. Multivariable analyses were used to assess the relationships between economic vulnerability during the index pregnancy-defined as a household income less than 200% of the estimated federal poverty level, part-time or no employment, and use of government insurance-and the prespecified outcomes. Tests of interaction were performed to assess whether the magnitude of association differed according to whether participants were married or completed more than a high school education. A sensitivity analysis was performed to limit the income criteria for economic vulnerability to household income of less than 100% of the estimated federal poverty level. Of 955 participants who met inclusion criteria, 406 (42.5%) were considered economically vulnerable. In bivariate analysis, the WPPSI-III score and Bayley-III subtest scores were significantly lower among children of the economically vulnerable. For the WPPSI-III, Bayley-III cognitive subtest, and Bayley-III language subtest scores, the associations between economic vulnerability and lower childhood neurodevelopmental scores were primarily seen only among those who were married or completed more than a high school education (P for interaction<.05). A similar pattern was noted when restricting the income criteria for economic vulnerability to less than 100% of the federal poverty level. Economic vulnerability during pregnancy is associated with an increased risk of adverse neurodevelopmental outcomes in their children at 2 and 5 years of life, particularly among those who are married or completed more than a high school education.

Enteral Iron Supplementation in Infants Born Extremely Preterm and its Positive Correlation with Neurodevelopment; Post Hoc Analysis of the Preterm Erythropoietin Neuroprotection Trial Randomized Controlled Trial

To test whether an increased iron dose is associated with improved neurodevelopment as assessed by the Bayley Scales of Infant Development, third edition (BSID-III) among infants enrolled in the Preterm Erythropoietin (Epo) Neuroprotection Trial (PENUT). This is a post hoc analysis of a randomized trial that enrolled infants born at 24-28 completed weeks of gestation. All infants in PENUT who were assessed with BSID-III at 2years were included in this study. The associations between enteral iron dose at 60 and 90days and BSID-III component scores were evaluated using generalized estimating equations models adjusted for potential confounders. In total, 692 infants were analyzed (355 placebo, 337 Epo). Enteral iron supplementation ranged from 0 to 14.7mg/kg/d (IQR 2.1-5.8mg/kg/d) at day 60, with a mean of 3.6mg/kg/d in infants treated with placebo and 4.8mg/kg/d in infants treated with Epo. A significant positive association was seen between BSID-III cognitive scores and iron dose at 60days, with an effect size of 0.77 BSID points per 50mg/kg increase in cumulative iron dose (P=.03). Greater iron doses were associated with greater motor and language scores but did not reach statistical significance. Results at 90days were not significant. The effect size in the infants treated with Epo compared with placebo was consistently greater. A positive association was seen between iron dose at 60days and cognitive outcomes. Our results suggest that increased iron supplementation in infants born preterm, at the doses administered in the PENUT Trial, may have positive neurodevelopmental effects, particularly in infants treated with Epo. Clinicaltrials.gov: NCT01378273.