Bayley Scales Of Infant And Toddler Development, Third Edition Research Articles

Music Therapy in Infancy and Neurodevelopmental Outcomes in Preterm Children: A Secondary Analysis of the LongSTEP Randomized Clinical Trial.

Preterm children are at risk for neurodevelopment impairments. To evaluate the effect of a music therapy (MT) intervention (parent-led, infant-directed singing) for premature children during the neonatal intensive care unit (NICU) stay and/or after hospital discharge on language development at 24 months' corrected age (CA). This predefined secondary analysis followed participants in the LongSTEP (Longitudinal Study of Music Therapy's Effectiveness for Premature Infants and Their Caregivers) randomized clinical trial, which was conducted from August 2018 to April 2022 in 8 NICUs across 5 countries (Argentina, Colombia, Israel, Norway, and Poland) and included clinic follow-up visits and extended interventions after hospital discharge. Participants were children born preterm (<35 weeks' gestation) and their parents. Participants were randomized at enrollment to MT with standard care (SC) or SC alone; they were randomized to MT or SC again at discharge. The MT was parent-led, infant-directed singing tailored to infant responses and supported by a music therapist and was provided 3 times weekly in the NICU and/or in 7 sessions across 6 months after discharge. The SC consisted of early intervention methods of medical, nursing, and social services, without MT. Primary outcome was language development, as measured by the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) language composite score, with the remaining BSID-III composite and subscale scores as the secondary outcomes. Group differences in treatment effects were assessed using linear mixed-effects models using all available data. Of 206 participants (103 female infants [50%]; mean [SD] GA, 30.5 [2.7] weeks), 51 were randomized to MT and 53 to SC at enrollment; at discharge, 52 were randomized to MT and 50 to SC. A total of 112 (54%) were retained at the 24 months' CA follow-up. Most participants (79 [70%] to 93 [83%]) had BSID-III scores in the normal range (≥85). Mean differences for the language composite score were -2.36 (95% CI, -12.60 to 7.88; P = .65) for the MT at NICU with postdischarge SC group, 2.65 (95% CI, -7.94 to 13.23; P = .62) for the SC at NICU and postdischarge MT group, and -3.77 (95% CI, -13.97 to 6.43; P = .47) for the MT group at both NICU and postdischarge. There were no significant effects for cognitive or motor development. This secondary analysis did not confirm an effect of parent-led, infant-directed singing on neurodevelopment in preterm children at 24 months' CA; wide CIs suggest, however, that potential effects cannot be excluded. Future research should determine the MT approaches, implementation time, and duration that are effective in targeting children at risk for neurodevelopmental impairments and introducing broader measurements for changes in brain development. ClinicalTrials.gov Identifier: NCT03564184.

Predicting 2-year neurodevelopmental outcomes in preterm infants using multimodal structural brain magnetic resonance imaging with local connectivity

The neurodevelopmental outcomes of preterm infants can be stratified based on the level of prematurity. We explored brain structural networks in extremely preterm (EP; < 28 weeks of gestation) and very-to-late (V-LP; ≥ 28 and < 37 weeks of gestation) preterm infants at term-equivalent age to predict 2-year neurodevelopmental outcomes. Using MRI and diffusion MRI on 62 EP and 131 V-LP infants, we built a multimodal feature set for volumetric and structural network analysis. We employed linear and nonlinear machine learning models to predict the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) scores, assessing predictive accuracy and feature importance. Our findings revealed that models incorporating local connectivity features demonstrated high predictive performance for BSID-III subsets in preterm infants. Specifically, for cognitive scores in preterm (variance explained, 17%) and V-LP infants (variance explained, 17%), and for motor scores in EP infants (variance explained, 15%), models with local connectivity features outperformed others. Additionally, a model using only local connectivity features effectively predicted language scores in preterm infants (variance explained, 15%). This study underscores the value of multimodal feature sets, particularly local connectivity, in predicting neurodevelopmental outcomes, highlighting the utility of machine learning in understanding microstructural changes and their implications for early intervention.

The Maternal Omega-3 Long-Chain Polyunsaturated Fatty Acid Concentration in Early Pregnancy and Infant Neurodevelopment: The ECLIPSES Study.

Omega-3 Long-Chain Polyunsaturated Fatty Acids (n-3 LCPUFAs) play a key role in early neurodevelopment, but evidence from observational and clinical studies remains inconsistent. This study investigates the association between maternal n-3 LCPUFA, Docosahexaenoic Acid (DHA), and eicosapentaenoic acid (EPA) concentrations during pregnancy and infant development functioning at 40 days. This study includes 348 mother-infant pairs. Maternal serum concentrations were assessed in the first and third trimesters alongside sociodemographic, clinical, nutritional, psychological, and obstetrical data. At 40 days, the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) was administered. An adjusted analysis revealed that lower first-trimester n-3 LCPUFA and DHA concentrations are associated with better infant motor development. These results underscore the potential significance of the maternal n-3 LCPUFA status in early pregnancy for influencing fetal neurodevelopment. However, the complexity of these associations necessitates further investigation, emphasizing the urgent need for additional studies to comprehensively elucidate the nuanced interplay between the maternal n-3 LCPUFA status and infant neurodevelopment.

Temporal evolution of electrographic seizures in newborn infants with hypoxic-ischaemic encephalopathy requiring therapeutic hypothermia: a secondary analysis of the ANSeR studies

Despite extensive research on neonatal hypoxic-ischaemic encephalopathy, detailed information about electrographic seizures during active cooling and rewarming of therapeutic hypothermia is sparse. We aimed to describe temporal evolution of seizures and determine whether there is a correlation of seizure evolution with 2-year outcome. This secondary analysis included newborn infants recruited from eight European tertiary neonatal intensive care units for two multicentre studies (a randomised controlled trial [NCT02431780] and an observational study [NCT02160171]). Infants were born at 36+0 weeks of gestation with moderate or severe hypoxic-ischaemic encephalopathy and underwent therapeutic hypothermia with prolonged conventional video-electroencephalography (EEG) monitoring for 10 h or longer from the start of rewarming. Seizure burden characteristics were calculated based on electrographic seizures annotations: hourly seizure burden (minutes of seizures within an hour) and total seizure burden (minutes of seizures within the entire recording). We categorised infants into those with electrographic seizures during active cooling only, those with electrographic seizures during cooling and rewarming, and those without seizures. Neurodevelopmental outcomes were determined using the Bayley's Scales of Infant and Toddler Development, Third Edition (BSID-III), the Griffiths Mental Development Scales (GMDS), or neurological assessment. An abnormal outcome was defined as death or neurodisability at 2 years. Neurodisability was defined as a composite score of 85 or less on any subscales for BSID-III, a total score of 87 or less for GMDS, or a diagnosis of cerebral palsy (dyskinetic cerebral palsy, spastic quadriplegia, or mixed motor impairment) or epilepsy. Of 263 infants recruited between Jan 1, 2011, and Feb 7, 2017, we included 129 infants: 65 had electrographic seizures (43 during active cooling only and 22 during and after active cooling) and 64 had no seizures. Compared with infants with seizures during active cooling only, those with seizures during and after active cooling had a longer seizure period (median 12 h [IQR 3-28] vs 68 h [35-86], p<0·0001), more seizures (median 12 [IQR 5-36] vs 94 [24-134], p<0·0001), and higher total seizure burden (median 69 min [IQR 22-104] vs 167 min [54-275], p=0·0033). Hourly seizure burden peaked at about 20-24 h in both groups, and infants with seizures during and after active cooling had a secondary peak at 85 h of age. When combined, worse EEG background (major abnormalities and inactive background) at 12 h and 24 h were associated with the seizure group: compared with infants with a better EEG background (normal, mild, or moderate abnormalities), infants with a worse EEG background were more likely to have seizures after cooling at 12 h (13 [54%] of 24 vs four [14%] of 28; odds ratio 7·09 [95% CI 1·88-26·77], p=0·0039) and 24 h (14 [56%] of 25 vs seven [18%] of 38; 5·64 [1·81-17·60], p=0·0029). There was a significant relationship between EEG grade at 12 h (four categories) and seizure group (p=0·020). High total seizure burden was associated with increased odds of an abnormal outcome at 2 years of age (odds ratio 1·007 [95% CI 1·000-1·014], p=0·046), with a medium negative correlation between total seizure burden and BSID-III cognitive score (rS=-0·477, p=0·014, n=26). Overall, half of infants with hypoxic-ischaemic encephalopathy had electrographic seizures and a third of those infants had seizures beyond active cooling, with worse outcomes. These results raise the importance of prolonged EEG monitoring of newborn infants with hypoxic-ischaemic encephalopathy not only during active cooling but throughout the rewarming phase and even longer when seizures are detected. Wellcome Trust, Science Foundation Ireland, and the Irish Health Research Board.

Vitamin B12 supplementation during pregnancy for maternal and child health outcomes.

Vitamin B12 deficiency is a major public health problem worldwide, with the highest burden in elderly people, pregnant women, and young children. Due to its role in DNA synthesis and methylation, folate metabolism, and erythropoiesis, vitamin B12 supplementation during pregnancy may confer longer-term benefits to maternal and child health outcomes. To evaluate the benefits and harms of oral vitamin B12 supplementation during pregnancy on maternal and child health outcomes. We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) on 2 June 2023, and reference lists of retrieved studies. Randomised controlled trials (RCTs), quasi-RCTs, or cluster-RCTs evaluating the effects of oral vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation during pregnancy. We used standard Cochrane methods. Four review authors independently assessed trial eligibility. Two review authors independently extracted data from included studies and conducted checks for accuracy. Three review authors independently assessed the risk of bias of the included studies using the Cochrane RoB 1 tool. We used GRADE to evaluate the certainty of evidence for primary outcomes. The review included five trials with 984 pregnant women. All trials were conducted in low- and middle-income countries, including India, Bangladesh, South Africa, and Croatia. At enrolment, 26% to 51% of pregnant women had vitamin B12 deficiency (less than 150 pmol/L), and the prevalence of anaemia (haemoglobin less than 11.0 g/dL) ranged from 30% to 46%. The dosage of vitamin B12 supplementation varied from 5 μg/day to 250 μg/day, with administration beginning at 8 to 28 weeks' gestation through to delivery or three months' postpartum, and the duration of supplementation ranged from 8 to 16 weeks to 32 to 38 weeks. Three trials, involving 609 pregnant women, contributed data for meta-analyses of the effects of vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation. Maternal anaemia: there may be little to no difference for maternal anaemia by intervention group, but the evidence is very uncertain (70.9% versus 65.0%; risk ratio (RR) 1.08, 95% confidence interval (CI) 0.93 to 1.26; 2 trials, 284 women; very low-certainty evidence). Maternal vitamin B12 status: vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain (25.9% versus 67.9%; RR 0.38, 95% CI 0.28 to 0.51; 2 trials, 272 women; very low-certainty evidence). Women who received vitamin B12 supplements during pregnancy may have higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (mean difference (MD) 60.89 pmol/L, 95% CI 40.86 to 80.92; 3 trials, 412 women). However, there was substantial heterogeneity (I2 = 85%). Adverse pregnancy outcomes: the evidence is uncertain about the effect on adverse pregnancy outcomes, including preterm birth (RR 0.97, 95% CI 0.55 to 1.74; 2 trials, 340 women; low-certainty evidence), and low birthweight (RR 1.50, 95% CI 0.93 to 2.43; 2 trials, 344 women; low-certainty evidence). Two trials reported data on spontaneous abortion (or miscarriage); however, the trials did not report quantitative data for meta-analysis and there was no clear definition of spontaneous abortion in the study reports. No trials evaluated the effects of vitamin B12 supplementation during pregnancy on neural tube defects. Infant vitamin B12 status: children born to women who received vitamin B12 supplementation had higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (MD 71.89 pmol/L, 95% CI 20.23 to 123.54; 2 trials, 144 children). Child cognitive outcomes: three ancillary analyses of one trial reported child cognitive outcomes; however, data were not reported in a format that could be included in quantitative meta-analyses. In one study, maternal vitamin B12 supplementation did not improve neurodevelopment status (e.g. cognitive, language (receptive and expressive), motor (fine and gross), social-emotional, or adaptive (conceptual, social, practical) domains) in children compared to placebo (9 months, Bayley Scales of Infant and Toddler Development Third Edition (BSID-III); 1 trial; low-certainty evidence) or neurophysiological outcomes (72 months, event-related potential measures; 1 trial; low-certainty evidence), though children born to women who received vitamin B12 supplementation had improved expressive language domain compared to placebo (30 months, BSID-III; 1 trial; low-certainty evidence). Oral vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency and may improve maternal vitamin B12 concentrations during pregnancy or postpartum compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain. The effects of vitamin B12 supplementation on other primary outcomes assessed in this review were not reported, or were not reported in a format for inclusion in quantitative analyses. Vitamin B12 supplementation during pregnancy may improve maternal and infant vitamin B12 status, but the potential impact on longer-term clinical and functional maternal and child health outcomes has not yet been established.

General Movements trajectories and outcome at 12 months in very preterm infants: An analysis of tendencies and pathological persistence

Very preterm infants (VPI) < 32 weeks are at increased risk of developmental disorders detectable using the Prechtl General Movements Assessment (GMA) and the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). The aim of this study was to investigate General Movements (GMs) trajectories from preterm to fidgety age including GMs tendencies and their association with cognitive and motor outcome. Retrospective analysis of VPI with GMA at preterm (35 ± 2 weeks postmenstrual age (PMA), T1) and fidgety age (12 ± 3 weeks corrected age CA), T2), and BSID-III (12 ± 3 months CA, T3) is performed. Data are analysed using Pearson χ2-test, Fisher-Freeman-Halton Exact test, and residual analyses. This study found significant associations between (a) GMs (T1) and (b) persistent pathological GMs (T1 + T2) with cognitive outcomes at 12 months (T3) considering the tendencies of GMs in addition to the global character (p = 0.007, p = 0.022, respectively), representing medium-sized effects. There were no significant associations between GMs or persistence of pathological GMs and gross and fine motor outcomes, regardless of GMs tendencies. Findings indicate that considering tendencies of GMs and the persistence of pathological GMs may be important in identifying children at risk of cognitive impairments early. This additional assessment parameter may have the potential for early identification of infants with milder motor and/or cognitive impairments. However, more research is needed using larger sample cohorts to generalise the results and to be able to recommend sequential GMA for clinical routine.

Time to Reaching Target Cooling Temperature and 2-year Outcomes in Infants with Hypoxic-Ischemic Encephalopathy

To determine if time to reaching target temperature (TT) is associated with death or neurodevelopmental impairment (NDI) at 2years of age in infants with hypoxic-ischemic encephalopathy (HIE). Newborn infants ≥36weeks of gestation diagnosed with moderate or severe HIE and treated with therapeutic hypothermia were stratified based on time at which TT was reached, defined as early (ie, ≤4hours of age) or late (>4hours of age). Primary outcomes were death or NDI. Secondary outcomes included neurodevelopmental assessment with Bayley Scales of Infant and Toddler Development, third edition (BSID-III) at age2. Among 500 infants, the median time to reaching TT was 4.3 hours (IWR, 3.2-5.7 hours). Infants in early TT group (n=211 [42%]) compared with the late TT group (n=289 [58%]) were more likely to be inborn (23% vs 13%; P<.001) and have severe HIE (28% vs 19%; P=.03). The early and late TT groups did not differ in the primary outcome of death or any NDI (adjusted RR,1.05; 95% CI,0.85-0.30; P=.62). Among survivors, neurodevelopmental outcomes did not differ significantly in the 2 groups (adjusted mean difference in Bayley Scales of Infant Development-III scores: cognitive, -2.8 [95% CI,-6.1 to 0.5], language -3.3 [95% CI,-7.4 to 0.8], and motor -3.5 [95% CI,-7.3 to 0.3]). In infants with HIE, time to reach TT is not independently associated with risk of death or NDI at age 2years. Among survivors, developmental outcomes are similar between those who reached TT at <4 and ≥4 hours of age. High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL); NCT02811263; https://beta. gov/study/NCT02811263.

Validity and Internal Consistency of the Indonesian-Translated Communication and Symbolic Behavior Scales Developmental Profile to Screen Language Delay in Children Aged 6–24 Months

The Communication and Symbolic Behavior Scales Developmental Profile (CSBS DP) is a valid and reliable screening tool for detecting language delay in children. However, it has not been translated into the Indonesian language. This study aimed to determine the validity and internal consistency of the Indonesian-translated CSBS DP as a screening tool for language delay in children aged 6–24 months. A cross-sectional study was carried out at the Growth and Development Clinic, Cipto Mangunkusumo Hospital, in 3 stages: (1) transcultural translation and adaptation of the measure into the Indonesian language; (2) determination of the internal consistency of the measure; and (3) determination of the concurrent validity of the measure by comparing CSBS DP with the Bayley Scales of Infant and Toddler Development, third edition (BSID-III) language scale on 149 caregivers–children dyads. We found good concurrent validity (r &gt; .3) and good internal consistency with Cronbach's α values of 0.876–0.896. The concurrent validity of the Indonesian-translated questionnaire showed a sensitivity of 71.43% and a specificity of 81.48%. CSBS DP Indonesian-translated questionnaire is a valid and reliable screening test for language delay in children aged 6–24 months.

Prevalence of developmental delay and associated risk factors among At Risk Surveillance System (ARSS) children at United Bulawayo Hospitals, Zimbabwe

Globally, 8.4% of children under five years of age have developmental disorders, with sub-Saharan Africa having the highest prevalence. In Zimbabwe, the At Risk Surveillance System (ARSS) follows up on babies with known developmental risk factors for early detection of developmental delay. This study aimed to determine the prevalence and severity of developmental delay in children under the ARSS at United Bulawayo Hospitals (UBH). A descriptive cross-sectional study systematically sampled 160 babies enrolled in the ARSS between 2019 and 2020. The Bayley Scales of Infant and Toddler Development Third Edition (BSID-III) tool was used to assess cognitive, motor, and language domains. Developmental delay risk factors were also noted from caregivers and patient files. A prevalence of 83.7% developmental delay was established in our sample, the majority of whom had mild developmental delay. The most important risk factors for developmental delay in all three domains were neonatal convulsions (Adjusted Odds Ratio, aOR, 5.6, p=0.03), Apgar scores of &lt;5 (aOR 2.6, p=0.02), and being a boy (aOR 7.1, p&lt;0.001). Developmental delay of 83.7% is higher than in previous findings because children included in this study had known risk factors for developmental delay. The risk factors were similar to those identified by other studies. Children with the most important risk factors need close monitoring as they have a high chance of developmental delay. Children with known risk factors should be closely monitored using the BSID-III, while the rest can be screened using cheaper and faster tools such as the Ages and Stages Questionnaire (ASQ).

The beneficial effect of early and prolonged kangaroo mother care on long-term neuro-developmental outcomes in low birth neonates - A cohort study.

Kangaroo mother care (KMC) has immense short-term benefits, but data on long-term outcomes are scarce. Hence, this study aimed to compare the neurodevelopmental outcomes at 12 months of corrected age (CA) in infants <2000 g receiving early and prolonged KMC to a control group. This was a cohort study that was conducted from January 2017 to November 2018. All neonates<2000 g were eligible for the study. Neonates that received early initiation (<72 h of life) and prolonged KMC comprised the intervention group and were compared to neonates without the intervention. Bayley Scales of Infant and Toddler Development, Third edition (BSID-III) was done at 12 months of CA, and this was analysed using t-test and multi-linear regression analysis. There were 75 neonates in the intervention and 69 in the control group. Baseline characteristics were comparable. We found higher composite scores for cognition (110.38 ± 9.89 vs. 105.44 ± 8.77, p value = 0.023), language (107.51 ± 10.72 vs. 101.05 ± 12.06, p value = 0.014) and adaptive behaviour (87.97 ± 9.97 vs. 80 ± 9.1, p value<0.001) in the early and prolonged KMC group in comparison to the control group. Infants with early and prolonged KMC have better neurodevelopmental outcomes in terms of cognition, language and adaptive behaviour at 12 months of CA.

Association of cerebral metabolic rate following therapeutic hypothermia with 18-month neurodevelopmental outcomes after neonatal hypoxic ischemic encephalopathy.

Therapeutic hypothermia (TH) is standard of care for moderate to severe neonatal hypoxic ischemic encephalopathy (HIE) but many survivors still suffer lifelong disabilities and benefits of TH for mild HIE are under active debate. Development of objective diagnostics, with sensitivity to mild HIE, are needed to select, guide, and assess response to treatment. The objective of this study was to determine if cerebral oxygen metabolism (CMRO2) in the days after TH is associated with 18-month neurodevelopmental outcomes as the first step in evaluating CMRO2's potential as a diagnostic for HIE. Secondary objectives were to compare associations with clinical exams and characterise the relationship between CMRO2 and temperature during TH. This was a prospective, multicentre, observational, cohort study of neonates clinically diagnosed with HIE and treated with TH recruited from the tertiary neonatal intensive care units (NICUs) of Boston Children's Hospital, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center between December 2015 and October 2019 with follow-up to 18 months. In total, 329 neonates ≥34 weeks gestational age admitted with perinatal asphyxia and suspected HIE were identified. 179 were approached, 103 enrolled, 73 received TH, and 64 were included. CMRO2 was measured at the NICU bedside by frequency-domain near-infrared and diffuse correlation spectroscopies (FDNIRS-DCS) during the late phases of hypothermia (C), rewarming (RW) and after return to normothermia (NT). Additional variables were body temperature and clinical neonatal encephalopathy (NE) scores, as well as findings from magnetic resonance imaging (MRI) and spectroscopy (MRS). Primary outcome was the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at 18 months, normed (SD) to 100 (15). Data quality for 58 neonates was sufficient for analysis. CMRO2 changed by 14.4% per °C (95% CI, 14.2-14.6) relative to its baseline at NT while cerebral tissue oxygen extraction fraction (cFTOE) changed by only 2.2% per °C (95% CI, 2.1-2.4) for net changes from C to NT of 91% and 8%, respectively. Follow-up data for 2 were incomplete, 33 declined and 1 died, leaving 22 participants (mean [SD] postnatal age, 19.1 [1.2] month; 11 female) with mild to moderate HIE (median [IQR] NE score, 4 [3-6]) and 21 (95%) with BSID-III scores >85at 18 months. CMRO2 at NT was positively associated with cognitive and motor composite scores (β (SE)=4.49 (1.55) and 2.77 (1.00) BSID-III points per 10-10moL/dl×mm2/s, P=0.009 and P=0.01 respectively; linear regression); none of the other measures were associated with the neurodevelopmental outcomes. Point of care measures of CMRO2 in the NICU during C and RW showed dramatic changes and potential to assess individual response to TH. CMRO2 following TH outperformed conventional clinical evaluations (NE score, cFTOE, and MRI/MRS) at predicting cognitive and motor outcomes at 18 months for mild to moderate HIE, providing a promising objective, physiologically-based diagnostic for HIE. This clinical study was funded by an NIH grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States (R01HD076258).

Relationship between Ventricular Size on Latest Ultrasonogram and Bayley Scores ≥18 months in Extremely Low Gestational Age Neonates: A Retrospective Cohort Study.

Objective A ventricle-to-brain index (VBI) >0.35 is associated with low scores on the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), in preterm infants with birthweight <1250 g. However, VBI obtained at the 3rd ventricle has only moderate interobserver reliability. The objective of this study was to test (1) reliability of VBI measured at the foramen of Monro on the latest ultrasonogram before discharge using the intraclass correlation coefficient (ICC) and (2) the relationship between VBI and BSID-III scores at ≥18 months corrected age. Study design Single-center retrospective cohort study Results The study included 270 preterm infants born at 230/7-286/7 weeks gestational age. The ICC of VBI between independent measurements by two study radiologists on the first 50 patients was 0.934. Factors associated with the value of VBI included severe intraventricular hemorrhage, bronchopulmonary dysplasia (BPD) and systemic steroid administration for BPD but not postmenstrual age. In multivariate analysis, VBI was negatively and independently associated with cognitive (P=0.002), language (P=0.004) and motor (P<0.001) BSID-III scores. The association between VBI and BSID-III scores was observed even in infants in whom the latest US was obtained before term equivalent age. The association between VBI and BSID-III scores was also observed after excluding those with severe intraventricular hemorrhage. Conclusion In this very preterm cohort the measurement of VBI had excellent reliability. Moreover, VBI measurements were negatively associated with motor, language and cognitive BSID-III scores.

Prediction of cord blood leptin on infant’s neurodevelopment: A birth cohort in rural Yunnan, China

BackgroundLeptin, one of the peptide hormones secreted by adipocytes, plays a vital part in metabolism, but its role in early-life neurodevelopment remains poorly understood. MethodsWe performed leptin analysis on 323 cord blood samples collected from a birth cohort in Yunnan rural area, China, and assessed infants’ neurodevelopment at one year of age by the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Multiple linear regression and binary logistic regression models were used to explore the associations between cord blood leptin (CBL) concentrations and infants’ neurodevelopment and the ability of CBL to predict the probabilities of infants’ neurodevelopment delay. ResultsOverall, 323 infants were included in this study. The median concentration of CBL was 4.7 ng/ml. The proportion of 1-year-old infants identified as being neurodevelopmental delayed was 34.5%, and delays in cognitive, language, and motor domains were 11.1%, 26.6%, and 13.9%, respectively. Multiple linear regression analyses manifested that the CBL concentration (log10-transformed) was positively correlated with the cognitive, language, and motor composite scores in infants, respectively (β = 7.76, 95%CI: 3.81–11.71; β = 6.73, 95%CI: 3.41–10.06; and β = 6.88, 95%CI: 3.48–10.29, respectively). Binary logistic regression analysis showed that compared with the higher, lower CBL (< 4.7 ng/ml) yielded a 1.41-fold increase in the risk of language development delay (OR = 2.41，95%CI: 1.42–4.09), a 1.49-fold higher risk of motor development delay (OR = 2.49, 95%CI: 1.25–4.96), and a 1.71-fold higher risk of neurodevelopment delay (OR = 2.71, 95%CI: 1.64–4.48) among infants. The prediction models showed that the probabilities of development delay in infants’ language, motor, and neurodevelopment increased with the decline of CBL concentrations [rs = −0.63 (95% CI: −0.71, −0.56), rs = −0.46 (95% CI: −0.55, −0.38), rs = −0.55 (95% CI: −0.63, −0.46), respectively]. ConclusionThe decline of CBL was associated with the decrease in infants’ neurodevelopment scores at one year of age. CBL below 4.7 ng/ml may increase the risk of infants’ neurodevelopment delay. The probabilities of infants’ neurodevelopment delay increased with the decrease of CBL concentrations. CBL may be a predictor of the probability of children’s neurodevelopment delay.

Neurometabolic changes in neonates with congenital heart defects and their relation to neurodevelopmental outcome

BackgroundAltered neurometabolite ratios in neonates undergoing cardiac surgery for congenital heart defects (CHD) may serve as a biomarker for altered brain development and neurodevelopment (ND).MethodsWe analyzed single voxel 3T PRESS H1-MRS data, acquired unilaterally in the left basal ganglia and white matter of 88 CHD neonates before and/or after neonatal cardiac surgery and 30 healthy controls. Metabolite ratios to Creatine (Cr) included glutamate (Glu/Cr), myo-Inositol (mI/Cr), glutamate and glutamine (Glx/Cr), and lactate (Lac/Cr). In addition, the developmental marker N-acetylaspartate to choline (NAA/Cho) was evaluated. All children underwent ND outcome testing using the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III) at 1 year of age.ResultsWhite matter NAA/Cho ratios were lower in CHD neonates compared to healthy controls (group beta estimate: −0.26, std. error 0.07, 95% CI: −0.40 – 0.13, p value <0.001, FDR corrected p value = 0.010). We found no correlation between pre- or postoperative white matter NAA/Cho with ND outcome while controlling for socioeconomic status and CHD diagnosis.ConclusionReduced white matter NAA/Cho in CHD neonates undergoing cardiac surgery may reflect a delay in brain maturation. Further long-term MRS studies are needed to improve our understanding of the clinical impact of altered metabolites on brain development and outcome.ImpactNAA/Cho was reduced in the white matter, but not the gray matter of CHD neonates compared to healthy controls.No correlation to the 1-year neurodevelopmental outcome (Bayley-III) was found.While the rapid change of NAA/Cho with age might make it a sensitive marker for a delay in brain maturation, the relationship to neurodevelopmental outcome requires further investigation.

Effects of prenatal and infant daily exposure to pyrethroid pesticides on the language development of 2-year-old toddlers: A prospective cohort study in rural Yunnan, China

BackgroundPrenatal and infant daily exposures to pyrethroid pesticides (PYRs), used in the elimination of harmful organisms in the family environment and agricultural activities, may have an impact on children's language development. ObjectivesTo determine the impacts of prenatal and infant PYRs exposure on 2-year-old toddlers’ language development. MethodsFrom January 2016 to December 2018, women in the third trimester of pregnancy, in Yunnan rural area, China, were recruited, and the development of their newborns was observed from birth till the age of two. We examined three PYRs metabolites: 3-phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), and cis-2,2dibromovinyl-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA) in urine samples collected from women in the third trimester of pregnancy and their infants of 6–8 months after birth, and assessed language development of 2-year-old toddlers by the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Generalized linear models were used to analyze the impacts of exposure to PYRs on 2-year-old toddlers’ language development. ResultsThe median concentrations of 3PBA, 4F3PBA and DBCA creatinine-adjusted were 0.21, 0.19, and 0.15 μg/g in pregnancy, and 0.25, 0.72, and <LOD μg/g in infancy, respectively. The average scores of Language Composite (LC), Receptive Communication (RC), and Expressive Communication (EC) in 2-year-old toddlers were 100.0 ± 16.5, 10.0 ± 3.1, and 10.0 ± 3.1, respectively. Multiple linear regression analyses manifested that the concentration of 4F3PBA in infancy was negatively correlated with toddlers’ RC scores [β = −0.43 (95 % CI: −0.85, −0.01), p = 0.046]; the total PYRs metabolites in infancy were negatively correlated with boys’ LC scores and RC scores [β = −1.14 (95 % CI: −2.25, −0.04, p = 0.042 and β = −0.23 (95 % CI: −0.44, −0.01), p = 0.039, respectively]. Generalized linear models showed that exposure versus non-exposure to PYRs with DBCA in infancy increased 4.58 times risk of language development delay (OR = 5.58, 95 % CI: 1.76–17.68, p = 0.004) and a 21 % risk of not passing expressive communication items (OR = 1.21, 95 % CI: 1.01–1.45, p = 0.040). The risk of not passing RC items increased 9 % with 4F3PBA increasing per 1 μg/g in infancy (OR = 1.09, 95 % CI: 1.02–1.15, p = 0.007). The probability of not passing RC items ascended with infant 4F3PBA (rs = 0.57, 95%CI: 0.48–0.67, p < 0.001). ConclusionWomen in the third trimester of pregnancy and their infants were widely exposed to low-dose PYRs. Infant daily exposure to PYRs may negatively impact toddlers’ language development, with the 6–8 months age bracket being a sensitive window. The probability of toddlers’ language development delay may be predicted by PYRs metabolites of infants aged 6–8 months.

Exposure to perfluoroalkyl substances and neurodevelopment in 2-year-old children: A prospective cohort study.

Humans are widely exposed to per- and polyfluoroalkyl substances (PFAS). As fetal stage is a critical window for neurodevelopment, it is important to know if in utero exposure to PFAS affects fetal neurodevelopment. However, previous human studies are both limited and inconsistent. To investigate the relationship between PFAS exposure during early pregnancy and the neurodevelopmental status at 2years of age in a prospective cohort study. We measured 10 PFAS in maternal plasma samples collected prior to 16weeks of gestation in the Shanghai Birth Cohort Study between 2013 and 2016. Childhood neurodevelopment was assessed at 2years of age using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Associations with domain specific scores for individual PFAS were assessed by multiple linear regression and binary logistic regression when scores were dichotomized. Quantile-based g-computation was used to estimate the joint effects of PFAS mixture. A total of 2257 mother-child pairs who had both PFAS and BSID measurements were included in our analyses. The means and standard deviations of comprehensive scores were 115±22, 96±15 and 108±15 for cognition, language, and motor, respectively. In multiple linear regressions, we observed significant negative associations of perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluoroundecanoic acid (PFUnDA) with cognitive scores; PFNA, PFDeA, PFUnDA and perfluorohexanesulfonate (PFHxS) negatively with language scores; and PFNA and PFUnDA negatively with motor scores. Quantile-based g-computation showed that PFAS mixture was significantly associated with decreased cognitive and language scores, with an estimated β of -2.1 [95% confidence interval (CI): -3.5, -0.7)] and -2.0 (95% CI: -2.9, -1.0) per one quartile increase in PFAS mixture for cognitive and language domains, respectively. PFAS mixture was associated with increased odds of low cognition (adjusted odds ratio [OR]=1.3, 95% CI:1.0, 1.6) and language scores (OR=1.2, 95% CI: 1.1, 1.3). PFAS exposure during early pregnancy was significantly associated with the adverse neurodevelopmental status at 2years of age, which raises a serious public health concern.

Early Childhood Neurodevelopmental Outcomes in Children with Prenatal Zika Virus Exposure: A Cohort Study in Puerto Rico

To describe anthropometric, sensory, and neurodevelopmental outcomes of children who were Zika virus-exposed from birth to 36months. The study cohort included 114 children born to mothers with confirmed and probable Zika virus pregnancy infection in 2016-2017. Children attending study visits from May 2017 through February 2020 underwent physical/neurologic, sensory examinations, and neurodevelopmental assessments with the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and Ages and Stages Questionnaires, Third Edition (ASQ-3). Three of the 114 children (2.6%) had microcephaly (z-score for head circumference≤-2) at birth, 19 of 35 (54.3%) had posterior eye abnormalities in retinal images, and 11 of 109 (10.1%) had nonspecific findings on brain ultrasound. Three of 107 children (2.8%) failed hearing screening at birth. Of those children with follow-up data, 17 of 97 (17.5%) failed age-appropriate vision screening. The BSID-III identified developmental delay in at least 1 domain in at least one-third of children, with higher prevalence in the language domain. ASQ-3 screen positive delay peaked at around 24 or 36months, with some domains showing a decrease at older ages. Correlations among BSID-III and ASQ-3 scores were observed, representing professional and parental perspectives at 24 and 36months (r=0.32-0.78; P<.05). The presence of neurodevelopmental sequelae in early childhood suggests that identification of long-term impairment remains critical to attaining optimal child development. Long-term follow-up highlights vulnerability in the language domain, which likely could be influenced by early intervention, promoting cognitive development and school readiness in exposed children.

Effects of prenatal exposure to pyrethroid pesticides on neurodevelopment of 1-year- old children: A birth cohort study in China

Pregnant women have been ubiquitously exposed to pyrethroid pesticides. Previous studies, mainly based on third trimester measurements of maternal urinary pyrethroid metabolites, have reported inconsistent findings in the effects of prenatal pyrethroid exposure on children's neurodevelopmental outcomes. The purpose of this study was to clarify if pyrethroid exposure during the entire three trimesters of pregnancy may be associated with deleterious effects on infant neurodevelopmental status, particularly at a high dosage of exposure. We measured maternal urinary concentrations of pyrethroid metabolites in all trimesters of pregnancy and assessed children’s neurodevelopment at one year of age using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Multiple linear regression models were used to estimate the effects of metabolites (3-PBA, 4 F-3-PBA, cis-DBCA) in each trimester on BSID-III composite scores. Logistic regression analyses were applied to predict developmental delay vs non-delayed status (cut-off composite score of below 80 for developmental delay) based on the maternal levels of pyrethroid metabolites. In the first, second and third trimesters of pregnancy, the detection rates of pyrethroid metabolites were 94.7%, 90.7%, and 89.0%; the 50th percentiles of exposure level were 0.24 μg/g, 0.24 μg/g and 0.21 μg/g for 3-PBA, 0.14 μg/g, 0.17 μg/g and 0.15 μg/g for 4 F-3PBA, 0.21 μg/g, 0.25 μg/g and 0.19 μg/g for cis-DBCA respectively. In the second trimester, 3-PBA was inversely associated with Cognition and Language scores [β = −3.34 (95% CI = −6.11, −0.57) and β = −2.90 (95% CI = −5.20, −0.61), respectively], and significantly increased the risk of Cognition and Language developmental delay [OR= 1.64 (95% CI = 1.03, 2.62) and OR = 1.52 (95% CI = 1.06, 2.19), respectively]; cis-DBCA was inversely associated with Adaptive Behavior scores [β = −0.73 (95% CI = −1.27, −0.19)], and significantly increased the risk of Adaptive Behavior developmental delay [OR= 1.11 (95% CI = 1.02, 1.21)]. When the maternal levels of pyrethroid metabolites were stratified into the regression models according to the 90th percentile of exposure, in the first trimester, Cognition and Motor scores were inversely associated with higher cis-DBCA [β = −7.19 (95% CI = −12.97, −1.41) and β = −8.20 (95% CI = −13.35, −3.05), respectively], Language scores were inversely associated with higher 3-PBA [β = −6.01 (95% CI = −10.96, −1.06)]; in the second trimester, Cognition scores were inversely associated with higher cis-DBCA [β = −6.64 (95% CI = −12.51, −0.76)], Language scores were inversely associated with higher 3-PBA [β = −5.17 (95% CI = −10.07, −0.27)] and cis-DBCA [β = −5.40 (95% CI = −10.28, −0.52)]. We concluded that pyrethroid exposure in the first and second trimesters was associated with poorer infants neurodevelopmental outcomes at one year of age, and these effects were particularly pronounced at high levels of pyrethroid exposure.

Turkish Validity and Reliability of the Hammersmith Infant Neurological Examination (HINE) with High-Risk Infant Group: A Preliminary Study.

Objective: The purpose of this study was to establish the reliability of the Turkish translation of the Hammersmith Infant Neurological Examination in infants at 8-12 months corrected age and compare Hammersmith Infant Neurological Examination scores to other predictive assessments.Materials and Methods: Perinatal risk factors, term-age magnetic resonance imaging, general movements at 3-month corrected age, and 12-month corrected age The Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) scores were obtained in 35 high-risk infants. The Hammersmith Infant Neurological Examination was evaluated using intra-rater and inter-rater reliability. Hammersmith Infant Neurological Examination scores were compared to the findings from the three other assessments.Results: Intra-rater and inter-rater reliability was high (intraclass correlation coefficient = 1.00; intraclass correlation coefficient = 0.969, P < .001, 95% CI = 0.939-0.984, respectively). Global Hammersmith Infant Neurological Examination scores were significantly lower in infants with magnetic resonance imaging evidence of brain injury than without (P < .05) and in infants without general movements Fidgety movements (P < .05), than with. There was a significant positive correlation between global Hammersmith Infant Neurological Examination scores and Bayley Scales-III cognitive (P < .001), language (P < .001), and motor composite scores (P < .001).Conclusion: This study strongly supports the use of the Turkish translation of the Hammersmith Infant Neurological Examination. Users found it readily understandable and easy to use, and the scores were consistent with 3 different methods of predicting neurodevelopmental outcomes. These findings will aid the early diagnosis, management, and support for children with neurodevelopmental problems.

Early initial video-electro-encephalography combined with variant location predict prognosis of KCNQ2-related disorder

BackgroundThe clinical features of KCNQ2-related disorders range from benign familial neonatal seizures 1 to early infantile epileptic encephalopathy 7. The genotype-phenotypic association is difficult to establish.ObjectiveTo explore potential factors in neonatal period that can predict the prognosis of neonates with KCNQ2-related disorder.MethodsInfants with KCNQ2-related disorder were retrospectively enrolled in our study in Children’s Hospital of Fudan University in China from Jan 2015 to Mar 2020. All infants were older than age of 12 months at time of follow-up, and assessed by Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III) or Wechsler preschool and primary scale of intelligence-fourth edition (WPPSI-IV), then divided into three groups based on scores of BSID-III or WPPSI-IV: normal group, mild impairment group, encephalopathy group. We collected demographic variables, clinical characteristics, neuroimaging data. Considered variables include gender, gestational age, birth weight, age of the initial seizures, early interictal VEEG, variant location, delivery type. Variables predicting prognosis were identified using multivariate ordinal logistic regression analysis.ResultsA total of 52 infants were selected in this study. Early interictal video-electro-encephalography (VEEG) (β = 2.77, 1.20 to 4.34, P = 0.001), and variant location (β = 2.77, 0.03 to 5.5, P = 0.048) were independent risk factors for prognosis. The worse the early interictal VEEG, the worse the prognosis. Patients with variants located in the pore-lining domain or S4 segment are more likely to have a poor prognosis.ConclusionsThe integration of early initial VEEG and variant location can predict prognosis. An individual whose KCNQ2 variant located in voltage sensor, the pore domain, with worse early initial VEEG background, often had an adverse outcome.