Bayley Scales Of Infant Development, Third Edition Research Articles

Long-term visual and neurodevelopmental outcomes in children with Congenital Zika Syndrome after undergoing strabismus surgery.

Purpose: To assess long-term visual and neurodevelopmental outcomes in children with congenital Zika syndrome (CZS) after strabismus surgery. Methods: A consecutive sample of five children with CZS who underwent strabismus surgery was enrolled. All children underwent a standardized pre- and postoperative protocol including binocular best-corrected visual acuity (BCVA) using the Teller Acuity Cards II (TAC II), ocular alignment, functional vision using the functional vision developmental milestones test (FVDMT), and neurodevelopmental milestone evaluation using the Bayley Scales of Infant Development-Third Edition (BSID-III). Scores of the FVDMT outcomes considering the child's developmental age based on the BSID-III score were compared with scores from postoperative assessment. Results: Five children with CZS (3 girls, 2 boys) were enrolled with a mean age at baseline (preoperative) of 35.0 ± 0.7 months (range, 34-36 months) and at final assessment of 64.4 ± 0.5 months (range, 64-65 months). Preoperative BCVA was 1.2 ± 0.5 logMAR and at final assessment 0.7 ± 0.1 logMAR. Successful strabismus surgery outcome was maintained in 4/5 (80.0%) of children at final assessment. The children's BSID-III scores showed significant neurodevelopment delay at the initial assessment (corresponding developmental mean age was 4.7 months) and at their final assessment (corresponding developmental mean age was 5.1 months). There was improvement or stability in 34/46 items evaluated in the FVDMT (73.9%) when comparing baseline with 2-year follow-up. Conclusions: Strabismus surgery resulted in long-term ocular alignment in the majority of children with CZS. All the children showed improvement or stability in more than 70.0% of the functional vision items assessed. Visual and neurodevelopmental dysfunction may be related to complex condition and associated disorders seen in CZS including ocular, neurological, and skeletal abnormalities.

The effect of paternal parenting behaviors on children development in western rural China

Despite the crucial role of fathers’ parenting activities in early child development and the increasing global attention to fathers’ parenting behaviors, these is a paucity of knowledge regarding paternal parenting in rural China. Using a rich dataset of 1145 infants from rural China, we described the prevalent paternal parenting behaviors in the sample area and explored the correlations between fathers’ parenting behaviors and children’s cognitive outcome and socio-emotional development. To assess children’s cognitive development, we utilized various scales based on their development stages: the Bayley Scales of Infant Development-Third Edition (BSID-III) for ages 6–24 months and the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) for ages 52–85 months. Our overall findings revealed positive correlations between paternal behaviors and developmental outcomes of sampled children, including cognitive skills and social-emotional development. Fathers’ parenting behaviors in rural China are insufficient and need to be improved. Specifically, less than a quarter of fathers reported engaging in activities such as telling stories using picture books, singing songs, or playing with toys with their children in the past three days. Based on our findings, we recommend that local government provide additional parenting instructions to heighten fathers’ awareness and participation in parenting activities, especially in rural low-income areas. Additionally, creating more employment opportunities in their hometowns for fathers with young children could substantially benefit these children.

Genetic and Congenital Anomalies in Infants With Hypoxic-Ischemic Encephalopathy

BackgroundInfants with hypoxic ischemic encephalopathy (HIE) may have underlying conditions predisposing them to hypoxic-ischemic injury during labor and delivery. It is unclear how genetic and congenital anomalies impact outcomes of HIE. MethodsInfants with HIE enrolled in a phase III trial underwent genetic testing when clinically indicated. Infants with known genetic or congenital anomalies were excluded. The primary outcome, i.e., death or neurodevelopmental impairment (NDI), was determined at age two years by a standardized neurological examination, Bayley Scales of Infant Development, Third Edition (BSID-III), and the Gross Motor Function Classification Scales. Secondary outcomes included cerebral palsy and BSID-III motor, cognitive, and language scores at age two years. ResultsOf 500 infants with HIE, 24 (5%, 95% confidence interval 3% to 7%) were diagnosed with a genetic (n = 15) or congenital (n = 14) anomaly. Infants with and without genetic or congenital anomalies had similar rates of severe encephalopathy and findings on brain magnetic resonance imaging. However, infants with genetic or congenital anomalies were more likely to have death or NDI (75% vs 50%, P = 0.02). Among survivors, those with a genetic or congenital anomaly were more likely to be diagnosed with cerebral palsy (32% vs 13%, P = 0.02), and had lower BSID-III scores in all three domains than HIE survivors without such anomalies. ConclusionsAmong infants with HIE, 5% were diagnosed with a genetic or congenital anomaly. Despite similar clinical markers of HIE severity, infants with HIE and a genetic or congenital anomaly had worse neurodevelopmental outcomes than infants with HIE alone.

Platelet Transfusion and Death or Neurodevelopmental Impairment in Children Born Extremely Preterm

Infants born extremely preterm receive transfusions at higher platelet count thresholds than older children and adults due to concerns for intracranial hemorrhage. A recent randomized trial comparing 2 platelet transfusion thresholds showed the higher threshold was associated with increased risk of long-term adverse neurodevelopmental outcomes. To evaluate the association of platelet transfusion exposure with death and severe neurodevelopmental impairment (NDI) at 2 years' corrected age in a cohort of infants born extremely preterm. An observational cohort study and secondary analysis of the Preterm Erythropoietin Neuroprotection Trial, a randomized, placebo-controlled clinical trial of erythropoietin neuroprotection in neonates born extremely preterm, was conducted in 30 neonatal intensive care units in the US from December 1, 2013, to September 31, 2016. This analysis included 819 infants born extremely preterm at 24 to 27 completed weeks of gestation who had a documented outcome (death or neurodevelopmental assessment). Analysis was performed in April 2023. Any platelet transfusion during neonatal intensive care unit hospitalization. The primary composite outcome was death or severe NDI evaluated at 2 years' corrected age using the Bayley Scales of Infant Development-Third Edition (BSID-III) and the Gross Motor Function Classification System and was defined as the presence of severe cerebral palsy or a BSID-III composite motor or cognitive score 2 SDs below the mean. Confounding by indication for platelet transfusion was addressed with covariate adjustment and propensity score methods. Of the 819 infants included in the analysis (429 [52.4%] male; mean [SD] gestational age, 25.5 [1.1] weeks), 245 (30.0%) received at least 1 platelet transfusion during their initial hospitalization. The primary outcome occurred in 46.5% (114 of 245) of infants exposed to a platelet transfusion and 13.9% (80 of 574) of nonexposed infants with a corresponding odds ratio of 2.43 (95% CI, 1.24-4.76), adjusted for propensity score, gestational age at birth, and trial treatment group. The individual components of death and severe NDI were directionally consistent with the overall composite outcome. The findings of this study suggest that platelet transfusion in infants born extremely preterm may be associated with an increased risk of death or severe NDI at 2 years' corrected age, although the possibility of residual confounding by indication cannot be excluded.

Adaptive functioning and neurodevelopment in patients with Dravet syndrome: 12-month interim analysis of the BUTTERFLY observational study

ObjectiveThe BUTTERFLY observational study aims to elucidate the natural trajectory of Dravet syndrome (DS) and associated comorbidities in order to establish a baseline for clinical therapies. We present the 12-month interim analysis of the study. Materials and methodsPatients with a genetically confirmed diagnosis of DS were enrolled in the study. Adaptive functioning and neurodevelopmental status were measured using the Vineland Adaptive Behavior Scale, Third Edition (Vineland-III), Bayley Scales of Infant Development, Third Edition (BSID-III), and Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Executive function, ambulatory function and locomotor activities, and overall clinical status were measured using the Behavior Rating Inventory of Executive Function – Preschool Version (BRIEF-P) scale, Gillette Functional Assessment Questionnaire (Gillette FAQ), and Clinician or Caregiver Global Impression of Change scales (CGI-C or CaGI-C) respectively. ResultsOverall, 36 patients were enrolled across three age groups, with 35 patients completing at least part or all of one post-baseline visit through Month 12. Significant improvements in receptive communication, as assessed by Vineland-III and BSID-III raw scores, and in verbal comprehension subtests, as assessed by WPPSI-IV raw scores, were observed in BUTTERFLY patients for the all-patient group. Many patients performed on the impaired end of the BRIEF-P Global Executive Composite scale at baseline suggesting difficulties in executive function, and no significant change was observed in BRIEF-P scores for the all-patient group. Most patients performed in the dynamic range of the Gillette FAQ at baseline, and no significant change was observed in Gillette FAQ scores for the all-patient group. Lastly, there was significant improvement observed in the CaGI-C scores for the all-patient group. SignificanceThis BUTTERFLY interim analysis shows small improvements in communication skills along with stability in other developmental abilities across patients with DS enrolled in the study from baseline to Month 12.

Neurodevelopment Outcomes in Very-Low-Birth-Weight Infants with Metabolic Bone Disease at 2 Years of Age.

Metabolic bone disease (MBD) predominantly affects preterm infants, particularly very-low-birth-weight (VLBW) infants weighing <1500 g. However, there are limited reports on MBD and neurodevelopmental outcomes. This study aimed to analyze the risk factors for MBD and understand its impact on neurodevelopmental outcomes at 2 years of corrected age. Overall, 749 VLBW infants weighing <1350 g at birth were enrolled. Exclusion criteria were major congenital abnormalities, chromosomal abnormalities, and loss of follow-up on the Bayley Scales of Infant Development, Third Edition (BSID-III) test at 24 months of corrected age. Infants were retrospectively assessed by a trained case manager using the BSID-III test at 6, 12, and 24 months old. Infants were categorized as with or without MBD according to radiographic signs. Of those enrolled, 97 VLBW infants were diagnosed with MBD, compared to 362 VLBW infants without MBD. The proportion of infants that completed three follow-ups was 86%. At the assessment at 2 years of age, infants with MBD had lower and more significant differences in motor, language, and cognitive composites. MBD is associated with poor neurodevelopmental outcomes in cognitive, motor, and language composites for VLBW infants at 24 months of corrected age.

Screen time: Implications for early childhood cognitive development

BackgroundExposure and introduction to digital media, especially in children, are a current cause for concern. The negative links associated with early screen exposure are extensive. AimsTo evaluate the association between the time of exposure to a screen in children at 18 months of age and cognitive development in a population-based sample in Southern Brazil. Study designThis was a cross-sectional study corresponding to the fourth wave of a population-based cohort study with pregnant women and later, their children living in the city of Pelotas, Southern Brazil. SubjectsThe sample consisted of 470 children who completed the cognitive assessment. Outcome measuresCognitive development was assessed using the Bayley Scales of Infant Development - Third Edition (BSID-III). Exposure to screen time was assessed using a questionnaire completed by the primary caregiver. ResultsOf the total, 58.8 % of the children had ≥1 h of screen time per day and the average on the cognitive scale of the entire sample was 96.1 (SD = 14.0). Cognitive development was lower in children whose mothers had lower levels of education (CI 95 % -4.9; −2.1), where boys (CI 95 % 3.2; 8.4) and in children exposed to 2 h or more of screen time/day (CI 95 % -3.6; −0.5). ConclusionsExposure to screens may have a significant negative association with children's cognitive development and, therefore, we seek to intervene and to give advice to parents and guardians about the true impact of digital media. Further studies are necessary to consolidate the findings and to disclose information on the topic.

Minor painful procedures in extremely preterm infants admitted to a tertiary neonatal intensive care unit: Opportunities to improve pain mitigation.

This study aims to characterise current pain management practices in extremely preterm infants (gestational age less than or equal to 28 weeks) admitted to neonatal intensive care unit (NICU). Retrospective audit pertaining to patient characteristics, as well as minor painful procedures (MPP), pain mitigation and pain scoring in 25 extremely preterm infants admitted to a tertiary NICU in 2016 over the first 14 days of NICU admission. Opportunities to bundle MPP were identified according to pre-specified criteria. Bayley Scales of Infant Development, Third Edition (BSID-III) cognitive, language and motor composite scores were available from the neurodevelopmental follow-up clinic at 12- and 24-months of corrected age. Linear mixed methods regression was used to examine for correlation between increased exposure to MPP and BSID-III scores at follow-up. Extremely preterm infants underwent an average of 11.24 ± 4.12 MPP per day for the first 14 days of NICU admission. Opportunities to bundle MPP were missed 75.98% (408/537) of the time; most of these were invasive blood collections. A total of 12.2% (481/3933) of MPP occurred within 4 h of pharmacological or non-pharmacological pain mitigation. BSID-III motor composite score was associated with an 11.75 (95% confidence interval 1.99, 21.27) decrease in patients experiencing more than or equal to the third quartile of MPP in the 14 days post-NICU admission (P=0.0329, n= 42). Association was not found for BSID-III cognitive and language composite scores. There is readily scope for quality improvement initiatives to reduce harm in extremely preterm infants admitted to NICU.

Influence of pre-eclampsia on 2-year neurodevelopmental outcome of very-low-birth-weight infants.

To evaluate the influence of maternal pre-eclampsia on neurodevelopmental outcome in very-low-birth-weight (VLBW) infants at 6, 12, and 24 months of corrected age. We conducted a retrospective cohort study of singleton VLBW infants between 2011 and 2018. The participants were divided into three groups: (1) mothers without pre-eclampsia, (2) pre-eclampsia without severe features, and (3) pre-eclampsia with severe features. The Bayley Scales of Infant Development third edition (BSID-III) was used to assess the neurodevelopment of participants. A BSID-III score < 85 was defined as neurodevelopmental impairment (NDI). Overall, 482 VLBW infants born to 482 mothers were enrolled, of whom 327 mothers did not have pre-eclampsia and 155 mothers had pre-eclampsia (58 without and 97 with severe features). The infants born to mothers with pre-eclampsia with severe features had the lowest BSID-III scores at 6, 12, and 24 months. After adjustments, maternal pre-eclampsia with severe features was significantly associated with cognitive NDI in their infants (adjusted odds ratio [aOR] 4.14) and language NDI (aOR 3.37) at 2 years of corrected age. VLBW fetuses born to mothers with pre-eclampsia with severe features have poorer 2-year neurodevelopmental outcome, which mainly manifests in the cognitive and language domains.

Maternal-fetal attachment and social-emotional development in infants at 3 months of age: A population-based study in southern Brazil

Studies relate Maternal-Fetal Attachment (MFA) to delays in child development, however, the relationship with the social-emotional development is still unclear. Thus, the aim of this study was to investigate the association between MFA and social-emotional development in infants at 3 months old, in a population-based sample in southern Brazil. This was a follow-up study corresponding to second and third wave of a population-based cohort study with pregnant women who were living in Pelotas (Southern Brazil). Social-emotional development was assessed using the Bayley Scales of Infant Development - Third Edition (BSID-III) and MFA was measured with the Maternal-Fetal Attachment Scale (MFAS). The sample consisted of 702 mother-infant dyads. In the adjusted analysis, MFA was a predictor of social-emotional development, even when controlled for sociodemographic, maternal mental health and infant characteristics. Thus, with each increase to one point in the MFA score, there was an increase of β = 0.14, 95% CI [0.05, 0.23] in the social-emotional development score. These findings highlight the importance of MFA in early child development. Thus, infants with positive experiences of affection since the gestational period will be able to develop positive social and emotional health.

Interim results of adaptive functioning and neurodevelopment in BUTTERFLY – An observational study of children and adolescents with Dravet syndrome

PurposeThe purpose of this study is to evaluate adaptive functioning and neurodevelopment study assessments in a prospective study of patients with Dravet syndrome (DS). We present 3-month interim adaptive functioning and neurodevelopment data from the prospective, observational BUTTERFLY study in patients with DS aged 2–18 years. ResultsBUTTERFLY enrolled thirty-six patients divided 1:1:1 across three age groups (2–7: 8–12: and 13–18 years). Most enrolled patients were female (61.1%), white (94.4%), and non-Latino (83.3%) with a mean (standard deviation; SD) age of 10.8 (5.2) years and a mean (range) age of seizure onset of 0.4 (0.2–1.0) years. Patients used a mean (SD) of 3.5 (1.63) anti-seizure therapies at baseline. Regression analysis of the baseline Vineland Adaptive Behavior Scale – third edition (VABS-III) composite score indicated that the gap in adaptive function between patients with DS (n = 33) and neurotypical children widens with age. Similarly, developmental quotients calculated for patients who completed all Bayley Scales of Infant Development – third edition (BSID-III) subtests at baseline (n = 15) highlighted a gap in intellectual functioning between patients with DS and neurotypical children that widens with age. More patients in the two older age groups were able to validly complete the Wechsler Preschool and Primary Scale of Intelligence – fourth edition (WPPSI-IV) at baseline compared with the youngest age group. There were trends towards higher raw scores, albeit of low magnitude, in the oldest age group compared with the younger age two groups across multiple VABS-III domains and WPPSI-IV subtests. All three measures showed no significant change in the all-patients analyses and demonstrated relatively low intra-patient variability from baseline to Month 3. ConclusionsThree-month interim data from BUTTERFLY demonstrated the feasibility of utilizing the VABS-III, BSID-III, and WPPSI-IV for the assessment of adaptive function and neurodevelopment in future clinical studies of DS. Moreover, many patients with DS appear to gain neurodevelopmental and adaptive function skills over time, although at a slower rate and lower magnitude than that seen in the neurotypical population.

Dexamethasone, Prednisolone, and Methylprednisolone Use and 2-Year Neurodevelopmental Outcomes in Extremely Preterm Infants

Practice variability exists in the use of corticosteroids to treat or prevent bronchopulmonary dysplasia in extremely preterm infants, but there is limited information on longer-term impacts. To describe the use of corticosteroids in extremely preterm infants and evaluate the association with neurodevelopmental outcomes. This cohort study was a secondary analysis of data from the Preterm Erythropoietin Neuroprotection (PENUT) randomized clinical trial, conducted at 19 participating sites and 30 neonatal intensive care units (NICUs) in the US. Inborn infants born between 24 0/7 and 27 6/7 weeks gestational age between December 2013 and September 2016 were included in analysis. Data analysis was conducted between February 2021 and January 2022. Cumulative dose of dexamethasone and duration of therapy for dexamethasone and prednisolone or methyl prednisolone were evaluated. Demographic and clinical characteristics were described in infants who did or did not receive corticosteroids of interest and survived to discharge. Neurodevelopmental outcomes at 2 years of age were evaluated using the Bayley Scales of Infant Development-Third Edition (BSID-III) at corrected age 2 years. A total of 828 extremely preterm infants (403 [49%] girls; median [IQR] gestational age, 26 [25-27] weeks) born at 19 sites who survived to discharge were included in this analysis, and 312 infants (38%) were exposed to at least 1 corticosteroid of interest during their NICU stay, including 279 exposed to dexamethasone, 137 exposed to prednisolone or methylprednisolone, and 79 exposed to both. Exposed infants, compared with nonexposed infants, had a lower birth weight (mean [SD], 718 [168] g vs 868 [180] g) and were born earlier (mean [SD] gestational age, 25 [1] weeks vs 26 [1] weeks). The median (IQR) start day was 29 (20-44) days for dexamethasone and 53 (30-90) days for prednisolone or methylprednisolone. The median (IQR) total days of exposure was 10 (5-15) days for dexamethasone and 13 (6-25) days for prednisolone or methylprednisolone. The median (IQR) cumulative dose of dexamethasone was 1.3 (0.9-2.8) mg/kg. After adjusting for potential confounders, treatment with dexamethasone for longer than 14 days was associated with worse neurodevelopmental outcomes, with mean scores in BSID-III 7.4 (95% CI, -12.3 to -2.5) points lower in the motor domain (P = .003) and 5.8 (95% CI, -10.9 to -0.6) points lower in the language domain (P = .03), compared with unexposed infants. These findings suggest that long duration and higher cumulative dose of dexamethasone were associated with worse neurodevelopmental scores at corrected age 2 years. Potential unmeasured differences in the clinical conditions of exposed vs unexposed infants may contribute to these findings. Improved standardization of treatment and documentation of indications would facilitate replication studies.

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.

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.

A randomized controlled trial testing the efficacy of a Nurse Home Visiting Program for Pregnant Adolescents

To test the efficacy of a nurse home visiting program (HVP) on child development, maternal and environmental outcomes in the first years of life. We conducted a randomized controlled trial to test the efficacy of Primeiros Laços, a nurse HVP for adolescent mothers living in a poor urban area of São Paulo, Brazil. Eighty adolescent mothers were included and randomized to receive either Primeiros Laços (intervention group, n = 40) or healthcare as usual (control group, n = 40). Primeiros Laços is a home visiting intervention delivered by trained nurses that starts during the first 16 weeks of pregnancy and continues to the child’s age of 24 months. Participants were assessed by blind interviewers at 8–16 weeks of pregnancy (baseline), 30 weeks of pregnancy, and 3, 6, 12, and 24 months of child’s age. We assessed oscillatory power in the mid-range alpha frequency via electroencephalography when the children were aged 6 months. Child development was measured by the Bayley Scales of Infant Development Third Edition (BSID-III). Weight and length were measured by trained professionals and anthropometric indexes were calculated. The home environment and maternal interaction with the child was measured by the Home Observation and Measurement of the Environment. Generalized estimating equation models were used to examine intervention effects on the trajectories of outcomes. Standardized effect sizes (Cohen’s d) were calculated using marginal means from endpoint assessments of all outcomes. The trial was registered at clinicaltrial.gov: NCT02807818. Our analyses showed significant positive effects of the intervention on child expressive language development (coefficient = 0.89, 95% CI [0.18, 1.61], p = 0.014), maternal emotional/verbal responsivity (coefficient = 0.97, 95% CI [0.37, 1.58], p = 0.002), and opportunities for variety in daily stimulation (coefficient = 0.37, 95% CI [0.09, 0.66], p = 0.009). Standardized effect sizes of the intervention were small to moderate. Primeiros Laços is a promising intervention to promote child development and to improve the home environment of low-income adolescent mothers. However, considering the limitations of our study, future studies should be conducted to assess Primeiros Laços potential to benefit this population.Clinical Trial Registration: The study was registered at clinicaltrial.gov (Registration date: 21/06/2016 and Registration number: NCT02807818).

Assessment of 2-Year Neurodevelopmental Outcomes in Extremely Preterm Infants Receiving Opioids and Benzodiazepines

Extremely preterm (EP) infants frequently receive opioids and/or benzodiazepines, but these drugs' association with neurodevelopmental outcomes is poorly understood. To describe the use of opioids and benzodiazepines in EP infants during neonatal intensive care unit (NICU) hospitalization and to explore these drugs' association with neurodevelopmental outcomes at 2 years' corrected age. This cohort study was a secondary analysis of data from the Preterm Erythropoietin Neuroprotection (PENUT) Trial, which was conducted among infants born between gestational ages of 24 weeks, 0 days, and 27 weeks, 6 days. Infants received care at 19 sites in the United States, and data were collected from December 2013 to September 2016. Data analysis for this study was conducted from March to December 2020. Short (ie, ≤7 days) and prolonged (ie, >7 days) exposure to opioids and/or benzodiazepines during NICU stay. Cognitive, language, and motor development scores were assessed using the Bayley Scales of Infant Development-Third Edition (BSID-III). There were 936 EP infants (448 [48%] female infants; 611 [65%] White infants; mean [SD] gestational age, 181 [8] days) included in the study, and 692 (74%) had neurodevelopmental outcome data available. Overall, 158 infants (17%) were not exposed to any drugs of interest, 297 (32%) received either opioids or benzodiazepines, and 481 (51%) received both. Infants exposed to both had adjusted odds ratios of 9.7 (95% CI, 2.9 to 32.2) for necrotizing enterocolitis and 1.7 (95% CI, 1.1 to 2.7) for severe bronchopulmonary dysplasia; they also had a longer estimated adjusted mean difference in length of stay of 34.2 (95% CI, 26.2 to 42.2) days compared with those who received neither drug. After adjusting for site and propensity scores derived for each exposure category, infants exposed to opioids and benzodiazepines had lower BSID-III cognitive, motor, and language scores compared with infants with no exposure (eg, estimated difference in mean scores on cognitive scale: -5.72; 95% CI, -8.88 to -2.57). Prolonged exposure to morphine, fentanyl, midazolam, or lorazepam was associated with lower BSID-III scores compared with infants without exposure (median [interquartile range] motor score, 85 [73-97] vs 97 [91-107]). In contrast, BSID-III scores for infants with short exposure to both opioids and benzodiazepines were not different than those of infants without exposure. In this study, prolonged combined use of opioids and benzodiazepines was associated with a risk of poorer neurodevelopmental outcomes as measured by BSID-III at 2 years' corrected age.

Comparison of the neurocognitive outcomes in term infants treated with levetiracetam and phenobarbital monotherapy for neonatal clinical seizures

PurposeThis study aims to compare the neurocognitive outcome in term infants who were treated using phenobarbital (PB) and levetiracetam (LEV) monotherapy for neonatal clinical seizures. MethodsTerm infants who were treated using PB or LEV monotherapy as the first-line anti-epileptic treatment for neonatal clinical seizures and followed-up in a pediatric neurology outpatient clinic were enrolled in this study. Neurodevelopmental outcome assessments were carried out using the Bayley Scales of Infant Development, third edition (BSID-III), including cognitive, receptive language, expressive language, fine motor and gross motor subscales. ResultsThe study group consisted of 62 infants who received monotherapy with PB monotherapy (n = 22) and LEV (n = 40). The mean duration of monotherapy treatment was 8 ± 6 months. There was no statistically significant difference between PB and LEV monotherapy groups concerning each outcome parameter on the BSID-III. There was also no statistically significant difference between PB and LEV monotherapy subgroups excluding the infants with neurodevelopmental impairment with a BSID-III scale score<7 or a composite score<85. ConclusionOur findings suggest that both LEV and PB therapy can be equally safe as monotherapy for neonatal clinical seizures for the neurodevelopmental outcome assessment with BSID-III.

Neurodevelopmental and behavioural outcomes of HIV-exposed uninfected and HIV-unexposed children at 2–3 years of age in Cape Town, South Africa

ABSTRACTSuccessful vertical HIV transmission prevention programmes (VTP) have resulted in an expanding population of HIV-exposed uninfected (HEU) infants whose growth, health and neurodevelopmental outcomes could have consequences for future resource allocation. We compared neurodevelopmental and behavioural outcomes in a prospective cohort of 2–3 year old HEU and HIV-unexposed uninfected (HU) children.Women living with and without HIV and their infants were enrolled within three days of birth from a low-risk midwife obstetric unit in Cape Town, South Africa during 2012 and 2013, under WHO Option A VTP guidelines. HIV-uninfected children aged 30–42 months were assessed using the Bayley scales of Infant Development-Third edition (BSID) and Strengths and Difficulties questionnaire (SDQ).Thirty-two HEU and 27 HU children (mean birth weight 3048g vs 3096g) were assessed. HEU children performed as well as HU children on BSID cognitive, language and motor domains. Mean scores fell within the low average range. Mothers of HEU children reported fewer conduct problems but stunting was associated with increased total difficulties on the SDQ.HEU and HU children’s performance on the BSID was similar. In this low-risk cohort, HIV exposure did not confer additional risk. Stunting was associated with increased behavioural problems irrespective of HIV exposure.

Serum neurotrophins at birth correlate with respiratory and neurodevelopmental outcomes of premature infants.

Preterm birth is a significant cause of infant morbidity and mortality, which are primarily the result of respiratory and neurodevelopmental complications. However, no objective biomarker is currently available to predict at birth the risk and severity of such complications. Thus, we sought to determine whether serum neurotrophins concentrations measured at birth correlate with risk for later development of bronchopulmonary dysplasia (BPD) and long-term neurodevelopmental outcomes. This study prospectively included 223 newborns admitted to neonatal intensive care units (NICU) and divided into three groups: (i) preterm infants who developed BPD; (ii) preterm infants who did not develop BPD; (iii) term infants. An exploratory cohort was enrolled in West Virginia, followed by a validation cohort recruited in four NICUs in Ohio. Specimens for serum and tracheal neurotrophins concentrations were collected within 48 h of admission. Infants requiring a fraction of inspired oxygen >0.21 for at least 28 days were diagnosed with BPD. Neurodevelopmental outcomes were extrapolated from Bayley Scales of Infant Development-Third Edition (BSID-III) administered at the 24-month follow-up visit. Serum brain-derived neurotrophic factor (BDNF) concentration at birth had significant negative correlation with later diagnosis of BPD (P = 0.011) and with duration of invasive ventilation and oxygen supplementation (P = 0.009 and 0.015, respectively). Serum nerve growth factor (NGF) concentration at birth had significant positive correlation with BSID-III cognitive and language composite scores at 24 months (P < 0.001 and 0.010, respectively). These data suggest that serum neurotrophins concentrations measured at birth provide prognostic information on subsequent respiratory and neurodevelopmental outcomes.

Prediction of long-term neurodevelopmental outcome in preterm infants using trajectories of general movement assessments.

To assess the predictive value of trajectories and individual assessment of quality of general movements (AQGM) for identification of neurodevelopmental impairment (NDI) at 18-24 months corrected age (CA) in infants <30 weeks gestational age and/or birth weight <1500 g. In this retrospective cohort study, AQGM at 6 weeks and 3 months CA were scored and categorized as normal (N) or abnormal (A). AQGM measures were compared with degree of NDI and Bayley Scales of Infant Development, Third Edition (BSID-III) composite motor and cognitive scores. 'Persistently abnormal' AQGM included both mildly abnormal (MA) and definitely abnormal (DA) assessments. A "modified AQGM" where MA assessments were considered normal variant/transient injury was used to conduct post-hoc analysis. Across 244 cases, persistently abnormal AQGM trajectory predicted the level of NDI (OR 2.5, 95% CI 1.2, 5.1) compared to AQGM trajectory that normalized. However, using the "modified AQGM", persistently DA trajectories were associated with significantly lower BSID-III composite motor and cognitive scores (p < 0.001 and p = 0.039, respectively). Categorizing MA assessments as transient injury increased the predictive value of AQGM trajectories and significantly predicted lower cognitive and motor scores at 18-24 months CA.