Stability of executive function in children born at risk of neonatal hypoglycemia.

Executive function plays an important role in promoting learning and social-emotional development in children. Neonatal hypoglycemia associates with executive function difficulties at 4.5 years, but little is known about the development of executive function over time in children born at risk of neonatal hypoglycemia. We aimed to describe the stability of executive function from early to mid-childhood in children born at risk of neonatal hypoglycemia and its association with neonatal hypoglycemia. Participants in a prospective cohort study of infants born at risk for neonatal hypoglycemia were assessed at ages 2, 4.5, and 9-10 years. We assessed executive function with batteries of performance-based and questionnaire-based measures, and classified children into one of four stability groups (persistent typical, intermittent typical, intermittent difficulty, and persistent difficulty) based on dichotomized scores (typical versus low at each age). Multinomial logistic regression was used to determine the associations between neonatal hypoglycemia and executive function stability groups. Three hundred and nine children, of whom 197 (64%) experienced neonatal hypoglycemia were assessed. The majority of children had stable and typical performance-based (63%) and questionnaire-based (68%) executive function across all three ages. Around one-third (30-36%) of children had transient difficulties, and only a few (0.3-1.9%) showed persistent difficulties in executive function at all ages. There was no consistent evidence of an association between neonatal hypoglycemia and the stability of executive function. Neonatal hypoglycemia does not appear to predict a specific pattern of development of executive function in children born at risk.

Associations Between Autism Spectrum Quotient and Integration of Visual Stimuli in 9-year-old Children: Preliminary Evidence of Sex Differences.

PURPOSE: The dorsal stream vulnerability hypothesis posits that the dorsal stream, responsible for visual motion and visuo-motor processing, may be particularly vulnerable during neurodevelopment. Consistent with this, autism spectrum disorder (ASD) has been associated with deficits in global motion integration, though deficits in ventral stream tasks, such as form identification, have also been reported. In the current study, we examined whether a similar pattern of results is found in a cohort of 381 children born with neurodevelopmental risk factors and exhibiting a wide spectrum of caregiver-reported autistic traits. METHODS: We examined the associations between global motion perception, global form perception, fine motor function, visual-motor integration, and autistic traits (autism spectrum quotient, AQ) using linear regression, accounting for possible interactions with sex and other factors relevant to neurodevelopment. RESULTS: All assessments of dorsal stream function were significantly associated with AQ such that worse performance predicted higher AQ scores. We also observed a significant sex interaction, with worse global form perception associated with higher AQ in boys (n = 202) but not girls (n = 179). CONCLUSION: We found widespread associations between dorsal stream functions and autistic traits. These associations were observed in a large group of children with a range of AQ scores, demonstrating a range of visual function across the full spectrum of autistic traits. In addition, ventral function was associated with AQ in boys but not girls. Sex differences in the associations between visual processing and neurodevelopment should be considered in the designs of future studies.

Executive function and behaviour problems in school-age children born at risk of neonatal hypoglycaemia.

AIM: To examine the relationship between neonatal hypoglycaemia and specific areas of executive function and behaviour in mid-childhood. METHOD: Participants in a prospective cohort study of infants born late preterm or at term at risk of neonatal hypoglycaemia were assessed at 9 to 10 years. We assessed executive function using performance-based (Cambridge Neuropsychological Tests Automated Battery) and questionnaire-based (Behavior Rating Inventory of Executive Function) measures and behaviour problems with the Strengths and Difficulties Questionnaire. Data are reported as adjusted odds ratio (aOR) with 95% confidence intervals, and standardized regression coefficients. RESULTS: We assessed 480 (230 females, 250 males; mean age 9 years 5 months [SD 4 months, range 8 years 8 months-11 years 0 months]) of 587 eligible children (82%). There were no differences in performance-based executive function between children who did and did not experience neonatal hypoglycaemia (blood glucose <2.6 mmoL/L). However, children who experienced hypoglycaemia, especially if severe or recurrent, were at greater risk of parent-reported metacognition difficulties (aOR 2.37-3.71), parent-reported peer (aOR 1.62-1.89) and teacher-reported conduct (aOR 2.14 for severe hypoglycaemia) problems. Both performance- and questionnaire-based executive functions were associated with behaviour problems. INTERPRETATION: Neonatal hypoglycaemia may be associated with difficulties in specific aspects of parent-reported executive functions and behaviour problems in mid-childhood.

Mid-Childhood Outcomes after Dextrose Gel Treatment of Neonatal Hypoglycaemia: Follow-Up of the Sugar Babies Randomized Trial.

INTRODUCTION: Dextrose gel is widely used as first-line treatment for neonatal hypoglycaemia given its cost-effectiveness and ease of use. The Sugar Babies randomized trial first showed that 40% dextrose gel was more effective in reversing hypoglycaemia than feeding alone. Follow-up of the Sugar Babies Trial cohort at 2 and 4.5 years of age reported that dextrose gel appeared safe, with similar rates of neurosensory impairment in babies randomized to dextrose or placebo gel. However, some effects of neonatal hypoglycaemia may not become apparent until school age. METHODS: Follow-up of the Sugar Babies Trial cohort at 9-10 years of age was reported. The primary outcome was low educational achievement in reading or mathematics. Secondary outcomes included other aspects of educational achievement, executive function, visual-motor function, and psychosocial adaptation. RESULTS: Of 227 eligible children, 184 (81%) were assessed at a mean (SD) age of 9.3 (0.2) years. Low educational achievement was similar in dextrose and placebo groups (36/86 [42%] vs. 42/94 [45%]; RR 1.04, 95% CI 0.76, 1.44; p = 0.79). Children allocated to dextrose gel had lower visual perception standard scores (95.2 vs. 100.6; MD -5.68, 95% CI -9.79, -1.57; p = 0.006) and a greater proportion had low (<85) visual perception scores (20/88 [23%] vs. 10/95 [11%]; RR 2.23, 95% CI 1.13, 4.37; p = 0.02). Other secondary outcomes, including other aspects of visual-motor function, were similar in both groups. CONCLUSION: Treatment dextrose gel does not appear to result in any clinically significant differences in educational achievement or other neurodevelopmental outcomes at mid-childhood.

Association of Neonatal Hypoglycemia With Academic Performance in Mid-Childhood.

Importance: Neonatal hypoglycemia is associated with increased risk of poor executive and visual-motor function, but implications for later learning are uncertain. Objective: To test the hypothesis that neonatal hypoglycemia is associated with educational performance at age 9 to 10 years. Design, Setting, and Participants: Prospective cohort study of moderate to late preterm and term infants born at risk of hypoglycemia. Blood and masked interstitial sensor glucose concentrations were measured for up to 7 days. Infants with hypoglycemic episodes (blood glucose concentration <47 mg/dL [2.6 mmol/L]) were treated to maintain a blood glucose concentration of at least 47 mg/dL. Six hundred fourteen infants were recruited at Waikato Hospital, Hamilton, New Zealand, in 2006-2010; 480 were assessed at age 9 to 10 years in 2016-2020. Exposures: Hypoglycemia was defined as at least 1 hypoglycemic event, representing the sum of nonconcurrent hypoglycemic and interstitial episodes (sensor glucose concentration <47 mg/dL for ≥10 minutes) more than 20 minutes apart. Main Outcomes and Measures: The primary outcome was low educational achievement, defined as performing below or well below the normative curriculum level in standardized tests of reading comprehension or mathematics. There were 47 secondary outcomes related to executive function, visual-motor function, psychosocial adaptation, and general health. Results: Of 587 eligible children (230 [48%] female), 480 (82%) were assessed at a mean age of 9.4 (SD, 0.3) years. Children who were and were not exposed to neonatal hypoglycemia did not significantly differ on rates of low educational achievement (138/304 [47%] vs 82/176 [48%], respectively; adjusted risk difference, -2% [95% CI, -11% to 8%]; adjusted relative risk, 0.95 [95% CI, 0.78-1.15]). Children who were exposed to neonatal hypoglycemia, compared with those not exposed, were significantly less likely to be rated by teachers as being below or well below the curriculum level for reading (68/281 [24%] vs 49/157 [31%], respectively; adjusted risk difference, -9% [95% CI, -17% to -1%]; adjusted relative risk, 0.72 [95% CI, 0.53-0.99; P = .04]). Groups were not significantly different for other secondary end points. Conclusions and Relevance: Among participants at risk of neonatal hypoglycemia who were screened and treated if needed, exposure to neonatal hypoglycemia compared with no such exposure was not significantly associated with lower educational achievement in mid-childhood.

Cognitive vulnerabilities to anxiety symptoms among Chinese adolescents: A 3-year longitudinal study.

OBJECTIVE: This study established cognitive vulnerability of anxiety symptoms among high school students. METHOD: A total of 72 grade 9-11 students completed measures on levels of anxiety sensitivity (AS), selective attentional processing, and anxiety symptoms annually between 2016 and 2018. RESULTS: Latent class growth analysis (unconditional model) showed a four-class model: High (stable) (6.94%), low (stable) (11.11%), medium (decreasing) (61.11%), and medium (increasing) (20.83%). The conditioned model controlling for the physical-concerns dimension of AS and negative attentional bias demonstrated that a two-class model consisted of a low anxiety class (n = 59, 81.9%) and a high anxiety class (n = 13, 18.1%) provided the best fit for the data. Negative attentional bias is a significant factor related to the development of anxiety trajectories. CONCLUSION: Attentional bias modification to disengage from negative stimuli may serve as a potential target of intervention to reduce chronic anxiety among high school students.

The contributions of intelligence and executive function to behaviour problems in school-age children born very preterm.

AIM: To examine the contributions of specific neurocognitive skills to behaviour problems in children born very preterm. METHODS: We assessed children born <30 weeks' gestation or <1500 g at age 7 years using subtests of the Wechsler Intelligence Scale for Children Fourth Edition, performance and questionnaire-based measures of executive function, and Child Behavior Checklist and Teacher Rating Form. We evaluated the contributions of IQ and executive function to behaviour problems and the moderating effect of sex using multiple regression. RESULTS: The 129 children (mean age = 7.2 years) had lower IQ, inferior executive function and increased internalising problems compared with normative samples. Verbal comprehension skills and working memory were associated with total, internalising and externalising problems at school. Performance-based and questionnaire-based executive function were associated with total and externalising behaviour problems both at home and school. Sex moderated the relationships between information processing and parent-reported total problems, and between teacher-rated executive function and total problems. CONCLUSION: Both IQ and executive function are related to behaviour problems in children born very preterm, but the relationships are different in boys and girls. Executive function may be a useful target for intervention.

Relationships between intelligence, executive function and academic achievement in children born very preterm.

BACKGROUND: Children born very preterm are at higher risk of adverse neurocognitive and educational outcomes. However, how low intelligence (IQ) and low executive function may each contribute to poorer academic outcomes at school age requires clarification. AIM: To examine the associations between intelligence, executive function and academic achievement in children born very preterm. DESIGN/METHODS: This cohort study assessed children born <30 weeks' gestation or <1500 g at age 7 years using the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) for IQ, and the Test of Everyday Attention for Children (TEA-Ch) and Behavior Rating Inventory of Executive Function (BRIEF) for executive function. Academic achievement was rated by teachers against curriculum standards. RESULTS: Of the 76 children (35 girls, 41 boys, mean age = 7.2 year), 22 (28%) were rated below expected level for reading, 32 (42%) for writing and 38 (50%) for mathematics. After adjustment for sex and socioeconomic status, low IQ (OR's 9.0-12.3) and most low executive function measures (OR's 4.1-9.3) were associated with below-expected achievement. After further adjustment for IQ, low cognitive flexibility (OR = 9.3, 95% CI = 1.2-71.5) and teacher ratings of executive function (OR = 5.3, 95% CI = 1.4-20.2) were associated with below-expected achievement. Mediation analysis showed IQ had indirect effects on writing (b = 1.5, 95% CI = 0.6-3.1) via attentional control; and on reading (b = 1.0, 95% CI = 0.2-3.2) and writing (b = 0.8, 95% CI = 0.1-2.5) via cognitive flexibility. CONCLUSIONS: Both low IQ and low executive function are associated with below-expected teacher-rated academic achievement in children born very preterm. IQ may influence academic achievement in part through executive function.