Children at risk of neonatal hypoglycemia who were screened and treated if needed showed no difference in educational achievement from controls at age 9-10 years, based on data from 480 children.
Previous studies have shown an increased risk of poor executive and visual-motor function in children with neonatal hypoglycemia, but the effect on later childhood academic performance remains unclear, wrote Rajesh Shah, PhD, of the University of Auckland, New Zealand, and colleagues.
In a prospective cohort study published in JAMA, the researchers enrolled moderate to late preterm and term infants born at increased risk for hypoglycemia; those with episodes of hypoglycemia were treated to maintain a blood glucose concentration of at least 47 mg/dL.
The study population was enrolled between 2006 and 2010 at a regional perinatal center in New Zealand, and their educational achievement was assessed 9-10 years later. The primary outcome of low educational achievement was defined as performing below the normal curriculum level in standardized tests of reading comprehension or math. The researchers also identified 47 secondary outcomes related to executive function, visual-motor function, psychosocial adaptation, and general health.
Rates of low educational achievement were not significantly different for children with and without neonatal hypoglycemia (47% vs. 48%, adjusted risk ratio 0.95).
No significant differences appeared between the two groups for any secondary outcomes, including reading comprehension, math, behavior manifestations of executive function, fine motor function, autism traits, and overall well-being, the researchers noted.
However, children with neonatal hypoglycemia were significantly less likely to be rated as below or well below reading curriculum level by teachers compared to those without neonatal hypoglycemia (24% vs. 31%).
The researchers cited a previous study of the same patient cohort at age 4.5 years, which suggested an association between adverse neurodevelopmental outcomes and infant hypoglycemia. However, the reason this association did not persist at age 9-10 years remains unclear, the researchers wrote in their discussion. “Early disturbances in brain development may have diminishing effects over time due to neuroplasticity, that is, reorganization of neural networks, or delayed maturation with mid-childhood catch-up in neurocognitive function,” they said.
The study findings were limited by several factors including the lack of data on several measures of cognition, notably processing speed, and a lack of adjustment for intelligence quotient at age 4.5 years, the lack of data on any treatment for developmental impairment, and the inclusion of a population with well-managed hypoglycemia, the researchers said.
However, the results were strengthened by having a sample size large enough to detect associations, the prospective design, and the accurate measure of neonatal glycemic exposure, they said. Although the results suggest that at-risk children reach similar endpoints by the end of primary school, “efforts to prevent and optimize adverse pregnancy conditions remain important, and developmental surveillance after birth should be considered for at-risk infants,” they concluded.
In a related study published in JAMA, Taygen Edwards and colleagues found that prophylactic oral dextrose gel had no significant effect on neurosensory function.
The study, a prospective follow-up of a multicenter randomized trial, included 1,197 later preterm or term infants deemed at risk for neonatal hypoglycemia. The infants (49% of whom were female) were randomized to prophylactic 40% dextrose gel or a placebo, massaged into the buccal mucosa at 1 hour after birth.
The primary outcome was neurosensory impairment at 2 years of age, which was assessed by neurologic examination, parent-reported medical questionnaires, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), performance-based executive function, Behavior Rating Inventory of Executive Function–Preschool Version, motion coherence thresholds, growth, and body composition.
At 2 years of age, the prevalence of neurosensory impairment was 21% and 19%, respectively, in infants randomized to prophylactic oral dextrose gel and placebo, a nonsignificant difference. No differences between the two groups were noted for cognitive and language delays, or low performance-based overall executive function. However, infants randomized to dextrose gel had significantly higher risk of motor delay compared to placebo (2.5% vs. 0.7%) and significantly lower Bayley-III composite scores for cognitive, language, and motor performance.
No significant differences were noted between the groups in the areas of moderate or severe neurosensory impairment, hearing impairment, cerebral palsy, developmental delay, above-average development, socioemotional and adaptive behavior, questionnaire-based executive function, low visual processing, history of seizures, allergic and infectious diseases, growth, and body composition.
The results are consistent with previous studies on the safety of dextrose gel, the researchers wrote in their discussion. However, the absolute difference of 7% in the primary outcome may be clinically important, they noted. “Caution is warranted before using prophylactic dextrose gel,” they said.
The researchers noted the results of a dose-finding trial that suggested improved scores on language, executive function, and motor skills in unadjusted analysis with higher doses of dextrose gel, but the reason for these findings remains unknown, they said.
The study findings were limited by the potential underpowering to detect small, but significant differences, and possible lack of generalizability because the majority of the participants were children of mothers with diabetes.
The results were strengthened by the high follow-up rate and comprehensive assessments, and highlight the need for additional research with longer follow-up, the researchers said.