for the Children With Hypoglycemia and Their Later Development (CHYLD) Study Team IMPORTANCE Hypoglycemia is common during neonatal transition and may cause permanent neurological impairment, but optimal intervention thresholds are unknown.OBJECTIVE To test the hypothesis that neurodevelopment at 4.5 years is related to the severity and frequency of neonatal hypoglycemia. DESIGN, SETTING, AND PARTICIPANTSThe Children With Hypoglycemia and Their Later Development (CHYLD) Study is a prospective cohort investigation of moderate to late preterm and term infants born at risk of hypoglycemia. Clinicians were masked to neonatal interstitial glucose concentrations; outcome assessors were masked to neonatal glycemic status. The setting was a regional perinatal center in Hamilton, New Zealand. The study was conducted from December 2006 to November 2010. The dates of the follow-up were September 2011 to June 2015. Participants were 614 neonates born from 32 weeks' gestation with at least 1 risk factor for hypoglycemia, including diabetic mother, preterm, small, large, or acute illness. Blood and masked interstitial glucose concentrations were measured for up to 7 days after birth. Infants with hypoglycemia (whole-blood glucose concentration <47 mg/dL) were treated to maintain blood glucose concentration of at least 47 mg/dL. EXPOSURES Neonatal hypoglycemic episode, defined as at least 1 consecutive blood glucose concentration less than 47 mg/dL, a severe episode (<36 mg/dL), or recurrent (Ն3 episodes). An interstitial episode was defined as an interstitial glucose concentration less than 47 mg/dL for at least 10 minutes. MAIN OUTCOMES AND MEASURESCognitive function, executive function, visual function, and motor function were assessed at 4.5 years. The primary outcome was neurosensory impairment, defined as poor performance in one or more domains. RESULTSIn total, 477 of 604 eligible children (79.0%) were assessed. Their mean (SD) age at the time of assessment was 4.5 (0.1) years, and 228 (47.8%) were female. Those exposed to neonatal hypoglycemia (280 [58.7%]) did not have increased risk of neurosensory impairment (risk difference [RD], 0.01; 95% CI, −0.07 to 0.10 and risk ratio [RR], 0.96; 95% CI, 0.77 to 1.21). However, hypoglycemia was associated with increased risk of low executive function (RD, 0.05; 95% CI, 0.01 to 0.10 and RR, 2.32; 95% CI, 1.17 to 4.59) and visual motor function (RD, 0.03; 95% CI, 0.01 to 0.06 and RR, 3.67; 95% CI, 1.15 to 11.69), with highest risk in children exposed to severe, recurrent, or clinically undetected (interstitial episodes only) hypoglycemia.CONCLUSIONS AND RELEVANCE Neonatal hypoglycemia was not associated with increased risk of combined neurosensory impairment at 4.5 years but was associated with a dose-dependent increased risk of poor executive function and visual motor function, even if not detected clinically, and may thus influence later learning. Randomized trials are needed to determine optimal screening and intervention thresholds based on assessment of neurodevelopment at le...

Aim To determine whether Bayley Scales of Infant and Toddler Development (3rd edition) (Bayley-III) motor scores and neurological examination at 2 years' corrected age predict motor difficulties at 4.5 years' corrected age. Method A prospective cohort study of children born at risk of neonatal hypoglycaemia in Waikato Hospital, Hamilton, New Zealand. Assessment at 2 years was performed using the Bayley-III motor scale and neurological examination, and at 4.5 years using the Movement Assessment Battery for Children (2nd edition) (MABC-2). Results Of 333 children, 8 (2%) had Bayley-III motor scores below 85, and 50 (15%) had minor deficits on neurological assessment at 2 years; 89 (27%) scored less than or equal to the 15th centile, and 54 (16%) less than or equal to the 5th centile on MABC-2 at 4.5 years. Motor score, fine and gross motor subtest scores, and neurological assessments at 2 years were poorly predictive of motor difficulties at 4.5 years, explaining 0 to 7% of variance in MABC-2 scores. A Bayley-III motor score below 85 predicted MABC-2 scores less than or equal to the 15th centile with a positive predictive value of 30% and a negative predictive value of 74% (7% sensitivity and 94% specificity). Interpretation Bayley-III motor scale and neurological examination at 2 years were poorly predictive of motor difficulties at 4.5 years.

Higher and unstable glucose concentrations in the first 48 hours in neonates at risk of hypoglycaemia have been associated with neurosensory impairment. It is unclear what defines and contributes to instability. This was a prospective study of term and late preterm babies (N = 139) born at risk of neonatal hypoglycaemia who had interstitial glucose (IG) monitoring and ≥1 hypoglycaemic episode <48 hours after birth (blood glucose concentration <2.6 mmol/l [<47 mg/dl]). For 6-hour epochs after each hypoglycaemic episode, masked IG parameters (time to reach maximum IG concentration [hours]; range, average, maximum and minimum IG concentrations; proportion of IG measurements outside the central band of 3–4 mmol/l [54–72 md/dl]; and total duration [hours] of IG concentrations <2.6 mmol/l) were analysed in tertiles and related to: (i) glycaemic instability in the first 48 hours (defined as the proportion of blood glucose concentrations outside the central band in the first 48 hours); (ii) risk factors and treatment for each episode; and (iii) risk of neurosensory impairment at 4.5 years, or at 2 years if a child was not seen at 4.5 years. Glycaemic instability in the first 48 hours was related to IG instability after hypoglycaemia. Risk factors for hypoglycaemia were not related to IG parameters. Treatment with intravenous dextrose was associated with higher IG maximum and range, and lower minimum compared to treatment with dextrose gel plus breast milk, breast milk alone or formula alone. The risk of neurosensory impairment was increased with both shorter and longer time to reach maximum epoch IG (P = 0.04; lower tertile [0.4–2.2 hours] vs middle [2.3–4.2 hours] OR 3.10 [95% CI 1.03; 9.38]; higher tertile [4.3–6.0 hours] vs middle OR 3.07; [95% CI 1.01; 9.24]). Glycaemic response to hypoglycaemia contributes to overall glycaemic instability in newborns and is influenced by treatment. Slow or rapid recovery of hypoglycaemia appears to be associated with neurosensory impairment.

Aim To compare detection of and referral for developmental and emotional problems in a school readiness screening programme (New Zealand Before School Check, B4SC) with that of a comprehensive neurodevelopmental assessment. Methods Prospective cohort study of children (n=274) born at risk of neonatal hypoglycaemia and recruited to a follow-up study of neurodevelopmental outcomes at 4.5 years (CHYLD Study). Children identified as of significant concern for developmental and emotional problems, and referrals made, were compared in the B4SC and CHYLD Study. Scores of the parent-completed Strengths and Difficulties Questionnaire (SDQ-P) used in both assessments were compared. Results Of 274 children who underwent clinical neurodevelopmental assessment at a mean (SD) age of 53.3 (1.8) months, 237 had the B4SC developmental and emotional health screening. Of these, 44 (19%) children met B4SC referral criteria and 15 (6%) were referred but only 21 (9%) children met CHYLD referral criteria and 10 (4%) were referred. Twelve children (5%) met both the B4SC and CHYLD referral criteria and 2 were referred by both. When assessed twice 39 (17%) children changed SDQ-P category. Children who did not have B4SC screening had higher mean total difficulties score (10.5 vs 8.2, P=0.009) and were more likely to have cognitive delay than those who were screened (19% vs 8%, P=0.04). Conclusions More children met referral criteria for the B4SC screening programme than for a more comprehensive neurodevelopmental assessment. Children who did not have screening had higher incidence of cognitive and behaviour problems than those who did.

AimTo determine whether teachers' reports of student academic performance can suffice for research purposes by comparing it with a curriculum‐based standardised test.MethodsIn this longitudinal cohort study of children born at risk of neonatal hypoglycaemia, teachers' global assessment of student performance was compared with assessment tools for teaching and learning (asTTle) at 9–10 years. Performance on asTTLe was rated as being below, at or above that expected on the national curriculum for year and term of schooling. Teachers similarly rated the child's performance against the national curriculum.ResultsOf 125 children assessed, 104 had paired data for analysis. On asTTLe, 28% were rated below, 55% at and 17% above the expected curriculum level in reading and 24, 54 and 22%, respectively, in mathematics. Equivalent teacher ratings were 23, 58 and 19% in reading and 36, 55 and 9% in mathematics, respectively. However, there was limited agreement between asTTle and teacher rating of achievement in reading (κ = 0.23 (95% confidence interval 0.07–0.40)) and no significant agreement in mathematics (κ = 0.07 (95% confidence interval −0.09–0.22)). Only 45% of children performing below the curriculum level in reading and 52% in mathematics were correctly identified by teachers.ConclusionIn cohort studies, teacher ratings cannot substitute standardised educational testing.