BABIES indicates Babies and Blood Sugar’s Influence on EEG Study.
Secondary analyses of the severity (A) and frequency (B) of hypoglycemic episodes are shown. P values represent comparison across all groups. Children who were not exposed to neonatal hypoglycemia are the referent. Data on the y-axis are outcome rates or mean (SD) for each group.
P values represent comparison across all groups. Quintile 3 for neurosensory impairment is the referent. BGC indicates blood glucose concentration; IG, interstitial concentration. The central band is 54 to 72 mg/dL. To convert BGC to millimoles per liter, multiply by 0.0555.
eTable 1. Scoring of Executive Function Tasks
eTable 2. Characteristics of Children, and Their Mothers, Who Were Assessed Only at 2 Years Compared With Those Assessed at Both 2 and 4.5 Years
eTable 3. Receiver Operating Characteristic (ROC) Curves for Neurosensory Impairment at 4.5 Years
eFigure. Neonatal Interstitial Glucose Profile and Neurosensory Function at 4.5 Years
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McKinlay CJD, Alsweiler JM, Anstice NS, et al. Association of Neonatal Glycemia With Neurodevelopmental Outcomes at 4.5 Years. JAMA Pediatr. 2017;171(10):972–983. doi:10.1001/jamapediatrics.2017.1579
What is the relationship between neonatal hypoglycemia, including the severity and frequency, and neurodevelopmental outcomes?
In this prospective cohort study of 477 at-risk children, neonatal hypoglycemia (<47 mg/dL) was not associated with combined neurosensory impairment at 4.5 years but was associated with impaired executive function and visual motor function. Severe, recurrent, and clinically undetected episodes increased this risk.
Neonatal hypoglycemia may increase the risk of impaired executive function and visual motor function in a dose-dependent fashion, even if not detected clinically, and may thus influence later learning; randomized trials to determine optimal intervention thresholds need to assess neurodevelopment at least to school age.
Hypoglycemia is common during neonatal transition and may cause permanent neurological impairment, but optimal intervention thresholds are unknown.
To test the hypothesis that neurodevelopment at 4.5 years is related to the severity and frequency of neonatal hypoglycemia.
Design, Setting, and Participants
The 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.
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 (≥3 episodes). An interstitial episode was defined as an interstitial glucose concentration less than 47 mg/dL for at least 10 minutes.
Main Outcomes and Measures
Cognitive 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.
In 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 least to school age.
The diagnosis and management of neonatal hypoglycemia has been widely debated for more than 40 years, with authorities recommending lower1 and higher2 thresholds for intervention and treatment, reflecting the paucity of high-quality evidence to guide management.3 The results of population studies4,5 have suggested that neonatal hypoglycemia may be one of the most readily preventable causes of neurodevelopmental impairment and learning disorders, but there is also the potential for iatrogenic harm from increased intervention, including decreased breastfeeding and altered cortical development from pain-induced stress with heel lancing.6
To address these concerns, our group established the Children With Hypoglycemia and Their Later Development (CHYLD) Study to determine the effects of transitional hypoglycemia, including its severity and frequency, on neurodevelopment and health outcomes.7 Herein, we report on neurodevelopmental function at age 4.5 years.
The CHYLD Study is a prospective cohort investigation of moderate to late preterm and term infants born from 32 weeks’ gestation with one or more risk factors for neonatal hypoglycemia, including the following: diabetic mother, preterm (<37 weeks), small (<10th centile or <2500 g), large (>90th centile or >4500 g), or acute illness. Infants were recruited to 1 of 2 studies (102 in the Babies and Blood Sugar’s Influence on EEG Study [BABIES] and 514 in the Sugar Babies Study; 2 infants were in both studies), conducted from December 2006 to November 2010, at Waikato Hospital, Hamilton, New Zealand.8,9 The dates of the follow-up were September 2011 to June 2015. Infants had regular measurement of whole-blood glucose by the glucose oxidase method (ABL800 FLEX; Radiometer) according to the clinical protocol; screening commenced at 1 to 2 hours after birth, then every 3 to 4 hours for the first 24 hours, and every 6 to 8 hours for the following 24 hours and up to 7 days, or until there was no ongoing clinical concern. Masked interstitial continuous glucose monitoring (CGM) (CGMS Gold; Medtronic MiniMed) was performed for up to 7 days, with off-line recalibration.10 Hypoglycemia, defined as whole-blood glucose concentration (BGC) less than 47 mg/dL, was treated with additional feeding, buccal dextrose gel, and intravenous dextrose, with the aim of maintaining a BGC of at least 47 mg/dL (to convert BGC to millimoles per liter, multiply by 0.0555). A subgroup of infants (n = 214) in the Sugar Babies Study were randomized to buccal dextrose gel or placebo for initial management of hypoglycemia, but all were eligible for subsequent open-label treatment with dextrose gel.9 Two-year neurodevelopmental outcomes have been reported.7,11
All surviving children remaining in the study were eligible for follow-up at 4.5 years’ corrected age. Both neonatal studies and the follow-up study were approved by the Northern Y Regional Health and Disability Ethics Committee. Written informed consent was obtained at study entry and at follow-up.
At 4.5 years’ corrected age (±2 months), children underwent assessment by a psychologist, a pediatrician, and an optometrist, who were masked to neonatal glycemic status. Cognitive ability was assessed by the Weschler Preschool and Primary Scale of Intelligence, Third Edition (WPPSI-3), including full-scale IQ and verbal, performance, and processing speed subscales, each with standardized mean (SD) of 100 (15).
A battery of 5 graded tasks was used to assess executive function, including working memory (Digit Span),12 flexibility and attention (Dimensional Change Card Sort),13,14 delay inhibition (Gift Wrap Delay),15 and complex or conflict inhibition (Bear and Dragon and Day and Night Stroop).16 One point was allocated for successfully completing the practice trials of a task (“can do it”), 2 points for completing lower levels of a task (“did do it”), and 3 points for completing more complex levels of a task (“did advanced task”). Therefore, up to 6 points could be scored for each task, and a composite executive function score was calculated as the sum of the individual task scores, up to a maximum of 30 points (eTable 1 in Supplement). If a child did not succeed with the practice or any trials, he or she received a score of zero for that task.
Motor function was assessed by the Movement Assessment Battery for Children-2 (MABC-2), with standardized mean (SD) of 10 (3),17 and the motor coordination subscale of the Beery-Buktenica Developmental Test of Visual Motor Integration, Sixth Edition (BBVMI-6), with standardized mean (SD) of 100 (15).18 Cerebral palsy was diagnosed using a structured neurological examination.
Optometric examination was performed as previously described.19 Blindness and visual impairment were defined as visual acuity in the better eye of at least 1.4 or at least 0.5 logMAR, respectively (Snellen ≥20/500 or ≥20/63, respectively). A single point was assigned to each of the following vision assessment categories if test results indicated the need for referral: (1) internal ocular pathology; (2) external ocular pathology; (3) presence of strabismus; (4) absence of motor fusion on the 20∆ prism test or muscle restrictions, weaknesses, or imbalance evident on standard tests of ocular motility, smooth pursuit, and near point of convergence; (5) if stereopsis was not measurable on either the Randot, Lang, or Frisby stereotests; and (6) visual acuity worse than 0.3 logMAR (Snellen 20/40) in either eye or difference between eyes worse than 0.1 logMAR (more than 1 line). A vision composite score was calculated as the sum of 6 vision assessment categories, up to a maximum of 6 points.
Global motion perception was measured as the motion coherence threshold, determined from random dot kinetograms of varying coherence using an adaptive staircase procedure (lower threshold indicates better perception).19 Visual processing was also assessed by the visual processing subscale of the BBVMI-6, with standardized mean (SD) of 100 (15).18
Deafness was defined as hearing impairment requiring aids. Auditory processing was assessed by the auditory subscale (items 6 to 8) of the Phelps Kindergarten Readiness Scale, with standardized mean (SD) of 10 (3).20 Visual motor integration was measured by the BBVMI-6, with standardized mean (SD) of 100 (15).18
Parental questionnaires were used to screen for emotional and behavioral problems (Strengths and Difficulties Questionnaire [SDQ]21 and Child Behavior Checklist [CBCL]22), executive dysfunction (Behavior Rating Inventory of Executive Function, Preschool Version [BRIEF-P]23), and autistic traits (Social Communication Questionnaire [SComQ] lifetime form24). Parental questionnaires were also used to obtain information on the home and family environment.
The sample size was limited by the size of the inception cohorts. We estimated that if 470 children were assessed and half were exposed to neonatal hypoglycemia,25 the study would have 80% power to detect an increase in the primary outcome from 25% to 37% (12% absolute increase and 48% relative increase) and, for normally distributed data, a difference of 0.25 SD at the 5% significance level.
All outcomes were defined and analyses conducted according to a prespecified study protocol unless stated otherwise. The primary outcome was neurosensory impairment, defined as any of the following: visual impairment, deafness, cerebral palsy, full-scale IQ or visual motor integration score exceeding 1 SD below the test mean, MABC-2 total score less than 15th centile, or motion coherence threshold or executive function score worse than 1.5 SDs from the cohort mean. Prespecified secondary outcomes included the following: (1) individual components of the primary outcome and associated subscales and proportion of children with low test scores; (2) SDQ, CBCL, BRIEF-P, and SComQ scores and proportion of children with scores in the clinical range; and (3) proportion of children with a neurodevelopmental disorder, history of afebrile seizures, sensorimotor impairment (cerebral palsy, visual impairment, deafness, or MABC-2 total score <5th centile), and combined emotional-behavioral difficulty (SDQ, CBCL, BRIEF-P, or SComQ score in the clinical range).
Hypoglycemic definitions were as reported previously.7 Hypoglycemia was defined as at least 1 episode of consecutive BGCs less than 47 mg/dL, severe hypoglycemia as an episode less than 36 mg/dL, and recurrent hypoglycemia as at least 3 episodes. Interstitial episodes were defined as at least 10 minutes below these thresholds. Hypoglycemic events were defined as the sum of nonconcurrent whole-blood and interstitial episodes less than 47 mg/dL more than 20 minutes apart.
The primary analyses compared primary and secondary outcomes between children with and without hypoglycemic episodes in the first week after birth using generalized linear regression models (binomial or normal distribution) adjusted for predefined potential confounders (socioeconomic decile,26 sex, and primary risk factor for neonatal hypoglycemia). The data analysis was performed using statistical software (SAS, version 9.4; SAS Institute Inc). Results are presented as risk ratios (RRs) on binary outcomes or mean differences on continuous outcomes, with 95% CIs. Two-sided tests with P < .05 were considered statistically significant, with no adjustment for multiple comparisons.
The secondary analyses related the primary outcome and full-scale IQ to the severity and frequency of hypoglycemia, undetected low glucose concentration (detected only on masked CGM), continuous measures of higher glucose (mean and maximum in the first 12 and 48 hours), and glucose instability (proportion of glucose concentrations outside the central band of 54 to 72 mg/dL in the first 48 hours).7 Receiver operating characteristic curves were used to explore the diagnostic value of continuous measures of hypoglycemia for the primary outcome, including the number of events, minimum BGC, and negative interstitial glucose increment (area above the interstitial glucose concentration curve and below thresholds ranging from 54 to 32 mg/dL).7 Repeated-measures mixed models explored trends over time.
Of 614 infants in the inception cohort, 3 died and 7 withdrew, leaving 604 children eligible for follow-up at 4.5 years. Of 477 children assessed, the primary outcome was available for 473 (78.3% of those eligible) (Figure 1). Compared with those assessed, children not assessed at 4.5 years were more likely to be of European or other ethnicity but were less likely to have been exposed to prenatal smoking and alcohol and neonatal hypoglycemia or admitted to neonatal intensive care (Table 1). Children assessed at 2 years but not at 4.5 years had higher risk of neurosensory impairment at 2 years compared with those assessed at both time points (55.1% [27 of 49] vs 35.2% [125 of 355]) (eTable 2 in Supplement).
Neonatal hypoglycemia occurred in 280 infants (58.7%), of whom 111 (39.6%) had at least 1 severe episode and 53 (18.9%) had recurrent hypoglycemia (≥3 episodes). Children who experienced hypoglycemia compared with those who did not were less likely to be an infant of a diabetic mother and were more likely to be female and to be admitted to neonatal intensive care (Table 1). Among infants with hypoglycemia, those with severe or recurrent episodes were more likely to have a mother with pregestational diabetes (14.2% [17 of 120] vs 6.6% [9 of 137], P = .04), but there was no association with other baseline maternal and infant characteristics. Masked CGM was performed in 377 infants (79.0%), of whom 32 had at least 1 episode of low interstitial glucose concentrations but normal BGCs (21.7% of those without clinically detected hypoglycemia).
Children who were and were not exposed to neonatal hypoglycemia had similar risk of neurosensory impairment (37.4% vs 38.5%; risk difference [RD], 0.01; 95% CI, −0.07 to 0.10 and RR, 0.96; 95% CI, 0.77 to 1.21) (Table 2). Among secondary outcomes, children exposed to hypoglycemia had a greater risk of low executive function score (10.6% vs 4.7%; RD, 0.05; 95% CI, 0.01 to 0.10 and RR, 2.32; 95% CI, 1.17 to 4.59) and low visual motor integration score (4.7% vs 1.5%; RD, 0.03; 95% CI, 0.01 to 0.06 and RR, 3.67; 95% CI, 1.15 to 11.69). Their greater risk of SDQ total difficulties scores within the clinical range did not reach statistical significance (10.7% vs 6.3%; RD, 0.04; 95% CI, −0.01 to 0.09 and RR, 1.84; 95% CI, 0.96 to 3.54). Other secondary outcomes did not differ between children who were and were not exposed to neonatal hypoglycemia.
The severity and frequency of hypoglycemic episodes or presence of undetected low interstitial glucose concentrations were not related to neurosensory impairment or full-scale IQ at 4.5 years (Figure 2). However, children in the lowest quintile for mean and maximum interstitial glucose concentrations in the first 12 hours after birth had increased risk of neurosensory impairment (Figure 3). There was no association between proportion of blood and interstitial glucose concentrations outside the central band in the first 48 hours and neurosensory impairment or full-scale IQ. The number of hypoglycemic events, minimum BGC, and negative interstitial glucose increment did not predict neurosensory impairment at 4.5 years (eTable 3 in Supplement). Interstitial glucose profiles of children with and without neurosensory impairment at 4.5 years were similar, including those who experienced neonatal hypoglycemia treated with dextrose, either intravenous or buccal (eFigure in Supplement).
In post hoc analysis, the risk of a low executive function score and a low visual motor integration score was greatest in children exposed to severe hypoglycemia (Figure 2). The risk of a low executive function score was similarly increased in children exposed to 1 or 2 episodes and at least 3 episodes, but the risk of a low visual motor integration score was greatest in those exposed to at least 3 episodes. A low executive function score was more common in children with exposure to clinically undetected low glucose concentrations (interstitial monitoring only) compared with children with no hypoglycemic events (12.5% [4 of 32] vs 3.5% [4 of 115]; RR, 4.0; 95% CI, 1.23-12.85), but the risk of low visual motor integration score was similar between these groups.
In a post hoc subgroup analysis, interstitial glucose profiles were examined in children assessed at both 2 years and 4.5 years. Children who developed neurosensory impairment between 2 years and 4.5 years had a steeper rise in interstitial glucose concentration after hypoglycemia, whereas children who had stable neurosensory status, either normal or impaired at both time points, had similar interstitial glucose concentrations in the first 48 hours (eFigure in Supplement).
Because follow-up at 2 years was limited to children born from 35 weeks’ gestation, we performed a sensitivity analysis that excluded children born at 32 to 34 weeks (n = 38). This exclusion did not substantially alter the association between neonatal hypoglycemia and the risk of low executive function score and visual motor integration score at 4.5 years.
Our group has previously shown that, in this cohort of at-risk infants who received regular screening and intervention aimed at maintaining a BGC of at least 47 mg/dL, neonatal hypoglycemia was not associated with adverse neurodevelopmental outcomes at 2 years.7 However, because many higher-order cognitive functions have not yet developed at that age and because hypoglycemia may have widespread effects in the developing brain, including the frontal cortex,27 later childhood follow-up was planned. The present study has shown that at 4.5 years, while neonatal hypoglycemia was not associated with major neurological deficits, it was associated with a 2-fold to 3-fold increased risk of poor executive and visual motor performance.
By age 4.5 years, children have markedly increased capacity for problem solving, planning, attention control, and goal-directed behavior, collectively referred to as executive function. Impaired development of these faculties is associated with increased risk of attention-deficit/hyperactivity disorder, conduct disorder, and learning problems.28 We found that the risk of poor performance across 5 executive function tasks was more than twice as common among children exposed to neonatal hypoglycemia, potentially leading to behavioral and educational difficulties at school age. Indeed, the increased SDQ scores in the clinical range, indicative of reduced emotional and behavioral regulation,21 may signal the start of such a trajectory.
The BBVMI-6 assesses integration of visual processing and motor coordination, and low visual motor integration scores have been associated with poor performance in reading, mathematics, and writing, which are skills with a strong visuospatial basis.29 Neonatal hypoglycemia, if associated with both reduced executive and visual motor function, may be an important risk factor for schooling difficulties, as found in a recent large population study.4
Neonatal hypoglycemia has been traditionally associated with injury of the occipital lobes,30 which include the primary visual cortices and several extrastriate visual areas. However, more widespread injury has been reported more recently,31 and we did not detect any other adverse effects on visual development, despite detailed testing, including global motion perception. This finding may be due to the fact that we used a prospective cohort study design, which is at less risk of selection bias than retrospective case series.
These results of an observational study must be interpreted cautiously. We tested a wide range of neuropsychological functions, most of which were similar between groups, so it is possible that our positive findings represent residual confounding or type I errors. However, we prospectively hypothesized that executive function and visual motor skills may be affected by hypoglycemia based on early reports32,33 and the fact that concurrent impairment of these skills is not uncommon in children with learning problems. Furthermore, the apparent dose-response relationship between the severity and frequency of hypoglycemic episodes and the risk of low executive and visual motor function also makes it more likely that our findings represent true associations.
Continuous glucose monitoring of neonates at risk detects more episodes of low glucose concentrations than does intermittent blood glucose monitoring, and our group has previously argued against routine use of this technology because the clinical significance of these additional episodes is unknown.8 To our knowledge, the present study shows for the first time that clinically undetected low glucose concentrations may be associated with a 4-fold increased risk of executive dysfunction. We also found that children with the lowest interstitial glucose concentrations in the first 12 hours after birth had increased risk of combined neurosensory impairment. This finding, taken together with a recent report that transient neonatal hypoglycemia detected on whole-population screening was associated with decreased school achievement in literacy and mathematics,4 raises the question of whether currently recommended intermittent blood glucose screening of infants at risk is sufficient or whether more intensive screening or prophylactic measures should be assessed.
Nevertheless, it should not be assumed that more aggressive intervention would necessarily improve outcomes. At 2 years, neurosensory impairment was associated with higher and less stable glucose concentrations in the first 48 hours, although still within the normal range.7 This association was strongest among hypoglycemic infants who received dextrose, raising concern that rapid correction of hypoglycemia to higher glucose concentrations may lead to poorer outcome. In animal studies, higher glucose concentrations after hypoglycemia can worsen neuronal injury due to generation of reactive oxygen species34 and changes in cerebral perfusion.35 Although we did not see the same relationship between interstitial glucose profiles and neurosensory impairment at 4.5 years, children who had worsening of neurological status between assessments had a more rapid rise in glucose concentrations after initial hypoglycemia, similar to that observed previously. It remains to be determined whether glucose instability is on the causal pathway of neuronal injury or is simply a marker of perinatal stress.
Our study was prospective, used masked interstitial glucose monitoring, involved a comprehensive neurodevelopmental assessment, and was adequately powered to detect clinically important differences in outcomes, but, like any observational study, was limited by inability to determine causation. In addition, only 78.3% of eligible children were assessed, and those lost to follow-up had slightly lower rates of several perinatal risk factors. However, results of children seen at 2 years but not at 4.5 years suggest that those lost to follow-up had higher rates of neurosensory impairment; therefore, our study may underestimate the risks associated with neonatal hypoglycemia.
In this longitudinal cohort study, we have demonstrated the potential for adverse outcomes with both undertreatment and overtreatment of neonatal hypoglycemia, particularly among infants with less stable glucose concentrations. Intervention studies are now needed to determine optimal glycemic management for improving long-term outcomes. Furthermore, because the relationship between neonatal hypoglycemia and neurodevelopment is complex and changes over time, it is essential that infants in randomized trials are followed up to school age. Such studies will be expensive; however, given that approximately 15% of all newborns experience hypoglycemia25 and hypoglycemia may influence educational outcomes, the potential for benefit may be great.
Neonatal hypoglycemia, when treated to maintain BGCs of at least 47 mg/dL, 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 and visual motor function. Randomized trials are needed to determine optimal screening and intervention thresholds based on assessment of neuropsychological development at least to school age.
Accepted for Publication: April 18, 2017.
Corresponding Author: Jane E. Harding, DPhil, Liggins Institute, The University of Auckland, Private Bag 92019, Victoria St W, Auckland, New Zealand 1142 (firstname.lastname@example.org).
Published Online: August 7, 2017. doi:10.1001/jamapediatrics.2017.1579
Author Contributions: Drs McKinlay and Harding had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: McKinlay, Alsweiler, Anstice, Chase, Gamble, Harris, Thompson, Wouldes, Harding.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: McKinlay, Alsweiler, Chakraborty, San Diego, Harding.
Critical revision of the manuscript for important intellectual content: McKinlay, Alsweiler, Anstice, Burakevych, Chase, Gamble, Harris, Jacobs, Jiang, Paudel, Thompson, Wouldes, Harding.
Statistical analysis: McKinlay, Chakraborty, Chase, Gamble, Jiang, San Diego.
Obtained funding: Anstice, Chase, Wouldes, Harding.
Administrative, technical, or material support: McKinlay, Alsweiler, Harris, Jacobs, Paudel, San Diego, Harding.
Study supervision: McKinlay, Alsweiler, Anstice, Jacobs, Thompson, Wouldes, Harding.
Conflict of Interest Disclosures: None reported.
Funding/Support: This research was supported by grant R01HD069622 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, by grant 10-399 from the Health Research Council of New Zealand, by the Auckland Medical Research Foundation, and by Gravida, National Research Centre for Growth and Development, New Zealand.
Role of the Funder/Sponsor: Funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Group Information: The Children With Hypoglycemia and Their Later Development (CHYLD) Study Team members are as follows: Liggins Institute, The University of Auckland, Auckland, New Zealand: Judith Ansell, PhD, Anne Jaquiery, PhD, Kelly Jones, PhD, Sapphire Martin, BNurs, Christina McQuoid, DipEdPsych, Jenny Rogers, MHSc, Heather Stewart, Anna Tottman, MBBS, Kate Williamson, MBBS, Ellen Campbell, PhD, Coila Bevan, BA, Tineke Crawford, Kelly Fredell, BNurs, Kate Sommers, Claire Hahnhaussen, BSc, Safayet Hossin, MSc, Karen Frost, BSc, Grace McKnight, Janine Paynter, PhD, Jess Wilson, MSc, Rebecca Young, BEd, Anna Gsell, PhD, and Jessica Brosnahan, MHSc. Waikato Hospital, Hamilton, New Zealand: Anna Timmings, MBChB, Arun Nair, MD, Alexandra Wallace, PhD, and Phil Weston, MBChB. University of Canterbury, Christchurch, New Zealand: Aaron Le Compte, PhD, and Matthew Signal, PhD. Canterbury District Health Board, Christchurch, New Zealand: Nicola Austin, DM. Bay of Plenty District Health Board, Tauranga, New Zealand: Jeremy Armishaw, MBChB. Mid-Central District Health Board, Palmerston North, New Zealand: Nicola Webster, MBBS. Women’s and Children’s Hospital, Adelaide, Australia: Ross Haslam, MBBS, and Pat Ashwood, BSc. Royal Women’s Hospital, Melbourne, Australia: Lex Doyle, MD, and Kate Callanan. John Hunter Children’s Hospital, Newcastle, Australia: Ian Wright, MBChB.
We acknowledge the contributions of the following members of the CHYLD Study Team:
Data Collection: Judith Ansell, PhD, Anne Jaquiery, PhD, Kelly Jones, PhD, Sapphire Martin, BNurs, Christina McQuoid, DipEdPsych, Jenny Rogers, MHSc, Heather Stewart, Anna Timmings, MBChB, Anna Tottman, MBBS, Kate Williamson, MBBS, Arun Nair, MD, Alexandra Wallace, PhD, Phil Weston, MBChB, Nicola Austin, DM, Jeremy Armishaw, MBChB, Nicola Webster, MBBS, Ross Haslam, MBBS, Pat Ashwood, BSc, Lex Doyle, MD, Kate Callanan, and Ian Wright, MBChB.
Study Coordination: Jessica Brosnahan, MHSc, Ellen Campbell, PhD, Coila Bevan, BA, Tineke Crawford, Kelly Fredell, BNurs, and Kate Sommers.
Data Management: Claire Hahnhaussen, BSc, Safayet Hossin, MSc, Karen Frost, BSc, Grace McKnight, Janine Paynter, PhD, Jess Wilson, MSc, Rebecca Young, BEd, Anna Gsell, PhD, Aaron Le Compte, PhD, and Matthew Signal, PhD.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development or the National Institutes of Health.
Additional Contributions: We are grateful to the children and families who participated in this study. We thank our International Advisory Group, including Heidi Feldman, MD, and Darrell Wilson, MD (Stanford University School of Medicine); William Hay, MD (University of Colorado School of Medicine); and Robert Hess, DSc (McGill Vision Research Unit, Department of Ophthalmology, McGill University).
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