Neonatal Hypoglycemia and Neurocognitive Function at School Age: A Prospective Cohort Study.

OBJECTIVE: To determine the relationship between transient neonatal hypoglycemia in at-risk infants and neurocognitive function at 6-7 years of corrected age. STUDY DESIGN: The pre-hPOD Study involved children born with at least 1 risk factor for neonatal hypoglycemia. Hypoglycemia was defined as ≥1 consecutive blood glucose concentrations <47 mg/dl (2.6 mmol/L), severe as <36 mg/dl (2.0 mmol/L), mild as 36 to <47 mg/dL (2.0 to <2.6 mmol/L), brief as 1-2 episodes, and recurrent as ≥3 episodes. At 6-7 years children were assessed for cognitive and motor function (NIH-Toolbox), learning, visual perception and behavior. The primary outcome was neurocognitive impairment, defined as >1 SD below the normative mean in ≥1 Toolbox tests. The 8 secondary outcomes covered children's cognitive, motor, language, emotional-behavioral, and visual perceptual development. Primary and secondary outcomes were compared between children who did and did not experience neonatal hypoglycemia, adjusting for potential confounding by gestation, birthweight, sex and receipt of prophylactic dextrose gel (pre-hPOD intervention). Secondary analysis included assessment by severity and frequency of hypoglycemia. RESULTS: Of 392 eligible children, 315 (80%) were assessed at school age (primary outcome, n = 308); 47% experienced hypoglycemia. Neurocognitive impairment was similar between exposure groups (hypoglycemia 51% vs 50% no hypoglycemia; aRD -4%, 95% CI -15%, 7%). Children with severe or recurrent hypoglycemia had worse visual motion perception and increased risk of emotional-behavioral difficulty. CONCLUSION: Exposure to neonatal hypoglycemia was not associated with risk of neurocognitive impairment at school-age in at-risk infants, but severe and recurrent episodes may have adverse impacts. TRIAL REGISTRATION: Hypoglycemia Prevention in Newborns with Oral Dextrose: the Dosage Trial (pre-hPOD Study): ACTRN12613000322730.

Psychosocial Support Provided to Parents of Infants in Neonatal Intensive Care Units: An International Survey.

OBJECTIVE: To describe current psychosocial support practices and programs for parents with infants in level II nurseries and level III neonatal intensive care units (NICUs) across Australia and New Zealand. STUDY DESIGN: A staff member from each level II and level III hospital completed an online survey about the psychosocial support services available for parents in Australia and New Zealand. Mixed methods (descriptive and statistical analysis; descriptive content analysis) were used to describe current services and practices. RESULTS: Of 66 eligible units, 44 participated in the survey (67%). Hospital-based pediatricians (32%) and clinical directors (32%) were the most common respondents. Level III NICUs reported providing significantly more services for parents than level II nurseries (median [IQR]: level III, 7 [5.25-8.75]; level II, 4.5 [3.25-5]; P < .001), with variability in the type and number of services available (range, 4-13). Less than half of units (43%) reported using standardized screening tools to assess parents for mental health distress, and just 4 units (9%) provided staff-led parent mental health support programs. In qualitative feedback, respondents frequently reported a lack of resources (staffing, funding, and training) to support parents. CONCLUSIONS: Despite the well-documented distress that parents with infants in neonatal units experience and the evidence-based practices known to reduce this distress, this study identifies significant gaps in parent support services in level II and level III NICUs across Australia and New Zealand.

Effect of Prophylactic Dextrose Gel on Continuous Measures of Neonatal Glycemia: Secondary Analysis of the Pre-hPOD Trial.

OBJECTIVE: To determine the effects of different doses of prophylactic dextrose gel on glycemic stability assessed using continuous glucose monitoring in the first 48 hours when given to babies at risk of neonatal hypoglycemia. STUDY DESIGN: Continuous glucose monitoring was undertaken for the first 48 hours in 133 infants at risk of hypoglycemia who participated in the pre-hPOD randomized dosage trial of dextrose gel prophylaxis. RESULTS: Low glucose concentrations were detected in 41% of infants by blood glucose monitoring and 68% by continuous interstitial glucose monitoring. The mean ± SD duration of low interstitial glucose concentrations was 295 ± 351 minutes in the first 48 hours. Infants who received any dose of dextrose gel seemed to be less likely than those who received placebo gel to experience low glucose concentrations (<47 mg/dL [2.6 mmol/L]; P = .08), particularly if they received a single dose of 200 mg/kg (relative risk, 0.70; 95% CI, 0.50-0.10; P = .049). They also spent a greater proportion of time in the central glucose concentration range of 54-72 mg/dL (3-4 mmol/L) (any dose, mean ± SD, 58.2 ± 20.3%; placebo, 50.0 ± 21.9%; mean difference, 8.20%; 95% CI, 0.43-15.9%; P = .038). Dextrose gel did not increase recurrent or severe episodes of low glucose concentrations and did not increase the peak glucose concentration. These effects were similar for all trial dosages. CONCLUSIONS: Low glucose concentrations were common in infants at risk of hypoglycemia despite blood glucose monitoring and treatment. Prophylactic dextrose gel reduced the risk of hypoglycemia without adverse effects on glucose stability.

Effects of Neonatal Hyperglycemia on Retinopathy of Prematurity and Visual Outcomes at 7 Years of Age: A Matched Cohort Study.

OBJECTIVE: To determine whether neonatal hyperglycemia is associated with retinopathy of prematurity (ROP), visual outcomes, and ocular growth at 7 years of age. STUDY DESIGN: Children born preterm (<30 weeks of gestational age) at a tertiary hospital in Auckland, New Zealand, who developed neonatal hyperglycemia (2 blood glucose concentrations ≥153 mg/dL [8.5 mmol/L] 4 hours apart) were matched with children who were not hyperglycemic (matching criteria: sex, gestational age, birth weight, age, socioeconomic status, and multiple birth) and assessed at 7 years of corrected age. The primary outcome, favorable overall visual outcome (visual acuity ≤0.3 logarithm of the minimum angle of resolution, no strabismus, stereoacuity ≤240 arcsec, not requiring spectacles) was compared between groups using generalized matching criteria-adjusted linear regression models. RESULTS: Assessments were performed on 57 children with neonatal hyperglycemia (hyperglycemia group) and 54 matched children without hyperglycemia (control group). There were no differences in overall favorable visual outcome (OR 0.95, 95% CI 0.42-2.13, P = .90) or severe ROP incidence (OR 2.20, 95% CI 0.63-7.63, P = .21) between groups. Children with hyperglycemia had poorer binocular distance visual acuity (mean difference 0.08, 95% CI 0.03-0.14 logarithm of the minimum angle of resolution, P < .01), more strabismus (OR 6.22, 95% CI 1.31-29.45, P = .02), and thicker crystalline lens (mean difference 0.14, 95% CI 0.04-0.24 mm, P < .01). Maximum blood glucose concentration was greater in the ROP-treated group compared with the ROP-not treated and no ROP groups after adjusting for sex, gestational age, and birth weight z score (P = .02). CONCLUSIONS: Neonatal hyperglycemia was not associated with overall visual outcomes at 7 years of age. However, there were between-group differences for specific outcome measures relating to interocular lens growth and binocular vision. Further follow-up is required to determine implications on long-term visual outcome.

Intermittent Hypoxemia in Infants Born Late Preterm: A Prospective Cohort Observational Study.

OBJECTIVE: To determine if late preterm infants are at increased risk of intermittent hypoxemic events compared with term infants. STUDY DESIGN: Prospective, cohort, observational study of late preterm infants (340/7-366/7 weeks gestational age) and term infants (390/7-416/7 weeks gestational age). Overnight pulse oximetry recordings were performed on days 2-3 after birth, at term equivalent age, and at 45 weeks postmenstrual age. The primary outcome was the frequency of intermittent hypoxemic events per hour (desaturation ≥10% below the preceding baseline SpO2) on the oximetry recording on days 2-3 after birth. Data were analyzed by the Student t test and general linear mixed model. RESULTS: Eighty-five infants were enrolled (late preterm n = 43; term infants n = 42). On days 2-3 after birth, late preterm infants had more intermittent hypoxemic events than term infants (events per hour, mean ± standard error of the mean, 2.5 ± 1.2 vs 1.0 ± 1.2; P < .0001). On mixed model analysis, late preterm infants had a higher frequency of intermittent hypoxemic events at term equivalent age, which decreased to a similar frequency as in term infants by 45 weeks postmenstrual age (events per hour; term equivalent age, late preterm: least squares mean, 3.7 [95% CI, 2.7-5.1] vs term: least squares mean, 1.7 [95% CI, 1.2-2.3]; 45 weeks postmenstrual age, late preterm: least squares mean, 1.5 [95% CI, 1.1-2.1] vs term: least squares mean, 1.9 [95% CI, 1.4-2.6]; P < .0005). CONCLUSIONS: Late preterm infants are at greater risk of intermittent hypoxemia than term infants soon after birth. We speculate that preventing intermittent hypoxemia in late preterm infants may improve neurodevelopmental outcomes.

Long-Term Outcomes of Hyperglycemic Preterm Infants Randomized to Tight Glycemic Control.

OBJECTIVE: To determine whether tight glycemic control of neonatal hyperglycemia changes neurodevelopment, growth, and metabolism at school age. STUDY DESIGN: Children born very low birth weight and randomized as hyperglycemic neonates to a trial of tight vs standard glycemic control were assessed at 7 years corrected age, including Wechsler Intelligence Scale for Children Fourth Edition, Movement Assessment Battery for Children 2, visual and neurologic examinations, growth measures, dual X-ray absorptiometry, and frequently sampled intravenous glucose tolerance test. The primary outcome was survival without neurodevelopmental impairment at age 7 years. Outcomes were compared using linear regression, adjusted for sex, small for gestational age, birth plurality, and the clustering of twins. Data are reported as number (%) or mean (SD). RESULTS: Of the 88 infants randomized, 11 (13%) had died and 57 (74% of eligible children) were assessed at corrected age 7 years. Survival without neurodevelopmental impairment occurred in 25 of 68 children (37%), with no significant difference between tight (14 of 35; 40%) and standard (11 of 33; 33%) glycemic control groups (P = .60). Children in the tight group were shorter than those in the standard group (121.3 [6.3] cm vs 125.1 [5.4] cm; P < .05), but had similar weight and head circumference. Children in the tight group had greater height-adjusted lean mass (18.7 [0.3] vs 17.6 [0.2] kg; P < .01) and lower fasting glucose concentrations (84.6 [6.30] vs 90.0 [5.6] mg⋅dL-1; P < .05), but no other differences in measures of body composition or insulin-glucose metabolism. CONCLUSION: Tight glycemic control for neonatal hyperglycemia does not change survival without neurodevelopmental impairment, but reduces height, increases height-adjusted lean mass, and reduces fasting blood glucose concentrations at school age. TRIAL REGISTRATION: ACTRN: 12606000270516.

Relationship between Measures of Neonatal Glycemia, Neonatal Illness, and 2-Year Outcomes in Very Preterm Infants.

OBJECTIVES: To investigate relationships between early neonatal glycemia, neonatal characteristics, neonatal illness, and developmental outcomes in very preterm infants. STUDY DESIGN: A retrospective, observational cohort study of 443 infants born weighing <1500 g or <30 weeks of gestation, and admitted within 24 hours to National Women's Hospital, Auckland, New Zealand. Glucose variability was defined as the standard deviation around the mean after log transformation of all blood glucose concentrations. Absolute glycemic excursions in the first week were used to divide the infants into 4 groups: normoglycemic; hypoglycemic; hyperglycemic, and unstable. RESULTS: Compared with normoglycemic infants, hypoglycemic and unstable infants had lower birth weight z-scores, and hyperglycemic and unstable infants were of lower birth weight. Hypoglycemic infants had similar outcomes to normoglycemic infants. Hyperglycemic and unstable infants were less likely to survive without neonatal morbidity and less likely to survive without neurodevelopmental impairment at 2 years of age. Higher mean blood glucose concentration was seen in the hyperglycemic and unstable groups, and was associated with worse neonatal and 2-year outcomes. Greater glucose variability was seen in the hypoglycemic and unstable groups, and was associated with worse neonatal illness but not outcome at 2 years. No associations between measures of neonatal glycemia and neonatal or 2-year outcomes remained after correction for gestation, birth weight z-score, and socioeconomic status. CONCLUSIONS: In very preterm infants, measures of neonatal glycemia are markers of gestational age and intrauterine growth, and are not independent predictors of neonatal illness or outcomes at 2 years of age.

Outcome at 2 Years after Dextrose Gel Treatment for Neonatal Hypoglycemia: Follow-Up of a Randomized Trial.

OBJECTIVE: To determine neurodevelopmental outcome at 2 years' corrected age in children randomized to treatment with dextrose gel or placebo for hypoglycemia soon after birth (The Sugar Babies Study). STUDY DESIGN: This was a follow-up study of 184 children with hypoglycemia (<2.6 mM [47 mg/dL]) in the first 48 hours and randomized to either dextrose (90/118, 76%) or placebo gel (94/119, 79%). Assessments were performed at Kahikatea House, Hamilton, New Zealand, and included neurologic function and general health (pediatrician assessed), cognitive, language, behavior, and motor skills (Bayley Scales of Infant and Toddler Development, Third Edition), executive function (clinical assessment and Behaviour Rating Inventory of Executive Function-Preschool Edition), and vision (clinical examination and global motion perception). Coprimary outcomes were neurosensory impairment (cognitive, language or motor score below -1 SD or cerebral palsy or blind or deaf) and processing difficulty (executive function or global motion perception worse than 1.5 SD from the mean). Statistical tests were two sided with 5% significance level. RESULTS: Mean (± SD) birth weight was 3093 ± 803 g and mean gestation was 37.7 ± 1.6 weeks. Sixty-six children (36%) had neurosensory impairment (1 severe, 6 moderate, 59 mild) with similar rates in both groups (dextrose 38% vs placebo 34%, relative risk 1.11, 95% CI 0.75-1.63). Processing difficulty also was similar between groups (dextrose 10% vs placebo 18%, relative risk 0.52, 95% CI 0.23-1.15). CONCLUSIONS: Dextrose gel is safe for the treatment of neonatal hypoglycemia, but neurosensory impairment is common among these children. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN 12608000623392.