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.

Associations between neonatal nutrition and visual outcomes in 7-year-old children born very preterm.

PURPOSE: There is uncertainty about the effect of increased neonatal protein intake on neurodevelopmental outcomes following preterm birth. The aim of this study was to assess the effect of a change in neonatal nutrition protocol at a major tertiary neonatal intensive care unit intended to increase protein intake on ophthalmic and visual development in school-age children born very preterm. METHODS: The study cohort comprised children (n = 128) with birthweight <1500 g or gestational age < 30 weeks born at Auckland City Hospital before (OldPro group, n = 55) and after (NewPro group, n = 73) a reformulation of parenteral nutrition that resulted in increased total protein intake during the first postnatal week and decreased carbohydrate, total parenteral fluid and sodium intake. Clinical and psychophysical vision assessments were completed at 7 years' corrected age, including visual acuity, global motion perception (a measure of dorsal stream function), stereoacuity, ocular motility and ocular health. Composite measures of favourable overall visual, binocular and functional visual outcomes along with individual vision measures were compared between the groups using logistic and linear regression models. RESULTS: Favourable overall visual outcome did not differ between the two groups. However, global motion perception was better in the NewPro group (p = 0.04), whereas the OldPro group were more likely to have favourable binocular visual outcomes (60% vs. 36%, p = 0.02) and passing stereoacuity (p = 0.02). CONCLUSIONS: These results indicate subtle but complex associations between early neonatal nutrition after very preterm birth and visual development at school age.

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.

Experiences of parents whose children participated in a longitudinal follow-up study.

BACKGROUND: Long-term follow-up is necessary to understand the impact of perinatal interventions. Exploring parents' motives and experiences in consenting to their children taking part in longitudinal studies and understanding what outcomes are important to families may enhance participation and mitigate the loss to follow-up. As existing evidence is largely based on investigators' perspectives using Western samples, the present pilot study explored parents' perspectives in a multicultural New Zealand context. METHODS: Data were generated using semi-structured interviews with parents whose children had participated in a longitudinal study after neonatal recruitment. Parents' experiences of being part of the study were analysed thematically using an inductive approach. RESULTS: Parents (n = 16) were generally happy with the outcomes measured. Additionally, parents were interested in lifelong goals such as the impact of parental diabetes. We identified three themes: (1) Facilitators: Research participation was aided by motives and parent and research characteristics such as wishing to help others and straightforward recruitment; (2) Barriers: A hesitancy to participate was due to technical and clinical research aspects, participation burden and cultural barriers, such as complex wording, time commitment and nonindigenous research and (3) Benefits: Children and parents experienced advantages such as the opportunity for education. CONCLUSIONS: Parents reported positive experiences and described the unexpected benefit of increasing families' health knowledge through participation. Improvements for current follow-up studies were identified. Different ethnicities reported different experiences and perspectives, which warrants ongoing research, particularly with indigenous research participants. PATIENT OR PUBLIC CONTRIBUTION: No active partnership with parents of patients took place.

Relationship between visual and neurodevelopmental measures at 2 years with visual acuity and stereopsis at 4.5 years in children born at risk of neonatal hypoglycaemia.

PURPOSE: Mild to moderate vision loss affects many children and can negatively impact a child's early literacy and academic achievement. Nevertheless, there is no consensus on which factors present in early childhood indicate the need for long-term ophthalmic follow up, particularly in children with a history of perinatal adversity. This study identified the relationship between visual, cognitive, motor and demographic factors at 2 years of age and visual acuity (VA) and stereoacuity at 4.5 years of age. METHODS: Five hundred sixteen children identified as being at risk of neonatal hypoglycaemia were recruited soon after birth. At 2 years of age, binocular VA, stereoacuity and non-cycloplegic refraction were measured and a clinical neuro-developmental assessment with the Bayley Scales of Infant Development III (BSID-III) was conducted by a trained examiner. Monocular VA and stereoacuity were measured at 4.5 years of age. RESULTS: Three hundred twenty-eight children completed both the 2 and 4.5 year vision and neurodevelopmental assessments. Multiple linear regression showed oblique astigmatism and motor function at 2 years were significantly associated with VA at 4.5 years of age, while spherical equivalent refraction, motor scores and stereoacuity at 2 years were significantly associated with stereoacuity at 4.5 years of age. BSID-III motor scores had the best sensitivity (81.8%) and specificity (51.5%) for identifying impaired stereoacuity at 4.5 years. However, all measures at 2 years were poorly associated with VA at 4.5 years old. CONCLUSION: Vision and neurodevelopmental measures at 2 years were poorly associated with visual function at 4.5 years of age. However, lower scores on tests of motor function at 2 years may be associated with vision abnormalities, particularly reduced stereopsis, at 4.5 years of age and referral for comprehensive vision assessment for these children may be warranted.

Prophylactic Oral Dextrose Gel and Neurosensory Impairment at 2-Year Follow-up of Participants in the hPOD Randomized Trial.

Importance: Prophylactic oral dextrose gel reduces neonatal hypoglycemia, but later benefits or harms remain unclear. Objective: To assess the effects on later development of prophylactic dextrose gel for infants born at risk of neonatal hypoglycemia. Design, Setting, and Participants: Prospective follow-up of a multicenter randomized clinical trial conducted in 18 Australian and New Zealand hospitals from January 2015 to May 2019. Participants were late preterm or term at-risk infants; those randomized in 9 New Zealand centers (n = 1359) were included and followed up between January 2017 and July 2021. Interventions: Infants were randomized to prophylactic 40% dextrose (n = 681) or placebo (n = 678) gel, 0.5 mL/kg, massaged into the buccal mucosa 1 hour after birth. Main Outcomes and Measures: The primary outcome of this follow-up study was neurosensory impairment at 2 years' corrected age. There were 44 secondary outcomes, including cognitive, language, and motor composite Bayley-III scores (mean [SD], 100 [15]; higher scores indicate better performance). Results: Of eligible infants, 1197 (91%) were assessed (581 females [49%]). Neurosensory impairment was not significantly different between the dextrose and placebo gel groups (20.8% vs 18.7%; unadjusted risk difference [RD], 2.09% [95% CI, -2.43% to 6.60%]; adjusted risk ratio [aRR], 1.13 [95% CI, 0.90 to 1.41]). The risk of cognitive and language delay was not significantly different between the dextrose and placebo groups (cognitive: 7.6% vs 5.3%; RD, 2.32% [95% CI, -0.46% to 5.11%]; aRR, 1.40 [95% CI, 0.91 to 2.17]; language: 17.0% vs 14.7%; RD, 2.35% [95% CI, -1.80% to 6.50%]; aRR, 1.19 [95% CI, 0.92 to 1.54]). However, the dextrose gel group had a significantly higher risk of motor delay (2.5% vs 0.7%; RD, 1.81% [95% CI, 0.40% to 3.23%]; aRR, 3.79 [95% CI, 1.27 to 11.32]) and significantly lower composite scores for cognitive (adjusted mean difference [aMD], -1.30 [95% CI, -2.55 to -0.05]), language (aMD, -2.16 [95% CI, -3.86 to -0.46]), and motor (aMD, -1.40 [95% CI, -2.60 to -0.20]) performance. There were no significant differences between groups in the other 27 secondary outcomes. Conclusions and Relevance: Among late preterm and term infants born at risk of neonatal hypoglycemia, prophylactic oral 40% dextrose gel at 1 hour of age, compared with placebo, resulted in no significant difference in the risk of neurosensory impairment at 2 years' corrected age. However, the study may have been underpowered to detect a small but potentially clinically important increase in risk, and further research including longer-term follow-up is required. Trial Registration: anzctr.org.au Identifier: ACTRN12614001263684.

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.

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.

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.

Multiple Tools Are Needed for the Detection of Prenatal Alcohol Exposure: Findings From a Community Antenatal Setting.

BACKGROUND: Although the toxic effects of prenatal alcohol exposure (PAE) on children are well established, there is emerging evidence about the dynamics and associated demographics of drinking patterns across pregnancy, with risky drinking more likely to take place in the period before pregnancy awareness. This study investigated the use of complementary measurement tools in the understanding of alcohol use across pregnancy and reports on the rates and patterns of alcohol use in a community antenatal setting. METHODS: Data on alcohol consumption before and after awareness of pregnancy were collected via multiple measurement tools: anonymous lifestyle questionnaire, TWEAK (Tolerance, Worried, Eye-opener, Amnesia, K/Cut down) screener questionnaire, and Substance Use Inventory interviews across multiple pregnancy timepoints. Additionally, phosphatidylethanol (PEth), a direct biomarker of alcohol metabolism, collected from newborns' dried blood spot cards, was analyzed. RESULTS: The TWEAK screener was more likely to identify risky drinking behavior than the lifestyle questionnaire. When pregnancy was unplanned, women were more likely to find out they are pregnant significantly later (p < 0.001) and consume alcohol at moderate-heavy levels (p = 0.03), prolonging the risk to the fetus. There was an association between maternal self-reported alcohol use on the lifestyle questionnaire and Substance Use Inventory interviews, but no association between maternal reports of alcohol use and PEth results (p = 0.72). Women self-reported moderate-heavy alcohol use in early pregnancy only and a positive PEth screen indicated PAE in late pregnancy, suggesting that these methods may identify different groups of women. CONCLUSIONS: Multiple measurement tools and methods are needed to identify PAE at different points across pregnancy. Prospective sensitive interviewing is better suited to detecting PAE in early pregnancy, but not later when social desirability bias is stronger, and the use of an objective biomarker, such a PEth, may be useful for identifying the risk of PAE in late pregnancy.

Relationships Between Early Neonatal Nutrition and Neurodevelopment at School Age in Children Born Very Preterm.

OBJECTIVES: The aim of this study was to determine whether a new nutrition protocol designed to increase early protein intakes while reducing fluid volume in infants born very preterm was associated with altered neurodevelopment and growth in childhood. METHODS: A retrospective, observational cohort study of children born <30 weeks' gestation or <1500 g and admitted to the neonatal unit, National Women's Hospital, Auckland, New Zealand, before and after a change in nutrition protocol. The primary outcome was neurodevelopmental impairment at 7 years (any of Wechsler Intelligence Scale for Children full scale IQ < 85, Movement Assessment Battery for Children-2 total score ≤5th centile, cerebral palsy, blind, or deaf requiring aids). Outcomes were compared between groups and for the overall cohort using generalized linear regression, adjusted for sex and birth weight z score. RESULTS: Of 201 eligible children, 128 (64%) were assessed (55/89 [62%] exposed to the old nutrition protocol, 73 of 112 [65%] to the new protocol). Children who experienced the new protocol received more protein, less energy, and less carbohydrate in postnatal days 1 to 7. Neurodevelopmental impairment was similar at 7 years (30/73 [41%] vs 25/55 [45%], adjusted odds ratio [AOR] [95% confidence interval] 0.78 [0.35-1.70], P = 0.55), as was the incidence of cerebral palsy (AOR 7.36 [0.88-61.40], P = 0.07). Growth and body composition were also similar between groups. An extra 1 g/kg parenteral protein intake in postnatal days 1 to 7 was associated with a 27% increased odds of cerebral palsy (AOR 1.27 [1.03-1.57], P = 0.006). CONCLUSIONS: Higher early protein intakes do not change overall rates of neurodevelopmental impairment or growth at 7 years. Further research is needed to determine the effects of higher early parenteral protein intake on motor development.

Post-discharge outcomes for mothers and the mother-infant relationship following admission to a psychiatric Mother-Baby Unit.

Mother-Baby Unit research has focussed on maternal psychopathology over the course of an admission. Less is known about the baby's well-being, the shared relationship, or the mother's recovery. In an initial sample of 45 women, we describe discharge and post-discharge outcomes for maternal psychopathology (using maternal report and the Global Assessment of Function, GAF) and the mother-infant relationship (using the Child and Adult Relational Experimental Index, CARE Index). Three months post-discharge, one third of women described themselves as "completely recovered," one third were experiencing significant deterioration and 17% were readmitted to inpatient care. Poorer GAF scores were associated with a clinical diagnosis of comorbid personality disorder, antenatal presence of the index illness, partner illicit substance use, maternal perception of her bond, infant social withdrawal, and child protection concern. Post-discharge, the mother-infant relationship results were concerning. Only 17% were regarded as adequate. Improvement was observed across this period in 56% but relational deterioration occurred for 35%. Maternal and relational outcomes were weakly correlated at discharge (r² = 0.29, p = 0.07) but this was lost post-discharge (r² = 0.03, p = 0.89). The shared relationship and infant mental health should both be targets for intervention; both during MBU admission, and post-discharge.

La investigación sobre la Unidad de Madres y Bebés se han enfocado en la sicopatología materna a lo largo del curso de una admisión. Se conoce menos del bienestar del bebé, la relación entre ellos o la presente recuperación de la madre. En un grupo muestra inicial de 45 mueres, describimos resultados posteriores a cuando se les dio de alta en cuanto a la sicopatología materna (usando el reporte materno y la Evaluación Global de la Función, GAF) y la relación infante-madre (usando el Índice de Relación Experimental entre Niño y Adulto, Índice CARE). Tres meses después de que se les dio de alta, un tercio de las mujeres se describió a sí mismas como "completamente recuperadas," un tercio de ellas estaba experimentando un deterioro significativo y 17% fueron readmitidas bajo el cuidado de paciente interno. Los más pobres puntajes de GAF se asociaron con un diagnóstico clínico de trastornos de personalidad comórbidos, presencia antenatal de la enfermedad en el índice, uso ilícito de sustancias por parte de la pareja, percepción maternal de su unión afectiva, despego social del infante, así como la preocupación por la protección del infante. Después de que se les diera de alta, los resultados de la relación entre madre e infante fueron preocupantes. Sólo el 17% fue considerado adecuado. Se observaron mejoras a lo largo de este período en 56% pero el deterioro de la relación ocurrió en el 35%. El resultado materno y el de relación fueron asociados débilmente al momento de darles de alta (r2+0.29. p = 0.07) pero esto se perdió posteriormente al momento en que se les dio de alta. La relación compartida y la salud mental del infante deben ambas ser metas de intervención; ambas durante la admisión a la Unidad de Madres y Bebés y con posterioridad al momento en que se les da de alta.

Les recherches sur l'Unité psychiatrique Maman Bébé (en anglais Mother Baby Unit) ont porté sur la psychopathologie maternelle au cours d'une admission. On sait moins de choses sur le bien-être du bébé, leur relation ou la récupération en cours de la mère. Dans un échantillon initial de 45 femmes, nous décrivons des résultats à la sortie pour la psychopathologie maternelle (en utilisant le rapport maternel et l'Evaluation Globale de Fonction, soit GAF pour Global Assessment of Function en anglais) et la relation mère-bébé (en utilisant l'Index Expérimental Relationnel Enfant et Adulte, soir CARE Index, pour Child and Adult Relational Experimental Index en anglais). Trois mois après la sortie, un tiers des mères se décrivaient comme "ayant totalement récupéré", un tiers faisaient l'expérience d'une détérioration importante et 17% étaient réadmises en soins hospitaliers. Des scores GAF moins élevés étaient liés à un diagnostic clinique de trouble de la personnalité comorbide, à une présence anténatale de la maladie index, à une toxicomanie illicite du partenaire, à une perception maternelle de son lien, au retrait social du bébé et à des inquiétudes pour la protection de l'enfant. Après la sortie les résultats de la relation mère-bébé étaient inquiétants. Seuls 17% des résultats ont été considérés comme étant adéquats. Une amélioration a été observée durant cette période chez 56% mais une détérioration relationnelle a eu lieu pour 35%. Les résultats maternels et relationnels étaient faiblement corrélés à la sortie (r² = 0s29, p = 0,07) mais cela s'est avéré perdu après la sortie (r² = 0,03, p = 0,89). La relation partagée et la santé mentale du bébé devraient être tous deux des cibles d'intervention; à la fois durant l'admission dans l'Unité Maman Bébé et aussi après la sortie. Mots clés: bébé, après la sortie, unité maman bébé, santé mentale périnatale, relation mère-bébé.

Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years.

BACKGROUND: Neonatal hypoglycemia is common and can cause neurologic impairment, but evidence supporting thresholds for intervention is limited. METHODS: We performed a prospective cohort study involving 528 neonates with a gestational age of at least 35 weeks who were considered to be at risk for hypoglycemia; all were treated to maintain a blood glucose concentration of at least 47 mg per deciliter (2.6 mmol per liter). We intermittently measured blood glucose for up to 7 days. We continuously monitored interstitial glucose concentrations, which were masked to clinical staff. Assessment at 2 years included Bayley Scales of Infant Development III and tests of executive and visual function. RESULTS: Of 614 children, 528 were eligible, and 404 (77% of eligible children) were assessed; 216 children (53%) had neonatal hypoglycemia (blood glucose concentration, <47 mg per deciliter). Hypoglycemia, when treated to maintain a blood glucose concentration of at least 47 mg per deciliter, was not associated with an increased risk of the primary outcomes of neurosensory impairment (risk ratio, 0.95; 95% confidence interval [CI], 0.75 to 1.20; P=0.67) and processing difficulty, defined as an executive-function score or motion coherence threshold that was more than 1.5 SD from the mean (risk ratio, 0.92; 95% CI, 0.56 to 1.51; P=0.74). Risks were not increased among children with unrecognized hypoglycemia (a low interstitial glucose concentration only). The lowest blood glucose concentration, number of hypoglycemic episodes and events, and negative interstitial increment (area above the interstitial glucose concentration curve and below 47 mg per deciliter) also did not predict the outcome. CONCLUSIONS: In this cohort, neonatal hypoglycemia was not associated with an adverse neurologic outcome when treatment was provided to maintain a blood glucose concentration of at least 47 mg per deciliter. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).

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.

Compared with Cow Milk, a Growing-Up Milk Increases Vitamin D and Iron Status in Healthy Children at 2 Years of Age: The Growing-Up Milk-Lite (GUMLi) Randomized Controlled Trial.

Background: Iron deficiency (ID) and vitamin D deficiency (VDD) are significant pediatric health issues in New Zealand and Australia and remain prevalent micronutrient deficiencies in young children globally. Objective: We aimed to investigate the effect of a micronutrient-fortified, reduced-energy growing-up milk (GUMLi) compared with cow milk (CM) consumed for 1 y on dietary iron and vitamin D intakes and the status of New Zealand and Australian children at 2 y of age. Methods: The GUMLi Trial was a multicenter, double-blind, randomized controlled trial in 160 healthy 1-y-old New Zealand and Australian children conducted in 2015-2017. Participants were randomly assigned 1:1 to receive GUMLi (1.7 mg Fe/100 mL; 1.3 µg cholecalciferol/100 mL) or CM (0.02 mg Fe/100 mL; 0.06 µg cholecalciferol/100 mL) for 12 mo. Secondary outcomes, reported here, included change in dietary iron and vitamin D intakes, iron status, and 25-hydroxyvitamin D [25(OH)D] concentrations from blood samples at age 2 y. All regression models were adjusted for baseline outcome and study center. Results: GUMLi was a large contributor to dietary intakes of iron and vitamin D after 12 mo when compared with intakes from food and CM. The adjusted mean difference between groups for serum ferritin concentrations was 17.8 µg/L (95% CI: 13.6, 22.0 µg/L; P < 0.0001), and for 25(OH)D it was 16.6 nmol/L (95% CI: 9.9, 23.3 nmol/L; P < 0.0001). After 12 mo, ID was present in 16 (24%) participants in the CM group and 5 (7%) participants in the GUMLi group (P = 0.009), and the prevalence of VDD in the CM group increased to 14% (n = 10) and decreased to 3% (n = 2) (P = 0.03) in the GUMLi group. Conclusion: In comparison with CM, GUMLi significantly improved dietary iron and vitamin D intakes and the iron and vitamin D status of healthy children at 2 y of age. This trial was registered with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12614000918628.

MOTHERS AND THEIR INFANTS CO-ADMITTED TO A NEWLY DEVELOPED MOTHER-BABY UNIT: CHARACTERISTICS AND OUTCOMES.

Research on Mother-Baby Units (MBUs) has mainly focused on maternal psychiatric outcomes, not the well-being of infants. This study investigated infant development and mental health along with maternal characteristics and the mother-infant relationship in 45 dyads (60% New Zealand European, 20% Maori, 11% Pacific) admitted to a new MBU. Maternal psychopathology was measured with the Health of the Nations Outcome Scale (HoNOS, J.K Wing et al., 1998) and Global Assessment of Functioning (GAF; I.M. Aas, 2010). The Parent-Infant Relationship Global Assessment Scale (PIR-GAS, Zero to Three, 2005) measured the mother-infant relationship. Infant measures included Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (Zero to Three Press, 2005) and the Ages & Stages-3 (J. Squires, E. Twombly, D. Bricker, & L. Potter, 2009). Maternal mental illness and functioning improved during the admission and were positively associated with longer inpatient duration and no illicit substance use. Well-being of the infants was concerning. In addition to lower birth weights and poorer health status, at discharge 51% were lagging behind developmentally, and 51% were exhibiting signs of infant mental health concerns. Relationally, 67% of mother-infant dyads had features of, and 29% met criteria for, a disordered relationship. Poorer mother-infant relationships were associated with a maternal diagnosis of schizophrenia or bipolar disorder, use of the Mental Health Act, leaving the MBU early, limited social support, and infant mental health diagnosis.

Bayley-III motor scale and neurological examination at 2 years do not predict motor skills at 4.5 years.

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.

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.

A New Zealand pilot randomized controlled trial of a web-based interactive self-management programme (MSInvigor8) with and without email support for the treatment of multiple sclerosis fatigue.

OBJECTIVE: To pilot and compare the efficacy of an internet-based cognitive behavioural therapy self-management programme with (MSInvigor8-Plus) and without (MSInvigor8-Only) the use of email support in reducing fatigue severity and impact (primary outcomes), and depressed and anxious mood (secondary outcomes). DESIGN: Randomized controlled trial using an independent randomization system built into the website and intention-to-treat analysis. SETTING: Participants were recruited through the local Multiple Sclerosis Society and hospital neurological services in New Zealand. SUBJECTS: A total of 39 people (aged 31-63 years), experiencing multiple sclerosis fatigue, able to walk with and without walking aids, were randomized to MSInvigor8-Only (n = 20) or to MSInvigor8-Plus (n = 19). INTERVENTIONS: MSInvigor8 is an eight-session programme based on cognitive behaviour therapy principles including psycho-education, self-monitoring, and changing unhelpful activity and thought patterns. MAIN MEASURES: Outcome measures included fatigue severity (Chalder Fatigue Scale) and impact (Modified Fatigue Impact Scale), and anxiety and depression (Hospital Anxiety and Depression Scale). Assessments were performed at baseline and at 10 weeks. RESULTS: The MSInvigor8-Plus condition resulted in significantly greater reductions in fatigue severity (F [1,36] = 9.09, p < 0.01) and impact (F [1,36] = 6.03, p < 0.02) compared with the MSInvigor8-Only condition. Large between-group effect sizes for fatigue severity (d = 0.99) and fatigue impact (d = 0.81) were obtained. No significant differences were found between the groups on changes in anxiety and depression. CONCLUSIONS: MSInvigor8 delivered with email-based support is a potentially promising, acceptable, and cost-effective approach to treating fatigue in people with multiple sclerosis in New Zealand.

Pre-school screening for developmental and emotional health: Comparison with neurodevelopmental assessment.

AIM: The study aim was 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: This is a 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 (Children with Hypoglycaemia and their Later Development (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 used in both assessments were compared. RESULTS: Of the 274 children who underwent clinical neurodevelopmental assessment at a mean (standard deviation) 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 two were referred by both. When assessed twice, 39 (17%) children changed parent-completed Strengths and Difficulties Questionnaire 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). CONCLUSION: More children met referral criteria for the B4SC screening programme than for a more comprehensive neurodevelopmental assessment. Children who did not have screening had a higher incidence of cognitive and behaviour problems than those who did.