Dataset Information

Association of Neonatal Glycemia With Neurodevelopmental Outcomes at 4.5 Years.

ABSTRACT:

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 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.

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 (?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.

Results

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.

SUBMITTER: McKinlay CJD

PROVIDER: S-EPMC5710616 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Publications

Association of Neonatal Glycemia With Neurodevelopmental Outcomes at 4.5 Years.

McKinlay Christopher J D CJD Alsweiler Jane M JM Anstice Nicola S NS Burakevych Nataliia N Chakraborty Arijit A Chase J Geoffrey JG Gamble Gregory D GD Harris Deborah L DL Jacobs Robert J RJ Jiang Yannan Y Paudel Nabin N San Diego Ryan J RJ Thompson Benjamin B Wouldes Trecia A TA Harding Jane E JE

JAMA pediatrics 20171001 10

<h4>Importance</h4>Hypoglycemia is common during neonatal transition and may cause permanent neurological impairment, but optimal intervention thresholds are unknown.<h4>Objective</h4>To test the hypothesis that neurodevelopment at 4.5 years is related to the severity and frequency of neonatal hypoglycemia.<h4>Design, setting, and participants</h4>The Children With Hypoglycemia and Their Later Development (CHYLD) Study is a prospective cohort investigation of moderate to late preterm and term in ...[more]

PMID: 28783802

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Project description:BackgroundNeonatal hypoglycemia is common and can cause neurologic impairment, but evidence supporting thresholds for intervention is limited.MethodsWe 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.ResultsOf 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.ConclusionsIn 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.).

Project description:BackgroundTo investigate mechanisms of injury and recovery in neonatal encephalopathy (NE), we performed targeted metabolomic analysis of plasma using liquid chromatography with tandem mass spectrometry (LC/MS/MS) from healthy term neonates or neonates with NE.MethodsPlasma samples from the NE (n = 45, day of life 0-1) or healthy neonatal (n = 30, ≥36 weeks gestation) cohorts had LC/MS/MS metabolomic profiling with a 193-plex targeted metabolite assay covering >366 metabolic pathways. Metabolite levels were compared to 2-year neurodevelopmental outcomes measured by the Bayley Scales of Infant and Toddler Development III (Bayley-III).ResultsOut of 193 metabolites, 57 met the pre-defined quality control criteria for analysis. Significant (after false discovery rate correction) KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways included aminoacyl-tRNA biosynthesis, arginine biosynthesis, and metabolism of multiple amino acids. Significant disease pathways included seizures. In regression models, histidine and C6 sugar amine were significantly associated with cognitive, motor, and language and betaine with cognitive and motor Bayley-III composite scores. The addition of histidine, C6 sugar amine, and betaine to a Sarnat score-based clinical regression model significantly improved model performance (Akaike information criterion and adjusted r2) for Bayley-III cognitive, motor, and language scores.ConclusionsPlasma metabolites may help to predict neurological outcomes in neonatal brain injury and enhance current clinical predictors.ImpactPlasma metabolites may help to predict neurological outcomes in NE and supplement current clinical predictors. Current metabolomics research is limited in terms of clinical application and association with long-term outcomes. Our study presents novel associations of plasma metabolites from the first 24 h of life and 2-year neurodevelopmental outcomes for infants with NE. Our metabolomics discovery provides insight into possible disease mechanisms and methods to rescue and/or supplement metabolic pathways involved in NE. Our metabolomics discovery of metabolic pathway supplementations and/or rescue mechanisms may serve as adjunctive therapies for NE.

Project description:Many premature infants are born without exposure to antenatal steroids (ANS) or with incomplete courses. This study evaluates the dose-dependent effect of ANS on rates of neonatal morbidities and early childhood neurodevelopmental outcomes of extremely premature infants.To compare rates of neonatal morbidities and 18- to 22-month neurodevelopmental outcomes of extremely premature infants exposed to no ANS or partial or complete courses of ANS.In this observational cohort study, participants were extremely premature infants (birth weight range, 401-1000 g; gestational age, 22-27 weeks) who were born at participating centers of the National Institute of Child Health and Human Development Neonatal Research Network between January 2006 and December 2011. Data were analyzed between October 2013 and May 2016.Rates of death or neurodevelopmental impairment at 18 to 22 months' corrected age. Neurodevelopmental impairment was defined as the presence of any of the following: moderate to severe cerebral palsy, a cognitive score less than 85 on the Bayley Scales of Infant and Toddler Development III, blindness, or deafness.There were 848 infants in the no ANS group, 1581 in the partial ANS group, and 3692 in the complete ANS group; the mean (SD) birth weights were 725 (169), 760 (173), and 753 (170) g, respectively, and the mean (SD) gestational ages were 24.5 (1.4), 24.9 (2), and 25.1 (1.1) weeks. Of 6121 eligible infants, 4284 (70.0%) survived to 18- to 22-month follow-up, and data were available for 3892 of 4284 infants (90.8%). Among the no, partial, and complete ANS groups, there were significant differences in the rates of mortality (43.1%, 29.6%, and 25.2%, respectively), severe intracranial hemorrhage among survivors (23.3%, 19.1%, and 11.7%), death or necrotizing enterocolitis (48.1%, 37.1%, and 32.5%), and death or bronchopulmonary dysplasia (74.9%, 68.9%, and 65.5%). Additionally, death or neurodevelopmental impairment occurred in 68.1%, 54.4%, and 48.1% of patients in the no, partial, and complete ANS groups, respectively. Logistic regression analysis revealed that complete (odds ratio, 0.63; 95% CI, 0.53-0.76) and partial (odds ratio, 0.77; 95% CI, 0.63-0.95) ANS courses were associated with lower rates of death or neurodevelopmental impairment compared with the no ANS group. The reduction in the rate of death or neurodevelopmental impairment associated with exposure to a complete ANS course may be mediated through a reduction in rates of severe intracranial hemorrhage and/or cystic periventricular leukomalacia in the neonatal period.Antenatal steroid exposure was associated with a dose-dependent protective effect against death or neurodevelopmental impairment in extremely preterm infants. The effect was partly mediated by ANS-associated reductions in rates of severe intracranial hemorrhage and/or cystic periventricular leukomalacia. These results support prompt administration of ANS, with the goal of a complete course prior to delivery.

Project description:Importance:Antibiotic exposures in early life may affect weight by altering gut microbiota, potentially increasing the likelihood of childhood obesity. Objective:To examine whether repeated antibiotic exposure by age 48 months is associated with higher body mass index (BMI) at age 54 months. Design, Setting, and Participants:This research was undertaken within a prospective cohort study in New Zealand (Growing Up in New Zealand) that recruited 6853 children antenatally during 2009 to 2010. At the 54-month follow-up, 5734 of 6156 children (93%) had their weight and height measured. Community pharmacy antibiotic dispensing data were obtained from the New Zealand Pharmaceutical Collection database for children whose parents consented to external data linkage. The analytic sample comprised singletons with 54-month weight and height measurements, community antibiotic dispensing and birth weight data, gestational age greater than 27 weeks, and no congenital anomalies. Data analysis took place from 2017 to 2018. Exposures:Antibiotic exposure (yes or no), the number of dispensings, age at first exposure, and timing (age) of exposures between birth and age 48 months. Main Outcomes and Measures:World Health Organization BMI-for-age z scores; and International Obesity Task Force overweight and obesity cutoff points that pass through adult BMI values of 25 and 30. Results:Of the 5128 singletons (2622 [51%] male; mean [SD] birth weight of 3527 [542] g), 4886 (95%) had an antibiotic prescription by age 48 months and 437 (9%) had obesity at age 54 months. Adjusted mean (SE) BMI-for-age z scores increased significantly with the number of antibiotic dispensings for 4 to 6, 7 to 9, and more than 9 dispensings (unexposed, 0.87 [0.09]; 1-3 exposures, 0.92 [0.06] [P = .57]; 4-6 exposures, 1.06 [0.06] [P = .02]; 7-9 exposures, 1.06 [0.06] [P = .02]; >9 exposures, 1.08 [0.05] [P = .01]). Additionally, receiving more than 9 dispensings was associated with greater likelihood of obesity compared with no exposure (adjusted odds ratio, 2.41; 95% CI, 1.07-5.41). Children whose exposure began in the first year of life had a higher adjusted mean (SD) BMI-for-age z score than those not exposed (1.06 [0.05] vs 0.89 [0.09]; P = .03), whereas those whose exposure commenced after the first year of life did not (1.02 [0.06] vs 0.89 [0.09]; P = .10). Conclusions and Relevance:In this study, repeated antibiotic exposure in early childhood was associated with higher mean BMI-for-age z score and an increased likelihood of obesity. Future research could examine whether interventions such as antibiotic stewardship programs, which are designed to reduce overprescribing of antibiotics, also reduce early childhood obesity.

Project description:BackgroundTherapeutic hypothermia (TH) is standard of care for moderate to severe neonatal hypoxic ischemic encephalopathy (HIE) but many survivors still suffer lifelong disabilities and benefits of TH for mild HIE are under active debate. Development of objective diagnostics, with sensitivity to mild HIE, are needed to select, guide, and assess response to treatment. The objective of this study was to determine if cerebral oxygen metabolism (CMRO2) in the days after TH is associated with 18-month neurodevelopmental outcomes as the first step in evaluating CMRO2's potential as a diagnostic for HIE. Secondary objectives were to compare associations with clinical exams and characterise the relationship between CMRO2 and temperature during TH.MethodsThis was a prospective, multicentre, observational, cohort study of neonates clinically diagnosed with HIE and treated with TH recruited from the tertiary neonatal intensive care units (NICUs) of Boston Children's Hospital, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center between December 2015 and October 2019 with follow-up to 18 months. In total, 329 neonates ≥34 weeks gestational age admitted with perinatal asphyxia and suspected HIE were identified. 179 were approached, 103 enrolled, 73 received TH, and 64 were included. CMRO2 was measured at the NICU bedside by frequency-domain near-infrared and diffuse correlation spectroscopies (FDNIRS-DCS) during the late phases of hypothermia (C), rewarming (RW) and after return to normothermia (NT). Additional variables were body temperature and clinical neonatal encephalopathy (NE) scores, as well as findings from magnetic resonance imaging (MRI) and spectroscopy (MRS). Primary outcome was the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at 18 months, normed (SD) to 100 (15).FindingsData quality for 58 neonates was sufficient for analysis. CMRO2 changed by 14.4% per °C (95% CI, 14.2-14.6) relative to its baseline at NT while cerebral tissue oxygen extraction fraction (cFTOE) changed by only 2.2% per °C (95% CI, 2.1-2.4) for net changes from C to NT of 91% and 8%, respectively. Follow-up data for 2 were incomplete, 33 declined and 1 died, leaving 22 participants (mean [SD] postnatal age, 19.1 [1.2] month; 11 female) with mild to moderate HIE (median [IQR] NE score, 4 [3-6]) and 21 (95%) with BSID-III scores >85 at 18 months. CMRO2 at NT was positively associated with cognitive and motor composite scores (β (SE) = 4.49 (1.55) and 2.77 (1.00) BSID-III points per 10-10 moL/dl × mm2/s, P = 0.009 and P = 0.01 respectively; linear regression); none of the other measures were associated with the neurodevelopmental outcomes.InterpretationPoint of care measures of CMRO2 in the NICU during C and RW showed dramatic changes and potential to assess individual response to TH. CMRO2 following TH outperformed conventional clinical evaluations (NE score, cFTOE, and MRI/MRS) at predicting cognitive and motor outcomes at 18 months for mild to moderate HIE, providing a promising objective, physiologically-based diagnostic for HIE.FundingThis clinical study was funded by an NIH grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States (R01HD076258).

Project description:BACKGROUND:Neonatal interventions are largely focused on reduction of mortality and progression towards Millennium Development Goal 4 (child survival). However, little is known about the global burden of long-term consequences of intrauterine and neonatal insults. We did a systematic review to estimate risks of long-term neurocognitive and other sequelae after intrauterine and neonatal insults, especially in low-income and middle-income countries. METHODS:We searched Medline, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, and Embase for studies published between Jan 1, 1966, and June 30, 2011, that reported neurodevelopmental sequelae after preterm or neonatal insult. For unpublished studies and grey literature, we searched Dissertation Abstracts International and the WHO library. We reviewed publications that had data for long-term outcome after defined neonatal insults. We summarised the results with medians and IQRs, and calculated the risk of at least one sequela after insult. FINDINGS:Of 28,212 studies identified by our search, 153 studies were suitable for inclusion, documenting 22,161 survivors of intrauterine or neonatal insults. The overall median risk of at least one sequela in any domain was 39·4% (IQR 20·0-54·8), with a risk of at least one severe impairment in any insult domain of 18·5% (7·7-33·3), of at least one moderate impairment of 5·0% (0·0-13·3%), and of at least one mild impairment of 10·0% (1·4-17·9%). The pooled risk estimate of at least one sequela (weighted mean) associated with one or more of the insults studied (excluding HIV) was 37·0% (95% CI 27·0-48·0%) and this risk was not significantly affected by region, duration of the follow-up, study design, or period of data collection. The most common sequelae were learning difficulties, cognition, or developmental delay (n=4032; 59%); cerebral palsy (n=1472; 21%); hearing impairment (n=1340; 20%); and visual impairment (n=1228; 18%). Only 40 (26%) studies included data for multidomain impairments. These studies included 2815 individuals, of whom 1048 (37%) had impairments, with 334 (32%) having multiple impairments. INTERPRETATION:Intrauterine and neonatal insults have a high risk of causing substantial long-term neurological morbidity. Comparable cohort studies in resource-poor regions should be done to properly assess the burden of these conditions, and long-term outcomes, such as chronic disease, and to inform policy and programme investments. FUNDING:The Bill & Melinda Gates Foundation, Saving Newborn Lives, and the Wellcome Trust.

Dataset Information

Association of Neonatal Glycemia With Neurodevelopmental Outcomes at 4.5 Years.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

Association of Neonatal Glycemia With Neurodevelopmental Outcomes at 4.5 Years.

Similar Datasets

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