Diabetes mellitus in pregnancy across Canada.

BACKGROUND: Contemporary estimates of diabetes mellitus (DM) rates in pregnancy are lacking in Canada. Accordingly, this study examined trends in the rates of type 1 (T1DM), type 2 (T2DM) and gestational (GDM) DM in Canada over a 15-year period, and selected adverse pregnancy outcomes. METHODS: This study used repeated cross-sectional data from the Canadian Institute of Health Information (CIHI) hospitalization discharge abstract database (DAD). Maternal delivery records were linked to their respective birth records from 2006 to 2019. The prevalence of T1DM, T2DM and GDM were calculated, including relative changes over time, assessed by a Cochrane-Armitage test. Also assessed were differences between provinces and territories in the prevalence of DM. RESULTS: Over the 15-year study period, comprising 4,320,778 hospital deliveries in Canada, there was a statistically significant increase in the prevalence of GDM and T1DM and T2DM. Compared to pregnancies without DM, all pregnancies with any form of DM had higher rates of hypertension and Caesarian delivery, and also adverse infant outcomes, including major congenital anomalies, preterm birth and large-for-gestational age birthweight. CONCLUSION: Among 4.3 million pregnancies in Canada, there has been a rise in the prevalence of DM. T2DM and GDM are expected to increase further as more overweight women conceive in Canada.

Les tests et le dépistage génétiques chez les enfants.

Les tests génétiques, qui ont évolué rapidement depuis vingt ans, deviennent monnaie courante en pédiatrie. Le présent document de principes procure un aperçu des récents développements qui peuvent avoir des répercussions sur les tests génétiques chez les enfants. La génétique est un domaine en constante évolution, et le présent document de principes s'attarde tout particulièrement au dépistage néonatal élargi, au séquençage de nouvelle génération, aux découvertes fortuites, aux tests commercialisés directement auprès des consommateurs, aux tests d'histocompatibilité et aux tests génétiques dans le contexte de la recherche.

Genetic testing and screening in children.

Genetic testing has progressed rapidly over the past two decades and is becoming common in paediatrics. This statement provides an overview of recent developments that may impact genetic testing in children. Genetics is a rapidly evolving field, and this statement focuses specifically on expanded newborn screening, next generation sequencing (NGS), incidental findings, direct-to-consumer testing, histocompatibility testing, and genetic testing in a research context.

Hyperglycemia and Glucose Variability Are Associated with Worse Brain Function and Seizures in Neonatal Encephalopathy: A Prospective Cohort Study.

OBJECTIVES: To investigate how glucose abnormalities correlate with brain function on amplitude-integrated electroencephalography (aEEG) in infants with neonatal encephalopathy. STUDY DESIGN: Neonates born at full term with encephalopathy were enrolled within 6 hours of birth in a prospective cohort study at a pediatric academic referral hospital. Continuous interstitial glucose monitors and aEEG were placed soon after birth and continued for 3 days. Episodes of hypoglycemia (≤50 mg/dL; ≤2.8 mmol/L) and hyperglycemia (>144 mg/dL; >8.0 mmol/L) were identified. aEEG was classified in 6-hour epochs for 3 domains (background, sleep-wake cycling, electrographic seizures). Generalized estimating equations assessed the relationship of hypo- or hyperglycemia with aEEG findings, adjusting for clinical markers of hypoxia-ischemia (Apgar scores, umbilical artery pH, and base deficit). RESULTS: Forty-five infants (gestational age 39.5 ± 1.4 weeks) were included (24 males). During aEEG monitoring, 16 episodes of hypoglycemia were detected (9 infants, median duration 77.5, maximum 220 minutes) and 18 episodes of hyperglycemia (13 infants, median duration 237.5, maximum 3125 minutes). Epochs of hypoglycemia were not associated with aEEG changes. Compared with epochs of normoglycemia, epochs of hyperglycemia were associated with worse aEEG background scores (B 1.120, 95% CI 0.501-1.738, P < .001), less sleep-wake cycling (B 0.587, 95% CI 0.417-0.757, P < .001) and more electrographic seizures (B 0.433, 95% CI 0.185-0.681, P = .001), after adjusting for hypoxia-ischemia severity. CONCLUSIONS: In neonates with encephalopathy, epochs of hyperglycemia were temporally associated with worse global brain function and seizures, even after we adjusted for hypoxia-ischemia severity. Whether hyperglycemia causes neuronal injury or is simply a marker of severe brain injury requires further study.

Adverse childhood experiences: Basics for the paediatrician.

In 1998, the Centers for Disease Control and Prevention Adverse Childhood Experiences study established the profound effects of early childhood adversity on life course health. The burden of cumulative adversities can affect gene expression, immune system development and condition stress response. A scientific framework provides explanation for numerous childhood and adult health problems and high-risk behaviours that originate in early life. In our review, we discuss adverse childhood experiences, toxic stress, the neurobiological basis and multigenerational and epigenetic transmission of trauma and recognized health implications. Further, we outline building resilience, screening in the clinical setting, primary care interventions, applying trauma-informed care and future directions. We foresee that enhancing knowledge of the far-reaching effects of adverse childhood events will facilitate mitigation of toxic stress, promote child and family resilience and optimize life course health trajectories.

Neonatal oesophageal perforation: The role for non-operative management.

AIM: Isolated oesophageal perforation in neonates is a rare but potentially life-threatening condition. Although management has historically been operative, conservative management (antibiotics, bowel rest, parenteral nutrition) is now more routinely used. The aim of this study was to evaluate the management of this condition in two large neonatal surgical centres. METHODS: A retrospective cohort study was conducted for neonates admitted to The Hospital for Sick Children (Toronto, Canada) or The Royal Children's Hospital (Melbourne, Australia) with a diagnosis of oesophageal perforation, from 2006 to 2016. Patients with oesophageal atresia or tracheo-oesophageal fistula were excluded. Data were collected from chart review regarding demographics, clinical course, management and outcomes. RESULTS: Eleven neonates with oesophageal perforation were identified over a 10-year period at the two centres. Median gestational age at birth was 25.3 weeks (interquartile range 24.2-28.8) and the majority (7/11, 64%) of neonates were extremely low birthweight. Diagnosis was made on day 1 of life for 9 of 11 (81%) neonates and was secondary to nasogastric tube insertion in 10 of 11 (91%) neonates. Only four (36%) neonates had symptomatic complications. All neonates were managed with bowel rest and intravenous antibiotics for a median of 7 days (interquartile range 7-10); two patients required operative intervention. Three neonates (27%) developed chronic lung disease and two (19%) died prior to discharge. CONCLUSIONS: Oesophageal perforation is severe complication secondary to instrumentation of the upper gastrointestinal tract in neonates. Prompt and accurate diagnosis is crucial. Non-operative management is effective for the majority, though morbidity is common.

Cardiovascular Associations with Abnormal Brain Magnetic Resonance Imaging in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia and Rewarming.

OBJECTIVE: This article compares hemodynamic characteristics of neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) with normal versus abnormal brain magnetic resonance imaging (MRI). METHODS: Serial echocardiography (echo) was performed within 24 hours, after 48 to 72 hours of cooling, within 24 hours of normothermia, and after starting feeds. Pulmonary hemodynamics, cardiac output, and ventricular function were evaluated. All neonates underwent brain MRI (day 4-5), per clinical standard of care. Clinical cardiovascular and echocardiography characteristics were compared between patients with normal versus abnormal MRI. Cardiovascular changes during TH and after rewarming were identified. RESULTS: Twenty neonates at median gestation and birth weight of 40 weeks (interquartile range [IQR]: 39, 41) and 3,410 g (IQR: 2,885, 4,093), respectively, were enrolled. Increased median left ventricular output (LVO) (106-159 mL/kg/min, p < 0.001) and reduced isovolumic relaxation time (IVRT) (48-42 ms, p < 0.001) were seen after rewarming. Echocardiography evidence of pulmonary hypertension (PH) was identified in five neonates. Eight neonates (40%) had brain injury identified on MRI (watershed [n = 4], basal ganglia [n = 4]); this subgroup were more likely to have echo evidence of PH at 24 hours. CONCLUSION: Longitudinal changes in cardiac output were noted in neonates with HIE during TH and rewarming. Echocardiography evidence of PH, however, was associated with abnormal MRI brain. The prognostic relevance of these physiologic changes requires more comprehensive delineation.

Early life environment and social determinants of cardiac health in children with congenital heart disease.

Congenital heart disease is a significant cause of infant mortality. Epidemiology and social context play a crucial role in conditioning disease burden and modulating outcomes, while diagnosis and treatment remain resource intensive. This review will address the role of social demographics, environmental exposure, epigenetics and nutrition in the aetiology of congenital heart disease. We then discuss the determinant effect of social factors on the provision and outcomes of care for congenital heart disease and implications for practice. It is our hope that enhanced knowledge of the intersection of social determinants of health and congenital heart disease will facilitate effective preventative strategies at the individual and population levels to optimize heart health outcomes across the life course.

Changes in the incidence and surgical treatment of ankyloglossia in Canada.

BACKGROUND: Recent reports show increases in rates of ankyloglossia and frenotomy in British Columbia. We carried out a study to determine temporal trends and regional variations in ankyloglossia and frenotomy in Canada. METHODS: The study included all hospital-based live births in Canada (excluding Quebec) between April 2002 and March 2015, with information obtained from the Canadian Institute for Health Information. Information on ankyloglossia and frenotomy was obtained from records of hospital admission for childbirth. Temporal trends and provincial/territorial variations were quantified using rate ratios (RR) and 95% confidence intervals (CI). RESULTS: Ankyloglossia rates increased from 6.86 in 2002 to 22.6 per 1000 live births in 2014 (P for trend < 0.001), while frenotomy rates increased from 3.76 in 2002 to 14.7 per 1000 live births in 2014 (P for trend < 0.001). Frenotomy rates among infants with ankyloglossia increased from 54.7% in 2002 to 63.9% in 2014 (RR: 1.18, 95% CI: 1.13-1.24). Compared with British Columbia, rates of ankyloglossia were over three-fold higher in Saskatchewan (RR: 3.40, 95% CI: 3.16-3.67), Alberta (RR: 3.50, 95% CI: 3.29-3.72) and the Yukon (RR: 3.62, 95% CI: 2.67-4.92), while rates of frenotomy were three- to four-fold higher in the Yukon (RR: 3.41, 95% CI: 2.28-5.10), Alberta (RR: 4.01, 95% CI: 3.71-4.33) and Saskatchewan (RR: 4.12, 95% CI: 3.76-4.52). CONCLUSION: A desire to increase rates of breast feeding initiation and absence of standardized criteria for the diagnosis of ankyloglossia have resulted in runaway rates of frenotomy for newborn infants in some parts of Canada.

Three hundred babies born to underhoused mothers in Toronto-understanding the problem and how we can help.

Little is known about pregnancy in underhoused women, possibly because the number of underhoused mothers with babies in Toronto has been significantly underestimated. Using a novel data collection method, it has been found that there are approximately 300 babies being born each year to underhoused women in Toronto. This finding has significant public health implications, as these women are at increased risk of multiple issues related to physical health, mental health, child protection, poverty and safety. This commentary presents a new data collection strategy, highlights the importance of accurate data collection and offers suggestions for supports for this over-looked population.

Associations of Perinatal Clinical and Magnetic Resonance Imaging Measures with Developmental Outcomes in Children Born Very Preterm.

OBJECTIVE: To identify perinatal risk factors associated with long-term neurocognitive and behavioral impairments in children born very preterm using a multivariate, partial least squares approach. STUDY DESIGN: Twenty-seven perinatal clinical and magnetic resonance imaging measures were collected at birth and during the neonatal intensive care stay for 105 neonates born very preterm (≤ 32 weeks gestational age). One-half of the children returned for neuropsychological assessments at 2 and 4 years of age. Parent-reported behavioral measures were also obtained at 4 years of age. Three partial least squares analyses were performed to determine associations between clinical and radiologic measures with cognitive outcomes at 2 and 4 years of age, as well as with behavioral measures at 4 years of age. RESULTS: Within the first components of each analysis, only intrauterine growth restriction, male sex, and absence of antenatal corticosteroid use were associated with poorer cognitive and language ability at 2 and 4 years of age, accounting for 79.6% and 71.4% of the total variance, respectively. In addition, white matter injury at term-equivalent age contributed to more problematic internalizing behaviors, behavioral symptoms, and impaired executive function at 4 years of age, accounting for 67.9% of the total variance. CONCLUSIONS: Using this data-driven multivariate approach, specific measures in prenatal and early postnatal life are shown to be selectively and significantly associated with cognitive and behavioral outcomes in children born very preterm. Early detection of risk factors can help inform prognoses of children at greatest risk of long-term impairments.

Low birthweight, gestational age, need for surgical intervention and gram-negative bacteraemia predict intestinal failure following necrotising enterocolitis.

AIM: Necrotising enterocolitis (NEC) is associated with high morbidity and mortality. The aim of this study was to identify predictors of intestinal failure (IF), morbidity and mortality following NEC. METHODS: We performed a retrospective study of all neonates treated for NEC stage II or greater at a tertiary referral NICU between 2000 and 2009. Demographic data, need for surgery, residual bowel length and rates of bacteraemia, cholestasis, IF and mortality were analysed. RESULTS: During the 10-year period, 301 patients were referred with NEC and 152 had surgical intervention. Overall mortality was 32%. Of the 230 infants who survived >42 days, 97 (42%) had IF at 42 days, decreasing to 15% at >90 days. The rate of IF was significantly higher in the surgical group than the medical group (OR 2.04, 95% CI, 1.25-3.35, p < 0.004), but 23% of the medically treated infants with NEC also developed IF. There was a significant relationship between IF and gram-negative bacteraemia, the need for surgery, cholestasis, liver failure and mortality. CONCLUSION: Intestinal failure occurred in a significant proportion of infants with NEC. Predictors for IF among infants with NEC were low birthweight, low gestational age, need for surgical intervention and gram-negative bacteraemia.

Brain metabolite concentrations are associated with illness severity scores and white matter abnormalities in very preterm infants.

BACKGROUND: Magnetic resonance spectroscopy allows for the noninvasive study of brain metabolism and therefore may provide useful information about brain injuries. We examined the associations of brain metabolite ratios in very preterm infants with white matter lesions and overall health status at birth. METHODS: Spectroscopy data were obtained from 99 very preterm infants (born ≤32 wk gestation) imaged shortly after birth and from 67 of these infants at term-equivalent age. These data were processed using LCModel. Multiple regression was used to examine the association of metabolite ratios with focal noncystic white matter lesions visible on conventional magnetic resonance imaging (MRI) and with at-birth illness severity scores. RESULTS: Within 2 wk of birth, the ratio of N-acetylaspartate + N-acetylaspartylglutamate to creatine + phosphocreatine was significantly lower in those infants showing white matter abnormalities on conventional MRI. Increased lactate to creatine + phosphocreatine and lactate to glycerophosphocholine + phosphocholine ratios were significantly associated with increasing severity of Clinical Risk Index for Babies II and Apgar scores taken at 1 and 5 min after birth. CONCLUSION: Both overall health status at birth and white matter injury in preterm neonates are reflected in metabolite ratios measured shortly after birth. Long-term follow-up will provide additional insight into the prognostic value of these measures.

A prospective comparison of intestinal sonography and abdominal radiographs in a neonatal intensive care unit.

BACKGROUND: No study reported in the literature comprehensively compares findings on neonatal abdominal radiographs with sonography. OBJECTIVE: To compare the findings on abdominal radiographs and sonograms in infants in intensive care, to better understand how the various intestinal gas patterns on radiographs relate to the spectrum of appearances on sonography and, second, to evaluate the ability of sonography to differentiate necrotizing enterocolitis from other intestinal pathology. MATERIALS AND METHODS: We prospectively evaluated sonograms and radiographs, blinded to the other modality and to clinical information. Patients' charts were reviewed by a third blinded reader and used as a reference standard for diagnosis. We made associations between sonographic findings, radiographic intestinal gas patterns and clinical diagnoses. RESULTS: We included 75 infants with gestational ages between 23 weeks and 41 weeks. Sonographic abnormalities were present in infants with all radiographic intestinal gas patterns, including normal patterns. We only saw absent intestinal perfusion and fluid collections on sonography (suggesting intestinal necrosis and sealed perforation) in infants with intestinal dilatation with elongation on radiographs. Separation of intestinal loops on radiographs was most commonly caused by reasons other than intestinal wall thickening. Increased intestinal echogenicity or free fluid with echoes on sonography correlated with a diagnosis of necrotizing enterocolitis, whereas anechoic free fluid correlated with absence of necrotizing enterocolitis. CONCLUSION: Sonography is complementary to radiographs in infants with suspected intestinal pathology, with a spectrum of appearances seen on each modality. Some sonographic findings either strongly suggest necrotizing enterocolitis or supply evidence against this diagnosis.

Severity and duration of dysglycemia and brain injury among patients with neonatal encephalopathy.

Background: Evidence is needed to inform thresholds for glycemic management in neonatal encephalopathy (NE). We investigated how severity and duration of dysglycemia relate to brain injury after NE. Methods: A prospective cohort of 108 neonates ≥36 weeks gestational age with NE were enrolled between August 2014 and November 2019 at the Hospital for Sick Children, in Toronto, Canada. Participants underwent continuous glucose monitoring for 72 h, MRI at day 4 of life, and follow-up at 18 months. Receiver operating characteristic curves were used to assess the predictive value of glucose measures (minimum and maximum glucose, sequential 1 mmol/L glucose thresholds) during the first 72 h of life (HOL) for each brain injury pattern (basal ganglia, watershed, focal infarct, posterior-predominant). Linear and logistic regression analyses were used to assess the relationship between abnormal glycemia and 18-month outcomes (Bayley-III composite scores, Child Behavior Checklist [CBCL] T-scores, neuromotor score, cerebral palsy [CP], death), adjusting for brain injury severity. Findings: Of 108 neonates enrolled, 102 (94%) had an MRI. Maximum glucose during the first 48 HOL best predicted basal ganglia (AUC = 0.811) and watershed (AUC = 0.858) injury. Minimum glucose was not predictive of brain injury (AUC <0.509). Ninety-one (89%) infants underwent follow-up assessments at 19.0 ± 1.7 months. A glucose threshold of >10.1 mmol/L during the first 48 HOL was associated with 5.8-point higher CBCL Internalizing Composite T-score (P = 0.029), 0.3-point worse neuromotor score (P = 0.035), 8.6-fold higher odds for CP diagnosis (P = 0.014). While the glucose threshold of >10.1 mmol/L during the first 48 HOL was associated with higher odds of the composite outcome of severe disability or death (OR 3.0, 95% CI 1.0-8.4, P = 0.042), it was not associated with the composite outcome of moderate-to-severe disability or death (OR 0.9, 95% CI 0.4-2.2, P = 0.801). All associations with outcome lost significance after adjusting for brain injury severity. Interpretation: Maximum glucose concentration in the first 48 HOL is predictive of brain injury after NE. Further trials are needed to assess if protocols to control maximum glucose concentrations improve outcomes after NE. Funding: Canadian Institutes for Health Research, National Institutes of Health, and SickKids Foundation.

Risk factors for prolonged mechanical ventilation in neonates following gastrointestinal surgery.

Background: Prolonged mechanical ventilation (MV) should be avoided in neonates. Noninvasive ventilation (NIV) can facilitate weaning from MV but has risks for patients immediately following foregut surgery due to the potential risk of anastomotic leak. We evaluated the risk factors for prolonged MV following intestinal surgery in neonates. Methods: We retrospectively reviewed 253 neonates undergoing intestinal surgery in 2017-2018 to identify risk factors for prolonged MV, and determine the correlation between NIV and anastomotic leak in a tertiary neonatal intensive care unit that performs the greatest number of neonatal surgeries in Ontario. Results: The most common diagnoses were necrotizing enterocolitis/spontaneous intestinal perforation (NEC/SIP) 21%, intestinal atresia 16%, esophageal atresia/tracheoesophageal fistula 14%, ano-rectal malformation 13%, malrotation/volvulus 11%, gastroschisis 9% and omphalocele 4%. The median (IQR) duration of MV post-surgery was 3 (1-8) days with 25.7 % (n=65) of neonates on MV for >7 days. Compared to infants on MV post-surgery for ≤7 days, those with MV>7 days were of lower gestational age, birth weight and weight at surgery, but a higher proportion underwent stoma creation, had a longer duration of opioid administration and higher rates of moderate to severe bronchopulmonary dysplasia (BPD) and mortality (P<0.05). Generalized linear regression analysis showed lower gestational age (GA) and longer opioid administration were associated with longer duration of MV (P<0.001), but indication for surgery, weight at surgery and stoma creation didn't correlate with longer duration of MV (P>0.05). Of the 122 patients handled by one-stage resection with primary anastomosis, 22.1% (n=27) received NIV with 74.1% (n=20) commenced on NIV after 7 days post-surgery, anastomotic leak was detected in 2.5 % (3/122) patients and didn't correlate with NIV. Conclusions: Lower GA and longer opioid administration were risk factors for prolonged MV in neonates following intestinal surgery. Further research is needed to investigate modifiable practices around pain assessment/ventilation in these patients, and the correlation between NIV and anastomotic leak.

Socioeconomic status and prevalence of congenital heart defects: does universal access to health care system eliminate the gap?

BACKGROUND: A twofold increase in the prevalence of congenital heart defects (CHDs) has been reported since the early 1970s with higher rates among children from low socioeconomic status (SES). This increase and the observed SES gap are postulated to be reflective of higher ascertainment, especially increased use of ultrasound and echography. The purpose of this study was to examine if trends over time in the prevalence of CHD were the same for high and low SES groups. METHODS: Using the child's health number as a unique identifier and through record linkage, children born in Ontario between 1994 and 2007 were followed for the diagnosis of CHD. Using postal codes and census information, SES quintiles were assigned to each child. We used adjusted rates and used multivariate models to compare trends in the prevalence rate among children born in different SES groups. RESULTS: Children born in low SES areas (23% of all births) had significantly higher rates of CHDs (rate ratio = 1.20; 95% confidence interval [CI] = 1.15-1.24). While prevalence of nonsevere CHDs declined in all SES groups since 2000, severe CHDs, especially atrial septal defects were on the rise during the study period. DISCUSSION: It is assumed that increased ascertainment is responsible for observed increase in the prevalence of CHD, especially minor defects. While the trend and pattern over time changed for severe and nonsevere CHDs, the SES gap remained consistent during the study period. Our results indicate that even free and universal access to a health care system does not eliminate the SES gap observed in the prevalence of CHD.

Childhood outcomes of neonates diagnosed with portal vein thrombosis.

AIM: The study aims to determine childhood outcomes of neonates diagnosed with portal vein thrombosis (PVT). METHODS: A retrospective chart review of neonates diagnosed with PVT who had documented follow up (physical examination, laboratory tests or ultrasonographic examination) at the age of 2 years or beyond was conducted. RESULTS: Data were available for 70 children (71% of eligible neonates) at a median age of 5 years (range 2-8 years). Physical examination was unremarkable in all who were examined (n= 68). Twenty-five children had liver functions assessed and only mild abnormalities were detected in nine children. Six of 25 patients tested for thrombophilia showed abnormalities. Thirty-seven children had ultrasonographic follow up. Left lobar atrophy (LLA) was noted in 20 children (16 had isolated LLA, two had LLA and splenomegaly, and two had LLA and portal hypertension). Five children who had normal ultrasound examinations at discharge had splenomegaly (two with additional finding of LLA) at follow up. Two children with portal hypertension diagnosed during neonatal period needed porta-caval shunting. CONCLUSION: Our results show that among patients, who had PVT as neonates, 28% still had asymptomatic LLA in childhood, 7% had slowly progressive splenomegaly and 3% required shunting because of progression of portal hypertension. Ultrasonographic follow up was the most sensitive method in detecting progression associated with neonatal PVT. Until more data are available, periodic long-term ultrasonographic follow up should be considered for neonates diagnosed with PVT.

Hyperglycemia associated with acute brain injury in neonatal encephalopathy.

OBJECTIVE: To identify how alterations in glucose levels are associated with regional brain injury in neonatal encephalopathy. METHODS: This was a prospective cohort study of 102 newborns with neonatal encephalopathy, with continuous glucose monitoring for 72 h. 97 (95%) completed 72 h of therapeutic hypothermia. Brain imaging around day 5 of life included diffusion tensor imaging and MR spectroscopy. Regions of interest were placed for both DTI and MR spectroscopy, and tractography of the optic radiation and corticospinal tract were evaluated. Linear regression models related each MR metric with minimum and maximum glucose values during each day of life, adjusting for 5-minute Apgar scores and umbilical artery pH. RESULTS: Higher maximum glucose levels on the first day of life were associated with widespread changes in mean diffusivity in the anterior and posterior white matter, splenium of the corpus callosum, lentiform nucleus, pulvinar nucleus of the thalamus, posterior limb of the internal capsule, and optic radiations, thus including regions traditionally associated with hypoxia-ischemia or hypoglycemia. No associations were found between lower minimum glucose levels and DTI changes in any regions tested, or between glucose levels and MR spectroscopy. CONCLUSIONS: In this cohort of neonatal encephalopathy with therapeutic hypothermia, higher maximal glucose on the first day of life was associated with widespread microstructural changes, but lower minimum glucose levels were not associated with changes in any of the regions tested. Long-term follow-up will determine if imaging findings translate to long-term outcomes.