Maternal deaths by suicide and drug overdose in two Canadian provinces; retrospective review.

OBJECTIVE: To identify and review factors associated with maternal deaths by suicide and drug overdose in the Canadian Coroner and Medical Examiners Database (CCMED), from 2017-2019. METHODS: We identified potential maternal deaths in Ontario and British Columbia by searching the CCMED narratives of deaths to females 10 to 60 years old for pregnancy-related terms. Identified narratives were then qualitatively reviewed in quadruplicate to determine if they were maternal deaths by suicide or drug overdose, and to extract information on maternal characteristics, the manner of death, and factors associated with each death. RESULTS: Of the 90 deaths identified in this study, 15 (16.7%) were due to suicide and 20 (22.2%) were due to a drug overdose. These deaths occurred to women of varying ages and across the pregnancy-postpartum period. Among the suicides, 10 were by hanging, and among the overdose-related deaths, 15 had fentanyl detected. Notably, 13 (37.1%) of the 35 deaths to suicide or drug overdose occurred beyond 42 days after pregnancy, 19 (54.3%) followed a miscarriage or induced abortion, and in 23 (65.7%) there was an established history of mental health illness. Substance use disorders were documented in 4 of the 15 suicides (26.7%), and 18 of the 20 overdose-related deaths (90.0%). CONCLUSION: Suicide and drug overdose may contribute more to maternal deaths in Canada than previously realized. Programs are needed to identify women at risk of these outcomes, and to intervene during pregnancy and beyond the conventional postpartum period.

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.

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.

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.

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.

Early neonatal heart rate variability patterns in different subtypes of perinatal hypoxic-ischemic brain injury.

BACKGROUND: This study aims to compare the longitudinal changes in heart rate variability (HRV) during therapeutic hypothermia in neonates with different subtypes of hypoxic-ischemic brain injury. METHODS: HRV was computed from 1 hour time-epochs q6 hours for the first 48 hours. Primary outcome was brain-injury pattern on MRI at 4(3-5) days. We fitted linear mixed-effect regression models with HRV metric, brain injury subtype and postnatal age. RESULTS: Among 89 term neonates, 40 neonates had abnormal brain MRI (focal infarct 15 (38%), basal-ganglia predominant 8 (20%), watershed-predominant 5 (13%), and mixed pattern 12 (30%)). There was no significant difference in the HRV metrics between neonates with normal MRI, focal infarcts and basal ganglia pattern. At any given postnatal age, the degree of HRV suppression (HRV measure in the brain-injury subtype group/HRV measure in Normal MRI group) was significant in neonates with watershed pattern (SDNN(0.63, p = 0.08), RMSSD(0.74, p = 0.04)) and mixed pattern injury (SDNN (0.64, p < 0.001), RMSSD (0.75, p = 0.02)). HRV suppression was most profound at the postnatal age of 24-30 h in all brain injury subtypes. CONCLUSION: Neonates with underlying watershed injury with or without basal-ganglia injury demonstrates significant HRV suppression during first 48 hour of hypothermia therapy. IMPACT: Our study suggests that suppression of heart rate variability in neonates during therapeutic hypothermia varies according to the pattern of underlying hypoxic-ischemic brain injury. Neonates with watershed predominant pattern and mixed pattern of brain injury have the most severe suppression of heart rate variability measures. Heart rate variability monitoring may provide early insights into the pattern of hypoxic-ischemic brain injury in neonates undergoing therapeutic hypothermia earlier than routine clinical MRI.

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.

Time trends, geographic variation and risk factors for gastroschisis in Canada: A population-based cohort study 2006-2017.

BACKGROUND: Previous studies showed increases in rates of gastroschisis in Canada in the first decade of the 21st century. OBJECTIVE: We sought to examine the epidemiologic characteristics of gastroschisis in Canada in recent years. METHODS: We conducted a retrospective population-based cohort study of all livebirths and stillbirths delivered in Canada (excluding Quebec) from 2006 to 2017, with information obtained from the Canadian Institute for Health Information. Gastroschisis rates by maternal age, region of residence, and maternal and infant characteristics were quantified using prevalence rate ratios (RR) and 95% confidence intervals (CI). Log-binomial regression was used to quantify the associations between risk factors and gastroschisis. RESULTS: There were 1314 gastroschisis cases among 3 364 116 births. The prevalence rate was 3.7 per 10 000 total births in 2006 and 3.4 per 10 000 total births in 2017, with substantial annual variation in rates. The proportion of mothers aged 20-24 years decreased from 16.5% in 2006 to 11.3% in 2017, while the proportion of mothers aged <20 years halved from 4.8% to 2.3%. The prevalence of gastroschisis at birth remained unchanged among mothers aged <20, 20-24 and 30-49 years but increased among mothers aged 25-29 years. The age-adjusted prevalence rate of gastroschisis increased across the period (for 2016-2017 versus 2006-2007 rate ratio [RR] 1.28, 95% CI 1.05, 1.56), and there was substantial regional variation. Risk factors included problematic use of substances (RR 2.61, 95% CI 2.01, 3.39) and hypothyroidism (RR 2.76, 95% CI 1.56, 4.88). There was a North-to-South difference in gastroschisis prevalence (adjusted RR Far North compared with South 1.54, 95% CI 1.11, 2.15). CONCLUSION: Gastroschisis birth prevalence rates in Canada have stabilised in recent years compared with the increase documented previously. The substantial geographic variation and North-to-South difference in gastroschisis prevalence may indicate variation in socio-economic status, lifestyle and nutritional patterns.

Prenatally diagnosed omphaloceles: Report of 92 cases and association with Beckwith-Wiedemann syndrome.

OBJECTIVE: Describe the prevalence, perinatal and long-term outcomes of Beckwith-Wiedemann syndrome (BWS) among prenatally detected omphaloceles. METHODS: All prenatally diagnosed omphaloceles from 2010 to 2015 within a single tertiary care centre were identified. An echocardiogram and detailed fetal ultrasound were performed, and amniocentesis was offered with karyotype/microarray analysis and BWS molecular testing. Perinatal, neonatal, and long-term outcomes were retrieved for BWS cases. RESULTS: Among 92 omphaloceles, 62 had additional anomalies. Abnormal karyotypes were identified in 23/62 (37%) non-isolated and 2/30 (7%) isolated cases. One BWS case (5%) was identified among non-isolated omphaloceles and six BWS cases (37.5%) were identified among isolated omphaloceles after exclusion of aneuploidy. Among 19 BWS cases, 21% were conceived by ART. All omphaloceles underwent primary closure. Prenatally, macrosomia and polyhydramnios were seen in 42%. Macroglossia and nephromegaly were more commonly detected postnatally. Preterm birth occurred in 10/19 (53%) cases and cesarean deliveries were performed in 7/19 (40%) cases. Overall mortality was 20% (4/19). Embryonal tumors were diagnosed in 2/16 (12.5%) children, and neurodevelopmental outcomes were normal in 9/12 (75%) survivors. CONCLUSIONS: After excluding aneuploidy, BWS was identified in 37.5% and 5% of isolated and non-isolated omphaloceles, respectively. Omphaloceles were small-moderate size with good long-term surgical and neurodevelopmental outcomes when isolated.

Stillbirth in Canada: anachronistic definition and registration processes impede public health surveillance and clinical care.

The archaic definition and registration processes for stillbirth currently prevalent in Canada impede both clinical care and public health. The situation is fraught because of definitional problems related to the inclusion of induced abortions at ≥20 weeks' gestation as stillbirths: widespread uptake of prenatal diagnosis and induced abortion for serious congenital anomalies has resulted in an artefactual temporal increase in stillbirth rates in Canada and placed the country in an unfavourable position in international (stillbirth) rankings. Other problems with the Canadian stillbirth definition and registration processes extend to the inclusion of fetal reductions (for multi-fetal pregnancy) as stillbirths, and the use of inconsistent viability criteria for reporting stillbirth. This paper reviews the history of stillbirth registration in Canada, provides a rationale for updating the definition of fetal death and recommends a new definition and improved processes for fetal death registration. The recommendations proposed are intended to serve as a starting point for reformulating issues related to stillbirth, with the hope that building a consensus regarding a definition and registration procedures will facilitate clinical care and public health.

RéSUMé: La définition et les méthodes d'enregistrement archaïques des mortinaissances qui prévalent actuellement au Canada entravent à la fois les soins cliniques et la santé publique. La situation est délicate à cause des problèmes de définition que pose l'inclusion des avortements provoqués à ≥ 20 semaines de gestation parmi les mortinaissances : le recours généralisé au diagnostic prénatal et les avortements provoqués en cas d'anomalies congénitales graves ont entraîné une augmentation temporelle artéfactuelle des taux de mortinatalité au Canada et placé le pays dans une position défavorable dans les classements internationaux (de la mortinatalité). Les autres problèmes dans la définition et les méthodes d'enregistrement canadiennes des mortinaissances sont l'inclusion de la réduction fœtale (pour les grossesses multifœtales) parmi les mortinaissances et l'emploi de critères de viabilité inconsistants pour déclarer les mortinaissances. Nous examinons ici l'histoire de l'enregistrement des mortinaissances au Canada, nous justifions une révision possible de la définition de la mort fœtale et nous recommandons une nouvelle définition et des méthodes d'enregistrement améliorées des morts fœtales. Les recommandations proposées se veulent un point de départ à une reformulation des questions liées à la mortinatalité, dans l'espoir que l'établissement d'un consensus sur une définition et sur les méthodes d'enregistrement facilitera les soins cliniques et la santé publique.

Population-based surveillance of severe microcephaly and congenital Zika syndrome in Canada.

PURPOSE: To estimate the minimum incidence of congenital Zika syndrome (CZS) and severe microcephaly in Canada and describe key clinical, epidemiological, aetiological and outcome features of these conditions. METHODS: Two separate national surveillance studies were conducted on CZS and severe microcephaly using the well-established Canadian Paediatric Surveillance Program from 2016 to 2019. Over 2700 paediatricians across Canada were surveyed monthly and asked to report demographic details, pregnancy and travel history, infant anthropometry, clinical features and laboratory findings of newly identified cases. Reports were reviewed to assign an underlying aetiology of severe microcephaly. Incidence rates were estimated using monthly live birth denominators. RESULTS: Thirty-four infants met the case definition for severe microcephaly and <5 met the case definition for CZS. The associated minimum incidence rates were 4.5 per 100 000 live births for severe microcephaly and 0.1-0.5 per 100 000 live births for CZS. Of severe microcephaly cases, 53% were attributed to genetic causes, 15% to infectious or ischaemic causes and 32% to unknown causes. The median head circumference-for-age Z-score at birth was -3.2 (IQR -3.8 to -2.6), and catch-up growth was often not achieved. Common clinical features included intracranial abnormalities (n=23), dysmorphology (n=19) and developmental delays (n=14). Mothers of infants with non-genetic aetiologies travelled during pregnancy more often (10/16) than mothers of infants with genetic aetiologies (<5/18; p<0.01). CONCLUSION: Severe microcephaly and CZS are both rare in Canada. Minimum incidence rates can be used as a baseline against which novel or re-emergent causes of severe microcephaly or CZS can be compared.

Abnormalities in evoked potentials associated with abnormal glycemia and brain injury in neonatal hypoxic-ischemic encephalopathy.

OBJECTIVE: To investigate how functional integrity of ascending sensory pathways measured by visual and somatosensory evoked potentials (VEP & SEP) is associated with abnormal glycemia and brain injury in newborns treated with hypothermia for hypoxic-ischemic encephalopathy (HIE). METHODS: Fifty-four neonates ≥ 36 weeks gestational age with HIE underwent glucose testing, VEPs, SEPs, and magnetic resonance imaging (MRI) the first week of life. Minimum and maximum glucose values recorded prior to evoked potential (EP) testing were compared with VEP and SEP measures using generalized estimating equations. Relationships between VEP and SEP measures and brain injury on MRI were assessed. RESULTS: Maximum glucose is associated with decreased P200 amplitude, and increased odds that N300 peak will be delayed/absent. Minimum glucose is associated with decreased P22 amplitude. Presence of P200 and N300 peaks is associated with decreased odds of brain injury in the visual processing pathway, with delayed/absent N300 peak associated with increased odds of brain injury in posterior white matter. CONCLUSIONS: Deviations from normoglycemia are associated with abnormal EPs, and abnormal VEPs are associated with brain injury on MRI in cooled neonates with HIE. SIGNIFICANCE: Glucose is a modifiable risk factor associated with atypical brain function in neonates with HIE despite hypothermia treatment.

Data Quality Assessment on Congenital Anomalies in Ontario, Canada.

Background: Congenital anomalies (CAs) are a major cause of infant morbidity and mortality in Canada. Reliably identifying CAs is essential for CA surveillance and research. The main objective of this study was to assess the agreement of eight sentinel anomalies including: neural tube defects (NTD), orofacial clefts, limb deficiency defects (LDD), Down syndrome (DS), tetralogy of Fallot (TOF), gastroschisis (GS), hypoplastic left heart syndrome (HLHS) and transposition of great vessels (TGA) captured in the BORN Information System (BIS) database and the Canadian Institute for Health Information (CIHI) Discharge Abstract Database (DAD). Methods: Live birth and stillbirth records between the BIS and CIHI-DAD in the fiscal years of 2012-2013 to 2015-2016 were linked using 10 digit infant Ontario Health Insurance Plan (OHIP) numbers. Percent agreement and Kappa statistics were performed to assess the reliability (agreement) of CAs identified in the linked BIS and CIHI-DAD birth records. Then, further investigations were conducted on those CA cases identified in the CIHI-DAD only. Results: Kappa coefficients of the eight selected CAs between BIS ("Confirmed" or "Suspected" cases) and CIHI-DAD were 0.96 (95% CI: 0.93-0.98) for GS; 0.81 (95% CI: 0.78-0.83) for Orofacial clefts; 0.75 (95% CI: 0.72-0.77) for DS; 0.71 (95% CI: 0.65-0.77) for TOF; 0.62 (95% CI: 0.55-0.68) for TGA; 0.59 (95% CI: 0.49-0.68) for HLHS, 0.53 (95% CI: 0.46-0.60) for NTD-all; and 0.30 (95% CI: 0.23-0.37) for LDD. Conclusions: The degree of agreement varied among sentinel CAs identified between the BIS and CIHI. The potential reasons for discrepancies include incompleteness of capturing CAs using existing picklist values, especially for certain sub-types, incomplete neonatal special care data in the BIS, and differences between clinical diagnosis in the BIS and ICD-10-CA classification in the DAD. A future data abstraction study will be conducted to investigate the potential reasons for discrepancies of CA capture between two databases. This project helps quantify the quality of CA data collection in the BIS, enhances understanding of CA prevalence in Ontario and provides direction for future data quality improvement activities.

Gastrointestinal hemodynamic changes during therapeutic hypothermia and after rewarming in neonatal hypoxic-Ischemic encephalopathy.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is associated with disturbances in visceral blood flow velocities. Therapeutic Hypothermia (TH) is a standard of care; however, its impact on gastrointestinal blood flow in infants with HIE is unknown. The objective of this study was to assess gastrointestinal (GI) blood flow and left ventricle output (LVO) in infants with hypoxic-ischemic encephalopathy during whole body TH and after rewarming. METHODS: Serial echocardiography and Doppler evaluation of intestinal blood flow (celiac (CA) and superior mesenteric (SMA) arteries) were prospectively performed in a cohort of 20 newborn infants with HIE at 4 time points during hypothermia and after rewarming. Demographic, clinical and biochemical data were collected and analyzed for their relevance. RESULTS: Median gestational age and birth weight was 40 weeks (37-41) and 3410 g (2190-4950) respectively. Celiac and mesenteric artery flow remained low during hypothermia and rose significantly after rewarming [peak systolic velocity in CA (0.63 m/s to 0.77 m/s, p = 0.004) and SMA (0.43 m/s to 0.55 m/s, p = 0.001)]. This increase was temporally associated with increased left ventricular output (106 ml/kg/min to 149 ml/kg/min, p < 0.0001). Median age to reach 25% of the feeds was 5 days (1-7 days). All patients survived. CONCLUSIONS: CA and SMA blood flow velocity and LVO did not vary during hypothermia but rose after rewarming. This may suggest protective effect of therapeutic hypothermia on gastrointestinal system. The association of these physiological changes with neonatal outcome needs further assessment.

Outcomes of multi-gestational pregnancies affected by esophageal atresia - tracheoesophageal fistula.

BACKGROUND: Contemporary outcomes of infants with esophageal atresia with or without tracheoesophageal fistula (EA/TEF) from multi-gestational pregnancies compared to those of singleton pregnancies have not been reported. METHODS: A single-center retrospective review of EA/TEF patients born from 1999 to 2013 was performed. Patient demographics, gestational age (GA), birth weight, associated anomalies, requirement for gastrostomy tube and mortality were reviewed. RESULTS: Singleton EA/TEF patients outnumbered those from multi-gestational pregnancies nearly 10:1 (214 vs 22 patients). EA/TEF patients from multi-gestational pregnancies were more likely to be premature (77% vs. 32%), have lower birth weight (mean 1766 g vs. 2695 g), have associated duodenal atresia (18% vs. 6%) and require gastrostomy tube (41% vs. 33%) for feeding challenges compared to EA/TEF singletons. Mortality was also significantly greater for multi-gestational EA/TEF patients compared to singleton EA/TEF patients (18% vs. 6%). CONCLUSION: EA/TEF infants from multi-gestational pregnancies have greater clinical complexity and mortality than singleton EA/TEF patients. Parents of EA/TEF multi-gestational infants should be appropriately counseled and supported.

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.

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.