Maternal Diabetes and Neurodevelopmental Outcomes of Infants Born Before 29 Weeks' Gestation.

OBJECTIVE: To compare the neurodevelopmental outcomes of infants born at <29 weeks' gestation and exposed to diabetes in pregnancy with those unexposed. STUDY DESIGN: This was a retrospective cohort study using the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-Up Network (CNFUN) databases. Infants born <29 weeks' gestation and admitted to a level 3 NICU from 2009 through 2018 who had neurodevelopmental assessments at 18 to 24 months corrected age (CA) were eligible. The two primary outcomes were: i) Neurodevelopmental Impairment (NDI) (≥1 of Bayley-III scores < 85 in any domain, cerebral palsy, or vision or hearing impairment); and ii) significant NDI (sNDI) (≥1 of Bayley-III scores < 70 in any domain, cerebral palsy GMFCS ≥ 3, bilateral blindness, or need for hearing aids or cochlear implants). Secondary outcomes were the individual components of NDI and sNDI. Adjusted odds ratios with 95% CIs were calculated to determine outcomes between groups. RESULTS: Of 13,988 eligible infants, 55% attended neurodevelopmental follow-up assessments. Infants exposed to diabetes had increased odds of NDI compared with those unexposed (aOR 1.09 (95% CI 1.08-1.54); there was no difference in sNDI (aOR 1.07 (95% CI 0.84-1.36). Language and motor delays were more common in those exposed to maternal diabetes. CONCLUSIONS: Higher rates of NDI, language, or motor delays were present in infants born at < 29 weeks' gestation exposed to diabetes in utero. Future research is needed to determine the etiology and clinical significance of these findings.

A population-based comparison of preterm neonatal deaths (22-34 gestational weeks) in France and Ontario: a cohort study.

BACKGROUND: The management and outcomes of preterm births can vary greatly even among developed nations with the same access to medicine, technology and expertise. We aimed to compare aspects of obstetrical management and mortality for preterm infants in France and Ontario, Canada. METHODS: The Better Outcomes Registry & Network (BORN) Information System in Ontario and Épidémiologique sur les petits âges gestationnels (EPIPAGE-2) in France collected information on maternal demographics, obstetrical characteristics, obstetrical interventions and neonatal outcomes for infants born between 22 and 34 weeks gestation. We used standardized covariate definitions and extracted data from 2011 (for EPIPAGE-2) and from 2012 and 2013 (for BORN) to conduct a cohort study comparing the 2 data sets (stratified into gestational age groups of 22-26, 27-31 and 32-34 wk) using multivariable logistic regression models. RESULTS: Mothers in the BORN cohort were older (30.7 yr v. 29.6 yr) but less likely to have gestational hypertension (13.4% v. 17.9%) than those in the EPIPAGE-2 cohort. Infants from EPIPAGE-2 had lower birth weights (1.3 kg v. 1.5 kg) and were more likely to be born in an institution with level 3 care (71.9% v. 55.8%). After adjustment for these differences, there was significantly higher neonatal mortality among infants from EPIPAGE-2 in the 22-26 week gestation age group (adjusted odds ratio 2.81; 95% confidence interval 1.17 to 6.74). INTERPRETATION: Even after we adjusted for both intrinsic population differences and differences in management between Ontario and France, we found a higher rate of neonatal mortality at earlier gestational ages in France. This may be related to differences in ethical approaches and/or postnatal management and should be explored further.

Subdural haemorrhage and severe coagulopathy resulting in transtentorial uncal herniation in a neonate undergoing therapeutic hypothermia.

Therapeutic hypothermia has been shown to be efficacious for improving long-term neurodevelopmental outcomes following perinatal asphyxia. Thus, cooling protocols have been adopted at most tertiary neonatal centres. We present a case of a term neonate who underwent therapeutic whole-body cooling for hypoxic ischaemic encephalopathy following a difficult forceps delivery. She abruptly deteriorated, exhibiting signs of transtentorial uncal herniation and severe disseminated intravascular coagulopathy. CT of the head confirmed a life-threatening subdural haematoma and a concealed skull fracture. Hypothermia has been shown to impair haemostasis in vivo and thus may potentially exacerbate occult haemorrhages in a clinical setting. Newborns that require instrument-assisted delivery are a particularly high-risk group for occult head injuries and should undergo careful clinical assessment for fractures and intracranial haemorrhage prior to initiation of therapeutic hypothermia.

A survey of Canadian medical student attitudes towards the ethics of pediatric clinical trials: are they different from Canadian and British health care professionals?

BACKGROUND: Due to ethical concerns and constraints inherent to research in children, the conduct of clinical trials in children has often been difficult. The views of medical professionals and trainees towards conducting clinical trials in children have been largely unexplored and are potentially important towards working to increase the number of appropriate trials conducted in children. OBJECTIVE: To explore the views of Canadian medical school trainees towards paediatric clinical trials and to compare these views with that of an earlier pilot study conducted amongst Canadian and British health care professionals. METHODS: Participants were given a questionnaire which consisted of direct questions as well as scenarios with ethical dilemmas. Responders were asked to state whether they would enter children in the trial documented in the scenario and to justify their reasons. RESULTS: 89 questionnaires were collected (74% response rate). 42% had formal teaching regarding paediatric ethical dilemmas but only 2% had formal teaching on pharmaceutical testing in children. The students were divided on whether children should only participate in trials where they receive direct benefit. Most students (85%; 95% CI: 77% to 91%) were comfortable with non-inferiority trials even with post-hoc consent. Only a third (33%; 95% CI: 24% to 43%) agreed with the use of placebo in an analgesia trial. CONCLUSION: Teaching on the ethics of paediatric clinical trials still appears to be lacking amongst medical trainees. However, there does seem to be increased willingness on the part of trainees compared to practicing medical professionals in enrolling children in clinical trials.

DAF-FM (4-amino-5-methylamino-2',7'-difluorofluorescein) diacetate detects impairment of agonist-stimulated nitric oxide synthesis by elevated glucose in human vascular endothelial cells: reversal by vitamin C and L-sepiapterin.

Elevated plasma glucose, as commonly seen in types I and II diabetes mellitus, is known to result in endothelial dysfunction, a condition characterized by a loss of nitric oxide (NO)-dependent regulation of vascular tone. In the present study, we have utilized a recently developed NO-sensitive fluorescent dye, DAF-FM (4-amino-5-methylamino-2',7'-difluorofluorescein) diacetate to directly examine the consequences of elevated glucose on agonist-evoked NO synthesis in cultured human vascular endothelial cells. Exposure of cells for 5 to 7 days to high (20 mM) external glucose markedly reduced NO production in response to ATP, histamine, or the calcium ionophore calcimycin A23187 compared with 5 and 10 mM glucose concentrations. However, high glucose did not affect agonist-evoked elevations in cytosolic-free calcium, as monitored by Fluo-3. The addition of vitamin C (150 microM) and L-sepiapterin (20 microM) for approximately 24 h to 20 mM glucose-treated cells improved stimulus-evoked NO synthesis but had no effect on cells exposed to either 5 or 10 mM glucose. Likewise, impaired NO production in high glucose-treated cells was largely reversed by exposure ( approximately 3 h) to superoxide dismutase. Cellular levels of endothelial nitric-oxide synthase protein were unaltered by elevated glucose treatment, and no further change was observed after the addition of vitamin C and l-sepiapterin. Taken together, the results of our study serve to directly explain at the cellular level how glucose-impaired NO production in human endothelial cells may be reversed by agents that are reported clinically to improve endothelium-dependent vasorelaxation in patients.