Prepartum and postpartum mothers' and fathers' feelings of frustration in response to infant crying.

In this cross-sectional study performed in Canada, we evaluated the frustration levels of prepartum and postpartum mother and father couple-pairs. Our goal was to determine if there were differences in frustration levels between mothers and fathers while listening to prolonged infant crying, and further, how frustration levels might differ between prepartum and postpartum samples. Using two discrete groups, prepartum (Sample 1; N = 48) and postpartum (Sample 2; N = 44) mother and father couple-pairs completed 600 s of listening to audio-recorded infant cry sounds. Participants continuously reported their subjective frustration using a computerized Continuous Visual Analog Scale (CVAS). There was no significant difference in frustration responses between mothers and fathers across both prepartum and postpartum samples. Postpartum mothers and fathers experienced greater frustration than their prepartum counterparts, and frustration increased faster in postpartum couples compared to prepartum couples. Informing first-time parents of the universal experiences of frustration to prolonged crying bouts that are characteristic of their infant's early weeks of life may lead to greater understanding towards their infant, and perhaps decreased instances of harmful responses.

En este estudio transeccional, evaluamos los niveles de frustración de las parejas de mamás y papás antes y después del parto. Nuestro propósito fue determinar si hay diferencias entre mamás y papás en cuanto a los niveles de frustración mientras escuchan el prolongado llanto del infante, y cómo los niveles de frustración pudieran diferir entre grupos­muestra antes y después del parto. Usando dos grupos discretos, antes del parto (grupo­muestra 1; N = 48) y después del parto (grupo­muestra 2; N = 44), las parejas de mamás y papás completaron 600 segundos escuchando sonidos grabados en audio de llanto de infante. Los participantes continuamente reportaron su frustración subjetiva usando una escala análoga visual continua computarizada (CVAS). No hubo diferencia significativa en las respuestas de frustración entre mamás y papás a lo largo de los grupos­muestra tanto antes del parto como después del parto. Las mamás y papás en el grupo­muestra después del parto experimentaron mayor frustración que sus homólogos en el grupo­muestra antes del parto, y la frustración aumentó más rápido en las parejas del grupo­muestra después del parto tal como se les comparó con las parejas del grupo­muestra antes del parto. Estos resultados sugieren que las parejas primíparas posterior al parto están más propensas a experimentar considerables cantidades de frustración como respuesta al llanto del infante después que el bebé ha nacido. Informarles a los progenitores primerizos acerca de las experiencias generales de la frustración a los prolongados ataques de llanto que son característicos de las primeras semanas de vida de su infante pudiera llevar a una mayor comprensión hacia su infante y quizás disminuir las instancias de respuestas dañinas.

Dans cette étude transversale nous avons évalué les niveaux de frustration des couples­paires mère et père avant et après la naissance. Notre but était de déterminer s'il existe des différences entres les mères et les pères dans leurs niveaux de frustration en entendant des pleurs de bébé prolongés et de quelle manière les niveaux pourraient différer entre les échantillons avant la naissance et après la naissance. En utilisant deux groupes discrets, avant la naissance (Echantillon 1; N = 48) et après la naissance (Echantillon 2; N = 44) les couples­paires mère et père ont écouté 600 seconds d'enregistrements de pleurs de bébés. Les participants ont fait état de leur frustration subjective en utilisant une échelle analogique visuelle continue informatisée (CVAS). Il s'est avéré n'y avoir aucune différence importante dans les réactions de frustration entre les mères et les pères au travers des échantillons à la fois avant l'accouchement et après l'accouchement. Ces résultats suggèrent que les coupes postpartum primipares sont plus à même de faire l'expérience de niveaux élevés de frustration en réaction aux pleurs du bébé une fois le bébé arrivé. Informer les parents qui sont parents pour la première fois des expériences universelles de frustration aux crises de pleurs prolongées qui caractérisent les premières semaines de la vie des bébés peut mener à une plus grande compréhension de leur bébé et peut­être à une baisse des case d réactions néfastes.

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.

The REDUCED trial: a cluster randomized trial for REDucing the utilization of CEsarean delivery for dystocia.

BACKGROUND: To reduce cesarean delivery rates in nulliparous women, guidelines for diagnosing nonprogressive labor have been developed by the National Institute of Child Health and Human Development, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine. These are mainly based on data from the Consortium for Safe Labor study. The guidelines have not been tested in a clinical trial, so the efficacy and safety of this new approach is uncertain. OBJECTIVE: This study aimed to assess whether adoption of new guidelines for diagnosing nonprogressing labor would reduce cesarean delivery rates. STUDY DESIGN: We conducted a cluster randomized controlled trial of a knowledge translation program of the guidelines in 26 Canadian hospitals (13 control sites and 13 intervention sites). The sites included all intrapartum care sites in Alberta that perform cesarean delivery and deliver at least 70 nulliparous women annually. The baseline period started on January 1, 2015. The intervention was initiated at the first intervention site in January 2017. The follow-up period began at the first intervention site in February 2017 and lasted till February 2020. The primary outcome was the rate of cesarean delivery in nulliparous women with vertex presentation in labor at term. The secondary outcomes included spontaneous vaginal birth and maternal and neonatal safety. The main data source for the primary and secondary outcomes was the Alberta Perinatal Health Program database. The cesarean delivery rates were assessed using repeated measures mixed effects logistic regression applied to individual births. RESULTS: The analysis was based on 45,193 deliveries at intervention sites and 43,725 deliveries at control sites. There was no evidence of a decrease in the rate of cesarean delivery in association with the intervention (baseline-adjusted odds ratio, 0.94; 95% confidence interval [0.85-1.05]; P=.259). The rate of spontaneous vaginal delivery increased slightly (baseline-adjusted odds ratio, 1.10; 95% confidence interval, [1.01-1.18]; P=.024). We did not observe any differences in adverse maternal or neonatal outcomes. CONCLUSION: Cesarean delivery rates in nulliparous women were not reduced by the application of recent guidelines for the diagnosis of nonprogressive labor. Spontaneous vaginal delivery-a secondary outcome-was increased in the intervention group. The intervention appears to be safe.

Severe Maternal Morbidity and Maternal Mortality Associated with Assisted Reproductive Technology.

OBJECTIVE: To assess the association between use of assisted reproductive technologies (ART) and severe maternal morbidity and maternal mortality (SMM). METHODS: We carried out a cohort study that included all hospital deliveries at ≥20 weeks gestation in Canada (excluding Québec) between April 2009 and March 2018. Outcomes of interest included composite SMM and SMM types (e.g., severe preeclampsia, HELLP syndrome, and eclampsia; severe hemorrhage; acute renal failure). Multivariable regression was used to estimate crude and adjusted rate ratios (RR and aRR) and 95% confidence intervals (CI). RESULTS: The study included 2 535 056 women, of whom 72 023 (2.8%) delivered following the use of ART. The composite SMM rate for women who used ART was 34.7 per 1000 deliveries (95% CI 33.0-36.0) versus 11.5 per 1000 deliveries (95% CI 11.4-11.6) for women who did not use ART (RR 3.01; 95% CI 2.89-3.14). ART use was associated with SMM types such as severe preeclampsia, HELLP syndrome, and eclampsia (RR 3.50; 95% CI 3.27-3.73), severe hemorrhage (RR 3.58, 95% CI 3.27-3.92), and acute renal failure (RR 6.79; 95% CI 5.78-7.98). Associations between ART and composite SMM were attenuated but remained elevated after adjusting for maternal characteristics (aRR 2.34; 95% CI 2.24-2.45). Women who used ART and had a multi-fetal pregnancy had a 4.7 times higher rate of composite SMM compared with women who did not use ART and delivered singletons. CONCLUSION: Women who deliver following the use of ART have increased risks of SMM and require counselling that includes mention of the lower risks of SMM associated with ART-conceived singleton pregnancy.

Prediction Model Performance With Different Imputation Strategies: A Simulation Study Using a North American ICU Registry.

OBJECTIVES: To evaluate the performance of pragmatic imputation approaches when estimating model coefficients using datasets with varying degrees of data missingness. DESIGN: Performance in predicting observed mortality in a registry dataset was evaluated using simulations of two simple logistic regression models with age-specific criteria for abnormal vital signs (mentation, systolic blood pressure, respiratory rate, WBC count, heart rate, and temperature). Starting with a dataset with complete information, increasing degrees of biased missingness of WBC and mentation were introduced, depending on the values of temperature and systolic blood pressure, respectively. Missing data approaches evaluated included analysis of complete cases only, assuming missing data are normal, and multiple imputation by chained equations. Percent bias and root mean square error, in relation to parameter estimates obtained from the original data, were evaluated as performance indicators. SETTING: Data were obtained from the Virtual Pediatric Systems, LLC, database (Los Angeles, CA), which provides clinical markers and outcomes in prospectively collected records from 117 PICUs in the United States and Canada. PATIENTS: Children admitted to a participating PICU in 2017, for whom all required data were available. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Simulations demonstrated that multiple imputation by chained equations is an effective strategy and that even a naive implementation of multiple imputation by chained equations significantly outperforms traditional approaches: the root mean square error for model coefficients was lower using multiple imputation by chained equations in 90 of 99 of all simulations (91%) compared with discarding cases with missing data and lower in 97 of 99 (98%) compared with models assuming missing values are in the normal range. Assuming missing data to be abnormal was inferior to all other approaches. CONCLUSIONS: Analyses of large observational studies are likely to encounter the issue of missing data, which are likely not missing at random. Researchers should always consider multiple imputation by chained equations (or similar imputation approaches) when encountering even only small proportions of missing data in their work.

Head circumference, total cerebral volume and neurodevelopment in preterm neonates.

OBJECTIVES: To assess the association of head circumference (HC) <10th percentile at birth and discharge from the neonatal intensive care unit (NICU) with neurodevelopment in very preterm (24-32 weeks' gestational age) neonates, and to compare the association of HC and total cerebral volume (TCV) with neurodevelopmental outcomes. DESIGN: In a prospective cohort, semiautomatically segmented TCV and manually segmented white matter injury (WMI) volumes were obtained. Multivariable regressions were used to study the association of HC and TCV with neurodevelopmental outcomes, accounting for birth gestational age, WMI and postnatal illness. SETTING: Participants born in 2006-2013 at British Columbia Women's Hospital were recruited. PATIENTS: 168 neonates had HC measurements at birth and discharge and MRI at term-equivalent age (TEA). 143 children were assessed at 4.5 years. MAIN OUTCOME MEASURES: Motor, cognitive and language outcomes at 4.5 years were assessed using the Movement Assessment Battery for Children Second Edition (M-ABC) and Wechsler Preschool and Primary Scale of Intelligence Third Edition Full Scale IQ (FSIQ) and Verbal IQ (VIQ). RESULTS: Small birth HC was associated with lower M-ABC and FSIQ scores. In children with small birth HC, small discharge HC was associated with lower M-ABC, FSIQ and VIQ scores, while normal HC at discharge was no longer associated with adverse outcomes. HC strongly correlated with TCV at TEA. TCV did not correlate with outcomes. CONCLUSIONS: Small birth HC is associated with poorer neurodevelopment, independent of postnatal illness and WMI. Normalisation of HC during NICU care appears to moderate this risk.

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.

Evaluating NeuroSENSE for assessing depth of hypnosis during desflurane anesthesia: an adaptive, randomized-controlled trial.

PURPOSE: Processed electroencephalography (EEG) monitors support depth-of-hypnosis assessment during anesthesia. This randomized-controlled trial investigated the performance of the NeuroSENSE electroencephalography (EEG) monitor to determine whether its wavelet anesthetic value for central nervous system (WAVCNS) index distinguishes consciousness from unconsciousness during induction of anesthesia (as assessed by the anesthesiologist) and emergence from anesthesia (indicated by patient responsiveness), and whether it correlates with changes in desflurane minimum alveolar concentration (MAC) during maintenance of anesthesia. METHODS: EEG was collected using a fronto-temporal bilateral montage. The WAVCNS was continuously recorded by the NeuroSENSE monitor, to which the anesthesiologist was blinded. Anesthesia was induced with propofol/remifentanil and maintained with desflurane, with randomized changes of -0.4, 0, or +0.4 MAC every 7.5 min within the 0.8-1.6 MAC range, if clinically acceptable to the anesthesiologist. During emergence from anesthesia, desflurane was stepped down by 0.2 MAC every five minutes. RESULTS: Data from 75 patients with a median [interquartile range] age of 41[35-52] yr were obtained. The WAVCNS distinguished consciousness from unconsciousness as assessed by the anesthesiologist, with area under the receiver operating characteristic curve of 99.5% (95% confidence interval [CI], 98.5 to 100.0) at loss of consciousness and 99.4% (95% CI, 98.5 to 100.0) at return of consciousness. Bilateral WAVCNS changes correlated with desflurane concentrations, with -8.0 and -8.6 WAVCNS units, respectively, per 1 MAC change in the 0.8-1.6 MAC range during maintenance of anesthesia and -10.0 and -10.5 WAVCNS units, respectively, in the 0.4-1.6 MAC range including emergence from anesthesia. CONCLUSION: The NeuroSENSE monitor can reliably discriminate between consciousness and unconsciousness, as assessed by the anesthesiologist, during induction of anesthesia and with a lower level of reliability during emergence from anesthesia. The WAVCNS correlates with desflurane concentration but plateaus at higher concentrations, similar to other EEG monitors, which suggests limited utility to titrate higher concentrations of anesthetic vapour. TRIAL REGISTRATION: clinicaltrials.gov, NCT02088671; registered 17 March, 2014.

Episiotomy use among vaginal deliveries and the association with anal sphincter injury: a population-based retrospective cohort study.

BACKGROUND: The rate of obstetric anal sphincter injury has increased in recent years, particularly among operative vaginal deliveries. We sought to characterize temporal trends in episiotomy use and to quantify the association between episiotomy and obstetric anal sphincter injury. METHODS: Using a population-based retrospective cohort study design of hospital data from 2004 to 2017, we studied all vaginal deliveries of singleton infants at term gestation in Canada (excluding Quebec). Rates of obstetric anal sphincter injury were contrasted between women who had an episiotomy and those who did not. Log-binomial regression was used to estimate the association between episiotomy and obstetric anal sphincter injury among women with spontaneous and operative vaginal deliveries after controlling for confounders. RESULTS: The study population included 2 570 847 deliveries. Episiotomy use declined significantly among operative vaginal deliveries (53.1% in 2004 to 43.2% in 2017, p < 0.0001) and spontaneous vaginal deliveries (13.5% in 2004 to 6.5% in 2017, p < 0.0001). Episiotomy was associated with higher rates of obstetric anal sphincter injury among spontaneous vaginal deliveries (4.8 with episiotomy v. 2.4% without; adjusted rate ratio [RR] 2.06, 95% confidence interval [CI] 2.00-2.11) and this association remained after stratification by parity and obstetric history. In contrast, episiotomy was associated with lower rates of obstetric anal sphincter injury among forceps deliveries in nulliparous women (adjusted RR 0.63, 95% CI 0.61-0.66), and women with vaginal birth after cesarean (adjusted RR 0.71, 95% CI 0.60-0.85), but not among parous women without a previous cesarean (adjusted RR 1.16, 95% CI 1.00-1.34). INTERPRETATION: Episiotomy use has declined in Canada for all vaginal deliveries. The protective association between episiotomy and obstetric anal sphincter injury among women who gave birth by operative vaginal delivery (especially forceps) warrants reconsideration of clinical practice among nulliparous women and those attempting vaginal birth after cesarean.

A transformation of oxygen saturation (the saturation virtual shunt) to improve clinical prediction model calibration and interpretation.

BACKGROUND: The relationship between peripheral oxygen saturation (SpO2) and the inspired oxygen concentration is non-linear. SpO2 is frequently used as a dichotomized predictor, to manage this non-linearity. We propose the saturation virtual shunt (VS) as a transformation of SpO2 to a continuous linear variable to improve interpretation of disease severity within clinical prediction models. METHOD: We calculate the saturation VS based on an empirically derived approximation formula between physiological VS and SpO2. We evaluated the utility of the saturation VS in a clinical study predicting the need for facility admission in children in a low resource health-care setting. RESULTS: The transformation was saturation VS = 68.864 × log10(103.711 - SpO2) - 52.110. The ability to predict hospital admission based on a dichotomized SpO2 produced an area under the receiver operating characteristic curve of 0.57, compared to 0.71 based on the untransformed SpO2 and saturation VS. However, the untransformed SpO2 demonstrated a lack of fit compared to the saturation VS (goodness-of-fit test p value < 0.0001 vs 0.098). The observed admission rates varied non-linearly with the untransformed SpO2 but varied linearly with the saturation VS. CONCLUSION: The saturation VS estimates a continuous linearly interpretable disease severity based on SpO2 and improves clinical prediction.

Autonomic Parameter and Stress Profile Predict Secondary Ischemic Events After Transient Ischemic Attack or Minor Stroke.

Background and Purpose- Traditional risk factors for ischemic stroke are body stressors that are related to autonomic autonomic system (ANS) dysfunction. The value of ABCD2 score (age, blood pressure, clinical features, duration of symptoms, diabetes) to predict ischemic stroke after transient ischemic attack is compromised by the inclusion of a limited number of stressors. We aimed to assess whether markers of ANS function and stress could predict the occurrence of secondary ischemic events after transient ischemic attack or minor stroke. Methods- This is a prospective cohort study in which 201 patients were recruited within 48 hours after initial transient ischemic attack or minor stroke and followed for 90 days to assess the development of secondary ischemic events. ABCD2 score, heart rate variability (HRV) parameters as markers of ANS function, and psychological stress were assessed. Logistic regression and area under the curve (AUC) were used to assess the models' predictive ability. Results- Morning high frequency (HF) HRV power and changes in HF HRV from morning to afternoon (daytime HF changes) were the most useful HRV predictors for both ischemic events (AUC=0.61 and 0.70) and ischemic stroke (AUC=0.62 and 0.72). Compared with ABCD2 score, 2 HRV-based stress models showed higher predictive ability for ischemic events (AUC=0.82 versus 0.63, 0.76 versus 0.63; P<0.05) and ischemic stroke (AUC=0.87 versus 0.64, 0.82 versus 0.64; P<0.05). Conclusions- Assessing the effects of stress on the ANS may be an innovative way to stratify the risk of ischemic events after transient ischemic attack or minor stroke. New risk stratification by assessing the dynamic features of ANS dysfunction and stress may help identify high-risk sub-populations that may benefit from added management.

Gymnastic-Based Movement Therapy for Children With Neurodevelopmental Disabilities: Results From a Pilot Feasibility Study.

Background: Developmental and behavioral issues often limit the participation of children with neurodevelopmental disabilities (NDD) in community-based activities with their peers, which decreases opportunities for their social learning and development. Parents of children with NDD seek out programs that address physical and psychosocial development. Several studies already support the positive effects for the child to attend physical activity programs (PAPs). However, these studies are highly prone to biases and Hawthorne effect. In the planning stage of a large prospective study to assess the effectiveness of PAPs we reviewed the records of children who participated in a gymnastic-based program, the Empowering Steps Movement Therapy (ESMT). Besides generating useful data for developing the prospective study we thought these data reflect the rate of changes in context of normal practice in a naturalistic environment; therefore protected from Hawthorne effect and other biases. Design: This is a historical cohort: the files of 67 children with NDD were examined across a 2-year period (Jan 2011 to Jan 2013). As part of standard practice, the ESMT therapists document changes in motor function every 6 months, using the ESMT's proprietary motor scale. Parents also completed a parental questionnaire in June 2011 regarding their perceptions of changes in their child's physical and psychosocial function, as well as family functioning since their child started the program. Results: Linear Mixed Effects Model clearly identified three groups according to changes in motor function: the ones with rapid changes (mostly functional children with autism spectrum disorder: n = 13), the ones with moderate changes (different types of NDD diagnoses: n = 41) and the ones that did not change or even decreased motor skills over the follow-up (children with complex diseases or uncontrolled epilepsy despite treatment: n = 13). Parental questionnaires (n = 39) reported improvement in most of the children's physical and psychosocial abilities; they also indicated improvement in some of the family parameters. There was no association between the changes in children's motor functions and parents' responses to the questionnaire. Conclusion: Despite limitations due to the retrospective nature of the study, the absence of a control group and the absence of validated measurement tools, the observed positive effects of attending movement therapy center on motor performance and psychosocial development confirm in a naturalistic environment what has been shown in context of clinical trials or quasi-experimental studies. These results are not conclusive. They warrant further, rigorous investigation using validated instruments, independent assessors, and control groups.

Calmer: a robot for managing acute pain effectively in preterm infants in the neonatal intensive care unit.

INTRODUCTION: For preterm infants in the neonatal intensive care unit, early exposure to repeated procedural pain is associated with negative effects on the brain. Skin-to-skin contact with parents has pain-mitigating properties, but parents may not always be available during procedures. Calmer, a robotic device that simulates key pain-reducing components of skin-to-skin contact, including heart beat sounds, breathing motion, and touch, was developed to augment clinical pain management. OBJECTIVE: Our objective was to evaluate the initial efficacy of Calmer for mitigating pain in preterm infants. We hypothesized that, compared to babies who received a human touch-based treatment, facilitated tucking, infants on Calmer would have lower behavioural and physiological pain indices during a single blood test required for clinical care. METHODS: Forty-nine preterm infants, born between 27 and 36 weeks of gestational age, were randomized either to facilitated tucking or Calmer treatment. Differences between groups in changes across 4 procedure phases (baseline 1, baseline 2, poke, and recovery) were evaluated using (1) the Behavioral Indicators of Infant Pain scored by blind coders from bedside videotape and (2) heart rate and heart rate variability continuously recorded from a single-lead surface ECG (lead II) (Biopac, Canada) sampled at 1000 Hz using a specially adapted portable computer system and processed using Mindware. RESULTS: No significant differences were found between groups on any outcome measures. CONCLUSION: Calmer provided similar treatment efficacy to a human touch-based treatment. More research is needed to determine effects of Calmer for stress reduction in preterm infants in the neonatal intensive care unit over longer periods.

Cannabis use as a risk factor for causing motor vehicle crashes: a prospective study.

AIM: We conducted a responsibility analysis to determine whether drivers injured in motor vehicle collisions who test positive for Δ-9-tetrahydrocannabinol (THC) or other drugs are more likely to have contributed to the crash than those who test negative. DESIGN: Prospective case-control study. SETTING: Trauma centres in British Columbia, Canada. PARTICIPANTS: Injured drivers who required blood tests for clinical purposes following a motor vehicle collision. MEASUREMENTS: Excess whole blood remaining after clinical use was obtained and broad-spectrum toxicology testing performed. The analysis quantified alcohol and THC and gave semiquantitative levels of other impairing drugs and medications. Police crash reports were analysed to determine which drivers contributed to the crash (responsible) and which were 'innocently involved' (non-responsible). We used unconditional logistic regression to determine the likelihood (odds ratio: OR) of crash responsibility in drivers with 0 < THC < 2 ng/ml, 2 ng/ml ≤ THC < 5 ng/ml and THC ≥ 5 ng/ml (all versus THC = 0 ng/ml). Risk estimates were adjusted for age, sex and presence of other impairing substances. FINDINGS: We obtained toxicology results on 3005 injured drivers and police reports on 2318. Alcohol was detected in 14.4% of drivers, THC in 8.3%, other drugs in 8.9% and sedating medications in 19.8%. There was no increased risk of crash responsibility in drivers with THC < 2 ng/ml or 2 ≤ THC < 5 ng/ml. In drivers with THC ≥ 5 ng/ml, the adjusted OR was 1.74 [95% confidence interval (CI) = 0.59-6.36; P = 0.35]. There was significantly increased risk of crash responsibility in drivers with blood alcohol concentration (BAC) ≥ 0.08% (OR = 6.00;95% CI = 3.87-9.75; P < 0.01), other recreational drugs detected (OR = 1.82;95% CI = 1.21-2.80; P < 0.01) or sedating medications detected (OR = 1.45; 95%CI = 1.11-1.91; P < 0.01). CONCLUSIONS: In this sample of non-fatally injured motor vehicle drivers in British Columbia, Canada, there was no evidence of increased crash risk in drivers with Δ-9-tetrahydrocannabinol < 5 ng/ml and a statistically non-significant increased risk of crash responsibility (odds ratio = 1.74) in drivers with Δ-9-tetrahydrocannabinol ≥ 5 ng/ml.

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.

Effects of Dexmedetomidine on Blood Glucose and Serum Potassium Levels in Children Undergoing General Anesthesia: A Secondary Analysis of Safety Endpoints During a Randomized Controlled Trial.

BACKGROUND: Dexmedetomidine is a highly selective α2-adrenergic agonist, which is increasingly used in pediatric anesthesia and intensive care. Potential adverse effects that have not been rigorously evaluated in children include its effects on blood glucose and serum potassium concentrations, which are relevant due to the associations of derangements of both parameters with undesired outcomes. We investigated the effects of 3 different doses of dexmedetomidine on these outcomes in a randomized controlled trial in children undergoing elective surgery. METHODS: Sixty-four American Society of Anesthesiologists I-II children were randomized to receive either dexmedetomidine 0.25 µg/kg, dexmedetomidine 0.5 µg/kg, dexmedetomidine 0.75 µg/kg, or 0 µg/kg (control), as a bolus administered over 60 seconds after induction of anesthesia. Changes in plasma glucose and serum potassium concentrations were measured in venous blood sampled before and at 15 and 30 minutes after study drug administration. Data were plotted within and between groups and analyzed using a constrained longitudinal data approach. RESULTS: Forty-nine children completed the study. Mean glucose levels at 15 and 30 minutes were elevated with estimated changes from baseline of 0.37 mmol/L (95% CI, 0.29-0.45 mmol/L) and 0.05 mmol/L (95% CI, 0.00-0.10 mmol/L), respectively. At 15 minutes, there was a linear dose-response relationship (1.07 mmol/L/µg/kg [95% CI, 0.57-1.58 mmol/L/µg/kg]), but there was no appreciable effect of dexmedetomidine at 30 minutes (0.15 mmol/L/µg/kg [95% CI, -0.40 to 0.70 mmol/L/µg/kg]). Potassium levels were depressed relative to baseline, with a mean difference at 15 minutes of -0.20 mEq/L (95% CI, -0.28 to -0.12 mEq/L) and at 30 minutes of -0.12 mEq/L (95% CI, -0.15 to -0.08 mEq/L), but there was no appreciable effect of dexmedetomidine at either time. CONCLUSIONS: Small elevations in glucose and decreases in potassium were observed after induction of anesthesia in children. The elevation in glucose at 15 minutes depended on the dose of dexmedetomidine administered. These preliminary data warrant further investigation.

Consecutive fecal calprotectin measurements for predicting relapse in pediatric Crohn's disease patients.

BACKGROUND: Asymptomatic children with Crohn's disease (CD) require ongoing monitoring to ensure early recognition of a disease exacerbation. AIM: In a cohort of pediatric CD patients, we aimed to assess the utility of serial fecal calprotectin measurements to detect intestinal inflammatory activity and predict disease relapse. METHODS: In this prospective longitudinal cohort study, children with CD on infliximab therapy in clinical remission were included. Fecal calprotectin levels were assessed at baseline and at subsequent 2-5 visits. Clinical and biochemical disease activity were assessed using the Pediatric Crohn's Disease Activity Index, C-reactive protein and erythrocyte sedimentation rate at baseline and at visits over the following 18 mo. RESULTS: 53 children were included and eighteen patients (34%) had a clinical disease relapse during the study. Baseline fecal calprotectin levels were higher in patients that developed symptomatic relapse [median (interquartile range), relapse 723 µg/g (283-1758) vs 244 µg/g (61-627), P = 0.02]. Fecal calprotectin levels > 250 µg/g demonstrated good predictive accuracy of a clinical flare within 3 mo (area under the receiver operator curve was 0.86, 95% confidence limits 0.781 to 0.937). CONCLUSION: Routine fecal calprotectin testing in children with CD in clinical remission is useful to predict relapse. Levels > 250 µg/g are a good predictor of relapse in the following 3 mo. This information is important to guide monitoring standards used in this population.

Pediatric oncology and stem cell transplant patients with healthcare-associated Clostridium difficile infection were already colonized on admission.

Clostridium difficile is the leading cause of healthcare-associated infections worldwide. The diagnosis of C. difficile infection (CDI) in pediatric oncology patients is complex as diarrhea is common, and there is a high rate of colonization in infants and young children. This study was conducted to assess the accuracy of the surveillance definitions of healthcare-associated CDI (HA-CDI) and to determine the prevalence of toxigenic C. difficile colonization among pediatric oncology and stem cell transplant patients. METHODS: A prospective cohort study was conducted over a three-year period in an inpatient pediatric oncology and stem cell transplant setting. Baseline stool samples were collected within three days of admission and were genotypically compared with clinically indicated samples submitted after three days of admission. RESULTS: A total of 175 patients were recruited with a total of 536 admissions. The adjusted prevalence of baseline toxigenic C. difficile colonization among admissions was 32.8%. Seventy-eight percent of positive admissions did not have history of CDI. Colonization with a toxigenic strain on admission was predictive of CDI (OR = 28.6; 95% CI, 6.58-124.39; P < 0.001). Nearly all clinical isolates (8/9) shared identical pulsed-field gel electrophoresis patterns with baseline isolates or were closely related (1/9). Only one of the 11 cases that were considered HA-CDI was potentially nosocomially acquired. CONCLUSION: The prevalence of colonization with toxigenic C. difficile in our cohort is high. Unfortunately, the current CDI surveillance definitions overestimate the incidence of HA-CDI in pediatric oncology and stem cell transplantation settings.

Plasma cholesterol levels and brain development in preterm newborns.

BACKGROUND: To assess whether postnatal plasma cholesterol levels are associated with microstructural and macrostructural regional brain development in preterm newborns. METHODS: Sixty preterm newborns (born 24-32 weeks gestational age) were assessed using MRI studies soon after birth and again at term-equivalent age. Blood samples were obtained within 7 days of each MRI scan to analyze for plasma cholesterol and lathosterol (a marker of endogenous cholesterol synthesis) levels. Outcomes were assessed at 3 years using the Bayley Scales of Infant Development, Third Edition. RESULTS: Early plasma lathosterol levels were associated with increased axial and radial diffusivities and increased volume of the subcortical white matter. Early plasma cholesterol levels were associated with increased volume of the cerebellum. Early plasma lathosterol levels were associated with a 2-point decrease in motor scores at 3 years. CONCLUSIONS: Higher early endogenous cholesterol synthesis is associated with worse microstructural measures and larger volumes in the subcortical white matter that may signify regional edema and worse motor outcomes. Higher early cholesterol is associated with improved cerebellar volumes. Further work is needed to better understand how the balance of cholesterol supply and endogenous synthesis impacts preterm brain development, especially if these may be modifiable factors to improve outcomes.

Risk factors for hospitalizations associated with depression among women during the years around a birth: a retrospective cohort study.

INTRODUCTION: Socio-economic status (SES) is an important determinant of health. Low SES is associated with higher rates of prenatal and post-partum depression, and prenatal and post-partum depression are associated with sub-optimal maternal and infant health. Furthermore, increased negative effects of post-partum depression have been reported in children from low SES backgrounds. OBJECTIVE: To assess whether SES was related to the risk of a medical or psychiatric hospitalization associated with depression (HAWD) and the risk of a HAWD by anti-depressant (AD) use during the years around a birth. METHODS: This retrospective cohort study used linked birth, hospitalization, prescription and tax-file records of the study cohort. We linked registry data of 243,933 women delivering 348,273 live infants in British Columbia (1999-2009). The outcomes of interest were a HAWD and a HAWD with the associated patient AD use. Ranked area-based measures of equivalised, family disposable income were used to create income deciles, our proxy for SES. Decile-1 represented the lowest income areas, and mothers from Decile-6 (middle-income) were the comparator group. Anti-depressant use was defined as having a prescription for a selective serotonin reuptake inhibitor (SSRI) or other AD during the years around a birth, defined as the period beginning 12 months before conception and ending 12 months after the birth. We analysed by pregnancy using mixed effects logistic regression whilst adjusting for maternal age and parity. RESULTS: Compared to mothers from middle-income areas (Decile-6), mothers from low income areas (Decile-1, Decile-2) had increased odds of a HAWD [adjusted OR=1.77 (CI: 1.43, 2.19); adjusted OR=1.56 (CI: 1.26, 1.94)]. Mothers from low income areas with depression and no AD use had even higher odds of a HAWD [adjusted OR=1.83 (CI: 1.33, 2.20); adjusted OR=1.71(CI: 1.33, 2.20)]. CONCLUSIONS: This study provides preliminary evidence to suggest that barriers to treating depression with ADs in mothers from low income areas during the years around a birth might contribute to their increased risk of a HAWD associated with non-pharmacologically treated depression. Further research is needed to understand the reasons for this increased risk. DISCLAIMER: All inferences, opinions, and conclusions drawn in this manuscript are those of the authors and do not reflect the opinions or policies of the Data Stewards of Population Data BC.