Elham Khodayari Moez

Bisphenol A Metabolites and Bisphenol S in Paired Maternal and Cord Serum

Human studies show associations between maternal bisphenol A (BPA) exposure and developmental effects in children, yet biomonitoring of BPA metabolites in maternal and fetal serum remains limited, and less is known for BPA alternatives. BPA-glucuronide, BPA-sulfate, and bisphenol S (BPS) were quantified in 61 pairs of maternal and cord sera from Chinese participants. Total BPS was only detectable in four maternal (<0.03-0.07 ng/mL) and seven cord sera (<0.03-0.12 ng/mL), indicating low exposure but providing the first evidence that BPS crosses the human placenta. Total BPA metabolites in cord serum were significantly higher than in maternal serum (p < 0.05), suggesting that these may be formed in the fetus or cleared more slowly from the fetoplacental compartment. Unlike the pharmacokinetic results from controlled oral exposure studies in which BPA-glucuronide is the major BPA metabolite, here, BPA-sulfate was the dominant metabolite (GM: 0.06 and 0.08 ng/mL), significantly higher than BPA-glucuronide (GM: 0.02 and 0.04 ng/mL) (p < 0.01) in both maternal and cord sera. Moreover, the proportion of BPA-sulfate increased with total BPA. These are the first human data for BPA metabolites in paired maternal and cord serum, and results suggest that the human fetus and pregnant mother have unique exposure to BPA metabolites. Direct analysis of BPA metabolites in serum provides complementary information for evaluating early life-stage exposure and risks of BPA.

Survival and neurocognitive outcomes in pediatric extracorporeal-cardiopulmonary resuscitation

OBJECTIVE Extracorporeal Cardiopulmonary Resuscitation (E-CPR) is the initiation of extracorporeal life support during active chest compressions. There are no studies describing detailed neurocognitive outcomes of this population. We aim to describe the survival and neurocognitive outcomes of children who received E-CPR. METHODS Prospective cohort study. Children who received E-CPR at the Stollery Childrens Hospital between 2000 and 2010 were included. Neurocognitive follow-up, including Wechsler Preschool and Primary Scales of Intelligence, was completed at the age of 4.5 years, and at a minimum of 6 months after the E-CPR admission. RESULTS Fifty-five patients received E-CPR between 2000 and 2010. Children with cardiac disease had a 49% survival to hospital discharge and 43% survival at age 5-years, with no survivors (n=4) in those with non-cardiac disease. Pediatric E-CPR survivors had a mean (SD) Full Scale Intelligence quotient (FSIQ) score of 76.5 (15.9); with 4 children (24%) having intellectual disability (defined as FSIQ over 2 standard deviations below the population mean; i.e., <70). Multiple Cox regression analysis found that mechanical ventilation prior to E-CPR, open chest CPR, longer duration of CPR, low pH and more red blood cells given on the first day of ECMO, and longer time for lactate to normalize on ECMO were associated with higher mortality at age 5-years. CONCLUSION Pediatric patients with cardiac disease who required E-CPR had 43% survival at age 5 years. Of concern, the intelligence quotient in E-CPR survivors was significantly lower than the population mean, with 24% having intellectual disability.

Chronic Neuromotor Disability After Complex Cardiac Surgery in Early Life.

BACKGROUND AND OBJECTIVES: Little is known about chronic neuromotor disability (CND) including cerebral palsy and motor impairments after acquired brain injury in children surviving early complex cardiac surgery (CCS). We sought to determine the frequency and presentation of CND in this population while exploring potentially modifiable acute care predictors. METHODS: This prospective follow-up study included 549 children after CCS requiring cardiopulmonary bypass at ≤6 weeks of age. Groups included those with only 1 CCS, mostly biventricular CHD, and those with >1 CCS, predominantly single ventricle defects. At 4.5 years of age, 420 (94.6%) children received multidisciplinary assessment. Frequency of CND is given as percentage of assessed survivors. Predictors of CND were analyzed using multiple logistic regression analysis. RESULTS: CND occurred in 6% (95% confidence interval [CI] 3.7%–8.2%) of 4.5-year survivors; for 1 CCS, 4.2% (CI 2.3%–6.1%) and >1, 9.8% (CI 7%–12.6%). CND presentation showed: hemiparesis, 72%; spasticity, 80%; ambulation, 72%; intellectual disability, 44%; autism, 16%; epilepsy, 12%; permanent vision and hearing impairment, 12% and 8%, respectively. Overall, 32% of presumed causative events happened before first CCS. Independent odds ratio for CND are age (days) at first CCS, 1.08 (CI 1.04–1.12; P < .001); highest plasma lactate before first CCS (mmol/L), 1.13 (CI 1.03–1.23; P = 0.008); and >1 CCS, 3.57 (CI 1.48–8.9; P = .005). CONCLUSIONS: CND is not uncommon among CCS survivors. The frequency of associated disabilities characterized in this study informs pediatricians caring for this vulnerable population. Shortening the waiting period and reducing preoperative plasma lactate levels at first CCS may assist in reducing the frequency of CND.

Schroth Physiotherapeutic Scoliosis-Specific Exercises Added to the Standard of Care Lead to Better Cobb Angle Outcomes in Adolescents with Idiopathic Scoliosis – an Assessor and Statistician Blinded Randomized Controlled Trial

Background The North American non-surgical standard of care for adolescent idiopathic scoliosis (AIS) includes observation and bracing, but not exercises. Schroth physiotherapeutic scoliosis-specific exercises (PSSE) showed promise in several studies of suboptimal methodology. The Scoliosis Research Society calls for rigorous studies supporting the role of exercises before including it as a treatment recommendation for scoliosis. Objectives To determine the effect of a six-month Schroth PSSE intervention added to standard of care (Experimental group) on the Cobb angle compared to standard of care alone (Control group) in patients with AIS. Methods Fifty patients with AIS aged 10–18 years, with curves of 10°-45° and Risser grade 0–5 were recruited from a single pediatric scoliosis clinic and randomized to the Experimental or Control group. Outcomes included the change in the Cobb angles of the Largest Curve and Sum of Curves from baseline to six months. The intervention consisted of a 30–45 minute daily home program and weekly supervised sessions. Intention-to-treat and per protocol linear mixed effects model analyses are reported. Results In the intention-to-treat analysis, after six months, the Schroth group had significantly smaller Largest Curve than controls (-3.5°, 95% CI -1.1° to -5.9°, p = 0.006). Likewise, the between-group difference in the square root of the Sum of Curves was -0.40°, (95% CI -0.03° to -0.8°, p = 0.046), suggesting that an average patient with 51.2° at baseline, will have a 49.3° Sum of Curves at six months in the Schroth group, and 55.1° in the control group with the difference between groups increasing with severity. Per protocol analyses produced similar, but larger differences: Largest Curve = -4.1° (95% CI -1.7° to -6.5°, p = 0.002) and Sum of Curves=−0.5° (95% CI -0.8 to 0.2, p = 0.006). Conclusion Schroth PSSE added to the standard of care were superior compared to standard of care alone for reducing the curve severity in patients with AIS. Trial Registration NCT01610908

Pilot randomized controlled trial on early and late remote ischemic preconditioning prior to complex cardiac surgery in young infants

Remote ischemic preconditioning involves providing a brief ischemia–reperfusion event to a tissue to create subsequent protection from a more severe ischemia–reperfusion event to a different tissue/organ. The few pediatric remote ischemic preconditioning studies in the literature show conflicting results.

Predicting early outcomes of liver transplantation in young children: The EARLY study

AIM To determine potentially modifiable predictors of early outcomes after liver transplantation in children of age < 3 years. METHODS This study was a retrospective chart review including all consecutive children of age less than 3-years-old having had a liver transplant done at the Western Canadian referral center from June 2005 to June 2015. Pre-specified potential predictor variables and primary and secondary outcomes were recorded using standard definitions and a case report form. Associations between potential predictor variables and outcomes were determined using univariate and multiple logistic [odds ratio (OR); 95%CI] or linear (effect size, ES; 95%CI) regressions. RESULTS There were 65 children, of mean age 11.9 (SD 7.1) mo and weight 8.5 (2.1) kg, with biliary-atresia in 40 (62%), who had a living related donor [LRD; 29 (45%)], split/reduced [21 (32%)] or whole liver graft [15 (23%)]. Outcomes after liver transplant included: ventilator-days of 12.5 (14.1); pediatric intensive care unit mortality of 5 (8%); re-operation in 33 (51%), hepatic artery thrombosis (HAT) in 12 (19%), portal vein thrombosis (PVT) in 11 (17%), and any severe complication (HAT, PVT, bile leak, bowel perforation, intraabdominal infection, retransplant, or death) in 32 (49%) patients. Predictors of the prespecified primary outcomes on multiple regression were: (1) HAT: split/reduced (OR 0.06; 0.01, 0.76; P = 0.030) or LRD (OR 0.16; 0.03, 0.95; P = 0.044) vs whole liver graft; and (2) ventilator-days: surgeon (P < 0.05), lowest antithrombin (AT) postoperative day 2-5 (ES -0.24; -0.47, -0.02; P = 0.034), and split/reduced (ES -12.5; -21.8, -3.2; P = 0.009) vs whole-liver graft. Predictors of the pre-specified secondary outcomes on multiple regression were: (1) any thrombosis: LRD (OR 0.10; 0.01, 0.71; P = 0.021) or split/reduced (OR 0.10; 0.01, 0.85; P = 0.034) vs whole liver graft, and lowest AT postoperative day 2-5 (OR 0.93; 0.87, 0.99; P = 0.038); and (2) any severe complication: surgeon (P < 0.05), lowest AT postoperative day 2-5 (OR 0.92; 0.86-0.98; P = 0.016), and split/reduced (OR 0.06; 0.01, 0.78; P = 0.032) vs whole-liver graft. CONCLUSION In young children, whole liver graft and surgeon was associated with more complications, and higher AT postoperative day 2-5 was associated with fewer complications early after liver transplantation.

Prospective cohort study on noise levels in a pediatric cardiac intensive care unit

Purpose: To describe noise levels in a pediatric cardiac intensive care unit, and to determine the relationship between sound levels and patient sedation requirements. Materials and Methods: Prospective observational study at a pediatric cardiac intensive care unit (PCICU). Sound levels were measured continuously in slow A weighted decibels dB(A) with a sound level meter SoundEarPro® during a 4‐week period. Sedation requirement was assessed using the number of intermittent (PRNs) doses given per hour. Analysis was conducted with autoregressive moving average models and the Granger test for causality. Results: 39 children were included in the study. The average (SD) sound level in the open area was 59.4 (2.5) dB(A) with a statistically significant but clinically unimportant difference between day/night hours (60.1 vs. 58.6; p‐value < 0.001). There was no significant difference between sound levels in the open area/single room (59.4 vs. 60.8, p‐value = 0.108). Peak noise levels were > 90 dB. There was a significant association between average (p‐value = 0.030) and peak sound levels (p‐value = 0.006), and number of sedation PRNs. Conclusion: Sound levels were above the recommended values with no differences between day/night or open area/single room. High sound levels were significantly associated with sedation requirements.