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BACKGROUND: Among adults with in-hospital cardiac arrest (IHCA), overall survival is lower in black patients compared to white patients. Data regarding racial differences in survival for pediatric IHCA are unknown. METHODS: Using 2000–2017 data from the American Heart Association Get With the Guidelines-Resuscitation® registry, we identified children >24 hours and < 18 years of age with IHCA due to an initial pulseless rhythm. We used generalized estimation equation to examine the association of black race with survival to hospital discharge, return of spontaneous circulation (ROSC), and favorable neurologic outcome at discharge. RESULTS: Overall, 2940 pediatric patients (898 black, 2042 white) at 224 hospitals with IHCA were included. The mean age was 3.0 years, 57% were male and 16% had an initial shockable rhythm. Age, sex, interventions in place at the time of arrest and cardiac arrest characteristics did not differ significantly by race. The overall survival to discharge was 36.9%, return of spontaneous circulation (ROSC) was 73%, and favorable neurologic survival was 20.8%. Although black race was associated with lower rates of ROSC compared to white patients (69.5% in blacks vs. 74.6% in whites; risk-adjusted OR 0.79, 95% CI 0.67 – 0.94, P= 0.016), black race was not associated with survival to discharge (34.7% in blacks vs. 37.8% in whites; risk-adjusted OR 0.96, 95% CI 0.80 – 1.15, P=0.68) or favorable neurologic outcome (18.7% in blacks vs. 21.8% in whites, risk-adjusted OR 0.98, 95% CI 0.80–1.20, p=0.85). CONCLUSIONS: In contrast to adults, we did not find evidence for racial differences in survival outcomes following IHCA among children.

The American Heart Association (AHA) recommends first defibrillation energy dose of 2 Joules/kilogram (J/kg) for pediatric cardiac arrest with ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT). However, optimal first energy dose remains unclear. Methods Using AHA Get With the Guidelines-Resuscitation® (GWTG-R) database, we identified children ≤12 years with IHCA due to VF/pVT. Primary exposure was energy dose in J/kg. We categorized energy doses: 1.7–2.5 J/kg as reference (reflecting 2 J/kg intended dose), 2.5 J/kg. We compared survival for reference doses to all other doses. We constructed models to test association of energy dose with survival; adjusting for age, location, illness category, initial rhythm and vasoactive medications. Results We identified 301 patients ≤12 years with index IHCA and initial VF/pVT. Survival to discharge was significantly lower with energy doses other than 1.7–2.5 J/kg. Individual dose categories of 2.5 J/kg were not associated with differences in survival. For patients with initial VF, doses >2.5 J/kg had worse survival compared to reference. For all patients ≤18 years (n = 422), there were no differences in survival between dosing categories. However, all ≤18 with initial VF receiving >2.5 J/kg had worse survival. Conclusions First energy doses other than 1.7–2.5 J/kg are associated with lower rate of survival to hospital discharge in patients ≤12 years old with initial VF/pVT, and first doses >2.5 J/kg had lower survival rates in all patients ≤18 years old with initial VF. These results support current AHA guidelines for first pediatric defibrillation energy dose of 2 J/kg.

Background: Cord blood leptin increases with advancing gestation. Preterm delivery leads to premature separation from the maternal and placental leptin source predisposing infants to postnatal leptin deficiency, but this has not been fully described. Method: Blood leptin levels were measured for infants born before 33 weeks gestation daily for the first 2 days, then weekly until 36 weeks postmenstrual age (PMA). Cord blood was obtained to provide gestational age (GA)-specific standards. Results: Cord blood leptin levels were positively associated with GA at birth, maternal body mass index (BMI) and pregnancy weight gain (all P

Background Amplitude spectral area (AMSA) predicts termination of fibrillation (TOF) with return of spontaneous circulation (ROSC) and survival in adults but has not been studied in pediatric cardiac arrest. We characterized AMSA during pediatric cardiac arrest from a Pediatric Resuscitation Quality Collaborative and hypothesized that AMSA would be associated with TOF and ROSC. Methods and Results Children aged 20 minutes without chest compressions. Univariate and multivariable logistic regression analyses controlling for weight, current, and illness category were performed. Primary end points were TOF and ROSC. Secondary end points were 24‐hour survival and survival to discharge. Between 2015 and 2019, 50 children from 14 hospitals with 111 shocks were identified. In univariate analyses AMSA was not associated with TOF and AMS‐Aavg was not associated with ROSC. Multivariable logistic regression showed no association between AMSA and TOF but controlling for defibrillation average current and illness category, there was a trend to significant association between AMSA‐avg and ROSC (odds ratio, 1.10 [1.00‒1.22] P =0.058). There was no significant association between AMSA‐avg and 24‐hour survival or survival to hospital discharge. Conclusions In pediatric patients, AMSA was not associated with TOF, whereas AMSA‐avg had a trend to significance for association in ROSC, but not 24‐hour survival or survival to hospital discharge. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02708134.

Introduction: Amplitude spectral area (AMSA) predicts termination of fibrillation (TOF) with return of spontaneous circulation (ROSC) and hospital survival in adults, but has not been studied during pediatric cardiac arrest (pCA). Hypothesis: We characterized AMSA during pCA from a pediatric resuscitation quality (pediRES-Q) collaborative and hypothesized that AMSA would be associated with TOF and ROSC. Methods: Children 20 mins without chest compressions. Univariate and multivariable logistic regression analyses controlling for weight, current, and illness category (cardiac vs non-cardiac) were performed. Primary endpoints were TOF and ROSC without ECMO. Secondary endpoints were 24-hr survival and survival to hospital discharge. Results: Between 2015-2019, 50 children from 14 hospitals (median age 3.7 years [IQR 0.6, 13.1]; median weight 16.3 kgs [IQR 6.9, 37.2]; 46% male; 73% cardiac illness category) were identified. IHCA occurred in 47 children and OHCA in 3 children. We analyzed 111 shocks with median number of DFs 1.0 [IQR 1.0, 3.0], median DF energy dose 3.27 J/kg [IQR 2.65,5.01], median DF current 0.64 A/kg [IQR 0.38,0.96], median AMSA 12.21 [IQR 7.17,17.03], and median AMSA-avg 14.6 [IQR 8.6,19.2]. TOF was achieved in 72 DFs (65%), ROSC without ECMO in 31 (62%), ROC with ECMO in 11 (22%), 24-hr survival in 40 (80%), and survival to hospital discharge in 26 (52%). Weight (OR 0.91 [0.84, 0.99] P=0.025) and DF current (OR 1.44 [0.97, 2.2] P=0.07), but not AMSA, were significantly associated with TOF for the first shock. Controlling for DF current and illness category, there was a significant association between AMSA-avg (OR 1.11 [1.0, 1.24] P=0.044) and ROSC without ECMO. There was no significant association between AMSA-avg and 24-hr survival or survival to hospital discharge. Conclusions: In pediatric patients, TOF was associated with weight and DF current, but not AMSA, whereas AMSA-avg was associated with ROSC without ECMO, but not 24-hr survival or survival to hospital discharge.

Associations have been made between maternal selective serotonin reuptake inhibitor (SSRI) use during pregnancy and altered behavior in offspring, including an increased risk of autism. Given the important role serotonin plays in behavior, we hypothesized SSRI exposure in the perinatal period would alter central serotonin receptor expression and program adult behaviors in mice.Female mice were injected with sertraline or saline throughout pregnancy. Offspring continued to receive injections on postnatal days 1-14, a time period in mice similar to the third trimester in human pregnancy. Adult offspring underwent behavioral testing, and serotonin receptor mRNA levels were quantified.Compared to controls, SSRI exposed mice did not have a reduction in social interactions, spatial learning, or exploratory behavior. As adults, sertraline exposed mice had significantly increased mRNA levels of multiple 5-HT receptors, serotonin transporter (5-HTT), and tryptophan hydroxylase isoform 2 in the cerebral cortex.Although no behavioral phenotype was observed, SSRI exposure in the perinatal period permanently alters cerebral receptor mRNA levels. We speculate these shifts in mRNA expression provide important compensation during SSRI exposure. Further pre-clinical and clinical investigation into additional serotonin-regulated phenotypes is necessary to further assess the long-term implications of perinatal SSRI exposure.

This 2019 focused update to the American Heart Association pediatric advanced life support guidelines follows the 2018 and 2019 systematic reviews performed by the Pediatric Life Support Task Force of the International Liaison Committee on Resuscitation. It aligns with the continuous evidence review process of the International Liaison Committee on Resuscitation, with updates published when the International Liaison Committee on Resuscitation completes a literature review based on new published evidence. This update provides the evidence review and treatment recommendations for advanced airway management in pediatric cardiac arrest, extracorporeal cardiopulmonary resuscitation in pediatric cardiac arrest, and pediatric targeted temperature management during post–cardiac arrest care. The writing group analyzed the systematic reviews and the original research published for each of these topics. For airway management, the writing group concluded that it is reasonable to continue bag-mask ventilation (versus attempting an advanced airway such as endotracheal intubation) in patients with out-of-hospital cardiac arrest. When extracorporeal membrane oxygenation protocols and teams are readily available, extracorporeal cardiopulmonary resuscitation should be considered for patients with cardiac diagnoses and in-hospital cardiac arrest. Finally, it is reasonable to use targeted temperature management of 32°C to 34°C followed by 36°C to 37.5°C, or to use targeted temperature management of 36°C to 37.5°C, for pediatric patients who remain comatose after resuscitation from out-of-hospital cardiac arrest or in-hospital cardiac arrest.

Successful resuscitation from cardiac arrest results in a post–cardiac arrest syndrome, which can evolve in the days to weeks after return of sustained circulation. The components of post–cardiac arrest syndrome are brain injury, myocardial dysfunction, systemic ischemia/reperfusion response, and persistent precipitating pathophysiology. Pediatric post–cardiac arrest care focuses on anticipating, identifying, and treating this complex physiology to improve survival and neurological outcomes. This scientific statement on post–cardiac arrest care is the result of a consensus process that included pediatric and adult emergency medicine, critical care, cardiac critical care, cardiology, neurology, and nursing specialists who analyzed the past 20 years of pediatric cardiac arrest, adult cardiac arrest, and pediatric critical illness peer-reviewed published literature. The statement summarizes the epidemiology, pathophysiology, management, and prognostication after return of sustained circulation after cardiac arrest, and it provides consensus on the current evidence supporting elements of pediatric post–cardiac arrest care.

Background: Selective serotonin reuptake inhibitors (SSRIs) are antidepressants prescribed in 10% of pregnancies in the USA. We have previously shown in preclinical studies that sertraline exposure impacts cardiomyocyte development, leading to reductions in left ventricular size and cardiac function. Objectives: We hypothesized that in utero SSRI exposure will lead to reduced left ventricular dimensions and cardiac function on echocardiography immediately after birth. Methods: Twenty term infants with and 21 term infants without in utero exposure to SSRIs underwent echocardiograms to assess cardiac size and function. The exclusion criteria for infants were prematurity, small or large for gestational age, any respiratory or cardiovascular support needed after birth, and any major congenital malformation. Results: Infants exposed to in utero SSRIs had significantly reduced right ventricular dimensions in the diastole (controls 1.0 cm [0.86, 1.20], SSRI 0.89 cm [0.730, 1.05], p = 0.03), and left ventricular lengths in the diastole and systole (diastole: controls 3.4 cm [3.25, 3.65], SSRI 3.25 cm [3.10, 3.45], p = 0.03; systole: controls 2.9 cm [2.65, 3.05], SSRI 2.6 cm [2.50, 2.85], p = 0.01). No differences were observed in cardiac function. Importantly, there were no differences in maternal conditions or infant birth weight, body surface area, or gestational age. Conclusions: Our findings suggest an association between in utero exposure to SSRIs and ventricular size in infants. Given the increasing use of SSRIs during pregnancy and the importance of early life programming on future cardiovascular health, larger studies need to be completed to determine if in utero SSRI exposure impacts ventricular size.

Selective serotonin reuptake inhibitors are prescribed to 6%-10% of pregnant women in the United States. Using an intrauterine plus neonatal exposure model to represent exposure throughout human pregnancy, we hypothesized sertraline exposure would impact intracardiac serotonin signaling and lead to small left heart syndrome in the absence of maternal psychopathology. C57BL/6 adult female mice received sertraline (5 mg·kg·d IP) or saline throughout pregnancy to time of delivery. Pups maintained exposure on postnatal days 1-14 to encompass the developmental window analogous to human gestation. Sertraline-exposed mice had increased cardiac hydroxyproline content, decreased 5-HT2B receptor mRNA levels, and increased 5-HT2A receptor and serotonin transporter mRNA levels on postnatal day 21 (P < 0.05). These changes were associated with diminished exercise capacity at 6 weeks (P < 0.05) and decreased adult shortening fraction and stroke volume at 5 months. Isolated cardiomyocytes from neonatal sertraline-exposed mice had significantly decreased proliferation, cross-sectional area, and phosphorylation of Akt (P < 0.05 vs. neonatal control mice). Perinatal sertraline exposure alters neonatal cardiac development and produces long-standing changes in adult cardiac function and exercise capacity. Further studies are needed to assess whether similar findings are present in the growing population that has been exposed to selective serotonin reuptake inhibitors during development.

Background: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed psychotropics for major depressive disorder during pregnancy and are used in up to 6.2% of pregnancies. Objective: To compare the perinatal outcomes of pregnancies complicated by maternal depression with or without SSRI therapy versus nondepressed pregnancies. Methods: International Classification of Diseases (ICD)-9 codes for depression were identified among women who delivered at the University of Iowa from April 2009 to March 2011. Data were extracted from linked maternal-neonatal records for all charts with an ICD-9 code for depression and an equal number of women without ICD-9 codes for depression. Results: Of the 3,695 women who delivered between 2009 and 2011, 238 had an ICD-9 code for depression. Sixteen women had depression listed in their records but did not have an ICD-9 code for depression. Their data were combined with those of the women with ICD-9 codes for depression, and it was found that 126 women (50%) in this combined depression cohort received an SSRI. Women with depression had increased alcohol and tobacco use, BMI and premature delivery rates (p < 0.01). Maternal depression was associated with an increased frequency of neonatal intensive care unit (NICU) admission (p < 0.001). In addition to depression, maternal SSRI use, obesity and smoking were univariate predictors of NICU admission. Conclusions: Among women with depression, the use of an SSRI was not associated with significant differences in any of the measured maternal or neonatal parameters, but further studies are needed to evaluate the specific effects of SSRI exposure in early or late gestation. Despite SSRI utilization, women with depression continue to have increased risks during pregnancy.

Perinatal growth restriction is associated with heightened sympathetic tone and hypertension. We have previously shown that naturally occurring neonatal growth restriction (GR) programs hypertension in male but not female mice. We therefore hypothesized that intact ovarian function or post-ovariectomy estrogen administration protects GR female mice from hypertension. Utilizing a non-interventional model that categorizes mice with weanling weights below the 10th percentile as GR, control and GR adult mice were studied at three distinct time points: baseline, post-ovariectomy (OVX), and post-OVX with oral estrogen replacement. OVX elicited hypertension in GR mice that was significantly exacerbated by psychomotor arousal (systolic blood pressure at light to dark transition: control 122+/−2; GR 119+/−2; control-OVX 116+/−3; GR-OVX 126+/−3 mmHg). Estrogen partially normalized the rising blood pressure surge seen in GR-OVX mice (23+/−7% reduction). GR mice had left ventricular hypertrophy, and GR-OVX mice in particular had exaggerated bradycardic responses to sympathetic blockade. For GR mice, a baseline increase in baroreceptor reflex sensitivity and high frequency spectral power support a vagal compensatory mechanism, and that compensation was lost following OVX. For GR mice, the OVX-induced parasympathetic withdrawal was partially restored by estrogen (40+/−25% increase in high frequency spectral power, P

Background Sertraline, a selective serotonin reuptake inhibitor (SSRI), is the most commonly prescribed therapy for maternal depression. Epidemiologic studies have linked SSRI exposure with decreased fetal growth, altered autonomic regulation, and cardiac malformations. We hypothesized SSRI exposure decreases left ventricular volumes and increases adult sympathetic nervous system activation, resulting in increased adult heart rates. Methods C57BL/6 mice received saline or sertraline (5 or 15 mg/kg/day i.p.) on postnatal days 1–14. Adult phenotypes were assessed at 5 months. Results Sertraline-exposed mice had smaller left ventricular internal diameters in diastole (control 4.0 ± 0.1 mm, SSRI 3.7 ± 0.1 mm, p < 0.05), decreased stroke volumes (control 46 ± 2.6 μL, SSRI 37 ± 2.3 μL, p < 0.05), higher heart rates (control 530 ± 13 beats per minute (bpm), SSRI 567 ± 6 bpm, p

Ventricular fibrillation occurs in 10-20% of pediatric cardiac arrests. Survival rates in children with ventricular fibrillation can be as high as 30% when the rhythm is identified and treated promptly. In the last 5 years, recommendations have been made for the use of automated external defibrillators in children between 1 and 8 years of age.The goal of this study was to determine the awareness of the ILCOR guidelines and statewide protocols concerning AED use in children ages 1-8 among emergency medical providers after new guideline release. Availability of pediatric capable AED equipment was also assessed.Surveys were distributed to EMS providers in Iowa and Montana within 1 year of the ILCOR advisory statement in 2003 recommending use of AEDs in children ages 1-8, and again approximately 1 year after the 2005 ILCOR guidelines on cardiopulmonary resuscitation were published. In Iowa, there were concentrated efforts to disseminate information about AED use in children, while there were minimal efforts in Montana.Awareness of ILCOR guidelines for use of AEDs in children was low in both states in 2003 (29% in Iowa vs. 9% in Montana, p0.001). After release of the 2005 guidelines, awareness improved significantly in both states but was still significantly greater in Iowa (83% vs. 60%, p0.002). In 2003, less than 20% of respondents in both states reported access to pediatric capable AEDs. Availability of pediatric pads and cables increased significantly in 2006 but remained low in Montana (74% in Iowa vs. 37% in Montana, p0.001).At the present time, publication of new or interim guidelines in the scientific literature alone is insufficient to ensure that new protocols are implemented. An effective and efficient method to disseminate new pediatric out-of-hospital protocols emergency care to become standard of care in a timely matter must be developed.

Background. Selective serotonin reuptake inhibitor (SSRI) therapy complicates up to 10% of pregnancies. During therapy, SSRIs exert pleiotropic antidepressant, anorexigenic, and neurotrophic effects. Intrauterine SSRI exposure has been modeled by neonatal administration to developmentally immature rodents, and it has paradoxically elicited features of adult depression. We hypothesized neonatal SSRI exposure likewise programs a rebound hypermetabolic state in adult mice.Methods. C57BL/6 pups were randomized to saline or sertraline (5 mg/kg/d) from P1–P14. Because estrogen increases tryptophan hydroxylase 2 (TPH2) expression, a subset of female mice underwent sham surgery or bilateral ovariectomy (OVX). Metabolic rate was determined by indirect calorimetry.Results. In both male and female mice, neonatal SSRI exposure increased adult caloric intake and metabolic rate. SSRI-exposed female mice had significantly decreased adult weight with a relative increase in brain weight and melatonin excretion, independent of ovarian status. Cerebral cortex TPH2 expression was increased in SSRI-exposed male mice but decreased in OVX SSRI-exposed female mice.Conclusions. SSRI exposure during a critical neurodevelopmental window increases adult caloric intake and metabolic rate. Ovarian status modulated central TPH2 expression, but not adult energy balance, suggesting programmed neural connectivity or enhanced melatonin production may play a more important role in the post-SSRI hypermetabolic syndrome.

Defibrillation is the only effective treatment for ventricular fibrillation (VF). Optimal methods for defibrillation in children are derived and extrapolated from adult data. VF occurs as the initial rhythm in 8-20% of pediatric cardiac arrests. This has fostered a new interest in determining the optimal technique for pediatric defibrillation. This review will provide a brief background of the history of defibrillation and a review of the current literature on pediatric defibrillation. The literature search was performed through PubMed, using the MeSH headings of cardiopulmonary resuscitation, defibrillation and electric countershock. The authors' personal bibliographic files were also searched. Only published articles were chosen. The recommended energy dose has been 2 J/kg for 30 years, but recent reports may indicate that higher dosages may be more effective and safe. In 2005, the European Resuscitation Council recommended 4 J/kg as the initial dose, without escalation for subsequent shocks. Automated external defibrillators are increasingly used for pediatric cardiac arrest, and available reports indicate high success rates. Additional research on pediatric defibrillation is critical in order to be able to provide an equivalent standard of care for children in cardiac arrest and improve outcomes.

Background: Weight in infancy correlates with risk of type 2 diabetes, hypertension, and obesity in adulthood. Clinical observations have been confounded by obesity-prone genotypes and obesity-linked lifestyles. Objectives: To define the effects of isolated neonatal macrosomia in isogenic animals, we compared macrosomic and control C57Bl6 mice co-fostered by healthy dams receiving standard laboratory feed. Methods: Naturally occurring neonatal macrosomia was identified by a gender-specific weanling weight above the 90th percentile for the colony. Macrosomic and control mice were phenotyped in adulthood by exercise wheel, tail cuff and intraperitoneal insulin or glucose challenge. Results: Compared to control males, adult males with a history of neonatal macrosomia had significantly increased body weight, reduced voluntary activity, insulin resistance, fasting hyperinsulinemia, and impaired glucose tolerance. In contrast, adult females with neonatal macrosomia had no significant alteration in body weight or endocrine phenotypes, but did have higher blood pressures and lower heart rates than control females. After these baseline studies, all mice were switched to a hypercaloric, high fat diet (5 kcal/g, 45% of energy as fat). Twenty weeks later, male mice had impaired glucose tolerance and insulin resistance, independent of their weanling weight classification. While on high fat feeds, macrosomic males maintained a significantly higher body weight than control males. Conclusions: We conclude that (1) in our murine model, neonatal macrosomia is an independent risk factor of adult metabolic syndrome, and (2) neonatal macrosomia accentuates the sexually dimorphic predisposition of C57Bl6 male mice towards glucose intolerance and C57Bl6 female mice towards hypertension.