Hypersensitivity of Zebrafish htr2b Mutant Embryos to Sertraline Indicates a Role for Serotonin Signaling in Cardiac Development.

ABSTRACT: Selective serotonin reuptake inhibitors (SSRIs) are antidepressants prescribed in 10% of pregnancies in the United States. Maternal use of SSRIs has been linked to an elevated rate of congenital heart defects, but the exact mechanism of pathogenesis is unknown. Previously, we have shown a decrease in cardiomyocyte proliferation, left ventricle size, and reduced cardiac expression of the serotonin receptor 5-HT 2B in offspring of mice exposed to the SSRI sertraline during pregnancy, relative to offspring of untreated mice. These results suggest that disruption of serotonin signaling leads to heart defects. Supporting this conclusion, we show here that zebrafish embryos exposed to sertraline develop with a smaller ventricle, reduced cardiomyocyte number, and lower cardiac expression of htr2b relative to untreated embryos. Moreover, zebrafish embryos homozygous for a nonsense mutation of htr2b ( htr2bsa16649 ) were sensitized to sertraline treatment relative to wild-type embryos. Specifically, the ventricle area was reduced in the homozygous htr2b mutants treated with sertraline compared with wild-type embryos treated with sertraline and homozygous htr2b mutants treated with vehicle control. Whereas long-term effects on left ventricle shortening fraction and stroke volume were observed by echocardiography in adult mice exposed to sertraline in utero, echocardiograms of adult zebrafish exposed to sertraline as embryos were normal. These results implicate the 5-HT 2B receptor functions in heart development and suggest zebrafish are a relevant animal model that can be used to investigate the connection between maternal SSRI use and elevated risk of congenital heart defects.

2019 American Heart Association Focused Update on Pediatric Advanced Life Support: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

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.

2019 American Heart Association Focused Update on Pediatric Basic Life Support: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

This 2019 focused update to the American Heart Association pediatric basic life support guidelines follows the 2019 systematic review of the effects of dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) on survival of infants and children with out-of-hospital cardiac arrest. This systematic review and the primary studies identified were analyzed by the Pediatric Task Force of the International Liaison Committee on Resuscitation. It aligns with the International Liaison Committee on Resuscitation's continuous evidence review process, with updates published when the International Liaison Committee on Resuscitation completes a literature review based on new published evidence. This update summarizes the available pediatric evidence supporting DA-CPR and provides treatment recommendations for DA-CPR for pediatric out-of-hospital cardiac arrest. Four new pediatric studies were reviewed. A systematic review of this data identified the association of a significant improvement in the rates of bystander CPR and in survival 1 month after cardiac arrest with DA-CPR. The writing group recommends that emergency medical dispatch centers offer DA-CPR for presumed pediatric cardiac arrest, especially when no bystander CPR is in progress. No recommendation could be made for or against DA-CPR instructions when bystander CPR is already in progress.

Pediatric Post-Cardiac Arrest Care: A Scientific Statement From the American Heart Association.

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.

2018 American Heart Association Focused Update on Pediatric Advanced Life Support: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

This 2018 American Heart Association focused update on pediatric advanced life support guidelines for cardiopulmonary resuscitation and emergency cardiovascular care follows the 2018 evidence review performed by the Pediatric Task Force of the International Liaison Committee on Resuscitation. It aligns with the International Liaison Committee on Resuscitation's continuous evidence review process, and updates are published when the group completes a literature review based on new published evidence. This update provides the evidence review and treatment recommendation for antiarrhythmic drug therapy in pediatric shock-refractory ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest. As was the case in the pediatric advanced life support section of the "2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care," only 1 pediatric study was identified. This study reported a statistically significant improvement in return of spontaneous circulation when lidocaine administration was compared with amiodarone for pediatric ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest. However, no difference in survival to hospital discharge was observed among patients who received amiodarone, lidocaine, or no antiarrhythmic medication. The writing group reaffirmed the 2015 pediatric advanced life support guideline recommendation that either lidocaine or amiodarone may be used to treat pediatric patients with shock-refractory ventricular fibrillation or pulseless ventricular tachycardia.

Origins of neonatal leptin deficiency in preterm infants.

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 < 0.05). Following birth, infant leptin levels decreased rapidly (74% decrease within 48 h). The extent of this decline correlated with GA (P < 0.05). Postnatal leptin began to increase by 33-36 weeks PMA, but remained below cord blood leptin levels (P < 0.01). At 36 weeks PMA, leptin levels were influenced by infant's weight and sex (P < 0.01), with females having higher leptin levels (1213 pg/ml vs. 984, P < 0.05). CONCLUSION: Cord blood leptin is influenced by maternal weight gain and BMI, suggesting an important role for trans-placental leptin delivery. Preterm delivery leads to sustained leptin deficiency through 36 weeks PMA, with the most premature male infants facing the longest and harshest deficiency.

Cardiac Outcomes After Perinatal Sertraline Exposure in Mice.

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.

Oral oestrogen reverses ovariectomy-induced morning surge hypertension in growth-restricted mice.

Perinatal growth restriction (GR) is associated with heightened sympathetic tone and hypertension. We have previously shown that naturally occurring neonatal GR programmes hypertension in male but not female mice. We therefore hypothesized that intact ovarian function or post-ovariectomy (OVX) oestrogen administration protects GR female mice from hypertension. Utilizing a non-interventional model that categorizes mice with weanling weights below the tenth percentile as GR, control and GR adult mice were studied at three distinct time points: baseline, post-OVX and post-OVX with oral oestrogen 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). Oestrogen 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 oestrogen (40 ± 25% increase in high frequency spectral power, P<0.05). In conclusion, GR alters cardiac morphology and cardiovascular regulation. The haemodynamic consequences of GR are attenuated in ovarian-sufficient or oestrogen-replete females. Further investigations are needed to define the role of hormone replacement therapy targeted towards young women with oestrogen deficiency and additional cardiovascular risk factors, including perinatal GR, cardiac hypertrophy and morning surge hypertension.

Association between survival and number of shocks for pulseless ventricular arrhythmias during pediatric in-hospital cardiac arrest in a national registry.

BACKGROUND: Annually 15,200 children suffer an in-hospital cardiac arrest (IHCA) in the US. Ventricular fibrillation or pulseless ventricular tachycardia (VF/pVT) is the initial rhythm in 10-15% of these arrests. We sought to evaluate the association of number of shocks and early dose escalation with survival for initial VF/pVT in pediatric IHCA. METHODS: Using 2000-2020 data from the American Heart Association's (AHA) Get with the Guidelines®-Resuscitation (GWTG-R) registry, we identified children >48 hours of life and ≤18 years who had an IHCA from initial VF/pVT and received defibrillation. RESULTS: There were 251 subjects (37.7%) who received a single shock and 415 subjects (62.3%) who received multiple shocks. Baseline and cardiac arrest characteristics did not differ between those who received a single shock versus multiple shocks except for duration of arrest and calendar year. The median first shock dose was consistent with AHA dosing recommendations and not different between those who received a single shock versus multiple shocks. Survival was improved for those who received a single shock compared to multiple shocks. However, no difference in survival was noted between those who received 2, 3, or ≥4 shocks. Of those receiving multiple shocks, no difference was observed with early dose escalation. CONCLUSIONS: In pediatric IHCA, most patients with initial VF/pVT require more than one shock. No distinctions in patient or pre-arrest characteristics were identified between those who received a single shock versus multiple shocks. Subjects who received a single shock were more likely to survive to hospital discharge even after adjusting for duration of resuscitation.

Sertraline exposure leads to small left heart syndrome in adult mice.

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 that SSRI exposure decreases left-ventricular (LV) 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 mo. RESULTS: Sertraline-exposed mice had smaller LV 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 <0.05), and increased urinary excretion of noradrenaline (control 174 ± 29.4 ng/ml, SSRI 276 ± 35.1 ng/ml, P < 0.05). These changes were associated with increased cerebral serotonin transporter (5-HTT) expression. CONCLUSION: Neonatal sertraline exposure causes long-term changes in cardiac morphology and physiology. We speculate that early-life SSRI exposure impairs cardiomyocyte growth and central serotonin signaling, leading to a small left heart syndrome in adult mice.

Impact of neonatal sertraline exposure on the post-myocardial infarction outcomes of adult male mice.

Neonatal exposure to a selective serotonin reuptake inhibitor (SSRI) leads to decreased left ventricular volumes and sympathetic activation in adult mice. We hypothesized this neonatal SSRI exposure-induced small left heart syndrome would increase post-myocardial infarction (MI) morbidity and mortality. C57BL/6 mice received saline or sertraline (5 mg/kg intraperitoneally) on postnatal days 1-14. At 5 months, male mice underwent coronary artery ligation and were monitored by radiotelemetry until death or 4 weeks after ligation. After ligation, SSRI-exposed mice had increased heart rates (SSRI, 516 ± 13 bpm; control, 470 ± 15 bpm; P < 0.05). SSRI-exposed mice had significant reductions in left ventricular systolic volumes both before and after coronary ligation (SSRI: baseline = 20 ± 3 µL, post-MI = 37 ± 10 µL; control: baseline = 30 ± 3 µL, post-MI = 65 ± 23 µL). Post-MI echocardiography showed significantly decreased ejection fraction in control mice (baseline = 60% ± 4%, post-MI = 41% ± 2%, P < 0.01) but not the SSRI-exposed mice (baseline = 65% ± 3%, post-MI = 53% ± 7%). Neonatal SSRI exposure did not significantly alter post-MI survival. We conclude that the preexisting SSRI-induced small left heart syndrome may provide protection from post-MI ventricular dilation.

Racial disparities in survival outcomes following pediatric in-hospital cardiac arrest.

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 h 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.

Effect of Amplitude Spectral Area on Termination of Fibrillation and Outcomes in Pediatric Cardiac Arrest.

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 <18 years with cardiac arrest and ventricular fibrillation were studied. AMSA was calculated for 2 seconds before shock and averaged for each subject (AMSA-avg). TOF was defined as termination of ventricular fibrillation 10 seconds after defibrillation to any non-ventricular fibrillation rhythm. ROSC was defined as >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.

Improved survival to hospital discharge in pediatric in-hospital cardiac arrest using 2 Joules/kilogram as first defibrillation dose for initial pulseless ventricular arrhythmia.

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), <1.7 J/kg and >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 <1.7 J/kg or >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.

2019 American Heart Association Focused Update on Pediatric Advanced Life Support: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

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.

2019 American Heart Association Focused Update on Pediatric Basic Life Support: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

This 2019 focused update to the American Heart Association pediatric basic life support guidelines follows the 2019 systematic review of the effects of dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) on survival of infants and children with out-of-hospital cardiac arrest. This systematic review and the primary studies identified were analyzed by the Pediatric Task Force of the International Liaison Committee on Resuscitation. It aligns with the International Liaison Committee on Resuscitation's continuous evidence review process, with updates published when the International Liaison Committee on Resuscitation completes a literature review based on new published evidence. This update summarizes the available pediatric evidence supporting DA-CPR and provides treatment recommendations for DA-CPR for pediatric out-of-hospital cardiac arrest. Four new pediatric studies were reviewed. A systematic review of this data identified the association of a significant improvement in the rates of bystander CPR and in survival 1 month after cardiac arrest with DA-CPR. The writing group recommends that emergency medical dispatch centers offer DA-CPR for presumed pediatric cardiac arrest, especially when no bystander CPR is in progress. No recommendation could be made for or against DA-CPR instructions when bystander CPR is already in progress.

A Prospective Study Evaluating the Effects of SSRI Exposure on Cardiac Size and Function in Newborns.

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.

Awareness of guidelines for use of automated external defibrillators in children within emergency medical services.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: Awareness of ILCOR guidelines for use of AEDs in children was low in both states in 2003 (29% in Iowa vs. 9% in Montana, p<0.001). After release of the 2005 guidelines, awareness improved significantly in both states but was still significantly greater in Iowa (83% vs. 60%, p<0.002). 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, p<0.001). CONCLUSIONS: 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.

Perinatal SSRI exposure permanently alters cerebral serotonin receptor mRNA in mice but does not impact adult behaviors.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Neonatal Growth Restriction Slows Cardiomyocyte Development and Reduces Adult Heart Size.

Prematurity is associated with reduced cardiac dimensions and an increased risk of cardiovascular disease. While prematurity is typically associated with ex utero neonatal growth restriction (GR), the independent effect of neonatal GR on cardiac development has not been established. We tested the hypothesis that isolated neonatal GR decreases cardiomyocyte growth and proliferation, leading to long-term alterations in cardiac morphology. C57BL/6 mice were fostered in litters ranging in size from 6 to 12 pups to accentuate normal variation in neonatal growth. Regardless of litter size, GR was defined by a weight below the 10th percentile. On postnatal day 8, Ki67 immunoreactivity, cardiomyocyte nucleation status and cardiomyocyte profile area were assessed. For adult mice, cardiomyocyte area was determined, along with cardiac dimensions by echocardiography and cardiac fibrosis by Masson's trichrome stain. On day 8, cardiomyocytes from GR versus control mice were significantly smaller and less likely to be binucleated with evidence of persistent cell cycle activity. As adults, GR mice continued to have smaller cardiomyocytes, as well as decreased left ventricular volumes without signs of fibrosis. Neonatal GR reduces cardiomyocyte size, delays the completion of binucleation, and leads to long-term alterations in cardiac morphology. Clinical studies are needed to ascertain whether these results translate to preterm infants that must continue to grow and mature in the midst of the increased circulatory demands that accompany their premature transition to an ex utero existence. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.