Changes in e-cigarette and cigarette use during pregnancy and their association with small-for-gestational-age birth.

BACKGROUND: Despite increased e-cigarette use, limited research has focused on changes in e-cigarette and combustible cigarette use around pregnancy and the subsequent effects on infant health. OBJECTIVE: This study aimed to characterize changes in e-cigarette and cigarette use from before to during pregnancy and examine their associations with small-for-gestational-age birth. STUDY DESIGN: This was a secondary data analysis of 2016-2018 data of the US Pregnancy Risk Assessment Monitoring System. We analyzed women aged ≥18 years who had a recent live birth (unweighted: n=105,438; weighted: n=5,446,900). Women were grouped on the basis of their self-reported e-cigarette and/or cigarette use 3 months before pregnancy (exclusive e-cigarette users, exclusive cigarette smokers, dual users, and nonusers) and change in e-cigarette and cigarette use during pregnancy (continuing use, quitting, switching, and initiating use). Small-for-gestational-age was defined as a birthweight below the 10th percentile for infants of the same sex and gestational age. We described the distributions of women's sociodemographic and pregnancy characteristics in both weighted and unweighted samples. We used multivariable log-binomial regression models to estimate the relative risks for the associations between changes in e-cigarette and cigarette use during pregnancy and risk of small-for-gestational-age, adjusting for significant covariates. RESULTS: The rates of cessation during pregnancy were the highest among exclusive e-cigarette users (weighted percentage, 80.7% [49,378/61,173]), followed by exclusive cigarette users (54.4% [421,094/773,586]) and dual users (46.4% [69,136/149,152]). Among exclusive e-cigarette users, continued users of e-cigarettes during pregnancy had a higher risk of small-for-gestational-age than nonusers (16.5% [1849/11,206]) vs 8.8% [384,338/4,371,664]; confounder-adjusted relative risk, 1.52 [95% confidence interval, 1.45-1.60]), whereas quitters of e-cigarettes had a similar risk of small-for-gestational-age with nonusers (7.7% [3730/48,587] vs 8.8% [384,338/4,371,664]; relative risk, 0.84 [95% confidence interval, 0.82-0.87]). Among exclusive cigarette users, those who completely switched to e-cigarettes during pregnancy also had a similar risk of small-for-gestational-age with nonusers (7.6% [259/3412] vs 8.8% [384,338/4,371,664]; relative risk, 0.83 [95% confidence interval, 0.73-0.93]). Among dual users before pregnancy, the risk of small-for-gestational-age decreased from 23.2% (7240/31,208) (relative risk, 2.53 [95% confidence interval, 2.47-2.58]) if continuing use to 16.9% (6617/39,142) (relative risk, 1.88 [95% confidence interval, 1.83-1.92]) if only quitting e-cigarettes or 15.1% (1254/8289) (relative risk, 1.61 [95% confidence interval, 1.52-1.70]) if only quitting cigarettes and further to 11.2% (7589/67,880) (relative risk, 1.23 [95% confidence interval, 1.20-1.25]) if both quitting e-cigarettes and cigarettes during pregnancy, compared with nonusers. CONCLUSION: Among exclusive e-cigarette users, quitting e-cigarettes during pregnancy normalized the risk of small-for-gestational-age. Among exclusive cigarette users, quitting smoking or completely switching to e-cigarettes normalized small for gestational age risk. Among dual users, smoking cessation has a greater effect than quitting e-cigarettes only, although discontinuing the use of both may lead to the greatest reduction in the risk of small-for-gestational-age.

Increased prevalence of severe neonatal hyperbilirubinaemia during social distancing.

AIM: Social distancing guidelines implemented with the COVID-19 pandemic impacted health-care utilisation and disrupted critical social supports. Resurgence of highly transmissible strains has resulted in revisiting restrictions with potential impacts on newborn health. With concerns for inadequate post-partum support, we sought to determine if social distancing correlated with increased rates of readmission for hyperbilirubinaemia. METHODS: Retrospective chart review identified all readmissions for hyperbilirubinaemia between 1/18 and 4/20 in Western New York. Infant/maternal demographics and data on hospital course were collected on control (1/1/18-31/1/20) and social distancing (1/2/20-30/4/20) cohorts. Nineteen outpatient clinics were surveyed regarding lactation support. RESULTS: Monthly readmissions for hyperbilirubinaemia nearly tripled during social distancing (0.90 ± 0.91 vs. 2.63 ± 2.29 per 1000 births during early COVID, P = 0.015). Comparable severity of disease at readmission was observed with no difference in the need for therapies (phototherapy, intravenous immunoglobulin or exchange transfusion) or length of hospital stay. Mothers were younger (25.8 ± 3.3 vs. 31.3 ± 4.7 years; P = 0.005) with higher rates of primiparity and exclusive breastfeeding than national norms, however not significantly higher than controls in our small cohort (62.5 vs. 37.0% for primiparity; 87.5 vs. 81.5% for breastfeeding). Of 19 clinics surveyed, only six confirmed a telemedicine option for lactation support. CONCLUSIONS: Rates of readmission for hyperbilirubinaemia increased during social distancing. Younger maternal age with high rates of primiparity and exclusive breastfeeding raise concern for inadequate social and/or lactation support. Proactive identification of mothers at risk and expansion of remote lactation services may be indicated with recurrent waves of the pandemic.

Effects of Partially Hydrolyzed Formula on Severity and Outcomes of Neonatal Abstinence Syndrome.

OBJECTIVE: This study compares the effect of partially hydrolyzed formula (PHF) and standard formula (SF) on the severity and short-term outcomes of neonatal abstinence syndrome (NAS). STUDY DESIGN: We performed a retrospective chart review of 124 opioid-dependent mothers and their term or near-term infants. Infants were categorized according to the predominant type of formula consumed during the hospital stay. Finnegan's scale was used to assess symptoms of withdrawal. RESULTS: A total of 110 infants met our inclusion criteria. Thirty-four (31%) infants were fed predominantly PHF, 60 (54%) infants were fed SF, and 16 (15%) infants were fed maternal breast milk. There was no difference between the infants in the PHF and SF groups with respect to requirement of morphine (MSO4) therapy, maximum dose of MSO4 used, duration of MSO4 treatment or length of hospital stay after performing multivariate analyses to control for type of drug used by the mother, maternal smoking, regular prenatal care, inborn status, and maximum Finnegan score prior to MSO4 treatment. CONCLUSION: Use of PHF failed to impact short-term outcomes in infants treated for NAS including maximum MSO4 dose, duration of MSO4 treatment, and length of hospital stay. A prospective randomized controlled trial may be indicated to confirm this finding.

Direct hyperbilirubinemia in newborns with gastroschisis.

BACKGROUND: Patients with gastroschisis and prolonged total (or partial) parenteral nutrition (PN) commonly develop direct hyperbilirubinemia (DH). OBJECTIVE: To quantify the prevalence and severity of DH in newborns with gastroschisis and characterize the diagnostic work-up for DH in this patient population. DESIGN/METHODS: Retrospective chart review of patients born with gastroschisis between 2005 and 2015 for the first 6 months of life. RESULTS: 29 patients were identified with gastroschisis. Mean gestational age and birthweight were 36.4 (± 1.8) weeks and 2.5 (± 0.6) kg. 41% were treated with primary reduction versus staged closure. Peak total and direct bilirubin (DB) levels were 10.17 ± 6.21 mg/dL and 5.58 ± 3.94 mg/dL, respectively. 23 patients (79.3%) were diagnosed with DH and 78.2% underwent additional work-up for hyperbilirubinemia consisting of imaging and laboratory studies, none of which revealed a cause for DH other than the presumed PN-associated cholestasis. In all patients, DB began to decline within 1-10 days of initiation of enteral feeds. CONCLUSION(S): DH is common in patients with gastroschisis and is unlikely to be associated with pathology aside from PN. Additional work-up may lead to unnecessary resource utilization. LEVELS OF EVIDENCE: Case series with no comparison group, Level IV.

Neonatal resuscitation in global health settings: an examination of the past to prepare for the future.

As rates of childhood mortality decline, neonatal deaths account for nearly half of under-5 deaths worldwide. Intrapartum-related events (birth asphyxia) contribute to approximately one-quarter of neonatal deaths, many of which can be prevented by simple resuscitation and newborn care interventions. This paper reviews various lines of research that have influenced the global neonatal resuscitation landscape. A brief situational analysis of asphyxia-related newborn mortality in low-resource settings is linked to renewed efforts to reduce neonatal mortality in the Every Newborn Action Plan. Possible solutions to gaps in care are identified. Building on international scientific evidence, tests of educational efficacy, and community-based trials established the feasibility and effectiveness of training in resource-limited settings and identified successful implementation strategies. Implementation of neonatal resuscitation programs has been shown to decrease intrapartum stillbirth rates and early neonatal mortality. Challenges remain with respect to provider competencies, coverage, and quality of interventions. The combination of resuscitation science, strategies to increase educational effectiveness, and implemention of interventions with high coverage and quality has resulted in reduced rates of asphyxia-related neonatal mortality. Further efforts to improve coverage and implementation of neonatal resuscitation will be necessary to meet the 2035 goal of eliminating preventable newborn deaths.

Postnatal growth restriction augments oxygen-induced pulmonary hypertension in a neonatal rat model of bronchopulmonary dysplasia.

BACKGROUND: Prematurity and fetal growth restriction are risk factors for pulmonary hypertension (PH) in infants with bronchopulmonary dysplasia (BPD). Neonatal rats develop PH and vascular remodeling when exposed to hyperoxia. We hypothesize that postnatal growth restriction (PNGR) due to under-nutrition increases the severity of PH induced by hyperoxia in neonatal rats. METHODS: Pups were randomized at birth to litters maintained in room air or 75% oxygen (hyperoxia), together with litters of normal milk intake (10 pups) or PNGR (17 pups). After 14 d, right ventricular hypertrophy (RVH) was assessed by Fulton's index (right ventricular weight/left ventricular plus septal weight) and PH by echocardiography. Lungs were analyzed by immunohistochemistry, morphometrics, western blotting, and metabolomics. RESULTS: Hyperoxia and PNGR each significantly increased pulmonary arterial pressure, RVH and pulmonary arterial medial wall thickness, and significantly decreased pulmonary vessel number. These changes were significantly augmented in pups exposed to both insults. Hyperoxia and PNGR both significantly decreased expression of proteins involved in lung development and vasodilation. CONCLUSION: PNGR induces right ventricular and pulmonary vascular remodeling and augments the effects of oxygen in neonatal rats. This may be a powerful tool to investigate the mechanisms that induce PH in low-birth-weight preterm infants with BPD.

Mouse lung development and NOX1 induction during hyperoxia are developmentally regulated and mitochondrial ROS dependent.

Animal models demonstrate that exposure to supraphysiological oxygen during the neonatal period compromises both lung and pulmonary vascular development, resulting in a phenotype comparable to bronchopulmonary dysplasia (BPD). Our prior work in murine models identified postnatal maturation of antioxidant enzyme capacities as well as developmental regulation of mitochondrial oxidative stress in hyperoxia. We hypothesize that consequences of hyperoxia may also be developmentally regulated and mitochondrial reactive oxygen species (ROS) dependent. To determine whether age of exposure impacts the effect of hyperoxia, neonatal mice were placed in 75% oxygen for 72 h at either postnatal day 0 (early postnatal) or day 4 (late postnatal). Mice exposed to early, but not late, postnatal hyperoxia demonstrated decreased alveolarization and septation, increased muscularization of resistance pulmonary arteries, and right ventricular hypertrophy (RVH) compared with normoxic controls. Treatment with a mitochondria-specific antioxidant, (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (mitoTEMPO), during early postnatal hyperoxia protected against compromised alveolarization and RVH. In addition, early, but not late, postnatal hyperoxia resulted in induction of NOX1 expression that was mitochondrial ROS dependent. Because early, but not late, exposure resulted in compromised lung and cardiovascular development, we conclude that the consequences of hyperoxia are developmentally regulated and decrease with age. Attenuated disease in mitoTEMPO-treated mice implicates mitochondrial ROS in the pathophysiology of neonatal hyperoxic lung injury, with potential for amplification of ROS signaling through NOX1 induction. Furthermore, it suggests a potential role for targeted antioxidant therapy in the prevention or treatment of BPD.

Right ventricular cyclic nucleotide signaling is decreased in hyperoxia-induced pulmonary hypertension in neonatal mice.

Pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) affect 25-35% of premature infants with significant bronchopulmonary dysplasia (BPD), increasing morbidity and mortality. We sought to determine the role of phosphodiesterase 5 (PDE5) in the right ventricle (RV) and left ventricle (LV) in a hyperoxia-induced neonatal mouse model of PH and RVH. After birth, C57BL/6 mice were placed in room air (RA) or 75% O2 (CH) for 14 days to induce PH and RVH. Mice were euthanized at 14 days or recovered in RA for 14 days or 42 days prior to euthanasia at 28 or 56 days of age. Some pups received sildenafil or vehicle (3 mg·kg(-1)·dose(-1) sc) every other day from P0. RVH was assessed by Fulton's index [RV wt/(LV + septum) wt]. PDE5 protein expression was analyzed via Western blot, PDE5 activity was measured by commercially available assay, and cGMP was measured by enzyme-linked immunoassay. Hyperoxia induced RVH in mice after 14 days, and RVH did not resolve until 56 days of age. Hyperoxia increased PDE5 expression and activity in RV, but not LV + S, after 14 days. PDE5 expression normalized by 28 days of age, but PDE5 activity did not normalize until 56 days of age. Sildenafil given during hyperoxia prevented RVH, decreased RV PDE5 activity, and increased RV cGMP levels. Mice with cardiac-specific overexpression of PDE5 had increased RVH in RA. These findings suggest normal RV PDE5 function is disrupted by hyperoxia, and elevated PDE5 contributes to RVH and remodeling. Therefore, in addition to impacting the pulmonary vasculature, sildenafil also targets PDE5 in the neonatal mouse RV and decreases RVH.

Regulation of hypoxia-induced pulmonary hypertension by vascular smooth muscle hypoxia-inducible factor-1α.

RATIONALE: Chronic hypoxia induces pulmonary vascular remodeling, pulmonary hypertension, and right ventricular hypertrophy. At present, little is known about mechanisms driving these responses. Hypoxia-inducible factor-1α (HIF-1α) is a master regulator of transcription in hypoxic cells, up-regulating genes involved in energy metabolism, proliferation, and extracellular matrix reorganization. Systemic loss of a single HIF-1α allele has been shown to attenuate hypoxic pulmonary hypertension, but the cells contributing to this response have not been identified. OBJECTIVES: We sought to determine the contribution of HIF-1α in smooth muscle on pulmonary vascular and right heart responses to chronic hypoxia. METHODS: We used mice with homozygous conditional deletion of HIF-1α combined with tamoxifen-inducible smooth muscle-specific Cre recombinase expression. Mice received either tamoxifen or vehicle followed by exposure to either normoxia or chronic hypoxia (10% O2) for 30 days before measurement of cardiopulmonary responses. MEASUREMENTS AND MAIN RESULTS: Tamoxifen-induced smooth muscle-specific deletion of HIF-1α attenuated pulmonary vascular remodeling and pulmonary hypertension in chronic hypoxia. However, right ventricular hypertrophy was unchanged despite attenuated pulmonary pressures. CONCLUSIONS: These results indicate that HIF-1α in smooth muscle contributes to pulmonary vascular remodeling and pulmonary hypertension in chronic hypoxia. However, loss of HIF-1 function in smooth muscle does not affect hypoxic cardiac remodeling, suggesting that the cardiac hypertrophy response is not directly coupled to the increase in pulmonary artery pressure.

Disrupted pulmonary artery cyclic guanosine monophosphate signaling in mice with hyperoxia-induced pulmonary hypertension.

Pulmonary hypertension (PH) occurs in 25 to 35% of premature infants with significant bronchopulmonary dysplasia (BPD). Neonatal mice exposed to 14 days of hyperoxia develop BPD-like lung injury and PH. To determinne the impact of hyperoxia on pulmonary artery (PA) cyclic guanosine monophosphate (cGMP) signaling in a murine model of lung injury and PH, neonatal C57BL/6 mice were placed in room air, 75% O2 for 14 days (chronic hyperoxia [CH]) or 75% O2 for 24 hours, followed by 13 days of room air (acute hyperoxia with recovery [AHR]) with or without sildenafil. At 14 days, mean alveolar area, PA medial wall thickness (MWT), right ventricular hypertrophy (RVH), and vessel density were assessed. PA protein was analyzed for cGMP, soluble guanylate cyclase, and PDE5 activity. CH and AHR mice had RVH, but only CH mice had increased alveolar area and MWT and decreased vessel density. In CH and AHR PAs, soluble guanylate cyclase activity was decreased, and PDE5 activity was increased. In CH mice, sildenafil attenuated MWT and RVH but did not improve mean alveolar area or vessel density. In CH and AHR PAs, sildenafil decreased PDE5 activity and increased cGMP. Our results indicate that prolonged hyperoxia leads to lung injury, PH, RVH, and disrupted PA cGMP signaling. Furthermore, 24 hours of hyperoxia causes RVH and disrupted PA cGMP signaling that persists for 13 days. Sildenafil reduced RVH and restored vascular cGMP signaling but did not attenuate lung injury. Thus, hyperoxia can rapidly disrupt PA cGMP signaling in vivo with sustained effects, and concurrent sildenafil therapy can be protective.

Sirtuin 3 deficiency does not augment hypoxia-induced pulmonary hypertension.

Alveolar hypoxia elicits increases in mitochondrial reactive oxygen species (ROS) signaling in pulmonary arterial (PA) smooth muscle cells (PASMCs), triggering hypoxic pulmonary vasoconstriction. Mice deficient in sirtuin (Sirt) 3, a nicotinamide adenine dinucleotide-dependent mitochondrial deacetylase, demonstrate enhanced left ventricular hypertrophy after aortic banding, whereas cells from these mice reportedly exhibit augmented hypoxia-induced ROS signaling and hypoxia-inducible factor (HIF)-1 activation. We therefore tested whether deletion of Sirt3 would augment hypoxia-induced ROS signaling in PASMCs, thereby exacerbating the development of pulmonary hypertension (PH) and right ventricular hypertrophy. In PASMCs from Sirt3 knockout (Sirt3(-/-)) mice in the C57BL/6 background, we observed that acute hypoxia (1.5% O2; 30 min)-induced changes in ROS signaling, detected using targeted redox-sensitive, ratiometric fluorescent protein sensors (roGFP) in the mitochondrial matrix, intermembrane space, and the cytosol, were indistinguishable from Sirt3(+/+) cells. Acute hypoxia-induced cytosolic calcium signaling in Sirt3(-/-) PASMCs was also indistinguishable from Sirt3(+/+) cells. During sustained hypoxia (1.5% O2; 16 h), Sirt3 deletion augmented mitochondrial matrix oxidant stress, but this did not correspond to an augmentation of intermembrane space or cytosolic oxidant signaling. Sirt3 deletion did not affect HIF-1α stabilization under normoxia, nor did it augment HIF-1α stabilization during sustained hypoxia (1.5% O2; 4 h). Sirt3(-/-) mice housed in chronic hypoxia (10% O2; 30 d) developed PH, PA wall remodeling, and right ventricular hypertrophy that was indistinguishable from Sirt3(+/+) littermates. Thus, Sirt3 deletion does not augment hypoxia-induced ROS signaling or its consequences in the cytosol of PASMCs, or the development of PH. These findings suggest that Sirt3 responses may be cell type specific, or restricted to certain genetic backgrounds.

Observational study comparing heart rate in crying and non-crying but breathing infants at birth.

BACKGROUND: Stimulating infants to elicit a cry at birth is common but could result in unnecessary handling. We evaluated heart rate in infants who were crying versus non-crying but breathing immediately after birth. METHODS: This was single-centre observational study of singleton, vaginally born infants at ≥33 weeks of gestation. Infants who were crying or non-crying but breathing within 30 s after birth were included. Background demographic data and delivery room events were recorded using tablet-based applications and synchronised with continuous heart rate data recorded by a dry-electrode electrocardiographic monitor. Heart rate centile curves for the first 3 min of life were generated with piecewise regression analysis. Odds of bradycardia and tachycardia were compared using multiple logistic regression. RESULTS: 1155 crying and 54 non-crying but breathing neonates were included in the final analyses. There were no significant differences in the demographic and obstetric factors between the cohorts. Non-crying but breathing infants had higher rates of early cord clamping <60 s after birth (75.9% vs 46.5%) and admission to the neonatal intensive care unit (13.0% vs 4.3%). There were no significant differences in median heart rates between the cohorts. Non-crying but breathing infants had higher odds of bradycardia (heart rate <100 beats/min, adjusted OR 2.64, 95% CI 1.34 to 5.17) and tachycardia (heart rate ≥200 beats/min, adjusted OR 2.86, 95% CI 1.50 to 5.47). CONCLUSION: Infants who are quietly breathing but do not cry after birth have an increased risk of both bradycardia and tachycardia, and admission to the neonatal intensive care unit. TRIAL REGISTRATION NUMBER: ISRCTN18148368.

Cigarette Smoking Abstinence Among Pregnant Individuals Using E-Cigarettes or Nicotine Replacement Therapy.

Importance: Smoking cigarettes during pregnancy can impair maternal and child health, and pregnant individuals have increasingly used electronic cigarettes (e-cigarettes) for various reasons, including quitting smoking. Objective: To assess smoking abstinence rates among pregnant individuals who used e-cigarettes compared with those who used nicotine replacement therapy (NRT). Design, Setting, and Participants: This cohort study is a secondary data analysis of phase 8 of the US Pregnancy Risk Assessment Monitoring System, conducted between 2016 and 2020. Eligible participants included pregnant individuals who smoked combustible cigarettes within the 3 months before pregnancy and either used e-cigarettes or NRT during pregnancy. Data analysis was conducted from March 2022 to April 2023. Exposures: Combustible cigarette use within 3 months before pregnancy and use of either e-cigarettes or NRT during pregnancy. Main Outcomes and Measures: The primary outcome was the individual's self-reported smoking abstinence status during the last 3 months of pregnancy. Weighted percentages were reported and weighted multivariable logistic regression models were used to examine the association of e-cigarette use vs NRT with smoking abstinence. A propensity score was used to control for confounding by sociodemographics, pregnancy characteristics, prepregnancy smoking intensity, depression, behavioral support, and hookah use. Results: The cohort included 1329 pregnant individuals (759 ≥25 years [60.2%]; 766 non-Hispanic White individuals [79.8%]) of whom 781 had an education level of high school or lower (61.4%), and 952 had an annual household income of $48 000 or less (81.5%). Of the 1329 individuals, 890 (unweighted percentage, 67.0%) were existing e-cigarette users, 67 (unweighted percentage, 5.0%) were new e-cigarette users, and 372 (unweighted percentage, 28.0%) were NRT users. Compared with individuals who used NRT during pregnancy, individuals who used e-cigarettes had a higher rate of smoking abstinence in late pregnancy (456 individuals [50.8%] vs 67 individuals [19.4%]; propensity score adjusted odds ratio [OR], 2.47; 95% CI, 1.17-5.20; P = .02). In the secondary analysis stratified by the timing of e-cigarette use initiation, existing users of e-cigarettes who initiated before pregnancy had a higher smoking abstinence rate than NRT users (446 users [53.1%] vs 67 users [19.4%]; adjusted OR, 2.61; 95% CI, 1.23-5.51; P = .01). However, new e-cigarette users who initiated use during pregnancy had a similar smoking abstinence rate in late pregnancy when compared with NRT users (10 users [20.6%] vs 67 users [19.4%]; adjusted OR, 1.13; 95% CI, 0.22-5.87; P = .88). Conclusions and Relevance: These findings suggest that individuals who used e-cigarettes during pregnancy had a higher smoking abstinence rate in late pregnancy than individuals who used NRT, especially for those who initiated e-cigarette use before pregnancy, indicating that replacement of cigarettes with e-cigarettes during pregnancy may be a viable strategy for harm reduction.

Impact of an Educational Clinical Video Combined with Standard Helping Babies Breathe Training on Acquisition and Retention of Knowledge and Skills among Ethiopian Midwives.

Helping Babies Breathe (HBB) is an evidence-based neonatal resuscitation program designed for implementation in low-resource settings. While HBB reduces rates of early neonatal mortality and stillbirth, maintenance of knowledge and skills remains a challenge. The extent to which the inclusion of educational clinical videos impacts learners' knowledge and skills acquisition, and retention is largely unknown. We conducted a cluster-randomized controlled trial at two public teaching hospitals in Addis Ababa, Ethiopia. We randomized small training group clusters of 84 midwives to standard HBB vs. standard HBB training supplemented with exposure to an educational clinical video on newborn resuscitation. Midwives were followed over a 7-month time period and assessed on their knowledge and skills using standard HBB tools. When comparing the intervention to the control group, there was no difference in outcomes across all assessments, indicating that the addition of the video did not influence skill retention. Pass rates for both the control and intervention group on bag and mask skills remained low at 7 months despite frequent assessments. There is more to learn about the use of educational videos along with low-dose, high-frequency training and how it relates to retention of knowledge and skills in learners.

Inadequate Bioavailability of Intramuscular Epinephrine in a Neonatal Asphyxia Model.

Background: Over half a million newborn deaths are attributed to intrapartum related events annually, the majority of which occur in low resource settings. While progress has been made in reducing the burden of asphyxia, novel approaches may need to be considered to further decrease rates of newborn mortality. Administration of intravenous, intraosseous or endotracheal epinephrine is recommended by the Newborn Resuscitation Program (NRP) with sustained bradycardia at birth. However, delivery by these routes requires both advanced skills and specialized equipment. Intramuscular (IM) epinephrine may represent a simple, low cost and highly accessible alternative for consideration in the care of infants compromised at birth. At present, the bioavailability of IM epinephrine in asphyxia remains unclear. Methods: Four term fetal lambs were delivered by cesarean section and asphyxiated by umbilical cord occlusion with resuscitation after 5 min of asystole. IM epinephrine (0.1 mg/kg) was administered intradeltoid after 1 min of positive pressure ventilation with 30 s of chest compressions. Serial blood samples were obtained for determination of plasma epinephrine concentrations by ELISA. Results: Epinephrine concentrations failed to increase following administration via IM injection. Delayed absorption was observed after return of spontaneous circulation (ROSC) in half of the studies. Conclusions: Inadequate absorption of epinephrine occurs with IM administration during asphyxial cardiac arrest, implying this route would be ineffective in infants who are severely compromised at birth. Late absorption following ROSC raises concerns for risks of side effects. However, the bioavailability and efficacy of intramuscular epinephrine in less profound asphyxia may warrant further evaluation.

Sustained Inflation Reduces Pulmonary Blood Flow during Resuscitation with an Intact Cord.

The optimal timing of cord clamping in asphyxia is not known. Our aims were to determine the effect of ventilation (sustained inflation-SI vs. positive pressure ventilation-V) with early (ECC) or delayed cord clamping (DCC) in asphyxiated near-term lambs. We hypothesized that SI with DCC improves gas exchange and hemodynamics in near-term lambs with asphyxial bradycardia. A total of 28 lambs were asphyxiated to a mean blood pressure of 22 mmHg. Lambs were randomized based on the timing of cord clamping (ECC-immediate, DCC-60 s) and mode of initial ventilation into five groups: ECC + V, ECC + SI, DCC, DCC + V and DCC + SI. The magnitude of placental transfusion was assessed using biotinylated RBC. Though an asphyxial bradycardia model, 2-3 lambs in each group were arrested. There was no difference in primary outcomes, the time to reach baseline carotid blood flow (CBF), HR ≥ 100 bpm or MBP ≥ 40 mmHg. SI reduced pulmonary (PBF) and umbilical venous (UV) blood flow without affecting CBF or umbilical arterial blood flow. A significant reduction in PBF with SI persisted for a few minutes after birth. In our model of perinatal asphyxia, an initial SI breath increased airway pressure, and reduced PBF and UV return with an intact cord. Further clinical studies evaluating the timing of cord clamping and ventilation strategy in asphyxiated infants are warranted.

Beyond Newborn Resuscitation: Essential Care for Every Baby and Small Babies.

Helping Babies Breathe (HBB) addresses a major cause of newborn mortality by teaching basic steps of neonatal resuscitation and improving survival rates of infants affected by intrapartum-related events or asphyxia. Addressing the additional top causes of mortality (infection and prematurity) requires more comprehensive education, including content on thermal and nutritional support, breastfeeding, and alternative feeding strategies, as well as recognition and treatment of infection. Essential Care for Every Baby (ECEB) and Essential Care for Small Babies (ECSB) use educational principles developed with HBB as a model for teaching basic newborn care. These programs complement the content provided with HBB, further integrate counseling of families, and advance the agenda of providing quality care to all infants at birth. ECEB and ECSB have further demonstrated that engagement of individuals through active participation in their education empowers providers at all levels. With added experience teaching and implementing ECEB and ECSB, the next generation of newborn educational programs will likely incorporate bedside teaching and clinical exposure, multimedia platforms for demonstrating clinical content, and added efforts toward quality improvement. Through ECEB and ECSB, the attention brought to the newborn health agenda with HBB has only grown. Although current global health issues pose new challenges in implementing this agenda, these programs together provide a critical framework to both educate and advocate for optimal care of every newborn.

Gastrostomy tube placement in neonates undergoing tracheostomy: an opportunity to coordinate care?

OBJECTIVES: To describe variations in timing of gastrostomy tube (GT) placement for neonates undergoing tracheostomy. METHODS: Database study of neonates undergoing tracheostomy and GT placement using the Pediatric Health Information System (2012-2015). The primary outcome was timing of GT relative to tracheostomy. Logistic regression evaluated associations of patient- and hospital-level characteristics with GT timing. RESULTS: Of 1156 patients undergoing GT and tracheostomy placement, 42.4% had concurrent GT placement, 23.3% GT placement prior to tracheostomy, and 34.3% GT placement after tracheostomy. The proportion of patients undergoing concurrent placement ranged from 0 to 80% among 47 hospitals. Neonates born at 31-35 weeks, having cardiovascular comorbidities, history of diaphragmatic hernia repair, or gastroesophageal reflux disorder were more likely to receive GT placement prior to tracheostomy. CONCLUSION: Significant variability exists in the timing of neonatal tracheostomy and GT placement. Opportunities may exist to optimize coordination of care for neonates and reduce anesthetic exposure and hospital resource utilization.

Bronchopulmonary Dysplasia and Pulmonary Outcomes of Prematurity.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease most commonly seen in premature infants who require mechanical ventilation and oxygen therapy. Despite advances in neonatal care resulting in improved survival and decreased morbidity, limited progress has been made in reducing rates of BPD. Therapeutic options to protect the vulnerable developing lung are limited as are strategies to treat lung injury, resulting in ongoing concerns for long-term pulmonary morbidity after preterm birth. Lung protective strategies and optimal nutrition are recognized to improve pulmonary outcomes. However, characterization of late outcomes is challenged by rapid advances in neonatal care. As a result, current adult survivors reflect outdated medical practices. Although neonatal pulmonary disease tends to improve with growth, compromised respiratory health has been documented in young adult survivors of BPD. With improved survival of premature infants but limited progress in reducing rates of disease, BPD represents a growing burden on health care systems. [Pediatr Ann. 2019;48(4):e148-e153.].

In Vitro Consequences of Electronic-Cigarette Flavoring Exposure on the Immature Lung.

Background: The developing lung is uniquely susceptible and may be at increased risk of injury with exposure to e-cigarette constituents. We hypothesize that cellular toxicity and airway and vascular responses with exposure to flavored refill solutions may be altered in the immature lung. Methods: Fetal, neonatal, and adult ovine pulmonary artery smooth muscle cells (PASMC) were exposed to popular flavored nicotine-free e-cigarette refill solutions (menthol, strawberry, tobacco, and vanilla) and unflavored solvents: propylene glycol (PG) or vegetable glycerin (VG). Viability was assessed by lactate dehydrogenase assay. Brochodilation and vasoreactivity were determined on isolated ovine bronchial rings (BR) and pulmonary arteries (PA). Results: Neither PG or VG impacted viability of immature or adult cells; however, exposure to menthol and strawberry flavored solutions increased cell death. Neonatal cells were uniquely susceptible to menthol flavoring-induced toxicity, and all four flavorings demonstrated lower lethal doses (LD50) in immature PASMC. Exposure to flavored solutions induced bronchodilation of neonatal BR, while only menthol induced airway relaxation in adults. In contrast, PG/VG and flavored solutions did not impact vasoreactivity with the exception of menthol-induced relaxation of adult PAs. Conclusion: The immature lung is uniquely susceptible to cellular toxicity and altered airway responses with exposure to common flavored e-cigarette solutions.