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OBJECTIVES: We sought to investigate how race, ethnicity, and socioeconomic status relate to tracheostomy insertion and post-tracheostomy mortality among infants with bronchopulmonary dysplasia. METHODS: The Vizient Clinical Database/Resource Manager was queried to identify infants born ≤32 weeks with bronchopulmonary dysplasia admitted to United States hospitals from January 2012-December 2020. Markers of socioeconomic status were linked to patient records from the Agency for Healthcare Research and Quality’s Social Determinants of Health Database. Regression models were used to assess trends in annual tracheostomy insertion rate and odds of tracheostomy insertion and post-tracheostomy mortality, adjusting for sociodemographic and clinical factors. RESULTS: There were 40,021 ex-premature infants included in the study, 1,614 (4.0%) of whom received a tracheostomy. Tracheostomy insertion increased from 2012-2017 (3.1% to 4.1%), but decreased from 2018-2020 (3.3% to 1.6%). Non-Hispanic Black infants demonstrated a 25% higher odds (aOR 1.25, 1.09-1.43) and Hispanic infants demonstrated a 20% lower odds (aOR 0.80, 0.65-0.96) of tracheostomy insertion compared to non-Hispanic White infants. Patients receiving public insurance had increased odds of tracheostomy insertion (aOR 1.15, 1.03-1.30), but there was no relation between other metrics of socioeconomic status and tracheostomy insertion within our cohort. In-hospital mortality among the tracheostomy-dependent was 14.1% and was not associated with sociodemographic factors. CONCLUSIONS: Disparities in tracheostomy insertion are not accounted for by differences in socioeconomic status or the presence of additional neonatal morbidities. Post-tracheostomy mortality does not demonstrate the same relationships. Further investigation is needed to explore the source and potential mitigators of the identified disparities.

Echocardiography is used to screen for the presence of pulmonary vein stenosis (PVS) in ex-preterm infants and children. However, there are no standard accepted criteria for screening or diagnosis of PVS by echocardiography. The aim of this study was to identify Doppler waveform features and Doppler systolic and diastolic velocity cutoff values associated with a diagnosis of PVS by cardiac catheterization.In this retrospective observational study, the echocardiograms of ex-preterm children3 years old who underwent cardiac catheterization at a single institution were reviewed. PVS on cardiac catheterization was defined by a mean pressure gradient of3 mm Hg in the pulmonary vein, with angiographic evidence of stenosis. Pulmonary vein Doppler waveforms, from echocardiograms obtained before catheterization, in children with and without PVS were compared. Nonstenosed veins in patients with PVS were excluded. The systolic and diastolic velocities of blood flow, phasic flow, and return of the Doppler waveform to baseline were analyzed.Forty-seven children were analyzed in the study, 18 children with 25 stenosed pulmonary veins and 29 children with 78 nonstenosed pulmonary veins. Stenosed pulmonary veins had higher peak systolic and diastolic velocities and higher peak and mean pressure gradients as measured by spectral Doppler. Peak systolic and diastolic velocities had areas under the receiver operating characteristic curve of 0.89 (95% CI, 0.79-0.99) and 0.93 (95% CI, 0.85-0.99) for PVS, respectively, and a threshold velocity of 0.7 m/sec had sensitivity of 80% and 84% and specificity of 94%. There was no correlation between Doppler-derived pulmonary vein mean gradient and measured pulmonary vein mean gradient during cardiac catheterization in stenosed pulmonary veins. Presence of phasic flow in the pulmonary vein and return of the Doppler waveform to baseline were associated with a nonstenosed pulmonary vein (sensitivity of 94% and 60% and specificity of 52% and 60%, respectively).Systolic and diastolic Doppler velocities and features of the waveform can discriminate stenosed pulmonary veins confirmed by cardiac catheterization in ex-preterm children. These results suggest the use of lower systolic and diastolic Doppler velocity cutoff values than currently published to screen for PVS in ex-preterm children. These cutoff values require validation in prospective studies.

OBJECTIVES Congenital diaphragmatic hernia (CDH) can cause a significant mass effect in the fetal thorax, displacing the heart into the opposite hemithorax. In left-sided CDH (L-CDH), this is associated with smaller left-sided cardiac structures and reduced left-ventricular cardiac output (LVCO). The effect of these physiologic changes on cerebral blood flow is not well understood. We sought to describe the middle cerebral artery (MCA) pulsatility index (PI), a measure of cerebrovascular impedance, in fetuses with L-CDH and those with right-sided CDH (R-CDH) compared with unaffected fetuses, and the relationship between MCA-PI and LVCO. We hypothesized that MCA-PI would be lower in fetuses with L-CDH and similar in those with R-CDH compared to controls, and that MCA-PI would be correlated with LVCO. METHODS We identified all fetuses with CDH evaluated at The University of California San Francisco, San Francisco, CA, USA from 2011 to 2018. Fetal echocardiograms and ultrasound scans were reviewed. Umbilical artery and MCA Doppler examinations were assessed to calculate pulsatility indices. Ventricular outputs were calculated using Doppler-derived stroke volume and fetal heart rate. Lung-to-head ratio (LHR), estimated fetal weight, biparietal diameter (BPD) and head circumference (HC) were obtained from fetal sonograms. Measurements in fetuses with CDH, according to the side of the defect, were compared with those in unaffected, gestational age-matched controls. A subset of CDH survivors had available data on neurodevelopmental outcome, as assessed using the Bayley Scales of Infant Development, 3rd edition. RESULTS A total of 64 fetuses with CDH (L-CDH, n = 53; R-CDH, n = 11) comprised the study groups, with 27 unaffected fetuses serving as controls. Mean gestational age at evaluation was similar between the three groups. Compared to controls, fetuses with L-CDH had significantly lower LVCO expressed as a percentage of combined cardiac output (CCO) (32%; 95% CI, 29-35% vs 38%; 95% CI, 33-42%; P = 0.04) and lower MCA-PI Z-score (-1.3; 95% CI, -1.7 to -1.0 vs 0.08; 95% CI, -0.5 to 0.6; P

Infant outcomes after maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not well described. In a prospective US registry of 263 infants, maternal SARS-CoV-2 status was not associated with birth weight, difficulty breathing, apnea, or upper or lower respiratory infection through 8 weeks of age.

Pulmonary artery acceleration time (PAAT) is considered useful for the non-invasive evaluation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). PAAT is dependent on PAP, PVR, pulmonary artery compliance, stroke volume, and heart rate. Its relative dependency on these determinants may differ between young and older children, raising uncertainty regarding its utility in young children. We aim to identify the primary determinants of the PAAT in children less than 36 months undergoing cardiac catheterization and its utility for the diagnosis of elevated PVR.We prospectively studied 42 children undergoing cardiac catheterization and simultaneous echocardiography. We determined the correlations of PAAT to the above-mentioned determinants and evaluated receiver operator characteristic (ROC) curves for diagnosis of PVR indexed to body surface area (PVRi) ≥3 Wu*mMedian age was 11.5 (IQR 5.2, 21.2) months. Moderate correlations were found between PAAT and mean PAP (R = -.66, p.001), PVRi (R = -.54, p = .004), pulmonary artery compliance (R = .65, p.001), transpulmonary gradient (R = -.67, p.001), stroke volume (R = .61, p = .002), and heart rate (R = -.63, p.001). In multivariate regression modeling, only transpulmonary gradient and heart rate were independent determinants of PAAT. PAAT ≤77 msec had acceptable utility for diagnosing PVRi ≥ 3 Wu*mTranspulmonary gradient and heart rate, but not pulmonary blood flow, are important determinants of PAAT in children36 months undergoing cardiac catheterization. PAAT has low sensitivity for diagnosing elevated PVRi, therefore, should not be solely relied upon in screening for elevated PVRi in young children.

BackgroundCumulative supplemental oxygen (CSO) and cumulative mean airway pressure (CMAP) are associated with bronchopulmonary dysplasia (BPD) in preterm infants, but their relationships to white matter injury (WMI) and neurodevelopment have not been evaluated.MethodsPreterm infants

Introduction: The Management of Myelomeningocele Study was a multicenter randomized trial to compare prenatal and standard postnatal repair of myelomeningocele (MMC). Neonatal outcome data for 158 of the 183 randomized women were published in The New England Journal of Medicine in 2011. Objective: Neonatal outcomes for the complete trial cohort (N = 183) are presented outlining the similarities with the original report and describing the impact of gestational age as a mediator. Methods: Gestational age, neonatal characteristics at delivery, and outcomes including common complications of prematurity were assessed. Results: Analysis of the complete cohort confirmed the initial findings that prenatal surgery was associated with an increased risk for earlier gestational age at birth. Delivery occurred before 30 weeks of gestation in 11% of neonates that had fetal MMC repair. Adverse pulmonary sequelae were rare in the prenatal surgery group despite an increased rate of oligohydramnios. There was no significant difference in other complications of prematurity including patent ductus arteriosus, sepsis, necrotizing enterocolitis, periventricular leukomalacia, and intraventricular hemorrhage. Conclusion: The benefits of prenatal surgery outweigh the complications of prematurity.

Rationale Pulmonary hypertension (PH) is relatively common in infants with severe bronchopulmonary dysplasia (BPD), however, hemodynamic data and factors associated with mortality in this patient group are sparsely described in the literature. Objectives To characterize the hemodynamics of former preterm infants with BPD and PH, as measured at cardiac catheterization, and to identify respiratory and cardiovascular predictors of mortality. Methods Single-center, retrospective cohort study, including, 30 patients born at less than 32-week gestational age (GA), who had an oxygen requirement at 36 weeks postmenstrual age and underwent cardiac catheterization between July 2014 and December 2017. Results Median GA at birth was 25 5/7 weeks (interquartile range [IQR], 24 4/7-26 6/7 weeks). Median birth weight was 620 g (IQR, 530-700 g). With a median of 23 months of follow up (IQR, 11-39 months), mortality as of July 2018 was 27% (8 of 30). The alveolar-arterial oxygen gradient as a measure of lung disease did not correlate with mortality (log-rank test P = 0.28). However, indexed pulmonary vascular resistance (PVR) of greater than 3 Woods units × m 2 showed a trend toward increased mortality (log-rank test P = 0.12). Pulmonary vein stenosis was the only predictor significantly associated with mortality (log-rank test P = 0.005). Conclusions In this cohort, the severity of lung disease as assessed by impaired oxygenation at cardiac catheterization did not correlate with mortality. The only factor significantly associated with mortality was the presence of pulmonary vein stenosis on cardiac catheterization, although PVR may also be an important factor.

Infants with congenital diaphragmatic hernia (CDH) who require non-invasive positive pressure ventilation or high flow nasal cannula are at risk for aspiration and delayed initiation of oral feeding. We developed a dysphagia provider-led protocol that involved early consultation with an occupational therapist or speech/language pathologist and modified barium swallow study (MBSS) to assess for readiness for oral feeding initiation/advancement on non-invasive positive pressure ventilation. The objective of this study was to retrospectively compare this intervention cohort to a historical control cohort to evaluate the protocol's impact on the time to initiate oral feeding. We describe the development and implementation of the protocol, the MBSS findings of the intervention cohort, and compared the control (n = 64) and intervention (n = 37) cohorts using Fischer's exact test and Mann-Whitney test. We found that both cohorts had similar prenatal and neonatal characteristics including age at extubation. Significantly more infants in the intervention cohort were on non-invasive positive pressure ventilation or high flow nasal cannula at the time of oral feeding initiation (84% vs. 28%, p 0.0001). None of the control cohort infants underwent MBSS while on respiratory support. Of the intervention cohort, 15 infants underwent a MBSS while on non-invasive positive pressure ventilation; 6 had no evidence of laryngeal penetration and/or aspiration during swallowing. Infants in the control cohort initiated oral feeds significantly sooner after extubation (6 versus 11 days, p = 0.001) and attained full oral feeds earlier (20 days versus 28 days, p = 0.02) than the intervention group. There was no difference in the rate of gastrostomy tube placement (38%). Appropriate monitoring by a dysphagia provider and evaluation with clinical and radiological means are crucial to determine the safety of initiating oral feeding in term infants with CDH. Continued surveillance is needed to determine the long-term impact on oral feeding progression in this population.

Objective: Describe NICU admission rate variation among hospitals in infants with birthweight ≥2500g and low illness acuity and describe factors that predict NICU admission. Study Design: Retrospective study from the Vizient Clinical Data Base/Resource Manager®. Support vector machine methodology was used to develop statistical models using 1) patient characteristics 2) only the indicator for the inborn hospital and 3) patient characteristics plus indicator for the inborn hospital. Results: NICU admission rates of 427,449 infants from 154 hospitals ranged from 0–28.6%. C-statistics for the patient characteristics model: 0.64 (Confidence Interval (CI) 0.62–0.65), hospital only model: 0.81 (CI, 0.81–0.82) and patient characteristic plus hospital variable model: 0.84 (CI, 0.83–0.84). Conclusion/Relevance: There is wide variation in NICU admission rates in infants with low acuity diagnoses. In all cohorts, birth hospital better predicted NICU admission than patient characteristics alone.

Background: Neonates with congenital heart disease are more likely to be small for gestational age. Few studies have investigated the effect of birth weight Z-score on outcomes after congenital heart surgery. Methods: Patients from the Society of Thoracic Surgeons Congenital Heart Surgery Database (2010 to 2016) undergoing cardiac surgery at a corrected gestational age ≤ 44 weeks were included, and classified as severely (birth weight Z-score -4 to -2), moderately (Z-score between -2 and -1) and mildly growth restricted (Z-score -1.0 to -0.5) and compared to a reference (Z-score 0 to 0.5). Multivariable logistic regression clustering on center was used to evaluate the association of birth weight Z-score with operative mortality, postoperative complications and length of stay, adjusting for other patient characteristics. Interaction between Z-score for birth weight and gestational age was assessed. Results: In 25,244 patients, operative mortality was 8.6% and major complications occurred in 19.4%. Compared to the reference group with no growth restriction, the adjusted odds (AOR) of mortality was increased in infants with severe (AOR 2.4, CI 2.0-3.0), moderate (AOR 1.7, CI 1.4-2.0) and mild growth restriction (AOR 1.4, CI 1.2-1.6). The AOR for major postoperative complications was increased for infants with severe (AOR 1.4, CI 1.2-1.7) and moderate growth restriction (AOR 1.2, CI 1.1-1.4), but not in mildly growth restricted infants (AOR 1.0, CI 0.9-1.2). Length of stay was prolonged for all growth restricted cohorts (adjusted Hazard Ratio38 weeks) and then preterm infants ( Conclusions: Even birth weight Z-scores that are slightly below average are independent risk factors for mortality and morbidity in neonates undergoing cardiac surgery. The strongest association between poor fetal growth and operative mortality exists in early-term neonates. These novel findings may account for some of the previously unexplained variation in cardiac surgical outcomes.

Background and ObjectivesTesting strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in school settings are needed to assess the efficacy of infection mitigation strategies and inform school reopening policies. We hypothesized that supervised serial self-collected non-nasopharyngeal testing in summer camp settings would be acceptable and feasible.MethodsWe performed a cohort study at two urban day camps for kindergarten-8th graders in June and July 2020. Eligible participants were campers, up to two adult household contacts, and camp staff. We assessed participation rates for providing, at two time points, supervised, self-collected anterior nares samples for reverse transcription polymerase chain reaction (RT-PCR) and saliva samples for antibody testing. We qualitatively assessed testing feasibility and adherence to stated camp infection mitigation strategies.Results76% (186/246) of eligible participants consented. The cohort completing both rounds of testing (n=163) comprised 67 campers, 76 household contacts, and 20 staff. Among those present, 100% of campers and staff completed test collection at both time points. Testing was feasible to implement, including staff participation supervising camper test collection. No virus was detected by RT-PCR; seven participants had antibodies. Observed adherence to stated camp mitigation policies for masking, physical distancing, and stable cohorting was generally high.ConclusionsSupervised, self-collected serial anterior nasal and saliva-based SARS-CoV-2 testing was acceptable, with successful repeated participation by children ages 5-14. This strategy for testing and the observed infection mitigation practices comprise potential core components for safe school reopening.

Bronchopulmonary dysplasia (BPD) following preterm birth and congenital diaphragmatic hernia (CDH) are both forms of developmental lung disease that may result in persistent pulmonary and pulmonary vascular morbidity in childhood. The pulmonary vascular disease (PVD) which accompanies BPD and CDH is due to developmental abnormalities and ongoing perinatal insults. This may be accompanied by evidence of elevated right heart pressures and pulmonary vascular resistance, leading to diagnosis of pulmonary hypertension (PH). The development of PH in these conditions is associated with increased morbidity and mortality in the vulnerable BPD and CDH populations. We present a review of PVD pathogenesis and evaluation in BPD and CDH and discuss management of related sequelae of PH co-morbidity for affected infants.

Cumulative supplemental oxygen (CSO) and cumulative mean airway pressure (CMAP) are associated with bronchopulmonary dysplasia (BPD) in preterm infants, but their relationships to white matter injury (WMI) and neurodevelopment have not been evaluated.Preterm infants32 weeks' gestation were prospectively imaged with 3 T MRI near term. CSO and CMAP were retrospectively summed over the first 14 and 28 days. Neurodevelopment was assessed at 30 months adjusted using the Bayley-III. ROC and linear regression were used to evaluate the relationship between CSO, CMAP, and BPD with WMI and neurodevelopmental performance, respectively.Of the 87 infants, 30 (34.5%) had moderate-severe BPD, which was associated with WMI (OR 5.5, 95% CI 1.1-34.9, p = 0.012). CSO and CMAP predicted WMI as well as BPD (AUC 0.68-0.77). CSO was independently associated with decreased language and cognitive performance (mean difference at 14 days: -11.0, 95% CI -19.8 to -2.2, p = 0.015 and -9.8, 95% CI -18.9 to -0.7, p = 0.035, respectively) at 30 months adjusted.BPD precursors predict WMI as well as BPD. Cumulative supplemental oxygen over the first 14 days of life is independently associated with lower language and cognitive performances. These data suggest that early respiratory status influences the risk of adverse neurodevelopment in preterm infants.Respiratory precursors to bronchopulmonary dysplasia (BPD), cumulative supplemental oxygen and mean airway pressure, over the first 14-28 days performed as well as BPD for the prediction of white matter injury on MRI in preterm infants. Cumulative supplemental oxygen was independently associated with lower language and cognitive performance on the Bayley-III at 30 months adjusted. These data suggest that early respiratory status may help explain why BPD is independently associated with adverse neurodevelopmental outcomes in the preterm population and highlights the importance of interventions targeting respiratory status as a potential avenue to improve neurodevelopmental outcomes.

To evaluate B-type natriuretic peptide (BNP) as a longitudinal biomarker of clinical outcome in infants with congenital diaphragmatic hernia (CDH).We conducted a retrospective study of 49 infants with CDH, classifying the cohort by respiratory status at 56 days, based on a proposed definition of bronchopulmonary dysplasia for infants ≥32 weeks' gestation: good outcome (alive with no respiratory support) and poor outcome (ongoing respiratory support or death). BNP levels were available at age 1-5 weeks. Longitudinal BNP trends were assessed using mixed-effects modeling. Receiver operating characteristic curves were generated to identify BNP cutoffs maximizing correct outcome classification at each time point. The time to reach BNP cutoff by outcome was assessed using Kaplan-Meier curves for weeks 3-5.Twenty-nine infants (59%) had a poor outcome. Infants with a poor outcome were more likely than those with a good outcome to have liver herniated into the thorax (90% vs 50%; P = .002) and to undergo nonprimary repair (93% vs 35%; P .001). Mixed-effects modeling demonstrated a differing decline in BNP over time by outcome group (P = .003 for interaction). BNP accurately predicted outcome at 3-5 weeks (area under the curve, 0.81-0.82). BNP cutoffs that maximized correct outcome classification decreased over time from 285 pg/mL at 3 weeks to 100 pg/mL at 4 weeks and 48 pg/mL at 5 weeks. Time to reach the cutoffs of 100 pg/mL and 48 pg/mL were longer in the poor outcome group (log-rank P = .006 and .0001, respectively).Elevated BNP accurately predicts poor outcome in infants with CDH at age 3-5 weeks, with declining cutoffs over 3-5 weeks of age.

BackgroundThe clinical utility of echocardiography for the diagnosis of pulmonary vascular disease (PVD) in former preterm infants with bronchopulmonary dysplasia (BPD) is not established. Elevated pulmonary vascular resistance (PVR) rather than pulmonary artery pressure (PAP) is the hallmark of PVD. We evaluated the utility of echocardiography in infants with BPD in diagnosing pulmonary hypertension and PVD (PVR >3 Wood units×m2) assessed by cardiac catheterization.MethodsA retrospective single center study of 29 infants born ≤29weeks of gestational age with BPD who underwent cardiac catheterization and echocardiography was performed. PVD was considered present by echocardiography if the tricuspid valve regurgitation jet peak velocity was >2.9m/sec, post-tricuspid valve shunt systolic flow velocity estimated a right ventricular systolic pressure >35mm Hg, or systolic septal flattening was present. The utility (accuracy, sensitivity, and positive predictive value [PPV]) of echocardiography in the diagnosis of PVD was tested. Subgroup analysis in patients without post-tricuspid valve shunts was performed. Echocardiographic estimations of right ventricular pressure, dimensions, function, and pulmonary flow measurements were evaluated for correlation with PVR.ResultsThe duration between echocardiography and cardiac catheterization was a median of 1day (interquartile range, 1-4days). Accuracy, sensitivity, and PPV of echocardiography in diagnosing PVD were 72%, 90.5%, and 76%, respectively. Accuracy, sensitivity, and PPV increased to 93%, 91.7%, and 100%, respectively, when infants with post-tricuspid valve shunts were excluded. Echocardiography had poor accuracy in estimating the degree of PAP elevation by cardiac catheterization. In infants without post-tricuspid valve shunts, there was moderate to good correlation between indexed PVR and right ventricular myocardial performance index (rho=0.89, P=.005), systolic to diastolic time index (0.84, P&nbsp

Bronchopulmonary dysplasia (BPD) remains a major cause of late morbidities and death after preterm birth. BPD is characterized by an arrest of vascular and alveolar growth and high risk for pulmonary hypertension; yet mechanisms contributing to its pathogenesis and early strategies to prevent BPD are poorly understood. Strong epidemiologic studies have shown that the “new BPD” reflects the long-lasting impact of antenatal factors on lung development, partly due to placental dysfunction, as reflected in recent data from animal models. Improved understanding of mechanisms through which antenatal stress alters placental function and contributes to BPD may lead to preventive therapies.

BACKGROUND:Many premature infants with respiratory failure are deficient in surfactant, but the relationship to occurrence of bronchopulmonary dysplasia (BPD) is uncertain. METHODS:Tracheal aspirates were collected from 209 treated and control infants enrolled at 7-14 days in the Trial of Late Surfactant. The content of phospholipid, surfactant protein B, and total protein were determined in large aggregate (active) surfactant. RESULTS:At 24 h, surfactant treatment transiently increased surfactant protein B content (70%, p

Objective We hypothesized that infants with fetal growth restrictions have increased mortality and morbidity after congenital heart disease surgery. Methods The study included patients in The Society of Thoracic Surgeons Congenital Heart Surgery Database (2010-2016) who underwent cardiac surgery at a corrected gestational age of ≤44 weeks. Patients were classified as severely (birth weight Z-score −4 to −2), moderately (Z-score −2 to −1), and mildly growth restricted (Z-score −1.0 to −0.5) and compared with a reference population (Z-score 0-0.5). Multivariable logistic regression clustering on center was used to evaluate the association of birth weight Z-score with operative mortality and postoperative complications and its interaction with gestational age was assessed. Results In 25,244 patients, operative mortality was 8.6% and major complications occurred in 19.4%. Compared with the reference group, the adjusted odds ratio (AOR) of mortality was increased in infants with severe (AOR, 2.4; 95% confidence interval [CI], 2.0-3.0), moderate (AOR, 1.7; 95% CI, 1.4-2.0), and mild growth restriction (AOR, 1.4; 95% CI, 1.2-1.6). The AOR for major postoperative complications was increased for severe (AOR, 1.4; 95% CI, 1.2-1.7) and moderate growth restriction (AOR, 1.2; 95% CI, 1.1-1.4). There was significant interaction between birth weight Z-score and gestational age (P = .007). Conclusions Even birth weight Z-scores slightly below average are independent risk factors for mortality and morbidity in infants who undergo cardiac surgery. The strongest association between poor fetal growth and operative mortality exists in early-term infants. These novel findings might account for some of the previously unexplained variation in cardiac surgical outcomes.

Objective The objective of this study was to examine laterality as a predictor of outcomes among fetuses with prenatally diagnosed congenital diaphragmatic hernia (CDH). Methods This is a retrospective cohort study of pregnancies with CDH evaluated at our center from 2008 to 2016 compared cases with right-sided CDH (RCDH) versus left-sided CDH (LCDH). The primary outcome was survival to discharge. Secondary outcomes included ultrasound predictors of poor prognosis (liver herniation, stomach herniation, lung area-to-head circumference ratio [LHR]), concurrent anomalies, hydrops, stillbirth, preterm birth, mode of delivery, small for gestational age, use of extracorporeal membrane oxygenation, and length of stay. Terminations and stillbirths were excluded from analyses of neonatal outcomes. Results In this study, 157 (83%) LCDH and 32 (17%) RCDH cases were identified. Survival to discharge was similar (64 vs. 66.4%, p = 0.49) with regard to laterality. RCDH had higher rates of liver herniation (90.6 vs. 72%, p = 0.03), hydrops fetalis (15.6 vs. 1.3%, p Conclusion Compared with LCDH, fetuses with RCDH had higher rates of adverse ultrasound predictors, but equivalent survival.

To compare mortality and early respiratory outcomes of very preterm infants conceived via assisted reproductive technology (ART) vs spontaneously.We identified inborn infants (July 2014-July 2019) with gestational age32 weeks (n = 439); 54 cases were ART conceived. Spontaneously conceived controls (n = 103) were matched by multiple gestation status and gestational age. Primary outcome was 1-year mortality. Secondary outcomes were receipt of respiratory support and supplemental oxygen at 7 and 28 days and 36 weeks of postmenstrual age. We evaluated the association between conception method and outcomes by logistic regression, with adjustment for sociodemographic status.Women who conceived via ART had increased rates of prepregnancy and gestational diabetes, and no differences in rates of hypertensive disorders. Infant 1-year mortality was not different by mode of conception (ART 11.8% vs spontaneous 7.1%, P = .49). Infants conceived by ART were less likely to receive respiratory support or supplemental oxygen at all time points, but this relationship only reached significance for receipt of oxygen at 28 days (ART 20.8% vs spontaneous 39.0%, P = .03); this remained true after adjustment for race/ethnicity and socioeconomic index.When controlling for gestational age and multiple gestation status, very preterm infants conceived following ART had similar outcomes as those conceived spontaneously.

Neonatal encephalopathy due to a hypoxic-ischemic event is commonly associated with cardiac dysfunction and acute pulmonary hypertension; both therapeutic hypothermia and rewarming modify loading conditions and blood flow. The pathophysiological contributors to disease are complex with a high degree of clinical overlap and traditional bedside measures used to assess circulatory adequacy have multiple confounders. Comprehensive, quantitative echocardiography may be used to delineate the relative contribution of lung parenchymal, pulmonary vascular, and cardiac disease to hypotension and/or hypoxemic respiratory failure. In this review, we provide a detailed overview of the contributors to hemodynamic instability following perinatal hypoxic-ischemic injury. Our proposed approach to therapy focuses on physiopathological considerations with interventions individualized to this potentially complex condition and considers the pharmacological idiosyncrasies, which may occur among neonates with NE presenting with multiorgan dysfunction while undergoing therapeutic hypothermia.

Background The use of medications to treat respiratory conditions of extreme prematurity is often based upon studies of adults or children over 2 years of age. Little is known about the spectrum of medications used or dosing ranges. To inform the design of future studies, we conducted a prospective analysis of respiratory medication exposure among 832 extremely low gestational age neonates. Methods The prematurity and respiratory outcomes program (PROP) enrolled neonates less than 29-week gestation from 6 centers incorporating 13 clinical sites. We collected recorded daily "respiratory" medications given along with dosing information through 40-week postmenstrual age or neonatal intensive care unit discharge if earlier. Results PROP participants were exposed to a wide range of respiratory medications, often at doses beyond published recommendations. Nearly 50% received caffeine and furosemide beyond published recommendations for cumulative dose. Those who developed bronchopulmonary dysplasia were more likely to receive treatment with respiratory medications. However, more than 30% of PROP subjects that did not develop bronchopulmonary dysplasia also were treated with diuretics, systemic steroids, and other respiratory medications. Conclusion Extremely preterm neonates in PROP were exposed to high doses of medications at levels known to generate significant adverse effects. With limited evidence for efficacy, there is an urgent need for controlled trials in this vulnerable patient population.

Background Infants with critical congenital heart disease ( CCHD ) are more likely to be small for gestational age ( SGA ) or born to mothers with maternal placental syndrome. The objective of this study was to investigate the relationship between maternal placental syndrome, SGA , and gestational age ( GA ) on 1‐year mortality in infants with CCHD . Methods and Results In a population‐based administrative database of all live‐born infants in California (2007–2012) we identified all infants with CCHD without chromosomal anomalies. Our primary predictor was an impaired fetal environment ( IFE ), defined as presence of maternal placental syndrome or SGA . We calculated hazard ratios to quantify the association between different components of IFE and 1‐year mortality and conducted a causal mediation analysis to assess GA at birth as a mediator. We identified 6863 infants with CCHD . IFE was present in 25.1%. Infants with IFE were more likely to die than infants without IFE (16.6% versus 11.1%; hazard ratios 1.55, 95% CI 1.34–1.78). Only SGA (hazard ratios 1.76, 95% CI 1.50–2.05) and placental abruption (hazard ratios 1.70, 95% CI 1.17–2.48) were significantly associated with mortality; preeclampsia and gestational hypertension had no significant association with mortality. The mediation analysis showed that 32.8% (95% CI 24.9–47.0%) of the relationship between IFE and mortality is mediated through GA . Conclusions IFE is a significant contributor to outcomes in the CCHD population. SGA and placental abruption are the main drivers of postnatal mortality while other maternal placental syndrome components had much less of an impact. Only one third of the effect between IFE and mortality is mediated through GA .

BACKGROUND There are limited data about the range of diseases, natural history, age-appropriate endpoints and optimal care for children with pulmonary hypertension (PH), including the need for developing high quality patient registries of children with diverse forms of PH to enhance care and research. OBJECTIVE To characterise the distribution and clinical features of diseases associated with pediatric PH, including natural history, evaluation, therapeutic interventions and outcomes, as defined by the WSPH Classification. METHODS 1475 patients were enrolled into a multisite registry across the Pediatric Pulmonary Hypertension Network (PPHNet), comprised of 8 interdisciplinary PH programs. RESULTS WSPH Groups 1 (PAH) and 3 (lung disease) were the most common primary classifications (45% and 49% of subjects, respectively). The most common Group 3 conditions were BPD and CDH. Group 1 disease was predominantly associated with congenital heart disease (60%) and idiopathic (23% of Group 1 cases). In comparison with Group 1, Group 3 subjects had better disease resolution (HR=3.1, p

Pulmonary hypertension in the perinatal period can present acutely (persistent pulmonary hypertension of the newborn) or chronically. Clinical and echocardiographic diagnosis of acute pulmonary hypertension is well accepted but there are no broadly validated criteria for echocardiographic diagnosis of pulmonary hypertension later in the clinical course, although there are significant populations of infants with lung disease at risk for this diagnosis. Contributing cardiovascular comorbidities are common in infants with pulmonary hypertension and lung disease. It is not clear who should be treated without confirmation of pulmonary vascular disease by cardiac catheterization, with concurrent evaluation of any contributing cardiovascular comorbidities.

Despite advances in therapy, outcomes for children with pulmonary hypertension remain poor. We sought to assess the validity of a pediatric-specific functional classification system for pulmonary hypertension (PH) in a heterogeneous population of children with PH diagnosed by echocardiogram or cardiac catheterization. A single-center, retrospective study of 65 infants and children with PH was performed. Pediatric Functional Class (FC) at diagnosis, at last visit, and change in FC over time were evaluated for their association with mortality and PH-associated morbidity in univariate, time-to-event, and multivariate regression analyses. Median age at PH diagnosis was 5.3 months (0 days–12.7 years). Twenty-five children (38 %) had idiopathic PH or PH secondary to congenital heart disease, one (2 %) had left heart disease, and 39 (60 %) had PH secondary to respiratory disease. Mortality was 25 % (16/63), primarily in the first year of follow-up. FC at diagnosis was not significantly associated with survival (p = 0.22), but higher FC (more impaired) at last visit (p

OBJECTIVES The disease burden and mortality of children with pulmonary hypertension are significantly higher than for the general PICU population. We aimed to develop a risk-adjustment tool predicting PICU mortality for pediatric pulmonary hypertension patients: the Pediatric Index of Pulmonary Hypertension Intensive Care Mortality score. DESIGN Retrospective analysis of prospectively collected multicenter pediatric critical care data. SETTING One-hundred forty-three centers submitting data to Virtual Pediatric Systems database between January 1, 2009, and December 31, 2015. PATIENTS Patients 21 years old or younger with a diagnosis of pulmonary hypertension. INTERVENTIONS Twenty-one demographic, diagnostic, and physiologic variables obtained within 12 hours of PICU admission were assessed for inclusion. Multivariable logistic regression with stepwise selection was performed to develop the final model. Receiver operating characteristic curves were used to compare the Pediatric Index of Pulmonary Hypertension Intensive Care Mortality score with Pediatric Risk of Mortality 3 and Pediatric Index of Mortality 2 scores. MEASUREMENTS AND MAIN RESULTS Fourteen-thousand two-hundred sixty-eight admissions with a diagnosis of pulmonary hypertension were included. Primary outcome was PICU mortality. Fourteen variables were selected for the final model: age, bradycardia, systolic hypotension, tachypnea, pH, FIO2, hemoglobin, blood urea nitrogen, creatinine, mechanical ventilation, nonelective admission, previous PICU admission, PICU admission due to nonsurgical cardiovascular disease, and cardiac arrest immediately prior to admission. The receiver operating characteristic curve for the Pediatric Index of Pulmonary Hypertension Intensive Care Mortality model (area under the curve = 0.77) performed significantly better than the receiver operating characteristic curves for Pediatric Risk of Mortality 3 (area under the curve = 0.71; p < 0.001) and Pediatric Index of Mortality 2 (area under the curve = 0.69; p < 0.001), respectively. CONCLUSIONS The Pediatric Index of Pulmonary Hypertension Intensive Care Mortality score is a parsimonious model that performs better than Pediatric Risk of Mortality 3 and Pediatric Index of Mortality 2 for mortality in a multicenter cohort of pediatric pulmonary hypertension patients admitted to PICUs. Application of the Pediatric Index of Pulmonary Hypertension Intensive Care Mortality model to pulmonary hypertension patients in the PICU might facilitate earlier identification of patients at high risk for mortality and improve the ability to prognosticate for patients and families.

Bronchopulmonary dysplasia in premature infants is a common and often severe lung disease with long term sequelae. A genetic component is suspected but not fully defined. We performed an ancestry and genome-wide association study to identify variants, genes and pathways associated with survival without bronchopulmonary dysplasia in 387 high-risk infants treated with inhaled nitric oxide in the Trial of Late Surfactant study. Global African genetic ancestry was associated with increased survival without bronchopulmonary dysplasia among infants of maternal self-reported Hispanic White race/ethnicity (OR=4.5, p=0.01). Admixture mapping found suggestive outcome associations with local African ancestry at 18q21 and 10q22 among infants of maternal self-reported African American race/ethnicity. For all infants, the top individual variant identified was within the intron of NBL1, which is expressed in mid-trimester lung and is an antagonist of bone morphogenetic proteins (rs372271081, OR=0.17, p=7.4 × 10−7). The protective allele of this variant was significantly associated with lower nitric oxide metabolites in the urine of non-Hispanic white infants (p= 0.006), supporting a role in the racial differential response to nitric oxide. Interrogating genes upregulated in bronchopulmonary dysplasia lungs indicated association with variants in CCL18, a cytokine associated with fibrosis and interstitial lung disease, and pathway analyses implicated variation in genes involved in immune/inflammatory processes in response to infection and mechanical ventilation. Our results suggest that genetic variation related to lung development, drug metabolism, and immune response contribute to individual and racial/ethnic differences in respiratory outcomes following inhaled nitric oxide treatment of high-risk premature infants.

Pulmonary hypertension is associated with diverse cardiac, pulmonary, and systemic diseases in neonates, infants, and older children and contributes to significant morbidity and mortality. However, current approaches to caring for pediatric patients with pulmonary hypertension have been limited by the lack of consensus guidelines from experts in the field. In a joint effort from the American Heart Association and American Thoracic Society, a panel of experienced clinicians and clinician-scientists was assembled to review the current literature and to make recommendations on the diagnosis, evaluation, and treatment of pediatric pulmonary hypertension. This publication presents the results of extensive literature reviews, discussions, and formal scoring of recommendations for the care of children with pulmonary hypertension.

Introduction: We sought to determine the relationship between the degree of stomach herniation by antenatal sonography and neonatal outcomes in fetuses with isolated left-sided congenital diaphragmatic hernia (CDH). Materials and Methods: We retrospectively reviewed neonatal medical records and antenatal sonography of fetuses with isolated left CDH cared for at a single institution (2000-2012). Fetal stomach position was classified on sonography as follows: intra-abdominal, anterior left chest, mid-to-posterior left chest, or retrocardiac (right chest). Results: Ninety fetuses were included with 70% surviving to neonatal discharge. Stomach position was intra-abdominal in 14% (n = 13), anterior left chest in 19% (n = 17), mid-to-posterior left chest in 41% (n = 37), and retrocardiac in 26% (n = 23). Increasingly abnormal stomach position was linearly associated with an increased odds of death (OR 4.8, 95% CI 2.1-10.9), extracorporeal membrane oxygenation (ECMO; OR 5.6, 95% CI 1.9-16.7), nonprimary diaphragmatic repair (OR 2.7, 95% CI 1.4-5.5), prolonged mechanical ventilation (OR 5.9, 95% CI 2.3-15.6), and prolonged respiratory support (OR 4.0, 95% CI 1.6-9.9). All fetuses with intra-abdominal stomach position survived without substantial respiratory morbidity or need for ECMO. Discussion: Fetal stomach position is strongly associated with neonatal outcomes in isolated left CDH. This objective tool may allow for accurate prognostication in a variety of clinical settings.

© 2015 ISUOG. Published by John Wiley & Sons Ltd. Objectives To assess whether severity of congenital diaphragmatic hernia (CDH) correlates with the degree of left heart hypoplasia and left ventricle (LV) output, and to determine if factors leading to abnormal fetal hemodynamics, such as compression and reduced LV preload, contribute to left heart hypoplasia. Methods This was a retrospective cross-sectional study of fetuses at 16-37 weeks' gestation that were diagnosed with CDH between 2000 and 2010. Lung-to-head ratio (LHR), liver position and side of the hernia were determined from stored ultrasound images. CDH severity was dichotomized based on LHR and liver position. The dimensions of mitral (MV) and aortic (AV) valves and LV were measured, and right and left ventricular outputs were recorded. Results In total, 188 fetuses with CDH were included in the study, 171 with left CDH and 17 with right CDH. Fetuses with severe left CDH had a smaller MV (Z = -2.24 ± 1.3 vs -1.33 ± 1.08), AV (Z = -1.39 ± 1.21 vs -0.51 ± 1.05) and LV volume (Z = -4.23 ± -2.71 vs -2.08 ± 3.15) and had lower LV output (26 ± 10% vs 32 ± 10%) than those with mild CDH. MV and AV in fetuses with right CDH (MV, Z = -0.83 ± 1.19 and AV, Z = -0.71 ± 1.07) were larger than those in fetuses with left CDH, but LV outputs were similarly diminished, regardless of hernia side. Severe dextroposition and abnormal liver position were associated independently with smaller left heart, while LHR was not. Conclusion The severity of left heart hypoplasia correlates with the severity of CDH. Altered fetal hemodynamics, leading to decreased LV output, occurs in both right- and left-sided CDH, but the additional compressive effect on the left heart is seen only when the hernia is left-sided. Improved knowledge of the physiology of this disease may lead to advances in therapy and better risk assessment for use in counseling affected families.