Longitudinal B-Type Natriuretic Peptide Levels Predict Outcome in Infants with Congenital Diaphragmatic Hernia.

OBJECTIVE: To evaluate B-type natriuretic peptide (BNP) as a longitudinal biomarker of clinical outcome in infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: 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. RESULTS: 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). CONCLUSIONS: Elevated BNP accurately predicts poor outcome in infants with CDH at age 3-5 weeks, with declining cutoffs over 3-5 weeks of age.

Clinical Utility of Echocardiography in Former Preterm Infants with Bronchopulmonary Dysplasia.

BACKGROUND: The 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. METHODS: A retrospective single center study of 29 infants born ≤29 weeks 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 >2.9 m/sec, post-tricuspid valve shunt systolic flow velocity estimated a right ventricular systolic pressure >35 mm 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. RESULTS: The duration between echocardiography and cardiac catheterization was a median of 1 day (interquartile range, 1-4 days). 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 < .001), right to left ventricular diameter ratio at end systole (0.66, P = .003), and pulmonary artery acceleration time (0.48, P = .05). CONCLUSIONS: Echocardiography performs well in screening for PVD in infants with BPD and may be diagnostic in the absence of a post-tricuspid valve shunt. However, cardiac catheterization is needed to assess the degree of PAP elevation and PVR. The diagnostic utility of echocardiographic measurements that correlate with PVR should be evaluated prospectively in this patient population.

Mortality in infants with bronchopulmonary dysplasia: Data from cardiac catheterization.

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.

Patterns and Outcomes of Care in Children With Advanced Heart Disease Receiving Palliative Care Consultation.

CONTEXT: Although access to subspecialty pediatric palliative care (PPC) is increasing, little is known about the role of PPC for children with advanced heart disease (AHD). OBJECTIVES: The objective of this study was to examine features of subspecialty PPC involvement for children with AHD. METHODS: This is a retrospective single-institution medical record review of patients with a primary diagnosis of AHD for whom the PPC team was initially consulted between 2011 and 2016. RESULTS: Among 201 patients, 87% had congenital/structural heart disease, the remainder having acquired/nonstructural heart disease. Median age at initial PPC consultation was 7.7 months (range 1 day-28.8 years). Of the 92 patients who were alive at data collection, 73% had received initial consultation over one year before. Most common indications for consultation were goals of care (80%) and psychosocial support (54%). At initial consultation, most families (67%) expressed that their primary goal was for their child to live as long and as comfortably as possible. Among deceased patients (n = 109), median time from initial consultation to death was 33 days (range 1 day-3.6 years), and children whose families expressed that their primary goal was for their child to live as comfortably as possible were less likely to die in the intensive care unit (P = 0.03) and more likely to die in the setting of comfort care or withdrawal of life-sustaining interventions (P = 0.008). CONCLUSION: PPC involvement for children with AHD focuses on goals of care and psychosocial support. Findings suggest that PPC involvement at end of life supports goal-concordant care. Further research is needed to clarify the impact of PPC on patient outcomes.

Maternal Obesity Affects Inflammatory and Iron Indices in Umbilical Cord Blood.

OBJECTIVE: To determine the impact of maternal obesity and gestational weight gain across pregnancy on fetal indices of inflammation and iron status. STUDY DESIGN: Eighty-five healthy term newborns delivered via elective cesarean were categorized by 2 maternal body mass index (BMI) thresholds; above or below 30 kg/m(2) or above or below 35 kg/m(2). Umbilical cord plasma levels of C-reactive protein, interleukin (IL)-6, tumor necrosis factor (TNF)-α, ferritin, and hepcidin were assayed. Cytokines released by phytohemagglutinin-stimulated umbilical cord mononuclear cells (MNCs) were assayed. RESULTS: Maternal class II obesity, defined as BMI of 35 kg/m(2) and above, predicted higher C-reactive protein and TNF-α in umbilical cord plasma (P < .05 for both), and also proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) from stimulated MNC (P < .05 for all). The rise in plasma TNF-α and MNC TNF-α was not linear but occurred when the threshold of BMI 35 kg/m(2) was reached (P < .005, P < .06). Poorer umbilical cord iron indices were associated with maternal obesity. When ferritin was low, IL-6 was higher (P < .04), but this relationship was present primarily when maternal BMI exceeded 35 kg/m(2) (P < .03). Ferritin was correlated with hepcidin (P < .0001), but hepcidin was unrelated to either maternal BMI or inflammatory indices. CONCLUSIONS: Class II obesity and above during pregnancy is associated with fetal inflammation in a threshold fashion. Although maternal BMI negatively impacted fetal iron status, hepcidin, related to obesity in adults, was related to iron status and not obesity in fetuses. Pediatricians should be aware of these relationships.