Prospective study of pulmonary hypertension in preterm infants with bronchopulmonary dysplasia

Abstract

Objective: To evaluate the prevalence, risk factors, and optimal timing of echocardiogram for pulmonary hypertension (PH) in infants with bronchopulmonary dysplasia (BPD).Design: In this prospective study, infants with gestational age (GA) <30 weeks admitted to a tertiary NICU between July 2015 and June 2017 who required positive pressure ventilation or oxygen therapy at ≥28 days of life were evaluated with serial echocardiograms at study enrollment (4-6 weeks of age), 32 weeks (only for ≤25 weeks), 36, and 40 weeks post-menstrual age (PMA) for PH.Results: Of 126 infants (mean birth weight 858 ± 221 g; mean GA 26.1 ± 1.6 wks), 48 (38%) developed PH at any time during their hospital stay. The first study echocardiogram was performed at a median age of 31 weeks PMA. The prevalence of PH was 36/126 (28.5%) at enrollment, at 6/30 (20%) at 32 weeks, 24/111 (21.6%) at 36 weeks, and 10/ 59 (17%) at 40 weeks. No new cases of PH were identified at 40 weeks. At 36 weeks, none of the infants with mild BPD had PH, whereas 20% of moderate and 32% of severe BPD infants had PH. After controlling for confounding variables severe BPD (OR 3.31, 95%CI 1.12, 9.74), and ventilator associated pneumonia (VAP) (OR 17.9, 95%CI 3.9, 82.11) remained independent risk factors for BPD-associated PH.Conclusion: Echocardiographic screening for PH can be safely restricted to infants with moderate or severe BPD at 36 weeks PMA. We identified VAP as an independent risk factor for PH. K E Y W O R D Sbronchopulmonary dysplasia, preterm, pulmonary hypertension, ventilator associated pneumonia Abbreviations: ASD, atrial septal defect; BPD, bronchopulmonary dysplasia; BW, birth weight; EI, eccentricity index; GA, gestational age; iNO, inhaled nitric oxide; IVH, intraventricular hemorrhage; LVEF, left ventricular ejection fraction; NEC, necrotizing enterocolitis; NICU, neonatal intensive care unit; PDA, patent ductus arteriosus; PFO, patent foramen ovale; PH, pulmonary hypertension; PMA, postmenstrual age; ROP, retinopathy of prematurity; RV, right ventricle; RVSP, right ventricular systolic pressure; SD, standard deviation; SNAP-II, score of neonatal acute physiology-version II; TAPSE, tricuspid annular plane systolic excursion; VAP, ventilator associated pneumonia.

Endothelial to mesenchymal transition during neonatal hyperoxia‐induced pulmonary hypertension

“…We rationalized that since mouse lung alveolar formation begins at pnd4, a short exposure early in neonatal life may be sufficient to result in long‐term sequelae and therefore exposed C57BL/6J newborn mice to hyperoxia for 3 days during the saccular stage of lung development. Mice were exposed to greater than 95% oxygen to mimic severe BPD, as pulmonary hypertension is observed in infants with moderate to severe BPD [12,38]. These mice gradually developed pulmonary vascular and RV remodeling as well as pulmonary hypertension by 4 months of age.…”

“…pulmonary hypertension) as adolescents and adults [2][3][4][5][6][7][8][9][10][11]. Indeed, 30% of infants with moderate to severe BPD develop pulmonary hypertension [7,9,10,12]. However, the mechanisms underlying BPD-associated pulmonary hypertension are not fully understood.…”

Pulmonary hypertension is an important co‐morbidity in developmental lung diseases of infancy: Bronchopulmonary dysplasia and congenital diaphragmatic hernia

“…Although PH is often not noted initially in BPD, abnormal echocardiograms as early as 1 week of age or by 36 weeks PMA are associated with increased odds of mortality, prolonged neonatal hospitalization, and increased rates of later hospitalization for respiratory illness and other respiratory morbidities by 2 years corrected age 3,20,21,28 . In 2015, joint guidelines released by the American Heart Association and American Thoracic Society, and endorsed by the Pediatric Pulmonary Hypertension Network, recommend screening all BPD infants with moderate to severe BPD at 36 weeks gestational age with echocardiogram 41‐43 . Infants at risk for BPD–PH development may be further identified by combining echo findings with early changes in brain natriuretic peptide levels 44 …”

“…As such, cardiac catheterization should be considered as a second line of evaluation to establish the diagnosis of PH, evaluate the burden of lung disease and its effect on pulmonary arterial pressures, assess the vasculature (including pulmonary veins), characterize intracardiac shunts and the associated net pulmonary circulatory load, perform acute vasoreactivity testing and assess for changes in left heart diastolic function 1,31,42,68‐73 . To optimize risk and benefit ratio, catheterization may be most helpful in the child whose burden of disease seems disproportionate to degree of developmental lung disease.…”

Pulmonary Hypertension Associated with Bronchopulmonary Dysplasia: A Review

“…Recent PH guidelines released by the American Heart Association in conjunction with the American Thoracic Society address the lack of standardized criteria and recommend echocardiography screening of all PH-BPD infants with moderate-to-severe BPD at 36 weeks gestational age. 16,17 This recommendation was echoed and specifically discussed by the Pediatric Pulmonary Hypertension Network with further details on the expectant management of the infant with PH-BPD. 18…”