Extremely Low Gestational Age Newborns (ELGANs) have a Substantial Risk for Chronic Pulmonary Hypertension at 3 and 12 Months of Corrected Gestational Age

 

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Objectives: Extremely low gestational age newborns (ELGANs) represent a particularly vulnerable population that inherits many clinical challenges. With increased survival of these patients, diagnosis and management of co-morbidities becomes increasingly important. We hypothesized that pulmonary hypertension (PH) is common in ELGANs, and that echocardiographic variables and serum markers of right ventricular (RV) pressure load would indicate increased PAP in the first 12 months of corrected gestational age (cGA).

Methods: Retrospective observational cohort study of low ELGANs (n = 47; male: 26; 23 + 0 to 25 + 6 weeks’ GA). Variables were neonatal morbidity, cardiac function measured using e.g., tricuspid annular plane systolic excursion, TAPSE, right ventricular systolic pressure (RVSP), end-systolic left ventricular eccentricity index (LVEI), pulmonary arterial acceleration time (PAAT), bronchopulmonary dysplasia (BPD), and pulmonary hypertension (PH) at 3 month and 1 years’ cGA. Degree of PH was based on RVSP. Mild PH correlates to about half systemic RVP, and moderate is half to three-fourths systemic RVSP.

Result: Out of our 47 low ELGANs, 13 died within the first 3 months. 44 patients had BPD (93.6%; 31 had mild, 8 moderate, and 5 severe BPD). Fifteen neonates had PH (31.9%, at 3 months’ cGA: 12 mild PH, 3 moderate PH; and 6 neonates at 12 months. cGA: 5 mild, 1 moderate PH). PH-targeted therapy at 3 months/1 year of cGA was: (sildenafil mono [n = 11/n = 4], dual oral combination (n = 4/n = 2). Serum NT-proBNP at 3 months’ cGA were higher in PH compared with non-PH patents (median, IQR; PH: 1306, 780–2135; no-PH: 479, 372–1,663 pg/mL). The ELGAN-Patients with PH versus no-PH had abnormal RVSP, LVEI, and PAAT, that is, higher estimated RVSP (3 months’ cGA: 34 [30–40] vs. 23 [19–27] mmHg; p < 0.001; at 12 months’ cGA: with PH: 24, 21–28, no-PH: 20, 18–21 mm Hg; p < 0.001), higher LVEI (at 3 months’ cGA: p < 0.001; 12 months’ cGA: p < 0.001), and lower PAAT (at 3 months’ GA: 45 ± 9 vs. 59 ± 10 milliseconds; p < 0.001; 12 months. cGA: 75 [66–82] vs. 85 [77–90] ms; p = 0.018). TAPSE varied in the first 12 months. cGA, and were not significantly different between the groups at both time points.

Conclusion: This is the largest ELGAN subgroup study with a specific focus on echocardiographic assessment of RV and PA systolic pressure, PAAT, and RV-LV interaction. We found that ELGANs with PH had signs of end-systolic leftward septum shift and increased PAP, and received PH-targeted medication at 3 months cGA, with respective improvement at 1 year of cGA.