Atrial Septal Defects Accelerate Pulmonary Hypertension Diagnoses in Premature Infants

Abstract

Between 4 and 16% of extremely premature infants have late pulmonary hypertension (PH) (onset >30 days of life), and infants with PH have a higher risk of tracheostomy and death. Atrial septal defects (ASD) increase pulmonary blood flow and may promote PH in at-risk infants. The objective of this study was to determine if infants with ASD develop PH sooner than those without ASD. Infants who were born at < 32 weeks' gestation, with an echocardiogram on day of life > 30, and without congenital anomalies were included. Infants with and without ASD were evaluated for the time to PH diagnosis, defined as the day of the first echocardiogram that showed PH. A multivariable model with ASD and significant variables on PH and a Cox proportional hazard model evaluating time to PH was determined. Of the 334 infants with echocardiograms, 57 had an ASD and 26% of these developed PH vs. 12% without ASD (p = 0.006). Infants with PH had lower gestational age (25.2 vs. 26.2 weeks, p = 0.005), smaller birthweight (699 vs. 816 gm, p = 0.001), and more prematurity complications than infants without PH. More PH infants had maternal African-American race (63.9 vs. 36.1%), right ventricular dysfunction (23.9 vs. 3.2%, p < 0.001), right ventricular dilation (52.1 vs. 8.6%, p < 0.001), or right ventricular hypertrophy (51.2 vs. 10.1%, p < 0.001), than infants without PH. At 150 days of life, 78.1% (95% CI 64.6-86.9%) of infants with ASD survived without PH, compared with 90.9% (95% CI 86.7-93.8%) of infants without ASD, and the unadjusted hazard for development of PH for infants with ASD was 2.37 (95% CI 1.29-4.36). When significant clinical variables were controlled, infants with ASD had a 2.44-fold (95% CI 1.27-4.68) increase in PH, compared with infants without ASD. Most PH in infants with or without ASD was diagnosed by day of life 150, but infants with ASD had an over 2-fold increased hazard for PH during their neonatal hospitalization. Premature infants with ASD should be followed closely for PH development and further studies to investigate the optimal timing of closure are needed.

Keywords: atrial septal defect; echocardiogram; left-to-right shunt; neonate; prematurity; pulmonary hypertension.

Figure 1

Flowchart of patient selection. An electronic health record database query was performed for < 32 weeks' gestation at birth, < 1,500 g birthweight, neonatal intensive care unit, and echocardiographic procedure. Six hundred and twenty-seven infants were identified, and 74 infants were excluded due to congenital anomalies or missing information, Of the 553 eligible infants, 334 had an echocardiogram after 30 days of life and could be evaluated for late pulmunory hypertension (PH). Of these, 57 infants had atrial septal defects (ASD) and 275 infants did not. PH was detected in 15 (26%) patients with ASD and 34 (12%) patients without ASD.

Figure 2

Kaplan-Meier curve for the association between ASD and time to PH. An unadjusted Kaplan-Meier curve was generated for infants with (red line) and without (blue line) atrial septal defects (ASD). Late PH was determined on echocardiographic studies performed after 30 days of life and infants were censored at death or 250 days of life.