Gastroesophageal Reflux Poses a Potential Risk for Late Complications of Bronchopulmonary Dysplasia: A Prospective Cohort Study

Background: Bronchopulmonary dysplasia (BPD) is the most common respiratory disorder in extremely low birth weight infants. Although most symptoms of BPD improve, some late complications exist, even with regular treatment. Gastroesophageal reflux (GER), also common in extremely premature infants, may be related to many cardiorespiratory symptoms. However, the potential of GER as a risk factor for late complications associated with BPD is still unclear.

Research question: The goal of this study was to determine if GER increases the risk of late complications of BPD in infants.

Study design and methods: A multicenter prospective cohort of 131 infants (79 male subjects, 52 female subjects) with BPD was enrolled. The development of late complications was assessed over an 18-month follow-up period. Twenty-four-hour pH-multichannel intraluminal impedance and gastric sodium concentrations were analyzed in all infants at 36 weeks' postmenstrual age and at the last interview. Prevalence and risk factors of late complications of BPD were analyzed by using forward logistic regression.

Results: The prevalence of late complications in BPD infants was 63.79% and included respiratory symptoms (49.14%), vomiting (38.79%), retinopathy of prematurity (25.86%), hypoxic-ischemic injury (3.45%), rehospitalization (26.72%), and sudden death (0.86%). Respiratory diseases constituted the most frequent complication. The prevalence of GER in BPD was 42.24% and included acid GER (18.10%) and duodenogastroesophageal reflux (DGER; 24.14%). Risk factors for respiratory symptoms were gestational age ≤ 30 weeks (OR, 3.213; 95% CI, 1.221-8.460), birth weight < 1,500 g (OR, 2.803; 95% CI, 1.014-7.749), invasive ventilation > 7 days (OR, 4.952; 95% CI, 1.508-16.267), acid GER (OR, 4.630; 95% CI, 1.305-16.420), and DGER (OR, 5.588; 95% CI, 1.770-17.648). Infants with BPD and DGER were more prone to late complications than those with acid GER or no reflux.

Interpretation: The prevalence of late complications is high in infants with BPD. GER (and in particular, DGER) poses a tentative risk for these late complications.

Trial registry: ClinicalTrials.gov; No.: NCT03014453; URL: www.clinicaltrials.gov.

Keywords: bronchopulmonary dysplasia; extremely premature infants; gastroesophageal reflux; late complications.