Association between gastroesophageal reflux and bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis

Related Experiment Video

Updated: Sep 16, 2025

Intratracheal Instillation of Stem Cells in Term Neonatal Rats

Intratracheal Instillation of Stem Cells in Term Neonatal Rats

Published on: May 4, 2020

XinYi Yu¹, MengKe Sun¹, Yu Hu¹

¹Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.

Frontiers in Nutrition

|July 9, 2025

Insights

Gastroesophageal reflux (GER) in preterm infants may increase bronchopulmonary dysplasia (BPD) risk when clinically diagnosed. However, GER diagnosed via pH monitoring showed no significant association with BPD development.

Area of Science:

Neonatology
Pediatric Pulmonology
Gastroenterology

Background:

Gastroesophageal reflux (GER) is a potential factor in lung injury.
Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants.
The association between GER and BPD requires further investigation.

Purpose of the Study:

To evaluate the association between GER and BPD in preterm infants.
To synthesize existing evidence through a meta-analysis.
To explore heterogeneity and potential biases in the reported association.

Main Methods:

Systematic literature search of major databases (PubMed, Embase, Web of Science, Cochrane Library).
Inclusion of seven studies assessing GER and BPD in preterm infants.
Random-effects models used for pooled risk ratios (RR) with 95% confidence intervals (CIs); sensitivity and subgroup analyses performed.

Main Results:

Overall non-significant association between GER and BPD (RR=1.35, 95% CI=0.91-2.01) with significant heterogeneity (I²=95.2%).
Subgroup analysis: clinically diagnosed GER (therapy or ICD-9 codes) significantly associated with BPD (RR=1.72-2.70).
GER diagnosed by pH monitoring showed no significant association with BPD (RR=0.86, 95% CI=0.71-1.05). Potential publication bias detected.

Conclusions:

Clinically diagnosed GER in preterm infants may be linked to an increased risk of BPD.
GER diagnosed by pH monitoring does not appear to be significantly associated with BPD.
Findings suggest diagnostic methods for GER influence its apparent association with BPD in preterm infants.

Read full analysis

Abstract

Objective:

Gastroesophageal reflux (GER) has emerged as a potential contributor to lung injury. This meta-analysis aimed to evaluate the association between GER and bronchopulmonary dysplasia (BPD) in preterm infants.

Methods:

A systematic literature search was conducted in PubMed, Embase, Web of Science, and Cochrane Library databases up to Oct 19, 2024. Studies assessing the association between BPD and GER in preterm infants were included. Random-effects models was used to calculate pooled risk ratios (RR) with 95% confidence intervals (CIs). Sensitivity analyses and subgroup analyses were performed to assess the robustness of the findings.

Results:

Seven studies were included in the meta-analysis. The overall analysis revealed a non-significant association between GER and BPD (RR = 1.35, 95% CI = 0.91-2.01), but significant heterogeneity was observed across the studies (p < 0.001, I ² = 95.2%). The pooled RR ranged from 1.17 (95% CI = 0.79-1.74) to 1.51 (95% CI = 1.02-2.22) with each study omitted. Funnel plot analysis showed noticeable asymmetry, and Egger's test confirmed potential publication bias (P > |t| = 0.076). Subgroup analysis revealed that GER diagnosed with clinical therapy or ICD-9 codes was significantly associated with BPD (RR = 1.72, 95% CI = 1.52-1.95 and RR = 2.70, 95% CI = 2.48-2.94, respectively). However, GER diagnosed by pH monitoring did not show a statistically significant association with BPD (RR = 0.86, 95% CI = 0.71-1.05).

Conclusion:

Preterm infants with clinically diagnosed GER may face an elevated risk of developing BPD. GER diagnosed by pH monitoring was not associated with BPD.

Systematic Review Registration:

https://www.crd.york.ac.uk/prospero/.

Keywords:

bronchopulmonary dysplasia gastroesophageal reflux infants preterm reflux

More Related Videos

International Expert Consensus and Recommendations for Neonatal Pneumothorax Ultrasound Diagnosis and Ultrasound-guided Thoracentesis Procedure

International Expert Consensus and Recommendations for Neonatal Pneumothorax Ultrasound Diagnosis and Ultrasound-guided Thoracentesis Procedure

Published on: March 12, 2020

Simultaneous Laryngopharyngeal and Conventional Esophageal pH Monitoring

Simultaneous Laryngopharyngeal and Conventional Esophageal pH Monitoring

Published on: December 14, 2020

Related Concept Videos

Gastroesophageal Reflux Disease I: Meaning and Pathophysiology

Gastroesophageal Reflux Disease I: Meaning and Pathophysiology

Gastroesophageal Reflux Disease (GERD) involves the recurrent backflow of the stomach or duodenal contents into the esophagus, leading to troublesome symptoms and potential esophageal mucosal damage. Although GERD is often referred to as a disease, it is more accurately described as a syndrome, as it encompasses a range of symptoms and complications rather than a singular pathological entity, impacting a large number of individuals as the most prevalent upper gastrointestinal problem. Roughly...

Gastroesophageal Reflux Disease II: Clinical Features and Management

Gastroesophageal Reflux Disease II: Clinical Features and Management

Gastroesophageal reflux disease, or GERD, is a persistent medical condition that affects many individuals worldwide. Its clinical manifestations can vary greatly, making diagnosis and management challenging for healthcare professionals. The following is a comprehensive overview of the clinical manifestations, assessment, and management strategies for GERD.
Clinical Manifestations
GERD presents itself in a multitude of ways, with symptoms varying from person to person. The hallmark symptoms are...

Pulmonary Cycle: Exhalation

Pulmonary Cycle: Exhalation

In terms of human respiration, the act of expelling air, known as exhalation (or expiration), operates on the principle of pressure gradients. During expiration, the pressure within the lungs exceeds that of the surrounding atmosphere. Under normal conditions, quiet breathing involves passive exhalation and is free of muscular contractions. This is because the exhalation process is driven by the natural elastic recoil of the lungs and chest wall, both of which have an inherent tendency to...

Breathing

Breathing

The process of breathing, inhaling and exhaling, involves the coordinated movement of the chest wall, the lungs, and the muscles that move them. Two muscle groups with important roles in breathing are the diaphragm, located directly below the lungs, and the intercostal muscles, which lie between the ribs. When the diaphragm contracts, it moves downward, increasing the volume of the thoracic cavity and creating more room for the lungs to expand. When the intercostal muscles contract, the ribs...

Esophageal Strictures-I: Introduction

Esophageal Strictures-I: Introduction

Esophageal strictures involve abnormal narrowing or tightening of the esophagus. They vary in length and severity, ranging from mild constriction to complete obstruction, and are classified as benign (noncancerous) or malignant (cancerous).
Etiology
The primary cause of esophageal strictures is long-standing gastroesophageal reflux disease (GERD), accounting for about 70 to 80% of adult cases. Chronic acid reflux can lead to injury and scarring of the esophageal lining, culminating in...

Barrett Esophagus-I: Introduction

Barrett Esophagus-I: Introduction

Barrett's esophagus is a medical condition where the esophageal mucosa is significantly damaged by stomach acid or other digestive fluids, often due to long-term exposure associated with gastroesophageal reflux disease (GERD). In GERD, a weakened or abnormally relaxed lower esophageal sphincter allows stomach acid to flow persistently into the esophagus.
This constant acid exposure transforms the esophagus's pink mucosal lining (stratified squamous epithelium) into a type of lining more...

Articles linked to this work by shared authors, journal, and citation graph.

Inflammatory burden index predicts long-term mortality: evidence from population-based cohorts with clinical validation.

Frontiers in oncology·2026

"Mud-sand structure"-Inspired synergistic reinforcement of gellan gum and xanthan gum on the 3D printing properties of protein-based high internal phase emulsions.

Current research in food science·2026

Correction: Trust tangles: Who do kids trust? Unraveling young children's attitudes in the gossip mill.

Frontiers in psychology·2026

Tafolecimab mitigates ox-LDL-induced macrophage foam cell formation and inflammation by modulating SR-A/ABCG1 expression and inhibiting the NF-κB/MAPK pathways.

Biomedical reports·2026

Comparative analysis of immune escape and BCR repertoire remodeling after Omicron BF.7 and JN.1 infections.

Frontiers in immunology·2026

Improving the preoperative diagnosis of invasive lung adenocarcinoma by combining multiplanar volume rendering (MPVR)-based solid component measurement with pathological analysis.

Quantitative imaging in medicine and surgery·2026

See all related articles