275 - Using urinary leukotriene E4 as an early predictor of severe histological chorioamnionitis exposure and the risk of developing chronic lung disease in extremely preterm infants

Publication Number: 275.7035

Yi-Li Hung, Cathay General Hospital, Taipei, Taipei, Taiwan (Republic of China); Wu-Shiun Hsieh, Department of Pediatrics Cathay General Hospital and Department of Pediatrics National Taiwan University College of Medicine, Taipei, Taiwan, Taipei City, Taipei, Taiwan (Republic of China); Chung-Min Shen, Cathay General Hospital, Taipei, Taipei, Taiwan (Republic of China)

Background: Severe histological chorioamnionitis (HCAM) or funisitis has been reported to be associated with chronic lung disease (CLD) in extremely preterm neonates. This type of CLD is triggered by an intrauterine inflammatory response and dysregulation of pro-inflammatory cytokines. In addition, preterm neonates with CLD are at a higher risk of developing childhood asthma. Cysteinyl leukotrienes is a well-known cytokine that modulates airway inflammation.

Objective: Our study aimed to investigate the association between urinary leukotriene E4 (LTE4), HCAM, and the subsequent development of CLD in preterm infants.

Design/Methods: Twenty-seven premature infants with a birth weight < 1800 g were prospectively enrolled. Urinary LTE4-to-creatine ratio (LTE4/Cre) was measured sequentially at postnatal days (PND) 1, 3, 7, 14, and 28 and postmenstrual age of 36 weeks by enzyme-linked immunosorbent assay. The HCAM stage was evaluated by two independent pathologists, and severe HCAM was defined as moderate to severe. Urinary LTE4 levels were adjusted for gestational age (GA), sex, prenatal steroid use, and family history of asthma. We compared the serial urinary LTE4 levels between neonates with and without severe HCAM and CLD.

Results: The enrolled 27 neonates had a mean GA of 28.2±2.6 weeks and a mean birth body weight of 1,060±265.7 g. Among them, 8 (29.6%) had severe HCAM and 6 (22.2%) had funisitis. Urinary LTE4/Cre increased significantly after PND 1 and reached its highest level on PND 3 or 7. The urinary LTE4/Cre level at PND 1 had a significant positive correlation among those neonates with exposure to maternal severe HCAM (β=0.655, r2=0.370, p=0.017) or funisitis (β=0.680, r2=0.445, p=0.006). However, this positive correlation was not found at PND 3 or 7. Neonates with antenatal steroid use had a significantly lower LTE4/Cre level at PND 7 than those without (β=-0.664, r2=0.436, p=0.003). Although serial urinary LTE4/Cre levels were not associated with the development of CLD among the five neonates with CLD, we found that the total in-hospital oxygen use duration was negatively correlated with GA and urinary LTE4/Cre at PND 7.

Conclusion(s): Urinary LTE4 levels measured on the first day of life in preterm infants could be a good biomarker for early identification of exposure to severe maternal HCAM or funisitis. In addition, the negative correlation between GA and LTE4/Cre levels at PND 7 and total oxygen use days might implicate the subsequent development of CLD in extremely preterm neonates.