Increased fecal human beta-defensin-2 expression in preterm infants is associated with allergic disease development in early childhood

Man-Chin Hua; Chien-Chang Chen; Sui-Ling Liao; Tsung-Chieh Yao; Ming-Han Tsai; Shen-Hao Lai; Kuan-Wen Su; Li-Chen Chen; Chih-Yung Chiu; Kuo-Wei Yeh; Jing-Long Huang

doi:10.1016/j.waojou.2022.100633

Increased fecal human beta-defensin-2 expression in preterm infants is associated with allergic disease development in early childhood

World Allergy Organ J. 2022 May 11;15(5):100633. doi: 10.1016/j.waojou.2022.100633. eCollection 2022 May.

Authors

Man-Chin Hua^{1

2}, Chien-Chang Chen^{2

3}, Sui-Ling Liao^{1

2}, Tsung-Chieh Yao^{2

4}, Ming-Han Tsai^{1

2}, Shen-Hao Lai^{2

5}, Kuan-Wen Su^{1

2}, Li-Chen Chen^{2

6}, Chih-Yung Chiu^{2

5}, Kuo-Wei Yeh^{2

4}, Jing-Long Huang^{2

6}

Affiliations

¹ Department of Pediatrics, Chang Gung Memorial Hospital, Keelung, Taiwan.
² Chang Gung University College of Medicine, Taoyuan, Taiwan.
³ Division of Gastroenterology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁴ Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁵ Division of Chest, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁶ Department of Pediatrics, Municipal TuCheng Hospital, Chang Gung Memorial Hospital, New Taipei City, Taiwan.

Abstract

Background: This study aimed to investigate whether fecal human beta-defensins (HBD)-2 and eosinophil cationic protein (ECP) expression in preterm infants are associated with allergic disease development by age 2 years.

Methods: Preterm infants' stool samples were collected at the age of 6 and 12 months postnatally. Information regarding medication exposure histories (antibiotics, antipyretics, probiotics) and physician-diagnosed allergic diseases was obtained using age-specific questionnaires and medical records. We compared the 6-month and 12-month fecal HBD-2 and ECP concentrations between the medication exposure and non-exposure group, respectively, and between children who developed allergic diseases and those who did not by 2 years of age. Univariate and multivariable logistic regression analyses were performed to investigate independent variables related to physician-diagnosed allergic diseases by 2 years of age.

Results: Seventy-four preterm infants (gestational age, 31-36 weeks) were included. Fecal HBD-2 levels were significantly increased at 12 months of age among children who developed allergic diseases compared to those who did not (37.18 ± 11.80 ng/g vs. 8.56 ± 4.33 ng/g, P = 0.011). This association was more apparent among allergic children given antibiotics (50.23 ± 16.15 ng/g vs. 9.75 ± 7.16 ng/g, P = 0.008) or antipyretics (46.12 ± 14.22 ng/g vs. 10.82 ± 6.81 ng/g, P = 0.018) during the first year, whereas among allergic children who were previously not exposed to antibiotics or antipyretics, the differences were not significant. Results of the multivariable logistic regression analysis indicated that HBD-2 concentration in 12-month stools was an independent indicator associated with physician-diagnosed allergic diseases by 2 years of age (adjusted odds ratio: 1.03 [95% confidence interval: 1.00-1.05], P = 0.036). Our data revealed a lack of association between fecal ECP and allergic diseases.

Conclusions: We found that preterm infants who expressed high fecal HBD-2 at 12 months of age were associated with physician-diagnosed allergic diseases by the age of 2 years. Further studies are needed to determine the role of fecal HBD-2 in the development of allergic diseases.

Keywords: Allergic diseases; Eosinophil cationic protein; Human beta-defensin 2; Infant stools; Prematurity.