Additive effect between IL-13 polymorphism and cesarean section delivery/prenatal antibiotics use on atopic dermatitis: a birth cohort study (COCOA).
BACKGROUND
Although cesarean delivery and prenatal exposure to antibiotics are likely to affect the gut microbiome in infancy, their effect on the development of atopic dermatitis (AD) in infancy is unclear. The influence of individual genotypes on these relationships is also unclear. To evaluate with a prospective birth cohort study whether cesarean section, prenatal exposure to antibiotics, and susceptible genotypes act additively to promote the development of AD in infancy.


METHODS
The Cohort for Childhood of Asthma and Allergic Diseases (COCOA) was selected from the general Korean population. A pediatric allergist assessed 412 infants for the presence of AD at 1 year of age. Their cord blood DNA was subjected to interleukin (IL)-13 (rs20541) and cluster-of-differentiation (CD)14 (rs2569190) genotype analysis.


RESULTS
The combination of cesarean delivery and prenatal exposure to antibiotics associated significantly and positively with AD (adjusted odds ratio, 5.70; 95% CI, 1.19-27.3). The association between cesarean delivery and AD was significantly modified by parental history of allergic diseases or risk-associated IL-13 (rs20541) and CD14 (rs2569190) genotypes. There was a trend of interaction between IL-13 (rs20541) and delivery mode with respect to the subsequent risk of AD. (P for interaction = 0.039) Infants who were exposed prenatally to antibiotics and were born by cesarean delivery had a lower total microbiota diversity in stool samples at 6 months of age than the control group. As the number of these risk factors increased, the AD risk rose (trend p<0.05).


CONCLUSIONS
Cesarean delivery and prenatal antibiotic exposure may affect the gut microbiota, which may in turn influence the risk of AD in infants. These relationships may be shaped by the genetic predisposition.
Department of Pediatrics, Hallym University College of Medicine, Anyang, Korea.
So-Yeon
SY
Lee
Childhood Asthma Atopy Center, Asan Medical Center, Seoul, Korea.
Jinho
J
Yu
Department of Pediatrics, Sungkyunkwan University of School of Medicine, Seoul, Korea.
Kang-Mo
KM
Ahn
Department of Pediatrics, College of Medicine, Yonsei University, Seoul, Korea.
Kyung Won
KW
Kim
Department of Pediatrics, CHA University of School of Medicine, Seoul, Korea.
Youn Ho
YH
Shin
The Asan Institute for Life Science, Seoul, Korea.
Kyung-Shin
KS
Lee
Childhood Asthma Atopy Center, Asan Medical Center, Seoul, Korea.
Seo Ah
SA
Hong
Childhood Asthma Atopy Center, Asan Medical Center, Seoul, Korea.
Young-Ho
YH
Jung
Childhood Asthma Atopy Center, Asan Medical Center, Seoul, Korea.
Eun
E
Lee
Childhood Asthma Atopy Center, Asan Medical Center, Seoul, Korea.
Song-I
SI
Yang
Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea.
Ju-Hee
JH
Seo
Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea.
Ji-Won
JW
Kwon
Department of Pediatrics, Inje University College of Medicine, Seoul, Korea.
Byoung-Ju
BJ
Kim
Department of Pediatrics, Inje University College of Medicine, Seoul, Korea.
Hyo-Bin
HB
Kim
Department of Pediatrics, Inje University College of Medicine, Seoul, Korea.
Woo-Kyung
WK
Kim
Department of Pediatrics, Korea University Guro Hospital, Seoul, Korea.
Dae Jin
DJ
Song
Department of Pediatrics, National Health Insurance Corporation Ilsan Hospital, Goyang, Korea.
Gwang Cheon
GC
Jang
Department of Pediatrics, Sungkyunkwan University of School of Medicine, Seoul, Korea.
Jung Yeon
JY
Shim
Department of Pediatrics, Ajou University School of Medicine, Suwon, Korea.
Soo-Young
SY
Lee
Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea.
Ja-Young
JY
Kwon
Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Suk-Joo
SJ
Choi
Department of Obstetrics and Gynecology, Pochon CHA University College of Medicine, Seoul, Korea.
Kyung-Ju
KJ
Lee
Department of Obstetrics and Gynecology, Pochon CHA University College of Medicine, Seoul, Korea.
Hee Jin
HJ
Park
Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Hye-Sung
HS
Won
The Asan Institute for Life Science, Seoul, Korea.
Ho-Sung
HS
Yoo
The Asan Institute for Life Science, Seoul, Korea.
Mi-Jin
MJ
Kang
Department of Pediatrics, Kosin University College of Medicine, Busan, Korea.
Hyung-Young
HY
Kim
Childhood Asthma Atopy Center, Asan Medical Center, Seoul, Korea.
Soo-Jong
SJ
Hong
D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002585:Cesarean Section; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D018793:Interleukin-13 / Q000235:genetics*; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000235:genetics*; D012306:Risk
D000900:Anti-Bacterial Agents; C578095:IL13 protein, human; D018793:Interleukin-13; D018950:Lipopolysaccharide Receptors