Prenatal Exposure to Lead and Chromium is Associated with IL-13 Levels in Umbilical Cord Blood and Severity of Atopic Dermatitis: COCOA Study

Jihyun Kim; Seonwoo Kim; Sook-young Woo; Jin-Yong Chung; Young-Seoub Hong; Se-Young Oh; Suk-Joo Choi; Soo-Young Oh; Kyung Won Kim; Youn Ho Shin; Hye-Sung Won; Kyung-Ju Lee; Soo Hyun Kim; Ja Young Kwon; Si Hyeon Lee; Soo-Jong Hong; Kangmo Ahn

doi:10.4110/in.2018.19.e42

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Kim, Kim, Woo, Chung, Hong, Oh, Choi, Oh, Kim, Shin, Won, Lee, Kim, Kwon, Lee, Hong, and Ahn: Prenatal Exposure to Lead and Chromium is Associated with IL-13 Levels in Umbilical Cord Blood and Severity of Atopic Dermatitis: COCOA Study

Original Article

Immune Netw 2019;19(6):e42.

Published online: 4 December 2019

DOI: https://doi.org/10.4110/in.2018.19.e42

Prenatal Exposure to Lead and Chromium is Associated with IL-13 Levels in Umbilical Cord Blood and Severity of Atopic Dermatitis: COCOA Study

Jihyun Kim^1,^2,^†, Seonwoo Kim^3,^†, Sook-young Woo³, Jin-Yong Chung⁴, Young-Seoub Hong^4,⁵, Se-Young Oh⁶, Suk-Joo Choi⁷, Soo-Young Oh⁷, Kyung Won Kim⁸, Youn Ho Shin⁹, Hye-Sung Won¹⁰, Kyung-Ju Lee¹¹, Soo Hyun Kim¹², Ja Young Kwon¹³, Si Hyeon Lee¹⁴, Soo-Jong Hong^14,, Kangmo Ahn^1,^2,^*

¹Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

²Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, Korea

³Statistics and Data Center, Samsung Medical Center, Seoul, Korea

⁴Heavy Metal Exposure Environmental Health Center, Dong-A University, Busan, Korea

⁵Department of Preventive Medicine, Dong-A University College of Medicine, Busan, Korea

⁶Department of Food and Nutrition, College of Human Ecology, Kyung Hee University, Seoul, Korea

⁷Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

⁸Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea

⁹Department of Pediatrics, CHA Gangnam Medical Center, CHA University College of Medicine, Seoul, Korea

¹⁰Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

¹¹Department of Obstetrics and Gynecology, Integrative Medicine Center, Korea University Medical College, Seoul, Korea

¹²Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University College of Medicine, Seoul, Korea

¹³Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea

¹⁴Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

^*Correspondence to Kangmo Ahn Department of Pediatrics and Environmental Health Center for Atopic Diseases, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. E-mail: kmaped@skku.edu

Soo-Jong Hong Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. E-mail: sjhong@amc.seoul.kr

^† These authors contributed equally to this work.

Conflict of Interest The authors declare no potential conflicts of interest.

Received 2 September 2019 Revised 5 November 2019 Accepted 10 November 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

There have been few studies investigating the association between atopic dermatitis (AD) and prenatal exposure to heavy metals. We aimed to evaluate whether prenatal exposure to heavy metals is associated with the development or severity of AD in a birth cohort study. A total of 331 subjects were followed from birth for a median duration of 60.0 months. The presence and severity of AD were evaluated at ages 6 and 12 months, and regularly once a year thereafter. The concentrations of lead, mercury, chromium, and cadmium in umbilical cord blood were measured by inductively coupled plasma mass spectrometry. Cord blood mononuclear cells (CBMCs) were isolated and stimulated for analysis of cytokine production using ELISA. Heavy metal levels in cord blood were not associated with the development of AD until 24 months of age. However, a positive correlation was observed between the duration of AD and lead levels in cord blood (p=0.002). AD severity was also positively associated with chromium concentrations in cord blood (p=0.037), while cord blood levels of lead, mercury, and cadmium were not significantly associated with AD severity (p=0.562, p=0.054, and p=0.055, respectively). Interleukin-13 production in CBMCs was positively related with lead and chromium levels in cord blood (p=0.021 and p=0.015, respectively). Prenatal exposure to lead and chromium is associated with the persistence and severity of AD, and the immune reaction toward a Th2 polarization.

Keywords: Dermatitis, atopic, Cohort studies, Chromium, Fetal blood, Interleukin-13

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Figure 1.

Correlation between lead levels in cord blood and the duration of AD in 103 children whose skin symptoms lasted for more than 6 months. Statistical analysis was done using partial Spearman's correlation analysis after adjustment for gender, presence of siblings, season of birth, and antibiotic treatment during the first 6 months of life (ρ=0.308, p=0.002).

Figure 2.

Association between mercury levels in cord blood and SCORAD in children with AD. Mixed model was applied after adjustment for season of birth (p=0.004).

Figure 3.

Relationship between heavy metal levels and IL-13 in umbilical cord blood. Mixed model was applied to analyze the association of IL-13 with (A) lead (Pb, µg/dl), (B) mercury (Hg, µg/l), (C) chromium (Cr, µg/l), and (D) cadmium (Cd, µg/l). IL-13 levels in cord blood was positively correlated with only lead levels in cord blood (p=0.028).

Table 1.

Characteristics of subjects (n=331)

Characteristic	No. of subjects (%)
Characteristic	Total (n=331)	AD (n=137)	Non-AD (n=194)
Male	142 (42.9)	51 (37.2)	91 (46.9)
Delivery method
Vaginal delivery	225 (68.0)	92 (67.2)	133 (68.6)
Cesarean section	106 (32.0)	45 (32.8)	61 (31.4)
Season of birth
Spring	82 (24.8)	35 (25.6)	47 (24.2)
Summer	73 (22.1)	25 (18.2)	48 (24.7)
Autumn	99 (29.9)	45 (32.8)	54 (27.8)
Winter	77 (23.3)	32 (23.4)	45 (23.2)
Maternal history of allergic diseases	95 (28.7)	41 (29.9)	54 (27.8)
Presence of older siblings	162 (48.9)	70 (51.1)	92 (47.4)
Pet ownership during pregnancy	20 (6.0)	9 (6.6)	11 (5.7)
Exclusive breastfeeding during the first 6	106 (32.0)	43 (31.4)	63 (32.5)
months
Antibiotic treatment during the first 6 months	129 (39.0)	60 (43.8)	69 (35.6)
Cord blood measurements^*
Total IgE (IU/ml)	0.3 (0–100.0)	0.2 (0–10.2)	0.3 (0–100.0)
Eosinophils (%)	3.0 (0–14.0)	2.9 (0–14.0)	3.0 (0–13.0)
IL-13 (pg/ml)	1,271.4 (20.1–6,574.6)	1,044.5 (26.3–5,955.7)	1,513.0 (20.1–6,574.6)
IFN-γ (pg/ml)	294.3 (0–2,923.7)	233.4 (0–2,923.7)	324.4 (0–2,450.8)

^* Values are presented as median (range).

Table 2.

Univariable and multivariable analyses for factors influencing the development of AD

Variables	Univariable analysis		Multivariable analysis
Variables	HR	95% CI	HR	95% CI
Lead^*	0.995	0.626–1.580	0.956	0.598–1.529
Mercury^*	0.972	0.730–1.294	0.981	0.726–1.324
Chromium^*	1.455	0.889–2.380	1.449	0.883–2.376
Cadmium^†	3.503	0.250–49.083	2.525	0.197–32.419

Multivariable analysis was performed after adjustment for gender and parental history of allergic diseases. CI, confidence interval; HR, hazard ratio.* The values were log-transformed;

^† The levels were transformed to log _e(log _e(Cd×10)+10).

Table 3.

Relationship between heavy metal levels in umbilical cord blood and SCORAD^* index in children with AD

Variables	Univariable analysis		Multivariable analysis
Variables	Beta coefficient	p value	Beta coefficient	p value
Lead^*	0.003	0.123	1.113	0.562
Mercury^*	0.115	0.072	2.179	0.054
Chromium^*	0.260	0.135	0.277	0.037
Cadmium^†	1.524	0.855	25.258	0.055

Multivariable analysis was performed after adjustment for maternal history of allergic diseases, maternal education level, exclusive breastfeeding during the first 6 months of life, and season of birth.* The values were log-transformed;

^† The levels were transformed to log _e(log _e(Cd×10)+10).

Table 4.

Relationship between IL-13 and heavy metal levels in umbilical cord blood

Variables	Univariable analysis		Multivariable analysis
Variables	Beta coefficient	p value	Beta coefficient	p value
Lead^*	0.676	0.028	0.692	0.021
Mercury^*	0.067	0.726	0.102	0.585
Chromium^*	0.530	0.075	0.713	0.015
Cadmium^†	−1.139	0.520	−0.388	0.824

Multivariable analysis was performed after adjustment for gender, presence of siblings, and season of birth.* The values were log-transformed;

^† The levels were transformed to log _e(log _e(Cd×10)+10).

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