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The association between phthalate exposure and pubertal development

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Abstract

Antiandrogenic effect of phthalates have been reported; however, results regarding the effect of phthalate exposure in pubertal children have been inconsistent. We aimed to investigate the relationship between phthalate exposure and pubertal development, especially whether high molecular weight phthalates (HMWP) and low molecular weight phthalates (LMWP) are differently associated in boys and girls. Urinary phthalate metabolites (4 HMWPs and 3 LMWPs) in Korean children (236 boys and 202 girls, aged 10 to 12 years) were measured. The association between phthalate levels and pubertal development (pubertal stages self-reported by parents and sex steroid levels) was analyzed by generalized linear regression after adjusting for age, body mass index z score, and premature birth and/or low birth weight. Both the highest quartile of HMWP (Q4 vs Q1, adjusted odds ratio [OR], 0.238; 95% confidence interval [CI], 0.090–0.627; p = 0.004) and LMWP (Q4 vs Q1, adjusted OR, 0.373; 95% CI, 0.151–0.918; p = 0.032) were inversely associated with pubertal stages in boys, whereas the highest quartile of LMWP (Q4 vs Q1, adjusted OR, 2.431; 95% CI, 1.024–5.768; p = 0.044) was significantly related to advanced pubertal stages in girls. Testosterone levels in boys were significantly lower at the highest quartile of HMWP (adjusted β = − 0.251; 95% CI, − 0.476 to − 0.027; p = 0.028). However, in girls, we could not find any significant relationship between HMWP or LMWP and estradiol levels.

Conclusions: Our results suggest that phthalate exposure, especially exposure to the HMWP, may have inverse association with male pubertal development. Further investigation is required to verify the relationship of phthalate exposure and pubertal development in girls.

What is Known:

• Exposure to phthalates may have antiandrogenic effects.

• Studies on the association between phthalates and pubertal development have yielded inconsistent results.

What is New:

• Phthalate levels were inversely associated with self-reported pubertal stages in boys.

• Exposure to phthalates might have a negative influence on male pubertal development.

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Data Availability

Data supporting the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

BMI:

Body mass index

CI:

Confidence interval

DBP:

Di-butyl phthalate

DEHP:

Di-(2-ethylhexyl) phthalate

DEP:

Di-ethyl phthalate

DiBP:

Di-isobutyl phthalate

DiNP:

Di-isononyl phthalate

DMP:

Di-methyl phthalate

DnBP:

Di-n-butyl phthalate

HMWP:

High molecular weight phthalate

IQR:

Interquartile range

LMWP:

Low molecular weight phthalate

LOQ:

Limit of quantification

MBzP:

Mono-benzyl phthalate

MCCP:

Mono-(3-carboxypropyl) phthalate

MECPP:

Mono-(2-ethyl-5-carboxypentyl) phthalate

MEHHP:

Mono-(2-ethyl-5-hydroxyhexyl) phthalate

MEOHP:

Mono-(2-ethyl-5-oxohexyl) phthalate

MEP:

Mono-ethyl phthalate

MHBP:

Mono-(3-hydroxybutyl) phthalate

MiBP:

Mono-isobutyl phthalate

MnBP:

Mono-n-butyl phthalate

MNCP:

Mono-carboxyisononyl phthalate

OR:

Odds ratio

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Funding

This work was supported by a grant from the Seongnam Atopy Project of the Seongnam City Government, Republic of Korea and Korea Health Technology R&D Through the Korea (HR22C1605030022).

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Authors and Affiliations

  1. Department of Pediatrics, CHA Ilsan Medical Center, CHA University School of Medicine, Goyang, Korea

    Mi Ra Kim

  2. Department of Pediatrics, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea

    Mo Kyung Jung, Hye Mi Jee, Man Yong Han & Eun-Gyong Yoo

  3. Department of Pediatrics, Kangnam Sacred Heart Hospital, Hallym University Medical Center, Seoul, Korea

    Eun Kyo Ha

  4. Center for Companion Biomarker, Seoul Clinical Laboratories Healthcare, Yongin, Korea

    Sanghoo Lee

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  1. Mi Ra Kim
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Contributions

Mi Ra Kim, Man Yong Han, and Eun-Gyong Yoo contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Mo Kyung Jung, Hye Mi Jee, Eun Kyo Ha, Sanghoo Lee, Man Yong Han, and Eun-Gyong Yoo. The first draft of the manuscript was written by Mi Ra Kim. Man Yong Han and Eun-Gyong Yoo commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Man Yong Han or Eun-Gyong Yoo.

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This study was performed in accordance with the Declaration of Helsinki. And this study was approved by the Institutional Review Board of CHA University (2017–04-049).

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Kim, M.R., Jung, M.K., Jee, H.M. et al. The association between phthalate exposure and pubertal development. Eur J Pediatr 183, 1675–1682 (2024). https://doi.org/10.1007/s00431-023-05416-z

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