Prenatal exposure to organophosphate pesticides, maternal paraoxonase 1 genotype, and childhood neurodevelopment at 24 months of age in Shandong, China

  • Yiwen Wang
  • Yan Zhang
  • Lin Ji
  • Yijun Zhou
  • Rong Shi
  • Michihiro Kamijima
  • Jun Ueyama
  • Yu GaoEmail author
  • Ying TianEmail author
Research Article


Prenatal organophosphate pesticide (OP) exposure was reported to negatively affect childhood neurodevelopment. Paraoxonase 1 (PON1) is a key enzyme in the metabolism of OPs and may affect an individual’s susceptibility to OP exposure. However, little is known about its role in the associations of prenatal OP exposure and childhood neurodevelopment. We measured dimethylphosphate (DM), diethylphosphate (DE), and total dialkylphosphate (DAP) metabolites in maternal urine (n = 436) as well as PON1–108C/T and PON1192Q/R genotypes in maternal blood (n = 244). We assessed the modifying effects of maternal PON1–108C/T and PON1192Q/R genotypes on relationships between prenatal OP exposure and developmental quotients (DQs) in 24-month-old children in Shandong, China (n = 172). Among children of mothers carrying PON1–108CC, a tenfold increase in prenatal DMs was associated with a 5.72-point decrease in social domain DQ scores. Among children of mothers carrying PON1192QQ, a tenfold increase in prenatal DMs and DAPs were associated with a 7.68- and 7.67-point decrease in gross motor domain DQ scores, respectively. Among children of mothers carrying PON1192QQ, a tenfold increase in prenatal DMs, DEs, and DAPs were associated with a 7.52-, 9.07-, and 9.60-point decrease in social domain DQ scores, respectively. Maternal PON1 genotype might modify the associations between prenatal OP exposure and children’s neurodevelopment at 24 months of age.


Organophosphate pesticides Neurodevelopment Prenatal exposure Paraoxonase 1 China 



organophosphate pesticide


Paraoxonase 1




developmental quotient


Gesell Developmental Schedules


Laizhou Wan Birth Cohort


intelligence quotient


gas chromatography-mass spectrometry














imit of detection


pre-pregnancy body mass index


Wechsler Intelligence Scale for Children



This work was supported by the National Natural Science Foundation of China (Grant No.81803185, 81630085, 81872629, 81773387, 81602823), National Key Research and Development Program of China (Grant No.2017YFC1600500, 2016YFC1000203), Scientific research program of Shanghai Municipal Commission of Health and Family Planning (201840180, 201640174), and the Science and Technology Commission of Shanghai Municipality (17ZR1415800).

We thank the Department of Environmental Health staff, students, participants, and hospital partners.

This study was approved by the Medical Ethics Committee of Xin Hua Hospital, affiliated to Shanghai Jiao Tong University School of Medicine.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11356_2019_6740_MOESM1_ESM.docx (36 kb)
ESM 1 (DOCX 36 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Yiwen Wang
    • 1
    • 2
  • Yan Zhang
    • 3
  • Lin Ji
    • 3
  • Yijun Zhou
    • 3
  • Rong Shi
    • 3
  • Michihiro Kamijima
    • 4
  • Jun Ueyama
    • 5
  • Yu Gao
    • 3
    Email author
  • Ying Tian
    • 1
    • 3
    Email author
  1. 1.MOE and Shanghai Key Laboratory of Children’s Environmental HealthXin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.Department of NeonatologyXin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
  3. 3.Department of Environmental Health, School of Public HealthShanghai Jiao Tong University School of MedicineShanghaiChina
  4. 4.Department of Occupational and Environmental HealthNagoya City University Graduate School of Medical SciencesNagoyaJapan
  5. 5.Department of Pathophysiological Laboratory Sciences, Field of Radiological and Medical Laboratory SciencesNagoya UniversityNagoyaJapan

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