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Association between phthalate metabolites in human amniotic fluid and offspring birth size: a sub-study of the PERSIAN birth cohort

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Abstract

As phthalate metabolites might cross the placenta, it is possible to find them in the amniotic fluid. This cross-sectional study aims to investigate the levels of phthalate metabolites in the amniotic fluid of a sample of Iranian women and its association with neonatal anthropometric measures. The other objective was to study the potential sources of maternal exposure to phthalates. This study was conducted from June 2019 to June 2021 in Isfahan, Iran. Pregnant women were recruited from their first trimester of pregnancy and followed up until their delivery. Amniotic fluid samples were collected from those who were assigned to have delivery by cesarean section. Overall, 158 samples of amniotic fluid were collected, of which 139 samples had sufficient volume and were free of blood. Data from 142 newborns were included in this study. Four phthalate metabolites were measured using gas chromatography–mass spectrometry (GC–MS). After extraction of phthalate metabolites, 4 phthalate metabolites including mono-butyl phthalate (MBP; normal: 0.08 ± 0.79; overweight: 0.20 ± 1.11; obese: 0.07 ± 1.07; p-value: 0.405), mono-benzyl phthalate (MBzP; normal: 7.54 ± 6.69; overweight: 7.48 ± 7.16; obese: 8.67 ± 12.75; p-value: 0.729), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP; normal: 4.27 ± 6.36; overweight: 3.03 ± 8.44; obese: 3.53 ± 7.04; p-value: 0.245), and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP; normal: 246.18 ± 189.80; overweight: 238.48 ± 200.23; obese: 287.65 ± 206.70; p-value: 0.723) were simultaneously detected in samples of maternal amniotic fluid. Our findings suggest that maternal exposure to phthalate metabolites is positively associated with in utero exposure of the developing fetus. The geometric means and medians of MBP, MBzP, MEOHP, and MEHHP of detected samples were 10.17 (9.52), 6.24 (3.47), 5.03 (11.72), and 174.79 (229.94) (μg/L), respectively. The median anthropometric measures of newborns were as follows: weight 3171.8 g, height 49.6 cm, head circumferences 34.9 cm, chest 33.3 cm, hip 31.5 cm, and arm circumferences 10.8 cm. There was no statistically significant association between phthalate metabolites concentration and newborn’s anthropometric measures (p > 0.05). Future studies should focus on the collection of amniotic fluid at different trimesters and the corresponding maternal samples to better characterize the association and health impacts of these endocrine-disrupting chemicals during fetal development.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

GC-MS:

Gas chromatography–mass spectrometry

MBP:

Mono-butyl phthalate

MBzP:

Mono-benzyl phthalate

MEOHP:

Mono(2-ethyl-5-oxohexyl) phthalate

MEHHP:

Mono(2-ethyl-5-hydroxyhexyl) phthalate

MSTFA:

N-Trimethylsilyl-N-methyl trifluoroacetamide

IUMS:

Isfahan University of Medical Sciences

DLLME:

Dispersive liquid–liquid micro extraction

BMI:

Body Mass Index

BIC:

Bayes Information Criterion

LOD:

Limit of detection

LOQ:

Limit of quantification

WHO:

World Health Organization

LCA:

Latent class analysis

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Acknowledgements

The authors acknowledge to the National Institute for Medical Research Development (NIMAD) and the Iranian Ministry of Health and Medical Education for financial support of the current study.

Funding

This study was supported by Elite Researcher Grant Committee under award number [977011] from the National Institute for Medical Research Development (NIMAD), Tehran, Iran. The main cohort was funded by the Iranian Ministry of Health and Medical Education, as the project number 194354 (Research Ethics code: IR.MUI.REC.1394.1.354).

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Authors and Affiliations

  1. Environment Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

    Mohsen Golestanzadeh & Karim Ebrahimpour

  2. Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Hezarjerib Ave, Isfahan, 8174673461, Iran

    Mohsen Golestanzadeh, Masoomeh Goodarzi-Khoigani, Seyede Shahrbanoo Daniali, Maryam Yazdi & Roya Kelishadi

  3. Department of Obstetrics and Gynecology, Fetal Medicine Unit, Isfahan University of Medical Sciences, Isfahan, Iran

    Elaheh Zarean & Zohreh Basirat

Authors
  1. Mohsen Golestanzadeh
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  2. Masoomeh Goodarzi-Khoigani
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  3. Seyede Shahrbanoo Daniali
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  4. Karim Ebrahimpour
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  5. Elaheh Zarean
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  6. Maryam Yazdi
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  7. Zohreh Basirat
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  8. Roya Kelishadi
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Contributions

M. Golestanzadeh: conceptualization, data curation, methodology, and writing of the original draft. M. GoodarziKhoigani: Samples and data curation. S. S. Daniali: Samples and data curation. K. Ebrahimpour: Providing the laboratory analysis and equipment and advisory. E. Zarean and Z. Basirat: Providing the amniotic samples through cesarean section and advisory. M. Yazdi: Expert in analyzing the data. R. Kelishadi: Principal investigator, head of the group, and paraphrase of the final draft. The authors read and approved the final manuscript.

Corresponding author

Correspondence to Roya Kelishadi.

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Ethical approval and consent to participate

Ethics approval was obtained [IR.NIMADREC.1397.410]; all participants gave written informed consent for participation in the study prior to sample collection.

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All participants gave written informed consent for participation in the study and its publication.

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The authors declare that they have no conflict of interest.

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Golestanzadeh, M., Goodarzi-Khoigani, M., Shahrbanoo Daniali, S. et al. Association between phthalate metabolites in human amniotic fluid and offspring birth size: a sub-study of the PERSIAN birth cohort. Environ Sci Pollut Res 29, 76970–76982 (2022). https://doi.org/10.1007/s11356-022-20839-1

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