PMID- 36959356
OWN - NLM
STAT- Publisher
LR  - 20230324
IS  - 1559-064X (Electronic)
IS  - 1559-0631 (Linking)
DP  - 2023 Mar 23
TI  - Individual and joint effects of phthalates exposure on the risk of early 
      miscarriage.
LID - 10.1038/s41370-023-00533-1 [doi]
AB  - BACKGROUND: The exposure levels of phthalates in humans have dropped 
      dramatically. Little is known about the individual and joint effects of 
      phthalates exposure at low levels on the risk of early miscarriage. OBJECTIVE: To 
      examine the association between exposure to phthalates individually or as a 
      mixture and early miscarriage. METHODS: A case-control study was conducted in 
      Shanghai, China during 2019-2020. A total of 291 women seeking medical services 
      due to miscarriage (cases) and 308 women planning to terminate an unintended 
      pregnancy (controls) within 12 gestational weeks were recruited. Urinary 
      concentrations of eight phthalate metabolites were determined by 
      ultra-performance liquid chromatography. We included 534 women in the main 
      analysis who had available data on both phthalates exposure and complete 
      information on potential confounders. We used logistic regression and Bayesian 
      kernel machine regression (BKMR) to examine the associations of concentrations of 
      phthalates with miscarriage. RESULTS: Among the phthalate metabolites, 
      mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) had the highest concentration 
      (8.10 ng/mL), followed by mono(2-ethyl-5-oxohexyl) phthalate (MEOHP, 2.68 ng/mL) 
      and monobutyl phthalate (MBP, 2.24 ng/mL). Higher concentrations of MBP, 
      mono(2-ethylhexyl) phthalate (MEHP), MEHHP, MEOHP and the molar sum of 
      di(2-ethylhexyl) phthalate (DEHP) metabolites ( summation operatorDEHPm) were associated with an 
      increased risk of miscarriage exhibiting a dose-response relationship. The most 
      evident association of miscarriage was found with  summation operatorDEHPm, with adjusted odds 
      ratio (95% confidence interval) of 1.94 (1.14, 3.31) for the second quartile, 
      2.83 (1.67, 4.79) for the third quartile and 4.28 (2.49, 7.37) for the fourth 
      quartile compared to the first quartile. Consistently, the phthalate mixture was 
      positively associated with the risk of miscarriage and DEHP was the predominant 
      contributor to the joint effect in BKMR model. IMPACT: Phthalates are a family of 
      synthetic chemicals mainly used as plasticizers, solvents and additives in a 
      large variety of industrial and consumer products, including food packing 
      materials, toys, gloves, medical devices and personal care products. Although 
      exposure levels of phthalates of pregnant women have declined sharply over the 
      past few decades, phthalates exposure was still associated with an increased risk 
      of early miscarriage. Our findings suggest that future researchers and policy 
      makers might need to take low-dose effects of phthalates into account regarding 
      the reproductive toxicity of phthalates exposure in humans. SIGNIFICANCE: Our 
      findings contribute to the awareness of the reproductive toxic potential of 
      phthalates at low levels in humans and support the ongoing efforts to further 
      reduce exposure to phthalates.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
FAU - Ji, Honglei
AU  - Ji H
AD  - NHC Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical 
      and Pharmaceutical Technologies, Shanghai, China.
FAU - Wu, Zhiping
AU  - Wu Z
AD  - Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and 
      Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
FAU - Chen, Da
AU  - Chen D
AD  - School of Environment, Guangdong Key Laboratory of Environment Pollution and 
      Health, Jinan University, Guangzhou, China.
FAU - Miao, Maohua
AU  - Miao M
AD  - NHC Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical 
      and Pharmaceutical Technologies, Shanghai, China.
FAU - Chen, Hexia
AU  - Chen H
AD  - School of Environment, Guangdong Key Laboratory of Environment Pollution and 
      Health, Jinan University, Guangzhou, China.
FAU - Shuai, Wen
AU  - Shuai W
AD  - Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and 
      Infant Hospital, School of Medicine, Tongji University, Shanghai, China. 
      shuaiwen@51mch.com.
FAU - Liang, Hong
AU  - Liang H
AUID- ORCID: 0000-0002-3430-9167
AD  - NHC Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical 
      and Pharmaceutical Technologies, Shanghai, China. lianghong@sibpt.com.
FAU - Yuan, Wei
AU  - Yuan W
AD  - NHC Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical 
      and Pharmaceutical Technologies, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20230323
PL  - United States
TA  - J Expo Sci Environ Epidemiol
JT  - Journal of exposure science & environmental epidemiology
JID - 101262796
SB  - IM
OTO - NOTNLM
OT  - Case-control study
OT  - Di(2-ethylhexyl) phthalate
OT  - Miscarriage
OT  - Phthalates
OT  - Spontaneous abortion
EDAT- 2023/03/25 06:00
MHDA- 2023/03/25 06:00
CRDT- 2023/03/24 00:23
PHST- 2022/11/07 00:00 [received]
PHST- 2023/02/27 00:00 [accepted]
PHST- 2023/02/25 00:00 [revised]
PHST- 2023/03/24 00:23 [entrez]
PHST- 2023/03/25 06:00 [pubmed]
PHST- 2023/03/25 06:00 [medline]
AID - 10.1038/s41370-023-00533-1 [pii]
AID - 10.1038/s41370-023-00533-1 [doi]
PST - aheadofprint
SO  - J Expo Sci Environ Epidemiol. 2023 Mar 23. doi: 10.1038/s41370-023-00533-1.