Volume 33 Issue 11
Nov.  2020
Turn off MathJax
Article Contents

JIN Yu Ting, DENG Xiao Kai, ZHAO Ying Ya, LI Jia Lin, SONG Qi, ZHANG Yun Hui, YANG Qing, CHEN Shang Qin. Concentrations of Polybrominated Diphenyl Ethers in Maternal Blood, Placental Size, and Risk for Fetal Growth Restriction: A Nested Case-control Study[J]. Biomedical and Environmental Sciences, 2020, 33(11): 821-828. doi: 10.3967/bes2020.112
Citation: JIN Yu Ting, DENG Xiao Kai, ZHAO Ying Ya, LI Jia Lin, SONG Qi, ZHANG Yun Hui, YANG Qing, CHEN Shang Qin. Concentrations of Polybrominated Diphenyl Ethers in Maternal Blood, Placental Size, and Risk for Fetal Growth Restriction: A Nested Case-control Study[J]. Biomedical and Environmental Sciences, 2020, 33(11): 821-828. doi: 10.3967/bes2020.112

Concentrations of Polybrominated Diphenyl Ethers in Maternal Blood, Placental Size, and Risk for Fetal Growth Restriction: A Nested Case-control Study

doi: 10.3967/bes2020.112
Funds:  This work was supported by the National Natural Science Foundation of China [No. 21577026]
More Information
  • Author Bio:

    JIN Yu Ting, female, born in 1993, Master candidate, majoring in pediatrics

  • Corresponding author: CHEN Shang Qin, Tel: 86-13819735725, E-mail: csq5725@126.com; YANG Qing, Tel: 86-18918282166, E-mail: yqzjj888@126.com
  • Received Date: 2020-02-09
  • Accepted Date: 2020-07-22
  •   Objective  To explore the effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on placental size and birth outcomes.  Methods  Based on the perspective Wenzhou Birth Cohort, this nested case-control study included 101 fetal growth restriction (FGR) and 101 healthy newborns. Maternal serum samples were collected during the third trimester and measured for PBDEs by gas chromatography tandem mass spectrometry. The basic information of mother-newborn pairs was collected from questionnaires, whereas the placental size and birth outcomes of newborns were obtained from hospital records.  Results  A total of 19 brominated diphenyle ether (BDE) congeners were detected in maternal serum samples. Higher concentrations of BDE-207, -208, -209, and ∑19PBDEs were detected in FGR cases than in controls. Increased BDE-207, -208, -209, and ∑19PBDEs levels in maternal serum were related to decreased placental length, breadth, surface area, birth weight, birth length, gestational age, and Quetelet index of newborns. After adjusting for confounders, BDE-207 and ∑19PBDE concentrations in maternal serum were significantly associated with an increased risk of FGR.  Conclusion  A negative association was found between PBDE levels in maternal serum and placental size and birth outcomes. Prenatal PBDE exposure may be associated with elevated risk of the incidence of FGR birth.
  • 加载中
  • [1] de Wit CA. An overview of brominated flame retardants in the environment. Chemosphere, 2002; 46, 583−624. doi:  10.1016/S0045-6535(01)00225-9
    [2] Abbasi G, Li L, Breivik K. Global historical stocks and emissions of PBDEs. Environ Sci Technol, 2019; 53, 6330−40. doi:  10.1021/acs.est.8b07032
    [3] Genuis SK, Birkholz D, Genuis SJ. Human excretion of polybrominated diphenyl ether flame retardants: blood, urine, and sweat study. Bio Med Res Int, 2017; 2017, 3676089.
    [4] Jiang H, Lin ZK, Wu YY, et al. Daily intake of polybrominated diphenyl ethers via dust and diet from an e-waste recycling area in China. J Hazard Mater, 2014; 276, 35−42. doi:  10.1016/j.jhazmat.2014.05.014
    [5] Ni K, Lu YL, Wang TY, et al. A review of human exposure to polybrominated diphenyl ethers (PBDEs) in China. Int J Hyg Environ Health, 2013; 216, 607−23. doi:  10.1016/j.ijheh.2013.02.002
    [6] Sharma D, Farahbakhsh N, Shastri S, et al. Intrauterine growth restriction-part 2. J Matern-Fetal Neonatal Med, 2016; 29, 4037−48. doi:  10.3109/14767058.2016.1154525
    [7] Kesavan K, Devaskar SU. Intrauterine growth restriction: postnatal monitoring and outcomes. Pediatr Clin North Am, 2019; 66, 403−23. doi:  10.1016/j.pcl.2018.12.009
    [8] Nardozza LMM, Caetano ACR, Zamarian ACP, et al. Fetal growth restriction: current knowledge. Arch Gynecol Obstet, 2017; 295, 1061−77. doi:  10.1007/s00404-017-4341-9
    [9] Gómara B, Herrero L, Ramos JJ, et al. Distribution of polybrominated diphenyl ethers in human umbilical cord serum, paternal serum, maternal serum, placentas, and breast milk from Madrid population, Spain. Environ Sci Technol, 2007; 41, 6961−8. doi:  10.1021/es0714484
    [10] Leonetti C, Butt CM, Hoffman K, et al. Brominated flame retardants in placental tissues: associations with infant sex and thyroid hormone endpoints. Environ Health, 2016; 15, 113. doi:  10.1186/s12940-016-0199-8
    [11] Zhao Y, Song Q, Cao ZJ, et al. Umbilical cord blood PBDEs concentrations in relation to placental size at birth. Chemosphere, 2018; 201, 20−4. doi:  10.1016/j.chemosphere.2018.02.121
    [12] van Abeelen AFM, de Rooij SR, Osmond C, et al. The sex-specific effects of famine on the association between placental size and later hypertension. Placenta, 2011; 32, 694−8. doi:  10.1016/j.placenta.2011.06.012
    [13] Hornung RW, Reed LD. Estimation of average concentration in the presence of nondetectable values. Appl Occup Environ Hyg, 1990; 5, 46−51. doi:  10.1080/1047322X.1990.10389587
    [14] McMaster-Fay RA. Failure of physiologic transformation of the spiral arteries of the uteroplacental circulation in patients with preterm labor and intact membranes. Am J Obstet Gynecol, 2004; 191, 1837−8.
    [15] Sheppard BL, Bonnar J. An ultrastructural study of utero-placental spiral arteries in hypertensive and normotensive pregnancy and fetal growth retardation. Br J Obstet Gynaecol, 1981; 88, 695−705. doi:  10.1111/j.1471-0528.1981.tb01268.x
    [16] Tong Z, Zhang XW, Chen BM, et al. The effect of subclinical maternal thyroid dysfunction and autoimmunity on intrauterine growth restriction: a systematic review and meta-analysis. Medicine, 2016; 95, e3677. doi:  10.1097/MD.0000000000003677
    [17] Mazdai A, Dodder NG, Abernathy MP, et al. Polybrominated diphenyl ethers in maternal and fetal blood samples. Environ Health Perspect, 2003; 111, 1249−52. doi:  10.1289/ehp.6146
    [18] Choi G, Kim S, Kim S, et al. Occurrences of major polybrominated diphenyl ethers (PBDEs) in maternal and fetal cord blood sera in Korea. Sci Total Environ, 2014; 491-2, 219−26. doi:  10.1016/j.scitotenv.2014.02.071
    [19] Shin MY, Lee S, Kim HJ, et al. Polybrominated diphenyl ethers in maternal serum, breast milk, umbilical cord serum, and house dust in a South Korean birth panel of mother-neonate pairs. Int J Environ Res Public Health, 2016; 13, 767. doi:  10.3390/ijerph13080767
    [20] Boon JP, Lewis WE, Tjoen-A-Choy MR, et al. Levels of polybrominated diphenyl ether (PBDE) flame retardants in animals representing different trophic levels of the North Sea food Web. Environ Sci Technol, 2002; 36, 4025−32. doi:  10.1021/es0158298
    [21] Thuresson K, Bergman Å, Jakobsson K. Occupational exposure to commercial decabromodiphenyl ether in workers manufacturing or handling flame-retarded rubber. Environ Sci Technol, 2005; 39, 1980−6. doi:  10.1021/es048511z
    [22] Darnerud PO, Lignell S, Aune M, et al. Time trends of polybrominated diphenylether (PBDE) congeners in serum of Swedish mothers and comparisons to breast milk data. Environ Res, 2015; 138, 352−60. doi:  10.1016/j.envres.2015.02.031
    [23] Miranda ML, Anthopolos R, Wolkin A, et al. Associations of birth outcomes with maternal polybrominated diphenyl ethers and thyroid hormones during pregnancy. Environ Int, 2015; 85, 244−53. doi:  10.1016/j.envint.2015.09.015
    [24] Vizcaino E, Grimalt JO, Fernández-Somoano A, et al. Transport of persistent organic pollutants across the human placenta. Environ Int, 2014; 65, 107−15. doi:  10.1016/j.envint.2014.01.004
    [25] Park HR, Kamau PW, Loch-Caruso R. Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro. Toxicol Appl Pharmacol, 2014; 274, 283−92. doi:  10.1016/j.taap.2013.11.015
    [26] Park HR, Loch-Caruso R. Protective effect of (±)α-tocopherol on brominated diphenyl ether-47-stimulated prostaglandin pathways in human extravillous trophoblasts in vitro. Toxicol in Vitro, 2015; 29, 1309−18. doi:  10.1016/j.tiv.2015.05.015
    [27] Manuguerra S, Espinosa Ruiz C, Santulli A, et al. Sub-lethal doses of polybrominated diphenyl ethers, in vitro, promote oxidative stress and modulate molecular markers related to cell cycle, antioxidant balance and cellular energy management. Int J Environ Res Public Health, 2019; 16, 588. doi:  10.3390/ijerph16040588
    [28] Zhao XM, Peng SQ, Xiang Y, et al. Correlation between prenatal exposure to polybrominated diphenyl ethers (PBDEs) and infant birth outcomes: a meta-analysis and an experimental study. Int J Environ Res Public Health, 2017; 14, 268. doi:  10.3390/ijerph14030268
    [29] Lopez-Espinosa MJ, Costa O, Vizcaino E, et al. Prenatal exposure to polybrominated flame retardants and fetal growth in the INMA Cohort (Spain). Environ Sci Technol, 2015; 49, 10108−16. doi:  10.1021/acs.est.5b01793
    [30] Zhao Y, Liu PC, Wang JY, et al. Umbilical cord blood PBDEs concentrations are associated with placental DNA methylation. Environ Int, 2016; 97, 1−6. doi:  10.1016/j.envint.2016.10.014
    [31] Kim S, Cho YH, Lee I, et al. Prenatal exposure to persistent organic pollutants and methylation of LINE-1 and imprinted genes in placenta: A CHECK cohort study. Environ Int, 2018; 119, 398−406. doi:  10.1016/j.envint.2018.06.039
  • 加载中
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Tables(5)

Article Metrics

Article views(197) PDF downloads(27) Cited by()

Proportional views
Related

Concentrations of Polybrominated Diphenyl Ethers in Maternal Blood, Placental Size, and Risk for Fetal Growth Restriction: A Nested Case-control Study

doi: 10.3967/bes2020.112
Funds:  This work was supported by the National Natural Science Foundation of China [No. 21577026]
  • Author Bio:

  • Corresponding author: CHEN Shang Qin, Tel: 86-13819735725, E-mail: csq5725@126.com YANG Qing, Tel: 86-18918282166, E-mail: yqzjj888@126.com

Abstract:   Objective  To explore the effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on placental size and birth outcomes.  Methods  Based on the perspective Wenzhou Birth Cohort, this nested case-control study included 101 fetal growth restriction (FGR) and 101 healthy newborns. Maternal serum samples were collected during the third trimester and measured for PBDEs by gas chromatography tandem mass spectrometry. The basic information of mother-newborn pairs was collected from questionnaires, whereas the placental size and birth outcomes of newborns were obtained from hospital records.  Results  A total of 19 brominated diphenyle ether (BDE) congeners were detected in maternal serum samples. Higher concentrations of BDE-207, -208, -209, and ∑19PBDEs were detected in FGR cases than in controls. Increased BDE-207, -208, -209, and ∑19PBDEs levels in maternal serum were related to decreased placental length, breadth, surface area, birth weight, birth length, gestational age, and Quetelet index of newborns. After adjusting for confounders, BDE-207 and ∑19PBDE concentrations in maternal serum were significantly associated with an increased risk of FGR.  Conclusion  A negative association was found between PBDE levels in maternal serum and placental size and birth outcomes. Prenatal PBDE exposure may be associated with elevated risk of the incidence of FGR birth.

JIN Yu Ting, DENG Xiao Kai, ZHAO Ying Ya, LI Jia Lin, SONG Qi, ZHANG Yun Hui, YANG Qing, CHEN Shang Qin. Concentrations of Polybrominated Diphenyl Ethers in Maternal Blood, Placental Size, and Risk for Fetal Growth Restriction: A Nested Case-control Study[J]. Biomedical and Environmental Sciences, 2020, 33(11): 821-828. doi: 10.3967/bes2020.112
Citation: JIN Yu Ting, DENG Xiao Kai, ZHAO Ying Ya, LI Jia Lin, SONG Qi, ZHANG Yun Hui, YANG Qing, CHEN Shang Qin. Concentrations of Polybrominated Diphenyl Ethers in Maternal Blood, Placental Size, and Risk for Fetal Growth Restriction: A Nested Case-control Study[J]. Biomedical and Environmental Sciences, 2020, 33(11): 821-828. doi: 10.3967/bes2020.112
    • Polybrominated diphenyl ethers (PBDEs) are flame-retardant additives that are widely used in aerospace, transportation, interior decoration, and other personal-care products to ensure fire safety[1]. PBDEs have been used since the 1970 s, until their toxicological effects (neurological, reproductive, immune toxicity and endocrine disruption) were found in a great deal of animal and epidemiological studies[2]. In general, people are exposed to PBDEs through dietary intake and respiratory and dermal absorption, and biological monitoring is used to estimate the exposure levels of PBDEs in humans. At present, the samples analyzed mainly include blood (e.g., whole blood, serum, plasma, and umbilical cord blood), urine, breast milk, hair, and tissues (e.g., fat, placenta, and liver)[3-5]. Maternal serum is the most commonly used bio sample to detect PBDE exposure level during pregnancy because of its easy availability.

      Fetal growth restriction (FGR) is defined as a developmental problem in which the growth rate of the fetus is lower than the expected growth potential of an infant due to placental compromise[6]. FGR is one of the prime reasons of perinatal–neonatal morbidity and mortality and one of the causes of long-term chronic diseases[7-8]. Previous PBDEs are detected in the umbilical cord blood and placental tissues, and the concentration of PBDEs in umbilical cord blood serum is closely related to the placental area, suggesting that PBDEs can pass through the placental barrier and further threaten fetal growth and development[9-11]. Nonetheless, no epidemiological evidence determines whether prenatal PBDE exposure can affect the FGR birth through disturbance of placental growth.

      In this study, we hypothesized that prenatal PBDE exposure can affect placental growth and lead to the increased risk of FGR birth. Therefore, a nested case-control study was designed to investigate the effects of prenatal PBDE exposure on placental size and birth outcomes of newborns based on a birth cohort in Wenzhou, China.

    • This research was a nested case-control study within the Wenzhou Birth Cohort, a prospective birth cohort study conducted at the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University in Wenzhou, China to investigate the associations of fetal growth and prenatal environmental endocrine disruptor exposure. Participants were enrolled in the cohort when they underwent prenatal examination at their second trimester. The exclusion criteria were pregnant women with pregnancy complications, including hypothyroidism and gestational diabetes mellitus, that have significant effects on fetal weight, who actively smoked or drank alcohol, and had delivered twins and malformed fetus. FGR was defined as the newborn infant with birth weight below the 10th percentile for the same gestational age. The healthy newborns were included as controls while matching with the FGR cases for infant sex and maternal age. FGR cases and controls were matched at 1:1 ratio. During the study period, we selected 101 FGR cases and matched 101 controls from 1,750 participants in Wenzhou Birth Cohort study. All participants signed written informed consent documents approved by the institutional review committee before participating in the study. The basic information of maternal-newborn pairs, such as maternal age, education level, monthly income, and pregnancy complications, was collected through questionnaires. Newborn birth weight, birth length, gestational age, sex, and delivery mode were obtained from hospital records. Quetelet index was calculated by the formula: birth weight/birth length × 1,000.

      Maternal serum samples were collected at 34 weeks of gestation by medical staff, coded, frozen, and kept at −80 °C until chemical analysis. The placenta parameters were measured by medical staff immediately after childbirth. Placental surface area (cm2) was calculated using the formula: length × breadth × π/4[12].

    • A total of 19 common brominated diphenyle ether (BDE) congeners (BDE-17, -28, -33, -47, -49, -66, -99, -100, -138, -153, -154, -183, -190, -196, -203, -206, -207, -208, and -209) were determined by gas chromatography coupled to mass spectrometry. The methods for extraction and instrumental analysis of PBDEs from blood specimen were described in our previous studies[11]. The limits of detection (LOD) of individual BDE congener were 0.10 ng/mL for lower-brominate BDE congeners and 0.25 ng/mL for higher-brominate BDE congeners. The concentrations of PBDEs were lipid weight adjusted (ng/g lipid weight). For concentrations below the LOD, we imputed a value equal to the LOD divided by the square root of two for data analysis[13].

    • Normally distributed continuous variables were expressed as mean ± standard deviation. For demographic characteristic, we used the Student’s t test to identify statistically significant differences in continuous variables and the χ2 test to identify differences in categorical variables. Mann–Whitney U test was used to assess the concentrations of BDE congeners between FGR cases and healthy controls in maternal serum samples.

      Multiple linear regression models were used to analyze the correlation of PBDE levels in maternal serum with placental growth indicator (length, breadth, and surface area) and birth outcomes (birth weight, birth length, gestational age, and Quetelet index). We used multivariate logistic regression to evaluate the correlation between the probability of FGR birth and the levels of PBDEs in maternal serum. Newborn’s sex, gestational age, maternal age, maternal education level, family annual income, and pregnancy syndrome were considered as potential confounders and adjusted in logistic regression models. SPSS 24.0 was used to perform statistical analyzes, and P < 0.05 was considered significant.

    • Overall, 202 maternal-infant pairs (101 FGR cases and 101 controls) were enrolled in the present study. The population characteristics of FGR cases and healthy newborns were listed and compared (Table 1). The average birth weight and gestational age of FGR cases were (2.29 ± 0.43) kg and (36.4 ± 4.0) weeks, respectively, which were significantly lower than those of the controls (3.31 ± 0.34) kg and (39.1 ± 1.1) weeks, respectively, P < 0.001). The Quetelet index of FGR cases was significantly lower than that of controls [(48.31 ± 7.56) vs. (66.03 ± 6.41), P < 0.001]. In terms of maternal feature, no significant difference was observed in the maternal age, delivery mode, monthly income, and pregnancy syndrome between the FGR cases and healthy controls. Regarding placental growth indicators, differences were detected in the placental length (17.03 vs. 18.37, P < 0.001), breadth (16.68 vs. 18.54, P < 0.001), and surface area (224.21 vs. 270.38, P < 0.001) between the FGR cases and controls.

      Demographic characteristicTotal (n = 202)FGR (n = 101)Control (n = 101)P-value
      Gestational age (weeks)37.8 ± 3.236.4 ± 4.039.1 ± 1.1< 0.001*
      Newborn’s birth weight (kg)2.81 ± 0.642.29 ± 0.433.31 ± 0.34< 0.001*
      Newborn’s birth length (cm)48.83 ± 3.7947.47 ± 5.0950.09 ± 0.69< 0.001*
      Quetelet index57.49 ± 11.2948.31 ± 7.5666.03 ± 6.41< 0.001*
      Maternal age (years)27.8 ± 4.327.1 ± 4.928.3 ± 3.70.097
      Placental indicator
       Length (cm)17.85 ± 2.2617.03 ± 1.9718.37 ± 2.29< 0.001*
       Breadth (cm)17.82 ± 2.2516.68 ± 2.1518.54 ± 2.00< 0.001*
       Surface area (cm2)252.39 ± 59.54224.21 ± 47.32270.38 ± 59.77< 0.001*
      Neonate’s sex0.778
       Male 964947
       Female1065254
      Delivery mode0.198
       Vaginal delivery 937122
       Cesarean delivery1097930
      Maternal education level0.011*
       Below high school 482721
       High school 885137
       College and above 662343
      Monthly income (Yuan)0.665
       < 5,000 793841
       > 5,0001236360
      Pregnancy syndrome0.150
       No1497079
       Yes 533122
        Note. *P-value < 0.05 is statistically significant.

      Table 1.  Demographic characteristic of maternal-newborn pairs

    • Table 2 shows the median (interquartile range) concentrations of PBDE congeners in maternal serum between the FGR and control groups. The detection rate of seven PBDE homologues were more than 50% (BDE-17, -47, -66, -153, -207, -208, and -209). The concentration of BDE-209 was the highest in the maternal serum of FGR cases and controls. The maternal serum PBDE concentrations of FGR group, especially BDE-207, -208, -209, and ∑19PBDEs, were significantly higher than those of healthy controls.

      PBDE congenerDetection rate (%)FGRControlP-value
      Median (P25, P75)Median (P25, P75)
      BDE-1764.40.644 (0.154, 1.594)0.436 (0.090, 1.040)0.140
      BDE-28&3340.00.175 (< LOD, 1.962)0.313 (< LOD, 1.498)0.934
      BDE-4756.90.524 (< LOD, 1.645)0.455 (<LOD, 1.255)0.279
      BDE-4926.7< LOD (< LOD, 0.322)< LOD (< LOD, 1.286)0.022*
      BDE-6663.90.540 (0.158, 3.751)0.526 (< LOD, 1.793)0.160
      BDE-9924.8< LOD (< LOD, 0.205)< LOD (< LOD, 0.435)0.929
      BDE-10029.2< LOD (< LOD, 0.298)< LOD (< LOD, 0.320)0.812
      BDE-13839.1< LOD (< LOD, 1.839)0.221 (< LOD, 1.941)0.371
      BDE-15365.32.531 (0.703, 5.348)1.825 (0.412, 3.122)0.059
      BDE-15431.2< LOD (< LOD, 0.391)< LOD (< LOD, 0.724)0.856
      BDE-1836.9< LOD (< LOD, < LOD)< LOD (< LOD, < LOD)0.040*
      BDE-1908.9< LOD (< LOD, < LOD)< LOD (< LOD, <LOD)0.366
      BDE-19624.3< LOD (< LOD, 0.704)< LOD (< LOD, 0.862)0.984
      BDE-20320.3< LOD (< LOD, 0.439)< LOD (< LOD, < LOD)0.690
      BDE-20646.01.709 (< LOD, 9.007)< LOD (< LOD, 3.379)0.035*
      BDE-20752.02.598 (< LOD, 8.449)0.698 (< LOD, 3.058)0.002*
      BDE-20855.01.562 (0.298, 5.259)1.041 (< LOD, 2.679)0.012*
      BDE-20957.47.867 (< LOD, 46.264)5.908 (< LOD, 18.732)0.045*
      19PBDEs83.731.948 (14.119, 93.455)22.630 (9.204, 43.939)0.009*
        Note. LOD: limit of detection.*P-value < 0.05 is statistically significant.

      Table 2.  PBDE level in maternal serum between FGR cases and controls (ng/g)

    • Table 3 shows the associations between maternal serum PBDE levels and placental size. A unit increase in BDE-17, -153, -207, -209, and ∑19PBDE concentrations in maternal serum was related to a decrease of 0.19–0.23 cm in placental length. Every unit increase in BDE-17, -153, -207, -208, -209, and ∑19PBDE concentrations was associated with 0.18–0.31 cm decrease in placental breadth. Similarly, concentrations of BDE-17, -153, -207, -208, -209, and ∑19PBDEs were significantly negatively correlated with the placental surface.

      PBDE congenerLengthBreadthSurface area
      BetaP-valueBetaP-valueBetaP-value
      BDE-17−0.2340.004*−0.1840.024*−0.2240.006*
      BDE-47−0.1220.135−0.0790.335−0.1070.191
      BDE-66−0.0310.705−0.0690.397−0.0410.618
      BDE-153−0.2330.004*−0.314< 0.001*−0.283< 0.001*
      BDE-207−0.1900.019*−0.2110.009*−0.2040.012*
      BDE-208−0.1040.201−0.2200.007*−0.1730.034*
      BDE-209−0.2090.010*−0.2700.001*−0.2520.002*
      19PBDEs−0.2280.005*−0.296< 0.001*−0.2740.001*
        Note. * P-value < 0.05 is statistically significant.

      Table 3.  Correlation between PBDE concentrations and placental indicator

    • Table 4 shows the relationships between maternal serum PBDE levels and birth outcome indicators, including birth weight, birth length, gestational age, and Quetelet index. A unit increase in BDE-47, -66, -153, -207, -208, -209, and ∑19PBDE concentrations was related to a decrease of 0.160.27 g in birth weight. Every unit increase in BDE-207, -208, -209, and ∑19PBDE concentrations were associated with 0.18, 0.21, 0.18, and 0.20 cm decreases in birth length, respectively. Meanwhile, gestational age significantly decreased with the increase in BDE-207, -208, -209, and ∑19PBDEs. Likewise, concentrations of BDE-47, -66, -153, -207, -208, -209, and ∑19PBDEs showed a significantly negative association with Quetelet index.

      PBDE congenerBirth weightBirth lengthGestational ageQuetelet index
      BetaP-valueBetaP-valueBetaP-valueBetaP-value
      BDE-17−0.1270.099−0.0410.599−0.0540.483−0.1260.106
      BDE-47−0.1620.036*−0.0580.461−0.1220.113−0.1730.026*
      BDE-66−0.2280.003*−0.1020.189−0.0860.266−0.2280.003*
      BDE-153−0.1830.017*−0.1390.075−0.1050.174−0.1800.020*
      BDE-207−0.268< 0.001*−0.1840.018*−0.1980.010*−0.2420.002*
      BDE-208−0.2530.001*−0.2130.006*−0.280< 0.001*−0.2040.008*
      BDE-209−0.2550.001*−0.1760.023*−0.2470.001*−0.2580.001*
      19PBDEs−0.284< 0.001*−0.2010.010*−0.2610.001*−0.277< 0.001*
        Note. * P-value < 0.05 is statistically significant.

      Table 4.  Correlation between PBDE concentrations and birth outcome indicator

    • The effect of each BDE congener on FGR birth was assessed after adjusting for potential confounders, including gestational age, education, monthly income, and pregnancy syndrome. As shown in Table 5, BDE-66 [odds ratio (OR) = 1.17; 95% confidence interval (CI): 1.04 to 1.32], BDE-153 (OR = 1.12; 95% CI: 1.01 to 1.23), BDE-207 (OR = 1.11; 95% CI: 1.04 to 1.19), BDE-208 (OR = 1.11; 95% CI: 1.03 to 1.20), BDE-209 (OR = 1.02; 95% CI: 1.01 to 1.03), and ∑19PBDEs (OR = 1.11; 95% CI: 1.00 to 1.02) concentrations in maternal serum were significantly associated with the increased risk of FGR. After adjusting for confounders, the association of BDE-207 (OR = 1.10; 95% CI: 1.02 to 1.19) and ∑19PBDE (OR = 1.01; 95% CI: 1.00 to 1.02) concentrations with FGR birth remained statistically significant.

      PBDE congenerUnadjustedAdjusteda
      OR (95% CI)P-valueOR (95% CI)P-value
      BDE-171.23 (0.92, 1.63)0.1571.21 (0.87, 1.67)0.254
      BDE-471.16 (0.99, 1.36)0.0581.13 (0.92, 1.38)0.249
      BDE-661.17 (1.04, 1.32)0.010*1.16 (0.98, 1.39)0.087
      BDE-1531.12 (1.01, 1.23)0.027*1.12 (0.98, 1.27)0.089
      BDE-2071.11 (1.04, 1.19)0.001*1.10 (1.02, 1.19)0.016*
      BDE-2081.11 (1.03, 1.20)0.006*1.10 (0.98, 1.23)0.125
      BDE-2091.02 (1.01, 1.03)0.003*1.01 (0.99, 1.03)0.092
      19PBDEs1.01 (1.00, 1.02)0.001*1.01 (1.00, 1.02)0.037*
        Note. *P-value < 0.05 is statistically significant;
      aAdjusting for gestational age, education, income, and pregnancy syndrome.

      Table 5.  Effects of PBDEs in maternal serum on FGR risk

    • Proper placental development is a necessary condition for a successful pregnancy, whereas abnormal placentation contributes to the pathophysiology of adverse birth outcomes[14-15]. FGR is a heterogeneous condition whose manifestation is usually due to placental compromise[16]. In the current study, we measured PBDE congener levels in maternal serum samples collected from 202 mother-newborn pairs to assess the contribution of prenatal exposure to PBDEs on placental size and FGR birth.

      The PBDE levels detected in the serum of pregnant women in Wenzhou city were lower than those in Indianapolis, USA[17] but higher than those in Korea[18-19]. Regional differences occurred in the concentration and congener profiles of PBDEs in vivo because of the diverse populations and environmental backgrounds and the usage of PBDEs in different areas and laboratory methods in various studies. In general, a low BDE-209 level was suspected in human blood because it is notably less likely to bioaccumulate[20]. High levels would thus mirror an ongoing high exposure to BDE-209, and in occupationally exposed individuals, the BDE-209 serum levels can be considerably higher. For example, a median level of BDE-209 of 35 ng/g was observed in the serum of Swedish rubber production workers[21]. In our study, the serum level of BDE-209 was the highest among all the PBDE congeners studied, followed by BDE-207 and BDE-153, which is similar to the research by Darnerud et al.[22]. BDE-209 is the most dominant congener in human serum from Southeast China. This condition may be due to the production and unrestricted usage of Deca-BDE in China.

      To our knowledge, PBDEs can cross the placenta, and maternal exposure may lead to fetal exposure during the period of gestation[23-24]. In this study, prenatal PBDE exposure may disturb placental growth as the result of reduced placental size, which is consistent with our previous finding[11]. Although the mechanism of improper placentation has not been fully elucidated, the role of impaired trophoblast invasion has been implicated in several studies[25-26]. Park et al.[26] showed that PBDEs increased the production of reactive oxygen species (ROS) to stimulate the response of prostaglandin, which might affect placental development because prostaglandins regulate the trophoblast functions necessary for placentation and pregnancy. Similarly, Manuguerra et al. observed that sub-lethal doses of PBDEs can increase the production of ROS over a long period time, altering the energetic metabolism, cell cycle, and antioxidant balance and determining possible adverse effects on cell multiplication balance[27].

      We also observed that the increased maternal serum PBDE concentration was related to the decrease in birth outcome indicators (birth weight, birth length, gestational age, and Quetelet index). The relationships among PBDE exposure, placenta size, and fetal growth support the assumption that the adverse effect of PBDE exposure on fetal growth may restrict placental growth. Zhao et al. discovered that prenatal PBDE exposure can adversely affect infant birth outcomes, especially birth weight[28]. Another research of Infancia y Medio Ambiente−Environment and Childhood Project in Spain also showed that PBDEs can impair fetal growth in late pregnancy and reduce birth size[29].

      Our study showed that maternal PBDE exposure level in FGR cases was significantly higher than that in controls, and the placental growth of FGR cases fell behind healthy infants. To the best of our knowledge, the size of placenta is directly proportional to its function, resulting in a reduction in the area of nutrition exchange between the pregnant woman and fetus[7]. Thus, maternal PBDE exposure may affect the development of the placenta and lead to FGR birth. Furthermore, the results of multivariate logistic regression indicated that high concentrations of PBDEs in maternal serum were associated with the risk of FGR birth. Our study raises growing concerns about the effect of exposure to PBDEs during pregnancy on birth outcomes.

      Changes in DNA methylation may play a critical key role in improper placenta development and therefore affect fetal growth. Placental DNA methylation is associated with intrauterine PBDE exposure[30]. A CHECK cohort study estimated the underlying relationship between DNA methylation in placental and neonatal outcomes. Their results showed that a unit percent increase in placental long interspersed element-1 methylation was correlated with a 0.19 cm decrease in birth length[31]. Thus, changes in DNA methylation in the placenta may be part of a potential biological pathway between PBDE exposure in the womb and FGR.

      The strength of this study lies in the design of nested case-control to evaluate the PBDE exposure of FGR infants during the prenatal and neonatal periods. Our results provide evidence for the important role of placenta in mediating the effects of prenatal exposure to PBDEs on fetal growth. Nevertheless, we acknowledge several limitations of our study. The sample size was relatively small, and maternal serum during pregnancy was only tested once. Although maternal blood in the third trimester may better reflect PBDE exposure during pregnancy, the availability of maternal blood in the first, second, and third trimester can yield more accurate findings. Thus, larger prospective cohort studies are needed to validate the findings of our study. Moreover, we lack data on other environmental contaminants, such as organochlorine, heavy metal pesticides, and polychlorinated biphenyls, which also adversely affect placenta and fetal growth.

    • In this study, we found a negative association between PBDE levels in maternal serum and placental size and birth outcome. Our results suggest that prenatal PBDE exposure may be associated with elevated risk of the incidence of FGR birth.

    • CHEN Shang Qin, ZHANG Yun Hui, and YANG Qing designed this work. JIN Yu Ting, ZHAO Ying Ya, LI Jia Lin, and SONG Qi performed the experiments and analyzed the data. JIN Yu Ting and DENG Xiao Kai wrote the manuscript.

    • The authors declare no conflicts of interest.

Reference (31)

Catalog

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return