北京学龄儿童有机磷酸酯暴露与血压的纵向关联

肖惠迪; 李梦龙; 叶尔林·阿斯哈尔; 关梦颖; 邹雨辰; 吐尔逊阿依·阿不都米吉提; 赵瑞兰; 胡翼飞

doi:10.16835/j.cnki.1000-9817.2024129

北京学龄儿童有机磷酸酯暴露与血压的纵向关联

doi: 10.16835/j.cnki.1000-9817.2024129

1.
首都医科大学公共卫生学院儿少卫生与妇幼保健学系，北京 100069
2.
北京市顺义区疾病预防控制中心学校卫生科

基金项目:

首都卫生发展科研专项项目首发2022-1G-4262

国家自然科学基金项目 82073574

详细信息

作者简介:
肖惠迪(1998-)，女，北京市人，在读硕士，主要研究方向为儿童青少年慢性病预防

通讯作者:
赵瑞兰，E-mail: zhrl_1999@163.com

胡翼飞，E-mail: huyifei@yahoo.com

利益冲突声明 所有作者声明无利益冲突。
中图分类号: R179 TQ453.2⁺² R544
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出版历程
- 收稿日期: 2024-03-05
- 修回日期: 2024-03-19
- 网络出版日期: 2024-04-25
- 刊出日期: 2024-04-25

Longitudinal associations between organophosphate esters exposure and blood pressure among school-aged children in Beijing

1.
Department of Child, Adolescent Health and Maternal Care, School of Public Health, Capital Medical University, Beijing (100069), China

摘要

摘要: 目的分析儿童有机磷酸酯(OPEs)暴露与血压的纵向关联，为识别OPEs暴露对儿童健康影响提供参考依据。方法采用病例队列研究设计，纳入404名来自北京儿童生长与健康队列(PROC)的儿童，于2018年进行基线体格检查、尿液收集、问卷调查，并于2019—2020年和2023年开展随访，根据随访期间是否新发血压偏高分为病例组(n=140)和对照组(n=264)。采用高效液相色谱-质谱联用法检测尿液中二乙基磷酸酯(DEP)、双(2-氯乙基)磷酸酯(BCEP)、双(1-氯-2-丙基)磷酸酯(BCIPP)、二苯基磷酸酯(DPHP)、二丁基磷酸酯(DnBP)、双(1，3-二氯-2-丙基)磷酸酯(BDCIPP)、双(2-丁氧基乙基)磷酸酯(BBOEP)、双(2-丁氧基乙基)-2-羟基乙基磷酸酯(BBOEHEP)和4-羟基苯基二苯基磷酸酯(4-OH-TPHP)9种OPEs代谢物质量体积浓度；建立广义线性混合模型和Quantile g-computation模型分析OPEs单独及混合暴露与儿童血压的纵向关联。结果 3个时点(基线、第1次随访、第2次随访)DEP、BCEP、BCIPP、DPHP、DnBP、BDCIPP、BBOEP、BBOEHEP、4-OH-TPHP检出率范围分别为27.7%~92.1%，24.0%~99.3%，39.2%~90.9%。未调整儿童性别、年龄、体质量指数、Tanner分期、父母受教育程度、家庭月收入、高血压家族史等协变量前，BDCIPP质量体积浓度增加和OPEs混合暴露均可能降低儿童收缩压(β值分别为-0.85，-2.40，95%CI分别为-1.69~-0.01，-3.30~-1.50，P值均<0.05)；而调整协变量后，OPEs单独或混合暴露与儿童血压的纵向关联均无统计学意义(P值均>0.05)。结论北京学龄儿童普遍暴露于OPEs，虽未发现OPEs暴露与儿童血压之间存在纵向关联，仍建议应尽可能减少儿童暴露。
- 有机磷酸酯 /
- 血压 /
- 纵向研究 /
- 儿童
Abstract: Objective To explore the longitudinal association between organophosphate esters (OPEs) exposure and blood pressure in children, so as to provide a reference for identifying the effects of OPEs exposure on child health. Methods A total of 404 children from the Beijing Child Growth and Health Cohort (PROC) were enrolled using a case cohort study design, baseline physical examination, urine collection, questionnaires survey were administered in 2018 and follow-up surveys in 2019-2020 and 2023. Participants were divided into case group (n=140) and control group (n=264) according to the observation of new onset of high blood pressure during the follow-up period. High performance liquid chromatography-tandem mass spectrometry was used to detect diethyl phosphate (DEP), bis (2-chloroethyl) phosphate (BCEP), bis (1-chloro-2-propyl) phosphate, (BCIPP), diphenyl phosphate(DPHP), dibutyl phosphate (DnBP), bis (1, 3-dichloro-2-propyl) phosphate(BDCIPP), bis(2-butoxyethyl) phosphate(BBOEP), bis (2-butoxyethyl) 2-hydroxyethyl phosphate (BBOEHEP), 4-hydroxyphenyl diphenyl phosphate (4-OH-TPHP). Generalized linear mixed models and Quantile g-computation models were developed to analyze the longitudinal associations between OPEs individual/mixed exposure and blood pressure in children. Results The detection range of 9 OPEs metabolites, including DEP, BCEP, BCIPP, DPHP, DnBP, BDCIPP, BBOEP, BBOEHEP and 4-OH-TPHP at three time points (baseline, first follow-up and second follow-up) were 27.7%-92.1%, 24.0%-99.3% and 39.2%-90.9% respectively. Without adjustment for covariates such as gender, age, body mass index, Tanner stage, parental education, and monthly household income, and family history of hypertension, the increase of BDCIPP concentration and mixed exposure of OPEs may reduce children's systolic blood pressure(β=-0.85, -2.40, 95%CI=-1.69-0.01, -3.30-1.50, P<0.05). After adjusting for the covariates, the longitudinal association of individual OPEs or mixed exposure with pediatric BP was not statistically significant (P>0.05). Conclusion Children are commonly exposed to OPEs, and although no significant longitudinal associations are observed between exposure to OPEs and blood pressure among school-aged children in Beijing, it is recommended that child exposure should be minimized whenever possible.
- Organophosphate /
- Blood pressure /
- Longitudinal studies /
- Child
注释:

1) 利益冲突声明 所有作者声明无利益冲突。

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表 1 病例组与对照组儿童不同时期BMI及血压比较[M(P₂₅，P₇₅)]

Table 1. Comparison of BMI and blood pressure between case group and control group[M(P₂₅, P₇₅)]

组别	人数	BMI/(kg·m^-2)			收缩压/mmHg			舒张压/mmHg
组别	人数	基线	第1次随访	第2次随访	基线	第1次随访	第2次随访	基线	第1次随访	第2次随访
病例组	140	16.6(15.3，19.0)	17.3(15.6，20.2)	21.3(18.0，25.4)	103(96，107)	106(100，116)	120(109，125)	54(49，60)	59(53，63)	65(61，72)
对照组	264	15.5(14.3，16.8)	15.9(14.4，17.6)	18.6(16.1，21.9)	96(89，102)	99(94，104)	107(101，113)	53(48，58)	55(52，58)	61(57，66)
合计	404	15.8(14.7，17.5)	16.3(14.8，18.4)	19.2(16.6，23.5)	98(91，105)	101(96，107)	109(103，118)	54(49，59)	57(53，60)	62(58，68)
Z值		4.90	5.21	4.43	6.04	8.31	9.49	1.81	5.25	5.63
P值		< 0.01	< 0.01	< 0.01	< 0.01	< 0.01	< 0.01	0.07	< 0.01	< 0.01
注： 1 mmHg=0.133 kPa。

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表 2 不同时期儿童尿OPEs代谢物检测质量体积浓度比较[μg/L，M(P₂₅，P₇₅)]

Table 2. Comparison of urinary OPEs metabolites concentrations in children at different periods[μg/L, M(P₂₅, P₇₅)]

时期	人数	DEP	BCEP	BCIPP	DPHP	DnBP	BDCIPP	BBOEP	BBOEHEP	4-OH-TPHP
基线	379	1.17(0.53, 1.85)	< LOD(< LOD, 1.14)	< LOD(< LOD, 5.43)	2.63(1.71, 3.71)	1.77(< LOD, 3.88)	2.34(0.49, 4.83)	0.56(0.24, 1.41)	0.13(< LOD, 0.23)	0.36(< LOD, 0.88)
第1次随访	400	0.79(0.31, 1.40)	< LOD(< LOD, 0.91)	< LOD(< LOD,<LOD)	2.28(1.80, 3.38)	2.07(< LOD, 8.61)	2.87(1.26, 5.95)	1.35(0.68, 2.92)	0.10(< LOD, 0.18)	0.15(< LOD, 0.33)
第2次随访	383	0.45(0.25, 0.82)	< LOD(< LOD, 1.42)	6.03(< LOD, 9.19)	3.44(2.08, 7.81)	1.52(< LOD, 3.29)	2.78(1.65, 5.43)	1.53(0.36, 2.46)	0.17(0.11, 0.25)	0.30(< LOD, 0.67)
H值		117.17	6.97	146.16	80.39	13.80	17.01	79.81	68.14	81.47
P值		< 0.01	0.03	< 0.01	< 0.01	< 0.01	< 0.01	< 0.01	< 0.01	< 0.01
注：质量体积浓度未进行比重校正。

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表 3 OPEs单独暴露对儿童血压的纵向关联[β值(95%CI)，n=404]

Table 3. Longitudinal associations of OPEs individual exposure with blood pressure in children[β(95%CI), n=404]

自变量	收缩压		舒张压
自变量	调整前	调整后	调整前	调整后
DEP	-1.03(-2.21~0.15)	-0.25(-1.35~0.85)	0.35(-0.54~1.23)	0.49(-0.39~1.38)
DPHP	-0.94(-2.69~0.81)	-0.46(-2.07~1.15)	-0.28(-1.59~1.03)	0.06(-1.26~1.37)
DnBP	0.22(-0.91~1.36)	0.40(-0.64~1.45)	-0.23(-1.11~0.65)	-0.15(-1.02~0.73)
BDCIPP	-0.85(-1.69~-0.01)^*	-0.63(-1.41~0.14)	-0.47(-1.11~0.16)	-0.44(-1.07~0.20)
BBOEP	-0.75(-1.66~0.16)	-0.65(-1.50~0.19)	0.12(-0.57~0.81)	0.11(-0.58~0.80)
BBOEHEP	-0.61(-2.47~1.26)	0.53(-1.22~2.28)	0.80(-0.58~2.18)	1.02(-0.36~2.39)
4-OH-TPhP	-0.77(-1.76~0.22)	-0.63(-1.54~0.28)	-0.08(-0.82~0.67)	0.01(-0.72~0.75)
注： *P<0.05。调整儿童性别、年龄、BMI、Tanner分期、父母受教育程度、家庭月收入、高血压家族史。

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