Association of prenatal exposure to phthalates and synthetic phenols with pubertal development in three European cohorts

IF 4.5 2区 医学 Q1 INFECTIOUS DISEASES International journal of hygiene and environmental health Pub Date : 2024-07-04 DOI:10.1016/j.ijheh.2024.114418
Carmen Freire , Francesca Castiello , Izaro Babarro , Augusto Anguita-Ruiz , Maribel Casas , Martine Vrijheid , Blanca Sarzo , Andrea Beneito , Manik Kadawathagedara , Claire Philippat , Cathrine Thomsen , Amrit Kaur Sakhi , Maria-Jose Lopez-Espinosa
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Abstract

Background

There is limited epidemiological evidence on the association of prenatal exposure to phthalates and synthetic phenols with altered pubertal timing.

Objective

To examine the association of prenatal exposure to phthalates, bisphenol A (BPA), parabens, benzophenone 3 (BP-3), and triclosan (TCS) with pubertal development in girls and boys from three European cohorts.

Methods

Urinary metabolites of six different phthalate diesters (DEP, DiBP, DnBP, BBzP, DEHP, and DiNP), BPA, methyl- (MePB), ethyl- (EtPB), propyl- (PrPB), and butyl-paraben (BuPB), BP-3, and TCS were quantified in one or two (1st and 3rd trimester) urine samples collected during pregnancy (1999–2008) from mothers in three birth cohorts: INMA (Spain), EDEN (France), and MoBa (Norway). Pubertal development of their children was assessed at a single visit at age 7–12 years (579 girls, 644 boys) using the parent-reported Pubertal Development Scale (PDS). Mixed-effect Poisson and g-computation and Bayesian Kernel Machine Regression (BKMR) were employed to examine associations of individual and combined prenatal chemical exposure, respectively, with the probability of overall pubertal onset, adrenarche, and gonadarche (stage 2+) in girls and boys. Effect modification by child body mass index (BMI) was also assessed.

Results

Maternal concentrations of the molar sum of DEHP and of DiNP metabolites were associated with a slightly higher probability of having started puberty in boys (relative risk, RR [95% CI] = 1.13 [0.98–1.30] and 1.20 [1.06–1.34], respectively, for a two-fold increase in concentrations), with a stronger association for DiNP in boys with overweight or obesity. In contrast, BPA, BuPB, EtPB, and PrPB were associated with a lower probability of pubertal onset, adrenarche, and/or gonadarche in all boys (e.g. overall puberty, BPA: RR [95% CI] = 0.93 [0.85–1.01] and BuPB: 0.95 [0.90–1.00], respectively), and the association with BPA was stronger in boys with underweight/normal weight. In girls, MEHP and BPA were associated with delayed gonadarche in those with underweight/normal weight (RR [95% CI] = 0.86 [0.77–0.95] and 0.90 [0.84–0.97], respectively). Most of these associations were trimester specific. However, the chemical mixture was not associated with any pubertal outcome in boys or girls.

Conclusions

Prenatal exposure to certain phthalates and synthetic phenols such as BPA may impact the pubertal development of boys, and weight status may modify this effect. BPA may also alter the pubertal development of girls.

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三个欧洲队列中产前接触邻苯二甲酸盐和合成酚与青春期发育的关系。
背景:关于产前暴露于邻苯二甲酸盐和合成酚与青春期时间改变之间的关系,流行病学证据有限:目的:研究三个欧洲队列中女孩和男孩产前接触邻苯二甲酸盐、双酚 A (BPA)、对羟基苯甲酸酯、二苯甲酮 3 (BP-3) 和三氯生 (TCS) 与青春期发育的关系:方法:从三个出生队列的母亲怀孕期间(1999-2008 年)采集的一份或两份(孕期第一和第三季度)尿液样本中,对六种不同邻苯二甲酸酯二聚体(DEP、DiBP、DnBP、BBzP、DEHP 和 DiNP)、双酚 A、甲基对羟基苯甲酸酯 (MePB)、乙基对羟基苯甲酸酯 (EtPB)、丙基对羟基苯甲酸酯 (PrPB) 和丁基对羟基苯甲酸酯 (BuPB)、BP-3 和三氯生 (TCS) 的尿液代谢物进行了定量分析:INMA(西班牙)、EDEN(法国)和 MoBa(挪威)。采用家长报告的青春期发育量表(PDS)对其子女(579 名女孩,644 名男孩)在 7-12 岁时的青春期发育情况进行了一次评估。采用混合效应泊松计算、g计算和贝叶斯核机器回归(BKMR)分别考察了单个和综合产前化学品暴露与女孩和男孩总体青春期发育、肾上腺发育和性腺发育(2+期)概率的关系。此外,还评估了儿童体重指数(BMI)对影响的修正作用:结果:母体中 DEHP 和 DiNP 代谢物摩尔总和的浓度与男童开始青春期的概率略高有关(浓度增加两倍,相对风险,RR [95% CI] = 1.13 [0.98-1.30] 和 1.20 [1.06-1.34]),在超重或肥胖的男童中,DiNP 的相关性更强。相比之下,BPA、BuPB、EtPB 和 PrPB 与所有男孩青春期开始、肾上腺皮质发育期和/或性腺发育期的概率较低有关(如整体青春期,BPA:RR[95%CI]=0.93[0.85-1.01],BuPB:0.95[0.90-1.00]),在体重不足/体重正常的男孩中,BPA 的相关性更强。在体重不足/体重正常的女孩中,MEHP 和 BPA 与性腺初潮延迟有关(RR [95% CI] 分别为 0.86 [0.77-0.95] 和 0.90 [0.84-0.97])。这些关联大多与孕期有关。然而,化学混合物与男孩或女孩的任何青春期结果都无关:结论:产前暴露于某些邻苯二甲酸盐和合成酚(如双酚 A)可能会影响男孩的青春期发育,而体重状况可能会改变这种影响。双酚 A 也可能会改变女孩的青春期发育。
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来源期刊
CiteScore
11.50
自引率
5.00%
发文量
151
审稿时长
22 days
期刊介绍: The International Journal of Hygiene and Environmental Health serves as a multidisciplinary forum for original reports on exposure assessment and the reactions to and consequences of human exposure to the biological, chemical, and physical environment. Research reports, short communications, reviews, scientific comments, technical notes, and editorials will be peer-reviewed before acceptance for publication. Priority will be given to articles on epidemiological aspects of environmental toxicology, health risk assessments, susceptible (sub) populations, sanitation and clean water, human biomonitoring, environmental medicine, and public health aspects of exposure-related outcomes.
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