背景:关于邻苯二甲酸酯和合成酚的产前暴露与青春期时间改变的关联的流行病学证据有限。
目的:研究产前邻苯二甲酸盐暴露的相关性,双酚A(BPA),对羟基苯甲酸酯,二苯甲酮3(BP-3),和三氯生(TCS)与青春期发育的女孩和男孩来自三个欧洲队列。
方法:六种不同邻苯二甲酸二酯的尿代谢产物(DEP,DiBP,DnBP,BBzP,DEHP,和DiNP),BPA,甲基-(MePB),乙基-(EtPB),丙基-(PrPB),和对羟基苯甲酸丁酯(BuPB),在怀孕期间(1999-2008年)从三个出生队列中的母亲那里收集的一个或两个(第1个和第3个月)尿液样本中对BP-3和TCS进行了定量:INMA(西班牙),EDEN(法国),和MoBa(挪威)。在7-12岁的一次访问中评估了其孩子的青春期发育(579名女孩,644名男孩)使用父母报告的青春期发育量表(PDS)。采用混合效应泊松和g计算以及贝叶斯核机器回归(BKMR)来检查个体和联合产前化学暴露的关联。分别,随着整体青春期发作的可能性,肾上腺素,女孩和男孩的性腺(第2阶段)。还评估了通过儿童体重指数(BMI)进行的效果修正。
结果:DEHP和DiNP代谢物摩尔总和的母体浓度与男孩开始青春期的概率稍高相关(相对风险,RR[95%CI]=1.13[0.98-1.30]和1.20[1.06-1.34],分别,浓度增加两倍),与超重或肥胖男孩的DiNP有更强的关联。相比之下,BPA,BuPB,EtPB,PrPB与青春期发作的概率较低有关,肾上腺素,和/或所有男孩的性腺(例如,整体青春期,BPA:RR[95%CI]=0.93[0.85-1.01]和BuPB:0.95[0.90-1.00],分别),在体重不足/体重正常的男孩中,与BPA的相关性更强。在女孩中,MEHP和BPA与低体重/正常体重者的迟发性性腺相关(RR[95%CI]=0.86[0.77-0.95]和0.90[0.84-0.97],分别)。这些关联中的大多数是特定于三个月的。然而,化学混合物与男孩或女孩的青春期结局无关.
结论:产前暴露于某些邻苯二甲酸盐和合成酚类如BPA可能会影响男孩的青春期发育,和体重状态可能会改变这种影响。BPA也可能改变女孩的青春期发育。
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.