Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA.
Chronic Disease Epidemiology, Yale School of Public Health, Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, New Haven, CT, USA.
Environ Res. 2019 Jan;168:254-260. doi: 10.1016/j.envres.2018.09.037. Epub 2018 Oct 1.
Phthalates and bisphenol A (BPA) are environmental contaminants that may affect early embryonic development.
To assess the association between phthalate metabolites and BPA with early pregnancy endpoints in a cohort of women followed from before conception.
We quantified 11 phthalate metabolites and BPA in 137 conception cycles from naturally conceived clinical pregnancies. Phthalate metabolites and BPA concentrations were measured in a pooled sample of three daily morning urine specimens. Daily urinary hormone measurements had previously been used to define ovulation, implantation, and corpus luteum rescue. We assessed associations between conception cycle exposures (phthalate biomarkers and BPA) and 1) time from ovulation to implantation; 2) type of corpus luteum rescue (timing and pattern of rise in progesterone: early, late, or no rise); and 3) rate of initial rise in hCG.
Mono(3-carboxypropyl) phthalate (MCPP) and mono-isobutyl phthalate (MiBP) were associated with earlier implantation (6-8 days vs. 9 days (the most commonly observed); per natural log-unit, OR (95% CI) = 2.8 (1.2, 6.7) and OR (CI) = 2.1 (1.2, 3.7), respectively). Monoethyl phthalate (MEP) was associated with later implantation (10-12 days vs. 9 days); OR (CI) = 1.5 (1.0, 2.1). Compared with implantation on day 9, BPA was significantly associated with both earlier and later implantation (OR=2.2 for both). Women with concentrations above the median of monobenzyl phthalate (MBzP) (p = 0.04) or above the median of the molar sum of four di(2-ethylhexyl) phthalate metabolites (∑DEHP) (p = 0.08) had a slower initial rise in hCG. Increasing MCPP was associated with an increased odds of a late rise rescue (OR (CI) = 2.9 (1.0, 8.5); late rise vs. early rise), while increasing MEP was associated with a no rise rescue (OR (CI) = 1.6 (0.9, 2.8); no rise vs. early rise).
The reported associations varied in their direction of effect, some potentially protective, others adverse. This may reflect the complexity with which these potential endocrine disrupting chemicals can be acting, but chance findings are also possible. Given that women continue to be exposed to these compounds (or their precursors), continued research on the effects they may have on pregnancy is warranted.
邻苯二甲酸酯和双酚 A(BPA)是环境污染物,可能会影响早期胚胎发育。
评估在一项从受孕前开始随访的女性队列中,邻苯二甲酸酯代谢物和 BPA 与早期妊娠结局之间的关联。
我们在 137 个自然受孕的临床妊娠周期中定量检测了 11 种邻苯二甲酸酯代谢物和 BPA。邻苯二甲酸酯代谢物和 BPA 浓度在每日清晨的三份尿液样本的混合样本中进行测量。此前,每日尿液激素测量曾用于定义排卵、着床和黄体补救。我们评估了受孕周期暴露(邻苯二甲酸酯生物标志物和 BPA)与 1)从排卵到着床的时间;2)黄体补救的类型(时间和孕酮升高模式:早期、晚期或无升高);以及 3)初始 hCG 升高率之间的关系。
邻苯二甲酸单(3-羧基丙基)酯(MCPP)和邻苯二甲酸单异丁酯(MiBP)与着床较早有关(6-8 天 vs. 9 天(最常见);每自然对数单位,OR(95%CI)=2.8(1.2, 6.7)和 OR(CI)=2.1(1.2, 3.7))。邻苯二甲酸单乙基己酯(MEP)与着床较晚有关(10-12 天 vs. 9 天);OR(CI)=1.5(1.0, 2.1)。与第 9 天着床相比,BPA 与着床过早和过晚均显著相关(OR=2.2)。单苄基邻苯二甲酸酯(MBzP)浓度中位数以上(p=0.04)或四种二(2-乙基己基)邻苯二甲酸酯代谢物摩尔总和中位数以上(∑DEHP)(p=0.08)的妇女 hCG 初始升高较慢。MCPP 浓度增加与黄体晚期升高的几率增加相关(OR(CI)=2.9(1.0, 8.5);晚期升高与早期升高),而 MEP 浓度增加与黄体无升高相关(OR(CI)=1.6(0.9, 2.8);黄体无升高与早期升高)。
报告的关联在其作用方向上存在差异,有些可能具有保护作用,有些则具有不利影响。这可能反映了这些潜在的内分泌干扰化学物质可能作用的复杂性,但也可能是偶然发现。鉴于女性仍在接触这些化合物(或其前体),有必要继续研究它们对妊娠可能产生的影响。