Maternal serum concentrations of bisphenol A and propyl paraben in early pregnancy are associated with male infant genital development
Maternal serum concentrations of bisphenol A and propyl paraben in early pregnancy are associated with male infant genital development
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DOI：
10.1093/humrep/deaa045
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发表时间：
2020-04-01
影响因子：
6.1
通讯作者：
Acerini, C. L.
中科院分区：
文献类型：
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作者：
Fisher, B. G.;Thankamony, A.;Acerini, C. L.
研究问题：在妊娠10-17周时测量的母体血清邻苯二甲酸酯代谢物、苯酚和对羟基苯甲酸酯浓度是否与出生时和出生后的男婴生殖器发育结局（特别是隐睾、肛门与生殖器距离（AGD）、阴茎长度和睾丸下降距离）相关？总结回答：母体血清双酚A（BPA）浓度在妊娠10-17周与先天性或产后获得性隐睾症呈正相关，尼泊金丙酯（n-PrP）浓度与从出生到24个月龄的较短AGD相关。动物研究表明，邻苯二甲酸酯，BPA和对羟基苯甲酸酯，人类无处不在。然而，流行病学研究产生了相互矛盾的结果，并且通常受到样本量小和/或在最相关的发育窗口之外测量化学暴露的限制。研究设计、规模、持续时间：隐睾症前瞻性队列研究的病例对照研究（剑桥婴儿成长研究），在2001年至2009年期间，从英国一个产科单位招募了经后10-17周的孕妇，并进行了24个月的婴儿随访。在2229名被招募的妇女中，1640名妇女在分娩后继续进行婴儿期研究，其中330名妇女生了334名男婴（30例先天性隐睾，25例出生后获得性隐睾，279例未配对对照）纳入本分析。在入组时采集母体血液，并使用液相色谱/串联质谱法测量16种邻苯二甲酸酯代谢物、9种酚类（包括BPA）和6种对羟基苯甲酸酯的血清水平。Logistic回归模型隐睾症与血清化学浓度的关联，调整假定的混杂因素。此外，在0、3、12、18和24月龄时评估后代AGD、阴茎长度和睾丸下降距离，并计算年龄特异性Z评分。血清化学水平和这些结果之间的关联进行了测试，使用线性混合models.Main结果和机会的作用：母体血清BPA浓度与后代所有类型的隐睾症，无论是当被认为是一个连续的暴露（每log（10）μ g/l的校正比值比：2.90，95% CI 1.31-6.43，P= 0.009）和四分位数（p（het）= 0.002）。母体血清中n-PrP的检测与从出生到24月龄的较短AGD（0.242标准差，95%CI 0.051-0.433，P= 0.01）相关;这种降低与体型和其他假定的混杂因素无关。我们没有发现任何一致的关联与后代的结果为其他酚类，对羟基苯甲酸酯，邻苯二甲酸酯代谢物measurement.Limitations，理由回避：我们不能折扣混淆其他人口因素或内分泌干扰化学品。由于使用单一血清测量，可能对化学品暴露进行了错误分类。该队列是不完全代表孕妇在英国，特别是在吸烟率和产妇ethnicity.WIDER影响的调查结果：我们的观察结果支持实验证据表明，宫内暴露于BPA和N-PrP在妊娠早期可能会对男性生殖发育产生不利影响。在提出具体的公共卫生建议之前，需要更多的证据。
STUDY QUESTION: Are maternal serum phthalate metabolite, phenol and paraben concentrations measured at 10-17 weeks of gestation associated with male infant genital developmental outcomes, specifically cryptorchidism, anogenital distance (AGD), penile length and testicular descent distance, at birth and postnatally?SUMMARY ANSWER: Maternal serum bisphenol A (BPA) concentration at 10-17 weeks of gestation was positively associated with congenital or postnatally acquired cryptorchidism, and n-propyl paraben (n-PrP) concentration was associated with shorter AGD from birth to 24 months of age.WHAT IS KNOWN ALREADY: Male reproductive disorders are increasing in prevalence, which may reflect environmental influences on foetal testicular development. Animal studies have implicated phthalates, BPA and parabens, to which humans are ubiquitously exposed. However, epidemiological studies have generated conflicting results and have often been limited by small sample size and/or measurement of chemical exposures outside the most relevant developmental window.STUDY DESIGN, SIZE, DURATION: Case-control study of cryptorchidism nested within a prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at 10-17 postmenstrual weeks of gestation from a single UK maternity unit between 2001 and 2009 and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 330 mothers of 334 male infants (30 with congenital cryptorchidism, 25 with postnatally acquired cryptorchidism and 279 unmatched controls) were included in the present analysis.PARTICIPANTS/MATERIALS, SETTING, METHODS: Maternal blood was collected at enrolment, and serum levels of 16 phthalate metabolites, 9 phenols (including BPA) and 6 parabens were measured using liquid chromatography/tandem mass spectrometry. Logistic regression was used to model the association of cryptorchidism with serum chemical concentrations, adjusting for putative confounders. Additionally, offspring AGD, penile length and testicular descent distance were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between serum chemical levels and these outcomes were tested using linear mixed models.MAIN RESULTS AND THE ROLE OF CHANCE: Maternal serum BPA concentration was associated with offspring all-type cryptorchidism both when considered as a continuous exposure (adjusted odds ratio per log(10) mu g/l: 2.90, 95% CI 1.31-6.43, P= 0.009) and as quartiles (p(het)= 0.002). Detection of n-PrP in maternal serum was associated with shorter AGD (by 0.242 standard deviations, 95% CI 0.051-0.433, P= 0.01) from birth to 24 months of age; this reduction was independent of body size and other putative confounders. We did not find any consistent associations with offspring outcomes for the other phenols, parabens, and phthalate metabolites measured.LIMITATIONS, REASONS FOR CAUTION: We cannot discount confounding by other demographic factors or endocrine-disrupting chemicals. There may have been misclassification of chemical exposure due to use of single serum measurements. The cohort was not fully representative of pregnant women in the UK, particularly in terms of smoking prevalence and maternal ethnicity.WIDER IMPLICATIONS OF THE FINDINGS: Our observational findings support experimental evidence that intrauterine exposure to BPA and n-PrP during early gestation may adversely affect male reproductive development. More evidence is required before specific public health recommendations can be made.