BACKGROUND Prenatal exposure to endocrine-disrupting chemicals (EDCs) may disrupt normal fetal and postnatal growth. Studies have mainly focused on individual aspects of growth at specific time points using single chemical exposure models. However, humans are exposed to multiple EDCs simultaneously, and growth is a dynamic process. OBJECTIVE The objective of this study was to evaluate the associations between prenatal exposure to EDCs and children's body mass index (BMI) growth trajectories using single exposure and mixture modeling approaches. METHODS Using data from the INfancia y Medio Ambiente (INMA) Spanish birth cohort (n=1,911), prenatal exposure to persistent chemicals [hexachlorobenzene (HCB), 4-4'-dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCB-138, -150, and -180), 4 perfluoroalkyl substances (PFAS)] and nonpersistent chemicals (8 phthalate metabolites, 7 phenols) was assessed using blood and spot urine concentrations. BMI growth trajectories were calculated from birth to 9 years of age using latent class growth analysis. Multinomial regression was used to assess associations for single exposures, and Bayesian weighted quantile sum (BWQS) regression was used to evaluate the EDC mixture's association with child growth trajectories. RESULTS In single exposure models exposure to HCB, DDE, PCBs, and perfluorononanoic acid (PFNA) were associated with increased risk of belonging to a trajectory of lower birth size followed by accelerated BMI gain by 19%-32%, compared with a trajectory of average birth size and subsequent slower BMI gain [e.g., relative risk ratio (RRR) per doubling in DDE concentration=1.19 (95% CI: 1.05, 1.35); RRR for PFNA=1.32 (95% CI: 1.05, 1.66)]. HCB and DDE exposure were also associated with higher probability of belonging to a trajectory of higher birth size and accelerated BMI gain. Results from the BWQS regression showed the mixture was positively associated with increased odds of belonging to a BMI trajectory of lower birth size and accelerated BMI gain (odds ratio per 1-quantile increase of the mixture=1.70; credible interval: 1.03, 2.61), with HCB, DDE, and PCBs contributing the most. DISCUSSION This study provides evidence that prenatal EDC exposure, particularly persistent EDCs, may lead to BMI trajectories in childhood characterized by accelerated BMI gain. Given that accelerated growth is linked to a higher disease risk in later life, continued research is important. https://doi.org/10.1289/EHP11103.

中文翻译：

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Prenatal Exposure to Multiple Endocrine-Disrupting Chemicals and Childhood BMI Trajectories in the INMA Cohort Study.,INMA 队列研究中产前接触多种内分泌干扰化学物质和儿童期 BMI 轨迹。

BACKGROUND Prenatal exposure to endocrine-disrupting chemicals (EDCs) may disrupt normal fetal and postnatal growth. Studies have mainly focused on individual aspects of growth at specific time points using single chemical exposure models. However, humans are exposed to multiple EDCs simultaneously, and growth is a dynamic process. OBJECTIVE The objective of this study was to evaluate the associations between prenatal exposure to EDCs and children's body mass index (BMI) growth trajectories using single exposure and mixture modeling approaches. METHODS Using data from the INfancia y Medio Ambiente (INMA) Spanish birth cohort (n=1,911), prenatal exposure to persistent chemicals [hexachlorobenzene (HCB), 4-4'-dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCB-138, -150, and -180), 4 perfluoroalkyl substances (PFAS)] and nonpersistent chemicals (8 phthalate metabolites, 7 phenols) was assessed using blood and spot urine concentrations. BMI growth trajectories were calculated from birth to 9 years of age using latent class growth analysis. Multinomial regression was used to assess associations for single exposures, and Bayesian weighted quantile sum (BWQS) regression was used to evaluate the EDC mixture's association with child growth trajectories. RESULTS In single exposure models exposure to HCB, DDE, PCBs, and perfluorononanoic acid (PFNA) were associated with increased risk of belonging to a trajectory of lower birth size followed by accelerated BMI gain by 19%-32%, compared with a trajectory of average birth size and subsequent slower BMI gain [e.g., relative risk ratio (RRR) per doubling in DDE concentration=1.19 (95% CI: 1.05, 1.35); RRR for PFNA=1.32 (95% CI: 1.05, 1.66)]. HCB and DDE exposure were also associated with higher probability of belonging to a trajectory of higher birth size and accelerated BMI gain. Results from the BWQS regression showed the mixture was positively associated with increased odds of belonging to a BMI trajectory of lower birth size and accelerated BMI gain (odds ratio per 1-quantile increase of the mixture=1.70; credible interval: 1.03, 2.61), with HCB, DDE, and PCBs contributing the most. DISCUSSION This study provides evidence that prenatal EDC exposure, particularly persistent EDCs, may lead to BMI trajectories in childhood characterized by accelerated BMI gain. Given that accelerated growth is linked to a higher disease risk in later life, continued research is important. https://doi.org/10.1289/EHP11103.,背景技术产前接触内分泌干扰化学物质（EDC）可能会破坏胎儿和产后的正常生长。研究主要集中在使用单一化学品暴露模型的特定时间点生长的各个方面。然而，人类同时接触多种EDC，生长是一个动态过程。目的 本研究的目的是使用单一暴露和混合建模方法评估产前 EDC 暴露与儿童体重指数 (BMI) 生长轨迹之间的关联。方法 使用 INfancia y Medio Ambiente (INMA) 西班牙出生队列 (n=1,911) 的数据，产前接触持久性化学物质 [六氯苯 (HCB)、4-4'-二氯二苯基二氯乙烯 (DDE)、多氯联苯 (PCB-138、- 150 和 -180)、4 种全氟烷基物质 (PFAS)] 和非持久性化学物质（8 种邻苯二甲酸酯代谢物、7 种苯酚）通过血液和点尿浓度进行评估。使用潜在类别增长分析计算从出生到 9 岁的 BMI 增长轨迹。使用多项回归评估单次暴露的关联性，使用贝叶斯加权分位数总和 (BWQS) 回归评估 EDC 混合物与儿童生长轨迹的关联性。结果 在单次暴露模型中，与 19%-32% 的轨迹相比，暴露于 HCB、DDE、PCB 和全氟壬酸 (PFNA) 与出生体重较小轨迹的风险增加相关，随后 BMI 加速增加 19%-32%。平均出生尺寸和随后较慢的 BMI 增加[例如，DDE 浓度每倍增的相对风险比 (RRR)=1.19 (95% CI: 1.05, 1.35)；PFNA 的 RRR=1.32 (95% CI: 1.05, 1.66)]。HCB 和 DDE 暴露也与较高的出生体重轨迹和 BMI 增加的可能性相关。BWQS 回归结果显示，该混合物与属于较小出生体型的 BMI 轨迹的几率增加以及 BMI 加速增长呈正相关（混合物每增加 1 分位数的优势比 = 1.70；可信区间：1.03、2.61），其中 HCB、DDE 和 PCB 贡献最大。讨论 本研究提供的证据表明，产前 EDC 暴露，特别是持久性 EDC，可能会导致儿童时期 BMI 轨迹的特征为加速 BMI 增加。鉴于加速生长与晚年较高的疾病风险有关，持续的研究很重要。https://doi.org/10.1289/EHP11103。