Department of Global and Community Health, George Mason University, Fairfax, VA, USA.
Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, NY, USA.
Environ Res. 2021 Apr;195:110763. doi: 10.1016/j.envres.2021.110763. Epub 2021 Jan 29.
Observational and experimental studies report associations between gestational phthalate exposure and fetal development, yet few data exist to characterize phthalate effects on head circumference (HC) or to estimate the impact of race or sex. To address this data gap, we enrolled 152 African American and 158 white mothers with uncomplicated singleton pregnancies from the Charleston, South Carolina (USA) metropolitan area in a prospective birth cohort. Study participants provided up to two urine specimens during mid and late gestation, completed a study questionnaire, and allowed access to hospital birth records. We measured eight phthalate monoester metabolites using liquid chromatography with tandem mass spectrometry, and calculated molar sums of phthalate parent diesters. After specific gravity correction, we tested for associations between phthalates and neonatal HC (cm) and cephalization index (cm/g) using multiple informant linear regression with inverse probability weighting to account for selection bias between repeated urine sampling, adjusted for maternal race, age, body mass index, education, and smoking. We explored interactions by maternal race and infant sex. A doubling of urinary monoethyl phthalate (MEP) concentration was associated with a -0.49% (95%CI: -0.95%, -0.02%) smaller head circumference, although seven other phthalate metabolites were null. There were no statistically significant associations with cephalization index. HC was larger for whites than African American newborns (p < 0.0001) but similar for males and females (p = 0.16). We detected interactions for maternal race with urinary monobutyl phthalate (MBP; p = 0.03), monobenzyl phthalate (MBzP; p = 0.01), monoethylhexyl phthalate (MEHP; p = 0.05), monomethyl phthalate (MMP; p = 0.02), and the sum of dibutyl phthalate metabolites (∑DBP; p = 0.05), in which reduced HC circumference associations were stronger among whites than African Americans, and interactions for sex with MBP (p = 0.08) and MiBP (p = 0.03), in which associations were stronger for females than males. Our results suggest that gestational phthalate exposure is associated with smaller neonatal HC and that white mothers and female newborns have greater susceptibility.
观察性和实验研究报告了妊娠邻苯二甲酸酯暴露与胎儿发育之间的关联，但很少有数据描述邻苯二甲酸酯对头围 (HC) 的影响，或估计种族或性别的影响。为了解决这一数据空白，我们招募了来自美国南卡罗来纳州查尔斯顿大都市区的 152 名非裔美国人和 158 名白人母亲，这些母亲均怀有单胎妊娠，她们参与了一项前瞻性出生队列研究。研究参与者在妊娠中期和晚期提供了多达两份尿液样本，完成了研究问卷，并允许我们查阅医院的分娩记录。我们使用液相色谱-串联质谱法测量了 8 种邻苯二甲酸单酯代谢物，并计算了邻苯二甲酸双亲二酯的摩尔总和。在比重校正后，我们使用具有逆概率加权的多信息线性回归来测试邻苯二甲酸与新生儿 HC（cm）和头围指数（cm/g）之间的关联，以解释重复尿液采样之间的选择偏差，调整了母亲的种族、年龄、体重指数、教育程度和吸烟状况。我们通过母亲的种族和婴儿的性别探索了相互作用。尿液中单乙基邻苯二甲酸酯 (MEP) 浓度增加一倍与头围缩小 0.49%（95%CI：-0.95%，-0.02%）相关，尽管另外 7 种邻苯二甲酸代谢物呈阴性。与头围指数无统计学显著关联。与非裔美国新生儿相比，白人新生儿的头围更大（p<0.0001），但男婴和女婴的头围相似（p=0.16）。我们检测到母体种族与尿液中单丁基邻苯二甲酸酯 (MBP；p=0.03)、单苄基邻苯二甲酸酯 (MBzP；p=0.01)、单乙基己基邻苯二甲酸酯 (MEHP；p=0.05)、单甲基邻苯二甲酸酯 (MMP；p=0.02) 和二丁基邻苯二甲酸酯代谢物总和 (∑DBP；p=0.05) 之间存在交互作用，其中 HC 周长关联在白种人中比非裔美国人更强，性别与 MBP（p=0.08）和 MiBP（p=0.03）之间存在交互作用，其中关联在女性中比男性更强。我们的结果表明，妊娠邻苯二甲酸酯暴露与新生儿头围较小有关，而白种母亲和女婴的易感性更高。
