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Abstract：
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been extensively used as synthetic fluorine-containing compounds in various consumer products, including surfactants, cookware, lubricants, clothing, and food packaging, since the 1950s. Evidence has shown that PFASs cross the placental barrier and interfere with fetal thyroid hormone homeostasis, which is crucial for fetal growth and neurobehavioral development in children aged 2-9 years. However, no epidemiological data on the association between prenatal PFAS exposure and neonatal neurobehavioral development are available. In this study, we explored the association between prenatal PFAS exposure and neonatal neurobehavioral development based on the Ezhou cohort study. Blood samples (10 mL) were collected during the third trimester of pregnancy (28-36 weeks) at the Ezhou maternal and child health hospital. The blood specimens were centrifuged at 4000 r/min for 15 min immediately after collection, separated, stored at -80 ℃. The samples were analyzed for seven PFASs, namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroheptanesulfonic acid (PFHpS), and perfluorooctane sulfonamide (PFOSA). The PFASs were separated using a C18 column (100 mm×2.1 mm, 1.7 μm) at an oven temperature of 40 ℃, injection volume of 10 μL, and flow rate of 0.4 mL/min via gradient elution with methanol and ammonium acetate aqueous solution. The instrument was operated in negative electrospray ionization mode with multiple reaction monitoring. The correlation coefficients (r2), limits of detection (LODs) and quantification (LOQs), and spiked recoveries of the seven PFASs were 0.993-0.999, 0.006-0.020 ng/mL, 0.020-0.066 ng/mL, and 84.6%-116.8%, respectively. Neonatal behavioral neurological assessment (NBNA) was used to evaluate newborn cognitive development 72 h after birth; this tool consisted of five clusters, including behavior (six items), passive muscle tone (four items), active muscle tone (four items), primitive reflexes (three items), and general assessment (three items). Each item was rated on a three-point scale (0, 1, or 2), with the 20 items having a maximum score of 40. A total of 379 mother-newborn pairs were included in the analysis. The PFASs with the highest exposure levels was PFOA, with median levels of 19.4 ng/mL. Linear regression models were used to test the effects of ln-converted PFAS levels in newborns. After adjusting for confounding factors, the linear regression model showed that PFOS exposure during pregnancy was associated with decreased active muscle tone(β(95% CI): 0.36(-0.64, 0.08)) and general assessment(β(95% CI): 0.34(-0.61, 0.07)) in all newborns. Furthermore, PFNA exposure was associated with decreased passive muscle tone(β(95% CI): 0.38(-0.74, 0.01)) and total NBNA(β(95% CI): 0.37(-0.68, 0.06)). PFDA exposure was associated with decreased behavior(β(95% CI): 0.28(-0.54, 0.01)), while PFHxS exposure was associated with elevated total NBNA(β(95% CI): 0.27(0.05-0.48)). Gender stratification analysis showed that PFOS exposure during pregnancy was associated with decreased active muscle tone(β(95% CI): 0.54(-0.73, 0.35)) and general assessment(β(95% CI): 0.50(-0.88, 0.13)), PFNA exposure during pregnancy was associated with decreased passive muscle tone(β(95% CI): 0.67(-1.2, 0.14)) and total NBNA(β(95% CI): 0.45(-0.91, 0.01)), PFDA exposure during pregnancy was associated with decreased behavior(β(95% CI): 0.44(-0.71, 0.17)), PFHxS exposure was associated with elevated total NBNA(β(95% CI): 0.41(0.02-0.80)) in male newborns, and PFOA exposure was associated with decreased general assessment(β(95% CI): -0.27(-0.51, 0.02)), and PFDA exposure was associated with elevated behavior(β(95% CI): 0.46(0.40-0.52)) in female newborns. The proposed method separates and detects various PFASs without the need for cumbersome pretreatment processes, and has the advantages of low LODs, satisfactory recoveries, and accurate precision. Thus, it allows for the simultaneous analysis of trace PFASs in microserum samples from pregnant women. Our results also showed that prenatal PFAS exposure can lead to neurobehavioral disorders in offspring, with male newborns showing greater sensitivity than female newborns.
摘要：
全氟烷基和多氟烷基物质（PFAS）已广泛用作各种消费品中的合成含氟化合物，包括表面活性剂,炊具,润滑剂服装,食品包装,自1950年代以来。有证据表明，PFASs穿过胎盘屏障并干扰胎儿甲状腺激素稳态，这对2-9岁儿童的胎儿生长和神经行为发育至关重要。然而,目前尚无关于产前PFAS暴露与新生儿神经行为发育之间关联的流行病学数据.在这项研究中,基于鄂州队列研究,我们探讨了产前PFAS暴露与新生儿神经行为发育的相关性.在鄂州市妇幼保健院收集妊娠晚期（28-36周）的血液样本（10mL）。血液标本采集后立即以4000r/min离心15min,分离,储存在-80℃。对样品进行了七个PFAS的分析，即,全氟辛酸（PFOA），全氟辛烷磺酸(PFOS)，全氟己烷磺酸盐(PFHxS)，全氟壬酸（PFNA），全氟癸酸（PFDA），全氟庚磺酸（PFHpS），和全氟辛烷磺酰胺(PFOSA)。使用C18柱(100mm×2.1mm，1.7μm),烘箱温度为40℃,注射体积为10μL，用甲醇和乙酸铵水溶液梯度洗脱,流速为0.4mL/min。仪器在负电喷雾电离模式下操作,具有多反应监测。相关系数(r2)，检测限(LOD)和定量(LOQ)，7种PFAS的加标回收率分别为0.993-0.999,0.006-0.020ng/mL,0.020-0.066ng/mL,和84.6%-116.8%，分别。新生儿行为神经评估（NBNA）用于评估新生儿出生后72小时的认知发育；该工具由五个聚类组成，包括行为(六个项目)，被动肌张力（四项），主动肌张力（四项），原始反射(三项)，和一般评估(三项)。每个项目都按三点量表(0、1或2)进行评级，20个项目的最高得分为40。共有379对母亲-新生儿被纳入分析。暴露水平最高的PFAS是PFOA，中位数水平为19.4ng/mL。线性回归模型用于测试ln转换的PFAS水平在新生儿中的影响。在调整混杂因素后，线性回归模型显示,在所有新生儿中,孕期全氟辛烷磺酸暴露与活动肌张力降低(β(95%CI):0.36(-0.64,0.08))和一般评估值(β(95%CI):0.34(-0.61,0.07))相关.此外，PFNA暴露与被动肌张力降低（β（95％CI）：0.38（-0.74，0.01））和总NBNA（β（95％CI）：0.37（-0.68，0.06））相关。PFDA暴露与行为减少相关（β（95％CI）：0.28（-0.54，0.01）），而PFHxS暴露与总NBNA升高相关(β(95%CI):0.27(0.05-0.48))。性别分层分析表明，怀孕期间全氟辛烷磺酸暴露与活动肌张力降低（β（95％CI）：0.54（-0.73，0.35））和一般评估（β（95％CI）：0.50（-0.88，0.13））有关，怀孕期间PFNA暴露与被动肌张力降低（β（95％CI）：0.67（-1.2，0.14））和总NBNA（β（95％CI）：0.45（-0.91，0.01））相关，怀孕期间PFDA暴露与行为减少相关（β（95％CI）：0.44（-0.71，0.17）），PFHxS暴露与男性新生儿的总NBNA升高相关（β（95％CI）：0.41（0.02-0.80）），PFOA暴露与一般评估降低相关（β（95％CI）：-0.27（-0.51，0.02）），PFDA暴露与女性新生儿行为升高相关(β(95%CI):0.46(0.40-0.52))。所提出的方法分离和检测各种PFAS，而无需繁琐的预处理过程，具有低LOD的优点，令人满意的回收率，和精确的精度。因此，它允许同时分析孕妇微血清样品中的痕量PFASs。我们的研究结果还表明，产前暴露于PFAS会导致后代的神经行为障碍，男性新生儿比女性新生儿表现出更大的敏感性。
