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Abstract：
BACKGROUND: Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder. Risk is attributed to genetic and prenatal environmental factors, though the environmental agents are incompletely characterized.
METHODS: In Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk in Babies Learning Early Signs (MARBLES), two pregnancy cohorts of siblings of children with ASD, urinary metals concentrations during two pregnancy time periods (< 28 weeks and ≥ 28 weeks of gestation) were measured using inductively coupled plasma mass spectrometry. At age three, clinicians assessed ASD with DSM-5 criteria. In an exposure-wide association framework, using multivariable log binomial regression, we examined each metal for association with ASD status, adjusting for gestational age at urine sampling, child sex, age at pregnancy, race/ethnicity and education. We meta-analyzed across the two cohorts.
RESULTS: In EARLI (n = 170) 17% of children were diagnosed with ASD, and 44% were classified as having non-neurotypical development (Non-TD). In MARBLES (n = 231), 21% were diagnosed with ASD, and 14% classified as Non-TD. During the first and second trimester period (< 28 weeks), having cadmium concentration over the level of detection was associated with 1.69 (1.08, 2.64) times higher risk of ASD, and 1.29 (0.95, 1.75)times higher risk of Non-TD. A doubling of first and second trimester cesium concentration was marginally associated with 1.89 (0.94, 3.80) times higher risk of ASD, and a doubling of third trimester cesium with 1.69 (0.97, 2.95) times higher risk of ASD.
CONCLUSIONS: Exposure in utero to elevated levels of cadmium and cesium, as measured in urine collected during pregnancy, was associated with increased risk of developing ASD.
METHODS: In Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk in Babies Learning Early Signs (MARBLES), two pregnancy cohorts of siblings of children with ASD, urinary metals concentrations during two pregnancy time periods (< 28 weeks and ≥ 28 weeks of gestation) were measured using inductively coupled plasma mass spectrometry. At age three, clinicians assessed ASD with DSM-5 criteria. In an exposure-wide association framework, using multivariable log binomial regression, we examined each metal for association with ASD status, adjusting for gestational age at urine sampling, child sex, age at pregnancy, race/ethnicity and education. We meta-analyzed across the two cohorts.
RESULTS: In EARLI (n = 170) 17% of children were diagnosed with ASD, and 44% were classified as having non-neurotypical development (Non-TD). In MARBLES (n = 231), 21% were diagnosed with ASD, and 14% classified as Non-TD. During the first and second trimester period (< 28 weeks), having cadmium concentration over the level of detection was associated with 1.69 (1.08, 2.64) times higher risk of ASD, and 1.29 (0.95, 1.75)times higher risk of Non-TD. A doubling of first and second trimester cesium concentration was marginally associated with 1.89 (0.94, 3.80) times higher risk of ASD, and a doubling of third trimester cesium with 1.69 (0.97, 2.95) times higher risk of ASD.
CONCLUSIONS: Exposure in utero to elevated levels of cadmium and cesium, as measured in urine collected during pregnancy, was associated with increased risk of developing ASD.
摘要：
背景：自闭症谱系障碍（ASD）是一种普遍存在的异质性神经发育障碍。风险归因于遗传和产前环境因素，尽管环境因子的特征不完全。
方法：在早期自闭症风险纵向调查（EARLI）和婴儿学习早期体征（MARBLES）的自闭症风险标志物中，ASD儿童的兄弟姐妹的两个怀孕队列，使用电感耦合等离子体质谱法测量两个怀孕时间段(<28周和≥28周)的尿中金属浓度.三岁的时候,临床医生用DSM-5标准评估ASD。在广泛曝光的关联框架中，使用多变量对数二项回归，我们检查了每种金属与ASD状态的关联，在尿液取样时调整胎龄，儿童性,怀孕的年龄,种族/民族和教育。我们对这两个队列进行了荟萃分析。
结果：在EARLI（n=170）中，有17％的儿童被诊断为ASD，44％被归类为非神经典型发育（非TD）。在MARBLES（n=231）中，21%被诊断为ASD，14%被归类为非TD。在第一和第二个三个月期间（<28周），镉浓度超过检测水平与ASD的1.69（1.08，2.64）倍风险相关，是非TD风险的1.29(0.95，1.75)倍。第一和第二三个月铯浓度的加倍与ASD的1.89（0.94，3.80）倍的风险几乎相关。妊娠晚期铯增加了一倍，ASD的风险增加了1.69倍（0.97，2.95）。
结论：子宫内镉和铯含量升高，在怀孕期间收集的尿液中测量，与发展ASD的风险增加有关。
方法：在早期自闭症风险纵向调查（EARLI）和婴儿学习早期体征（MARBLES）的自闭症风险标志物中，ASD儿童的兄弟姐妹的两个怀孕队列，使用电感耦合等离子体质谱法测量两个怀孕时间段(<28周和≥28周)的尿中金属浓度.三岁的时候,临床医生用DSM-5标准评估ASD。在广泛曝光的关联框架中，使用多变量对数二项回归，我们检查了每种金属与ASD状态的关联，在尿液取样时调整胎龄，儿童性,怀孕的年龄,种族/民族和教育。我们对这两个队列进行了荟萃分析。
结果：在EARLI（n=170）中，有17％的儿童被诊断为ASD，44％被归类为非神经典型发育（非TD）。在MARBLES（n=231）中，21%被诊断为ASD，14%被归类为非TD。在第一和第二个三个月期间（<28周），镉浓度超过检测水平与ASD的1.69（1.08，2.64）倍风险相关，是非TD风险的1.29(0.95，1.75)倍。第一和第二三个月铯浓度的加倍与ASD的1.89（0.94，3.80）倍的风险几乎相关。妊娠晚期铯增加了一倍，ASD的风险增加了1.69倍（0.97，2.95）。
结论：子宫内镉和铯含量升高，在怀孕期间收集的尿液中测量，与发展ASD的风险增加有关。
