Neonatal thyroid function in Seveso 25 years after maternal exposure to dioxin.
Neonatal thyroid function in Seveso 25 years after maternal exposure to dioxin.
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DOI：
10.1371/journal.pmed.0050161
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发表时间：
2008-07-29
期刊：
影响因子：
15.8
通讯作者：
Bertazzi PA
中科院分区：
文献类型：
--
作者：
Baccarelli A;Giacomini SM;Corbetta C;Landi MT;Bonzini M;Consonni D;Grillo P;Patterson DG;Pesatori AC;Bertazzi PA
在动物模型中，新生儿甲状腺功能减退与母亲暴露于几种环境污染物有关；然而，人类存在这种关联的证据并不一致。我们评估了母亲暴露于2,3,7,8-四氯二苯并-对二恶英（TCDD）（一种持久性和广泛存在的有毒环境污染物）是否与意大利塞韦索大量高暴露人群的新生儿甲状腺功能改变有关。在1994年至2005年期间，我们对1976年Seveso事故后暴露于TCDD的个体进行了：(i)对污染最严重地区（a，非常高污染；B，高污染）的1772名育龄妇女所生的1014名儿童进行了基于住所的人口研究，以及来自周围非污染地区的1772名年龄匹配的妇女（参考）；（ii）对51对可获得近期母体血浆二恶英测量值的母子进行生物标志物研究。对所有儿童进行新生儿血促甲状腺激素（b-TSH）测定。我们对性别、出生体重、出生顺序、产妇年龄、医院和分娩类型进行了调整，并进行了粗略和多变量分析。参考区（n = 533）新生儿平均B - tsh为0.98 μU/ml(95%可信区间[CI] 0.90-1.08)， B区（n = 425）新生儿平均B - tsh为1.35 μU/ml (95% CI 1.22-1.49)， A区（n = 56）新生儿平均B - tsh为1.66 μU/ml (95% CI 1.19-2.31) （p < 0.001）。B - tsh浓度为5 μU/ml的儿童在参比区为2.8%，B区为4.9%，A区为16.1% （p < 0.001）。新生儿b-TSH与当前母体血浆TCDD （n = 51, β = 0.47, p < 0.001）和血浆共面二恶英样化合物毒性当量（n = 51, β = 0.45, p = 0.005）相关。我们的数据表明，环境污染物，如二恶英有一个长期的能力，改变新生儿甲状腺功能后，初次接触。Andrea Baccarelli和他的同事发现，1976年意大利Seveso的工业事故发生后，母亲接触到二恶英，即使多年后新生儿甲状腺功能也会发生改变。甲状腺是颈部的一个蝴蝶状腺体，控制着人体将食物转化为生命所需的能量和化学物质的速度。在健康人体内，甲状腺制造和释放两种激素（在体内传播并调节特定细胞活动的化学信使），分别是甲状腺素（T4）和三碘甲状腺原氨酸（T3）。T4和T3的释放是由甲状腺分泌激素（TSH）控制的，TSH是由脑垂体对来自大脑的电信号作出反应而产生的。如果甲状腺停止产生足够的T4和T3，就会出现甲状腺功能减退症（甲状腺功能减退）。患有甲状腺功能减退症的成年人体重增加，感到寒冷，经常感到疲倦；患有甲状腺功能减退症的儿童也可能生长发育和智力发育不良。因为即使甲状腺激素水平的轻微下降也会增加垂体分泌的促甲状腺激素，所以甲状腺功能减退症通常是通过测量血液中促甲状腺激素的含量来诊断的；治疗方法是每日服用合成甲状腺激素左甲状腺素。虽然甲状腺功能减退症在老年妇女中最常见，但新生儿有时也有甲状腺功能减退症。如果不治疗，“新生儿”甲亢会导致严重的智力和身体发育迟缓，因此，在许多国家，血液TSH水平是在出生后不久测量的。这样，左旋甲状腺素治疗就可以在甲状腺激素缺乏对婴儿发育中的身体和大脑造成永久性损害之前开始。但是是什么导致了新生儿甲状腺功能减退呢？动物实验（以及一些但不是全部的人体研究）表明，母亲接触被称为二恶英的有毒化学物质可能是一个原因。二恶英是垃圾焚烧的副产品，在环境中持续存在，并在人体内积累。在这项研究中，研究人员通过研究1994年至2005年在意大利塞韦索附近出生的儿童，调查暴露于二恶英（二恶英中毒性最大的一种- 2,3,7,8-四氯二苯并对二恶英）是否会影响新生儿的甲状腺功能。1976年，一家化工厂的事故严重污染了这个小镇周围的地区，即使是现在，当地人的体内也含有大量的二恶英。研究人员确定了1772名育龄妇女，她们在事故发生时或事故发生后不久住在离Seveso工厂很近的地方（污染最严重的地区，A区），或离污染程度较低但仍然很高的地方（B区）稍远一些。作为对照，他们选择了居住在周围未受污染（参考）地区的1772名妇女。这些妇女在1994年至2005年间总共生了1014个孩子。生活在参考区的母亲所生的婴儿的新生儿血液TSH水平平均低于生活在A区的母亲所生的婴儿；B区婴儿的TSH水平中等。A区婴儿的年龄为6.6岁。TSH水平超过5 μU/ml的可能性是参照地区婴儿的两倍（进一步调查的TSH阈值为10 μU/ml，参照地区婴儿的平均TSH水平为0.98 μU/ml）。研究人员还对51对母婴进行了新生儿TSH测量和分娩时母体二恶英测量之间的关系（根据1992年至1998年的测量结果推断）。母亲血液中二恶英含量最高的婴儿，其新生儿TSH水平最高。这些发现表明，母亲接触二恶英对新生儿甲状腺功能有长期的有害影响。由于在这项研究中没有对儿童的长期进展进行检查，因此尚不清楚与二恶英接触有关的新生儿TSH测量值的增加是否会引起任何发育问题。然而，在轻度缺碘的地区（唯一与人类新生儿甲状腺功能下降一贯相关的环境暴露），促甲状腺激素水平升高到类似程度，并有证据表明智力和身体发育下降。未来对这群儿童的调查应该表明，塞维索事故（以及其他地方环境中高浓度的二恶英）的长期影响是否包括对儿童生长发育的任何影响。请通过本摘要的在线版本http://dx.doi.org/10.1371/journal.pmed.0050161访问这些网站。MedlinePlus百科全书提供有关甲状腺功能减退和新生儿甲状腺功能减退的信息；MedlinePlus提供了关于甲状腺疾病的更多信息的链接（英语和西班牙语）英国国家卫生服务直接健康百科全书提供了关于甲状腺功能减退的信息Nemours基金会的kidhealth网站有关于儿童甲状腺疾病的信息Toxtown，这是一个来自美国国家科学图书馆的互动网站。提供有关环境健康问题的信息，包括接触二恶英（英语和西班牙语）有关二恶英的更多信息由美国环境保护署和美国食品和药物管理局提供，维基百科有一个关于塞韦索灾难的页面（注：维基百科是一个免费的在线百科全书，任何人都可以编辑；有几种语言版本）
Neonatal hypothyroidism has been associated in animal models with maternal exposure to several environmental contaminants; however, evidence for such an association in humans is inconsistent. We evaluated whether maternal exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a persistent and widespread toxic environmental contaminant, is associated with modified neonatal thyroid function in a large, highly exposed population in Seveso, Italy. Between 1994 and 2005, in individuals exposed to TCDD after the 1976 Seveso accident we conducted: (i) a residence-based population study on 1,014 children born to the 1,772 women of reproductive age in the most contaminated zones (A, very high contamination; B, high contamination), and 1,772 age-matched women from the surrounding noncontaminated area (reference); (ii) a biomarker study on 51 mother–child pairs for whom recent maternal plasma dioxin measurements were available. Neonatal blood thyroid-stimulating hormone (b-TSH) was measured on all children. We performed crude and multivariate analyses adjusting for gender, birth weight, birth order, maternal age, hospital, and type of delivery. Mean neonatal b-TSH was 0.98 μU/ml (95% confidence interval [CI] 0.90–1.08) in the reference area (n = 533), 1.35 μU/ml (95% CI 1.22–1.49) in zone B (n = 425), and 1.66 μU/ml (95% CI 1.19–2.31) in zone A (n = 56) (p < 0.001). The proportion of children with b-TSH > 5 μU/ml was 2.8% in the reference area, 4.9% in zone B, and 16.1% in zone A (p < 0.001). Neonatal b-TSH was correlated with current maternal plasma TCDD (n = 51, β = 0.47, p < 0.001) and plasma toxic equivalents of coplanar dioxin-like compounds (n = 51, β = 0.45, p = 0.005). Our data indicate that environmental contaminants such as dioxins have a long-lasting capability to modify neonatal thyroid function after the initial exposure. Andrea Baccarelli and colleagues show that maternal exposure to a dioxin following the industrial accident in Seveso, Italy in 1976 is associated with modified neonatal thyroid function even many years later. The thyroid, a butterfly-shaped gland in the neck, controls the speed at which the human body converts food into the energy and chemicals needed for life. In healthy people, the thyroid makes and releases two hormones (chemical messengers that travel around the body and regulate the activity of specific cells) called thyroxine (T4) and triiodothyronine (T3). The release of T4 and T3 is controlled by thyroid secreting hormone (TSH), which is made by the pituitary gland in response to electrical messages from the brain. If the thyroid stops making enough T4 and T3, a condition called hypothyroidism (an underactive thyroid) develops. Adults with hypothyroidism put on weight, feel the cold, and are often tired; children with hypothyroidism may also have poor growth and mental development. Because even a small reduction in thyroid hormone levels increases TSH production by the pituitary, hypothyroidism is often diagnosed by measuring the amount of TSH in the blood; it is treated with daily doses of the synthetic thyroid hormone levothyroxine. Although hypothyroidism is most common in ageing women, newborn babies sometimes have hypothyroidism. If untreated, “neonatal” hyperthyroidism can cause severe mental and physical retardation so, in many countries, blood TSH levels are measured soon after birth. That way, levothyroxine treatment can be started before thyroid hormone deficiency permanently damages the baby's developing body and brain. But what causes neonatal hypothyroidism? Animal experiments (and some but not all studies in people) suggest that maternal exposure to toxic chemicals called dioxins may be one cause. Dioxins are byproducts of waste incineration that persist in the environment and that accumulate in people. In this study, the researchers investigate whether exposure to dioxin (this name refers to the most toxic of the dioxins—2,3,7,8-Tetrachlorodibenzo-p-dioxin) affects neonatal thyroid function by studying children born near Seveso, Italy between 1994 and 2005. An accident at a chemical factory in 1976 heavily contaminated the region around this town with dioxin and, even now, the local people have high amounts of dioxin in their bodies. The researchers identified 1,772 women of child-bearing age who were living very near the Seveso factory (the most highly contaminated area, zone A) or slightly further away where the contamination was less but still high (zone B) at the time of the accident or soon after. As controls, they selected 1,772 women living in the surrounding, noncontaminated (reference) area. Altogether, these women had 1,014 babies between 1994 and 2005. The babies born to the mothers living in the reference area had lower neonatal blood TSH levels on average than the babies born to mothers living in zone A; zone B babies had intermediate TSH levels. Zone A babies were 6.6. times more likely to have a TSH level of more than 5 μU/ml than the reference area babies (the threshold TSH level for further investigations is 10 μU/ml; the average TSH level among the reference area babies was 0.98 μU/ml). The researchers also examined the relationship between neonatal TSH measurements and maternal dioxin measurements at delivery (extrapolated from measurements made between 1992 and 1998) in 51 mother–baby pairs. Neonatal TSH levels were highest in the babies whose mothers had the highest blood dioxin levels. These findings suggest that maternal dioxin exposure has a long-lasting, deleterious effect on neonatal thyroid function. Because the long-term progress of the children in this study was not examined, it is not known whether the increases in neonatal TSH measurements associated with dioxin exposure caused any developmental problems. However, in regions where there is a mild iodine deficiency (the only environmental exposure consistently associated with reduced human neonatal thyroid function), TSH levels are increased to a similar extent and there is evidence of reduced intellectual and physical development. Future investigations on the progress of this group of children should show whether the long-term legacy of the Seveso accident (and of the high environmental levels of dioxin elsewhere) includes any effects on children's growth and development. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050161. The MedlinePlus encyclopedia provides information about hypothyroidism and neonatal hypothyroidism; MedlinePlus provides links to additional information on thyroid diseases (in English and Spanish) The UK National Health Service Direct health encyclopedia provides information on hypothyroidism The Nemours Foundation's KidsHealth site has information written for children about thyroid disorders Toxtown, an interactive site from the US National Library of Science, provides information on environmental health concerns including exposure to dioxins (in English and Spanish) More information about dioxins is provided by the US Environmental Protection Agency and by the US Food and Drug Administration Wikipedia has a page on the Seveso disaster (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
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DOI：
10.1080/026520300283351
发表时间：
2000-04-01
影响因子：
2.9
作者：
Birnbaum, LS;Tuomisto, J
通讯作者：
Tuomisto, J
影响因子：
168.9
作者：
Landi, MT;Needham, LL;Caporaso, N
通讯作者：
Caporaso, N
影响因子：
10.4
作者：
Maervoet J;Vermeir G;Covaci A;Van Larebeke N;Koppen G;Schoeters G;Nelen V;Baeyens W;Schepens P;Viaene MK
通讯作者：
Viaene MK
影响因子：
8.8
作者：
Baccarelli, A;Pfeiffer, R;Landi, MT
通讯作者：
Landi, MT
影响因子：
12.7
作者：
CHEN, YCJ;YU, MLM;HSU, CC
通讯作者：
HSU, CC