Although this column usually reviews the safety and risks of medications during pregnancy and lactation, the safety of fish consumption during pregnancy is among the issues clinicians are asked about by their patients, and is among the queries we regularly receive at the Motherisk program at Toronto’s Hospital for Sick Children, because of the continuing controversy surrounding fetal safety.

This issue can be highly stressful for women. Although fish are a healthy source of protein that is low in saturated fat and contains omega-3 fatty acids, which may be important for fetal brain development, fish contain methylmercury, which is known to exert adverse effects on fetal brain development. The amount of methylmercury in fish varies widely depending on the type of fish. The U.S. Food and Drug Administration and the U.S. Environmental Protection Agency recommend that pregnant women not eat swordfish, shark, king mackerel, or tilefish, and that they limit their fish and shellfish intake to no more than 12 ounces a week (two average meals) of a variety of fish and shellfish that are lower in mercury.

The fact that methylmercury is a developmental neurotoxin has been established. What has not been clearly defined is the lowest concentration of maternal mercury that is associated with observable neurodevelopmental effects in the unborn child – a question that has been addressed by many scientists in many countries. In two recent studies, we provided new evidence that support testing maternal hair for mercury levels in some groups of pregnant women and suggests that analyzing a woman’s hair mercury content before she becomes pregnant might be useful.

In an attempt to define the lowest observable adverse effect level (LOAEL) of mercury, our group conducted a systematic literature review of 48 studies on the effects of prenatal exposure to mercury on the fetus, which used mercury levels in maternal hair samples to estimate prenatal methylmercury exposure. In the studies, adverse neurodevelopmental abnormalities were found at a range of maternal mercury levels based on results of hair sample analyses. We decided that the precautionary principle should prevail: There were variabilities among the studies, but we concluded that the lowest level – 0.3 mcg/g – at which adverse events were documented in at least one or two studies should be the level that should not be exceeded (Ther. Drug Monit. 2009;31:670-82).

We concluded that testing hair samples for methylmercury exposure is a powerful method of determining long-term exposure and is more accurate than estimating the amount of fish consumed.

We applied these consensus results to the clinical setting, which involved analyzing hair mercury levels and associating those levels with the amount of fish in the diet in three populations of reproductive-aged women living in Ontario: 23 Japanese women living in Toronto who ate fish every day, 22 pregnant women who ate fish regularly and called Motherisk with concerns, and 20 Canadian women who had no concerns about excessive consumption of fish. All the Japanese women, two-thirds of the women who called Motherisk, and 15% of the Canadian women who were not pregnant had levels that exceeded 0.3 mcg/g. The median level of mercury in the hair samples of the Japanese women was 1.7 mcg/g, significantly higher than the median level among those women who called Motherisk (0.4 mcg/g) and those in the general population (0.2 mcg/g). The study was published online in the Journal of Pediatrics (2010 March 24 [doi:10.1016/j.jpeds.2010.01.020]).

The median number of servings of fish per month was also significantly different among the three groups, with 10 servings a month among the Japanese women, 4 servings a month among the women who called Motherisk, and 3 servings a month among the Canadian women. As in other studies, the hair mercury level correlated with the amount of fish consumed. But the data suggested that in only half of the cases could the variability in hair mercury be accounted for by the amount of mercury estimated in the fish the women consumed: Even among some of the women whose fish intake fell within U.S. government recommendations for pregnant women, levels exceeded 0.3 mcg/g, which in the previous study, was assigned as the LOAEL.

Therefore, although women who follow the U.S. government recommendations are probably under the limit, our data show this is not universally true. The study had some limitations, but the results still indicate that following these guidelines may not be adequate to prevent the risk of exposure to levels exceeding the minimum associated with neurodevelopmental effects, and that checking mercury levels in women could be considered for certain groups of women before they get pregnant.

These findings are the basis of a new initiative at Motherisk, where women who call with concerns about fish intake are counseled about the recommended amount during pregnancy but are also offered the hair test. The test can be used to reassure these women that their levels are below 0.3 mcg/g.

The federal recommendations are based on the type of fish and amount eaten per week. The amount of mercury in fish is widely variable, however, so we recommend a hair mercury analysis for those women who eat more than the recommended amount of fish (more than two servings a week). Mercury hair testing is not widely available yet, but it is performed at most university medical centers.

This column, “Drugs, Pregnancy, and Lactation,” regularly appears in Ob.Gyn. News, an Elsevier publication. Dr. Koren is a professor of pediatrics, pharmacology, pharmacy, medicine, and medical genetics at the University of Toronto. He heads the Research Leadership in Better Pharmacotherapy During Pregnancy and Lactation at the Hospital for Sick Children, Toronto, where he is director of the Motherisk Program. He also holds the Ivey Chair in Molecular Toxicology at the department of medicine, University of Western Ontario, London. He had no disclosures related to the topic of this column. E-mail him at .

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

虽然本栏目通常讨论的是妊娠期和哺乳期药物治疗的安全性及风险，但妊娠期吃鱼的安全性也是患者向临床医生咨询的问题之一，鉴于围绕胎儿安全的争论持续存在，这也是加拿大多伦多儿童医院“母亲风险(Motherisk)”项目经常收到的问题之一。

 

这一问题可能会令妇女感到非常紧张。虽然鱼类是一种健康的蛋白质来源，其饱和脂肪含量低且含有ω-3脂肪酸，这对于胎儿的大脑发育可能起到了重要的作用，但鱼类还含有甲基汞，现已证实这种物质会对胎儿的大脑发育产生不良影响。不同的鱼类其甲基汞的含量也大不相同，具体取决于鱼的种类。美国食品药品管理局和美国环境保护署建议孕妇避免食用剑鱼、鲨鱼、马鲛鱼或马头鱼，对于其他汞含量相对较低的各种鱼类和贝类，则应将鱼类和贝类食品的摄入量控制在每周12盎司以内(平均两餐)。

 

甲基汞是一种神经发育毒素的事实已经得到了证实。目前尚未明确的是，对胎儿造成可观察到的神经发育影响的母体最低汞浓度是多少，这是一个来自各个国家的许多科学家一直在探索的问题。两项近期开展的研究显示，有新证据支持对于部分孕妇，应采集母体的头发样本以测定汞含量；研究还表明，在妇女怀孕之前就对其头发中的汞含量进行测定可能也很有用。

 

为了确定汞的可观察到有害作用的最低浓度(LOAEL)，我所在的研究小组对48项关于出生前汞暴露对胎儿影响的研究进行了系统评价，所纳入的研究是采用母体头发样本中的汞含量来估计出生前甲基汞的暴露量。这些研究表明，基于头发样本的分析结果，神经发育异常见于各种母体汞含量范围内。我们最终认为应以预防原则为主：虽然不同研究之间结果差异较大，但我们的结论是至少有一项或两项研究发现0.3 μg/g的汞浓度导致了不良事件，因此母体头发中的汞含量不应超过这一最低浓度(Ther. Drug Monit. 2009;31:670-82)。

 

我们总结道，通过检测头发样本来确定甲基汞的暴露量是一种测定长期暴露量的有效方法，较之估计鱼类的摄入量，这种方法更为准确。

 

我们将这些共识结果应用于临床，对3个居住在安大略省的育龄期妇女人群进行了头发中汞含量的测定，并分析了所测结果与膳食中鱼类摄入量之间的关系。这3个人群分别是：23例居住在多伦多且每天都食用鱼类的日本妇女；22例定期食用鱼类且曾致电“母亲风险”项目咨询问题的孕妇；以及20例对过量摄入鱼类并无担忧的加拿大妇女。在所有日本妇女、2/3的曾致电“母亲风险”项目的孕妇以及15%的非妊娠期加拿大妇女中，汞含量超过0.3 μg/g。日本妇女头发样本中的中位汞含量为1.7μg/g，显著高于曾致电“母亲风险”项目的孕妇(0.4μg /g)和一般人群(0.2μg /g)。该研究已在线发表于《儿科杂志》(Journal of Pediatrics) (2010 March 24 [doi:10.1016/j.jpeds.2010.01.020])。

 

这3个人群每个月食鱼份数的中位数也存在显著差异，日本妇女每个月10份，曾致电“母亲风险”项目的孕妇每个月4份，而加拿大妇女每个月3份。与其他研究所得出的结果一样，头发中的汞含量与鱼类的摄入量相关。但研究数据表明，只有一半的案例其头发中汞含量的差异是因这些妇女摄入的鱼类的汞含量有所不同所致：即便对于部分鱼类摄入量在美国政府推荐的范围之内的孕妇，其头发中的汞含量也超过了0.3 μg/g，0.3 μg/g即是前一项所确定的LOAEL。

 

因此，虽然那些遵照了美国政府推荐意见的妇女很可能不会超标，但我们的数据表明该原则并非普遍适用。这项研究固然存在一定的局限性，但结果仍提示遵从该指南建议可能不足以预防汞含量超标影响胎儿神经发育的风险。结果还表明，对于某些妇女，在怀孕前可能就需要考虑接受汞含量的检测。

 

基于上述研究发现，“母亲风险”项目开展了一项新行动，针对那些致电咨询鱼类摄入量问题的妇女，提供有关妊娠期推荐摄入量的咨询，并测定其头发中的汞含量。检测结果可用于打消这些妇女的疑虑，确认其头发中的汞含量低于0.3 μg/g。

 

联邦政府的推荐意见是基于鱼的种类以及每周的摄入量。但鉴于鱼类中的汞含量存在很大差异，因此我们建议那些鱼类摄入量超过了推荐摄入量(每周2份以上)的妇女，检测其头发中的汞含量。虽然这种检测技术目前尚未广泛普及，但大多数的大学附属医疗中心都可以开展这种检测。

 

本栏目“药物、妊娠与哺乳” 定期出现在Elsevier旗下期刊《妇产科新闻》（Ob.Gyn. News）中。Koren博士是加拿大多伦多大学儿科学、药学、药理学、内科学和医学遗传学教授，领导多伦多儿童医院“妊娠期和哺乳期药物治疗领先研究”计划，同时也是多伦多“母亲风险”项目的负责人。Koren博士还是位于伦敦市的西安大略大学内科系分子毒理学教席教授。Koren博士声明无相关利益冲突。如需回复，请致信Koren博士：。

 

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