A few days ago, an article from the WeChat public account The Intellectual — titled “A Tracking Study of Over Ten Thousand Pregnant Women Suggests: Some Traditional Chinese Medicines Double the Risk of Infant Deformities” — went viral across the internet and sparked widespread concern. I was initially unaware of this, until one of my patients — a female PhD candidate hoping to use Chinese medicine during preconception — returned barely ten minutes after her consultation, medication in hand, waving the article at me: “Can I still take this medicine?”
I was rather taken aback. Had high-quality evidence finally emerged? Had the medical world made a groundbreaking discovery? After quickly skimming through the article, I had a general sense of the situation: this was essentially a popular science piece in the vein of Under the Dome — compelling in its narrative, but not constituting clinical evidence. I proceeded to offer a professional explanation and reassured her that she could take her medication with confidence.
After returning home, I carefully studied the article. All of its content was sourced from a newly published cohort study: Peng T, Yin L-L, Xiong Y, et al. Maternal traditional Chinese medicine exposure and risk of congenital malformations: a multicenter prospective cohort study. Acta Obstet Gynecol Scand. 2023; 00: 1–9. doi:10.1111/aogs.14553
Upon close reading of the paper, I identified numerous concerns, which I present below for discussion.
Additionally, when I tried to reopen the article published by The Intellectual the following day, I found it had been deleted from the entire internet. However, I clearly remember that when I first saw the article, it had 96,000 views.
This piece is solely an academic discussion and does not concern any other matters. My heartfelt personal views can be found in the related video on Bilibili.
1. The paper states that the study received ethical approval from Suzhou People’s Hospital on March 14, 2017, and was registered with the Chinese Clinical Trial Registry on March 25, 2017, under registration number ChiCTR-SOC-17010976. Upon verification, this registration number was indeed filed by the paper’s authors — but the research content of the registered trial has no direct connection to the published paper.
The registered trial was a large-scale screening study aimed at establishing a systematic and standardized first-trimester (11–13+6 weeks) ultrasound screening protocol in China, including large-sample first-trimester ultrasound measurements, standard screening views, statistics on first-trimester ultrasound detection rates of fetal malformations across various systems, and analysis of related high-risk factors.
The registered study design listed only three hospitals and involved no traditional Chinese medicine (TCM) content whatsoever. It did not collect information on pregnant women’s TCM use, nor did it track the incidence of neonatal malformations at 42 days postpartum. Yet all of these elements appear in the published paper. This constitutes clinical research conducted without ethical review — a violation of research regulations. Furthermore, the failure to report results in accordance with the registered study protocol raises serious questions about the paper’s authenticity.
2. The paper acknowledges funding from the National Natural Science Foundation of China (Grant No. 81671484), with the first author serving as the principal investigator. However, the paper’s content appears to have little connection to the funded project’s scope. Moreover, the ChiCTR registration explicitly states that the study was “sponsored by GE Healthcare Systems Trading & Development (Shanghai) Co., Ltd.” — a fact not disclosed in the paper, which states: “The authors have stated explicitly that there are no conflicts of interest in connection with this article.” This clearly fails to meet conflict-of-interest disclosure standards.
3. In the study design section, the paper cites Reference 14, which is the primary research report of the registered trial. The two papers share identical research methodologies but present different findings — a discrepancy the authors neither explain nor address, casting further doubt on the data’s authenticity.
4. According to the paper’s results, 289 pregnant women were exposed to TCM, of whom 10 developed congenital malformations. The authors analyzed the TCM medications taken by these 10 mothers. Most were Chinese patent medicines, but the specific dosage forms and active ingredients were not reported. The problem cannot be simply attributed to specific traditional Chinese medicines.
Furthermore, the authors’ discussion in Section 3.5 is perplexing. First, the third-to-last line reads “Among 28 TCM-exposed women” — likely a typographical error; it should read “Among 282 TCM-exposed women.” Second, the authors contend that “among the 289 pregnant women exposed to TCM, 2 of the 3 children born with congenital heart malformations had been exposed to medicines containing Spatholobus (Jixueteng), suggesting that Spatholobus may be associated with malformations.” This claim lacks clear supporting data. The relevant statistical P-value is 0.088, which does not meet the paper’s own threshold of P < 0.05 for statistical significance.
Third, the conclusion that Spatholobus may be teratogenic is not only unsupported by statistically significant data, but also accompanied by a puzzling absence of data in the paper. Figure S3, cited to support this claim, does not exist in the supplementary files — it is fabricated evidence. Although the authors did not mention Spatholobus in the abstract, the suggestion that it may be teratogenic appears in the results, discussion, and conclusion, and was prominently featured in The Intellectual‘s article.
1. Based on the study design, TCM exposure information prior to the first screening likely relied on subjects’ recall, introducing recall bias. In the supplementary file’s detailed TCM exposure information for mothers of infants with congenital malformations, one subject’s TCM exposure status is listed as “unknown” — meaning the medications taken (and thus the risks encountered) are not known. Such data carry considerable uncertainty and can, at best, establish a potential correlation.
2. As I mentioned earlier, Chinese patent medicines — particularly TCM injections and oral liquids — are more complex in composition than raw herbal decoctions due to manufacturing processes and other factors. They typically contain artificial sweeteners and preservatives. These additives themselves carry some teratogenic risk, and their interactions with TCM-derived extract components remain unknown, making it even more difficult to pinpoint the source of teratogenic risk.
3. Traditional Chinese medicine emphasizes pattern differentiation and individualized treatment. Blood-activating herbs such as Spatholobus are inherently contraindicated during pregnancy, and Pudilan was required to update its labeling in 2018 to add “use with caution during pregnancy.” A properly trained TCM practitioner would almost never prescribe such medications to pregnant women or those trying to conceive. As a TCM physician, I have reason to suspect that most of these prescriptions were written by Western medicine doctors. The teratogenic risks arising from such inappropriate prescribing should have been discussed in the paper — or at least acknowledged — especially given that the Longdan Xiegan Wan incident at the turn of the century already provided evidence of toxicity resulting from irrational use of Chinese medicine without proper pattern differentiation.
4. The paper makes no mention of data monitoring or quality control procedures, which could introduce measurement bias that statistical models cannot correct, while further undermining confidence in the data’s authenticity.
1. I believe the motivation behind this study was well-intentioned, its significance is considerable, and it was much needed — indeed, it should have been conducted long ago. This is essential work in the modernization of Chinese medicine, and it would greatly contribute to improving both the efficacy and safety of TCM therapies.
2. I hope that future TCM-related research will involve TCM researchers. Disciplinary barriers still exist, and it would be beneficial to hear more diverse perspectives. This is, after all, interdisciplinary work — not merely integrative East-West medicine research.
3. Given that the public account article triggered by this paper has already been deleted, it is evident that the original piece was rife with misinterpretations that would have misled the public. Its prompt removal was a wise decision.
I have reflected on why so many “popular science” articles misrepresent academic research — it likely stems from insufficient training in clinical research methodology among clinicians, or a fundamental lack of understanding of clinical science. I hope that medical schools will place greater emphasis on teaching medical research methodology. To my knowledge, there are still relatively few graduate programs in China that offer courses on TCM research methodology, and the quality of instruction leaves much to be desired.
4. I recommend that the authors promptly and proactively retract the paper, or at minimum issue a correction statement.
中文原文 / Chinese Original
这几天，一篇来自知识分子公众号《来自上万名孕妇的跟踪研究提示：部分中药导致婴儿畸形风险翻倍》文章火爆全网，引发了诸多关注。我本是不知道此事的，是我的一位病人，一位想用中药备孕的女博士，刚刚看完病拿完药，没过十分钟就拿着这篇文章来问我：这药还能吃吗？
我很是错愕，心想难道有高质量证据了？还是医学界有了惊天大发现？当快速浏览了一遍后心中大致有了数，这应该就是一篇类似于穹顶之下的科普文，不构成临床证据，于是我非常专业地解释并安慰她放心服药。
回家后，我仔细研读了那篇文章，里面的所有内容来自于一篇刚刚发表的队列研究报告：Peng, T, Yin, L-L, Xiong, Y, et al. Maternal traditional Chinese medicine exposure and risk of congenital malformations: a multicenter prospective cohort study. Acta Obstet Gynecol Scand. 2023; 00: 1–9. doi:10.1111/aogs.14553
当我仔细研读了这篇论文后，发现了诸多疑点，列出供诸位商榷。
另外，当我第二天再想打开知识分子发布的那篇文章时，我发现他已经被全网删除了。但是我清晰地记得，我在第一次看到那篇文章的时候，阅读量是9.6万。
本文仅为学术讨论，不涉及其他任何问题，本人发自肺腑的观点可见B站相关视频。
1、文中明确该研究已于2017年3月14日在苏州人民医院通过医学伦理审查，并于3月25日在中国临床试验注册中心注册，注册号为ChiCTR-SOC-17010976，经查证，该注册号确实是该文作者注册，但开展的研究内容与论文并无直接关联。
这是一个大规模筛查试验，主要研究建立中国系统规范的早孕期（孕11-13+6周）超声筛查体系，包括早孕期的大样本超声测值及筛查的标准切面，统计早孕期胎儿各系统畸形超声检出率，并分析相关的高危因素。
在该研究设计中，只列举了3家医院，完全不涉及任何中医药内容，不采集孕妇服用中药的信息，不统计产后42天新生儿畸形发生情况，然而这些内容均在论文中出现。这属于未经伦理审查的临床研究行为，属于违规操作，同时未按照研究方案报告研究结果，文章的真实性存疑。
2、该论文标注了中国国家自然科学基金National Natural Science Foundation of China (81671484)，该基金负责人为论文第一作者，论文内容与项目内容目测关系不大。同时，在ChiCTR注册的经费来源中明确该研究由”通用电气医疗系统贸易发展（上海）有限公司提供赞助”，在该论文中并未进行声明，”The authors have stated explicitly that there are no conflicts of interest in connection with this article.”显然不符合利益冲突声明规范。
3、论文中在研究设计部分引用了参考文献14，该文为注册项目的主要研究报告，这两篇论文的研究方法一致，但研究结果存在差异，这个差异论文作者并未进行解释，数据的真实性存疑。
4、论文结果中，中药暴露的孕妇共有289例，其中10例出现了先天畸形，作者分析了这10位母亲服用过的中药，其中绝大部分为中成药，但未报告具体的剂型、成分，不能简单将问题归因于具体中药上。
并且作者在3.5节的论述令人难以捉摸，首先倒数第三行”Among 28 TCM-exposed women,”可能是书写错误，应该为”Among 282 TCM-exposed women,”；其次，作者认为”289例中药暴露孕妇中出生了3例先天心脏畸形儿中有2例服用了含有鸡血藤的药物，所以鸡血藤可能与畸形的产生有关”，这个观点并没有明确的数据支撑，相关的统计学P值为0.088，不符合该论文规定的P<0.05为差异有统计学意义要求。
第三，鸡血藤可能致畸观点的得出不仅没有具有统计学意义的数据支撑，而且在论文中出现了令人难以理解的数据缺失，用于支持以上观点的Figure S3并不存在于补充文件中，属于无源之水。虽然作者并未在摘要中提及鸡血藤，但论文结果、讨论和结论中都出现了鸡血藤可能致畸的观点，并在知识分子公众号的文章中得到了重点宣传。
1、按照研究设计推断，第一次筛查前的中医药暴露信息可能主要依靠受试者回忆，存在回忆偏倚，在论文补充文件提供的先天畸形母亲中医药暴露详情中，有一个受试者的中医药暴露情况为”未知”，也就是不知道吃了什么药或者说暴露在什么风险下。这样的数据存在很大的不确定性，最多只能得出潜在的相关关系。
2、我在前文已经提及，中成药尤其是中药注射剂和中药口服液，在药物成分方面由于工艺及其他问题较中药饮片更为复杂，一般情况下都添加了甜味素和防腐剂。这些添加剂本身就存在一定的致畸风险，同时与中药提取成分的反应未知，更加难以确定致畸的风险来源。
3、中医讲究辨证论治，个体化诊疗，”鸡血藤”一类的活血中药本身就是孕妇的用药禁忌，蒲地蓝也已经在2018年被要求修改说明书，增加”孕妇慎用”字样。正常的中医基本不可能给孕妇或备孕妇女开具相关处方，作为一名中医我有理由怀疑这些大部分都是西医开具的处方，这种不合理用药造成的致畸风险情况应当在文中进行讨论，至少应当提出，毕竟本世纪初的龙胆泻肝丸事件已经对非辨证论治前提下不合理使用中药造成的毒性问题给出了一定证据。
4、论文中并未提到数据监督和质量控制方法，这会造成难以用统计学模型修正的测量偏倚，同时增加对数据真实性的怀疑。
1、我认为该研究的出发点是好的，意义很重大，很有必要做，而且早就应该做了，这是中医药现代化过程中必须要开展的一项工作，对于提高中医药疗效，提升中医药疗法的安全性具有很好的帮助。
2、我希望今后开展跟中医药相关的研究能够吸纳中医药科研人员，毕竟还是存在隔阂，多听听意见也是好的，而且这也属于学科交叉，并不是单纯的中西医结合研究。
3、鉴于由该文引发的公众号文章已经被删除，可见那篇文章中充满了对此文的误读，势必会对公众产生误导，及时删除是明智的选择。
我思考了一下为什么会出现这么多误读学术论文的”科普”文章，可能还是临床医生的临床科研思维不足或者对临床科学研究不了解所致，希望各大医学院校能够重视医学科研方法学的教学。据我所知，国内像我这样开设中医药科研方法学课程的研究生院还不是很多，讲授的内容差强人意。
4、建议论文作者及时主动撤稿，或者刊发更正声明。
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