A study links prenatal acetaminophen with reproductive changes in girls. Doctors say it remains safe to use when needed

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A new study found that some girls born to mothers who took acetaminophen during pregnancy developed reproductive organ changes that could affect fertility later in life. It’s a finding the study authors say should drive future research but shouldn’t yet change how certain symptoms are treated during pregnancy.

The new research doesn’t show that acetaminophen, also known as paracetamol or Tylenol, caused the reproductive changes. Women shouldn’t be “alarmed” by the findings because the research does not establish cause and effect, study co-author Dr. Margit Bistrup Fischer said.

It also does not mean pregnant women should stop taking acetaminophen if they need it, she noted, but “it’s definitely something we need as a society to talk about and inform pregnant women more about, so they can make an informed decision.”

Acetaminophen has long been known as the safest over-the-counter option to treat fever or pain during pregnancy, although doctors advise using it in moderation and only when necessary. An untreated fever can endanger both mother and fetus, possibly leading to birth defects or miscarriage .

Much more research is needed to determine whether it’s the over-the-counter medicine itself causing the changes or something else, said Fischer, a postdoctoral researcher in the Department of Growth and Reproduction at the Rigshospitalet in Copenhagen, Denmark.

The American College of Obstetricians and Gynecologists agreed that more study is needed, saying in a statement that the findings “do not indicate that current clinical recommendations should change. Consistent with ACOG’s existing guidance, acetaminophen remains one of the only safe medications that can be used during pregnancy when indicated, and patients should consult their obstetric care professional before making any changes to medication use.”

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Acetaminophen use during pregnancy became a hot-button issue last year when President Donald Trump told pregnant women with pain or fever to “tough it out” and avoid acetaminophen if possible, blaming, without evidence, the medicine and certain vaccines for autism .

Last year, the US Food and Drug Administration initiated a label change suggesting that acetaminophen use during pregnancy could put the fetus at risk of neurological conditions and alerted doctors that acetaminophen use during pregnancy can be associated with a “very increased risk of autism,” despite decades of evidence that it does not cause neurological problems and unsettled science on the connection between the medicine and autism.

Acetaminophen is the only over-the-counter drug that doctors and medical societies recommend pregnant people take for pain or fever, but organizations such as the American College of Obstetricians and Gynecologists advise using it only as needed, in moderation and after patients talk to their doctors. Aspirin and ibuprofen can pose serious risks to the mother and fetus, including miscarriage .

The new study focused on girls’ reproductive organs and did not examine any links to autism.

Fischer said she wanted to conduct the new research because several experimental animal studies showed that offspring of mothers given acetaminophen during pregnancy had smaller ovaries and fewer eggs. The medication appeared to interfere with egg formation and division in those experiments, Fischer said.

The new study , published this week in the journal Human Reproduction Open, is one of the first to assess human use. The scientists enrolled 685 women in Denmark during the first trimester of pregnancy, a crucial time for fetal development, and evaluated 302 of their baby girls when they were 3 months old.

The pregnant women logged their acetaminophen use and submitted urine samples so researchers could measure how much of the drug was in their system.

The study found that girls exposed to acetaminophen in the womb had, on average, 40% smaller ovarian volume, 13% smaller uterine volume and 23% fewer ovarian follicles — the structures that contain immature eggs — compared with girls whose mothers did not use acetaminophen during pregnancy. They also showed lower levels of a hormone linked to ovarian reserve.

Smaller ovaries can signal that a person has fewer eggs , which may make it harder to get pregnant. Girls are born with all the eggs they will ever have; the body cannot make more.

Having fewer eggs can also hasten earlier menopause . Early menopause, defined as beginning before age 45, is a health concern because it means a prolonged absence of estrogen, a hormone that protects the brain, bones and heart.

However, this study captured only a snapshot in time; the researchers did not follow the girls long-term to determine future fertility.

In its statement, ACOG noted that the “clinical significance of these findings is uncertain or unknown. The oldest participants evaluated were adolescents, and the study cannot determine whether the observed differences are associated with future reproductive outcomes such as fertility, ovulatory function, reproductive lifespan, or other measures of reproductive health.”

The researchers also analyzed data from 1,210 girls in the Copenhagen Mother-Child Cohort who were followed from infancy to adolescence; their mothers reported paracetamol use during the third trimester.

That data showed that fetal acetaminophen exposure was associated with smaller ovaries during adolescence and smaller uteruses at puberty.

Fischer said the new findings shouldn’t stop pregnant women from taking acetaminophen if they need it. More research is needed to determine whether the drug directly caused the reproductive organ changes.

“But on average, we do see a difference between groups, and we do feel concerned about it,” she said.

Many women in the study took acetaminophen for headaches and musculoskeletal pain, Fischer said, and women should weigh alternatives before reaching for an over-the-counter pill.

“I think we really need to have a discussion of why paracetamol is the first thing you grab in your gym bag,” she said. Alternative treatments may help with certain conditions, such as heat for some back pain.

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What pregnant people should know about acetaminophen

Dr. Christian De Geyter, a retired senior scientist at the University of Basel who studies fertility and reproductive toxicology, wrote in a commentary accompanying the research that the “eminent importance” of the findings “cannot be stressed enough!” He said the “duration and dose must be taken into consideration” and argued that recommendations about the use of acetaminophen should be reversed.

The drug “is still safe, to some extent; take it if you need it, but consider alternatives when possible,” he told CNN. “There are many, many things that can be avoided, rather than just always taking medicine.”

But other experts were more cautious about the new study’s findings and worried it could easily be misinterpreted.

Dr. Gavin Stewart, a senior lecturer in evidence synthesis at Newcastle University, said the study size is small, and because researchers measured many different potential effects, false positive findings could be difficult to distinguish from true effect.

“When you hunt really hard for a pattern, you inevitably find one. I’m worried that the authors are over-interpreting the one they found,” Stewart, who did not work on the new study, told the Science Media Centre.

“I am very concerned that this exploratory study will be misinterpreted. Pregnant women already have a limited choice of pain medication, and paracetamol has an extremely high safety profile. They should not conclude from this study that paracetamol will harm their child,” he said.

While “impressive,” the new study does not show that acetaminophen exposure causes reproductive organ changes, noted Dr. Hugh Taylor, a specialist in obstetrics and gynecology and reproductive endocrinology at Yale School of Medicine.

“What are the other things they took the Tylenol for? Did they have a fever during pregnancy? Was an infection at play, which we know causes congenital defects, as do infectious diseases and high temperatures. So is it really the Tylenol or the reason they took the Tylenol? This study cannot answer that,” said Taylor, who was not involved with the new research.

There are good reasons pregnant people need relief from pain and fever, he said, and “Tylenol is the safest drug we have when it’s needed.”

“We shouldn’t take it like candy,” Taylor added. “But it’s the safest drug to take in pregnancy, and there’s some darn good reasons why you should use it in pregnancy if needed. But like any other drug, take it in moderation.”

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一项新研究发现，一些母亲在孕期服用对乙酰氨基酚所生的女孩，其生殖器官发生了变化，这可能会影响她们日后的生育能力。研究作者表示，这一发现应推动未来的研究，但目前尚不应改变某些孕期症状的治疗方法。

这项新研究并未表明对乙酰氨基酚（也称扑热息痛或泰诺）会导致生殖系统变化。研究合著者玛吉特·比斯特鲁普·费舍尔博士表示，女性不应为此感到“恐慌”，因为这项研究并未确立因果关系。

她还指出，这并不意味着孕妇如果需要服用对乙酰氨基酚就应该停止服用，但“这绝对是我们作为一个社会需要讨论并向孕妇提供更多相关信息的事情，以便她们能够做出明智的决定。”

对乙酰氨基酚长期以来被认为是治疗孕期发烧或疼痛最安全的非处方药，但医生建议适量使用，且仅在必要时服用。未经治疗的发烧会危及母亲和胎儿，可能导致出生缺陷或流产。

丹麦哥本哈根 Rigshospitalet 医院生长与生殖系博士后研究员 Fischer 表示，还需要进行更多研究来确定是这种非处方药本身导致了这些变化，还是其他原因造成的。

美国妇产科医师学会也认为需要进行更多研究，并在声明中表示，研究结果“并不表明目前的临床建议需要改变。根据美国妇产科医师学会现有的指南，对乙酰氨基酚仍然是少数几种在孕期有指征时可以使用的安全药物之一，患者在改变用药方案前应咨询其产科医生。”

科学如何看待泰诺与自闭症的关系 | 桑杰·古普塔博士的《追寻生命》节目 | CNN音频

去年，唐纳德·特朗普总统告诉怀孕期间出现疼痛或发烧症状的孕妇要“忍着”，并尽可能避免服用对乙酰氨基酚，毫无证据地将自闭症归咎于这种药物和某些疫苗，这引发了人们对孕期服用对乙酰氨基酚的担忧。

去年，美国食品药品监督管理局启动了一项标签变更，暗示孕期服用对乙酰氨基酚可能会使胎儿面临神经系统疾病的风险，并提醒医生孕期服用对乙酰氨基酚可能与“自闭症风险显著增加”有关，尽管数十年的证据表明它不会引起神经系统问题，而且关于该药物与自闭症之间联系的科学研究也尚未定论。

对乙酰氨基酚是唯一一种医生和医学协会建议孕妇用于缓解疼痛或退烧的非处方药，但美国妇产科医师学会等机构建议仅在必要时适量服用，并在咨询医生后使用。阿司匹林和布洛芬可能对母亲和胎儿造成严重风险，包括流产。

这项新研究的重点是女孩的生殖器官，并没有研究其与自闭症的任何联系。

菲舍尔表示，她之所以想开展这项新研究，是因为几项动物实验表明，怀孕期间服用对乙酰氨基酚的母鼠所产的后代卵巢较小，卵子数量也较少。菲舍尔说，这些实验表明，这种药物似乎会干扰卵子的形成和分裂。

这项发表于本周《人类生殖开放期刊》（Human Reproduction Open）的新研究，是首批评估该技术在人体应用的研究之一。科学家们在丹麦招募了685名孕妇，她们均处于妊娠早期（胎儿发育的关键时期），并在302名女婴出生3个月后对她们进行了评估。

孕妇们记录了她们对乙酰氨基酚的使用情况，并提交了尿液样本，以便研究人员能够测量她们体内药物的含量。

研究发现，与母亲在孕期未服用对乙酰氨基酚的女孩相比，子宫内接触过对乙酰氨基酚的女孩，其卵巢体积平均缩小40%，子宫体积缩小13%，卵泡（含有未成熟卵子的结构）数量减少23%。她们体内一种与卵巢储备相关的激素水平也较低。

卵巢较小可能意味着卵子数量较少，这会使怀孕更加困难。女孩出生时就拥有了她们一生中所有的卵子；身体无法产生更多卵子。

卵子数量减少也会加速更年期的到来。更年期提前，即45岁之前开始绝经，是一个健康问题，因为它意味着雌激素长期缺乏，而雌激素是一种保护大脑、骨骼和心脏的激素。

然而，这项研究只是捕捉到了某个时间点的快照；研究人员并没有对这些女孩进行长期跟踪，以确定她们未来的生育能力。

美国妇产科医师学会（ACOG）在声明中指出，“这些发现的临床意义尚不确定或未知。接受评估的参与者中最年长的是青少年，该研究无法确定观察到的差异是否与未来的生殖结果相关，例如生育能力、排卵功能、生殖寿命或其他生殖健康指标。”

研究人员还分析了哥​​本哈根母子队列中 1210 名女孩的数据，这些女孩从婴儿期一直被追踪到青春期；她们的母亲报告说，她们在怀孕第三阶段使用了扑热息痛。

数据显示，胎儿时期接触对乙酰氨基酚与青春期卵巢较小和青春期子宫较小有关。

菲舍尔表示，新的研究结果不应阻止孕妇在必要时服用对乙酰氨基酚。还需要更多研究来确定该药物是否直接导致了生殖器官的变化。

“但平均而言，我们确实看到不同群体之间存在差异，我们对此感到担忧，”她说。

菲舍尔说，研究中的许多女性服用对乙酰氨基酚来缓解头痛和肌肉骨骼疼痛，女性在服用非处方药之前应该权衡其他替代方案。

“我觉得我们真的需要讨论一下，为什么扑热息痛会成为你健身包里第一个拿的东西，”她说。其他疗法或许对某些症状有帮助，例如热敷可以缓解一些背痛。

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孕妇应该了解对乙酰氨基酚

巴塞尔大学退休高级科学家克里斯蒂安·德·盖特博士研究生育和生殖毒理学，他在随附该研究的评论中写道，这些发现的“极其重要”“怎么强调都不为过！”他表示，“必须考虑持续时间和剂量”，并认为应该改变关于使用对乙酰氨基酚的建议。

他告诉CNN：“这种药在某种程度上仍然是安全的；如果需要就服用，但尽可能考虑其他替代方案。有很多很多事情是可以避免的，而不是总是依赖药物。”

但其他专家对这项新研究的发现持更为谨慎的态度，并担心它很容易被误解。

纽卡斯尔大学证据综合高级讲师加文·斯图尔特博士表示，这项研究的规模很小，而且由于研究人员测量了许多不同的潜在影响，因此假阳性结果可能很难与真实影响区分开来。

“当你努力寻找某种规律时，你必然会找到它。我担心作者们过度解读了他们发现的规律，”斯图尔特告诉科学媒体中心，他并没有参与这项新研究。

“我非常担心这项探索性研究会被误解。孕妇可选择的止痛药本来就有限，而扑热息痛的安全性极高。她们不应该从这项研究中得出扑热息痛会伤害胎儿的结论，”他说。

耶鲁大学医学院妇产科和生殖内分泌专家休·泰勒博士指出，虽然这项新研究“令人印象深刻”，但并未表明对乙酰氨基酚暴露会导致生殖器官发生变化。

“她们服用泰诺还有哪些其他原因？怀孕期间发烧了吗？是否感染了某种疾病？我们知道，感染、传染病和高烧都会导致先天缺陷。所以，究竟是泰诺本身的问题，还是她们服用泰诺的原因导致的？这项研究无法解答这个问题。”泰勒说道，他并未参与这项新研究。

他说，孕妇需要缓解疼痛和发烧是有充分理由的，“泰诺是我们在需要时最安全的药物”。

“我们不应该把它当糖果吃，”泰勒补充道。“但它是孕期最安全的药物之一，而且如果需要的话，孕期服用它也有一些非常充分的理由。但和其他任何药物一样，一定要适量服用。”