Migraine Treatment in Pregnancy and Lactation

妊娠期和哺乳期偏头痛的治疗

DOI: https://doi.org/10.1007/s11916-017-0646-4

Abstract-Summary A review of articles published in the last year on the treatment of migraine during pregnancy and lactation found dishearteningly little.

摘要 关于过去一年发表的关于妊娠期和哺乳期偏头痛治疗的文章综述，发现相关研究令人失望地少。

This article will review the risk/safety information related to migraine treatment

本文将回顾与妊娠期和哺乳期偏头痛治疗相关的风险/安全性信息，引用新的以及较早发表的文献。

There is little if any formal research is being carried out on pharmacotherapy for migraine that occurs during pregnancy or lactation.

目前几乎没有针对妊娠期或哺乳期偏头痛药物治疗的正式研究。

Treatment in Pregnancy Categories B and C—which lay in between—were defined thus as follows: Animal reproduction studies have failed to demonstrate a risk to the fetus, and there are no adequate and well-controlled studies in pregnant women.

妊娠期治疗

B类和C类——介于两者之间——的定义如下：动物生殖研究未能证明对胎儿有风险，且在孕妇中没有充分且对照良好的研究。

Animal reproduction studies have shown an adverse effect on the fetus, and there are no adequate and well- controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

动物生殖研究已显示对胎儿有不良影响，且在人类中没有充分且对照良好的研究，但潜在获益可能足以证明尽管存在潜在风险，在孕妇中使用该药物是合理的。

Since adequate, well-controlled studies in pregnant women are rarely if ever done, the difference between Categories B and C was simply determined by the outcomes of animal studies.

由于在孕妇中很少进行充分、对照良好的研究，B类和C类之间的区别实际上仅由动物研究的结果决定。

4.5 妊娠

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Two of its three component drugs (butalbital and caffeine), though, are Category C, and the third (acetaminophen) had inadequate studies in animals.

然而，其三种成分药物中有两种（布他比妥和咖啡因）属于C类，第三种（对乙酰氨基酚）在动物中的研究不充分。

Migraine Treatment During Pregnancy Associations between NSAID exposure in pregnancy and congenital malformations have been assessed in studies covering more than 20,000 pregnancies [414].

妊娠期偏头痛治疗

涉及超过20,000例妊娠的研究已评估了妊娠期NSAID暴露与先天性畸形之间的关联[414]。

This data included a prospective pregnancy registry that was conducted in the US and Canada [415] as well as the large Norwegian Mother and Child Cohort in which 2.2% of the 69,929 pregnant women in the study used a triptan during pregnancy (mostly sumatriptan).

这些数据包括在美国和加拿大进行的前瞻性妊娠登记[415]，以及大型的挪威母婴队列研究，在该研究中69,929名孕妇中有2.2%在妊娠期使用了曲普坦类药物（大多数为舒马曲普坦）。

There was no association between triptan use during pregnancy and congenital malformations compared to controls; adjusted odds ratios were 0.9 (0.7–1.2) for any malformation and 1.0 (0.7–1.3) for major congenital malformation [416].

与对照组相比，妊娠期使用曲普坦与先天性畸形之间没有关联；任何畸形的调整后比值比为0.9（0.7-1.2），主要先天性畸形的调整后比值比为1.0（0.7-1.3）[416]。

One case-control study and five-cohort studies met inclusion criteria and pro- vided data on 4208 infants of women who used triptans (mostly sumatriptan), and 1,466,994 children of female migraineurs who did not use triptans during pregnancy.

一项病例对照研究和五项队列研究符合纳入标准，提供了4208名使用曲普坦类药物（大多数为舒马曲普坦）的妇女所生婴儿的数据，以及1,466,994名在妊娠期未使用曲普坦类药物的女性偏头痛患者的子女的数据。

Preventive Treatments in Pregnancy Subjects then received either five behavioral sleep modification (BSM) instructions or five placebo instructions (that addressed diet and exercise).

妊娠期预防性治疗

受试者随后接受五项行为睡眠调整（BSM）指导或五项安慰剂指导（涉及饮食和运动）。

By the second visit, the BSM group reported a statistically significant reduction in headache frequency and intensity compared to the placebo group and had a high likelihood of reverting to episodic migraine.

到第二次随访时，BSM组报告头痛频率和强度有统计学显著降低，与安慰剂组相比，且恢复为发作性偏头痛的可能性较高。

By the third visit, 48.5% of all subjects had reversed over 11 years of chronic migraine and reverted to episodic.

到第三次随访时，48.5%的受试者已逆转超过11年的慢性偏头痛并恢复为发作性。

Among participants who adhered to all five BSM instructions, only one did not revert to episodic (a subject who was sleeping with a pet that she was allergic to; she immediately gave the pet to a relative, then she reverted as well); nonadherence with three or more instructions was associated with no reversion to episodic.

在遵守全部五项BSM指导的参与者中，仅有一人未恢复为发作性偏头痛（该受试者与她过敏的宠物一起睡觉；她立即将宠物送给了亲属，随后她也恢复了）；不遵守三项或更多指导与未恢复为发作性相关。

Treatment in Lactation How much drug transfers into breast milk is commonly described quantitatively using the milk to plasma (M/P) concentration ratio, whereby the infant dose (mg/ kg) is expressed as a percentage of the maternal dose (mg/kg) [417].

哺乳期治疗

药物转移至母乳中的量通常使用乳汁与血浆（M/P）浓度比进行定量描述，由此将婴儿剂量（mg/kg）表示为母体剂量（mg/kg）的百分比[417]。

The authors provide recommendations for breastfeeding, basing their judgment on data such as milk and maternal plasma levels, infant drug levels after exposure, and reported adverse events.

作者基于乳汁和母体血浆水平、暴露后婴儿药物水平以及报告的不良事件等数据，提供了母乳喂养的建议。

When a drug is compatible with breastfeeding, the next concern is the concentra- tion of that drug that will be present in breast milk.

当一种药物与母乳喂养相容时，下一个需要关注的是该药物在母乳中的浓度。

Virtually all drugs taken by the mother will be present to some extent in breast milk, but the relative infant dose (RID) can be determined and expressed as a per- centage of the maternal dose.

几乎所有母亲服用的药物都会在一定程度上出现在母乳中，但相对婴儿剂量（RID）可以被确定并表示为母体剂量的百分比。

As rizatriptan is concentrated in rat breast milk, with RID at least five-times higher than maternal plasma concentrations [418], it would not be a good choice for use during lactation until further information is available.

由于利扎曲普坦在大鼠母乳中浓缩，其RID至少比母体血浆浓度高五倍[418]，在获得进一步信息之前，它不是哺乳期使用的良好选择。

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4 治疗

Conclusion Migraine is a common problem in women who are pregnant or breastfeeding, yet there is inadequate clear information for these patients on appropriate and safe treatment.

结论

偏头痛是孕妇或哺乳期妇女的常见问题，然而对于这些患者，关于适当和安全治疗方面的明确信息仍然不足。

They could furthermore research and promulgate the best treatments of medical conditions that occur during pregnancy and lactation. (2) Because of the concern related to litigation when birth defects occur (affecting 3–5% of all pregnancies), an official list of drugs that are considered “legally safe” in pregnancy should be devel- oped and maintained, in keeping with the best medical information at the time.

他们还可以进一步研究和推广妊娠期和哺乳期发生的内科疾病的最佳治疗方法。（2）由于出生缺陷发生时涉及诉讼的担忧（影响3-5%的妊娠），应制定并维护一份被认为在妊娠期"法律上安全"的药物官方清单，与当时最佳医学信息保持一致。

A similar “legally safe” list should be developed for treatment during lactation to avoid any concern that providers might otherwise experience related to potential lawsuits for conditions that might develop years later.

类似地，应为哺乳期治疗制定一份"法律上安全"的清单，以避免医疗服务提供者因可能多年后出现的疾病而面临潜在诉讼的担忧。

Let us remember the Norwegian women cited in the opening reference [419]: they clearly expressed frustration with the conflicting information they received related to treatment of their migraines during pregnancy and lactation.

让我们记住开篇引用中提到的挪威妇女[419]：她们明确表达了对在妊娠期和哺乳期偏头痛治疗方面所获矛盾信息的沮丧。

[Section 6] Most headache centers report that roughly 85% of their migraine patients are women—and at least 70% of female migraineurs report menstrual association of their attacks, as well as changes in their headaches related to hormonal contracep- tion, pregnancy, and menopause.

[第6节]

大多数头痛中心报告其偏头痛患者中约85%为女性——且至少70%的女性偏头痛患者报告其发作与月经相关，以及与激素避孕、妊娠和绝经相关的头痛变化。

Almost three quarters of them confirmed that they had looked for safety informa- tion related to their acute and preventive migraine agents during pregnancy.

其中近四分之三的人确认她们曾寻找过与妊娠期使用的急性和预防性偏头痛药物相关的安全性信息。

Although observational studies have shown that migraine tends to improve dur- ing pregnancy [420], some women experience an increase in frequency or intensity [421], particularly towards the end of the first trimester when human chorionic gonadotropin levels are falling.

尽管观察性研究表明偏头痛在妊娠期趋于改善[420]，但部分女性的发作频率或强度反而增加[421]，特别是在妊娠早期末尾人绒毛膜促性腺激素水平下降时。

When improvement is not seen after this point, migraine is likely to continue throughout the pregnancy and extend into the postpartum period [422].

如果在此时点之后未见改善，偏头痛可能会持续整个妊娠期并延续至产后[422]。

In women who bottle-feed, the frequency of migraine attacks that they experi- enced prior to the pregnancy tends to recur very quickly; women who breastfeed tend to maintain the protective effect of anovulatory cycles for an extended period, usually until their menses resume [422].

在奶瓶喂养的女性中，妊娠前经历的偏头痛发作频率往往很快复发；而母乳喂养的女性倾向于在较长时间内维持无排卵周期的保护作用，通常持续到月经恢复[422]。

Acknowledgement A machine generated summary based on the work of Calhoun, Anne H. 2017  in Current Pain and Headache Reports.

致谢

基于Calhoun, Anne H. 2017年发表于Current Pain and Headache Reports的论文由机器生成的摘要。

Patterns and predictors of analgesic use in pregnancy: a longitudinal drug utilization study with special focus on women with migraine

妊娠期镇痛药使用的模式和预测因素：一项纵向药物利用研究，特别关注偏头痛女性