Introduction
Migraine is a common primary form of headache (TH), which manifests itself in the form of repeated attacks, often accompanied by nausea, vomiting, photo- and phonophobia.
The prevalence of migraine, according to various estimates, ranges from 2.6% to 21.7%, and the average rate is 14.7% [1]. In Russia, the prevalence of migraine reaches 20.8%, which is approximately more than 30 million people [2]. The prevalence of migraine in women is more than 2 times higher than that in men, and the highest prevalence of migraine within the female population occurs during reproductive age [3]. For this reason, issues of tactics for managing patients with migraine during pregnancy are of high relevance. Issues of pregnancy planning, as well as rules for taking medications for pain relief and approaches to preventive treatment of migraine during pregnancy are discussed very often.
The course of migraine during pregnancy
In 50–70% of women during pregnancy, migraine without aura improves [4]. Migraine attacks become mild, extremely rare, and in most patients in this group the migraine completely disappears. Improvement occurs after the first trimester, starting from the 12th–14th week. pregnancy. This is due to the fact that by the beginning of the second trimester, the level of estrogen stabilizes and begins to increase, and its fluctuations stop (Fig. 1). Migraine with aura stops less often during pregnancy, in approximately 40% of patients.
At the same time, if headache persists during this period, it is necessary to carry out differential diagnosis and determine the form of headache. Alarming symptoms during pregnancy are:
the appearance of a new, unusual headache;
a sharp increase in migraine attacks;
the addition of new, unusual symptoms of hypertension, including visual impairment, sensitivity, aphasia, paresis of the limbs;
the appearance of migraine aura in patients with previous migraine without aura;
increased blood pressure during hypertension;
convulsions.
The presence of active migraine during pregnancy does not affect the course of pregnancy itself and the development of the fetus, but increases the risk of preeclampsia and gestational hypertension. Moreover, the persistence of active migraine, especially migraine with aura, during pregnancy increases the risk of acute cerebrovascular accidents (ACVA) by 15–17 times [5]. The prevalence of stroke during pregnancy and the early postpartum period is 34.2 cases per 100,000 births [5].
Stopping attacks
The selection of drug therapy for patients with migraine during pregnancy poses significant difficulties. The severity of migraines can be especially high during the first trimester. Full-blown, unrelieved migraine attacks are often accompanied by nausea, vomiting and lead to unnecessary suffering and dehydration, especially in patients suffering from early toxicosis. Despite the desire to avoid taking medications (especially in early pregnancy) to minimize the risk of fetal developmental disorders, many patients with hypertension begin to take analgesics uncontrollably. Therefore, the importance of preliminary counseling and education of patients on the proper control of hypertension cannot be overemphasized.
Non-pregnant women are recommended to take medications to relieve migraine attacks as early as possible, no later than 1 hour after the onset of the attack. This approach allows you to speed up relief and completely stop a migraine attack in a short time. Pregnancy is the only period in a woman’s life when this recommendation can be temporarily ignored. For patients seeking to minimize drug use, a stepwise approach may be recommended, in which treatment of mild to moderate attacks begins with non-drug methods.
If the patient decides not to use analgesics, control of nausea becomes a priority to avoid dehydration. Patients should avoid strong odors and drink more fluids, such as juices diluted 1:1 with water. Feelings of nausea can also be reduced by eating easily digestible foods, such as crackers, applesauce, bananas, rice, and pasta. Metoclopramide or ondansetron can also be used [6].
Neurostimulation methods play a major role in non-drug approaches to the treatment of migraine. The only device registered in Russia for non-invasive transcutaneous stimulation of the supraorbital nerve - Cefaly (Cefaly®) - is specially designed for the treatment of migraines and can be a good alternative to medications for relieving migraine attacks. Using the Cefaly device at the very beginning of an attack allows you to reduce the intensity of headaches and in some cases completely stop the attack. Thus, the intensity of migraine pain decreases by 4.3 points after 1 hour [7]. Cefaly can also be used in conjunction with pain medications to increase their effectiveness.
Despite the fact that, in general, paracetamol is less effective for relieving an acute attack of migraine than acetylsalicylic acid and nonsteroidal anti-inflammatory drugs (NSAIDs), its safety during pregnancy is higher [6]. Caffeine, which has the ability to enhance the analgesic effect, is an important addition to painkillers. Adding 100 mg of caffeine to the analgesic increases its effect by 1.5 times.
The safety of NSAIDs is controversial [6]. Prescribing NSAIDs in the first trimester may be associated with an increased risk of miscarriage and the development of congenital anomalies. Taking NSAIDs and aspirin in the third trimester can lead to premature closure of the ductus arteriosus
. For these reasons, the use of NSAIDs should be limited to the second trimester. It is especially important to stop taking them after the 32nd week. Taking high doses of aspirin may also increase the risk of bleeding.
Triptans are the most effective analgesics for the relief of migraine attacks. The safety of triptans during pregnancy is assessed through pregnancy registries, where a huge amount of data has now been accumulated for sumatriptan, for example. Despite the prohibition of its use during pregnancy indicated in the official instructions for the use of sumatriptan, there is no evidence of an increased risk of congenital malformations when taken by pregnant women [8]. Patients who took triptans in early pregnancy (without knowing they were pregnant) should be advised that the likelihood of adverse effects of this drug on the fetus is extremely low. Women who experience severe, disabling migraine attacks that cause vomiting may be advised to use triptans during pregnancy. To date, this information has not been included in official recommendations for the treatment of migraine, but the safety of sumatriptan is confirmed by the analysis of a huge number of observations and expert recommendations.
It should be borne in mind that the safety of triptans varies. Sumatriptan, as the most hydrophilic of the triptans, has difficulty penetrating the placental barrier, while other triptans (including eletriptan) are lipophilic.
Prednisolone can only be used as an “ambulance” remedy in the event of a prolonged and severe migraine attack [9]. The use of prednisolone is preferable to dexamethasone, since the latter penetrates the placenta better. Nuchal nerve blocks with lidocaine, bipuvacaine and/or a corticosteroid can be used as an ambulance to relieve severe attacks.
What are the dangers of diarrhea at 30 weeks of pregnancy?
Diarrhea at this stage often signals the development of late toxicosis. But this period is a turning point, so diarrhea must be taken seriously: with the urge to defecate, the uterus may begin to contract intensively.
This can lead to premature birth, but the babies are not yet ready to be born.
In no case should you allow dehydration of the body - this can lead to thrombosis, which is extremely dangerous. It is good that at this time it is allowed to take medications that were contraindicated in the early stages - the doctor can prescribe treatment that will quickly eliminate both diarrhea and the symptoms that accompany it.
Preventative treatment
The attending physician must promptly identify the group of patients in whom preventive treatment of migraine will be most successful. While most pregnant women begin migraine remission at the end of the first trimester, others experience migraine remission by the 10th–12th week. Frequent attacks may persist, which will most likely indicate the persistence of headache throughout pregnancy. Refusal to treat such patients can lead to malnutrition, dehydration, the development of affective disorders and a significant decrease in quality of life.
Preventive treatment of migraine is necessary in the following cases:
high frequency of attacks (more than 3 days a week);
the presence of severe or prolonged attacks;
significant disability;
dehydration and malnutrition;
poor response to analgesics.
The current frequency of headaches and the effectiveness of the analgesics used should be monitored using a headache diary. For patients who require preventive treatment, it is necessary to select the optimal combination of drug and non-drug approaches.
There are a number of non-drug methods that can effectively manage hypertension during pregnancy and are an important addition to pharmacological methods; when combined, the amount of drugs used during pregnancy and lactation is reduced. Relaxation techniques, cognitive behavioral therapy and biofeedback can be used during pregnancy.
Trigeminal neurostimulation also plays a major role in the preventive treatment of migraine during pregnancy. Regular use of Cefaly daily for 20 minutes, preferably in the evening, leads to a 2-fold reduction in migraine headache attacks in 38% of patients with episodic migraine and 35% of patients with chronic migraine [10, 11]. The high safety of this method (the probability of adverse events is 2–3%) allows it to be used without fear during pregnancy. It is also important that the Cefaly device has a mild sedative effect [12] and is not prohibited for use during pregnancy.
Information about the safety of drugs is collected through clinical trials of their use in the treatment of other diseases, including mood disorders, cardiovascular diseases and epilepsy. The safety of most drugs during pregnancy has not been directly assessed, but accumulated data have allowed these drugs to be assigned a certain safety category. In addition, the choice of drugs for the treatment of migraine in pregnancy may be based on additional information about the safety of a number of drugs that are used in pregnancy to treat hypertension, depression and epilepsy.
If it is necessary to prescribe drug therapy to reduce migraine attacks, it is recommended to start with the use of β-blockers. Due to its widespread use in the treatment of arterial hypertension during pregnancy, propranolol (anaprilin) is considered the drug of first choice for the preventive treatment of migraine [13]. At the same time, taking β-blockers is associated with a risk of hypoglycemia, hypotension, bradycardia and respiratory disorders in the newborn. The drug should also be used with caution in patients with bronchial asthma, a tendency to arterial hypotension and bradycardia. In the absence of propranolol or if there are contraindications to it, metoprolol can be used. It is recommended to gradually reduce the dose of beta-blockers during the last weeks of pregnancy (starting from the 36th week) and discontinue them at least 2-3 days before delivery.
No adverse effects on fetal development have been demonstrated with the use of calcium channel blockers, but insufficient data and the low effectiveness of verapamil do not allow it to be recommended for widespread use for the preventive treatment of migraine during pregnancy [13].
Lisinopril exhibits a teratogenic effect when used in the 2nd and 3rd trimesters and should be discontinued. Candesartan, which has a mechanism of action similar to lisinopril, should also not be used to treat migraine in pregnant women [14].
Despite the high effectiveness of antiepileptic drugs in the treatment of migraines, their use during pregnancy is prohibited. Valproic acid preparations are absolutely contraindicated during conception and pregnancy due to their teratogenic effect (disrupting the development of the fetal neural tube) and blood clotting disorders in the mother and fetus. In addition, data have accumulated on the possible teratogenic effects (development of hypospadias, cleft lip and palate) of topiramate [14].
Gabapentin has low effectiveness in the preventive treatment of migraine; the safety of its use during pregnancy has been poorly studied. Its use should be stopped in the third trimester due to its possible effect on bone development [6].
Tricyclic antidepressants are highly effective in the preventive treatment of migraine. Amitriptyline is relatively safe during this period and is the second choice drug for the preventive treatment of migraine [6, 13, 15].
The use of the serotonin and norepinephrine reuptake inhibitor venlafaxine in the third trimester increases the risk of developing behavioral syndrome of newborns by 3 times. Symptoms are usually mild in severity.
The safety of botulinum toxin type A preparations for the treatment of migraine during pregnancy has not been studied. At the same time, data have accumulated on the absence of teratogenic and embryotoxic effects of botulinum toxin type A in pregnant women who reported using the drug for various indications [16]. At the same time, the use of botulinum toxin for the preventive treatment of migraine during pregnancy is not recommended.
New drugs for the preventive treatment of migraine - antibodies to calcitonin gene-related peptide - erenumab and fremanezumab have not been studied for use in pregnant women and are not recommended for the treatment of migraine.
In addition to the above medications allowed during pregnancy, various vitamins and minerals can be mentioned. In particular, there is evidence of the benefits of magnesium for the preventive treatment of migraine during pregnancy [13, 15]. Pyridoxine (vitamin B6) at a dose of 80 mg/day alone or in combination with other drugs at a dose of 25 mg/day, for example with folic acid, can have a mild preventive effect against migraine.
Table 1 summarizes the safety data of the main groups of drugs used for the preventive treatment of migraine during pregnancy.
Pros and cons of drug pain relief
During the administration of any medicine, including analgesics, there is always a risk of it penetrating the placental barrier and causing harm to the baby. Currently, almost all drugs approved for use during labor are not dangerous for infants, but can cause minor abnormalities in the respiratory system and a decrease in the overall Apgar score.
Often, if very severe pain occurs during contractions, doctors use narcotic analgesics. They not only act like antispasmodics, relieving spasm of the cervical muscles, but also stimulate contractions at the level of brain receptors and significantly reduce pain. These drugs are administered intramuscularly or intravenously, many women after fifteen minutes notice a decrease in pain during contractions, the appearance of mild drowsiness and peace.
However, narcotic analgesics penetrate in full into the blood of the fetus, provoking depression of respiratory functions and a general lethargic state of the baby. The problem also arises from the fact that the drug is eliminated from the baby’s body seven times slower than in an adult, and therefore, immediately after birth, such children may need the help of a resuscitator. Knowing these problems, doctors may inject an antagonist drug into the baby's umbilical vein to speed up the elimination of the drug.
If a woman’s anxiety and muscle tension are too high, she may be prescribed mild tranquilizers, which do not relieve pain but relieve tension. An injection of such a medicine usually has a positive effect on emotionally labile women prone to hysteria and has a mild sedative effect. Tranquilizers can harm a child, causing allergic reactions and depression. The severity of side effects depends on the dose of the drug.
During childbirth, the doctor may give an injection into the perineal area to prevent sharp pain when it is stretched or torn. This is done mainly with the drug lidocaine or similar. It does not cause side effects and does not harm the baby, but it also cannot be used as an effective pain reliever.
Of course, in case of very severe, unbearable pain or a long labor, the woman in labor has the right to ask for an injection of a narcotic drug, but the expectant mother must remember that the harm from the drug to the baby can be irreparable. Therefore, before giving birth, you need to do everything that is necessary to ensure the normal development of the birth process, try all the relaxation and breathing techniques that relieve pain. After all, restoring a child’s normal condition after complications caused by the use of narcotic analgesics can be quite lengthy and difficult.
Take the first step
make an appointment with a doctor!
