Migraine and Pregnancy

A recent study out of Denmark retrospectively assesses the risk that maternal migraine has had on the health of newborn babies. The study suggested that maternal migraine were associated with an increased risk for various poor pregnancy outcomes for the mother as well as with various poor birth and neurological outcomes (1).

Poor outcomes included:

• A higher risk of newborns requiring intensive care.
• A higher risk of respiratory distress syndrome.
• A higher risk of febrile seizures after birth.

While the study does bring up some interesting considerations, by no means is it a definitive one, and more studies are required to validate this data. That being said, for those women going through a pregnancy, be cautious when considering taking any oral and or injectable medication and always consult with your physician first.

There were, however, limitations within this study that the authors acknowledged. It was done as a look back study without a control. Secondly, there were other factors that could have played major roles in causing these outcomes, including the ingestion of over-the-counter medications and various differences in the prenatal care of the mothers prior to giving birth. It was also noted that the severity of the migraine was not taken into consideration.

What is the current thinking about pregnancy and migraine?

Pregnancy is a time when a woman's hormone levels change. For those women whose migraine attacks are triggered by hormones, the frequency of migraine may actually decrease. This is especially true in the second and third trimesters. Before menstruation, estrogen levels fall, and this is thought the be the migraine trigger. In pregnancy, estrogen levels remain high. Interestingly, while more than half of all pregnant women see a decrease in their number of migraine attacks, some women actually experience their first migraine attack at that time. Migraine with aura is less likely to improve as opposed to those without aura (2).

There are other various pregnancy related environmental factors that can independently trigger migraine attacks, such as fatigue, emotional stress, and heat intolerance. Additionally, in the first trimester, when the unborn child is developing, special care has to be taken as to what a person with migraine can ingest. With this in mind, there are various strategies that can be applied during pregnancy that can help ward off or improve the quality of life when migraine attacks are consistent.

If a pregnant woman does however see an onset of new migraine episodes during her pregnancy or sees a worsening of her baseline migraine attack frequency or duration, this needs to be taken very seriously. Migraine symptoms in association with high blood pressure can increase the risk of preeclampsia, which can cause serious harm.

What Are Some Ways Pregnant Women Prevent Migraine?

• Keep a headache diary so that you can start identifying your migraine triggers. This may help women understand for example if such triggers as not eating regular meals, or sleep deprivation, or eating specific foods that contain caffeine, such as coffee or chocolate, may precipitate a migraine episode. At that point, specific trigger avoidance will be helpful.
• Remain stress free and practice relaxation techniques like yoga, meditation, and massage.
• Stay clear of your known triggers (e.g. light, food, strong smells and fragrances).
• When an attack occurs, try such techniques as applying an ice pack, using massages, and finding a quiet dark room.

Medications, Migraine, and Pregnancy

One of the biggest pregnancy related issues for women with migraine are what and if any medications can be taken during pregnancy. This is very important as 70% of all pregnant women report taking at least one prescription medicine (2). It is essential that all women, before taking any medication during pregnancy contact their own physician for direction. No medication should be taken without first consulting a medical professional. Many migraine specific pharmaceutical treatments are not safe to be taken during pregnancy. That being said, we'll discuss some of the general pharmaceutical classes below.

ABORTIVE MEDICATIONS

Pain Relievers - While these medications are not specifically targeting any of the known migraine pathways, they can potentially provide some relief. Speak with your healthcare provider and take caution in deciding the best treatment for you.

• Acetaminophen is a medication generally considered to not be high risk during pregnancy. It has been reportedly used by 65% of all pregnant women (4).
• Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, can create a risk of bleeding and miscarriage if taken during the first trimester of pregnancy. A risk of potential heart complications can occur if taken during the third trimester of pregnancy (5).
• Metoclopramide is a drug that can be used to treat the nausea and vomiting that can occur as a migraine symptom. It is the preferred drug of its class that can be used in pregnancy (6).
• Narcotics, opioids (like morphine), and other stronger severe pain relievers have their own risks and should be avoided.

Ergotamines are an older migraine treatment, but they are very specifically contraindicated during pregnancy. In the first trimester, they could cause various birth defects. In the third trimester, they have been associated with premature labor (7).

Triptans are perhaps the most prescribed prescription migraine treatment. They specifically target the causative pathways that result in migraine attacks. Triptans should only be taken after direct consultation with your physician. In one prospective observational study when triptans were used in pregnancy, there was no noted increased risk of birth defects, spontaneous abortions, or premature delivery (8).

PREVENTIVE MEDICATIONS

In addition to the abortive medications described above, there are different preventives available.

Vitamins and Minerals - Oral magnesium has not been associated with birth defects and may be considered as a viable preventive option (9) Other vitamins such a riboflavin and CoQ10 may be effective in preventing migraine attacks in pregnancy but there are limited studies (10,11).

Oral Medications - Beta blockers such as propranolol have been historically used to prevent migraine headaches. There are however conflicting reports as to whether there is a potential for harm to the unborn fetus. Fetal growth appears to be the biggest concern and will need to be monitored (12).

Monoclonal Antibodies - The new class of calcitonin gene related peptide (CGRP)- blocking monoclonal antibodies approved for the prevention of migraine headaches were not tested during pregnancy. There are concerns about its safety, and since these medications have a long duration in our bodies, it is recommended to stop these preventive medications 5 months before becoming pregnant (13).

Botulinum Toxin A - The data surrounding this well-known preventive migraine treatment is still not totally clear and thus consultation with your physician is very important. Most of the data relates to single case reports and a retrospective review of pregnant woman who inadvertently had taken botulinum toxin injections before or during pregnancy. While no specific increased incidence of fetal abnormalities was noted, this a decision that you and your obstetrician should make together, in consultation with other health care professionals (14,15).

Non-Pharmacological Options

Nerve Blocks - Occipital and trigeminal peripheral nerve blocks can be used can be used in pregnant patients who have migraine. There have been no reported fetal malformations.

Neuromodulation - There are three current modalities approved by the FDA for the treatment of migraine. they are single-pulse transcranial magnetic stimulation, supraorbital nerve stimulation and vagal nerve stimulation. The first two are approved for both abortive treatment and prevention, while the latter for abortive treatment only. While there are no specific human studies on pregnancy and fetal abnormalities, animal studies and post marketing surveillance have been negative (16,17,18).

Precision Optical Filters - Precision optical filters, like Avulux, work by blocking certain harmful wavelengths of light. In recent studies, specific wavelengths of light (colors of light) were found to initiate and worsen migraine related headaches. Those wavelengths include blue light, red light, and amber light. The Avulux filter specifically and purposely allows in more green light, which has shown to be beneficial for individuals with migraine in a 2016 Harvard study.

Avulux has been shown to help manage light for people with migraine and light sensitivity as it effectively filters up to 97% of the most harmful light. Approximately 80% of people with migraine have light sensitivity (19). Additionally, light has been shown to initiate migraine attacks in those who are susceptible (20). The Avulux optical filter can help those with migraine leave their darkened room. From a safety perspective, there have been no known side effects associated with optical filters like Avulux.

Conclusion

Migraine is the third most prevalent diseases in the world according to the World Health Organization. Over one billion people worldwide have migraine disease. 75% of people with migraine and migraine related headaches are women, and those most often in their childbearing and productive years. As a result, addressing the special nature of migraine in pregnancy is crucial, both in prevention and in treatment. We have looked at some of the current thinking, but emphasize that a carefully designed multidisciplinary program between the pregnant migraine patient and her team of physicians, encompassing behavioral, medication, and other medical device based approaches is optimal.

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References:

1. Skajaa N, Szepligeti SK, Xue F, et al. Pregnancy, birth, neonatal, and postnatal neurological outcomes after pregnancy with migraine. Headache Volume 59, Issue 6 First published 08 May 2019
2. Granella F, Sances G, Pucci E, et al.. Migraine with aura and reproductive life events: a case control study. Cephalalgia.2000;20(8):701-707.
3. Reefhuis J, Gilboa SM, Anderka M, et al. The national birth defects prevention study: a review of the methods. Birth Defects Res A Clin Mol Teratol. 2015;103(8):656-669.
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14. Brin MF, Kirby RS, Slavotinek A, et al. Pregnancy outcomes following exposure to onabotulinumtoxinA. Pharmacoepidemiol DrugSaf.2016;25(2):179-187.
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16. Miller S, Sinclair AJ, Davies B, Matharu M. Neurostimulation in the treatment of primary headaches. Pract Neurol. 2016;16(5):362-375.
17. Bhola R, Kinsella E, Giffin N, et al. Single-pulse transcranial magnetic stimulation (sTMS) for the acute treatment of migraine: evaluation of outcome data for the UK post market pilot program. J Headache Pain. 2015;16:535.
18. Judkins A, Johnson RL, Murray ST, Yellon SM, Wilson CG. Vagus nerve stimulation in pregnant rats and effects on inflammatory markers in the brainstem of neonates. Pediatr Res. 2018;83(2):514-519.
19. Rodrigo Noseda, David Copenhagen, Rami Burstein Current understanding of photophobia, visual networks and headaches Cephalgia 2019 Nov;39(13): 1623-34
20. Vincent AJ, Spierings EL, Messinger HB. A controlled study of visual symptoms and eye strain factors in chronic headache. Headache. 1989;29:523–527