Indian Journal of Pain

REVIEW ARTICLE
Year
: 2015  |  Volume : 29  |  Issue : 3  |  Page : 135--141

Common primary headaches in pregnancy


Anuradha Mitra, Amitava Rudra 
 Department of Anaesthesiology and Pain Management, Kalipada Chaudhuri Medical College and Hospital, Kolkata, West Bengal, India

Correspondence Address:
Dr. Anuradha Mitra
B1 Sourav Abasan, ED Block, Salt Lake, Kolkata - 700091
India

Abstract

Headache is a very common problem in pregnancy. Evaluation of a complaint of headache requires categorizing it as primary or secondary. Migrainous headaches are known to be influenced by fluctuation of estrogen levels with high levels improving it and low levels deteriorating the symptoms. Tension-type Headaches (TTHs) are the most common and usually less severe types of headache with female to male ratio 3:1. Women known to have primary headache before conception who present with a headache that is different from their usual headache, or women not known to have primary headache before conception who present with new-onset of headache during pregnancy need neurologic assessments for potential secondary cause for their headache. In addition to proper history and physical examination, both non-contrast computed tomography (CT) and Magnetic Resonance Imaging (MRI) are considered safe to be performed in pregnant women when indicated. Treatment of abortive and prophylactic therapy should include non-pharmacologic tools, judicious use of drugs which are safe for mother and fetus.



How to cite this article:
Mitra A, Rudra A. Common primary headaches in pregnancy.Indian J Pain 2015;29:135-141


How to cite this URL:
Mitra A, Rudra A. Common primary headaches in pregnancy. Indian J Pain [serial online] 2015 [cited 2019 Dec 13 ];29:135-141
Available from: http://www.indianjpain.org/text.asp?2015/29/3/135/165823


Full Text

 Introduction



Headache is a very common problem in pregnancy. In the 2009 survey, one in five of all women aged 18-44 years reported a severe headache or migraine within the past 3 months and headache was the most common neurological complaint during pregnancy. [1] Headache during pregnancy is also one of the commonest reasons for referral to the neurologist. Evaluation of a complaint of headache requires categorizing the headache as primary or secondary. Secondary headache can occur following a relatively benign condition such as flu or can result from serious underlying cerebral pathology. However, primary headache itself is a disorder. Furthermore, primary headaches are more common in pregnant women than those with secondary causes. [2] Migraine headaches are those most likely to be affected by the hormonal changes in pregnancy. [3]

In this article, we focus on the common primary headache disorders in pregnancy, those in which there is no underlying primary causation, save the patient's own natural physiology, and genetics. Treatment focus is highlighted upon evidence-based approaches to management in so far as possible with expert opinion where evidence is insufficient to provide guidance.

 Classification of Headache

[4]

(adapted from International Headache Society (IHS), 2004).

Primary headache

Migraine with or without aura

Tension-type

Cluster or other Trigeminal autonomic Cephalgias

Other primary headaches

Secondary headache

Head or neck trauma

Cranial or cervical vascular disorders

Intracranial nonvascular disorders

Substance use

Infection

Head and neck disorders

Psychiatric cranial neuralgias

Although migraine and tension-type headaches are the most common forms of primary headaches, cluster headaches are not commonly reported in obstetrics. [5]

 Migraine



Migraine is a primary headache disorder defined by the IHS as headache with some particular features such as unilateral often throbbing headache associated with nausea, vomiting and sensitivity to light, sound and head movement.

The IHS (2004) classifies three migrainous types of headaches based on the presence or absence of aura as well as chronicity:

Migraine without aura, characterized by unilateral throbbing headache, nausea, vomiting, photophobia.Migraine with aura, characterized by similar symptoms but preceded by certain neurological phenomenon such as visual scotomata or hallucination.Chronic migraine, defined by migrainous headache occurring at least 15 days per month for more than 3 months. [6]

 Pathophysiology



The pathophysiology of migraine during pregnancy is poorly understood. The clinical effect of hormonal events implicates sex hormones in the pathophysiology of migraine. Most of the research to date has studied the effects of the ovarian hormones, progesterone and estrogen. Headache of migraine is thought to occur due to vasodilatation of extracranial and meningeal blood vessels which in turn stimulate the trigeminal sensory neurons and the perivascular nerve endings leading to headache. [7] Inhibitory neurotransmitters such as serotonin [5-hydroxy tryptamine] (5HT) and gamma amino butyric Acid (GABA) decrease and excitatory neurotransmitters such as norepinephrine and dopamine increase at the onset of headache. [8] Serotonin depletion can induce migraine and selective serotonin agonists such as triptans can alleviate it. [9]

 Effect of Pregnancy on Migraine



Migrainous headaches are known to be influenced by fluctuation of estrogen levels with high levels improving and low levels deteriorating the symptoms. [10] Migraines may improve during pregnancy when estrogen levels are higher and constant. [11] Prospective and observational studies have shown that up to 11% women in first trimester, 53% in the second and 79% of women in third trimester who had suffered from migrainous headaches before becoming pregnant, experience improvement in headache recurrence during pregnancy. [12] In the week immediately postpartum, headache affects around 30-40% of women. [13],[14],[15]

 Effect of Migraine on Pregnancy



Recurrence of migrainous headaches during pregnancy would increase both maternal and fetal risks. [16] Preeclampsia and other cardiovascular morbidities are increased. [17] There is an increased risk of stroke in pregnant women who are having recurrence of migrainous headaches. [18] Moreover, young women who are suffering from migraine with aura would be more prone to develop stroke. [19]

 Management of Migraine in Pregnant Women



As most women with migraine improve after the first trimester, they could usually be managed with reassurance and nonpharmacological methods such as ice packs, massage, relaxation and biofeedback. [20] Avoidance of triggers, lack of sleep, and psychological stress together with the habits of regular exercise, regular meals and regular sleep patterns help. [21] Some women, however, continue to have debilitating headache associated with nausea and vomiting and consequent dehydration. Above mentioned women require pharmacological treatment.

The pharmacological management of migraines can be grouped into prophylactic therapy and abortive therapy.

Prophylactic therapy

Pharmacological prophylaxis is indicated in one of the following conditions: [22]

More than two disabling headaches per month.Ineffective symptomatic treatment.Use of abortive treatment more than twice a week or,Migrainous headache with neurological sequelae.

Agents used

Low dose aspirin (75 mg daily) has been suggested as the first-line prophylactic drug because of its widely-accepted safety in pregnant women. [23]Beta blockers are the drug category representing an established first treatment choice for reducing migraine attacks by preventing cerebral artery vasodilatation thereby reducing frequency and severity, however there would not be any effects on the duration of migrainous attacks. [24] Propranolol 20-40 mg three times daily and metoprolol 50-100 mg two times daily have been used with reasonable success. [25] Care should be taken not to lower maternal blood pressure while administering this group of agents. Common side effects are reduced energy and tiredness. The use of both propranolol and metoprolol is contraindicated in patients affected by asthma. Tricyclic antidepressants (TCA) such as amitriptyline is the only antidepressant agent with fairly constant findings for efficacy in migraine prevention. [26] Amitriptyline appears to reduce the severity, frequency and duration of migraine attacks by a poorly understood mechanism involving central inhibition of 5-HT and histamine receptors. [24] Low dose amitriptyline (10-50 mg at night) has been widely used and well-tolerated throughout pregnancy for many years without adverse fetal consequences. [27] Dosages higher than 50 mg did not prove to be superior in terms of efficacy. Common adverse events are drowsiness, urinary retention, and arrhythmias. [28]Calcium channel blockers such as nifedipine, nimodipine and verapamil have modest effect as prophylactic agents in migrainous headaches. [29] The above mentioned agents would be considered as safe during pregnancy as long as the blood pressure of the patient remains within normal limits. [30]Other agents used for the prophylaxis of migrainous headaches in non pregnant women such as antiepileptics and ergot alkaloids are contraindicated in pregnancy because of their teratogenic and vasoconstrictive effects of the agents respectively.

Abortive therapy

Paracetamol is the first-line treatment for mild to moderate pain in pregnancy due to its safety to fetus. [31]The use of opiates represents a second-line treatment for migraine attacks. A particular role is played by drugs with codeine association. Codeine in combination with paracetamol have been used. There have been no association with the incidence of birth defects and use of this group of agents. [32] Their main limitation consists in the possibility of abuse. [33]Analgesic doses of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be safe in first and second trimesters of pregnancy. [34] However, chronic exposure to high doses in the third trimester is associated with premature closure of ductus arteriosus and restriction of renal blood flow in some fetuses. [35] Use of high dose of NSAIDs in the third trimester has been linked with antepartum and postpartum hemorrhage. [36]Caffeine, a cerebral vasoconstrictor, also acts as an analgesic. Daily intake of upto 300 mg caffeine appears to be safe in pregnancy; intake beyond this may be associated with miscarriage and fetal growth restriction. [37]Ergotamine, a potent vasoconstrictor, is contraindicated during pregnancy because of concern about premature labor. [38]The use of triptans (sumatriptan, rizatriptan, zolmitriptan etc.), which are serotonin 5HT 1B/2D receptor agoninsts, relieves headache by causing vasoconstriction. [39] Contraindications to their use consists in the presence of cardiovascular issues in view of their vasoconstrictive capacity. Frequent adverse events are represented by dizziness, somnolence, asthenia, and chest tightness. Sumatriptan has been the first drug introduced in such treatments. 50 and 100 mg tablets proved to be superior to placebo in headache relief at 4 hours. Sumatriptan has not been associated with adverse pregnancy outcomes, but data are limited. [40] The Sumatriptan registry has the largest number of cases with 7 in 183 pregnancies showing birth defects, which is consistent with the 2-4% background rate of congenital anomalies in the general population. [41] Sumatriptan, therefore, has a role in second or third line treatment of headaches in pregnancy. [42]Long acting beta-blockers such as propranolol has been associated with the possible risk of intra uterine growth retardation (IUGR). However, studies with propranolol have been done mostly among women with underlying hypertention, also a risk factor for growth restriction. Therefore, the concern with the use of beta blocker in pregnant women is widely questioned. [43]Magnesium sulphate 1 g IV has been used to treat an attack of migraine in pregnancy. [44]Evidences regarding TCA such as amitriptyline, nortriptyline and doxepin indicate that they are safe during pregnancy. [45]Antiemetics are often needed for the associated nausea and vomiting. Moreover some medications used to treat migraines can cause nausea. Centrally acting dopaminergic antagonists such as prochlorperazine and promethazine can relieve the symptoms and have been found to be safe during pregnancy. [46]Corticosteroids have been used for intractable attack refractory to the above treatments. Both prednisone and methylprednisolone are metabolized by placenta and therefore are not associated with risk of birth defects. [47] Dexamethasone and betamethasone are not metabolized by placenta and thus they are potentially harmful to the fetus.

 Tension-Type Headaches (TTHs)



TTHs are the most common and usually less severe types of headache with female to male ratio 3:1. Symptoms typically consist of generalized pressure or tightness in the head. Tension headaches are usually bilateral and constant, while migraines are usually unilateral and associated with photophobia, phonophobia, nausea and exacerbated by physical activity. It may, however, be difficult to distinguish these from secondary headaches. TTHs are frequently associated with anxiety or stress and can be a symptom of postpartum depression. [48]

 Pathophysiology of TTHs



The pathophysiology of TTHs is even less clear than that of migraines. Involvement of serotonin and endorphins appear to play a major role affecting the trigeminal nucleus. [49] TTHs to some extent improve during pregnancy as the level of the neurotransmitters are altered by the influence of the higher estrogen level during pregnancy. Improvement is, however, less marked than that seen with migraines. [50]

 Management of TTH



Nonpharmacologic therapies such as relaxation, stress management and EMG biofeedback are highly effective for the management of TTH in pregnancy with no side effect to mother and fetus. [51]

The goal of relaxation training to help the patient to recognize and control tension as it arises in the course of daily activities.

The aim of stress therapy is to teach the patient to identify thoughts and beliefs that generate stress and aggravates headaches. These thoughts are then challenged, and alternate adaptive coping self-instructions are considered.

The aim of EMG biofeedback is to help the patient to recognize and control muscle tension by providing continuous feedback about muscle activity. The effect is long lasting and enhanced by combination with relaxation therapy. It would not be possible to draw reliable conclusions as to whether the effect differed between patients with episodic and chronic TTH.

Non drug management should always be considered, although the scientific basis is limited. Information, reassurance, and identification of trigger factors may be rewarding. EMG biofeedback has a documented effect in TTH. While cognitive-behavioral therapy and relaxation training most likely are effective, there is no convincing evidence.

A review [52] and a metaanalysis [53] concluded that there is no evidence for efficacy of acupuncture in TTH.

Among other pharmacologic interventions, the dose of caffeine should be limited to 300 mg/day in pregnant women to prevent intrauterine growth retardation. [54]

Ergotamine is contraindicated as it increases uterine tone affecting placental blood flow and fetal oxygenation. [55]

NSAIDs should only be used during third trimester because of concern about their association with premature closure of fetal ductus arteriosus and increased chances of hemorrhage. [35],[36]

Administration of benzodiazepines is debatable because of the conflicting evidence of association of orofacial clefts with exposure to this drug in the first trimester. [56]

TCAs can be used safely as it has no proven association with the neurodevelopment of children exposed in utero. [57] Amitriptyline should be started at low dosage (10-25 mg/day) and titrated by 10-25 mg weekly until the patient has either good therapeutic effect or side effects are encountered. It is important the patients are informed that this is an antidepressant agent but has an independent action on patient. The maintenance dose is usually 20-50 mg daily administered 1-2 hours before bedtime to help to circumvent any sedative adverse effects. A significant effect of amitriptyline may be observed already in the first week on the therapeutic dose. It is therefore advisable to change to other prophylactic therapy, if the patient does not respond after 3 weeks on maintenance dose.

 Cluster Headaches (CHs)



It is a severe primary headache disorder characterized by autonomic symptoms such as ipsilateral nasal congestion, rhinorrhoea, lacrimation, conjunctival hyperaemia, facial diaphoresis, palpebral oedema and Horners'syndrome. CHs are frequently recurring, short lasting extremely severe headaches that can occur in bouts (clusters) without any aura typically of 6-12 weeks' duration once a year or 2 years and at the same time of the year. [58]

CH is relatively rare (prevalence0.04-0.4%) even more so during pregnancy as this headache has a male predominance (male: female ratio;9:1). [59] Female hormones seem to have little influence on CHs. [60]

 Pathophysiology of CHs



Pathogenesis of CHs is not well understood. CHs are thought to originate at the pericarotid/cavernous sinus complex which receives sympathetic and parasympathetic input from the brain stem which may explain the autonomic involvement. [61]

 Management of CHs During Pregnancy



CHs during pregnancy may be difficult to treat, but may include corticosteroids, narcotics or calcium channel blockers such as verapamil. Inhalation therapy with 100% oxygen, 12L/ minute, delivered by non-rebreathing face mask at symptom is more likely to result in being pain free at 15 minutes than compared to placebo (high-flow air). [62] It has been found to be effective in 70% of attacks. [63]

 Evaluation of Women Presenting with Primary Headache During Pregnancy



Women complaining of headache during pregnancy can be categorized into the following groups:

Women known to have primary headache before conception who present with their typical headache during pregnancy.Women known to have primary headache before conception who present with a headache that is different from their usual headache which they had encountered before becoming pregnant.Women not known to have primary headache before conception who present with new-onset of headache during pregnancy.

Women mentioned in the groups 2 and 3 need neurologic assessments for potential secondary cause for their headache.

History

A thorough history including the location, duration, severity and frequency of headache together with any associated complaint such as nausea, vomiting, fever, numbness, weakness and visual or sensory disturbances should be considered. Patient should also be enquired about any history of recent trauma to the head.

Following are the signs and symptoms indicating a serious underlying cause. [64]

Sudden onset of headache.New-onset headache.Severe headaches.Headaches increasing in frequency and severity.Headache following head injury.Associated neurologic symptoms such as change in mental status, seizures, focal deficit, visual changes, slurred speech, gait disturbances, meningeal signs etc.Fever associated with headache.

Physical examination

Physical examination should include vital signs such as temperature, heart rate and blood pressure assessment and a thorough neurologic examination of the cranial nerves, motor, sensory and cerebellar function, tendon reflexes etc. Examination of the head and sinuses, ears, nose throat should be done for signs of infection, and meningismus. Also, fundoscopic examination of the eyes is to be done to detect papilledema.

Investigation

Full blood count, biochemistry, coagulation profile, liver function tests and urine analysis should be done.

Non contrast computed tomography (CT) is the first line of investigation in patients with high suspicion for intracranial hemorrhage or head injury.

Lumbar puncture is indicated in patients suspected for possible subarachnoid hemorrhage as sensitivity to non contrast CT falls to 76% by 2 days after the onset of the event. [65]

Magnetic resonance imaging (MRI) is indicated for suspected space occupying lesions, inflammatory processes, cerebral venous thrombosis and vascular malformations. [66]

Both non contrast CT and MRI are considered safe to be performed in pregnant women when indicated. Radiation exposure of less than 5 rads is considered safe for fetus. A non contrast head CT results in 0.05 rads of radiation exposure to the fetus while MRI does not use ionizing radiation. [67]

 Conclusion



Headache is a common morbidity in pregnant women. Most headaches are primary and benign and can be easily treated with reassurance, nonpharmacological remedies and simple analgesics. However, headache in a pregnant woman with atypical features should generate high index of suspicion for serious underlying pathology. Prompt management of these patients can prevent serious consequences.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Pleis JR, Lucas JW, Ward DW. Summary health statistics for U. S. adults: National Health Interview Survey, 2008. Vital Health Stat 10 2009;1-157.
2Digre KB. Headaches during pregnancy. Clin Obstet Gynecol 2013;56:317-29.
3Torelli P, Allais G, Manzoni GC. Clinical review of headache in pregnancy. Neurol Sci 2010;31:S55-8.
4Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders. 2 nd edition. Cephalalgia 2004;24:9-160.
5Giraud P, Chauvet S. Cluster headache during pregnancy: Case report and literature review. Headache 2009;49:136-9.
6Headache Classification Subcommittee of the International Headache Society (IHS), The International Classification of Headache Disorders, 2 nd ed, 1 st revision, (ICHD-IIRI), May 2005. Available from: http://www.ihs-classification.org. [Last accessed on 2015 Jun 22].
7Neurological disorders. In: Cunningham FG, Leveno KJ, Bloom SL, Spong CY, Dashe JS, Hoffman BL, et al. editors. 24 th ed. Williams Obstetrics. New York: McGraw-Hill Education; 2014. p. 1187-89.
8D′Andrea G, Leon A. Pathogenesis of migraine: From neurotransmitters to neuromodulators and beyond. Neurol Sci 2010;31:S1-7.
9Shields KG, Goadsby PJ. Serotonin receptors modulate trigeminovascular responses in ventroposteromedial nucleus of thalamus: A migraine target? Neurobiol Dis 2006;23:491-501.
10Marcus DA, Scharff L, Turk D. Longitudinal prospective study of headache during pregnancy and postpartum. Headache 1999;39:625-32.
11Marcus DA. Interrelationships of neurochemicals, estrogen, and recurring headache. Pain 1995;62:129-39.
12Chen TC, Leviton A. Headache recurrence in pregnant women with migraine. Headache 1994;34:107-10.
13Sances G, Granella F, Nappi RE, Fignon A, Ghiotto N, Polatti F, et al. Course of migraine during pregnancy and postpartum: A prospective study. Cephalalgia 2003;23:197-205.
14Scharff L, Marcus DA, Turk DC. Headache during pregnancy and in the postpartum: A prospective study. Headache 1997;37:203-10.
15Stein G, Morton J, Marsh A, Collins W, Branch C, Desaga U, et al. Headaches after childbirth. Acta Neurol Scand 1984;69:74-9.
16Allais G, Gabellari IC, Borgogno P, De Lorenzo C, Benedetto C. The risks of woman with migraine during pregnancy. Neurol Sci 2010;31:S59-61.
17Facchinetti F, Allais G, Nappi RE, D′Amico R, Marozio L, Bertozzi L, et al. Migraine is a risk factor for hypertensive disorders in pregnancy: A prospective cohort study. Cephalalgia 2009;29:286-92.
18Kittner SJ, Stern BJ, Feeser BR, Hebel R, Nagey DA, Buchholz DW, et al. Pregnancy and the risk of stroke. N Engl J Med 1996;335:768-74.
19Tietjen GE. The relationship of migraine and stroke. Neuroepidemiology 2000;19:13-9.
20Marcus DA, Schraff L, Mercer S, Turk DC. Nonpharmacological treatment for migraine: Incremental utility of physical therapy with relaxation and thermal biofeedback. Cephalalgia 1998;18:266-72.
21Silberstein SD, Lipton RB. Overview of diagnosis and treatment of migraine. Neurology 1994;44:S6-16.
22Silberstein SD. Preventive migraine treatment. Neurol Clin 2009;27:429-43.
23Nelson-Piercy C, De Sweit M. Diagnosis and management of migraine. Low dose aspirin maybe used for prophylaxis. BMJ 1996;313:691-2.
24Ziegler DK, Hurwitz A, Preskorn S, Hassanein R, Seim J. Propranolol and amitriptyline in prophylaxis of migraine: Pharmacokinetic and therapeutic effects. Arch Neurol 1993;50:825-30.
25Contag SA, Bushnell C. Contemporary management of migraine disorders in pregnancy. Curr Opin Obstet Gynecol 2010;22:437-45.
26Couch JR, Hassanein RS. Amitriptyline in migraine prophylaxis. Arch Neurol 1979;36:695-9.
27Clavel AL Jr. Migraine prevention. The choices continue to grow. BMJ 2001;78-9.
28Lampl C, Huber G, Adl J, Luthringshausen G, Franz G, Marecek S, et al. Two different doses of amitriptyline ER in the prophylaxis of migraine: Long-term results and predictive factors. Eur J Neurol 2009;16:943-8.
29Magee LA, Schick B, Donnenfeld AE, Sage SR, Conover B, Cook L, et al. The safety of calcium channel blockers in human pregnancy: A prospective, multicentre cohort study. Am J Obstet Gynecol 1996;174:823-8.
30Davies WB, Wells SR, Kuller JA, Thorp JM Jr. Analysis of the risks associated with calcium channel blockade: Implications for the obstetrician-gynecologist. Obstet Gynecol Surv 1997;52:198-201.
31Peatfield RC, Petty RG, Rose FC. Double blind comparison of mefenamic acid and acetaminophen (paracetamol) in migraine. Cephalalgia 1983;3:129-34.
32Bourean F, Joubert JM, Lasserre V, Prum B, Delecoeuillerie G. Double-blind comparison of acetaminophen 400 mg-codeine 25 mg versus aspirin 1000 mg and placebo in acute migraine attack. Cephalalgia 1994;14:156-61.
33Taylor FR. Acute treatment of migraine headaches. Semin Neurol 2010;30:145-53.
34Slone D, Siskind V, Heinonen OP, Monson RR, Kaufman DW, Shapiro S. Aspirin and congenital malformations. Lancet 1976;1:1373-5.
35Veille JC, Hanson R, Sivakoff M, Swain M, Henderson L. Effects of maternal ingestion of low-dose aspirin on the fetal cardiovascular system. Am J Obstet Gynecol 1993;168:1430-7.
36Hainline B. Headache. Neurol Clin 1994;12:443-60.
37Mills JL, Holmes LB, Aarons JH, Simpson JL, Brown ZA, Jovanovic-Peterson LG, et al. Moderate caffeine use and the risk of spontaneous abortion and intrauterine growth retardation. JAMA 1993;269:593-7.
38Silberstein SD. Headaches and women: Treatment of the pregnant and lactating migraineur. Headache 1993;33:533-40.
39Duong S, Bozzo P, Nordeng H, Einarson A. Safety of triptans for migraine headaches during pregnancy and breastfeeding. Canadian Family Physician 2010;56:537-39.
40Olesen C, Steffensen FH, Sorensen HT, Nielsen GL, Olsen J. Pregnancy outcome following prescription for Sumatriptan. Headache 2000;40:20-4.
41Reif- Eldridge R, Heffner CR, Ephross SA, Tennis PS, White AD, Andrews EB. Monitoring pregnancy outcomes after prenatal drug exposure through prospective pregnancy registries: A pharmaceutical company commitment. Am J Obstet Gynecol 2000;182:159-63.
42Soldin OP, Dahlin J, O′Mara DM. Triptans in pregnancy. Ther Drug Monit 2008;30:5-9.
43Pruyn SC, Phelan JP, Buchanan GC. Long-term propranolol therapy in pregnancy: Maternal and fetal outcome. Am J Obstet Gynecol 1979;135:485-9.
44Peikert A, Wilimzig C, Kohne-Voland R. Prophylaxis of migraine with oral magnesium: Results from a prospective multi-center placebo-controlled and double blind randomized trial. Cephalalgia 1996;16:257-63.
45Kalra S, Born L, Sarkar M, Einarson A. The safety of antidepressant use in pregnancy. Expert Opin Drug Saf 2005;4:273-84.
46Miklovich L, van den Berg BJ. An evaluation of the teratogenicity of certain antinauseant drugs. Am J Obstet Gynecol 1976;125:244-8.
47Park-Wyllie L, Mazzotta P, Pastuszak A, Moretti ME, Beique L, Hunnisett L, et al. Birth defects after maternal exposure to corticosteroids: Prospective cohort study and meta-analysis of epidemiological studies. Teratology 2000;62:385-92.
48Prudy IB, Wiley DJ. Perinatal corticosteroids: A review of research. Part I: Antenatal administration. Neonatal Netw 2004;23:15-30.
49Jensen R. Pathophysiological mechanisms of tention-type headache: A review of epidemiological and experimental studies. Cephalalgia 1999;19:602-21.
50Marcus DA. Estrogen and chronic daily headache. Curr Pain Headache Rep 2004;8:66-70.
51Marcus DA, Scharff L, Turk DC. Nonpharmacological management of headaches during pregnancy. Psychosom Med 1995;57:527-35.
52Silver N. Headache (chronic tension-type). American Family Physician 2007;76:114-6.
53Davis MA, Kononowech RW, Rolin SA, Spierings EL. Accupuncture for tension-type headache: A meta-analysis of randomized, controlled trials. J Pain 2008;9:667-77.
54Heinozen O, Slone D, Shapiro S. editors. Birth defects and drugs in pregnancy. Littleton: Publishing Sciences Group; 1977. p. 336-7.
55Reik L Jr. Headaches in pregnancy. Semin Neurol 1988;8:187-92.
56Safra MJ, Oakley GP Jr. Association between cleft lip with or without cleft palate and prenatal exposure to diazepam. Lancet 1975;2:478-80.
57Nulman I, Rovet J, Stewart DE, Wolpin J, Gardner HA, Theis JG, et al. Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 1997;336:258-62.
58Menon R, Bushnell CD. Headache and pregnancy. Neurologist 2008;14:108-19.
59Bahren A, May A, Goadsby PJ. Cluster headache: A prospective clinical study with diagnostic implications. Neurology 2002;58:354-61.
60Van Vliet JA, Favier I, Helmerhorst FM, Haan J, Ferrari MD. Cluster headache in women: Relation with menstruation, use of oral contraceptives, pregnancy, and menopause. J Neurol Neurosurg Psychiatry 2006;77:690-2.
61Drummond PD. Mechanisms of autonomic disturbance in the face during and between attacks of cluster headache. Cephalalgia 2006;26:633-41.
62Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster headache: A randomized trial. JAMA 2009;302:2451-7.
63Fogan L. Treatment of cluster headache. A double- blind comparison of oxygen v air inhalation. Arch Neurol 1985;42:362-3.
64Edmeads J. Emergency management of headache. Headache 1988;28:675-9.
65Edlow JA, Caplan LR. Avoiding pitfalls in the diagnosis of subarachnoid hemorrhage. N Engl J Med 2000;342:29-36.
66Martin SR, Foley MR. Approach to the pregnant patient with headache. Clin Obstet Gynecol 2005;48:2-11.
67Guidelines for diagnostic imaging during pregnancy. The American College of Obstetricians and Gynecologists. Int J Gynecol Obstet 1995;51:288-91.