70 Headache Medicine, v.3, n.2, p.70-75, Apr./May/Jun. 2012

Headache and pregnancy

Cefaleia e gravidez

VIEW AND REVIEWVIEW AND REVIEW

VIEW AND REVIEW

ABSTRACTABSTRACT

ABSTRACT

Headache in pregnancy is a peculiarity of woman life phase.

Correct diagnosis in pregnancy is the best thing for a

management gold standard. Some secondary headaches that

mimic migraine may begin during pregnancy, and can be

caused by vasculitis, brain tumor, pituitary tumor, arteriovenous

malformation, sinus disease, idiopathic intracranial

hypertension, subarachnoid hemorrhage, stroke, cerebral

venous thrombosis, pre-eclampsia and eclampsia. These

headaches must be correctly diagnosed. At the conclusion, if

a pregnant patient presents primary headache, it will be

necessary to treat her. The classic teratogenic risk occurs from

the 29

day to the 70

day of gestation. Women with severe

headache during this period should be treated because nausea

and vomiting in association with pain can be teratogenic to

the fetus. Non-pharmacological techniques are effective for

acute and preventive treatment and should be applied. If drugs

are necessary, will be choose minimal doses and medications

that causes fewer problems in pregnancy. Management of

pregnant women with migraine should be done with caution,

keeping in mind the low level of scientific evidences.

ey words: ey words:

ey words: Pregnancy; Headache; Migraine; Treatment.

RESUMORESUMO

RESUMO

Cefaleia na gestação é uma peculiaridade de uma fase da

vida da mulher. O diagnóstico correto da cefaleia na gravidez

é a chave para um tratamento de excelência. Algumas cefaleias

secundárias que mimetizam migrânea podem se iniciar durante

a gestação, e podem ser causadas por vasculites, tumor

cerebral, tumor hipofisário, malformação arteriovenosa,

sinusopatias, hipertensão intracraniana idiopática, hemorragia

subaracnóidea, acidente vascular encefálico, trombose venosa

cerebral, pré-eclâmpsia e eclâmpsia. Tais cefaleias devem ser

diagnosticadas corretamente. Ao se concluir que a paciente

grávida apresenta cefaleia primária, é necessário tratá-la. O

risco teratogênico clássico das drogas ocorre a partir do 29º

até o 70º dia a partir do 1º dia da última menstruação da

mulher. Mulheres com cefaleia intensa nesse período devem

ser tratadas, pois náuseas e vômitos em associação com dor

podem ser teratogênicos ao feto. Técnicas não farmacólogicas

são efetivas para tratamento agudo e preventivo e devem ser

empregadas. Se drogas forem necessárias, escolher as

menores doses e que causem menos problemas na gravidez.

O tratamento da gestante com enxaqueca deve ser realizado

com muita cautela, tendo-se em mente que o nível de evidência

é baixo.

alavrasalavras

alavras

chave:chave:

chave: Cefaleia; Gravidez; Enxaqueca; Tratamento

INTRODUCTION

Pregnancy is a peculiar woman life phase, considered

optional. It usually occurs during woman´s professional

highest peak. Headache in pregnancy is a woman's

particularity, and like other disturbances in this phase, must

be seen with caution. Its progress must be followed and

its treatment must be carefully addressed.

(1)

Correct diagnosisCorrect diagnosis

Correct diagnosis

The diagnosis of a headache disorder must be correct

for a suitable management. In pregnant and lactating

woman this is done through the Classification of the

International Headache Society (2004).

(2)

On the anamnesis of a pregnant woman with

headache, it´s important to always ask her if she had

headaches before pregnancy, or if the headaches started

during pregnancy, or if she had a prior headache and

there were changes in the headache characteristics during

the pregnancy.

Eliana Meire Melhado, Andressa Regina Galego

Faculdade de Medicina de Catanduva das Faculdades Integradas Padre Albino (FIPA), Catanduva, SP, Brazil

Melhado EM, Galego AR. Headache and pregnancy. Headache Medicine. 2012;3(2):70-5

Headache Medicine, v.3, n.2, p.70-75, Apr./May/Jun. 2012 71

It is always necessary to distinguish between pre-

existing headaches and those initiated during pregnancy

because there may be three possibilities: (1) monitoring

the behavior of an existing headache prior to pregnancy,

during pregnancy; (2) appearance of a new headache

during pregnancy; and (3) the woman had presented a

headache before getting pregnant and then develops a

new one during pregnancy.

SECONDARY HEADACHES

Migraine-like headache that began during pregnancy

may be secondary to vasculitis, brain tumor, chorio-

carcinoma, pituitary tumor, arteriovenous malformation

(AVM), sinus disease, idiopathic intracranial hypertension,

subarachnoid hemorrhage, stroke, cerebral venous

thrombosis, pre-eclampsia and eclampsia.

(3,4)

Some comments about specific secondary headaches:

1. The diagnosis of sinusitis is often overstated,

chronic sinus does not cause headache;

(3,4)

2. Only 48% of brain tumor patients develop

headache during pregnancy. Pregnancy does not increase

the risk of brain tumor;

3. Pregnant women have 13 times the risk of having

a stroke. One of the most common stroke during

pregnancy is cerebral venous thrombosis. Most cases

present neurological deficits, but the superior sagittal sinus

thrombosis may present with progressive headache,

without neurological signs or symptoms;

4. Subarachnoid hemorrhage explains 50% of

intracranial bleeding during pregnancy. Subarachnoid

hemorrhage may mimic eclampsia. Most cases of

intracranial hemorrhage, especially in the eclampsia

group, result from hypertension. Illicit substances (alcohol

and cocaine) is a cause of subarachnoid and intracerebral

hemorrhage during pregnancy;

(3)

5. Differential diagnosis of thunderclap headaches

of sudden onset includes reversible cerebral vaso-

constriction syndrome, subarachnoid hemorrhage by

aneurysm, cerebral venous thrombosis, dissection of the

carotid or vertebral artery, intraparenchymal hemorrhage

and pituitary apoplexy. Neuroimaging is required in such

cases. Reversible cerebral vasoconstriction syndrome

encompasses a diverse group of conditions, including

hypertensive encephalopathy and vasculopathy

associated with pregnancy and the postpartum period

(postpartum angiopathy). Reversible cerebral vaso-

constriction syndrome is characterized by sudden onset of

a severe headache that subsides within a few days to weeks

and resolves in most patients, approximately 12 weeks

after the presentation. A similar syndrome can be seen

with pre-eclampsia and eclampsia occurring before birth

or postpartum. A diagnosis of reversible cerebral vaso-

constriction syndrome requires the exclusion of other causes

of headache accompanied by tomography or magnetic

resonance imaging and magnetic angiography

resonance to evaluate arterial and venous vasoconstriction

or cerebral edema, and exclude cerebral venous

thrombosis. Cerebrospinal fluid obtained via lumbar

puncture can eliminate vasculitis or infection.

(5)

Symptomatic headaches require neuroimaging or

lumbar puncture to diagnose. The guidelines for neuro-

imaging in patients who are or may be pregnant are:

1. Determinate the necessity and the potential risks

of the procedure.

2. If possible, perform the examination during the

first 10 days postmenses, or if the patient is pregnant,

delay the examination until the third trimester or preferably

postpartum.

3. Pick the procedure with the highest accuracy

balanced by the lowest radiation.

4. Use MRI if possible.

5. Avoid direct exposure to the abdomen and pelvis;

6. Avoid contrast agents.

7. Do not avoid radiologic testing purely for the sake

of the pregnancy.

8. If significant exposure in incurred by a pregnant

patient, consult a radiation biologist.

9. Consent forms are neither required nor

recommended.

(4)

Head CT is relatively safe during pregnancy and is

the study of choice for head trauma and possible non-

traumatic subarachnoid, subdural or intraparenchymal

haemorrhage.

MRI is preferable for all other non-traumatic or non-

haemorrhagic craniospinal pathologies. The potential

risks of MRI in pregnancy are still controversial. First use

angiography to evaluate suspected vascular pathology,

but, when necessary, angiography is reasonably safe in

pregnant patient.

(4)

A CT scan exposes the mother to a radiation of

<0.01 Gray (Gy), while the threshold of fetal damage

with ionizing radiation directly into the maternal pelvis is

>0.1 to 0.2 Gy. To maintain the safety margin, the

National Council for Radiation Protection and

Measurements grouped the acceptable limits of radiation

in all scan sat 0.05 Gy. MRI does not show the same

level of risk associated with ionizing radiation.

72 Headache Medicine, v.3, n.2, p.70-75, Apr./May/Jun. 2012

Gadolinium-based contrast agents have been

associated with the development of nephrogenic systemic

sclerosis . This condition is rare and has been reported

to occur in patients with compromised renal function.

Gadolinium can cross the placenta into the fetal

circulation and, subsequently, is excreted into the amniotic

fluid, where the agent can remain for an extended period

of time. No prospective studies with large numbers of

patients have evaluated the risk of teratogenic or

mutagenic effects.

The American College of Radiology Guidelines

Document for Safe MR Practices recommends that

pregnant patient should only receive gadolinium-contrast

agents after careful consideration of the risk-benefit ratio.

Iodinated CT contrast agent has been associated with

contrast-induced nephropathy in as many as 21% of

patients who had a baseline glomerular filtration rate of

<50 ml/min/1.73 m

. Nephropathy induced by iodinated

CT contrast agent is usually reversible, but the condition

can be associated with nonrenal complications that can

prolong hospital stays and increase in-hospital mortality.

Free iodide in the contrast medium given to the mother

has the potential to depress fetal and neo natal thyroid

function. Neonatal thyroid function should, therefore, be

checked after delivery in such patients. The risk associated

with absorption of contrast medium during lactation is small

and can be considered insufficient to warrant stopping of

breastfeeding. The neonatal thyroid should be checked

after labor in such patients.

(5-10)

Potential indications for computed tomography or MRI

in headache investigation during pregnancy are the same

as an average patient with suspected secondary headache

(Table 1).

MEDICATIONS ON PREGNANCY AND FETUS

If the conclusion is that the pregnant patient presents

primary headache, it will be necessary to treat headaches

during pregnancy. Then, there will be a concern with

regarding the treatment.

ManagementManagement

Management

Treatment of pregnant women is a part of medicine

based in low scientific quality of evidence. The experience

in treating these women comes from case-control studies

and and populational retrospectives.

Tables with drugs risks in pregnancy risk of learning

disabilities are deficient, and 40% of the drugs do not

have a listed category. The decision about what to use

during pregnancy should be made case by case, using

incomplete information.

It must always be applied in migraineurs pregnant

women non-pharmacological treatment which is free from

risk to fetus and mother.

(1,11)

The classic teratogenic risk occurs from the 29

day

to the 70

day of gestation (after the first day of the

woman's last menstruation). Women with severe headache

during this period should be treated because nausea and

vomiting resulting due to pain may be teratogenic to the

fetus.

(12)

The evaluation of the first trimester is therefore a

serious methodological error, only the second and third

months represent the critical period of most major

congenital abnormalities (CAs). On the other hand, we

know that the critical period of some CAs exceeds the end

of third month, e.g., the critical period of posterior cleft

palate and hypospadias covers the 12

-14

and 14

weeks of gestation, while the critical period of

undescended testis and patent ductus arteriosus is 7 to 9

months and 9 to 10 months, respectively. Thus, the optimal

approach is to consider the specific critical period of each

CA separately.

(12)

The FDA (Food and Drug Administration) lists five

categories of labeling for drug use in pregnancy. These

categories provide therapeutic guidance, weighting the

risks as well as the benefits of the drug. An alternate

rating system is TERIS (an automated teratogen

information resource wherein ratings for each drug or

agent are based on a consensus of expert opinion and

MELHADO EM, GALEGO AR

Headache Medicine, v.3, n.2, p.70-75, Apr./May/Jun. 2012 73

the literature) which was designed to measure the

teratogenic risk to the fetus from drug exposure (Tables

2 and, 3).

Table 4 presents some drugs and their risk categories

(FDA and TERIS)

(3-5,12-16)

Magnesium, riboflavin, pyridoxine hydro-Magnesium, riboflavin, pyridoxine hydro-

Magnesium, riboflavin, pyridoxine hydro-

chloridechloride

chloride – there is no evidence of risk of multiple

congenital anomalies associated with periconceptional use

of vitamin supplementation.

(17)

Symptomatic treatment of migraineurSymptomatic treatment of migraineur

Symptomatic treatment of migraineur

pregnant womenpregnant women

pregnant women

Measures that can be used taken symptomatic therapy

in migraine of pregnant women are:

– Hydration.

– NSAIDs (ibuprofen, naproxen, can close the fetal

ductus arteriosus), corticosteroids (useful, occasional).

– Aspirin (low dose).

– Common analgesics (acetaminophen).

– Narcotic analgesics.

– Chlorpromazine, promethazine, metoclopramide;

– Triptans (naratriptan and sumatriptan) (no evidence

of abnormality, can be used if other drugs do not solve,

to avoid during the 2

and 3

months).

– Pyridoxine (for nausea – not teratogenic).

What not to use in pregnant women withWhat not to use in pregnant women with

What not to use in pregnant women with

headacheheadache

headache

Natural or herbal therapy (because they are less

studied); feverfew (by presenting possible teratogenicity);

ergotamine, dihydroergotamine (are contraindicated for

showing an association with increased risk of neural tube

defects and a higher proportion of premature births,

neonatal lower weight birth and low gestational age;

(18)

benzodiazepines and barbiturates (for cleft palate

occurrence and heart and urogenital defects), valproate

and divalproex

(1)

(for neural tube defects such as bifid

spina and myelomeningocele, cardiac abnormalities, such

as levocardia, aortic stenosis, patent ductus arteriosus,

tetralogy of Fallot, partial right bundle branch block,

ventricular septal defect, and various facial defects);

Receptor inhibitors of the angiotensin converting enzyme

(ACE) (association with fetal kidney problems).

(1)

CONCLUSIONS

It is recommend that women at childbearing age take

vitamin supplement with 0.4 g of folic acid to reduce risk

of neural tube defect. If pregnancy is desired by the

migraineurs, discontinuation of medications must be made

before conception. If the woman becomes pregnant during

treatment, the conduct will depend of the used medication.

Non-pharmacological techniques are effective for

acute and preventive treatment.

Preventive or prophylactic treatmentPreventive or prophylactic treatment

Preventive or prophylactic treatment

Classes of drugs that can be used like prophylactic

on pregnant woman migraine:

Beta-blockersBeta-blockers

Beta-blockers

– Propranolol – adverse events: delay uterine growth,

hypoglycemia, bradycardia and breathless;

– Atenolol – adverse events: lower weight at birth;

– Metoprolol -adverse effects: growth delay;

– Labetalol

(11)

Corticosteroids Corticosteroids

Corticosteroids – helpful for occasional use in a

regimen of short prophylaxis helps in the maturation of

fetal lungs.

(15)

Prednisone and prednisolonePrednisone and prednisolone

Prednisone and prednisolone – no risk, they must

have preference over dexamethasone, as the latter crosses

the placental barrier.

Serotonin reuptake inhibitors (SSRIs)Serotonin reuptake inhibitors (SSRIs)

Serotonin reuptake inhibitors (SSRIs) – fluoxetine

and sertraline are useful in migraine and comorbid

conditions such as anxiety or depression.

HEADACHE AND PREGNANCY

74 Headache Medicine, v.3, n.2, p.70-75, Apr./May/Jun. 2012

MELHADO EM, GALEGO AR

Headache Medicine, v.3, n.2, p.70-75, Apr./May/Jun. 2012 75

If drugs are necessary, you will choose small doses

and drugs that cause fewer problems in pregnancy.

Experts (Hungarian, American and European) after

several reviews, ask if we can improve our uncertain ties

about the treatment of the pregnant migraineurs and

answer that little can be expected about changing the

situation in the future. Forbidding to use drugs during

pregnancy is mostly due to ignorance of its action over

the fetus than the opposite.

The treatment of pregnant women with migraine

should be done with caution, bearing in mind that the

evidence is low, and this fact will not change in the future.

Headache in pregnancy is a vast theme and should be

studied in a more complex way because it involves two

beings: the pregnant woman and the fetus. The message

here is that there is still much to be done in order to

clarify this so great universe of headache in pregnant

women.

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Correspondence

Eliana Meire MelhadoEliana Meire Melhado

Eliana Meire Melhado

Rua Teresina 502 – Centro,

15800-300 – Catanduva, SP, Brazil

elianamelhado@unimedcatanduva.com.br

Received: 6/23/2012

Accepted: 6/30/2012

HEADACHE AND PREGNANCY