Headache Medicine, v.5, n.2, p.33-38, Apr./May/Jun. 2014 33

Migraine as a risk factor associated with hypertensive

disorders of pregnancy

Enxaqueca antes da gravidez como fator associado para distúrbios

hipertensivos da gestação

ORIGINAL ARTICLE

ABSTRACTABSTRACT

ABSTRACT

Objectives: Objectives:

Objectives: To identify if the presence of migraine before

pregnancy predisposes to hypertensive disorders of pregnancy.

Methods:Methods:

Methods: Observational study undertaken from a database

of a follow-up study, composed of women consecutively

assisted, at the first postnatal week, at IMIP. Its objective was

to evaluate the course of migraine during pregnancy and

postpartum in women with migraine before pregnancy. The

Fisher exact test was used considering the significance level of

less than 5%.

Results: Results:

Results: Of the 686 women, 38.8% were

migraine sufferers before pregnancy. 14.3% referred

hypertensive disorders of pregnancy. The presence of migraine

before pregnancy and to have been submitted to a cesarean

section (p<0.001) were factors associated with the presence

of hypertensive disorders in pregnancy.

Conclusion: Conclusion:

Conclusion: Migraine

before pregnancy is an associated factor to hypertensive

disorders of pregnancy. The diagnosis of migraine should

always be taken into consideration during antenatal care, for

the prevention of complications.

KeywordsKeywords

Keywords: Migraine with aura; Migraine without aura;

Pregnancy; Hypertension

Gabriel Braga Diégues Serva

, Leonardo Santos Calvacanti Guerra

, Vilneide Maria Santos Braga Diégues Serva

Waldmiro Antônio Diégues Serva

, Marcela Patrícia Macêdo Belo

Marcelo Moraes Valença

, Maria de Fátima Costa Caminha

Medical Doctor, Faculdade Pernambucana de Saúde (FPS). Recife, PE, Brazil

MsC in Mother and Child Heath at the University of London and Head of the Breast Milk Bank and Center of

Incentive of Breastfeeding at IMIP (BLH/CIAMA/IMIP). Recife, PE, Brazil

PhD in Neurophychiatry and Behavior Sciences of the UFPE, Mphill in Neuroradiology at the University of London,

Associate Professor of the Department of Neuropsychiatry of the UFPE. Recife, PE, Brazil

Nurse Resident in Pediatrics at the IMIP and MsC student in Pediatrics of the UFPE. Recife, PE, Brasil

PhD in Physiology (USP - Ribeirão Preto) and Associate Professor at the Department of Neuropsiquiatry of the

Federal University of Pernambuco (UFPE). Recife, PE, Brazil

PhD in Nutrition at the Universidade Federal de Pernambuco (UFPE) and Researcher at the Research Department

the of the Instituto de Medicina Integral Professor Fernando Figueira (IMIP). Recife, PE, Brazil

Serva

GB, Guerra LS, Serva VM, Serva WA, Belo MP, Valença MM, Caminha MF. Migraine as a risk factor

associated with hypertensive disorders of pregnancy. Headache Medicine. 2014;5(2):33-38

RESUMORESUMO

RESUMO

Objetivos:Objetivos:

Objetivos: Identificar se a enxaqueca antes da gravidez

predispõe aos distúrbios hipertensivos da gestação.

Método: Método:

Método:

Estudo observacional, realizado a partir de banco de dados,

composto por mulheres consecutivamente assistidas na

primeira semana pós-parto em hospital de referência no

Nordeste do Brasil. Foi utilizado o teste exato de Fisher

considerando o nível de significância menor que 5%.

Resultados:Resultados:

Resultados: Das 686 puérperas, 38,8% eram portadoras

de enxaqueca antes da gestação. 14,3% referiram distúrbios

hipertensivos na gestação. Ter enxaqueca antes da gravidez

e ser submetida à cesariana (p<0,001) mostraram-se como

fatores associados aos distúrbios hipertensivos na gestação.

Conclusão: Conclusão:

Conclusão: Enxaqueca antes da gravidez é um fator

associado aos distúrbios hipertensivos da gestação. O

diagnóstico da enxaqueca deve ser sempre levado em

consideração no pré-natal para que haja prevenção de

complicações.

alavrasalavras

alavras

chavechave

chave

: Enxaqueca sem aura; Enxaqueca com

aura; Gravidez; Hipertensão.

34 Headache Medicine, v.5, n.2, p.33-38, Apr./May/Jun. 2014

SERVA GB, GUERRA LS, SERVA VM, SERVA WA, BELO MP, VALENÇA MM, CAMINHA MF

INTRODUCTION

Migraine is a primary headache considered by the

World Health Organization in the nineteenth place among

all diseases causing incapacity.

(1)

In 1938, Graham and Wolff

(2)

were the first to develop

a consistent theory to explain migraine attacks. They

claimed that there was an initial intracranial vaso-

constriction followed by vasodilatation, causing aura and

pain, respectively. Currently, there is evidence that the pain

in migraine is mediated by the trigeminal nerve and that

this may be due to a form of neurogenic inflammation.

(3)

The vasodilatation caused by stimulation of the Gasserian

ganglion is accompanied by the mast cells degranulation

and increased vascular permeability with release of

neuropeptides.

(3)

Furchgott and Zawadzki

(4)

reported that

vasodilatation induced by acetylcholine depended on

an intact endothelium, but nitric oxide, the mediator of

this endothelium-dependent vasodilatation was

identified, also plays a role in hyperalgesia.

(5)

On the

other hand, gestational hypertension and preeclampsia

are disorders that arise during pregnancy, after the

twentieth week.

(6)

The physiopathology of hypertensive disorders of

pregnancy, especially preeclampsia, is not yet fully known,

but it is known that it is multifactorial, involving multiple

organs and even genetic and immunological factors.

(6,7)

During normal pregnancy, the uterine spiral arteries

are transformed from high-resistance vessels into low-

resistance ones, to meet the needs of the growing fetus.

This transformation is the result of trophoblastic invasion

of the arterial layers. In women with preeclampsia,

trophoblastic invasion ceases to occur, or occurs

inappropriately, resulting in high resistance vessels and

placental circulation with low flow. Placental ischemia and

hypoxia determine injury of the the vascular endothelium.

Then, a vicious circle follows up. Placental hypoxia

increases the production of free radicals which damage

the endothelium. Endothelial injury, in turn, triggers platelet

activation, the release of thromboxane (TXA2) and

serotonin and platelet aggregation, with obstruction of

placental blood flow. The placental hypoxia also increases

the production of lipid peroxides which damage the

synthesis of prostacyclin, a potent vasodilatator.

(8)

Thus,

the vascular changes that occur in hypertensive disorders

of pregnancy are similar to those in migraine.

(6,9)

That is why, the etiological relationship between the

two conditions needs investigation because it remains

relatively obscure.

(10)

The literature reports a high risk for

pregnancy-induced hypertension or preeclampsia, among

women with migraine before pregnancy.

(9-13)

So, the present study investigated whether migraine

before pregnancy predisposes to hypertensive disorders

of pregnancy.

METHODS

This is an observational study undertaken from the

database of a follow-up study with two components

(prospective and retrospective), whose main objective was

to evaluate the course of migraine with (MA) and without

aura (MO) during pregnancy and postpartum among

women identified as migraine sufferers before pregnancy,

classified according to International Classification of

Headache Disorders (ICHD-2004).

(1)

Data collection was

conducted from June to November 2009, at the Breast

Milk Bank of the Instituto de Medicina Integral Professor

Fernando Figueira (BMB/IMIP). For the present study,

variables related to socio-demographic, obstetric and

biological characteristics were selected, according to the

research objectives.

The sample used in the initial research that was part

of the follow-up study was composed of mothers who

had given birth at the IMIP. The data collection instrument

was applied in the first postnatal visit around the eighth

day after birth (between the seventh and tenth) at the Out-

patient Clinic of the BMB/IMIP, after signing the Consent

Form. Women with neurological diseases that characterized

secondary headache before pregnancy (epilepsy,

aneurysm, brain tumor, vascular malformation) were

excluded. There was no bias in the sample selection, given

the fact that all women were consecutively admitted in the

study. The sample for the current study consisted of 686

mothers, the same as the total sample of the original

database. There has been no refusal to participate.

The data collection form included questions related

to socio-demographic (education, per capita income,

maternal age, race/color of the skin, marital status,

occupation), obstetric (number of pregnancies and

hypertensive disorders of pregnancy) and biological

factors (MO and MA before pregnancy). All the possible

categories of hypertension during pregnancy

(preeclampsia/eclampsia, chronic hypertension,

preeclampsia superimposed on chronic hypertension or

nephropathy and gestational hypertension) were grouped

under the nomination of hypertensive disorders in

pregnancy.

Headache Medicine, v.5, n.2, p.33-38, Apr./May/Jun. 2014 35

For the processing of the data from the follow-up

study, Epi-info version 6.04.b was used with double data

entry. From this database, we selected the variables of

interest that allowed to identify and compare the frequency

of hypertensive disorders of pregnancy in patients with or

without migraine before pregnancy, thus, an "ad hoc"

database was undertaken. The comparative analysis was

performed using Fisher's exact test. The significance level

of <5% was used to reject the null hypothesis. Data were

processed with SPSS for Windows, version 13.1 (SPSS Inc.,

Chicago, IL, USA). To describe the sample categorical

variables were expressed in terms of absolute and relative

frequencies. For continuous data, according to its

distribution, the result was described by a measure of central

tendency and its associated dispersion.

The present study is in accordance with Resolution

196/96 of the National Ethics Committee. It was approved

in a regular meeting of the Ethics Committee of the IMIP

on December 12

, 2011, under the number 2747-11.

The authors asked the Ethics Committee on Human

Research of IMIP to liberate the Consent Form, since the

article had, as source of information, a database

approved by the same Committee at a Regular Meeting

of April 16

, 2009, under the number 1389.

RESULTS

The sample consisted of 686 postpartum women who

corresponded to the total sample of the original study.

266 (38.8%) were identified as having migraine before

pregnancy, where 237 (34.5%) had MO and 29 (4.3%)

MA, respectively.

The mean age was 25 years, varying from 13 to 46

years old. 71.7% had nine or more years of schooling,

74.8% per capita income less than half of the minimum

wage, and 55.0% reported themselves as brown [most of

them were married or had a consensual union (79.7%),

primigravids (57.1%) and did not work (59.9%)]. The

majority of them had vaginal deliveries (66.5%).

Of the 686 women, 98 (14.3%) reported that they

had suffered hypertensive disorders of pregnancy. Of these

60 (22.6%) occurred in women with MO and MA before

pregnancy and 38 (9.0%) among the other women.

Table 1 shows analyzes the factors associated with

hypertensive disorders during pregnancy. The presence

of migraine before pregnancy and to have been

submitted to a cesarean section (p<0.001) were factors

associated with the presence of hypertensive disorders

in pregnancy.

DISCUSSION

During childhood, girls and boys have similar

prevalence of migraine, however, after puberty there is a

clear predominance among women.

(14)

Lipton et al.,

(15)

a prospective and community based study, showed a

prevalence of migraine during the women's reproductive

life of 25%. In the study by Maggioni et al.

(16)

where the

interviews were conducted after delivery, asking

retrospectively about the presence of MA and MO before

pregnancy, the prevalence was 29%. The frequency was

higher in the present study where 38.8% of the women

suffered from MA and MO before pregnancy. This

difference can be justified because it was a hospital

centered sample, with data collection performed

retrospectively, although consecutively, which reduced the

possibility of bias. However, a prospective study of 720

pregnant women followed from the 11

-16

week of

gestation until postpartum showed a prevalence of 38.5%.

25.5% of these women were MO sufferers, 5% had MA

and 6.9% were probable migraine sufferers.

(9)

The present

study did not show different results, showing frequencies

of 34.5% and 4.3% for MO and MA, respectively.

Facchinetti et al.

(9)

concluded that the prevalence of

migraine in their study, greater than other studies in the

literature,

(15,16)

was not due to selection bias, since the

subjects were recruited from the general population. They

believed that their finding were consistent with the age

range studied and also because it was a population of

white women who have a higher prevalence of migraine.

(9)

That was not true in the present study, where the sample

was mostly composed of women who referred themselves

as brown or black (74.5%).

Hypertensive disorders of pregnancy were present in

14.3% of the pregnant women. This finding did not differ

with those of the literature that shows a prevalence of 10

to 22% of hypertensive disorders of pregnancy, being the

most common complication of the gestational period.

(17,18)

Another observational and retrospective study in a referral

hospital in Recife, evaluating medical records of 12,272

pregnant women, showed that 10.26% of them met the

inclusion criteria for hypertension, both gestational and

chronic hypertension

(19)

and again reporting similar

frequency of that of the present study.

Women with migraine before pregnancy suffer a

significant and progressive decrease of their seizures

during the gestational period.

(20,21)

However, these

women are at greater risk for developing gestational

hypertension, preeclampsia and eclampsia.

(9-13)

Although

MIGRAINE AS A RISK FACTOR ASSOCIATED WITH HYPERTENSIVE DISORDERS OF PREGNANCY

36 Headache Medicine, v.5, n.2, p.33-38, Apr./May/Jun. 2014

SERVA GB, GUERRA LS, SERVA VM, SERVA WA, BELO MP, VALENÇA MM, CAMINHA MF

the primary mechanisms of migraine and preeclampsia

are not completely understood, both diseases are

characterized by having an altered vasoreactivity and

platelet abnormal behavior,

(9-11)

and can therefore share

a common etiology.

(12)

It is believed that migraine as well

as gestational hypertension, preeclampsia and eclampsia

have some characteristics that may increase the risk of

ischemic disorders

(9)

due to vascular alterations that occur

in such conditions, as platelet hyperaggregation,

(22,23)

reduced magnesium availability

(24,25)

and decreased

production of prostacyclines.

(26,27)

Although the latest

physiological findings suggest that migraine is more a

disorder of the nervous system, rather than of the vascular

system,

(13)

Kruit et al.

(28)

showed that patients with migraine

have an increased risk of developing subclinical brain

infarcts.

The risk of developing hypertensive disorders of

pregnancy was higher in patients with migraine before

pregnancy (9.1%) compared with those without the disease

(3.1%), adjusted for age, family history of hypertension

and smoking with the OR of 2.85 (95% IC 1.40-5.81).

(9)

In that study, hypertension was defined as the onset of

gestational hypertension and preeclampsia. They

excluded women with chronic hypertension before

pregnancy and those who had suffered from hypertensive

disorders of pregnancy in previous gestational periods.

(9)

Both women with MO and MA before pregnancy showed

gestational hypertension and preeclampsia during

Headache Medicine, v.5, n.2, p.33-38, Apr./May/Jun. 2014 37

pregnancy in a similar frequency, 10.3% and 11.1%,

respectively.

(9)

Adeney et al.

(13)

showed that a history of

migraines before pregnancy increased by 1.8 times the

risk of preeclampsia (95% CI 1.1-2.7). That study also

highlighted the importance of age, women who were

diagnosed as being migraine sufferers with 30 years or

more had a higher risk of developing preeclampsia during

pregnancy (OR 2.8, 95% CI 0.8-9,0).

(13)

The association

of migraine and preeclampsia in overweight women

compared to controls without migraine and without

overweight was even greater, with a 12 fold greater risk

of preeclampsia (95% CI 5.9-25.7).

(13)

The present study

showed a statistically significant difference p<0.001 in

relation to the association among women with MO and

MA before pregnancy and a higher frequency of

hypertensive disorders of pregnancy. All possible causes

of hypertension during pregnancy were grouped under

the scope of hypertensive disorders of pregnancy. Age,

however, was not a statistically significant variable,

probably because the age at onset of the migraine attacks

was not investigated.

In the present study there was a significant higher

chance of hypertensive disorders among the women with

migraine versus the ones without migraine [60/266

(22.6%) vs. 38/420 (9.1%), OR 2.928 95%CI 1.885-

4.548] (Figure 1).

obstetric and not solely due to the hypertensive disorders

of pregnancy.

(9)

Although it was not possible in the present study to

classify the type of hypertension disorder of pregnancy,

once the study was realized from the database collected

from postpartum women, the association between

migraine before pregnancy and hypertensive disorders

of pregnancy may indicate that certain women are

predisposed to placental ischemia and brain, and are

thus at high risk for stroke and severe brain damage.

(13)

There is no absolute agreement among the authors to

explain the pathophysiology of migraine and

hypertensive disorders of pregnancy, especially

preeclampsia, however, the hemodynamics of migraine

is similar to that of pre-eclampsia, with reduced perfusion,

possibly mediated by endothelial dysfunction oxidative

stress.

(13)

In conclusion, women with migraine before

pregnancy are more likely to have hypertensive disorders

during the pregnancy.

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although the indication of the type of delivery should be

MIGRAINE AS A RISK FACTOR ASSOCIATED WITH HYPERTENSIVE DISORDERS OF PREGNANCY

38 Headache Medicine, v.5, n.2, p.33-38, Apr./May/Jun. 2014

Correspondence

aldmiro Antônio Diégues Servaaldmiro Antônio Diégues Serva

aldmiro Antônio Diégues Serva

Rua Astronauta Neil Armstrong, 120/1302. Casa Amarela, CEP:

52060-170 – Recife, PE, Brasil

Telephone: 55 (81) 3268-4638 / Fax: 55 (81) 2126-8523

e-mail: wserva@hotmail.com

e-mail: amanda-aas@hotmail.com

Received: June 3,2014

Accepted: June 20, 2014

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SERVA GB, GUERRA LS, SERVA VM, SERVA WA, BELO MP, VALENÇA MM, CAMINHA MF