Longitudinal Prospective Study of Headache During Pregnancy and Postpartum

Dawn A. Marcus, MD; Lisa Scharff, PhD; Dennis Turk, PhD

Chronic headache fluctuates in response to changes in hormonal levels. Headache generally improves with

rising estrogen levels, and worsens with falling levels. Headache should, therefore, predictably improve with preg-

nancy and worsen postpartum. Several retrospective studies have confirmed this pattern. In this study, 49 pregnant

women with chronic headache (18 with migraine, I6 with tension-type, and 15 with combined migraine and

tension-type) were followed prospectively. Headache activity was recorded daily throughout pregnancy and for 3

months postpartum. Overall, there was a 30% improvement in headache between the second and third trimesters

for the entire sample. This was not statistically significant. Headache improved significantly for 41% of the women,

with a slightly greater tendency for headache to improve in women with migraine compared to those with tension-

type or combined migraine and tension-type headaches. Headache activity was not influenced by history of

menstrual migraine, history of headache change with prior pregnancies, parity, or breast-feeding. In general,

women reporting headache at the end of their first trimester continued to report headache throughout pregnancy

and postpartum.

Key words: pregnancy, postpartum, migraine, tension-type

Abbreviations: WHYMPI West Haven-Yale Multidimensional Pain Inventory, CES-D Center for Epidemiological

Studies Depression Scale, HALOC Headache Locus of Control Scale, STPI State-Trait Personality

Inventory, HI headache index, LOC locus of control

(Headache 1999;39:625-632)

A number of studies have reported that pain threshold

increases during pregnancy.‘-’ Dawson-Basoa and

Gintzler demonstrated increasing pain threshold in rodents

in direct relationship with increasing estrogen.” Estrogen

influences pain by its ability to alter neural function, as

well as altering levels of neurotransmitters important in

the development of pain, such as serotonin, norepineph-

rine, dopaminc, and endorphins.’ These same

neurotransmitters, such as serotonin, are important in the

pathogenesis of chronic headache, such as migraine and

From the Departments of Anesthesiology and Neurology, University of Pittsburgh (Penn) School of Medicine (Drs. Marcus and Scharff) and the Department of Anesthesiology, University of Washington School of Medicine, St. Louis, MO (Dr. Turk).

Address all correspondence to Dr. Dawn A. Marcus, Pain Evaluation and Treatment Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213.

Accepted for publication March 2,1999.

Headache

tension-type headache.ror review,6 As estrogen levels

increase, there is a corresponding increase in peripheral

serotonin,T which should provide an increased inhibitory

influence on headache pathways. Therefore, increased

estrogen should result in a protective effect against

headache. with headache triggered by estrogen withdraw-

al. Somerville confirmed this relationship between

headache and estrogen, demonstrating relief of menstrual

migraine by estrogen supplementation.8.”

Pregnancy is associated with sustained high estrogen

levels, with a precipitous drop in estrogen at delivery.

These estrogen changes suggest that pregnancy should

result in improved headache during pregnancy, and wors-

ening of headache after delivery. Several retrospective

studies have confirmed this hypothesis. A number of stud-

ies have reported retrospective improvement in migraine

during pregnancy of between 50% and 80%.‘0-1J

Rasmussen evaluated both migraine and tension-type

headache, reporting improvement in 48% of women with

625

migraine and 28% with tension-type headache during

pregnancy.ld For most other women, headache remained

unchanged during pregnancy. Stein and colleagues report-

ed increased headache during the first week after delivery

in 39% of all women and 58% of migraineurs.15Yt” A recent

retrospective study, however, failed to confirm these earli-

er findings. (Paul0 de Queiroz L, Camargo CF. Headache

and pregnancy: study on 100 patients from a university

hospital. Presented at the International Brazilian Headache

Congress; 1998.) In this study of 40 mixed headache suf-

ferers, headache began with the current pregnancy in lo%,

worsened in 34%, stayed the same in 33%, and improved

in only 23%. Interestingly, and also contrary to earlier

studies, they also noted that headache worsened in the

third trimester.

Several factors may affect headache during

pregnancy, in addition to headache type. These include

history of menstrual migraine, parity, prior experience of

changes in headache during pregnancy, and breast-feed-

ing. Retrospective studies report relief of migraine during

pregnancy in 64% with a history of menstrual migraine

and only 48% without a history of menstrual migraine.17

Prior experiences of physical changes with pregnancy or

changes in headache during pregnancy might lead to an

expectancy about anticipated headache changes with

future pregnancies. This is supported by a study in which

primiparous women experienced decreasing somatic

symptoms throughout pregnancy. whereas somatic symp-

toms did not decrease or worsen in multiparous women.‘”

Finally, migraine may be affected by breast-feeding,

although this change has only been seen in about 0.2% of

headache sufferers who breast-feed. 19-21 Breast-feeding

might be expected to reduce headache because of increas-

es in levels of the antinociceptive hormones, vasopressin

and oxytocin.**JJ

Psychological factors may also influence headache

complaints.*” Symptoms of depression or anxiety or both

are identified in 20% to 50% of sufferers of chronic

headache.25 Ho et al demonstrated increased headache

severity and frequency in relation to Zung depression

scores.26 Depression and anxiety may also be associated

with pregnancy. Nine percent of women complain of

depression during pregnancy and 12% postpartum.27

Symptoms of anxiety have been reported in 33% of preg-

nant women.2* These reports of symptoms of depression

and anxiety may negatively influence headache during

pregnancy. Thus, changes in psychological symptoms may

also influence headache activity during pregnancy.

Retrospective data supports improvement of headache

during pregnancy, particularly in the 60% of women with

a history of menstrually associated headache. Based on the

available literature, other factors that appear to predict

reduction in headache with pregnancy include a diagnosis

of migraine, first pregnancy, and a prior history of

headache improvement during pregnancy. The results of a

preliminary prospective analysis of headache during preg-

nancy suggested similar trends; however, the patient

number was insufficient to show statistically significant

changes. z9 The present study is an extension of our pre-

liminary study, with increased numbers of subjects.

SUBJECTS AND METHODS

Women in early pregnancy were recruited through

advertisements placed in obstetricians’ offices and local

newspapers. Women qualified for inclusion in the study if

they were at least 18 years old, no more than 16 weeks

pregnant, and were currently experiencing headache at

least twice a month. A total of 64 women were evaluated

for the study, and 56 (87.5%) agreed to participate. Seven

women (12.5%) dropped out during the course of the

study, with 4 citing time constraints for completing the

forms. Three of the 7 were dropped by the study coordina-

tor due to noncompliance in returning the headache

diaries.

The mean age of the 49 women who completed the

study was 29.4 years (SD=4.9), with a mean headache

duration of 9.1 years (SD=8.9). Most women reported a

chronic history of headache; however, 14 (28.6%) report-

ed headache onset with the current pregnancy. The mean

weeks of gestation at study enrollment was 12.4 weeks

(SD=2.4), with a range from 8 to 16 weeks. Twenty-one

women (42.9%) were experiencing their first full-term

pregnancy. The sample was ethnically representative of the

Pittsburgh region: 85.7% (r-+2) of the women were white,

10.3% (n=5) were African Americans, 2% (n=l ) Asian

American, and 2% (n=l) were Hispanic. The majority

(95.9%) had at least a high school education, and 27

women (55.1 O/o) had at least an undergraduate degree.

Thirty-eight (77.6%) were married, and 26 (53.1%) were

employed in full-time or part-time work outside of

626 Octobec 1999

the home.

All subjects were evaluated by a board-certified neu-

rologist and a psychologist. The neurological assessment

included a general medical and headache history and a

physical examination including general medical, neurolog-

ical, and musculoskeletal assessments. The psychological

evaluation included a semistructured interview and

several self-report assessment questionnaires described

below. Psychological testing allowed comparisons

between this sample and other headache populations, as

well as the identification of symptoms of depression and

anxiety that may influence headache activity. Subjects

scored similarly on the psychological tests to patients with

headache in previous studies.j@32

Headache diagnoses were assigned using criteria

established by the International Headache Society.

Inclusion criteria for the study required the diagnosis of

migraine, tension-type, or coexisting migraine and ten-

sion-type headache. This latter group is labeled as having

combined headache. Migraine was diagnosed in 18

women (12 with and 6 without aura), tension-type

headache in 16, and combined headache in 15.

Subjects completed self-report questionnaires at the

initial assessment, at 5 months’ and 8 months’ gestation,

and 12 weeks after delivery. All questionnaires were sent

and returned in the mail. The following questionnaires

were utilized:

The West Haven-Yale Multidimensional Pain

Inventory (WHYMPI)JO assesses the psychosocial and

behavioral aspects of pain in relation to an individual’s

perceptions of pain intensity, life impact, responses of sig-

nificant others, and performance of common activities.

The WHYMPI is a 60-item self-report inventory with

items scored on a range of 0 (none) to 6 (extreme reports).

It has been demonstrated to have good reliability and

validity,30 and has also been used previously in samples of

patients with headache.33J4

The Center for Epidemiological Studies Depression

Scale (CES-D)35 is a 20-item questionnaire developed by

the Center for Epidemiological Studies of the National

Center for Health Statistics. This scale measures depres-

sive symptomatology with an emphasis on affective

symptoms. The CES-D was developed for use with com-

munity rather than psychiatric samples. It has excellent

psychometric properties and has been used with patients

with headache.33 Scores of 16 or greater represent clini-

cally significant depressive symptoms.

The Headache Locus of Control Scale (HALOC)Q is

a 33-item questionnaire that assesses individuals’ beliefs

that they are able to control their headaches (internal locus

of control), that headaches come and go by chance or are

uncontrollable (chance locus of control), or that a health

cart professional is able to control their headaches (health

care professional locus of control). The possible score

range for each of these three scales is 11 (least perceived

control) to 55 (maximal perceived control). The HAVOC

has been shown to be a reliable and valid instrument with

sufferers of headache.‘”

The Trait section of the State-Trait Personality

Inventory (STPI)37 consists of three subscales with 10

items each: T-anger, T-anxiety, and T-curiosity. Only the

T-anxiety scale was of interest for this study. The T-anxiety

scales use a 4-point Likert scale, ranging from almost

never (1) to always (4). Higher ratings on the T-anxiety

scale indicate a higher frequency of anxious feelings.

In addition to the above questionnaires, study partici-

pants recorded headache intensity four times daily on

prestamped weekly diary postcards. These postcards were

mailed to the research office weekly by each subject.

Diary recording began at initial assessment, and continued

until 12 weeks after delivery. A monthly headache index

(HI) was calculated as mean headache intensity of all 28

ratings per week. The HI reflects changes in overall

headache activity, including severity, frequency, and dura-

tion_ Missing data was replaced by a series mean, or the

mean of the two values before and after the missing data

point in the series. Study participants were quite compliant

with headache diary recording, and a total of only 29 miss-

ing values, or 2.1% of the data, were replaced with mean

values.

After each subject had completed participation, a

monthly HI was calculated from the month before the date

of birth back to enrollment in the study. Six pregnancy HIS

per subject were calculated in this manner. A similar

monthly HI was calculated from the date of birth forward

for 3 months, resulting in three postpartum HIS.

RESULTS

Headache Diary Recordings.-Monthly HI mean

scores for the group were plotted for 6 months before birth

Headache 627

and the first 3 months after delivery. These data for the

entire group are shown in Figure 1. These data in Figure 1

show a trend toward headache improvement between the

second and third trimesters. A repeated-measures analysis

was conducted with all nine of the indices and a between-

subjects factor of headache diagnosis (with three levels:

tension-type, migraine, and combined diagnosis).

Mauchly’s test revealed the assumption of sphericity was

violated (~2~~ =97.27, fc.00 1 ), thus a Greenhouse-Geisser

correction was used as a conservative approach to interpret

the analyses. Tests of within-subjects effects demonstrated

trends for a main effect of time (F4 ,=.84, P=.O7) and for a

time by headache diagnosis interaction (F. ,=0.73, P=.O6).

There was no main effect for diagnosis (<,=0.69, P=.5 1).

Headache indices for different headache diagnostic groups

are presented in Figure 2.

A HI change score was calculated for each subject to

evaluate groups of subjects who experienced clinically sig-

nificant alteration in headache activity between the second

and third trimesters (50% or more worsening or improve-

ment) and those who did not. The change score was

calculated by comparing a HI of the last 16 weeks of preg-

nancy with the previous 12 weeks as follows:

Second Trimester HI - Third Trimester HI

Change score = Second Trimester HI x 100

No significant change in headache occurred between

the second and third trimesters for 25 women (5 1%).

Twenty women (40.8%) had significantly improved HI

scores and 4 (8.2%) had significant worsening. T tests

comparing women who significantly improved during

pregnancy to those who did not demonstrated a significant

association between headache improvement during preg-

nancy and age (P=.87) or headache duration (F.61).

Contrary to prediction, there was also no relationship

between significant headache improvement and a history

of headaches associated with the menstrual cycle

(although only 29 women responded to this question;

x2,=1.80, P=.l 9). An association between headache diag-

nosis and menstrual headache history with headache

change with pregnancy was not analyzed due to low num-

bers in each group. Similarly, there was no association

with parity and headache improvement when comparing

primiparous and multiparous women (~‘~=2.28, P=. 13).

628

Pre Pre Pre Pre Pre Pre Birthto 4107 8toll weeks weeks weeks weeks 9 weeks 5 weeks 1 3 weeks weeks weeks

21 to24 171020 13to16 to12 IO 6 io 4 post post post

Fig l.-Headache index during pregnancy and in the postpartum.

2.5

2

* f 1.5

f

% ’

0.5

0 ‘Inweeks Preweds Prawn&s Preveeks Pre\*eekS Pm weeks BirthtoJ 4 to 7 81011

21 to24 171020 1310 16 91012 5 IO a 1104 wecspost -posl -pasl

+Migraine *Tension-Type tcombined

Fig 2.-Headache index change by diagnosis.

At the initial evaluation, subjects were asked to com-

pare their headaches during the early weeks of pregnancy

to their headaches before pregnancy. This information was

used to assess headache changes during the first trimester,

before enrollment in the study. Four women reported

headache improvement, 7 reported no change, 24 reported

worsening of headache, and 14 reported onset of headache

with the current pregnancy. Chi-square analyses revealed

no relationship between significant improvement and

reports of how headaches had changed during the first

trimester (xz3=l .35, P=.72).

Another HI was calculated from the 11 weeks of post-

partum data and compared to the second-trimester scores.

As shown in Figure 1, the majority of women (33 or

67.3%) reported headaches that were not significantly dif-

ferent from second-trimester headaches. Information on

breast-feeding was collected to determine any influence on

postpartum headache change. Thirty-three of the 45

respondents to this inquiry reported breast-feeding. Again,

October, I999

WHY MPI Pain lntensity Score CES-D Depression Score

2.5 - 2-- 1.5 - 4 ;;

1 . 8-

0.5 -

0 4- I I I

First Second Third 3 Months First Second Third 3 Months

Trimester Trimester Trim ester Postpartum Trimester Trimester Trimester Postpartum

Internal Headache LOC

37

36

35

34

33

32

31 First Second

Trimester Trimester . Third

Trimester 3 Months

Postpartum

Fig 3.-Overall changes in psychological questionnaire scores.

contrary to expectations, there was no significant associa-

tion between headache improvement from the second

trimester to the postpartum and breast-feeding (x*,=0.24,

P-.12).

Psychological Questionnaire Scores.-Scores from

the WHYMPI and locus of control (LX) subscales were

examined using a double multivariate (multiple qualita-

tively distinct measures at multiple times) approach to

repeated measures, based on the unweighted general linear

model. The four time periods were the first trimester (I 9

women, or 38.8% of the sample, responded retrospective-

ly to first-trimester questionnaires during or after the 14th

week of pregnancy), second trimester (sometime during

the fifth month of pregnancy), third trimester (sometime

during the eighth month of pregnancy), and at 12 weeks

postpartum. A total of five scales were selected (due to the

sample size) as dependent variables: the WHYMPI pain

scale (comprised of past week and current ratings of pain),

the WHYMPI affective distress scale, the HALOC internal

LOC scale, the CES-D score, and the STPI anxiety scale.

Complete information was available for 44 women

(89.8% of the sample). Two women had given birth before

they could complete the third-trimester forms, and 3

women had not completed their 12-week-postpartum

forms. The MANOVA was significant (Pillais trace = .98;

F ,s ,,-2.30, P<.OO 1). Follow-up univariate repeated-mca-

sures ANOVAs revealed significant change in three of the

scales: pain (F,=6.02, P<.OOl), CES-D score (F,=3.20,

P<.O3), and internal LOC (F,=5.12, P<.OO2). Overall

changes in these scales are depicted in Figure 3 using the

estimated marginal means. Polynomial contrasts were sig-

nificant on the quadratic order for the pain (F,=9.60,

R.005) and CES-D scales (F,=5.30, P<.O3), and on the

linear order for the internal LOC scale (F,=9.68, Px.003).

Pain scores decreased and depression and internal LOC

scores increased during the third trimester.

Headache 629

COMMENTS

For women in whom headache persists beyond the

first trimester of pregnancy, headache will likely continue

for the remainder of pregnancy and postpartum. There was

nonsignificant trend toward improved headache activity

between the second and third trimesters, as evidenced by

daily diary recordings. Headache improved for only 41%

of the women in our sample. There was also a nonsignifi-

cant trend toward greater headache improvement in

migraineurs compared to those with tension-type

headache. Other factors traditionally linked to outcome of

headache during pregnancy and postpartum, such as pari-

ty, history of headache change with earlier pregnancy, and

breast-feeding, did not predict changes in headache.

History of menstrual migraine did not predict headache

improvement, although 40.8% of subjects did not provide

information about menstrual headache history. The

WHYMPI data revealed a relatively modest, though

significant reduction in headache during pregnancy for the

group. These differences between diary and WHYMPI

data may be related to differences in the power of each

analysis (I -p=.74 with diary data, I -p=.95 with WHYMPI

data). Scores from the WHYMPI show that headaches do

change during pregnancy, with a reduction during the third

trimester. This reduction, as revealed by the daily diary

recordings, however, is relativrely small.

There were also changes in psychological scores dur-

ing pregnancy, with significant increases in depression and

internal LOC. During the third trimester, CES-D scores

increased-a finding often associated with an increase in

headache, but is more likely due to the pregnancy itself

and the nature of the questions on the CES-D. Items such

as “I felt that everything I did was an effort,” “My sleep

was restless,” and “I could not get ‘going”’ are likely to be

endorsed during the third trimester, in association with

increased fetus size and weight. Other researchers have

reported similar findings in longitudinal studies of popu-

lation samples of pregnant women.3x

The results of the present study extend our previous

research29 and provide prospective confirmation of the ret-

rospective results of Rasmussen. Headache activity

improved in our population for a minority of women

(41%), with nonsignificant trend toward better improve-

ment for migraineurs. The results of this study, however,

contradict earlier retrospective studies in which the major-

ity of migraineurs reported headache improvement during

pregnancy. This study also failed to confirm earlier reports

of worsening of headache postpartum. As the magnitude

of headache change is not specified in many of the retro-

spective studies, the trend that is evidenced in our study

may be equivalent to the degree of headache improvement

that women reported in those studies. In addition, increase

in internal LOC may account for the more dramatic

improvement in headaches reported in retrospective stud-

ies compared to our findings. Perception of internal

control is significantly related to decreases in headache

reporting.‘y Pregnancy is associated with increased inter-

nal LOC40 Thus, by the end of pregnancy, perhaps

memories of decreases in headache are affected by the

increased perceptions of control over them, leading to a

report of a more significant decrease than that which

actually occurred.

The neurovascular model of headache suggests that

alterations in estrogen with pregnancy and delivery should

result in predictable changes in headache for the majority

of women, Why this model fails to predict headache

change for the majority of women in this study is unclear.

It is possible that, for the nearly 60% of women in this

study who failed to experience headache improvement

with pregnancy, there was a lesser degree of hormonal

change than in those who did experience headache relief.

In addition, other variables, such as psychological symp-

toms, also affect headache activity, and changes in these

variables may temper the headache changes expected to

occur in relation to changes in estrogen levels.

This study is limited by the self-selection of the sub-

ject sample. It is possible that there is a larger percentage

of headache sufferers in whom headache improves during

pregnancy who would have been ineligible for this study

because they experienced resolution of headache during

the first trimester, before possible enrollment in the study.

Despite this limitation, however, our data are similar to the

retrospective results of Paulo de Queiroz and Camargo

who obtained headache sufferers from consecutive admis-

sions to a delivery suite.

The results of our study suggest that headache will

likely continue throughout pregnancy for women who con-

tinue to report headache at the end of their first trimester.

Although there is a slight reduction in headache in the

third trimester, this reduction is small, with the entire

630 October; 1999

group showing only a 30% reduction in HI scores.

Significant improvement does occur for a minority of

women; however, in the majority headache continues. In

addition, factors such as history of menstrual migraine,

diagnosis of migraine. or history of headache change with

prior pregnancies did not predict headache change with the

current pregnancy. Pregnant women should be offered

effective management of their headaches during pregnan-

cy rather than recommendations to wait for spontaneous

improvement. Nonmcdication therapies, such as relax-

ation, biofeedback, and physical therapy, are safe and

effective treatment alternatives for 80% of pregnant

women.3”.41

Acknowledgments: This research was supported by

gran?.~ from the Raymond and Eiizabefh Bloch

Educational and Charitable Foundation and the National

Headache Foundation.

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