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The present study endeavored to identify predictors of headache during pregnancy, shortly after delivery, and at 8-week follow-up.
Many women suffer from headaches during pregnancy and the postpartum period. However, little is known about factors that predict headache surrounding childbirth.
Secondary analysis of longitudinal cohort study of 2434 parturients hospitalized for cesarean or vaginal delivery in four university hospitals in the United States and Europe. Data were gathered from interviews and review of medical records shortly after delivery; 972 of the women were contacted 8 weeks later to assess persistent headache. The primary outcome measures were experiencing headache during pregnancy, headache within 72 hours after delivery, and headache at 8 weeks after delivery.
Of the parturients, 10% experienced headache during pregnancy, 3.7% within 72 hours after delivery, and 3.6% at 8 weeks post delivery. Compared to those without a history of headache, a history of headache prior to pregnancy was the strongest predictor of headache during pregnancy (9.8% versus 23.5%; RR 2.4; 95% CI: 1.4 to 4.0). Experiencing headache during pregnancy (adjusted HR 3.8; 95% CI: 2.4 to 6.2) and receiving needle-based regional anesthesia for pain treatment (adjusted HR 2.2; 95% CI: 1.1 to 4.5) were independently associated with headache within 72 hours after delivery with event rates of 11.1% and 10.5%, respectively. Compared to those without such a history, headache before pregnancy was significantly associated with experiencing headache 8 weeks after delivery (4.0% versus 23.8%; RR = 6.0; 95% CI: 2.0 to 8.0), but headache during pregnancy or shortly after delivery was not. Several other psychosocial predictors (e.g., somatization, smoking before pregnancy) were statistically associated with at least one headache outcome.
A history of headache prior to pregnancy is a strong predictor of headache during and after pregnancy, the latter independent of but compounded by spinal injection. Physicians should attend to prior headache history when making decisions about pain management during and after childbirth. As the lack of formal ICHD-II headache diagnoses is a limitation of this study, future longitudinal studies should replicate the present design while including headache subtyping consistent with ICHD-II nosology.
Migraine and other headaches disproportionately affect women of childbearing age.1 Dramatic physiologic fluctuations in circulating estrogen concentrations are associated in some women with headache frequency and severity.2 Estrogen concentrations rise rapidly during pregnancy, coinciding with changes in headache patterns.3 Most women (40–80%) with preexisting migraine will experience resolution or improvement during pregnancy4–9 with most improvement occurring in patients without aura symptoms.10 However, a significant minority of parturients will evidence worsening or no improvement in headache, and 2–7% will experience headache de novo during pregnancy.6,11
Although preexisting headache often improves during pregnancy, approximately one-third of mothers experience postpartum headache within the first week after delivery,9, 12 making headache one of the three most common reasons for acute care visits during the puerperium.13 The large majority of postpartum headaches are recurrences of preexisting primary headache disorders, which recur within a month after delivery in 55% of prior migraineurs.9 Prior headache history, dural puncture, increasing age, multiparity, and shorter length of second-stage pushing have been identified as potential risk factors for postpartum headache shortly after delivery,12 though studies are needed of large and geographically diverse samples that assess headache at multiple time points surrounding childbirth and that assess women at multiple time points surrounding childbirth.
With over 4 million annual live births in the United States alone, poorly-controlled headache during or subsequent to pregnancy carries significant public health consequences, foremost among them increased risk of chronic pain, prolonged hospitalization and related costs, delayed resumption of usual activities, and potential impairments in bonding with and care of the newborn.14,15 The objective of the present study was to examine predictors of headache during pregnancy, after delivery, and at 8-week follow-up. We hypothesized that previous headache history would be related to headache events during pregnancy and after delivery.
A secondary analysis was performed on data from the longitudinal cohort Pain After Delivery (PAD) study.16 Institutional Review Board approval was obtained for the original study, and the present secondary analysis was considered exempt. Parturients were recruited from September 2004 to December 2005 at four university hospitals (Winston-Salem, NC, USA; New York, NY, USA; Geneva, Switzerland; Brussels, Belgium) and provided written informed consent. All parturients hospitalized for cesarean or vaginal delivery at each hospital were invited to participate, except during weekends and holidays when research personnel were unavailable. These women were queried within 72 hours after delivery about acute pain after delivery, pain history before and during pregnancy, other medical history, and demographic information (Entrance Questionnaire, Appendix). At the two U.S. hospitals, post-delivery questions were administered by research personnel in the form of a scripted interview; patients at the European sites completed the questionnaire in written format. Patient medical records were also reviewed by on-site research personnel, who directly transcribed data pertaining to age, body mass index, and gestational age. Women from the two U.S. hospitals were contacted 8 weeks later and interviewed by telephone using a computer-assisted scripted interview that inquired about persistent pain.
Headache prior to pregnancy was identified from several responses to the Entrance Questionnaire. Women who either indicated they had “chronic pain that started before this pregnancy” (question 4) or were “seeing a doctor regularly for any medical problems in the year before your pregnancy” (question 8) and listed head, headache, or migraine as the pain location or condition (questions 4a, 8b, and 8b1) were considered to have headache prior to pregnancy. Women who answered “yes” to “taking daily pain medications before this pregnancy” (question 5) or “taking any medications regularly (daily or > 3 days a week) during the year before pregnancy” (question 9) and listed medications exclusively used for migraine (e.g., a triptan) (questions 5a, 9a, and 9b) also were considered to have headache prior to pregnancy.
The principal outcome measures were headache during pregnancy, headache within 72 hours after delivery, and headache at 8 weeks after delivery. Headache during pregnancy was identified from questions 15 and 16 of the Entrance Questionnaire. Women were considered to have headache during pregnancy if they identified “headache” as the location of pain during pregnancy (question 15d) or reported taking regular medications during pregnancy for headache or migraine (questions 16a and 16b). Headache within 72 hours of delivery was identified from endorsements of “headache” as the site of current pain subsequent to delivery (question 24f). Women were considered to have headache at 8 weeks after delivery if they identified headache or migraine as an ongoing health problem or were currently taking a headache or migraine medication at the 8-week follow-up phone interview.
In addition to headache variables, the Entrance Questionnaire assessed many demographic and delivery characteristics. This information included self-reported general state of health, presence of chronic pain before pregnancy, use of daily pain medications before pregnancy, presence of chronic pain in family members, level of menstrual pain, regular doctor visits for medical problems before pregnancy, use of medications regularly (> 3 times per week) before pregnancy, smoking more than 1 pack of cigarettes a week in the year before pregnancy, level of alcohol consumption in the year before pregnancy, pain from previous operations, pain level during pregnancy, regular medications during pregnancy, and prolonged pain after previous birth. The questionnaire also included a somatization scale (questions 3a-j).17 Data on receipt of regional anesthesia injections were obtained from a separate Delivery Information Questionnaire (as described in Eisenach et al., 200816).
This is a secondary analysis of the Pain After Delivery (PAD) study, and a description of the primary analyses, including the original statistical power considerations, has been reported previously.16 Due to the secondary nature of this analysis (i.e., the study was not originally powered to examine these hypotheses), care was taken to report and interpret point estimates of effect size with 95% confidence intervals. Descriptive statistics are presented as mean (SD) for normally distributed scaled data and frequency counts with percentages for categorical data.
To examine the associations between patient characteristics and the presence of headache during pregnancy, a multivariable logistic regression model was created. The model was specified based on forced entry of this set of a priori selected predictors. The model controlled for study site, and care was taken to consider the correlations among predictors prior to analysis (i.e., none of the predictors were so highly correlated as to present estimation problems in the analysis). To predict the presence of headache within 72 hours after delivery, a multivariable Cox proportional-hazards model was created. Based on the modest number of parturients who experienced headache after delivery (n = 92), care was taken to specify a model that employed a suitably limited number of predictors (to avoid overfitting the data). The proportional-hazards assumption was tested and satisfied prior to interpretation of the model.
To express the relative risks of the various predictors, odds ratios (logistic regression model), hazard ratios (Cox proportional-hazards model), and risk ratios all with respective 95% confidence intervals are reported. The RR was chosen to express the relative risk of experiencing headache at one measurement occasion conditional on previous occasions because of the relative frequency of the observed event rates (odds ratios and risk ratios are only similar for rare events) and ease of interpretation that this metric provides. For example, a RR of 3.0 indicates that experiencing a headache is three times more likely in one group versus another. All analyses were conducted using SAS 9.2 (SAS, Inc. Cary, NC). Where appropriate, all hypotheses are two-tailed with p < 0.05.
2434 deliveries were carried out during the study period. The greatest number of participants (n = 876) was recruited from Winston-Salem, NC. Demographic and delivery characteristics of the four sites were similar in most cases (Table 1).
The percentage of women from all sites who experienced headache before pregnancy was 6.3% (154/2434) (Table 2). The percentage of women who explicitly reported experiencing migraine as a type of headache was 3.6%. However, some variation in reporting of chronic pain and headache prior to pregnancy was observed, and this resulted in post hoc revisions to the analytical plan. Specifically, women from Brussels reported a higher rate of headache before pregnancy than women at the other sites (20.2% vs. 2.3–3.2%) (Figure 1; Table 2). This site difference was taken into account during subsequent analyses: Headache history as a univariate predictor of headache during or after pregnancy was based only on data from the New York, Winston-Salem, and Geneva sites; for all other analyses all participants were used.
Of the parturients, 10% (244/2434) experienced headache during pregnancy, with similar rates across sites (8.6%–12.9%; Table 2). A regression model was conducted using all of the predictors in Table 3. Compared to those without a history of headache, experiencing headache prior to pregnancy was associated with an increased risk of experiencing headache during pregnancy (9.8% versus 23.5%; RR 2.4; 95% CI: 1.4 to 4.0; Figure 2). Having a history of chronic pain (adjusted OR 2.18; 95% CI: 1.42 to 3.37), smoking prior to pregnancy (adjusted OR 1.50; 95% CI: 1.05 to 2.13), and prolonged pain after previous birth (adjusted OR 1.42; 95% CI: 1.04 to 1.94) were also associated with increased odds of experiencing headache during pregnancy (Table 3). Other patient history and demographic variables were not associated with increased risk for headache during pregnancy.
Of the women, 3.7% (91/2434) experienced a headache within 72 hours after delivery (Table 2), with generally similar rates across sites (2.5%-5.4%). A Cox proportional-hazards model was conducted using all of the predictors in Table 4. Of the variables pertaining to prior headache history and analgesic use surrounding pregnancy, experiencing headache during pregnancy (adjusted HR 3.83; 95% CI: 2.37 to 6.18) and receiving regional anesthesia injections (epidural/spinal/Combined Spinal Epidural (CSE)) (adjusted HR 2.19; 95% CI: 1.07 to 4.50) were most strongly associated with increased risk of developing headache within 72 hours after delivery (Table 4). Although an association with acetaminophen was identified (adjusted HR 1.71; 95% CI: 1.32 to 2.22), this medication often is given in response to pain and as such may not be predictive. As several of these medications are given both as a part of routine pain treatment and for additional pain relief for those in acute distress, interpretation of the model must be made with caution.
The survival curve in Figure 3 depicts the proportion of patients who remained free from headaches up to 72 hours after delivery by (a) whether or not they experienced headache during pregnancy and (b) whether or not regional anesthesia was used. Women who did not experience headache during pregnancy and did not receive regional anesthesia injections were the group most likely to be free from headache at any time during the 72 hours after delivery. Conversely, women who experienced headache during pregnancy and received regional anesthesia injections were least likely to be free from headache during the 72 hours after delivery. Headache prior to pregnancy was not associated with increased risk of headache within 72 hours after delivery.
Of the 972 women from the two U.S. sites who were interviewed at 8 weeks after delivery, 4.5% experienced headache after delivery (Table 2). Compared to those without such a history, having headache before pregnancy was significantly associated with experiencing headache 8 weeks after delivery (4.0% versus 23.8%; RR 6.0; 95% CI: 2.0 to 8.0). However, neither experiencing headache during pregnancy (RR 0.82; 95% CI: 0.04 to 1.23) or experiencing headache within 72 hours of delivery (RR 0.66; 95% CI: 0.003 to 1.5) were associated with increased risk of headache at 8 weeks post-delivery (Figure 2).
Headache during and after pregnancy is a common occurrence resulting in significant public health consequences and resulting impairments in childcare at a time that is integral to maternal bonding. Despite its prevalence, however, headache surrounding pregnancy remains poorly understood, and only recently have researchers attempted to identify potentially modifiable predictors of headache surrounding pregnancy. Limited cross-sectional data have implicated previous headache history, dural puncture, multiparity, and increasing age as risk factors associated with headache in the postpartum period.7, 12, 18
The present study extended prior research to a very large and geographically diverse sample of 2,434 women from two hospitals in the U.S. and two in Europe. Most notably, we found that prior headache history consistently emerged as a strong predictor of headache surrounding pregnancy. At each of the three time points (during pregnancy, within 72 hours after delivery, and at 8 weeks after delivery), a history of headache was more strongly associated with current headache than were multiple other health, demographic, and psychosocial variables. At the initial and last time point, prediction of headache was afforded most strongly by a prior history of headache predating pregnancy, whereas headache shortly after pregnancy was most strongly predicted by a prior history of headache during pregnancy.
Specifically, headache during pregnancy and at 8 weeks after delivery were strongly predicted by a history of headache prior to pregnancy, with risk increasing nearly 2.5 times for headache during pregnancy and 6 times for headache at 8 weeks after delivery. These findings are consistent with the notion that many headaches during pregnancy and postpartum represent ongoing primary headache disorders.9 Headache within 72 hours after delivery was predicted very strongly by a history of headache during pregnancy (but not by headache prior to pregnancy) and by epidural/spinal/CSE injection, either for labor analgesia or cesarean delivery anesthesia. Patients with headache during pregnancy were nearly 4 times more likely to experience headache shortly after delivery, and those receiving regional anesthesia were 3 times more likely to experience headache. Participants with a history of headache during pregnancy and receiving regional anesthesia were far more likely than any other participants to experience a headache within 72 hours after delivery, confirming that these variables have independent but synergistic effects.
Inadvertent dural puncture with an epidural needle carries a high risk of headache 12,19 due to leakage of cerebrospinal fluid into the epidural space through the large hole produced by the epidural needle.20 We did not have a clear representation of which women received spinal insertions versus epidurals for vaginal deliveries, and therefore women who had spinal needle insertion in labor are not identified in this study. As such, we cannot determine the precise rate or risk of inadvertent dural puncture specifically as contributing to our findings regarding headache related to regional anesthesia. However, the majority of caesarean regional anesthesia in this study was spinal-based (62% spinal/CSE), and thus it is likely that the spinal route of administration strongly contributes to these findings. In contrast to dural puncture with an epidural needle, however, a dural puncture made with a pencil-pointed 25- or 27-gauge spinal needle, as used in these women for cesarean delivery, results in a smaller hole in the dura and a much lower incidence (1–2%) of headache after the procedure. The finding that headache history and needle-based regional anesthesia confer independent and synergistic effects can be used to inform physician practice, treatment choices, and regularity of monitoring following discharge. Because headache during the puerperium period is of central importance to predicting subsequent headache after delivery, identification and management of headache during pregnancy is essential. The relative benefits and headache risks, among others, of spinal anesthesia should be carefully weighed in a patient with a history of severe and frequent headaches. Women routinely are instructed to notify health care personnel of the presence of headache within 72 hours of delivery, and most anesthesiologists inject autologous blood into the epidural space (epidural blood patch) to treat this headache prior to patient discharge from the hospital.
Strengths of this study include its large sample of participants from three countries and four research sites, multivariate data analytic strategy to adjust for other predictors of headache, and assessment of headache symptoms at multiple points surrounding pregnancy and childbirth. The assessment of numerous pain, general health, demographic, and psychosocial variables as risk factors also is more comprehensive than previous studies on headache surrounding pregnancy. Despite its strengths, the present study has several limitations, most of which center around the means by which headache was assessed and classified. The principal limitation of this study lies in our reliance on self-reported past and current headache problems rather than assessment using formal ICHD-II diagnostic criteria.21 Although this limitation was dictated by the format of the Entrance Questionnaire used in the main study, it did preclude precise specification and comparisons of specific headache subtypes, and thus readers should exercise caution in extrapolating our findings as they pertain to specific headache subtypes. However, our observed rates of headache both before and after pregnancy were somewhat lower than those obtained in other studies1,9, 12 suggesting our participation characterization strategy did not result in overly liberal headache endorsement.
Our relatively lower rates of headache prior to pregnancy are likely a function of the fact that prior headache was defined by endorsement of “chronic” head pain, regular medical visits for headache, or regular use of headache-specific agents in the year prior to pregnancy. Higher rates of prior headache likely would have been obtained had headache symptoms specifically been assessed in a more standardized format, in which case less frequent or disabling headaches would more likely be identified. Lower rates of headache shortly after delivery may be attributable to potential sampling bias insofar as patients in extreme pain may have declined participation and patients delivering on weekends and holidays were not assessed, or to potential recall bias to the extent that assessment in the 72 hours post-delivery is a time beset with strong emotions and potential reporting inaccuracies. Higher rates of headache during this time frame might have been observed had we inquired about any headache within this 72-hour period rather than current head pain and included more frequent periodic assessment instead of two discrete follow-up intervals (72 hours and 8 weeks post-delivery).
More minor limitations surround the loss of the European participants at the 8-week follow-up and the different formats in which participants at the U.S. versus European sites provided data for the Entrance Questionnaire (scripted interview versus self-report measure). Although patients at all sites responded to the same questions, varied administration formats and translation into French (for the European sites) may have affected participant responses. We attempted to control for observed differences in pre-pregnancy headache across sites (ie, Brussels’ participants endorsing higher prevalence of prior headache) by sub-setting the analyses pertaining to prior headache history by using data only from the Winston-Salem, New York, and Geneva sites. In light of these limitations, replication with similarly large samples using ICHD-II nosology and longer follow-up intervals is warranted. Future studies of headache patterns during and after pregnancy also should focus on further disentangling the relative contributions of prior headache history and anesthesia procedures, with comparison between spinal and epidural routes of administration for identification of suspected dural puncture. Such studies should focus on following pregnant women longitudinally and further clarifying the clinical implications of these and other previously-established risk factors.
Financial Support: This analysis was funded by NIH/NINDS R01NS065257. The original PAD study was funded by NIH GM48085 and a grant from the Sceptor Foundation.
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|3a. I can’t stand smoke, smog, or pollutants in the air||□||□||□||□||□|
|3b. I am often aware of various things happening within my body||□||□||□||□||□|
|3c. When I bruise myself, it stays noticeable for a long time||□||□||□||□||□|
|3d. I sometimes can feel the blood flowing in my body||□||□||□||□||□|
|3e. Sudden loud noises really bother me||□||□||□||□||□|
|3f. I can sometimes hear my pulse or my heartbeat throbbing in my ear||□||□||□||□||□|
|3g. I hate to be too hot or too cold||□||□||□||□||□|
|3h. I am quick to sense the hunger contractions in my stomach||□||□||□||□||□|
|3i. Even something minor, like an insect bite or a splinter, really bothers me||□||□||□||□||□|
|3j. I can’t stand pain||□||□||□||□||□|
|9.d. Bladder/lower urinary tract infection||□|
|9.e. Kidney infection||□|
|9.f. Vaginal/other gynecological infection||□|
Conflicts of Interest:
Dana P. Turner: Ms. Turner receives research support from Merck.
Todd A. Smitherman: Dr. Smitherman reports no conflicts of interest.
James C. Eisenach: Dr. Eisenach is a consultant with Medtronics, Adnyxx, Vertex, and Glaxo-Smith-Kline and receives research support from King Pharmaceuticals.
Donald B. Penzien: Dr. Penzien receives research support from Merck.
Timothy T. Houle: Dr. Houle receives research support from GlaxoSmithKline and Merck and is a consultant for Allergan.