Epistaxis is a common problem, occurring at least once over the lifetime in up to 60% of the general population.1 Of those affected, a smaller subgroup will have recurrent or habitual epistaxis. Because studies have suggested that these individuals are at increased risk of disordered hemostasis,2–6 obtaining a history of epistaxis has become an important preoperative tool for identifying those who may be at risk of significant intraoperative bleeding.7–8 Whether this association between epistaxis, bleeding disorders, and postpartum bleeding complications holds true for pregnant women is unknown. It is commonly believed by obstetricians that the prevalence of epistaxis in pregnancy is increased compared with the general nonpregnant population. This observation has been attributed to estrogen-associated vascular congestion and mucosal edema9 as well as to increased rhinitis during pregnancy. To date, however, there has been little research to support this hypothesis, and little is known about the actual prevalence of epistaxis in pregnancy. Additionally, it remains unknown if epistaxis of pregnancy is associated with disordered hemostasis and if it might be predictive of increased risk for obstetric hemorrhage or complications of neuraxial anesthesia.
This study aimed to estimate the prevalence of epistaxis among pregnant women and a population of reproductive-aged nonpregnant women. A second aim was to determine the relationship between epistaxis of pregnancy and postpartum hemorrhage. Given that epistaxis during pregnancy is thought to be associated with local nasal mucosal and vascular changes, rather than an underlying bleeding disorder, we hypothesized that we would not find an association between epistaxis of pregnancy and postpartum hemorrhage.
PATIENTS AND METHODS
The study was a single-institution, prospective cohort study involving pregnant women at term (cohort 1; n=1,475) and nonpregnant reproductive-aged women (cohort 2; n=275). Women presenting to our labor and delivery unit between 36 and 42 weeks estimated gestational age in spontaneous labor, for induction of labor or for scheduled cesarean delivery, were eligible for study participation (cohort 1), as were women aged 18 to 45 years presenting for gynecologic care at one of two different hospital-associated gynecologic clinics (cohort 2). Patients with a known bleeding or clotting disorder, pregnancy-induced hypertension, or preeclampsia were excluded, as were those on anticoagulation therapy at any point during the pregnancy or at the time of survey administration. Permission to approach each patient for study enrollment was obtained from the attending physician caring for the patient before initiating any contact.
The Institutional Review Board of Northwestern University approved the study, and informed written consent was obtained from all participants. Participation entailed filling out an 18-question survey about the patient's epistaxis history and other traditional risk factors for bleeding. Patients were asked about the use of nonsteroidal anti-inflammatory drugs, aspirin, blood thinners, and garlic and gingko supplements. The survey instrument was developed in consultation with experts from obstetric anesthesiology, hematology, and otolaryngology. The survey was informally piloted among nonpregnant gynecologic patients to ensure that the questions were understandable. Estimated delivery blood loss was abstracted from the medical records of women in the pregnant cohort. Blood loss was determined by the delivering obstetrician or midwife for vaginal deliveries and by the obstetrician and anesthesiologist for cesarean deliveries. Need for uterotonic agents beyond routine postpartum oxytocin was also recorded. All patient enrollment and data collection took place between September of 2007 and December of 2008.
Women were considered to have epistaxis of pregnancy if they had a history of two or more episodes of epistaxis during their pregnancy or, for the nonpregnant cohort, during the preceding year. To distinguish true nose-bleeds from small amounts of blood noted with nose-blowing, women were specifically asked to distinguish “active nose bleeds” and “blood on the tissue when you blow your nose.” Only women who reported “active nose bleeds” were considered to have epistaxis. Frequency of active nose bleeds was then further delineated as “once,” “two to five times,” or “more than five times.”
Postpartum hemorrhage was defined as estimated blood loss greater than 500 mL for a vaginal delivery or greater than 1,000 mL for a cesarean delivery. The primary outcomes were 1) rates of epistaxis in pregnant compared with nonpregnant women, and 2) rates of postpartum hemorrhage in women with epistaxis compared with those without.
Epi Info software 3.1, from the Centers for Disease Control and Prevention, was used to calculate sample size. All calculations assumed an α=0.05 and β=0.2. The baseline prevalence of epistaxis in the nonpregnant population was assumed to be 6%,9 and a doubling of risk (to 12%) among the pregnant population was chosen as a clinically significant increase. Initial sample size analysis to detect an increase in epistaxis from 6% to 12% demonstrated a need to recruit 1,027 pregnant and 257 nonpregnant women for the initial phase of the study. To account for possible incomplete data collection, we recruited a total of 275 nonpregnant women (7% above calculated need).
For the postpartum hemorrhage sample size analysis, the known institutional rate of postpartum hemorrhage of 5% was used as the baseline risk and doubling of risk (to 10%) was felt to be a clinically significant increase and was used for sample size calculation. Exposed women were defined as those with a history of epistaxis, and unexposed women were those with no history of epistaxis. We used the most conservative estimate of “exposed” pregnant women, 6%, which assumes that the prevalence of epistaxis is not increased among pregnant women. Based on this assumption, a group size of 1,425 pregnant women was required. We recruited 1,475 pregnant women to account for possible incomplete data collection.
All statistical data analysis was carried out using SPSS for Windows, 16.0 (SPSS Inc., Chicago, IL). All data were transformed into categorical data and the χ2 test used to compare the prevalence of epistaxis between pregnant and nonpregnant participants as well as to compare rates of postpartum hemorrhage between pregnant women with and without epistaxis. Odds ratios with 95% confidence intervals were calculated. Univariate analysis was also performed using the χ2 test for comparison of other study variables between pregnant women with and without a history of epistaxis: history of seasonal allergies, recent respiratory infection, easy bruising, patient's blood type and delivery mode. If significant differences were identified in the univariate analysis, a logistic regression analysis was planned to assess the effect of those variables on postpartum hemorrhage. For all statistical analysis a P<.05 was considered statistically significant.
Final data analysis was performed on 1,470 pregnant women and 275 nonpregnant women. Among pregnant women, the average age (±standard deviation) was 32 years (±6.1) and among nonpregnant women it was 31 years (±5.2.) Race and ethnicity were similar between the pregnant and nonpregnant cohorts, with the largest proportion in each cohort being non-Hispanic white (60% pregnant, 57% nonpregnant of those with race data) followed by African American, Latina, and Asian. In the pregnant cohort, the cesarean delivery rate was 28.5%.
Pregnant women were significantly more likely to have epistaxis, 20.3%, than nonpregnant women, 6.2%, (odds ratio [OR] 3.8, 95% confidence interval [CI] 2.3–6.4; P<.001). Pregnant women were also more likely to have gingival bleeding (bleeding gums on at least a weekly basis), 32.1% compared with 10.2% in the nonpregnant population (OR 3.5, 95% CI 2.4–5.2).
For the second part of the study, pregnant women with a history of epistaxis were compared with those without epistaxis. The two groups did not differ in terms of age, medical history, or history of recent upper respiratory infection (data not shown). There were no statistically significant differences in the rates of epistaxis among ethnic groups (21.8%, 21.7%, 20.3%, and14.4% for white, Latina, Asian, and African-American women, respectively).
The incidence of cesarean delivery in women with epistaxis was 33.1% compared with 27.9% in women without epistaxis (P=.08). Because cesarean delivery is a known risk factor for postpartum hemorrhage, delivery mode was controlled for in subsequent analysis. Pregnant women with epistaxis were more likely to report a history of seasonal allergies. However, allergies alone were not associated with postpartum hemorrhage in our study, so this variable was not included in our regression analysis. Women with epistaxis of pregnancy were more likely to have a history of epistaxis before pregnancy and this was accounted for in further analysis. Some survey variables were so rare within the pregnant cohort that they were excluded from further analysis, including family history of bleeding disorders, history of prior blood transfusion, history of prior heavy postprocedural bleeding, or use of blood-thinning medications (nonsteroidal antiinflammatory drugs, aspirin or supplements such as garlic or gingko).
Women with epistaxis of pregnancy were at a significantly increased risk of postpartum hemorrhage compared with women without epistaxis, 10.7% compared with 6.7%, respectively (OR 1.7, 95% CI 1.08–2.6; P=.02). The risk of postpartum hemorrhage remained increased when controlled for mode of delivery (P=.04). The risk of postpartum hemorrhage also increased as the number of reported episodes of epistaxis of pregnancy increased. Pregnant women without epistaxis had a 7.5% chance of postpartum hemorrhage compared with 8.1% with one nosebleed (OR 1.09, 95% CI 0.51–2.33), 8.2% with two to five nosebleeds (OR 1.11, 95% CI 0.61–2.01), and 14.0% with more than five nosebleeds in pregnancy (OR 2.01, 95% CI 1.16–3.48; P=.004.) Similarly, women with epistaxis of pregnancy were more likely to require use of uterotonics at delivery, 11% compared with 6% (OR 1.9, 95% CI 1.2–3.0).
Pregnant women with a history of epistaxis before pregnancy (more than two bleeds during their adult life, n=103) were also at increased risk for postpartum hemorrhage, 12.6%, compared with those without epistaxis before pregnancy, 7.2% (OR 1.9, 95% CI 1.0–3.5). Therefore, to eliminate epistaxis outside of pregnancy as a confounding variable, we compared the incidence of postpartum hemorrhage in women with and without epistaxis of pregnancy after excluding women with a history of epistaxis before pregnancy. Women with epistaxis of pregnancy only were still at increased risk of postpartum hemorrhage, 10.5%, compared with women without epistaxis of pregnancy, 6.9% (OR 1.6, 95% CI 1.0–2.5). Other traditional risk factors for bleeding were not associated with postpartum hemorrhage (gingival bleeding at least a weekly [7.5% compared with 7.6%; P=1.0], easy bruising [7.6% compared with 7.3%; P=.84], or O blood type [8.0% compared with 7.1%; P=.50]).
This study confirms the long-held belief that pregnant women are more likely than nonpregnant women to suffer from epistaxis and gingival bleeding. More importantly, our data suggest that a history of epistaxis in pregnancy is in fact associated with a greater risk for postpartum hemorrhage even when controlled for cesarean delivery and history of epistaxis before pregnancy. This association was contrary to our expectations. Because we hypothesized that pregnancy-related epistaxis was due to estrogen-induced nasal mucosal edema and vascular change, we did not anticipate that epistaxis of pregnancy would be a risk factor for postpartum hemorrhage. It is possible, however, that in addition to these local mucosal changes, subtle changes in hemostasis and ability to form clots may lead to epistaxis of pregnancy and therefore also to an increased likelihood of postpartum hemorrhage. Another possible explanation of our results is that epistaxis is the result of abnormalities in vessel integrity or structure that also predisposes to postpartum hemorrhage. Future studies to investigate these possibilities are planned.
It is unclear whether a history of epistaxis during pregnancy is associated with an increased risk of spinal–epidural hematoma during neuraxial procedures. The incidence of spinal–epidural hematoma in this patient population is rare,10 and therefore a prohibitively large study would be required to test this association.
The strengths of our study include the large size of our study population and the completeness of our data collection. Because the prevalence of epistaxis among pregnant women was higher than anticipated, our study was well powered to detect even small differences in outcomes between the two groups. The data were collected from each cohort consistently throughout an entire year, eliminating seasonal or climate-induced causes of epistaxis as a confounding factor in our study. Additionally, in only a few rare cases were the survey or data collectors the ones involved in the actual delivery or the estimation of delivery-associated blood loss, thus limiting the role of provider knowledge of a patient's bleeding history as a confounding factor.
Weaknesses include the fact that study data on epistaxis and bleeding risk factors, including medication use during the pregnancy, were collected retrospectively and were therefore subject to recall bias. Another weakness was that due to the low prevalence of some study variables such as significant family history and history of prior bleeding, we were unable to include these variables in our analysis.
One interesting factor in our data set was that the overall rate of postpartum hemorrhage, 7.4%, was higher than the previously documented institutional rate of 5%. This finding was despite the fact that standard definitions of postpartum hemorrhage were used in the study and that the cesarean delivery rate in the study, 28%, was consistent with our institutional rate. Two possible explanations for this finding exist. The first is that due to the way patients were recruited, women undergoing a scheduled cesarean delivery, either a repeat or primary, were the least likely to be included in the study. These women spent little time on the labor and delivery unit before their delivery and therefore were often missed by study recruiters. Additionally, just before the study onset, all providers of obstetric care at our institution underwent a mandatory training module on estimation of blood loss. This training may have resulted in higher, and likely more accurate, estimations of blood loss. It is of note that this training module was entirely separate from our study.
In conclusion, epistaxis is a common problem in pregnancy, with at least one in every five women experiencing two or more nosebleeds during pregnancy. As in the nonpregnant population, eliciting this history of active nosebleeds may help to identify women at increased risk for disordered hemostasis. With this in mind, obstetricians and obstetric anesthesiologists may be better able to prepare for postpartum hemorrhage, for example by obtaining preoperative blood bank specimens and having uterotonics readily available in the delivery room. Further studies are planned to elucidate the underlying mechanisms for this disordered hemostasis.