Rhinologic Conditions of Pregnancy: A Retrospective Cohort Study

Abstract

Objective

To better understand the prevalence, risk factors, and management strategies of pregnancy‐related rhinologic conditions.

Study Design

Retrospective cohort study from January 2013 to January 2023.

Setting

Tertiary level Otolaryngology–Head and Neck Surgery clinic.

Methods

Pregnant patients with rhinologic concerns were included. Data were collected on various parameters including age during pregnancy, gestational age at evaluation for rhinologic complication, obstetric history, history of pregnancy loss, primigravida status, rhinologic condition, aspirin usage during pregnancy, and presence of advanced maternal age (AMA, ≥35 years old). Stata/SE 17.0 Software was used for statistical analysis. A P‐value of <.05 was considered significant.

Results

Fifty‐seven pregnant patients were included. Patients presented with epistaxis (N = 25, 43.9%), chronic rhinosinusitis exacerbations (N = 22, 38.6%), and rhinitis of pregnancy (N = 10, 17.5%). Mean age at presentation was 34.7 years (22‐53). Multivariate analysis revealed associations between epistaxis and primigravida status (P = .008) and rhinitis of pregnancy with a history of pregnancy loss (P = .012). Gestational diabetes mellitus was significantly associated with epistaxis on univariate analysis (P = .011).

Conclusion

There is a need for increased awareness among health care providers, including otolaryngologists, regarding the diagnosis and management of rhinologic conditions of pregnancy.

Many pregnancy‐related health issues are underreported and understudied. Rhinologic complications of pregnancy include epistaxis, exacerbation of chronic rhinosinusitis (CRS), and rhinitis of pregnancy. ¹ An estimated 20% to 40% of people in their childbearing years report symptoms of rhinitis and sinonasal disease, and 10% to 30% experience worsened symptoms while pregnant. ² Although these do not frequently pose a severe risk to mother and baby, they profoundly affect quality of life, sleep, daily activities, and mental well‐being. ¹

The pathophysiology of these conditions is not fully understood, but hormonal changes during pregnancy, which affect nasal physiology and lead to inflammation, edema, and congestion, are believed to be the primary contributing factors. ³ Estrogen may influence vascular function through modulation of the nitric oxide pathway. ³ Progesterone increases blood volume, which may exacerbate vascular changes linked to severe epistaxis, and placental growth hormone could contribute to the risk through systemic vasodilation effects. ³ , ⁴

The scarcity of literature exploring rhinologic conditions during pregnancy may partly stem from the historic neglect of women's health issues in medical research, as well as ethical concerns surrounding experimental treatments during pregnancy. ⁵ , ⁶ Consequently, there is a notable lack of data regarding the appropriate diagnosis and best treatment options for patients suffering from pregnancy‐related rhinologic conditions.

We aim to better understand the prevalence and risk factors of pregnancy‐related rhinologic conditions through a 10‐year retrospective cohort study at a tertiary Otolaryngology–Head and Neck Surgery (OHNS) center.

Methods

Patient Selection

A retrospective cohort study of pregnant patients with rhinologic concerns (epistaxis, exacerbation of CRS, and rhinitis of pregnancy) evaluated at a tertiary Otolaryngology clinic from 2013 to 2023 was undertaken. Patients were evaluated by multiple rhinologists within the same tertiary otolaryngology clinic. To identify patients for enrollment, we queried all encounters at the clinic during the specified date range containing any of the following International Statistical Classification of Diseases, Tenth Revision (ICD‐10) codes: Z33 (pregnant state), Z33.1 (pregnancy incidental), or Z33.3 (pregnant state, gestational carrier). We then performed chart reviews on these encounters to confirm pregnancy at the time of evaluation, and all patients meeting this criterion were included. Subjects were excluded if they were either not pregnant at the time of evaluation or had insufficient documentation in the Electronic Medical Record (EMR). Data collected included demographics, age, gestational age at evaluation, obstetric history including obstetric comorbidities like gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension, anemia, chronic hypertension, history of pregnancy loss, primigravida status, pertinent history of rhinologic conditions, and medication use.

Ethical Approval and Informed Consent

This study received ethical approval from the University of California San Francisco Institutional Review Board (23‐38956) on 22 June, 2023.

Statistical Analysis

Stata/SE 17.0 Software (StataCorp) was used to perform all statistical analyses. t‐Tests were used to compare two dichotomous variables and dichotomous versus normal continuous variables. Fisher's exact test was used to compare dichotomous versus nonnormal categorical variables. Logistic regression was used to perform univariate and multivariate analyses. A two‐sided P‐value < .05 was considered significant.

Results

Fifty‐seven pregnant patients with rhinologic concerns were evaluated. Chief complaints included epistaxis (25/43.9%), exacerbation of CRS (22/38.6%), and rhinitis of pregnancy (10/17.5%) (Table 1). The mean age at presentation to the OHNS clinic was 34.68 years (range: 22‐53) (Table 1). Thirty‐three patients (57.9%) were white, 13 (22.8%) Asian, 9 (15.8%) Hispanic or Latin American, and 2 (3.5%) black or African American (Table 1). Thirty‐three (57.9%) were advanced maternal age (AMA, defined as ≥35 years of age), 15 (26.3%) had GDM, 9 (15.8%) had preeclampsia, 9 (15.8%) had gestational hypertension, and 21 (36.8%) had diagnosed anemia (Table 2). Thirty‐four patients were primigravida (59.6%), 19 (33%) had a history of pregnancy loss, and 13 (22.8%) had taken aspirin during pregnancy (Table 2).

Table 1.

Demographic Data of Pregnant Patients Referred to an Otolaryngologist for Rhinologic Conditions

Demographics (N = 57)	Total	Epistaxis (N = 25)	CRS exacerbation (N = 22)	Rhinitis of pregnancy (N = 10)
Mean age, y (standard deviation; range)	34.68 (5.28; 22‐53)	34.92 (6.11; 25‐53)	34 (4.81; 22‐41)	35.36 (4.78; 26‐38)
Mean gestational age, wk at evaluation (standard deviation; range)	19.1 (10.65; 4‐38)	23.48 (9.31; 4‐34)	14.48 (10.512; 4‐32)	21.3 (12.03; 5‐38)
Race or ethnicity N (%)
White	33 (57.9)	11 (44)	16 (72.7)	6 (60)
Asian	13 (22.8)	9 (36)	1 (4.5)	3 (30)
Hispanic/Latin American	9 (15.8)	5 (20)	3 (13.6)	1 (10)
Black/African American	2 (3.5)	0 (0)	2 (9.1)	0 (0)
Other Pacific Islander	0 (0)	0 (0)	0 (0)	0 (0)

Abbreviation: CRS, chronic rhinosinusitis.

Table 2.

Comorbidities of Pregnant Patients Referred to an Otolaryngologist for Rhinologic Conditions

Comorbidities N (%)	Total (N = 57)	Epistaxis (N = 25)	CRS exacerbation (N = 22)	Rhinitis of pregnancy (N = 10)
Advanced maternal age	33 (57.9)	15 (60)	10 (45.5)	8 (80)
Gestational diabetes	15 (26.3)	11 (44)	3 (13.6)	1 (10)
Preeclampsia	9 (15.8)	5 (20)	3 (13.6)	1 (10)
Gestational hypertension	9 (15.8)	4 (16)	4 (18.2)	1 (10)
Anemia	21 (36.8)	10 (40)	8 (36.4)	3 (30)
Primigravida status	34 (59.6)	20 (80)	10 (45.5)	4 (40)
History of pregnancy loss	19 (33.3)	5 (20)	7 (31.8)	7 (70)
Aspirin usage	13 (22.8)	7 (28)	4 (18.2)	2 (20)

Abbreviation: CRS, chronic rhinosinusitis.

Epistaxis

Of the 57 subjects, 25 (43.9%) experienced epistaxis during pregnancy. Of the 25 patients with epistaxis, 6 patients (24%) had concurrent worsening CRS symptoms, and 14 (56%) had concurrent rhinitis of pregnancy. The mean age of onset was 34.9 years, and epistaxis began at a mean gestational age of 23.5 weeks. Twenty patients (80%) were primigravida, and 5 (20%) had a history of pregnancy loss. Four (16%) had pyogenic granulomas (Figure 1), 7 (28%) were taking aspirin, and 1 had hereditary hemorrhagic telangiectasia (HHT) with worsening in baseline epistaxis frequency and severity. There was a positive correlation between epistaxis and primigravida status on univariate (P = .017) and multivariate (P = .008) analysis (Table 3). On univariate analysis, GDM was significantly associated with epistaxis (P = .011) but did not remain significant on multivariate analysis (Table 3). No associations were found with AMA, preeclampsia, history of pregnancy loss, anemia, aspirin usage, or hypertension (Table 3). Although 19 patients (76%) were treated conservatively, 6 (24%) required invasive procedures. In the OR setting, one patient underwent left sphenopalatine artery and left anterior ethmoid artery ligation after a failed sphenopalatine artery embolization, one patient with concurrent CRS underwent endoscopic sinus surgery to address CRS with simultaneous bilateral cauterization, and one patient underwent endoscopic control of epistaxis with cauterization. In the office setting, three patients underwent cautery with silver nitrate.

Figure 1.

Endoscopic view of a pyogenic granuloma in a patient with epistaxis of pregnancy. The lesion appears as a well‐defined, vascular mass on the nasal septum. Four patients in this study had a pyogenic granuloma.

Table 3.

Factors Associated With Epistaxis Prompting Referral to an Otolaryngology Specialist During Pregnancy

Demographics N = 25	Odds ratio	Standard error	P‐value	95% CI
History of pregnancy loss	0.321	0.197	.065	0.096‐1.071
Primigravida status	5.14	3.16	.008*	1.543‐17.133
Advanced maternal age	0.871	0.47	.798	0.302‐2.511
Gestational diabetes	5.49	3.68	.011*	1.48‐20.42
Preeclampsia	1.75	1.28	.445	0.417‐7.35
Gestational Hypertension	1.03	0.75	.969	0.245‐4.312
Anemia	1.272	0.703	.662	0.431‐3.758
Aspirin usage	1.685	1.07	.411	0.485‐5.852

^*Maintained significance on multivariate analysis.

Exacerbation of CRS

Of the 57 subjects, 22 (38.6%) presented with a new diagnosis of CRS or symptomatic exacerbation in the setting of known CRS. Seventeen patients were new referrals, whereas five were established patients with CRS. For new patients, a diagnosis of CRS was made using the presence of both subjective (two or more of the following symptoms: nasal obstruction, nasal drainage, facial pressure, and/or decreased smell) and objective (positive imaging or endoscopy findings) criteria for 12 weeks or more. Univariate analysis showed no correlation between exacerbation of CRS and primigravida status, GDM, AMA, preeclampsia, history of pregnancy loss, anemia, aspirin usage, or hypertension (Table 4). Nineteen (86.4%) patients were treated medically with a combination of intranasal corticosteroids, saline rinses, and oral antibiotics. Three (13.6%) were refractory to medical management and required surgical intervention, including in‐office polypectomy at 24 weeks gestational age, endoscopic sinus surgery in the early postpartum period, and bilateral functional endoscopic sinus surgery with simultaneous bilateral cauterization in a patient with concurrent epistaxis.

Table 4.

Factors Associated With Chronic Rhinosinusitis Prompting Referral to an Otolaryngology Specialist During Pregnancy

Demographics N = 22	Odds ratio	Standard error	P‐value	95% CI
History of pregnancy loss	0.655	0.3711	.455	0.215‐1.988
Primigravida status	0.45	0.248	.148	0.152‐1.325
Advanced maternal age	0.526	0.286	.238	0.181‐1.527
Gestational diabetes	0.875	0.527	.825	0.269‐2.85
Preeclampsia	0.8	0.584	.760	0.191‐3.347
Gestational Hypertension	2.364	1.806	.260	0.249‐10.511
Anemia	1.23	0.676	.707	0.418‐3.612
Aspirin usage	0.370	0.249	.140	0.099‐1.385

Rhinitis of Pregnancy

Ten (17.5%) of the 57 subjects were diagnosed with rhinitis of pregnancy. Rhinitis of pregnancy is defined as nasal congestion lasting at least 6 weeks in a pregnant individual without signs of an allergic cause or a respiratory tract infection (Figure 2). In our cohort, seven patients were referred for rhinitis lasting over 12 weeks without improvement, one patient was referred for primary ciliary dyskinesia and had concurrent rhinitis of pregnancy, one for an initial suspicion of CRS, and one patient with a history of inverted papilloma with new nasal congestion. Univariate and multivariate analyses found a significant association between rhinitis of pregnancy and pregnancy loss (P = .012) (Table 5). Most patients (90%) were treated with intranasal corticosteroids in spray or irrigation form. One was treated with saline rinses only.

Figure 2.

Endoscopic view showing septal inflammation in a patient with rhinitis of pregnancy. The nasal septum appears swollen and erythematous, consistent with inflammatory changes.

Table 5.

Factors Associated With Rhinitis of Pregnancy Prompting Referral to an Otolaryngology Specialist During Pregnancy

Demographics N = 10	Odds ratio	Standard error	P‐value	95% CI
History of pregnancy loss	6.80	5.22	.012*	1.51‐30.6
Primigravida status	0.377	0.269	.172	0.0933‐1.53
Advanced maternal age	3.52	2.97	.135	0.675‐18.4
Gestational diabetes	0.262	0.288	.224	0.0302‐2.268
Preeclampsia	0.542	0.608	.585	0.0599‐4.896
Gestational Hypertension	0.542	0.608	.585	0.0599‐4.896
Anemia	0.690	0.519	.623	0.158‐3.018
Aspirin usage	0.818	0.706	.816	0.151‐4.435

^*Maintained significance on multivariate analysis.

Discussion

There are multiple hypotheses to explain the pathophysiology of rhinologic conditions during pregnancy. During pregnancy, hormonal changes and an up to 50% increased blood volume lead to vasodilation and mucosal swelling, particularly affecting the nasal vessels. ⁴ , ⁷ This causes vascular congestion and heightened fragility of the nasal mucosa, which may also be amplified by increased levels of progesterone. This results in an increased incidence of epistaxis, which is three times more common in pregnant individuals when compared to nonpregnant people. ³ , ⁴ , ⁸ Furthermore, estrogen influences vascular walls by modulating nitric oxide (NO) and vascular endothelial growth factor (VEGF) and VEGFR‐2, which are known vasodilators, further worsening nasal conditions during pregnancy. ³ , ⁸ , ⁹

This study identified a significant association between epistaxis and primigravida status, which supports previous reports of severe epistaxis in primigravida patients. ⁴ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ , ¹⁵ , ¹⁶ The heightened severity of epistaxis in primiparous patients may be secondary to increased hormonal concentrations during first pregnancies compared to subsequent ones. ¹⁷ Furthermore, the available literature is skewed towards primigravida patients rather than multigravida patients, potentially because multiparous patients are more likely to possess knowledge, experience, and support systems to differentiate bodily changes during pregnancy and avoid seeking out specialized medical care. ³

In contrast, no association between GDM and epistaxis was found in our cohort. Although Abrich et al ¹⁸ demonstrated a link between recurrent epistaxis and diabetes mellitus, there is only one case report documenting a pregnant individual with GDM experiencing severe epistaxis. ¹⁹ Pathophysiologically, diabetes is known to damage blood vessels by forming atherosclerotic plaques, rendering blood vessels more prone to thinning and rupture and potentially predisposing patients to epistaxis. ¹⁸ However, this was not observed in our cohort.

Although we did not find a significant link between epistaxis and pregnancy loss, previous reports have detailed this relationship. Shirzadi et al described epistaxis in a pregnant individual with congenital factor V deficiency who experienced recurrent miscarriages. ²⁰ One theory links previous pregnancy loss to underlying clotting disorders, which can lead to vascular occlusion and fetal demise. ²¹ This finding emphasizes the importance of monitoring and managing epistaxis during pregnancy to mitigate potential complications.

Conditions like CRS and rhinitis of pregnancy are exacerbated by the same hormonal vasodilatory effects contributing to epistaxis risk, which can result in worsening of preexisting symptoms. ²² The placenta's contribution to physiologic changes includes the release of placental growth hormone, triggering systemic effects like vasodilation. Ulkumen et al observed the physiological and gestational pattern of VPAC1 and VPAC2 expression in the nasal mucosa in rats. ²³ VPAC1 and VPAC2 receptors are part of the vasoactive intestinal peptide (VIP) pathway, a potent vasodilator upregulated in conditions like allergic rhinitis. ²³ , ²⁴ Ulkumen's study showed the upregulation in VPAC1 and VPAC2 in pregnant rats with rhinitis of pregnancy, contributing to the overall understanding of rhinologic conditions during pregnancy. ²³

In this study, 40% of patients with rhinitis of pregnancy were primigravida, and 80% were AMA. Previous studies report a cumulative incidence of rhinitis of pregnancy of 22%, with smoking identified as a significant risk factor. ²⁵ Additionally, cross‐sectional observational studies highlighted a decrease in rhinosinusitis‐specific quality of life in the third trimester, emphasizing the impact of rhinitis on the overall well‐being of pregnant individuals. ²⁶ Because one in five pregnant patients has rhinitis of pregnancy, pregnant patients usually present to an otolaryngologist only when symptoms are severe or initial treatments by primary care providers or obstetricians have failed. In fact, although precise data on referral rates are limited, it is reasonable to estimate that less than 1% of pregnant patients require otolaryngologic evaluation for rhinologic issues. ² Every year, thousands of pregnant patients are seen by our hospital's OBGYN group, with a limited cohort needing specialized rhinologic care. ² This estimate aligns with clinical observations and the understanding that, often, only severe or refractory cases are referred to specialists.

Interestingly, our study also found an association between rhinitis of pregnancy and patients with a history of pregnancy loss (P = .012). As there have not been direct studies linking rhinitis of pregnancy and pregnancy loss, we investigated additional factors that could have contributed to our results. There have been prior studies describing a relationship between antiasthmatic medications and an increased risk of complications leading to pregnancy loss. ²⁷ A study observing complications in pregnant patients who were prescribed antiasthmatics during pregnancy compared to controls who had given birth during the same period found that pregnant patients on antiasthmatics, particularly beta‐2‐adrenergic agonists, had significantly higher rates of gestational diabetes, preeclampsia, hemorrhage at delivery, and premature rupture of membranes. ²⁷ Based on these findings, we hypothesized that in our rhinitis of pregnancy cohort, there may have been higher rates of patients on antiasthmatic medications.

Although there are no direct relations comparing rhinitis of pregnancy and asthma, it has been shown that more than 80% of asthmatics have allergic rhinitis, and 10% to 40% of individuals with allergic rhinitis have asthma. ²⁸ In our study, 4/10 patients with rhinitis of pregnancy had concurrent asthma, 3/4 were prescribed albuterol, and 2/3 of the patients on albuterol had prior pregnancy losses. Given the small sample size, we cannot establish a definitive link between rhinitis and increased rates of pregnancy loss. Moreover, it remains unclear whether the observed relationship is causal or merely correlational, with external factors such as our high cohort percentage of AMA potentially influencing the outcomes. ²⁹ , ³⁰

The management of epistaxis, CRS, and rhinitis of pregnancy has not been critically evaluated in the literature, though several studies have addressed this topic. ⁴ , ¹⁰ , ¹¹ , ¹² , ¹⁹ , ³¹ , ³² , ³³ , ³⁴ , ³⁵ , ³⁶ , ³⁷ , ³⁸ Piccioni et al identified and studied 13 cases of severe epistaxis of pregnancy and proposed a stepwise management algorithm. ⁴ The treatment of epistaxis suggested follows similar algorithms typically applied to nonpregnant patients, including starting with a conservative approach such as moisturizing measures for nasal dryness. ⁴ If symptoms persist, nasal packing with a vasoconstrictor is used, followed by cauterization if needed. Tranexamic acid may be considered in severe cases. ⁴ In very severe and refractory cases, surgical intervention, such as sphenopalatine artery ligation, anterior or posterior ethmoidal artery ligation, or embolization, might be necessary. ¹⁵ Treatment of exacerbations of CRS and rhinitis during pregnancy focuses on conservative approaches to avoid harm to the fetus. In the setting of gestational rhinitis, symptoms should resolve postpartum. ²² Initial measures include education, reassurance, dietary changes, exercises to enhance nasal blood flow, and positional adjustments for better airflow. ²² , ³⁹ , ⁴⁰ , ⁴¹ , ⁴² If these are insufficient, saline rinses, intranasal corticosteroids, decongestants, intranasal cromolyn, anticholinergics, antibiotics, and/or oral antihistamines can provide relief, ensuring medications are not teratogenic. ²² , ³⁹ Oral corticosteroids are also an option but only recommended after the first trimester, as they have been associated with a small risk of cleft lip and palate in newborns. ⁸ , ⁴³

In managing pregnant patients with rhinologic conditions, our approach to choosing between in‐office procedures and operating room (OR) interventions was individualized, considering disease severity, symptomatology, and patient preferences. Many patients wanted to avoid general anesthesia due to concerns about potential fetal or maternal risks. For instance, the American College of Obstetricians and Gynecologists (ACOG) notes that although nonobstetric surgery is sometimes necessary during pregnancy, careful consideration of the benefits and risks is essential, and nonurgent procedures are often deferred until after delivery. ⁴⁴ In our practice, conservative management strategies were initially prioritized. When procedural intervention became necessary, in‐office treatments such as silver nitrate cauterization were preferred for appropriate cases, minimizing anesthesia exposure. However, patients with more severe or refractory conditions required OR‐based interventions. In these cases, regional anesthesia was favored over general anesthesia, when appropriate, aligning with recommendations that suggest regional techniques can be safe during any trimester, depending on the individual patient's needs and medical history. ⁴⁵ Special anesthetic considerations included positioning to avoid aortocaval compression, maintaining normotension, and ensuring adequate oxygenation to safeguard both maternal and fetal well‐being. ⁴⁶

There are limitations to the study, including the retrospective nature of our data collection, which limits our evaluation to symptoms reported in the EMR. Furthermore, our study focused on cases that prompted otolaryngologic evaluation, and thus, the results cannot be generalized to the broader pregnant population as these likely represented more severe cases of rhinologic conditions of pregnancy. Additionally, the current literature has notable limitations, including variability in study designs, interventions, and outcome measures, which require cautious interpretation.

Conclusion

In our cohort of pregnant patients seeking out otolaryngologic care, epistaxis of pregnancy was significantly associated with primigravida status on multivariate analysis and GDM on univariate analysis. Rhinitis of pregnancy was also significantly associated with a history of pregnancy loss. As with many women's health issues, resources allocated to pregnancy‐related rhinologic conditions are lacking. It is important to better understand these diagnoses, their associated risk factors, and the available treatment options so that primary care physicians and otolaryngologists can better identify and treat patients suffering from these conditions.

Author Contributions

Yasmin Eltawil, conception, design, and drafting of the work, interpretation of data for the work; critically revising the work for important intellectual content; approval of the final submission; agreement to be accountable for all aspects of the work. Jacquelyn K. Callander, conception, design, and drafting of the work, interpretation of data for the work; critically revising the work for important intellectual content; approval of the final submission; agreement to be accountable for all aspects of the work. Patricia A. Loftus, conception, design, interpretation of data for the work; critically revising the work for important intellectual content; approval of the final submission; agreement to be accountable for all aspects of the work.

Disclosures

Competing interests

None.

Funding source

None.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request. All data generated or analyzed during this study are included in this published article.