Tolle Causam

Kris Somol, ND
Mary Schroeder, BSC
Kathryn Hightower, BA
Francisco Miranda, BSC

Urinary tract infection (UTI) is a common ailment in female-bodied individuals. Certain populations are at an increased risk for UTI, including, but not limited to, pregnant and postpartum women.1 Due to catheterization, there is an increased risk of bacteriuria in post-Cesarean section (CS) patients.2 Current standards of care for acute, uncomplicated cystitis call for the use of an antibiotic such as nitrofurantoin and/or trimethoprim-sulfamethoxazole, both of which are excreted in breast milk.3,4 Though the amount excreted is relatively low, the presence of antibiotics in breast milk has the potential to alter bowel flora in neonates.4 Currently, the World Health Organization recommends avoiding nitrofurantoin while breastfeeding infants less than 1 month of age.4 Given the increased risk of UTI in post-CS patients and concerns about neonatal exposure to antibiotics, there is a need for alternative interventions for preventing UTIs.
In a recent randomized controlled trial conducted by Seifi et al (2018), researchers investigated the effectiveness of Rosa canina fruit in preventing UTIs following CS.1 Rosa canina is a wild plant whose fruits, known as rose hips, are widely used for their immune-modulating and antioxidant properties. They contain high amounts of vitamin C, in addition to vitamins A, B1, B2, B6, D, E, and K.5 They are also rich in carotenoids, including lycopene and β-carotene. In the Seifi et al study, the 400 subjects were patients in the postpartum period following CS, who were matched socioeconomically.1 For the 20 days following surgery, the intervention group (n=200) was administered Rosa canina fruit (500 mg standardized capsules, twice daily by mouth), and the control group (n=200) was administered a placebo consisting of cornstarch capsules (twice daily by mouth).
The subjects were assessed for UTI at 7-10 and 20 days post-surgery, based on symptom evaluation and urine culture.1 The primary outcome was the incidence of any UTI (asymptomatic or symptomatic) up to 20 days postpartum. In our paper, the methods, results, and conclusions of the Seifi et al study were analyzed in order to answer the following clinical question: “What is the effectiveness of Rosa canina in preventing UTI in post-CS patients?” In order to be inclusive of trans men and gender-non-conforming individuals, this paper was written using gender-neutral language.

Methods

The study of interest was located on PubMed, using the search term “Urinary Tract Infections,” and with the following filters applied: Clinical Trial, Humans, 5 years, and Complementary Medicine.

Results

At 7-10 days post-CS, 4 subjects in the experimental group developed a UTI, as compared with 17 in the control group (odds ratio=0.22).1 At 20 days, the numbers were 8 and 23, respectively (OR=0.32).
Seifi et al listed no statistical analyses beyond odds ratios. Unfortunately, odds ratios are not always the most accurate reflection of treatment effect. As stated by Schechtman, “An odds ratio will always exaggerate the size of the effect compared to a relative risk.”6 Consequently, we made our own calculations:
Among subjects who developed a UTI, Absolute Risk Reductions (ARRs) and Relative Risk Reductions (RRRs) were modest: ARR=0.066 at 7-10 days, and 0.078 at 20 days; 0.5<RRR<1. The Number Needed to Treat (NNT) was somewhat high at both 7-10 days and 20 days: NNT=15 at 7-10 days; NNT=13 at 20 days.
The most significant results were found in the outcome of asymptomatic bacteriuria. At 7-10 days post-surgery, the RRR was 0.69 and the ARR was 0.046, with an NNT of 22. The 20-day mark is where this intervention demonstrated the most benefit: RRR=0.838; ARR=0.8; NNT=12 (p=0.006)
In contrast, the outcome of cystitis (symptomatic) was equivocal. At the 7-10-day follow-up, 2.6% of the control group developed cystitis, in comparison to 0% of the experimental group (RRR=1).1 However, at the 20-day follow-up, the incidence of cystitis was actually increased in the experimental group in comparison to the control group, albeit to a small degree (1.6% vs 0%, respectively).
The researchers’ clinical question was answered through the study’s final results. Although the results were not overwhelmingly positive, the researchers did show that Rosa canina was mildly effective at preventing UTIs in post-CS women.

Discussion

For the outcome of any UTI (asymptomatic or symptomatic), the absolute numbers in this study looked encouraging, as the development of a UTI was significantly lower among subjects taking Rosa canina compared to those taking placebo. However, the AARs are not staggering, and the RRRs are greater than 0.5 but less than 1. The NNT for both points in time is somewhat high; the NNT of 13 at 20 days is not quite low enough to warrant prophylactic treatment with only this intervention. The most promising results of the study were found in the outcome of asymptomatic bacteriuria, especially at the 20-day mark.
Since the subjects with asymptomatic bacteriuria received prophylactic antibiotic treatment, there was a reduction in symptomatic cystitis in both groups. The low incidence of symptomatic UTIs may have been one reason that Rosa canina didn’t appear to be effective for symptomatic cystitis, even though it did appear to be relatively effective for asymptomatic bacteriuria. It is also likely that larger subject groups and a longer treatment time-frame may be necessary to detect any significant effects of this treatment on cystitis incidence.
Overall, this was a well-designed and thorough study. The randomization process was clearly stated (“block randomization with block sized 4 and 6 and allocation ratio of 1:1”) and was performed by someone who was not involved in the sampling or data analysis.1 It was also triple-blinded, involving blinding of clinicians, participants, and analysts. A thorough demographic survey was conducted at the start of the study, and no significant differences were observed between the 2 groups, aside from spouse education (p=0.006).
There are 3 major limitations to this study. First, despite the authors explicitly stating they would perform an intention-to-treat analysis, they did not. During the course of the study, 8% of the intervention group and 5.5% of the control group had discontinued follow-up.1 The statistical analysis only included the remaining subjects, raising the possibility of attrition bias. However, the attrition rate was slightly lower in the placebo group, and the satisfaction rate was nearly equal by the end of the study. This suggests that the cornstarch capsules were relatively effective as placebo. Second, as the researchers acknowledge in their paper, the trial period should have been closer to 40 days in order to more adequately represent the postpartum period (in which UTI risk is still relatively high). Third, the way in which patients were screened and treated for asymptomatic and symptomatic UTIs did not mirror clinical practice. During the course of the study, they screened subjects for the presence of pathogenic bacteriuria. Subjects with detected uropathogens were treated for 7 days with antibiotics (either cephalexin 500 mg or nitrofurantoin 100 mg). In clinical practice, patients would only be treated for a UTI if they presented with symptoms. This prophylactic treatment of asymptomatic subjects may have decreased the apparent effectiveness of Rosa canina in treating symptomatic cystitis.

Conclusions

Rosa canina fruit may help prevent UTIs in post-CS patients. While the Seifi et al study did show a statistically significant reduction in urethral bacteriuria in post-CS patients, its effectiveness in preventing cystitis in this population is unclear at best. Further studies should investigate the effectiveness of Rosa canina in preventing UTIs in postpartum women throughout the full postpartum period (that is, up to 40 days postpartum and/or post-CS) as well as in other high-risk populations, including patients with urinary catheterization and post-menopausal women. Additional research on other safe botanical medicines for post-CS and postpartum people is also warranted.

References:

1. Seifi M, Abbasalizadeh S, Mohammad-Alizadeh-Charandabi S, et al. The effect of Rosa (L. Rosa canina) on the incidence of urinary tract infection in the puerperium: A randomized placebo-controlled trial. Phytother Res. 2018;32(1):76-83.
2. Feteke T. Catheter-associated urinary tract infections in adults. Last updated October 2, 2018. UpToDate Web site. https://www.uptodate.com/contents/catheter-associated-urinary-tract-infection-in-adults. Accessed August 14, 2018.
3. Hooton TM, Gupta K. Acute Simple Cystitis in Women. Last updated October 17, 2018. UpToDate Web site. https://www.uptodate.com/contents/acute-simple-cystitis-in-women. Accessed August 14, 2018.
4. World Health Organization. Breastfeeding and Maternal Medication: Recommendations for Drugs in the Eleventh WHO Model List of Essential Drugs. 2002. Available at: https://tinyurl.com/y8x8t8br. Accessed August 12, 2018.
5. Koczka N, Stefanovits-Bányai É, Ombódi A. Total Polyphenol Content and Antioxidant Capacity of Rosehips of Some Species. Medicines (Basel). 2018;5(3). pii: E84. doi: 10.3390/medicines5030084.
6. Schechtman E. Odds ratio, relative risk, absolute risk reduction, and the number needed to treat—which of these should we use? Value Health. 2002;5(5):431-436.

Kris Somol, ND, has spent 20 years in the healing profession and 10 years as a public educator on botanical medicine. She has written articles for the Seattle Times and has been consulted for multiple online publications. She is a lecturer on women’s health, pediatrics, and more. Dr Somol is an adjunct faculty member at Bastyr Center for Natural Health, where she sees patients in private practice. She received an ND degree from Bastyr University and a BA in Russian language and literature from Wesleyan University. She has served as secretary on the board of directors for the Washington Association of Naturopathic Physicians.

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Mary Schroeder, BSc, is a 5th-year student in Bastyr University’s Naturopathic Medicine and Acupuncture and East Asian Medicine dual-track program. She completed her undergraduate degree in environmental science at McGill University, where she conducted research in botany and ecology. Mary has received additional training in advanced gynecology, Ayurvedic medicine, herbal medicine, and trans health. In her future practice, she plans to use a combination of Naturopathy and Traditional Chinese Medicine, with a focus on gynecological and digestive conditions.

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Kathryn Hightower, BA, is in her final year of the Naturopathic Medicine program at Bastyr University. Her professional passions include LGBTQ+ health, community healthcare, hydrotherapy, homeopathy, and counseling. Kathryn has received additional training at the Kneipp Schule in Germany, the New England School of Homeopathy, and Gender Odyssey. Kathryn currently serves as a mental health counselor at Bastyr University, where she is also a teacher’s assistant and research assistant.

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Francisco Miranda, BSc, graduated from Bastyr University’s Naturopathic Medicine program in the summer of 2018. Francisco’s medical philosophy involves empowering patients to achieve optimal health through education, support, and guidance. His clinical interests include type 2 diabetes, CVD, digestive wellness, and physical medicine with osseous manipulations and injection therapies. With a background in chiropractic, he believes in finding the best approach to support his patient’s health goals while using modern research with safe, effective therapies to get to the root of the problem. He currently sees patients at Bastyr Center for Natural Health.