New data show no miscarriage link for HPV vaccination
September 23, 2015
A new study looks at whether or not the HPV vaccine increases miscarriage risk. And, is there a link between nocturnal enuresis and sleep apnea in postmenopause? Plus: The impact of the Mediterranean diet on breast cancer risk.
A study by investigators from Costa Rica and the National Cancer Institute provides reassurance about the safety of human papillomavirus (HPV) vaccination for women who may become pregnant soon after receiving the vaccine. The findings, published in BMJ, show no increased risk of miscarriage for pregnancies conceived <90 days after vaccination, adding to results of an earlier study that found a similar trend for pregnancies conceived ≥90 days after vaccination.
Conducted in Costa Rica, the observational single-center study represented long-term follow up of a randomized double-blind trial combined with an independent, unvaccinated population-based cohort. The participants were 7466 women in the trial and 2836 women in the unvaccinated cohort who enrolled at the end of the randomized trial and in parallel with the observational trial component.
Women in the trial were randomized to 3 doses of either the experimental bivalent HPV L1 virus-like particle AS04 vaccine (n=3727) or the control hepatitis A vaccine (n=3739). Crossover bivalent HPV vaccination occurred in the hepatitis A vaccine arm at the end of the trial. Women in the unvaccinated cohort (n=2836) received no vaccination and were enrolled to allow continued evaluation of efficacy and safety of the vaccine despite loss of the original controls because of the crossover vaccination.
Of the 3394 pregnancies that occurred at any time after HPV vaccination, 318 were conceived <90 days after vaccination. Unexposed pregnancies comprised 2507 pregnancies conceived after hepatitis A vaccination and 720 conceived in the women who had not been vaccinated.
Miscarriages occurred in 451 (13.3%) of the exposed pregnancies, 50 (13.1%) of the pregnancies conceived <90 days after HPV vaccination, and 414 (12.8%) of the unexposed pregnancies. Of the latter pregnancies, 316 (12.6%) were in the hepatitis A vaccine group and 98 (13.6%) in the unvaccinated cohort. The relative risk (RR) for miscarriage of pregnancies conceived <90 days after vaccination versus all unexposed pregnancies was 1.02 (95% confidence interval [CI] 0.78 to 1.34, one sided P=0.436) in unadjusted analyses. Results were similar after adjustment for age at vaccination, age at conception, and calendar year, and in stratified analyses.
For pregnancies conceived at any time after HPV vaccination, exposure to the vaccine was not associated with an increased risk of miscarriage overall or in subgroups, except for miscarriages at weeks 13 to 20 of gestation (RR 1.35, 95% CI 1.02 to 1.77, one sided P=0.017). The outcome in this subgroup, the authors said, is compatible with chance and may be an artifact of a thorough set of sensitivity analyses. However, because they could not totally rule out a genuine association, the investigators recommend further exploration in ongoing and future studies. Curiously, the rate of miscarriages at 13 to 20 weeks in the women exposed to hepatitis A vaccine was lower than that in both the HPV-vaccinated group and the women who had no vaccination.
Surprising enuresis/sleep apnea link in postmenopause
A new study based on data from the Women’s Health Initiative (WHI) suggests that nocturnal enuresis may signal an increased risk of obstructive sleep apnea (OSA) in postmenopausal patients. The findings are from a cross-sectional study published in Menopause.
The study cohort was 2789 women aged 50 to 79 years who participated in the WHI from 1993 to 2005 in 40 clinical centers around the United States. The association between OSA risk factors and nocturnal enuresis was determined with multiple variable logistic regression analysis.
Nocturnal enuresis was reported by 1.7% of the women enrolled. The condition was linked to obesity (odds ratio [OR], 2.29; 95% CI, 2.00-2.62), snoring (OR, 2.01; 95% CI, 1.74-2.32), poor sleep quality (OR, 1.70; 95% CI, 1.52-1.91), sleep fragmentation (OR, 2.44; 95% CI, 2.14-2.79), daytime sleepiness (OR, 1.50; 95% CI, 1.33-1.68), and hypertension (OR, 1.13; 95% CI, 1.01-1.26). With every additional risk factor for OSA in the predefined OSA score, the odds that a woman had nocturnal enuresis increased in a dose-response fashion (OR of 1.38, 2.00, 2.80, 3.87, 5.10, and 7.02 for scores of 1-6, respectively).
The investigators concluded that risk factors for OSA were associated with nocturnal enuresis in postmenopausal women. They speculated that one of the mechanisms for the link between OSA and nocturnal enuresis may be changes in intrathoracic pressure, which could lead to increased urine output. Questioning at-risk postmenopausal women with nocturnal enuresis about other OSA risk factors, the authors said, should be considered by providers.
Could a Mediterranean diet impact breast cancer risk?
Eating a Mediterranean diet with more extra virgin olive oil may have a positive impact on primary prevention of breast cancer, according to results of a multiyear study by Spanish investigators. Published in JAMA Internal Medicine, the analysis is the first randomized trial to show that a long-term dietary intervention can help lower breast cancer incidence.
The single-blind PREDIMED study was conducted in primary healthcare centers across Spain from 2003 to 2009. The participants-4282 women-were recruited by their primary care physicians. All were aged 60 to 80 years and at high cardiovascular risk; 4152 had no prior history of breast cancer. Randomization was to a Mediterranean diet supplemented with extra virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet, which was advice to reduce dietary fat. To ensure high consumption of the key foods, the women in the two intervention arms were given free supplementary foods (extra virgin olive oil or mixed nuts, respectively) for their families.
Over the course of a median 4.8 years of follow up, 35 confirmed incident cases of breast cancer were identified in the women. The observed rates per 1000 person-years were 1.1 for the Mediterranean diet with extra-virgin olive oil group, 1.8 for the Mediterranean diet with nuts group, and 2.9 for the control group. When compared to the control group, the women who consumed a diet supplemented with extra virgin olive oil had a 68% lower risk for breast cancer.
The investigators concluded that a Mediterranean diet supplemented with extra virgin olive oil can have a beneficial effect on preventing breast cancer. They noted that their results are from secondary analysis of a previously run trial and, therefore, require confirmation in longer-term and larger trials. The authors also cautioned that because the cohort included only white postmenopausal women at high cardiovascular risk, the findings may not be generalizable to other age groups or ethnicities.