On April 26, 2022, the FDA approved inhibitor that targets CYP51 and is available as oteseconazole (Vivjoa), an oral azole antifungal indicated to reduce the incidence of recurrent vulvovaginal candidiasis (RVVC) in women with a history of RVVC who are not of reproductive potential.1 Oteseconazole is an azole metalloenzyme a single-drug regimen or in combination with fluconazole. Antifungal therapy may be instituted before the results of the cultures are known and adjusted accordingly when results become available.2

The first 2 clinical trials (NCT03562156 and NCT03561701)3,4 included a total of 656 adults and postmenarcheal pediatric women with RVVC who were randomly assigned to receive either oteseconazole only or placebo.

A third trial (NCT03840616)5 evaluated safety of oteseconazole vs fluconazole and placebo in 219 adults and postmenarcheal pediatric women with RVVC.2

Trials 1 and 2 each included an open-label induction phase and an 11-week maintenance phase. During the induction phase, participants received 3 sequential doses of fluconazole 150 mg every 72 hours on days 1, 4, and 7. At 14 days following the first fluconazole dose, if the acute VVC episode was resolved, participants were randomly assigned 2:1 to receive either oteseconazole 150 mg or placebo for 7 days, followed by 11 weekly doses during the maintenance phase; 326 and 330 patients, respectively, entered this phase. Primary efficacy end points were the proportion of patients with greater than or equal to 1 culture-verified acute VVC episode during the maintenance phase through week 48.3 The average percentage of patients with an acute VVC episode was lower in the oteseconazole group vs the placebo group in both trials (6.7% vs 42.8% and 3.9% vs 39.4%, respectively).2

Trial 3 evaluated the efficacy and safety of oteseconazole vs fluconazole and placebo. This trial also included induction and maintenance phases. Participants received a total dose of oteseconazole 150 mg over 2 days (600 mg [4 × 150 mg] on day 1 and 450 mg [3 × 150 mg] on day 2) or 3 sequential doses of fluconazole 150 mg every 72 hours on days 1, 4, and 7. Patients returned 14 days after the first dose and moved to the maintenance phase if the acute VVC episode was resolved. During the maintenance phase, patients received oteseconazole 150 mg or placebo weekly for 11 weeks.5 The primary efficacy end point was the proportion of patients with greater than or equal to 1 culture-verified acute VVC during the maintenance phase or who failed to clear their infection during the induction phase. The average percentage of patients with greater than or equal to 1 culture was lower in the oteseconazole group vs the fluconazole and placebo group (10.3% vs 42.9%, respectively).2

The most frequently reported adverse events were headache (7.4%) and nausea (3.6%). One patient discontinued therapy because of allergic dermatitis. Because of the risk of embryo-fetal toxicity, oteseconazole is contraindicated in women of reproductive potential and in women who are pregnant or lactating. Medication administration in conjunction with a high-fat, high-calorie meal increased concentrations, but no significant differences were observed with a low- fat, low-calorie meal.2

The oteseconazole-only dosage regimen is initiated as a 600-mg capsule on day 1 and 450 mg on day 2, each as a single dose. The next dose is administered on day 14 as a 150-mg capsule once weekly for 11 weeks.

The fluconazole/oteseconazole dosage regimen is initiated with fluconazole 150 mg orally on days 1, 4, and 7, followed by oteseconazole 150 mg once daily for 7 days, starting on day 14 through day 20. After day 20, the next oteseconazole dose is administered on day 28 as a 150-mg capsule once weekly for 11 weeks. Oteseconazole must be taken with food.2

FDA approves Mycovia Pharmaceuticals’ VIVJOA (oteseconazole), the first and only FDA-approved medication for recurrent vulvovaginal candidiasis (chronic yeast infection). News release. Mycovia Pharmaceuticals; April 28, 2022. Accessed July 12, 2022. 

https://mycovia.com/wp-content/uploads/2022/04/FINAL-Press-Release_04.28.22.pdf

Vivjoa. Prescribing information. Mycovia Pharmaceuticals Inc; 2022. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215888s000lbl.pdf

A study of oral oteseconazole for the treatment of patients with recurrent vaginal candidiasis (yeast infection)(VIOLET). ClinicalTrails.gov. Updated April 6, 2022. Accessed July 12, 2022. 

https://clinicaltrials.gov/ct2/show/NCT03562156

A study of oral oteseconazole (VT-1161) for the treatment of patients with recurrent vaginal candidiasis (yeast infection) (VIOLET). ClinicalTrials.gov. Updated December 20, 2021. Accessed July 12, 2022. 

https://clinicaltrials.gov/ct2/show/NCT03561701

Study of oral oteseconazole (VT-1161) for acute yeast infections in patients with recurrent yeast infections (ultraVIOLET). ClinicalTrials.gov. Updated February 4, 2022. Accessed July 12, 2022. 

https://clinicaltrials.gov/ct2/show/NCT03840616

Articles

Oteseconazole is a treatment option for those living with a previously unmet medical need.

Vivjoa approved for recurrent vulvovaginal candidiasis

 and joined the MJH Life Sciences team in December 2019. She graduated from Youngstown State University in 2019 with a bachelor's degree in journalism and a minor in political science. Prior to graduating, Morgan worked as the editor-in-chief of her college newspaper. She went on to work as an assignment editor at a broadcast news station in Youngstown, Ohio before joining 

Myovant announced the US Food and Drug Administration (FDA) has approved relugolix combination tablets (Myfembree; Myovant Sciences and Pfizer) for the treatment of moderate-to-severe endometriosis-associated pain.

Previously, Myfembree was only approved for the management of uterine fibroid-related heavy menstrual bleeding in premenopausal women.

“This approval is an important milestone reflecting Pfizer and Myovant’s commitment to women’s health in areas of significant unmet need,” said James Rusnak, MD, PhD, senior vice president, chief development officer, Internal Medicine and Hospital, Global Product Development at Pfizer. “We look forward to making Myfembree available to women with endometriosis and broadening their options in managing this complex disorder.”

This decision by the FDA is supported by 

 from two phase 3 studies (SPIRIT 1 and SPIRIT 2) investigating the combination tablet for treatment of dysmenorrhea.

In both studies, 75% of women using the once-daily relugolix combination therapy experienced a significant reduction in dysmenorrhea, compared to 27% and 30% of women in the placebo groups at Week 24, respectively (both p < 0.0001). Relugolix combination therapy also significantly reduced non-menstrual pelvic pain in 59% and 66% of women, compared to 40% and 43% in the placebo groups (p <0.0001).

In SPIRIT 1 and 2, the relugolix combination therapy group also showed reductions in dyspareunia and opioid use compared to the placebo groups. Additionally, more women undergoing relugolix combination therapy were opioid free at Week 24 compared with placebo (86% and 82% vs 76% and 66%, respectively).

The most frequently reported adverse events by women in both the relugolix combination therapy and placebo groups included headaches, nasopharyngitis, and hot flashes.

"The data from the SPIRIT studies showed the clinical benefit that relugolix combination therapy can have on moderate to severe pain associated with endometriosis and how it can impact patients,” said Linda Giudice, MD, PhD, distinguished professor at the University of California, San Francisco (UCSF), and chair, SPIRIT Program Steering Committee. “This newly approved option for patients with pain from endometriosis offers the convenience of one pill taken once daily with a mean change in bone mineral density of <1% that did not appear to worsen at 12 months of treatment; however, monitoring is recommended.”

Myfembree is now available with a prescription to patients with moderate-to-severe pain associated with endometriosis.

1. Myovant Sciences and Pfizer Receive U.S. FDA Approval of MYFEMBREE, a Once-Daily Treatment for the Management of Moderate to Severe Pain Associated With Endometriosis. Myovant Sciences. August 5, 2022. Accessed August 5, 2022. https://investors.myovant.com/news-releases/news-release-details/myovant-sciences-and-pfizer-receive-us-fda-approval-myfembreer

2. Giudice LC, As-Sanie S, Arjona Ferreira JC, et al. Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomized, double-blind, studies (SPIRIT 1 and 2). 

. 2022;399(10343):2267-2279. doi:10.1016/s0140-6736(22)00622-5

Myovant Sciences and Pfizer announces the US Food and Drug Administration has approved Myfembree (relugolix combination tablets) for the once-daily treatment of moderate-to-severe endometriosis-associated pain. 

FDA approves Myfembree for endometriosis pain

You can reach her a lcarr@mjhlifesciences.com.

Cervical cancer screening guidelines for adolescents

Teenaged girls at average risk don’t need Papanicolaou tests, but some special populations do.

Best practices on discussing birth control for adolescents.

FDA grants ibrexafungerp sNDA priority review for RVVC

If approved, ibrexafungerp would be the first and only approved therapy for both the treatment of vulvovaginal candidiasis (VVC) and the prevention of recurrent vulvovaginal candidiasis (RVVC).

The latest resources from the American Urogynecologic Society

Check out these latest resources from the American Urogynecologic Society.

Changes for ICD-10 documentation codes that go into effect in October 2022.

How much money are you losing in unnecessary meetings?

Tips to avoid wasting time and optimize meetings you do need.

In case you missed it: Aug 1 to Aug 5

Monkeypox has been declared a public health emergency (PHE) in the United States.

U.S. Department of Health and Human Services (HHS) Secretary Xavier Becerra announced 

 Aug. 4 to “strengthen and accelerate the Biden-Harris administration’s response in recognition of the continued rapid transmission of monkeypox in the U.S. and globally, and to signal the seriousness and urgency with which the administration is responding.”

“Ending the monkeypox outbreak is a critical priority for the Biden-Harris Administration,” Becerra said in a news release. “We are taking our response to the next level by declaring a public health emergency.”

The same day, the U.S. case count reach 7,102 confirmed cases, according to the U.S. Centers for Disease Control and Prevention (CDC). More than 500 cases have been reported in New York, Georgia, Florida, Illinois, Texas and California, and just two states, Montana and Wyoming, have had no reported cases. Cities and states were quicker in their declarations than the federal government.

There were 26,864 confirmed cases in 88 countries around the world, with most of those in 81 countries that historically have not reported the disease. The World Health Organization on July 23 declared monkeypox to be a public health emergency of international concern.

 found some American believe it is a sexually transmitted disease. It is not, according to CDC, but can be spread through close, personal, often skin-to-skin contact, including sexual contact.

Along with the PHE declaration, the U.S. Food and Drug Administration (FDA) is working on new strategies to get vaccines to affected communities across the country, including a new dose-sparing approach that could increase up to five-fold the number of doses available, according to HHS.

As of Aug. 4, HHS announced it has shipped more than 602,000 doses of the Jynneos vaccine to states and jurisdictions, an increase of 266,000 in the past week. HHS has allocated 1.1 million doses to states and jurisdictions in total and is making more doses available as jurisdictions use their current supply. HHS has accelerated delivery of 150,000 additional doses to arrive in the U.S. next month instead of November.

So far, 51 jurisdictions have signed data use agreements to provide CDC with information related to vaccine administration. Declaring an emergency may provide the justification the remaining jurisdictions need to sign their agreements. The PHE provides authorities to the Centers for Medicare & Medicaid Services to collect testing and hospitalization data.

The developments came two days after the White House announced appointments of Robert Fenton, a regional administrator of the Federal Emergency Management Agency, as White House National Monkeypox Response Coordinator and Demetre Daskalakis, MD, MPH, director of HIV prevention for the Centers for Disease Control and Prevention (CDC), as White House National Monkeypox Response Deputy Coordinator.

“President Biden has called on us to explore every option on the table to combat the monkeypox outbreak and protect communities at risk,” Fenton said in the HHS announcement. “We are applying lessons learned from the battles we’ve fought – from COVID response to wildfires to measles, and will tackle this outbreak with the urgency this moment demands.”

This article originally appeared on Medical Economics®. 

White House ramps up efforts to fight outbreak.

HHS declares monkeypox a public health emergency in U.S.

The national rate of people without health insurance dropped to a record low 8% in the first quarter of 2022, according to federal researchers.

 estimated about 26.4 million people lacked health insurance in the first quarter of 2022, down from an annual estimated of 31.6 million people without insurance in 2020. That indicates about 5.2 million people – an estimated 4.1 million adults aged 18 to 64 years, and 1 million children aged 17 years or younger – gained health coverage since 2020.

The figures were in an analysis published Aug. 2 by the Office of Health Policy in the 

Assistant Secretary for Planning and Evaluation

 (ASPE) in the U.S. Department of Health and Human Services (

). APSE credited the administration of President Joe Biden for 2021 actions that built on large reductions in uninsured rates due to the 2014 Affordable Care Act (ACA).

“Overall, these results highlight the significant gains in health insurance coverage that occurred in 2021 and early 2022 associated with the Biden-Harris Administration’s policies to support health insurance expansion,” the report said. “These gains build on the large reductions in the uninsured rate that occurred after the implementation of the Affordable Care Act (ACA) in 2014, which research demonstrates produced improved health outcomes, better access to care, and improved financial security for families.”

Before 2022, the previous record low uninsured rate was 9% in 2016, for the annual rate. The lowest quarterly estimate was 8.6% in the first quarter of 2016, though the report noted quarterly estimates are more volatile due to smaller sample sizes.

About 5.4% of adults aged 18 to 64 years reported having ACA Marketplace coverage in early 2022, up about 2 million people from the 4.4% Marketplace coverage rate of 2020.

The American Rescue Plan,the administration’s response to the economic woes caused by the COVID-19 pandemic, included enhanced subsidies for people seeking insurance through the Marketplace at HealthCare.gov. The subsidies were retroactive to the start of 2021, boosted the size of premium tax credits for people with incomes between 100% and 400% of the federal poverty level (FPL), and extended tax credits to those with incomes above 400% of the FPL for the first time, the report said.

The Inflation Reduction Act, introduced in the Senate, would extend ACA Marketplace insurance subsidies through 2025.

“And I'm hopeful that with Congressional action we can continue the work to lower costs for more Americans by both extending the enhanced Affordable Care Act tax credits that have helped drive the uninsured rate to an all-time low and increasing the affordability of prescription drugs for Medicare beneficiaries – reducing their cost sharing and allowing Medicare to negotiate a better deal on prescription drug prices,” HHS Secretary Xavier Becerra said in a statement.

Without an extension, there have been predictions that millions of people will face premium increases for Marketplace plans, leading to a decline in overall health care spending. Regardless of subsidies, at least one report has forecasted a spike in 2023 premiums due to inflation.

Additional factors for the declining uninsured rate included the continuous enrollment provision in Medicaid for adults aged 19 to 64 with incomes less than 138% of the FPL.

Five states expanded Medicaid for adults in 2019 and 2020. From 2018 to 2020, the most recent year data are available, those states had the largest decreases in uninsured rates: Idaho (-8.4%), Virginia (-7.2%), Maine (-4.9%), Nebraska (-2.8%), and Utah (-1.4%).

Two states that expanded Medicaid in 2021 posted increases in the rates of uninsured: Missouri (1.7%) and Oklahoma (2.9%). The report did not explain why.

Among the 50 states and the District of Columbia, only four – Washington D.C., Massachusetts, Rhode Island and Vermont – had single digit uninsured rates for those who qualify for Medicaid.

 that “Medicaid expansion was shown to have improved preventive care and financial security for adults with disabilities.”

More people getting health coverage, but 26.4 million still don’t have it.

Rate of people without health insurance hits record low

The increases were highest for Hispanic and non-Hispanic Black women.

“We are very familiar with the potential and limitations of current data on maternal death,” said co-author Eugene Declercq, PhD, a professor of community health sciences at Boston University School of Public Health in Massachusetts. “Hence, we thought it relevant to use that experience to explore the potential impact of COVID on maternal deaths.”

The study, which used data from the National Center for Health Statistics (NCHS), stratified deaths by month or year: deaths before COVID (2018, 2019, and January to March 2020) and deaths during the pandemic (April to December 2020).

A total of 1,588 maternal deaths (18.8 per 100,000 live births) occurred before the pandemic versus 684 deaths (25.1 per 100,000 live births) during the pandemic, for a relative increase of 33.3%.

Late maternal mortality (between 43 and 365 days after birth) increased by 41%.

Absolute and relative changes were highest for Hispanic (increases of 8.9 per 100,000 live births and 74.2%, respectively) and non-Hispanic Black women (16.8 per 100,000 live births and 40.2%) compared to non-Hispanic White women (2.9 per 100 000 live births and 17.2%).

For underlying cause-of-death codes, the largest relative increase was among indirect causes (56.9%), specifically other viral diseases, diseases of the respiratory system and diseases of the circulatory system.

Relative increases in direct causes (27.7%) were mostly linked to diabetes in pregnancy (95.9%), hypertensive disorders (39.0%) and other specified pregnancy-related conditions (48.0%).

COVID-19 was also commonly listed as a secondary condition with other viral diseases and diseases of the respiratory system.

“The somewhat surprising finding was the high rate of COVID cases (32%) among Hispanic mothers and the 74% increase in maternal deaths in this population,” Declercq told 

. “For a number of years, Hispanic mothers have had a maternal mortality rate lower than non-Hispanic White mothers. However, during the 9 months of the pandemic, Hispanic maternal deaths rose so quickly that their maternal mortality ratio slightly exceeded that for non-Hispanic Whites.”

The study focused on public health rather than clinical concerns. “Our findings suggest that the notable efforts that maternity care providers have engaged in to improve hospital outcomes need to be extended to community-level care for prevention of not only COVID infections, but future infectious diseases as they arise,” Declercq said.

The expansion of women’s health services to reduce what the March of Dimes has described as “maternity care deserts” and allow for a more robust response to subsequent outbreaks can help reduce racial and ethnic disparities, according to Declercq, who noted that the pandemic exacerbated existing disparities.

“Mortality ratios for non-Hispanic Black mothers rose to an astonishing 59 per 100,000 during the first 9 months of the pandemic, a ratio that would rank close to 100th in the world,” he said. “While some of that increase appears related to COVID cases, the proportion of COVID cases as a multiple cause of death among Black women (13%) was not particularly high and therefore the jump in maternal mortality may be related to the continued limitations of care for women of color.”

The critical question is the degree to which clinicians can learn from the pandemic and “establish robust, integrated healthcare systems that serve women at the community and hospital levels, and provide needed supports throughout the lifespan,” Declercq said.

Thomas ME, Declercq ER. All-cause maternal mortality in the US before vs during the COVID-19 pandemic. 

. Published online June 28, 2022. doi:10.1001/jamanetworkopen.2022.19133

Maternal deaths in the United States rose by a staggering 33% after the onset of the COVID-19 pandemic in March 2020, which is a significantly higher percentage than the 22% overall excess death estimate linked to the pandemic, according to a research letter published in JAMA Network Open.

Maternal mortality before and during COVID pandemic

“A body of literature shows associations between neighborhood socioeconomic context and health outcomes,” said first author Mary Willis, PhD, MPH, a postdoctoral research scholar in environmental epidemiology at Oregon State University in Corvallis. “Dozens of studies examine health outcomes related to birth and asthma, for example. However, the world of fertility research is largely focused on individual-level interventions, mainly healthy eating or exercise, as opposed to structural-level interventions that may influence fertility for an entire population.”

The study is the first to directly examine fecundabilty, the per-cycle probability of conception, with respect to neighborhood deprivation, according to Willis. “We do not know what factors in the neighborhood environment may be most important for fecundability,” she told 

. “Our team hypothesized that it could be anything from crime levels to community poverty to green space access.”

The prospective preconception cohort study, which used baseline data from the Pregnancy Study Online, comprised 6,356 participants, aged 21 to 45 (mean baseline age 30.0 years), who were attempting conception without fertility treatment.

Overall, 83.3% of the participants were non-Hispanic White and 65.7% nulliparous.

Questionnaires were completed every 8 weeks for 12 months, until conception or a censoring event, between 2013 and April 2019.

A total of 3,725 pregnancies were reported for 27,427 menstrual cycles of follow-up.

Comparing the top decile to the bottom decile of disadvantaged neighborhood status, adjusted fecundability ratios were 0.79 (95% confidence interval [CI]: 0.66 to 0.96) for national-level area deprivation index (ADI) rankings and 0.77 (95% CI: 0.65 to 0.92) for within-state ADI rankings.

These connections were slightly stronger among participants with lower annual incomes of less than $50,000.

Willis noted that neighborhood context, including a socioeconomically disadvantaged neighborhood environment, “is a complex phenomenon that encompasses a variety of chronic stress exposure pathways.”

Public policies that influence decisions about neighborhood investment, as well as disinvestment like redlining, “may perpetuate a cycle of chronic stress and continued neighborhood socioeconomic disadvantage,” Willis said. “For instance, higher neighborhood unemployment has been associated with decreased population-level fertility rates.”

Likewise, less affluent areas often have higher concentrations of air pollution, resulting in adverse fertility outcomes.

“In addition, less affluent areas may have fewer amenities, such as green spaces, to restore capacity in residents to reduce stress,” Willis said.

By contrast, urban renewal programs demonstrate positive health benefits for local populations.

“Both income and educational attainment may be influenced by neighborhood disadvantage earlier in life; therefore, they are potential mediators of the exposure-outcome association,” Willis said. “However, our study examined neighborhood disadvantage in adulthood.”

If people are socially immobile, there would likely be similar ADI levels over time, “so we could argue that educational attainment and income in adulthood are mediators,” Willis said. “On the other hand, if we assume a noteworthy change in neighborhood context with the transition from adolescence to adulthood, it is more probable that these socioeconomic attributes, along with race and ethnicity, influence the neighborhoods in which people live as adults, although these residential locations may not be by choice.”

Therefore, adjusting for individual socioeconomic factors depends largely on the conceptual framework. “Disentangling the influence of individual versus neighborhood factors may not be possible,” Willis said. “Nonetheless, if our results can be confirmed by other studies, I hope it will inspire clinicians to think about fertility in a structural context.”

Willis MD, Orta OR, Ncube C, et al. Association between neighborhood disadvantage and fertility among pregnancy planners in the US. 

. Published online June 30, 2022. doi:10.1001/jamanetworkopen.2022.18738

Residing in a socioeconomically disadvantaged neighborhood was linked to moderately decreased fecundability, according to a study published in JAMA Network Open.

Neighborhood disadvantage and fertility rates

“Previous studies suggest that altered growth patterns in fetal life and infancy are related to increased risks of cardiovascular diseases in adulthood,” said leading investigator Romy Gonçalves, MSc, who is a PhD candidate in pediatric epidemiology at Erasmus MC, University Medical Center in Rotterdam, the Netherlands. “For example, low birth weight is associated with an unfavorable body composition, higher blood pressure, and higher levels of cholesterol and triglycerides.”

Carotid intima-media thickness and carotid distensibility can both be measured by ultrasound. “The intima-media thickness reflects the inner and middle layer of an artery, and plaque buildup can be identified this way,” Gonçalves told 

Arterial distensibility reflects the elasticity of an artery, according to Gonçalves. “Decreased distensibility is associated with increased risk of arterial wall damage,” she said. “In adults, suboptimal quality of the carotid artery, such as increased carotid intima-media thickness and reduced carotid distensibility, is related to the development of atherosclerosis and cardiovascular diseases. However, this relationship is less clear in children.”

The population-based prospective cohort study was conducted from early fetal life onward in 4,484 offspring (50.4% girls and 57.5% Dutch ethnicity) of women in Rotterdam, the Netherlands, delivering between April 2002 and January 2006.

Estimated fetal weight was measured in the second and third trimester, whereas infant weight was measured at 6, 12 and 24 months.

Follow-up measurements were available for the children at a median age of 9.7 years.

Gestational age at birth was not associated with markers of arterial health; however, a 500 g higher birth weight was linked to significantly increased carotid intima-media thickness and a lower carotid distensibility.

Compared to children with a birth weight of 2500 g to 4500 g, those weighing more than 4500 g had the lowest carotid distensibility.

In addition, compared to children with normal fetal and infant growth, children with normal fetal growth that was followed by accelerated infant growth had the highest carotid intima-media thickness.

The observed associations were mostly explained by childhood body mass index (BMI).

“We hypothesized that children born with low or high birth weight would have increased carotid intima-media thickness and lower carotid distensibility,” Gonçalves said. “But we did not find associations of low birth weight with arterial health.”

The relations of higher fetal weight and infant weight growth with arterial health outcomes are quite novel and indicate that very early-in-life increased weight gain has an effect on the carotid intima-media thickness and carotid distensibility, according to Gonçalves. “Our results suggest that high birth weight followed by higher infant and childhood weight gain is associated with an increased risk of adverse arterial health,” she said.

Gonçalves said further research is needed to examine the extent that adverse arterial health in childhood persists into adulthood. “Our outcomes imply that optimizing growth in early life might be beneficial for arterial health in later life,” she said. “Because our results were partly explained by childhood BMI, preventing high infant weight gain and childhood obesity could aid in reducing adverse arterial health.”

Exemplary prenatal care and information for caregivers and parents on reducing excessive infant weight gain could aid in reducing childhood obesity and subsequent cardiovascular diseases.

“I believe further studies should focus on longitudinal carotid measurements and determining if adverse childhood arterial health persists into adulthood,” Gonçalves said. “Thereby, it could be determined if measurements of childhood arterial health might add to prevention strategies to improve cardiovascular health later in life.”

Gonçalves R, Wiertsema CJ, Silva CCV, et al. Associations of fetal and infant growth patterns with early markers of arterial health in school-aged children. 

. Published online June 29, 2022. doi:10.1001/jamanetworkopen.2022.19225

Both higher fetal and infant weight growth patterns are linked to early markers of impaired arterial health, according to a study published in JAMA Network Open.

Fetal/infant growth patterns and early markers of arterial health

“Maternal mortality rates in the U.S. are higher than other countries with similar resources; therefore, advancing our understanding of factors that contribute to the maternal death rate is critical,” said principal investigator Heather Frey, MD, MSCI, an associate professor of maternal-fetal medicine at The Ohio State University in Ohio.

Frey noted that obesity, which affects about one-third of pregnant women, is a known risk factor for complications, such as diabetes and hypertension, in pregnancy and is associated with higher rates of mortality in non-pregnant women. “However, some of the previous research is conflicting as to the association between obesity and SMM, so we wanted to better understand this relationship,” she said.

The study accessed the vital records and linked Medicaid claims data in the state of Ohio from January 2012 to December 2017 to determine both mortality and SMM from 20 weeks’ gestation through 1-year postpartum.

In the cohort of 347,497 pregnancies among 276,691 Medicaid beneficiaries, the median maternal age at delivery was 25 years, of whom 60.6% were non-Hispanic White women. The prevalence of maternal obesity was 30.5%.

Composite SMM and/or mortality outcome occurred in 5.3% of pregnancies.

The adjusted risk ratio for an elevated risk of SMM and/or mortality during pregnancy to 1-year postpartum compared to a healthy body mass index (BMI) was 1.07 (95% confidence interval [CI]: 1.03 to 1.11) for overweight (25.0 -- 29.9 BMI); 1.19 (95% CI: 1.13 to 1.24) for class 1 obesity (30.0 -- 34.9 BMI); 1.37 (95% CI: 1.30 to 1.44) for class 2 obesity (35.0 --39.9 BMI); and 1.71 (95% CI: 1.63 to 1.80) for class 3 obesity (≥40.0 BMI).

Results were comparable when the follow-up period was shortened to 42 days postpartum or the delivery hospitalization.

Hypertension mediated 65.1% of the association between obesity and SMM and/or mortality.

“While we were not surprised that hypertension was a mediator, the proportion of the relationship between obesity and the outcome that was explained by hypertension was higher than expected,” Frey told 

. “This highlights the need to develop and implement effective interventions to reduce the risk of hypertensive complications during pregnancy, particularly among obese women.”

The frequency with which women experienced different morbidities within the timeframe also differed by maternal BMI class. For instance, women with increased BMI had high rates of sepsis, while transfusion was the most common indicator of SMM in those with lower BMI when assessed through 42 days postpartum.

“Our data suggest that women who are obese may require increased medical surveillance during pregnancy and, perhaps more importantly, after delivery,” Frey said. “Interventions to improve the delivery of postpartum care and enhance the transition of care from the obstetrician to a primary care provider are needed.”

The study also underscores the importance of identifying and managing hypertensive disorders in pregnant women, particularly those with obesity.

“Unfortunately, efforts to reduce rates of obesity in the U.S. have been largely ineffective on a population level,” Frey said. “On the individual level, though, weight reduction strategies should be employed prior to conception, which starts with appropriate counseling in the preconception period.”

But there is no perfect approach, so discussions and interventions must be tailored to the individual patient, according to Frey. “In the appropriate patient who is interested and motivated to pursue weight-loss surgery, referrals prior to conception should be facilitated,” she said.

Meanwhile, obesity is one of the most common medical comorbidities of pregnancy, and rates of obesity in the pregnant population are expected to continue to increase over the next decade. “Thus, improving our understanding of the risks associated with this condition, then identifying effective interventions to improve the health of pregnant individuals with obesity, are imperative,” Frey said.

1. Frey HA, Ashmead R, Farmer A, et al. Association of prepregnancy body mass index with risk of severe maternal morbidity and mortality among Medicaid beneficiaries. 

Published online June 28, 2022. doi:10.1001/jamanetworkopen.2022.18986

A study published in JAMA Network Open found that maternal prepregnancy obesity in the United States is associated with an elevated risk of severe maternal morbidity (SMM) and/or mortality. 

Prepregnancy BMI and risk of severe maternal morbidity and mortality

Melissa M. Mauskar, MD, is an associate professor of dermatology and obstetrics and gynecology at UT Southwestern Medical Center in Dallas, Texas. She is the founder and director of the Gynecologic Dermatology clinic at UT Southwestern.

Hunter J. Pyle is a fourth-year medical student at the UT Southwestern Medical Center in Dallas, Texas.

Audrey K. Rutherford, MD, is a dermatologist who recently graduated from the dermatology residency program at UT Southwestern in Dallas, Texas. Her current practice is in Salt Lake City, Utah, where she treats women with vulvar dermatoses as well as practices general medical, surgical, and cosmetic dermatology.

Recognizing and appropriately managing common vulvar conditions is essential to preserve patient quality of life and prevent irreversible architectural sequelae. Patients with vulvar dermatoses often report a significant delay from symptom onset to diagnosis. This delay is multifactorial and includes patient and provider reluctance to discuss vulvovaginal or other intimate symptoms. In addition, most women do not examine their vulvas.

Results of a study showed that only 15% of participants were able to correctly sketch vulvar anatomy, 67% had not heard of vulvar self-examination, and 61% approached their genitalia with feelings of shame and embarrassment.

 It is important that providers be comfortable initiating these conversations to prevent diagnostic delay and to give patients accurate information and timely treatment.

Using the correct terms allows providers to develop a wide differential diagnosis 

. An important concept in vulvovaginal dermatology is lichenoid eruption, a diverse group of inflammatory skin diseases sharing common morphology and/or histopathology. Distinguishing among the various lichenoid conditions of the genitalia, including vulvar lichen sclerosus (VLS), vulvovaginal lichen planus (VLP), and vulvar lichen simplex chronicus (LSC), is important because optimal treatments vary. 

Figure 1. Select Dermatology Terminology. 

Although all 3 conditions may present primarily with pain or pruritus, features such as anatomic involvement, risk factors, and associations may differ. VLS and VLP are primary cutaneous disorders, whereas vulvar LSC is a secondary skin condition resulting from another underlying dermatosis, infection, or psychological or neurologic condition. VLS primarily affects external genitalia, whereas VLP may affect both the vulva and vagina.

VLS is a chronic, often progressive dermatologic condition that involves the anogenital region. The prevalence of VLS is not well established, though it is likely an underrecognized and undermanaged condition. Results of large cohort study showed an estimated prevalence in the United States of 0.05%, with 79% of diagnoses in women between the ages of 45 and 65 years but 16% of diagnoses in women between the ages of 18 and 44 years.

 Most patients present with vulvar pain, pruritus, or irritation, but patients may be asymptomatic. Patients eventually diagnosed with VLS may have yeast infections for years 

Figure 2-1. Pustules on an erythematous base in a patient with vulvovaginal candidiasis.

Figure 2-2. Hypopigmented macules in a patient with vulvar lichen sclerosus.

Early detection of VLS is critical to preventing irreversible architectural sequelae and vulvar squamous cell carcinoma (SCC). Skin changes that may be evident upon vulvar inspection include white, atrophic papules that may coalesce into plaques, often affecting the labia minora or majora 

Figure 2-3. Typical hypopigmented tissue paper wrinkling in a patient with vulvar lichen sclerosus. (Figures provided by author)

Early VLS may have a nonspecific presentation, so a high degree of suspicion must be maintained. Varying degrees of architectural change may be present in later disease stages. It is important to note indurations and small erosions, which could be signs of SCC, even in younger patients. First-line treatment is early use of a superpotent topical corticosteroid with continued topical corticosteroid for maintenance therapy. Patient education emphasizing treatment adherence is critical. In a study that spanned 8 years, patients adherent to topical corticosteroid treatment did not develop SCC or precursor vulvar intraepithelial neoplasia (VIN), and adhesions and scarring developed in only 3% of patients.

 Reports of symptomatic control also were higher in adherent patients. In contrast, in patients only partially adherent with treatment, 5% developed SCC or VIN and 40% developed adhesions
and scarring.

VLP is an inflammatory condition and subtype of lichen planus (LP) that most commonly affects women between 50 and 60 years of age.

 Although the incidence and prevalence of VLP is unknown, most women with LP have genital lesions.

 Most frequently, patients will present with soreness, pruritus, or genital burning. 

Allergic and irritant contact dermatitis of the vulva

Allergic and irritant contact dermatitis (ACD/ICD) frequently occur concomitantly with other vulvar conditions as preexisting dermatosis impairs skin barrier function. In patients with vulvar ACD, the most common concomitant vulvar diagnoses are VLS followed by LSC.

 This may complicate the clinical picture and lead to diagnostic and management delays. Therefore, vulvar ACD/ICD should be considered when patients with vulvar disease are not improving with standard treatment.

Figure 2-4. Introitus erosions with surrounding lacy/reticular border in a patient with erosive vulvovaginal lichen planus.

Vulvar ICD may occur acutely or, more commonly, chronically. Symptoms in vulvar ACD may become apparent 1 to 2 days after allergen exposure, but commonly the exposure is unrecognized and may only slowly produce symptoms and eruption. This frequently leads to difficulty in identifying the culprit allergen. Patients with ACD/ICD often present with nonspecific vulvar pruritus or burning. Skin changes in vulvar ACD/ICD are similar and include erythema, edema, vesicles, bullae, and oozing. Thus, clinical differentiation of vulvar ACD/ICD is not reliable. The diagnosis of vulvar ICD is based on history and establishment of a potential irritant, whereas vulvar ACD may be established with patch testing.

Patients with vulvovaginal symptoms have often tried various topicals for symptom resolution before seeking medical attention. Common vulvar irritants include body fluids, hygiene or personal care products, heat, excessive bathing, medications, soaps, and detergents.

 The most commonly identified allergens in ACD are fragrances, preservatives, and medications including neomycin and topical anesthetics.

 Patients may have an allergy to topical corticosteroids,

 which are an important first-line treatment for many vulvar dermatoses 

ACD/ICD treatment includes discontinuing potential irritants and allergens, using petroleum on erosions, and educating patients. Patients should be counseled on the importance of cleaning the vulva with lukewarm water without harsh or fragranced soaps, cleansers, or detergents, and using sitz baths for additional symptomatic relief. Topical corticosteroid ointments may be used in severe or chronic disease, and antihistamines may be used for pruritus. Patients may benefit from a dermatology referral for patch testing to identify possible culprit allergens, which is a more appropriate testing modality to identify contact allergens than the skin prick test commonly performed by allergist physicians.

Figure 2-5. Erythematous thickened, corrugated plaques with accentuation of skin markings on the labia majora and inguinal folds characteristic of lichenification found in lichen simplex chronicus. There is also a thin white scale on the leftinguinal fold. (Figures provided by author).

LSC is a reactive skin disorder secondary to chronic skin rubbing or scratching, often in response to persistent pruritus or irritation, regardless of primary problem. It results in secondary changes of skin including thickening and lichenification 

, with a moderately well-defined scaly plaque. Patients with other vulvar dermatoses often develop LSC in response to chronic scratching. Patients with LSC can pose a diagnostic challenge as primary skin conditions cannot be appropriately diagnosed until there is improvement in LSC symptoms and cutaneous changes. LSC is typically a clinical diagnosis, and management centers on disrupting the itch-scratch cycle, in which pruritus leads to scratching, which perpetuates and worsens inflammation. First-line medical treatment often includes a short course of medium-potency topical corticosteroid to promote active lesion resolution. Upon treatment of LSC, an underlying primary vulvovaginal dermatosis may be more readily identifiable and addressed.

Genitourinary syndrome of menopause (GSM), formerly called vulvovaginal atrophy or atrophic vaginitis, refers to a collection of signs and symptoms that occur in menopausal women secondary to decreased stimulation of estrogen-sensitive tissues, including the vulva, vagina, urethra, and bladder. GSM is very common. In fact, vulvovaginal symptoms occur in 39% to 51% of postmenopausal women, with the majority having moderate to severe symptoms, and one-third stopping sexual activity because of their symptoms.

 Unfortunately, many women do not recognize vulvovaginal atrophy and are reluctant to discuss vaginal or sexual symptoms with health care professionals.16 Most women with GSM believe that their vaginal symptoms are a normal part of aging.

 Symptoms seen in GSM include genital dryness, discomfort, burning, dyspareunia, dysuria, urinary incontinence, and recurrent urinary tract infections. Physical changes may include a vaginal epithelium that is a paler pink hue with decreased rugation, diminished pubic hair, decreased turgor and elasticity of the vulva, and minimization of the labia minora. GSM is a clinical diagnosis. Women have a strong desire for health care professionals to initiate conversations regarding GSM.16 First-line treatment includes vaginal moisturizers, personal lubricants, and low-dose vaginal estrogen. Of note, multiple studies have shown no increase in risk of cardiovascular disease or cancer with low-dose vaginal estrogen use.

 In addition, low-dose vaginal estrogen has minimal systemic absorption and does not increase plasma estradiol to premenopausal levels, study results show.19 In cases of advanced symptoms, pelvic physical therapy may be beneficial, particularly for urinary incontinence
and dyspareunia.

Correct terms and education can help normalize the conversation for patients.
