Volume 66 No 4: April 2021

US health officials are recommending a pause in the administration of the single-dose Johnson & Johnson COVID-19 vaccine following 6 reports of a rare and severe type of blood clot, according to a joint statement issued on Tuesday by the CDC and FDA.

The FDA will further investigate the cases, in which a blood clot called cerebral venous sinus thrombosis (CVST) was seen in combination with low levels of blood platelets, called thrombocytopenia. The CDC will also convene a meeting of the Advisory Committee on Immunization Practices (ACIP) on Wednesday to review the cases and assess their potential significance.

In a media briefing held on Tuesday, Peter Marks, MD, PhD, director of the FDA Center for Biologics Evaluation and Research; Janet Woodcock, MD, acting commissioner of the FDA; and Anne Schuchat, MD, principal deputy director of the CDC, discussed the details regarding the recommendation.

"We're recommending this pause while we work together to fully understand these events and also while we get information out to health care providers and [vaccine] recipients," Woodcock said in the briefing.

More than 6 millon doses of the Johnson & Johnson vaccine have been administered so far. Reports of these types of blood clots following the vaccine include 6 cases, all of which occurred in women between the ages of 18 and 48. Symptoms developed 6 to 13 days after vaccination. Of the clots seen in the United States, 1 case was fatal and 1 patient is in critical condition.

"Right now, these events seem to be extremely rare," Marks emphasized. "That said, COVID-19 vaccine safety is a top priority for the federal government." Marks added that the FDA will revise the fact sheet for health care providers and recipients to include this adverse event information. Health care providers who observe patients presenting to them with either low blood platelet counts or blood clots should establish whether or not the patient has recently been vaccinated, he said.

For individuals who have already received the Johnson & Johnson vaccine, Schuchat noted that the risk is very low for those who received the vaccine at least 1 month ago. Individuals who received the vaccine in the last couple of weeks should be aware of any symptoms.

However, Schuchat emphasized that these symptoms are different from the mild flu-like symptoms that many recipients experience in the couple of days following vaccination. Individuals who receive the Johnson & Johnson vaccine and develop severe headache, abdominal pain, leg pain, or shortness of breath within 3 weeks after vaccination should contact their health care providers.

No cases of clotting events with low platelet counts have been seen with the Moderna or Pfizer-BioNTech COVID-19 vaccines.

The ACIP will convene tomorrow to review the data on these initial cases to determine next steps.

This article was originally published on Drug Topics®

1. Joint CDC and FDA Statement on Johnson & Johnson COVID-19. News Release. FDA, CDC; April 13, 2021. Accessed April 13, 2021. 

https://www.prnewswire.com/news-releases/joint-cdc-and-fda-statement-on-johnson--johnson-covid-19-vaccine-301267526.html

Articles

The CDC and FDA will further investigate the reports of blood clots following administration of the vaccine.

FDA, CDC Recommend Temporary Pause for Johnson & Johnson COVID-19 Vaccine

European Journal of Obstetrics & Gynecology and Reproductive Biology

 surmises that for population-level screening, a notable proportion of positive screening tests are likely false-positives.

“There are a significant number of false-positive screening tests we see clinically on a regular basis,” said primary investigator Jacques Balayla, MD, MPH, an Osler Fellow in ob/gyn at McGill University in Montreal, Canada. “The implications for patient counseling and resource allocation that a false-positive result may carry are consequential, yet rarely addressed in modern medicine.”

The authors searched Medline, EMBASE, Google Scholar, Scopus, ISI Web of Science, Cochrane database and PubMed to obtain the sensitivity and specificity estimates for 10 screening tests, then used those estimates to calculate disease-specific prevalence thresholds and compare them to the actual estimates of disease prevalence.

Equation that helps calculate the prevalence threshold.

The prevalence thresholds and average estimates of disease prevalence (shown in parenthesis) were 31% (6%) for 50 g-oral glucose tolerance test (GDM-50 g); 7% (0.2%) for noninvasive prenatal testing (NIPT); 19.5% (0.2%) for combined first trimester screening (FTS); 18% (15% to 45%) for vagino-rectal swab for group B streptococcus (GBS) in pregnancy; 21% (0.2%) for cervical cytology (Pap) testing; 27% (0.2%) for human papillomavirus (HPV) testing; 25% (12.5%) for mammography; 25% (12.5%) for manual breast exam; 6% to 13% (4.2% to 4.7%) for cervical-vaginal swab testing for gonorrhea and chlamydia; and 32% (10%) for testing serum anti-Müllerian hormone (AMH) levels for polycystic ovary syndrome (PCOS).

“We were surprised how poor the predictive value of most tests for ob/gyn actually is, particularly when carrying out universal screening programs,” Balayla said. “More disturbing perhaps is the significant discrepancy between the prevalence threshold – the prevalence level above which the screening test yields the most reliable results – and the actual prevalence of disease. Such a large difference may explain why we observe false-positive results at the bedside so frequently.”

In reaction to the significant number of false-positive results observed in clinical practice, a number of guidelines have begun to transition to a risk-based approach to the diagnosis and management of certain conditions in ob/gyn, according to Balayla.

“In the meantime, having an understanding of Bayes’ theorem and the prevalence threshold can aid the clinical counselling of patients,” said Balayla, who developed the prevalence threshold statistic for the study. “If an individual’s risk is below the threshold, such as amongst patients with no symptoms or risk factors, a patient’s results may not be reliable; therefore, counseling should reflect this fact to avoid undue stress, until diagnostic testing can be conducted.”

Conversely, for women whose risk lies above the threshold, “resource allocation and ease of access to the health care system should be prioritized,” Balayla said.

Developing new tests and screening technologies with sensitivity and specificity parameters that improve upon current standards is one strategy to reduce the rate of false-positives.

“Adopting a risk-based approach to primarily screen those at higher risk would also accomplish this goal,” Balayla said.

The sensitization of health care providers to the Bayesian limitations of the screening process “will undoubtedly result in a more nuanced discussion with the patient about her risk of disease,” he said. “And on a larger scale, implementation of risk-based screening programs may enhance access to the health care system for those who need it most, and reduce costs and anxiety for patients and their loved ones.”

Balayla reports no relevant financial disclosures.

Elfassy L, Lasry A, Gil Y, Balayla J.Prevalence threshold of screening tests in obstetrics and gynecology. 

. Published online February 18, 2021. doi:10.1016/j.ejogrb.2021.02.015

A literature review has found that the prevalence thresholds of various screening tests used in ob/gyn health care settings are significantly higher than the estimated disease prevalence. 

Prevalence thresholds of screening tests

AUGS was established in 1979 and represents more than 1,900 members, including practicing physicians, nurse practitioners, physical therapists, nurses and health care professionals, and researchers from many disciplines.

This document was originally developed by the American Urogynecologic Society (AUGS) Guidelines Committee with the assistance of Tonya N. Thomas, MD, and Mark D. Walters, MD. 

This document was updated by the Publications Committee, September 2020.

Overactive bladder affects a significant portion of the overall population and has substantial impact on daily activities and quality of life. 

First-line treatment of overactive bladder includes behavioral therapies, which may be combined with pharmacologic management as indicated. 

Anticholinergic medications and β-3 agonists are often used as initial pharmacologic therapy, but caution should be taken in prescribing anticholinergic medications in frail or cognitively impaired patients. 

Recently, additional concerns have emerged regarding prolonged use of anticholinergic medications and the associated risk of cognitive impairment, dementia, and Alzheimer's disease in the general population. 

Given the available evidence, which has shown significant associations between anticholinergic medication use and increased risk of cognitive impairment and dementia, providers should counsel on the associated risks, prescribe the lowest effective dose, and consider alternative medications in patients at risk.

overactive bladder, anticholinergic, antimuscarinic, cognitive impairment, dementia

Overactive bladder (OAB) is a clinical diagnosis characterized by urinary urgency, with or without urgency incontinence, usually with increased daytime frequency and nocturia with urinary incontinence (OAB-wet) or without (OAB-dry) in the absence of urinary tract infection or other detectable disease. The overall prevalence of OAB in the general population is as high as 12% to 17%, and it significantly impacts the quality of life of affected individuals.

The underlying pathophysiology of OAB is detrusor overactivity (DO), a urodynamic diagnosis defined by involuntary detrusor contraction during filling cystometrogram.6 In patients desiring treatment for symptoms of OAB/DO, behavioral therapies, including fluid management, bladder training, urge suppression, and pelvic floor muscle strengthening, should be instituted first. If behavioral therapies do not control symptoms, then the American Urological Association and the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction Guideline on OAB recommends antimuscarinic or β-3 agonists as pharmacologic treatment.

Trials of different medications in these classes in varying doses are acceptable; however, extended-release formulations are preferred because of lower rates of dry mouth. The guideline does note that clinicians should use caution in prescribing antimuscarinic or β-3 agonists for OAB in frail patients or those with cognitive deficits. 

The American Urogynecologic Society’s “Choose Wisely” campaign recommends the avoidance of anticholinergic medications to treat OAB in women older than 70 years.

When behavioral therapies fail and pharmacologic treatment of OAB/DO is considered, providers should counsel on the associated risk of cognitive impairment, dementia, and Alzheimer's disease associated with anticholinergic medications in comparison with the potential benefits related to improvement in quality of life 

To reduce overall anticholinergic burden, the lowest effective dose should be prescribed, and consideration should be given to alternative medications such as 

Consideration should be given to changing or decreasing the dosage of other anticholinergic medications that a patient may be taking.

As recommended by the American Urogynecologic Society’s “Choosing Wisely” campaign, use of anticholinergic medications to treat OAB in women older than 70 years should be avoided.

When anticholinergic medications have to be used in elderly patients, consideration should be given to use those that have low potential to cross the blood-brain barrier, recognizing that there are limited clinical data.

Third-line therapies such as intradetrusor onabotulinum toxin A or neuromodulation should also be considered in patients not desiring to use medications for OAB/DO because of their adverse effects.

The full PDF of this Clinical Consensus Statement can be found here.

This was created in partnership with the American Urogynecologic Society (AUGS). AUGS was established in 1979 and represents more than 1,900 members, including practicing physicians, nurse practitioners, physical therapists, nurses and health care professionals, and researchers from many disciplines.

1. Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. 

 2003;20(6):327-336. doi:10.1007/s00345-002-0301-4

2. Irwin DE, Milsom I, Hunskaar S, et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. 

2006;50(6):1306-1314. doi:10.1016/j.eururo.2006.09.019

3. Lawrence JM, Lukacz ES, Nager CW, Hsu JWY, Luber KM. Prevalence and co-occurrence of pelvic floor disorders in community-dwelling women. 

. 2008;111(3):678-685. doi:10.1097/AOG.0b013e3181660c1b

4. Liberman JN, Hunt TL, Stewart WF, et al. Health-related quality of life among adults with symptoms of overactive bladder: results from a U.S. community-based survey. 

. 2001;57(6):1044-1050. doi:10.1016/s0090-4295(01)00986-4

5. Abrams P, Kelleher CJ, Kerr LA, Rogers RG. Overactive bladder significantly affects quality of life.

6. Haylen BT, de Ridder D, Freeman RM, et al. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. 

. 2010;21(1):5-26. doi:10.1007/s00192-009-0976-9

7. Gormley EA, Lightner DJ, Faraday M, Vasavada SP; American Urological Association; Society of Urodynamics, Female Pelvic Medicine. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline amendment. 

8.Ten things physicians and patients should question. American Urogynecologic Society. Accessed September 17, 2020. https://www.augs.org/assets/1/6/AUGS_10things_List_Draft_1.pdf

Association of Anticholinergic Medication Use and Cognition in Women With Overactive Bladder

Partner at Aaronson, Rappaport, Feinstein & Deutsch, LLP in New York City, specializing in medical malpractice defense and healthcare litigation.

A 32-year-old gravida 0 was seen for her wellness visit in March. She had no complaints. Her pelvic examination revealed adnexal fullness. An ultrasound performed in the physician’s office revealed a slightly enlarged left ovary, measuring 6 cm by 4 cm, with two cysts, 1.9 cm and 1.7 cm in diameter. The right ovary was not visualized on the vaginal ultrasound. An abdominal ultrasound was not performed. An evaluation 3 months later (June) again revealed adnexal fullness. 

An ultrasound identified a right ovary measuring 7 cm by 3.9 cm, with 3 small cysts. The left ovary was 4.5 cm by 2.9 cm, with a 1 cm cyst. A 6-month follow-up was recommended. The patient was seen the following December with complaints of postcoital bleeding. An endometrial biopsy revealed proliferative endometrium.

The patient was seen for her annual exam the following March, at the age of 33 years. It was noted that she had been on sertraline (Zoloft) for 2 years for treatment of depression. Her examination was normal. No additional studies or laboratory testing were performed. Four months later (July) she was seen in the emergency department for abdominal and pelvic pain. A CT revealed ovarian cysts bilaterally, the right measuring 5.2 cm by 4.6 cm by 3.5 cm, and the left measuring 5.1 cm by 4.9 cm by 3.5 cm.

Documentation is critical to defending a one’s actions. Although some states have passed laws that allow brief, truncated documentation, eg, “RBA (risks, benefits, alternatives) discussed” as adequate to reflect informed consent, it is prudent to know the requirements in one’s own state. In general, adequate informed consent requires a discussion of the medical condition or finding requiring treatment or surgery, the planned procedure, the alternatives for treatment, including observation only, and the substantial risks of the procedure. Such documentation enhances patient understanding while enhancing the defensibility if litigation occurs.

The patient was seen by her gynecologist 3 months later (October). She requested testing for ovarian cancer as her mother had recently been diagnosed with breast cancer. Her physician ordered an ultrasound and a CA 125. The patient was seen for her annual exam 3 months later (January), at 34 years of age. She relayed increasing difficulties in her marriage and noted she was now on citalopram (Celexa) for depression. A review of a recent pelvic ultrasound revealed a right adnexal cyst measuring 7.3 cm by 8.5 cm by 6.7 cm, with no further description. A CA 125 obtained on the day of the ultrasound was 46 U/mL. The patient was placed on combined oral contraceptives, with follow-up planned in 3 months.

The patient was seen in April, about 25 months from her initial presentation. An ultrasound revealed an enlarging right ovary, now 14.4 cm by 8.5 cm by 9.8 cm. Although her gynecologist recommended surgical treatment, the patient was reluctant to undergo surgery at that time due to an unstable work situation. 

The patient in her initial interview with her attorney stated that she wanted to hear an explanation of why things were handled the way they were. She wanted an explanation and an apology. Had this been done, she may not have sued. It is recognized that the lack of clear communication is one of the main issues that lead to litigation. This case illustrates how an open and clear explanation of what happened, with an empathetic approach to the patient’s concerns, may have avoided litigation altogether.

She was seen one month later (May), with an exam confirming an adnexal mass. She underwent another pelvic ultrasound that revealed a right ovarian cyst measuring 10 cm by 11 cm with a smaller secondary cyst. The gynecologist’s impression was, “Adnexal cyst, probably benign.” The patient was scheduled for surgery. Her preoperative consultation documentation was, “Surgery discussed, consents signed.” There was no additional documentation of the discussion, nor mention of more extensive surgery. The consent for surgery indicated, “Exploratory laparotomy with probable removal of ovary.”

The patient underwent an exploratory laparotomy via a transverse lower abdominal incision. An enlarged right ovary measuring 10 cm by 16 cm was removed and sent for frozen section, which found a serous tumor of at least low malignant potential (LMP). A left ovarian cyst was removed and sent for frozen section. The gynecologist elected to proceed with a total abdominal hysterectomy and bilateral salpingo-oophorectomy (BSO) before the results of the frozen section returned, which revealed a benign serous cyst. The total surgical time was 1 hour and 10 minutes. Final pathology revealed a uterus weighing 100 grams, with adenomyosis and a small leiomyoma. The right ovary had a serous tumor of LMP. 

The left ovary had endosalpingiosis and a benign serous cyst. Peritoneal washings were negative. The patient had an uncomplicated recovery from surgery. However, she did experience significant difficulties with hot flashes, which were poorly responsive to estrogen replacement therapy. She had worsening depression that significantly impacted her marriage, which ended in divorce 9 months following surgery.

The patient changed physicians about 1 year later. Her new gynecologist noted she was experiencing lots of hot flashes, significant memory change, and an exacerbation of depressive symptoms. Over the next 9 months, the new gynecologist received several calls from the patient requesting medications for worsening premenstrual syndrome. This culminated in a call in which the patient described panic attacks and worsening anxiety. She requested sertraline (Zoloft). The physician prescribed diazepam (Valium) and made an appointment for the following day, advising her that no further medications would be prescribed until she was seen. The patient did not show for this scheduled appointment.

The expert for the plaintiff had an excellent presence in the courtroom. He was down to earth, established an immediate rapport with the jury, and was able to explain complex concepts in a clear, understandable manner. The concessions addressed during his testimony further established credibility. Too often, experts on both sides take an uncompromising position that antagonizes jurors. Balanced testimony enhances the jury’s acceptance of an expert and their opinions.

About two months later, the patient filed a malpractice suit against the original gynecologist claiming the performance of unnecessary surgery, specifically a hysterectomy and BSO; a breach of the standard of care by not referring to a gynecologic oncologist; the loss of procreative potential; significant pain and suffering, including uncontrollable symptoms related to surgical menopause; and worsening depression and anxiety, ultimately resulting in dissolution of her marriage.

Following discovery, the case went to trial. The plaintiff’s gynecology expert stated that an abdominal ultrasound should have been performed when the right ovary was not identified on the initial vaginal ultrasound. Noting that the right ovary was visualized on the study 3 months later, measuring 7. by x 3.9 cm, with 3 small cysts, it was conceded that immediate surgical intervention was not required. Further, this expert volunteered that the two-year delay in performing surgery did not appreciably impact the patient’s prognosis with a tumor of LMP.

This expert opined that the documentation was lacking. There was inadequate documentation of the preoperative counseling, particularly addressing the probable diagnosis and treatment options. There is no documentation about the possibility of a hysterectomy and BSO, with resultant surgical menopause and the difficulties often encountered in treating related symptoms in younger women. Simply documenting, “Surgery discussed, consents signed,” was deemed wholly inadequate. Further, the patient’s consent did not reflect the possibility of a complete hysterectomy and removal of both ovaries.

The expert testified that controversy exists whether surgical staging is required for LMP tumors. However, with a frozen section revealing a serous tumor of LMP, a right oophorectomy or right salpingo-oophorectomy would have been appropriate and adequate, with staging performed at a later date if necessary. The expert further opined that although it would have been ideal, a gynecologic oncology consultation was not required preoperatively or intraoperatively.

 The defendant presented a defensive posture without displaying empathy for the patient. Such posturing leads to a poor connection with the jury, which may lead to a less favorable ruling.

The plaintiff’s expert opined that surgical castration was unwarranted. Before proceeding with surgical castration, the surgeon should have consulted with the patient’s husband regarding the probable diagnosis and immediate treatment options. The expert opined that there was no surgical emergency necessitating removal of the uterus and the remaining tube and ovary. Even with cancer, conservative surgery with staging can be appropriate in a nulliparous patient.

A social worker testified that the patient likely would remain childless. It was highly unlikely that she had the option of adoption, particularly with her relatively recent divorce.

A psychologic expert for the plaintiff testified that despite having premenstrual dysphoric syndrome and long-standing depression, surgery triggered a posttraumatic response that remarkably exacerbated her symptoms. As a result, her treatment had become much more difficult, resulting in major difficulties with interpersonal relationships, one outcome being the dissolution of her marriage.

The patient testified that she felt a mistake had been made, specifically the performance of the hysterectomy and removal of her “good” ovary. She wanted to hear an explanation of why things were handled the way they were. She felt there was a complete lack of recognizing the impact that surgery had on her life. She wanted an explanation and an apology. As a result, she was angry and felt betrayed.

The defense’s gynecologic expert stated that although the CA 125 was mildly elevated, it can be elevated in conditions unrelated to malignancies. Thus, gynecologic oncology consultation was not required before or during surgery. The documentation of the preoperative consultation, although brief, memorializes a more extensive discussion. It is not expected that such documentation includes every facet of that discussion. Further, the operative consent included a statement consenting to indicated procedures, thus covering the performance of the performed surgery. This expert opined that hysterectomy and BSO are perfectly appropriate, as a tumor of low malignant potential can recur and may even progress to more severe disease with metastasis. Further, acknowledging that surgical menopause in younger women can present unique challenges in managing menopausal symptoms, her physician tried various estrogen formulations and nonhormonal therapies to no avail.

A psychological expert for defense stated that the patient’s preexisting and long-standing depression, which required several changes in her medication, had significant potential to progress even without surgery. It was noted that at a gynecology appointment almost 6 months before the surgery, the patient relayed that there were significant difficulties in her marriage. Thus, the dissolution of her marriage was a result of long-standing and unresolved issues, rather than the surgery.

After 6 hours of deliberation, the jury found for the plaintiff, awarding $700,000 in damages.

Polling of the jurors following the trial’s conclusion revealed that they placed great credence in the plaintiff’s expert. He conceded some issues while clearly explaining the rationale behind his expressed opinions. He explained complicated concepts clearly, appeared empathetic, and seemed to “connect” with the jury. Conversely, the defendant was defensive and gave evasive answers to direct questions. Further, the jurors said, the defendant seemed dismissive and lacked empathy. 

This case illustrates how a clear explanation and empathy for the patient’s concerns may have avoided litigation altogether.

Were a Hysterectomy and a Bilateral Salpingo-oophorectomy Necessary?

Wanting clarification on a possible higher risk of adult-onset 

 from a preterm live birth, or gestation of less than 37 weeks, investigators from Sweden conducted a national cohort study of all live singleton births in the country between 1973 and 2014.

Their data show a 42% greater risk of new adult-onset heart failure between the ages of 18 and 43 years if the individual was born before 37 weeks gestation, according to the study published in 

. There also was an overall 0.1% incidence of heart failure, with a median age of 15.4 years at diagnosis.

“Preterm birth has been associated with increased risk of heart failure early in life, but its association with new-onset heart failure in adulthood appears to be unknown,” the authors noted when explaining why they looked into this outcome.

With a primary outcome of heart failure, the authors also stratified their data by several measures of gestational age: extremely preterm births (22-27 weeks), moderately preterm births (28-33 weeks), late preterm births (34-36 weeks), and early term births (37-38 weeks).

The median age of the 4 million-plus individuals included in the study was 22.5 years, and there were 85 million person-years of follow-up. Among this entire cohort, preterm birth age was associated with elevated risk of heart failure at any age vs full-term birth (39-41 weeks):

Younger than 1 year (adjusted HR [aHR], 4.49; 95% CI, 3.86-5.22)

Aged 1 to 17 years (aHR, 3.42; 95% CI, 2.75-4.27)

Aged 18 to 43 years (aHR, 1.42; 95% CI, 1.19-1.71)

When stratifying by each measure of gestational age among the adult cohort, the risks remained elevated, as did the incidence of heart failure (per 100,000 person years), but both measures dropped with the longer gestational periods:

Extremely preterm births (HR, 4.72; 95%CI, 2.11-10.52); 31.7 cases

Moderately preterm births (HR, 1.93; 95% CI, 1.37-2.71); 13.8 cases

Late preterm births (HR, 1.24; 95% CI, 1.00-1.54); 8.7 cases

Early term births (HR, 1.09; 95% CI, 0.97-1.24); 7.3 cases

The incidence of heart failure among full-term single births was 6.6 cases per 100,000 person-years in comparison. This association was seen even after “excluding persons with structural congenital cardiac anomalies,” the authors noted.

Male and female participants also had similar case totals of heart failure stemming from a preterm birth, preterm infants were more likely to be born to mothers either younger than 20 years or 40 years and older, and most preterm births in the study were first in birth order.

An important distinction the authors add is that the greater risk of heart failure among those aged 18 to 43 years may be linked to family histories of heart failure and preterm birth, whereas this is not the case for individuals with young-onset heart failure.

All diagnoses of heart failure were identified by 

International Classification of Diseases, Eighth Revision

 codes, and the entire study cohort was followed up with from their earliest heart failure diagnosis after birth through the end of the study period. Variables adjusted for included birth year, sex, birth order, family history of ischemic heart disease, and maternal factors such as age, education level, smoking status, and diabetes history before delivery.

“To our knowledge, this is the largest population-based study of preterm birth in association with heart failure risks and the first to examine such risks into mid-adulthood or include co-sibling analyses,” the authors concluded, with study strengths that included the large national cohort design, highly complete nationwide birth and medical registry data, and the large sample size.

Their findings indicate a possible long-term need for clinical follow-up among adult survivors of preterm births, with monitoring for heart failure one of the focus areas, especially with the median age of heart failure onset dropping, they added.

This article was originally published on The American Journal of Managed Care

Crump C, Groves A, Sundquist J, Sundquist K. Association of preterm birth with long-term risk of heart failure into adulthood. 

. Published online April 5, 2021. doi:10.1001/jamapediatrics.2021.0131

A higher risk of adult-onset heart failure was found in this Swedish study that investigated its association with singleton live births before 37 weeks gestation.

Possible Link Found Between Adult-Onset Heart Failure, Preterm Birth

The study, based upon findings from a National Registry, appeared in 

, the journal of the American College of Obstetricians and Gynecologists (ACOG). The investigators’ goal was to estimate receipt of recommended gynecologic care, including cancer screening and menstrual care, among women with Down syndrome in the US. For the research, investigators used patient-reported data from DS-Connect, which is a national registry of individuals with Down syndrome. It is a centralized national registry funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the investigators said.

Down syndrome is one of the most common identified causes of intellectual disability in the U.S., the investigators reported. Women make up 40% of the population of those with the syndrome, also known as trisomy-21. The investigators noted that over the past two decades, the lifespan nearly has doubled for those with Down syndrome. This further underscores the need for patient-centered gynecologic care that takes into consideration the full lifetime needs of an individual.

“Our first outcome was receipt of all gynecologic components of ACOG-recommended, age-appropriate well-woman care among women with Down syndrome at least once during their lifetimes,” the investigators wrote. 

“We then measured lifetime receipt of specific components of recommended well-woman care: any gynecologic examination (for women age 18 years and older), Pap test (age 21 years or older), or mammography (age 40 years or older).We also measured breast examination by self or family member (age 18 years or older), although we did not include it in our estimate of guideline-adherent well-woman care because the breast self-examination was removed from ACOG guidelines during the study period. 

We compared receipt of recommended well-woman care to receipt of non-gynecologic care recommended for individuals with Down Syndrome, including physical examinations, vision, hearing, and dental care.”

Their second outcome was the receipt of menstrual regulation treatments, such as oral contraceptive pills, Depo-Provera injections, and intrauterine devices, they said. “The questionnaire distinguishes between use of contraceptives for intended menstrual regulation compared with pregnancy prevention,” they wrote. “We do not report use of contraceptives for pregnancy prevention, given the small number of respondents to this component of the questionnaire. We also characterized the age at menarche, regularity, and length of menstrual cycle.”

The results included the following: Of the 3,441 U.S. individuals enrolled in DS-Connect from 2013 to 2019, 1,625 were women, and 70 women (4% of female enrollees) had complete responses to the questionnaire on women’s health outcomes. The mean age of study participants was 33 years (95% CI, 30-36; range 19-74). The majority were White (94%; 95% CI, 89-100). 

Twenty-one percent had a history of physical abuse (95% CI, 12-31), and 24% (95% CI, 14-35) had experienced unwanted sexual advances. Six percent had potential or confirmed sexually activity (95% CI, 0-12) with no reported history of sexually transmitted infections. Fourteen percent of participants were postmenopausal (95% CI, 6-23) with a mean age of menopause of 40 (95% CI, 34-46).

Only 26% of age-appropriate women with Down syndrome reported ever having a Pap test, and 50% reported ever receiving a mammogram, the investigators wrote. By contrast, 89% of women with Down syndrome had received recommended non-gynecologic preventive care. Comparatively, according to the National Health Interview Survey, 93% of US women aged 21-65 years have ever received a Pap test, and 95% of US women aged 50-74 years have ever received a mammogram.

“Our research demonstrates considerable disparity in women with Down syndrome receiving the recommended preventative cancer screenings, on par with findings in women with other intellectual disabilities,” the investigators wrote. 

1. Smith AJB, Applebaum J, Tanner EJ, Capone GT. Gynecologic Care in Women With Down Syndrome: Findings From a National Registry. 

. 2020 Sep;136(3):518-523. doi: 10.1097/AOG.0000000000003997. PMID: 32769650.

A team of investigators has found that women with Down Syndrome received gynecologic care at lower-than-recommended rates and at substantially lower rates than other forms of health care. The investigators have called for efforts to improve gynecologic care for this vulnerable population.

Gynecologic Care Needs to Improve in Women With Down Syndrome

You can expect a variety of topics to be covered this week on 

Was a laparoscopic approach to this salpingectomy proper?

Association of Anticholinergic Medication Use and Cognition in Women with Overactive Bladders

In case you missed it: April 5 to April 9

What to look for this week on Contemporary OB/GYN® 

This week on Contemporary OB/GYN®: April 12 to April 16

Glick is a board-certified dermatologist and dermatologic surgeon with clinical and academic practices in South Florida. He also is the director of the dermatology residency at the Larkin Hospital, Palm Springs, and clinical assistant professor of dermatology at the Herbert Wertheim College of Medicine at Florida International University. He serves as president of the Florida Society of Dermatology and Dermatologic Surgery as well as principal investigator for GSI Clinical Research in Margate, Florida.

Zaiac is a board-certified dermatologist with the Greater Miami Skin & Laser Center and is also professor and chair of dermatology at the Herbert Wertheim College of Medicine at Florida International University.

Ojong is a chief resident at Larkin Community Hospital Palm Springs Campus’ Dermatology Residency, in Hialeah, Florida.

For an easy-to-use reference, print out this 

Dermatoses of Pregnancy Physician Flow Chart

A 28-year-old primigravid patient presents for her routine prenatal visit. She is 36 weeks pregnant and complains that the stretch marks on her abdomen have become extremely itchy, red, and bumpy. She has no other obstetric complaints. Vital signs and fetal monitoring are within normal limits. 

On physical exam you see this (Figure 1):

 Multiple pink to red papules coalescing into plaques within striae on abdomen, consistent with polymorphic eruption of pregnancy.

This scenario describes polymorphic eruption of pregnancy (PEP), also known as pruritic urticarial papules and plaques of pregnancy (PUPPP). Clinically, this presents as an abrupt onset of pruritic urticarial papules and plaques, targets, and vesicles within and around abdominal striae distensae, trunk, buttocks, and thighs. It typically spares the umbilicus, palms, and soles. There are no associated maternal or fetal morbidities. 

Risk factors for development of PEP include rapid weight gain, multiple gestation pregnancy, nulliparous, and primigravid.

 It usually self-resolves in the postpartum period and does not recur with subsequent pregnancies.

Recommended initial management by obstetrician:

Order complete blood count (CBC), liver function tests (LFTs), thyroid function tests (TFTs), and bile acids to rule out other dermatoses of pregnancy.

If necessary, perform two 3-0 punch biopsies, one from a papule or plaque for hematoxylin and eosin (H&E) staining and the other on perilesional uninvolved skin for direct immunofluorescence (DIF) studies. DIF will show nonspecific C3 staining of basement membrane and scant immunoglobulin (Ig) G staining in the epidermis, whereas H&E will show nonspecific lymphohistiocytic infiltrate in dermis, edema, and eosinophils.

Start mild to moderate topical corticosteroid and pregnancy-safe sedating or nonsedating oral antihistamines (diphenhydramine, chlorpheniramine, loratadine, cetirizine) to manage rash and pruritus.

Refer to dermatologist if rash becomes intractable.

A 30-year-old primigravid patient at 37 weeks of pregnancy comes in complaining of itchy hives and blisters that suddenly developed on her abdomen and thighs. She denies fever, malaise, or any other systemic symptoms. 

On physical exam you see this (Figure 2):

 Multiple tense bullae on an erythematous urticarial base on the abdomen and thighs, consistent with pemphigus gestationis.

This scenario describes pemphigoid gestationis, also known as herpes gestationis, which typically presents in late pregnancy or the postpartum period as an abrupt onset of PUPP that progress to tense vesicles and bullae on an erythematous base. Of note, these lesions involve the umbilicus or are immediately adjacent to it and spread to extremities, including palms and soles. Fetal risks include prematurity and small for gestational age.

 Early-onset disease correlates with disease severity. This usually self-resolves during the postpartum period but can recur in subsequent pregnancies.

Herpes gestationis typically presents in late pregnancy or the postpartum period.

Take two 4-0 punch biopsies, one from a vesicle for H&E staining and the other from perilesional uninvolved skin for DIF. H&E will show a subepidermal blister and eosinophilic spongiosis, whereas DIF will show linear C3/IgG staining along the basement membrane.

Check TFTs to monitor for maternal risk of Graves disease, and perform a fetal non-stress test ultrasound for fetal monitoring.

Treat with moderate- to high-potency topical corticosteroids and oral antihistamines. The mainstay of treatment is 20 to 60 mg oral prednisone equivalent daily, with taper after blisters disappear.

Refer to dermatology and endocrinology departments for further management.

A 21-year-old woman at 12 weeks of pregnancy presents with a complaint of new itchy bumps that started a week ago on her face and neck, under her arms, under her breasts, and on her arms and legs. She reveals she has never had a rash like this but did have eczema as a child. She does not complain about any other symptoms. Vital signs and fetal monitoring are within normal limits. 

On physical exam you see the following (Figure 3):

 Multiple excoriated papules on bilateral thighs, consistent with atopic eruption of pregnancy.

This scenario describes atopic eruption of pregnancy, which is the most common rash seen in pregnancy. Onset is typically before the second or third trimester. It is a spectrum of conditions that includes prurigo of pregnancy, eczema of pregnancy, and pruritic folliculitis of pregnancy. 

Clinically, it presents as excoriated papules or nodules, eczematous papules and plaques, or monomorphic follicular-based papules on the abdomen, flexural areas, and extremities. It typically occurs in patients with a history of atopic dermatitis but could be of new onset. It is due to an immune system shift from a T-helper (Th)1-predominant to a Th2-predominant system during pregnancy. 

Patients who already have this imbalance due to atopic dermatitis experience flares. It is self-limited and there are no maternal or fetal risks.

Rule out other potentially severe conditions such as intrahepatic cholestasis of pregnancy and pemphigoid gestationis, scabies, pityriasis rosea, drug eruptions, and viral exanthems, which can present similarly.

Perform punch biopsies for H&E staining and DIF. Order CBC, comprehensive metabolic panel (CMP), and TFTs. CBC will show elevated IgE.

Treat rash with moisturizers and emollients rich in ceramides, mild to moderate topical corticosteroids, oral antihistamines, and narrow band UV-B.

Culture lesions if any sign of infection is present and prescribe daily topical mupirocin once infection is confirmed.

A 22-year-old gravida 2 para 1 woman at 33 weeks of pregnancy presents with the complaint that she has been itchy all over her body for the past 3 days. She states that itching prevents her from sleeping at night and she experienced something similar during her first pregnancy but not as intensely. She reports that her first child was born at 35 weeks. Physical exam shows normal-appearing skin without any rash or secondary lesions

This scenario describes intrahepatic cholestasis of pregnancy, which is characterized by extreme pruritus in absence of rash, followed by secondary excoriation and prurigo papules and nodules. There is no long-term morbidity to the mother, but fetal risks include premature birth, meconium staining of amniotic fluid, abnormal fetal heart rate, and stillbirth.

 This condition is self-limited, with itching resolving days after delivery. It recurs with subsequent pregnancies.

Check CBC; CMP, with a focus on aspartate aminotransferase, alanine aminotransferase, and bilirubin; prothrombin time; activated partial thromboplastin time; international normalized ratio; hepatitis C; and genetic testing for genetic mutations in various hepatobiliary bile transporters.

Monitor fetus for fetal anoxia caused by toxic bile crossing the placenta.

Prescribe ursodeoxycholic acid 10 to 20 mg/kg/d and increase to maximum dose of 2 g/d.

Prescribe anti-itch over-the-counter emollients and moisturizers and topical corticosteroids.

Culture erosions if infection is suspected and prescribe topical mupirocin ointment once infection is confirmed.

A 25-year-old woman at 30 weeks of pregnancy presents with complaint of new-onset rash located in her axilla and groin, as well as malaise and fever. She states that she has never had a rash like this. 

On physical exam you note the following (Figure 4):

Multiple pink, annular, scaly plaques with surrounding sterile pustules on arms, chest, and abdomen, consistent with impetigo herpetiformis.

This scenario presents a case of impetigo herpetiformis, also known as generalized pustular psoriasis of pregnancy. This presents in the third trimester of pregnancy as eczematous scaly plaques surrounded by 1- to 3-mm pustules in flexural areas, which then extend to the trunk and extremities. 

Patients usually have no prior history of psoriasis. Maternal risk includes seizures, tetany, delirium, and cardiac arrhythmias secondary to hypocalcemia.

 Fetal risk includes placental insufficiency.

 The condition typically self-resolves in the postpartum period, and it recurs with earlier onset and a more severe course in subsequent pregnancies.

Check CBC for elevated white blood cell count; check CMP for hypocalcemia and hypoalbuminemia.

Perform 2 punch biopsies for DIF and H&E. DIF will be negative for any immunoglobulins.

Counsel patient on natural progression of disease, with potential for early delivery if condition becomes life-threatening.

Curbside Consults delivers expert perspectives from physicians outside of the OB/GYN specialty to provide insight into various health issues affecting pregnant women. This new section is the brainchild of Editorial Advisory Board member Christine Isaacs, MD.