This month's cover story examines iron-deficiency anemia in pregnancy and the role of intravenous iron.

Vol 66 No 07: July 2021

Chief of the Division of Academic Specialists in 

The new ASCCP guidelines expand recommendations for cervical cancer screening to include screening every 5 years with primary high-risk human papillomavirus (hrHPV) testing. If you missed Isaacs' presentation at the 2021 ACOG ACSM, “While You Were Slee(PPE)ing: Women’s Health Updates Beyond the Pandemic’s Priorities,” 

The guidelines were released in 2020 and, in 2021, were endorsed by the 

American College of Obstetricians and Gynecologists

 (ACOG) and the Society of Gynecologic Oncology (SGO).

 at ACOG’s Annual Clinical and Scientific Meeting earlier this year.

Videos

We hear from Christine Isaacs, MD about the new ASCCP guidelines and what they mean for ob/gyns. 

ASCCP guidelines and breast imaging on the heels of COVID-19

Ms. Hester is Content Specialist with Contemporary OB/GYN and Contemporary Pediatrics.

Although mastitis is more often connected to new mothers who are breastfeeding, the condition can occur in infants. A 

 offered information on the clinical presentation, prevalence, and outcomes of a simultaneous serious bacterial infection with mastitis.1

The investigators reviewed the records of infants aged ≤90 days who were treated for mastitis at 28 sites in the United States, Canada, and Spain that were part of the Pediatric Emergency Medicine Collaborative Research Committee. The infants had been seen in the emergency department.

There were 657 infants included in the study and nearly all of them were well-appearing at the time of presentation. There was a history of fever either at home or the emergency department for 138 of the infants and 63 of them had reported poor feeding or fussiness. Blood was collected in 581 infants; Urine was collected in 274 infants; and cerebrospinal fluid cultures were taken for 216 infants. There were pathogens in 0.3%of (95% [CI] 0.04–1.2) of blood, 1.1% (95% CI 0.2–3.2) of urine, and 0.4% (95% CI 0.01–2.5) of cerebrospinal fluid cultures. Site of infection cultures were collected for 335 infants and 77% of those cultures grew a pathogen. The most commonly grown pathogen was methicillin-resistant 

 were the other commonly grown pathogens. Ninety percent of the infants were admitted to inpatient care at the hospital and 22 had to be admitted to the intensive care unit. There were 10 (1.5% [95% CI 0.7–2.8]) cases that had either sepsis or shock and 2 (0.3% [95% CI 0.04–1.1]) had severe cellulitis or necrotizing soft tissue infection. No cases required the use of vasopressors or endotracheal intubation and no infant died.

The investigators concluded that in most cases of neonatal the condition was mild and localized. A serious bacterial infection and adverse outcomes were highly uncommon. When presented with an afebrile, well-appearing infant with mastitis, evaluating for serious bacterial infection is likely not necessary.

This article was originally published on Contemporary Pediatrics®. 

1. Kaplan R, Cruz A, Michelson K. Neonatal mastitis and concurrent serious bacterial infection. 

. July 1, 2021. Epub ahead of print. doi:10.1542/peds.2021-051322

Articles

A report in Pediatrics offered information on the clinical presentation, prevalence, and outcomes of a simultaneous serious bacterial infection with mastitis.

Neonatal mastitis prevalence and treatment outcomes

Breast cancer patients need personalized follow up care after breast cancer treatment due to a wide spectrum of varying health burdens, according to a study presented at the European Society for Medical Oncology’s ESMO Breast Cancer Virtual Congress 2021.

The study was conducted by Kelly de Ligt, PhD, of the division of psychosocial oncology and epidemiology at the Netherlands Cancer Institute at the Antoni van Leeuwenhoek Hospital in Amsterdam, Netherlands, and colleagues.

“We wanted to measure the overall burden on their health-related quality of life and see if any patterns emerged that would better inform us on which individuals require active symptom management,” de Ligt 

Women were selected from the Netherlands Cancer Registry and were 1 to 5 years out from a stage I to stage III breast cancer diagnosis that was surgically treated with or without adjuvant treatment. Researchers asked 404 breast cancer survivors about their post-treatment experience with pain, nausea, fatigue, shortness of breath, appetite, constipation, diarrhea, insomnia, and cognitive and emotional symptoms.

Researchers analyzed women’s answers, and reported 3 subgroups based on women's responses, classifying them as having low, intermediate, or high symptom burdens. Nearly 1/3 of women belonged to the low burden group and were less affected than the representative sample of 1,300 Dutch women who had filled out the researcher’s questionnaire.1 In the ESMO press release, de Ligt said she was pleasantly surprised that this group of women was doing better than that representative sample.

Fifty-five percent of women fell into the intermediate burden category, researchers said, adding that their results were similar to the representative sample. However, the intermediate group reported slightly worse insomnia, fatigue, and cognitive symptoms.

Fifteen percent of the women were in the high burden group, with 1 in 6 reporting worse symptoms than the representative sample.1 “The differences, ranging between 15 and 20 percentage points, were large enough to be considered not just statistically significant, but clinically relevant as well,” de Ligt said in the release. Patients with heart disease, diabetes, and other comorbidities were more likely to be in the high burden group, researchers said.

 de Ligt said the association was so strong that researchers were unable to connect the level of symptom burden with the type of treatment patients had received. 

“However, because we measured symptom burden and comorbidities at the same time in the study, we cannot draw conclusions from these findings alone. Future research should attempt to measure patients’ health-related quality of life through Patient Reported Outcome Measures (PROMs) before the start of treatment for breast cancer and afterward to allow us to measure the effect of the therapy,” de Ligt commented.

Another study that looked at 621 breast cancer survivors treated between 2003- 2013 at Oulu University Hospital in Finland showed the need for personalized care.

 That study found only 25% of cancer recurrences were detected during pre-planned control visits, according to the ESMO release. In addition, more than half of recurrences in 95 cases were found when the patient contacted their physician with new symptoms, most often pain.

Breast cancer expert Nadia Harbeck, MD, PhD, head of the Breast Center at LMU University Hospital of Munich, Germany, and who is unaffiliated with either study, commented in the ESMO press release on the findings. She said, “Gathering data from a larger group of women could help us to gain more insight, and it would be interesting to see this study reproduced in other countries to ascertain whether there are also cultural and social factors impacting patients’ answers.”

, de Ligt said that while previous studies have examined these symptoms as separate, independent items, survivors usually experience multiple symptoms that can add up. “We therefore studied the overall symptom burden in breast cancer survivors and tried to identify patterns in this. We believe this may be more relevant, as currently the needs of breast cancer survivors are not fully met and there is a growing demand for personalized follow-up care,” de Ligt said.

De Ligt noted that the first practical step towards care personalization is that providers need to be able to detect these needs. “Regular assessment with Patient Reported Outcome Measures (PROMs) before the start of treatment for breast cancer and afterwards up can play an important part of regular clinical care in detecting bothersome symptoms in patients. We are currently implementing regular PROM assessment in our daily clinical practice at the Netherlands Cancer Institute in Amsterdam,” she said.

For next steps in research towards personalized care, de Ligt said that finding out which patient and treatment characteristics are associated with symptom burden would be helpful. “Ideally, health care providers would want to know early in the care process which follow-up arrangements would probably serve their patients. Patients with comorbidities may be served better by follow-up arrangements that are sensitive to their more complex, comorbid health status. However, because we measured symptom burden and comorbidities at the same time in the study, we cannot draw conclusions from these findings alone. Regular assessment with PROMs before the start of treatment for breast cancer and afterwards up to several years will also allow us to better measure the effect of treatment,” de Ligt said.

de Ligt KM, de Rooij BH, Walraven I, et al. Towards tailored follow-up care for breast cancer survivors: cluster analyses based on symptom burden. Presented at: ESMO Breast Cancer Virtual Congress 2021. Abst # 134P_PR. 

Myller S, Jukkola A, Jääskeläinen A, Roininen N, Karihtala P. How breast cancer recurrences are found? - a real-world, prospective cohort study. ePoster: ESMO Breast Cancer Virtual Congress 2021. Abst #140P 

, Volume 32, Supplement 2, May 2021.https://doi.org/10.1016/j.annonc.2021.03.154

The unmet need for personalized follow-up care due to a wide variety of health burdens after treatment needs to be addressed.

Breast cancer patients need personalized follow-up care

; Professor and Vice-Chair of Obstetrics and Gynecology; Gillette Professorship of Obstetrics and Gynecology; and Chief of Maternal-Fetal Medicine at 

I applaud providers for encouraging COVID-19 vaccination for pregnant and lactating women. Recent data published from the V-safe pregnancy registry, v-safe after vaccination health checker surveillance system, and the vaccine Adverse Event Reporting System provides reassurance of the use of the mRNA vaccine in pregnancy.

This report of 35,691 pregnant women who received the COVID vaccine did not identify safety signals. Given that neither pregnant nor lactating women were included in the preauthorization clinical trials, post-authorization monitoring was performed to evaluate the safety of the vaccine. As we have previously highlighted, pregnant and lactating women need to be included in the evaluation of new therapeutic products.

 Importantly, given the risks of COVID, professional societies and organizations encouraged vaccination for these women even without such data. 

Moving forward it is essential for us, as practitioners, to advocate for our patients and continue to push for their inclusion in the development and evaluation of products important for their care.

® highlights another area of vital importance for our patients. With the emphasis on severe maternal morbidity and public reporting of adverse maternal outcomes, attention is driven to optimize maternal health. By optimizing health prior to and in pregnancy, both maternal and fetal outcomes may be improved. One example is maternal anemia, which is estimated to affect 42% of pregnant women globally.

 Maternal anemia is associated with a number of adverse maternal outcomes including preterm birth, fetal growth restriction, and transfusion. Transfusion is a leading cause of severe maternal morbidity. Therefore, prevention of anemia is an important goal both for the practitioner and the pregnant woman.

Maternal anemia is in part a physiologic response to the doubling of blood volume and increased requirements of the development of the fetus and placenta. It is usually due iron deficiency. Iron demands increase substantially in pregnancy, when there is an estimated total iron requirement of 1040 mg, with the greatest need in the third trimester. These needs are met through both dietary iron intake and mobilization of maternal iron stores (which often are insufficient).

Although oral iron supplementation is routinely recommended in pregnancy, it is often poorly tolerated. Furthermore, iron absorption is poor, thus increasing intake does not necessarily parallel iron uptake. Intravenous iron supplementation is increasingly available, and formulations have mitigated adverse outcomes and complications. Shrayva Govindappagari, MD, and colleagues provide insight on the role of IV iron in the setting of iron deficiency anemia in pregnancy in this issue. As they describe, the evidence base is growing and now include clinical trials, systematic reviews, and meta-analyses. In the first and second trimesters, reliance on oral supplementation and dietary counseling is best, with progression to IV iron if these fail, given the importance of adjudication of anemia prior to delivery.

As practitioners, advocating for our patients and managing common conditions to facilitate optimal pregnancy outcomes through preventative measures such as vaccination and addressing anemia have the potential for major impact. 

Shimabukuro TT, Kim SY, Myers TR, et al. Preliminary findings of mRNA Covid-19 vaccine safety in pregnant persons. 

 2021; 384 (24):2273-2282.doi: 10.1056/NEJMoa2104983. Epub 2021 Apr 21.

Spong CY. Addressing inequities in women's health research. 

Adhikari EH, Spong CY. COVID-19 vaccination in pregnant and lactating women. 

. 2021;325(11):1039–1040. doi:10.1001/jama.2021.1658

Goonewardene M, Shehata M, Hamad A. Anaemia in pregnancy. 

2012; 26(1):3-24. doi: 10.1016/j.bpobgyn.2011.10.010

As practitioners, advocating for our patients and managing common conditions to facilitate optimal pregnancy outcomes through preventative measures such as vaccination and addressing anemia have the potential for major impact.

Steps to optimize maternal health

A 40-and-2/7 week gestational age boy was born to a 30-year-old G4P0121 mother via vaginal delivery. The mother’s past medical history is significant for preeclampsia, previous opiate and cocaine abuse, and current tobacco use. Social history is significant as mother was incarcerated during this pregnancy. The mother reports being drug-free throughout this pregnancy despite prior opiate and cocaine use, and her urine drug screen on admission was negative. She received morphine on the maternity ward for pain. In the newborn nursery, the infant showed signs of irritability, high tone, and tremors on day of life 1, at which point he became febrile to 100.4 °F. Upon further inquiry, the mother admitted to cigarette smoking daily in pregnancy, and now admits to daily vaping, as much as 2 vaporized pods daily. The patient was transferred to the neonatal intensive care unit (NICU) for further evaluation.

The physical examination revealed a newborn who was alert, irritable, and difficult to console. He was tachycardic and tachypneic with lungs clear to auscultation bilaterally. His abdomen was soft with active bowel sounds. On neurologic exam, he had increased tone with tremors.

Given the patient’s age, physical exam, and maternal history, a drug withdrawal syndrome was the leading diagnosis. Table 1 shows the differential diagnosis for a newborn with fever and tremors which includes infectious, metabolic, and neurovascular etiologies.

A metabolic panel revealed sodium 143 mmol/L, potassium 4.4 mmol/L, chloride 110 mmol/L, CO2 18 mmol/L, BUN 14 mg/dL, creatinine 1.42 mg/ dL, and glucose 75 mg/dL. Urine drug screen was positive for opiates (after maternal morphine was given). Meconium drug screen was negative. C- reactive protein 0.02 mg/dL and blood culture showed no growth for 5 days. Urine nicotine level was less than 2 ng/mL (ref: 2 ng/mL) and urine 3-OH cotinine level was 1399 ng/dL (ref: < 50 ng/dL).

In the NICU, the patient underwent a septic work-up and evaluation for drug exposure. He was started on ampicillin and gentamicin for a 48-hour sepsis rule-out. Because maternal cocaine use is associated with neonatal cerebral infarction, a CT of the head was performed and was unremarkable. A lumbar puncture was attempt- ed but was unsuccessful. The patient was treated with supportive care, including ad lib breast and bottle feedings, swaddling, and a low stimulation environment and improved. Anticonvulsant medications (phenobarbital) were considered, but not needed.

Nicotine can cross the placenta and cause a significant withdrawal syndrome in newborns. Nicotine metabolite levels, particularly 3-OH cotinine, can be measured in the urine and may be the only positive lab result in a withdrawing infant. In our patient, the urine 3-OH cotinine level of 1399 ng/ dL (ref: < 50 ng/dL) is 28 times the upper limit of normal. All other lab work/ imaging were within normal limits.

Vaping, or electronic cigarette use, is a popular mode of nicotine consumption among young adults. Many vaping-related illnesses have been described in the medical literature.1-3 Vaping can affect more than just the individuals who participate. In this case report, we describe the clinical course of a newborn exposed to a significant amount of nicotine in utero secondary to maternal vaping. Because of the popularity of vaping among young adults, it is likely that clinicians will see an emergence of vaping-related complications in both the young adults who vape, and their children.

Differential diagnoses were considered and systemically ruled out. Neonatal abstinence syndrome from opiates is a common etiology for neonatal drug withdrawal symptoms; this was ruled out with the negative maternal urine drug screen and negative newborn meconium drug screen. Neonatal sepsis remains high on the index of suspicion for all newborns with fever. For this reason, the patient was started on empiric antibiotic therapy for 48 hours; however sepsis secondary to bacteremia was ruled out when blood cultures were no growth for 5 days. Hypoglycemia is a common cause of tremors in a newborn; this was ruled out with normal glucose levels. Those who consume nicotine may abuse other drugs simultaneously. The use of maternal cocaine during pregnancy is associated with neonatal cerebral infarction.

 This was on the differential diagnosis for our patient and was ruled out with a normal head CT. In the presence of an elevated urine 3-OH cotinine level and negative work-up for other causes, our patient was given a diagnosis of neonatal nicotine withdrawal.

Nicotine is an addictive substance that is small enough to cross the placenta.

 In the brain, nicotine binds to nicotinic acetylcholine receptors (nAChRs), which are highly expressed in dopaminergic and GABAergic neurons in the ventral tegmental area and the nucleus accumbens.

 Mouse models of nicotine withdrawal have demonstrated that the nAChRs in the medial habenula of the diencephalon and its projection to the interpeduncular nucleus are particularly important mediators of nicotine withdrawal symptoms.

 Multiple organs in the fetus are adversely affected by nicotine exposure. This may manifest as orofacial defects, growth restriction, preterm birth, stillbirth, sudden infant death syndrome, or neonatal withdrawal symptoms.

 In the newborn, withdrawal from nicotine can present in a similar way to opiate withdrawal including irritability, high tone and tremors. Both opiate and nicotine withdrawal will result in high Neonatal Abstinence Scoring System/Finnegan Scores, making the 2 difficult to distinguish. The mother in our study consumed 2 vaporized pods per day, roughly equivalent to 2 packs of tobacco cigarettes per day. The patient’s urine metabolite result of 1399 mg/dL represents a value 28 times the upper limit of normal. This value correlated with the severity of our patient’s withdrawal syndrome.

Among teenagers, e-cigarette use has more than doubled between 2017 and 2019.

 showed 3.6 million middle and high school students had used an e-cigarette in the past 30 days. Nicotine is the most commonly abused substance during pregnancy. Given the popularity of vaping, physicians will encounter more cases of nicotine-related complications than in recent decades. In the newborn nursery or NICU, this may manifest as neonatal nicotine withdrawal.

Providers must maintain a high index of suspicion when evaluating newborns with signs of withdrawal, especially when initial testing for opiates is negative. Meconium drug screening identifies substances that can elicit newborn withdrawal symptoms. Including nicotine and/or its metabolites in the meconium drug screen helps discern the level of exposure and assists in the management of withdrawal symptoms. Here, a urine level of 3-OH cotinine was measured. Although not a routine newborn screen for drug withdrawal, measuring urine 3-OH cotinine was invaluable in confirming the diagnosis of nicotine withdrawal. With this lab result, we were steered away from opioid-related interventions such as methadone and morphine. Measurement of nicotine and/or its metabolites (either in the urine or meconium) should be considered in routine screening tests for newborns with withdrawal symptoms.

Nicotine withdrawal in newborns should be managed with supportive care and will self-resolve in days. Phenobarbital may be considered for seizures related to severe withdrawal. IV fluids may be administered if symptoms interfere with feeding and result in dehydration. Our patient’s symptoms resolved over 4 to 5 days. He was followed by a pediatrician for outpatient evaluation and management. Understanding the prevalence of nicotine abuse via e-cigarettes and the severity of the neonatal withdrawal syndrome are essential components of care for exposed newborns.

 pulmonary illness related to e-cigarette use in Illinois and Wisconsin- final report. 

.2020;382(10):903-916. doi: 10.1056/NEJMoa1911614.

Christiani DC. Vaping-induced acute lung injury. 

2020;382(10):960-962. doi:10.1056/NEJMe1912032.

Maddock SD, Cirulis MM, Callahan SJ, et al. Pulmonary lipid-laden macrophages and vaping. 

2019;381(15):1488-1489. doi:10.1056/NEJMc1912038.

Chasnoff IJ, Bussey ME, Savich R, Stack CM. Perinatal cerebral infarction and maternal cocaine use. 

 1986;108(3):456-459. doi:10.1016/s0022-3476(86)80896-4.

Bailey NA, Diaz-Barbosa N. Effect of maternal substance abuse on the fetus, neonate and child. 

 2018;39(11):550-558. doi:10.1542/pir.2017-0201.

Picciotto MR, Kenny PJ. Mechanisms of nicotine addiction. 

2021:11:a039610. doi:10.1101/cshperspect.a039610.

Salas R, Sturm R, Boulter J, De Biasi M. Nicotinic receptors in the habenulo-interpeduncular system are necessary for nicotine withdrawal in mice. 

2009; 29:3014-3018. doi:10.1523/JNEUROSCI.4934-08.2009.

Mc-Grath-Morrow SA, Gorzkowski J, Groner JA, et al. The effects of nicotine on development. 

2020;145(3): e20191346. doi:10.1542/peds.2019-1346.

Miech R, Johnston L, O’Malley PM, Bachman JG, Patrick ME. Trends in adolescent vaping, 2017-2019. 

 2019;381(15):1490‐1491. doi:10.1056/NEJMc1910739.

Glasser AM, Johnson AL, Niaura RS, Abrams DB, Pearson JL. youth vaping and tobacco use in context in the United States: results from the 2018 National Youth Tobacco Survey. 

. 2021;23(3):447-453. doi:10.1093/ntr/ntaa010

This article was originally published in Contemporary Pediatrics®. 

His mother’s past medical history is significant for preeclampsia, previous opiate, and cocaine abuse, and current tobacco use, and she was incarcerated during the pregnancy. What's the diagnosis?

Newborn with fevers and tremors: What's the diagnosis? 

Iron-deficiency anemia in pregnancy and the role of intravenous iron

Anemia in pregnancy should be treated due to its connection to adverse maternal and neonatal outcomes.

Breast cancer patients need personalized follow-up care after breast cancer treatment due to a wide spectrum of varying health burdens, according to a study presented at the European Society for Medical Oncology’s ESMO Breast Cancer Virtual Congress 2021.

In 2018, the FBI investigated a solo ob/gyn for submitting tens of thousands of fraudulent claims to various health care benefit programs. He was ultimately charged with 26 counts of health care fraud. 

We hear from Christine Isaacs, MD about the new ASCCP guidelines and what they mean for ob/gyns.

It's been a busy week for the Contemporary OB/GYN® team.

In case you missed it: July 12 to July 16

The Society for Maternal-Fetal Medicine supports the clinical practice of maternal-fetal medicine by providing education, promoting research, and engaging in advocacy to optimize the health of high-risk pregnant women and their babies.

Attendance is limited to the first 100 registrants to ensure engaging interaction among presenters and attendees.

: Royal Sonesta Chicago Downtown, Chicago, IL

: Luis D. Pacheco, MD and George Saade, MD 

: Uri Elkayam, MD; Brenna Hughes, MD; Torri Metz, MD, MSCR; Emily Miller, MD, MPH; Nancy Reau, MD; Baha Sibai, MD; Bob Silver, MD

Registration fees include meals during the meeting, access to course materials online, and CME. Pre-registration will close one week prior to the event. An administration fee of $100 will be applied to those who register onsite.

For registration details and a full course brochure, visit 

The course will cover a range of high-risk OB topics with an emphasis on clinical management, in the form of lectures, case presentations, panel discussions and audience participation.

SMFM’s 5th Annual 2021 Maternal Medicine Course

“The true number is likely even larger because our study only measured diagnosed type 2 diabetes,” said principal investigator Teresa Janevic, PhD, MPH, associate director of the Blavatnik Family Women’s Health Research Institute, which is sponsored by the Ichan School of Medicine at Mount Sinai in New York City. 

 “Women who are never tested for diabetes would not show up in our study as a case.”

Janevic noted that women with GDM are at increased risk of developing type 2 diabetes, a leading cause of premature mortality. “While data suggest racial/ethnic minority women bear the disproportionate burden of GDM, current postpartum GDM cohorts lack adequate diversity to examine whether racial/ethnic disparities persist in the transition to type 2 diabetes,” Janevic said.

To address this gap, the investigators culled 2 New York City public health surveillance databases to construct a novel population-based cohort of women with gestational diabetes who gave birth between 2009 and 2011. The women were then followed for up to 8 years using linked New York City vital statistics and HbA1c diabetes registry data.

Of 16,231 women with gestational diabetes, the cumulative incidence of type 2 diabetes in 8 years of follow-up was 14.4% (n = 2,333 cases).

Among GDM cases, 18.2% of type 2 diabetes cases occurred in non-Hispanic Black women, 14.0% in Hispanic women, 11.3% in Asian women, and 5.5% in non-Hispanic White women.

“One preliminary finding that surprised me is that the risk of type 2 diabetes was higher among immigrant women,” Janevic told 

. “We have previously seen this in studies of gestational diabetes; however, no one has detected this disparity in postpartum diabetes. If the finding holds with more detailed analyses, it suggests that immigrant women are an important patient population to target in postpartum interventions to prevent type 2 diabetes.”

The study indicates that more attention should be focused on the long-term postpartum follow-up of women with gestational diabetes, particularly women of color, according to Janevic. “Although awareness has recently been raised about the importance of follow-up of gestational diabetes in the immediate postpartum period of 4 to 12 weeks, clinicians may be less aware that the ADA recommends that women with a history of GDM should have lifelong screening for the development of type 2 diabetes or prediabetes at least once every 3 years,” she said. “Because ob-gyns often serve as a primary point of care for women, they have the potential to play an active role in this lifelong follow-up.”

Future analysis of the diverse cohort will further examine racial/ethnic disparities in disease progression among women with gestational diabetes, such as from diabetes to glycemic control, “which has not been well studied in prior cohorts,” said Janevic, who also is an associate professor of ob-gyn and reproductive science at the Ichan School of Medicine at Mount Sinai. “By identifying what is fueling these disparities, not only among patients but also in neighborhoods, health systems and health policies, we can better target interventions to reduce disparities.”

Janevic reports no relevant financial disclosures.

Janevic T. Racial/Ethnic Differences in Type 2 Diabetes Diagnosis among Women with Gestational Diabetes: Creation of a Diverse Population-Based Eight-Year Postpartum Diabetes Cohort. American Diabetes Association Scientific Sessions 2021; virtual. Accessed June 28, 2021.

Nearly 1 in 5 Black women and 1 in 6 Latina women who experience gestational diabetes mellitus (GDM) during pregnancy are diagnosed with type 2 diabetes within only 8 years postpartum, according to a study poster at the American Diabetes Association (ADA) virtual conference.

Racial and ethnic differences among women with gestational diabetes

Kathryn Wheeler, PharmD, BCPS, is an associate dean for academic affairs and clinical associate professor at the University of Connecticut School of Pharmacy.

Ibrexafungerp is a triterpenoid antifungal that works by inhibiting the formation of the fungal cell wall. Ibrexafungerp (pronounced eye-BREX-ah-FUN- jerp) is the first approved drug of a novel class of antifungals.

Two randomized placebo-controlled positive for 

. Participants clinical trials evaluated the safety and received two 150-mg tablets (300-mg dose) efficacy of ibrexafungerp. Participants were of ibrexafungerp or placebo 12 hours apart postmenarche, nonpregnant females with VVC. In trials, a diagnosis of VVC is defined as a minimum composite vulvovaginal signs and symptoms (VSS) score greater than or equal to 4 and a minimum of 2 moderate signs or symptoms (score of 2 or greater), positive microscopic examination in a sample demonstrating yeast, and a normal vaginal pH. Signs and symptoms were scored along a scale: 0 (absent) to 3 (severe). Median VSS scores at baseline in trials 1 and 2 were 9 and 10, respectively, at baseline; range, 4 to 18. In both trials, the majority of cultures were in a single day, a total daily dose of 600 mg. Participants were reassessed at a test-of-cure (TOC) visit between days 8 to 14 and a follow-up visit between days 21 to 29. Participants with a positive culture for 

 who had at least 1 dose of the study drug were included in a modified intention to treat analysis. Compared with placebo, a greater percentage of participants on ibrexafungerp demonstrated negative cultures at the TOC visit (

 < .001) and VSS scores of 0 (ie, complete clinical response) at the TOC (

In trials, a total of 545 participants were exposed to a dose of ibrexafungerp. The most common adverse effects (AEs) noted in participants administered ibrexafungerp are diarrhea (16.7%), nausea (11.9%), abdominal pain (11.4%), dizziness (3.3%), and vomiting (2.0%). For comparison, the most common AE noted in participants administered placebo in trials is abdominal pain (5.1%). Ibrexafungerp is metabolized by cytochrome P450 (CYP3A). Concomitant administration of strong inhibitors or moderate to strong inducers of CYP3A may alter the patient’s exposure to ibrexafungerp. A reduced dose of ibrexafungerp, 150 mg (1 tablet), should be given when concomitantly administered with strong CYP3A inhibitors. Ibrexafungerp is potentially teratogenic. The use of ibrexafungerp is contraindicated in pregnant women. A patient’s pregnancy status should be confirmed prior to use. The manufacturer recommends the use of contraception for 4 days after the last dose of ibrexafungerp for all women of reproductive potential. If a woman is pregnant or pregnancy is detected within 4 days after the last dose of ibrexafungerp, patients should report the pregnancy to the manufacturer to include in an ongoing safety analysis by calling 1-888- 982-7299.

The recommended dosage of ibrexafungerp for treatment of VVC is 300 mg. This dose is provided as two 150-mg tablets. To complete a full course of therapy, patients should take two 150-mg tablets for the first dose and two 150-mg tablets 12 hours later. This medication may be taken with or without food.

1. Brexafemme. Prescribing Information. Scynexis, Inc; 2021. Accessed June 14, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214900s000lbl.pdf

This article was originally published in Drug Topics®. 

On June 2, 2021, ibrexafungerp (Brexafemme; Scynexis, Inc) was approved by the FDA for vulvovaginal candidiasis (VVC) in adult women and girls of reproductive age.

FDA approves novel antifungal treatment for vaginal candidiasis

Shwayder is an adjunct professor at the University of Florida at the Gainesville Medical Center. He is a graduate of the University of Colorado School of Medicine and the University of Denver College of Law. As a nationally and internationally recognized expert in gynecology ultrasound and minimally invasive surgery, he actively consults on legal matters in medicine, including liability in ultrasound and gynecologic surgery, as well as issues surrounding privileging and insurance fraud.

The Federal Bureau of Investigation (FBI) initiated an investigation of a solo ob-gyn physician in 2018. Ultimately, the United States Department of Justice (DOJ) filed an indictment against the physician for submitting tens of thousands of fraudulent claims to various health care benefit programs, including Medicaid, Medicare, and TRICARE, for unnecessary, uninformed, and/or fraudulent gynecologic procedures. 

Between 2010 and 2019, private and government payors experienced $21 million in losses for unnecessary surgeries and procedures. The FBI concluded that the physician knowingly and willfully executed a scheme to defraud Medicaid and Medicare. 

Further, he made materially false statements in connection with submissions to Medicaid and Medicare. As such, he was charged with 26 counts of health care fraud in violation of title 18 US Code, sections 1347 and 1349 (18 USC §1347 and §1349) and 32 counts of making false statements relating to health care matters in violation of 18 USC §1035. 

He was alleged to have executed a scheme for enrichment through submission of claims for services that were: “(a) not medically necessary and contrary to the medical standard of care; (b) based upon fraudulent and falsified purported patient statements, diagnoses, and diagnostic procedures; (c) not, in fact, performed; and (d) based upon altered and fraudulent sterilization consent forms.”

The investigation found numerous fraudulent claims for ob-gyn care. In obstetrics, he altered due dates to be earlier than they actually were. For example, he would conduct elective induction of labor at “39 weeks of gestation” when he was already in the hospital performing gynecologic surgery. By altering the due date, he would comply with the standard of care and subvert hospital policies against the elective induction of labor in late preterm patients. 

Further, insurers would not reimburse for elective inductions prior to 39 weeks. For example, 1 patient, based on her last menstrual period and ultrasound, had an estimated date of delivery (EDD) of March 12. Without medical indication, he changed her EDD to March 7 and performed an elective induction of labor on March 1. 

Over a 2-year period, the physician billed more than $102,000 to Medicaid and TRICARE for patients who were actually less than 39 weeks of gestation at the time of elective induction of labor. Gynecologic findings were more dramatic. 

He performed as many as 30 surgeries in 1 day. 

From 2014 to 2018, the physician performed surgical procedures on 40% of the practice’s Medicaid beneficiaries—about 510 patients—with 42% having 2 or more surgeries. He often performed bundled procedures, such as dilation and curettage (D&C), laparoscopy, and lysis of adhesions.

Claims of unnecessary surgeries were rampant. Patients were frequently told they had cancer and required a hysterectomy. Such patients would undergo a total vaginal hysterectomy and colporrhaphy, with the diagnosis submitted to insurance stating that the patient had complaints of pelvic and back pain and felt something in her vagina, with symptoms of uterine prolapse. When questioned, patients denied any symptoms related to uterine prolapse, and no such symptoms were documented in the office chart. 

Patients with fibroids were told they were at an increased risk of cancer and were submitted to a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pathology did not reveal any precancerous cells, at times failing to demonstrate any fibroids. The diagnosis submitted to insurance would include frequent, prolonged, and extremely heavy vaginal bleeding with pelvic pain. Interviewed patients denied such symptoms. Further, the medical record and laboratory studies failed to support such diagnoses.

In several cases, an ultrasound revealed a simple cyst. No repeat ultrasound was recommended, but the patient would be told that there was an increased risk of cancer. To justify surgery, the ultrasound report would be changed to reflect the presence of a complex ovarian cyst, with surgical pathology being benign.

Numerous patients underwent unnecessary testing and procedures. One patient who presented with an abnormal Papanicolaou test underwent 2 colposcopies, a cold knife cone, a hysteroscopy, a D&C, multiple ultrasounds, and a laparoscopic bilateral salpingo-oophorectomy. The patient was told the procedures showed abnormal cells that could lead to cancer. She ultimately had a total vaginal hysterectomy with anterior and posterior colporrhaphy, with a diagnosis of symptomatic uterine prolapse. Pathology was negative for any premalignant findings. The patient was asymptomatic.

In violation of Federal Code 42 CFR §50.205, this physician would perform sterilization procedures without waiting the 30-day period required by Medicaid after the patient initially consents to the procedure. Instead, the physician would insert a false date to satisfy the 30-day waiting period.

Between 2010 and 2019, private and government payors experienced 

 for unnecessary surgeries and procedures.

He routinely billed health care benefit programs for hysteroscopies and colposcopies that were not actually performed. The investigation found that the physician performed more than 12 times the number of office hysteroscopies than the next leading provider in the insurance panel. 

Further, it was discovered that the physician’s only hysteroscope was often inoperable and had been sent for repair, even while billing for such procedures. It also was discovered that the physician performed office hysteroscopy without using any type of distension. It was estimated that over a 9-year period, he had billed health care benefit programs about $620,856 for false and fraudulent diagnostic hysteroscopies.

The physician performed colposcopies without using any solution to augment the presence of cellular abnormalities. In fact, the physician rarely performed biopsies at the time of the colposcopies, documenting that the patients refused a biopsy. The physician billed health care benefit programs $137,806 over the 9-year period. During this time, the physician billed the benefit programs $2,338,106 for gynecologic procedures and surgeries based on, at least in part, never-performed hysteroscopies and colposcopies.

To obtain surgical preauthorization from Medicaid, it was found, the physician used boilerplate language to describe a patient’s symptoms. The physician routinely noted, “enlarged uterus, bleeding for 8+ days, frequent menstruation every 3 weeks, cyclic pelvic pain, perineal pain, painful periods, no relief from NSAIDs [nonsteroidal anti-inflammatory drugs], unable to take hormones due to high blood pressure, unable to examine uterus—see weight, tender adnexa, and history of anemia.”

After a 4 ½-week trial, he was found guilty on 51 counts and sentenced to 59 years in prison. In addition, he was forced to forfeit to the United States any property, real or personal, derived from gross proceeds traceable to the violations. This included $1,461,445 obtained as a result of the fraud scheme, the physician’s personal residence, both medical offices, and the physician’s interest in a surgical center.

This case, although an extreme example, demonstrates the reach of federal statutes enacted to prevent and punish those who commit health care fraud. Sanctions include civil penalties (fines that can now be up to $15,000 for each item or service), imprisonment, and forfeiture of offices and assets obtained or improved as a result of the fraud.

Summarizing several concepts can reinforce best practices.

1. Providers should submit claims only for medically necessary services they render and maintain patient records to verify that the services were provided. By submitting a claim, a provider certifies under penalty of perjury that the services were medically indicated and performed by the provider.

 Elective induction of labor prior to 39 weeks of gestation results in higher neonatal morbidity compared with babies delivered at 39 weeks of gestation.

 Falsifying an EDD to subvert rules against elective induction of labor constitutes fraud, which, in addition to criminal charges, may result in nonpayment for the global obstetrical care for the provider and, occasionally, the facility.

Fraudulently reporting symptoms or investigational findings to obtain surgical preauthorization and subsequent reimbursement is a violation of various statutes. Such violations may result in steep fines and criminal penalties. In addition, facilities and providers found to participate in a scheme to defraud health care benefit programs can be excluded from Medicaid and Medicare for 3 to 5 years. Defrauding government programs (eg, Medicaid, Medicare, and TRICARE) triggers a coordinated response from various federal agencies, including the DOJ, the Office of the Inspector General (OIG), and the FBI. Further, Medicare has established 5 Recovery Audit Contractors to detect and correct (recoup) improper payments so that actions can be implemented to prevent future improper payments.

 It is recommended to establish a compliance program to prevent, detect, and correct any erroneous billing.

 Efforts to establish a compliance program may mitigate the penalties that would otherwise be levied. The 7 components recommended by the OIG include the following:

Conduct internal monitoring through period audits.

Implement compliance and practice standards with written standards and procedures.

Designate a compliance officer to monitor compliance efforts and enforce practice standards.

 Conduct appropriate training and education on practice standards and procedures.

Respond appropriately to detected violations through investigation and disclosure of the incidents to the appropriate governmental entities.

Develop open lines of communication, such as discussions at staff meetings and bulletin boards regarding compliance activities.

Enforce disciplinary standards through well-publicized guidelines.

2. Medicaid requires a valid consent form for all sterilization procedures.

 At least 30 days must pass between the date of the patient’s signature on the consent form and the date of the sterilization procedure for reimbursement. This requirement was instituted to provide protection for vulnerable populations from coerced sterilization.8 Altering the dates to meet the 30-day waiting period constitutes fraud. The waiting period is reduced to 72 hours if the patient delivers prematurely. However, the definition of what constitutes a premature delivery varies dramatically. A 2018 study found that 8% of physicians used more than 38 weeks of gestation as the definition of preterm labor (3.2% used 38 weeks, 1.6% used 39 weeks, and 3.2% used 40 weeks).

a. Performing a postpartum sterilization that does not comply with the requirements for informed consent (42 CFR, part 441, subpart F) will result in denial of payment of both the physician and the hospital costs related to the sterilization. Although presumably not allowed by federal policy, findings from a recent study showed that 12% of respondents reported that a rejected sterilization consent form resulted in loss of the entire obstetrical global payment for both the provider and the facility.

3. Some physicians opine that the alternative is to not file an insurance claim for the sterilization procedure. There are potential consequences of this practice.

a. Not charging patients for their sterilization may violate the Anti-Kickback Statute (42 USC §1320a-7b), which prohibits the exchange of anything of value in an effort to induce the referral of patients or generation of business reimbursable by federal health care programs.

The provision of quality care requires that it is performed, appropriately documented, and properly billed. Attempts to subvert any of these tenets can result in devastating consequences to patients, providers, and our health care facilities. 

United States of America v Javaid Perwaiz

. Superseding indictment:11. June 19, 2020. Accessed June 11, 2021. https://www.justice.gov/archives/usao-edva/page/file/1291026/download

United States of America vs Javaid Perwaiz

. Superseding indictment:24-25. June 19, 2020. Accessed June 11, 2021. https://www.justice.gov/archives/usao-edva/page/file/1291026/download

US Department of Justice. Affidavit in support of an application for an arrest warrant. November 8, 2019, Accessed June 11, 2021. https://www.justice.gov/usao-edva/page/file/1401921/download

. Superseding indictment:40. June 19, 2020. Accessed June 11, 2021. https://www.justice.gov/archives/usao-edva/page/file/1291026/download

American College of Obstetricians and Gynecologists Committee Opinion No. 765: avoidance of nonmedically indicated early-term deliveries and associated neonatal morbidities

 2019;133(2):e156-e163. doi:10.1097/AOG.0000000000003076

U.S. Department of Health and Human Services. Office of the Inspector General Compliance Program for Individual and Small Group Physician Practices, 2000;

 65(194):59434-59452. https://oig.hhs.gov/authorities/docs/physician.pdf

Electronic Code of Federal Regulations. Title 42, CFR 441, subpart F (1982). Accessed June 11, 2021. https://www.ecfr.gov/cgi-bin/text-idx?node=sp42.4.441.f&rgn=div6

Aurora KS, Castleberry N, Schulkin, J. Variation in waiting period for Medicaid postpartum sterilization: results of a national survey of obstetricians-gynecologists. 

The penalties of deception can be much worse than medical negligence.