Judith M. Orvos, ELS, is an editorial consultant for Contemporary OB/GYN.

Judith M. Orvos, ELS

Results from a longitudinal study suggest that bacteria in the cervicovaginal microbiome (CVM) may play a role in risk of progression of high-risk human papillomavirus (HR-HPV) to cervical precancer. 

If the connection is validated in future studies, it could hold promise for development of microbial biomarkers for progression risks of HR-HPV to cervical intraepithelial neoplasia 2 (CIN2).

, the findings are from a nested study within the placebo arm of the Costa Rica HPV Vaccine Trial, which included women aged 18 to 25. The authors looked at the prospective role of the CVM on the natural history of HR-HPV by assessing cervical samples from 273 women with HR-HPV taken during two visits. Their focus was on infection clearance, persistence, and progression to CIN2 and CIN3.

Analysis of the samples from Visit 1 showed that an abundance of 

 was associated with clearance of incident HR-HPV infections (Linear Discriminant Analysis [LDA] > 4.0) whereas 

 was the dominant biomarker for HR-HPV progression (LDA > 4.0). At Visit 2, increased microbial Shannon diversity was significantly associated with progression to CIN2 (P = 0.027).

Multivariate analysis showed that the positive association between Gardnerella and CIN2 progression was a result of the increased cervicovaginal diversity seen in the swabs from Visit 2.

A full multivariate model of key components of the CVM showed significant protective effects via Visit 1 genus 

 (OR = 0.41 [0.22 to 0.79]), fungal diversity (OR = 0.90 [0.82 to 1.00]) and functional cell motility pathway (OR = 0.75 [0.62 to 0.92]) whereas Visit 2 bacterial diversity (OR = 1.19 [1.03 to 1.38]) was shown to be predictive of progression to CIN2.

 that “rather than directly causing the CIN2+ lesions, [it] appears to induce a higher diversity CVM over time as measured at V2 which in turn mediates the observed effect of Gardnerella in HR-HPV disease progression.”

Further, “the association may be tied to the ability of 

 to be immunosuppressive in the cervicovaginal region. Whereas, it seems that the presence of commensal bacteria (e.g. 

) with the ability to stimulate a local immune response may be contributing factors to the clearance of incident HR-HPV infections.”

Additional prospective studies are needed, the researchers concluded, to establish a causal link between the CVM, the immune system, and the natural history of HPV.

How prevalent is HPV in vaccinated adolescents? 

Usyk M, Zolnik CP, Castle PE, et al. Cervicovaginal microbiome and natural history of HPV in a longitudinal study. PLOS Pathog. 2020;16(3). doi:10.1371/journal.ppat.1008376

Articles

Results from a longitudinal study suggest that bacteria in the cervicovaginal microbiome (CVM) may play a role in risk of progression of high-risk human papillomavirus (HR-HPV) to cervical precancer.

Cervicovaginal microbiome and HPV progression

A new systematic review and meta-analysis suggests that women with inflammatory bowel disease (IBD) may be at increased risk of adverse pregnancy outcomes such as gestational diabetes mellitus (GDM) and preterm premature rupture of membranes (PPROM). The authors caution, however, their results need to be confirmed in larger, prospective studies.

, the findings are by Canadian researchers who searched Medline, Embase, and the Cochrane library through May 2019 for studies reporting adverse maternal, placental and obstetric outcomes in patients with IBD. Nearly 8000 pregnancies complicated by IBD and more than 3,200 control pregnancies were represented in the 53 studies selected for analysis. 

The authors hypothesized that women who took medication for IBD during pregnancy might have an increased risk of adverse outcomes such as cesarean delivery, GDM, preeclampsia, chorioamnionitis, placental abruption, PPROM, early pregnancy loss, elective termination of pregnancy, termination of pregnancy, and ectopic pregnancy.

The medications considered were 5-aminosalicylates (5-ASA), corticosteroids, thiopurines, anti-tumor necrosis factor (TNF) therapy, vedolizumab, ustekinumab, and tofacitinib. 

Analysis of the data from the studies showed that cesarean delivery was more common in patients with IBD compared to healthy controls (OR 1.79, 95% CI 1.16 to 2.77). This remained significant for ulcerative colitis but not Crohn’s disease (OR 1.48, 95% CI 0.94 to 2.34). GDM also was more common in women with IBD (OR 2.95, 95% CI 1.47 to 5.98). 

Incidences of placental disease were 2.0% (95% CI 0.9% to 3.1%) for preeclampsia, 3.3% (95% CI 0% to 7.2%) for placental abruption, 0.5% (95% CI 0.2% to 0.9%) for placenta previa and 0.3% (95% CI 0% to 0.5%) for chorioamnionitis. Women with IBD were more likely to experience PPROM (OR 12.10, 95% CI 2.15 to 67.98) but not early pregnancy loss (OR 1.63, 95% CI 0.49 to 5.43). 

Anti-TNF therapy was not associated with chorioamnionitis (OR 1.12, 95% CI 0.16 to 7.67), early pregnancy loss (OR 1.49, 95% CI 0.83 to 2.64) or placenta previa (OR 1.58, 95% CI 0.30 to 8.47). 

The authors noted, however, that the study sample sizes were small and control group comparisons were lacking so definitive conclusions about the drugs cannot be made. They are, however, in line with recent guidelines from the American Gastroenterological Association to continue anti-TNF therapy in pregnant women to maintain IBD remission. 

Tandon P, Govardhanam V, Leung K, Maxwell C, Huang V. Systematic review with meta-analysis: risk of adverse pregnancy-related outcomes in inflammatory bowel disease. Aliment Pharm Ther. 2020;51(3):320-333. doi:10.1111/apt.15587.

A new systematic review and meta-analysis suggests that women with inflammatory bowel disease (IBD) may be at increased risk of adverse pregnancy outcomes such as gestational diabetes mellitus (GDM) and preterm premature rupture of membranes (PPROM).

Inflammatory bowel disease and pregnancy outcomes

A package of nine individual bills has just been introduced that aim to improve health for black mothers in the United States. “Black Maternal Health Momnibus Act of 2020”

 is led by Senator Kamala D. Harris (D-CA) and Representatives Lauren Underwood (IL-14) and Alma Adams (NC-12). 

All three are members of the Black Maternal Health Caucus, founded in 2019 to improve black maternal health outcomes.

Statistics show that black women are nearly four times more likely than white women and more than twice as likely as women of other races to die from preventable, pregnancy-related complications. They also experience higher rates of maternal complications and infant mortality.

The Act is designed to fill gaps in existing legislation to comprehensively address every dimension of the black maternal health crisis in the nation. 

If passed, the bills included in it will result in the following

 Critical investments in social determinants of health that influence maternal health outcomes, such as housing, transportation, and nutrition; 

Funding for community organizations working to improve maternal health outcomes for black women;

Comprehensive study of the unique maternal health risks facing women veterans and investment in Veterans Administration maternity care coordination;

Growth and diversification of the perinatal workforce to ensure that every mother in America receives maternity care and support from people she can trust;

Improved data collection processes and quality measures to better understand the causes of the maternal health crisis in the United States and inform solutions to address it;

Investment in treatments for maternal health care and substance use disorders;

Improved maternal health care and support for women who are incarcerated;

Investment in digital tools like telehealth to improve maternal health outcomes in underserved areas; and

Promotion of innovative payment models to incentivize high-quality maternal care and continuity of health insurance coverage from pregnancy through labor and delivery and up to 1 year postpartum.

 100 organizations endorsing the Act are the American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine, American College of Nurse-Midwives, and Planned Parenthood.

Said Senator Harris in a press release about the legislative package, “Black women across the country are dying from pregnancy and childbirth complications at astounding rates and the disparity transcends income and education levels. It is critical that the federal government work with states, local health providers, and mothers and their families to address the crisis and save lives.”

1. Black Maternal Health Momnibus. Black Maternal Health Caucas. https://blackmaternalhealthcaucus-underwood.house.gov/Momnibus. Published March 18, 2020.

“Black Maternal Health Momnibus Act of 2020” is led by Senator Kamala D. Harris (D-CA) and Representatives Lauren Underwood (IL-14) and Alma Adams (NC-12).

‘Momnibus’ legislation aims to help black moms

Rates of vaginal birth after cesarean (VBAC) in the United States are on the rise, but the Healthy People 2020 goal for the marker-18.3%-isn’t likely to be reached for another 10 years, according to a new 

 from the Centers for Disease Control and Prevention (CDC).

The analysis is based on information amassed in the National Vital Statistics System about VBAC from 2016 to 2018. In 2016, all reporting areas implemented the 2003 revision to the U.S. Standard Certificate of Live Birth, marking the first time since 2004 that VBAC were available.

Year over year, VBAC rates overall in the United States increased from 12.4% to 12.8% to 13.3%, in 2016, 2017 and 2018, respectively. During that period, rates in women aged 20 to 29 rose from 12.7% to 13.6% and for women aged 30 to 39, they rose from 12.4% to 13.3%.

Looking at trends by race and Hispanic origin, the authors found that Native Hawaiian and Other Pacific Islander women were the only groups that did not see increases in VBAC during the report period. Non-Hispanic American Indian and Alaska Native women had the greatest increases, at 11%, compared with 10% for Hispanic women, and 5% for non-Hispanic white, non-Hispanic black, and non-Hispanic Asian women.

Considering trends associated with geographic, only one state-Wisconsin-had significantly lower VBAC rates in 2018 (19.2%) versus 2016 (20.5%). Twelve states had nonsignificant declines, whereas 20 states and the District of Columbia had increases that were not statistically significant. In contrast, in 17 states, VBAC rates increased. The four states with increases of more than 20% over time were Arkansas, California, Florida, and New Hampshire.

Variations also were seen in rates of VBAC by gestational age at birth. They increased 5% to 13% among births delivered at 38, 39, 40 and 41 or more weeks of gestations. VBAC was less likely to occur with births delivered at < 28 weeks in 2018 (26.4%) than in 2018 (27.9%) but the trend was not significant.

Rates of vaginal birth after cesarean (VBAC) in the United States are on the rise, but the Healthy People 2020 goal for the marker-18.3%-isn’t likely to be reached for another 10 years, according to a new report from the Centers for Disease Control and Prevention (CDC).

CDC: VBAC rates increasing

 A “living document” with a comprehensive set of 

 for treatment of COVID-19 has been released by the National Institutes of Health (NIH). Developed by a panel of physicians, statisticians and other experts, it includes recommendations for care of pregnant women.

Currently based on published and preliminary data on COVID-19 and the panelists’ own experience, the guidelines will be revised in keeping with authoritative emerging scientific reports. The key highlights from the report are that the panel: (1) doesn’t recommend use of any form of pre-exposure prophylaxis or post-exposure prophylaxis for SARS-CoV-2 outside of clinical trials; (2) recommends no additional laboratory testing or specific treatment for individuals suspected to have or confirmed to have asymptomatic or pre-symptomatic SARS-CoV-2; and (3) acknowledges lack of data on which to recommend for or against any antiviral or immunomodulatory therapy in patients with COVID-19 who have mild, moderate, severe, or critical illness.

The panel noted that individuals with mild symptoms of COVID-19 can be managed as outpatients or through telemedicine or remote visits. For moderate to severe illness, hospitalization is likely to be required. Use of airborne infection isolation rooms (AIIRs) and oxygen therapy is required for patients with severe illness, defined as SpO

 ≤ 93% on room air at sea level, respiratory rate > 30, PaO

 < 300, or lung infiltrates > 50%, as well as pulmonary imaging and laboratory tests. AAIRs also should be used for patients with COVID-19 who are critically ill.

In the section of the guidelines on considerations in patients who are pregnant or have recently delivered, the panel noted that their recommendations supplement those from the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine. The same recommendations for care for non-pregnant patients generally apply to those who are pregnant. For pregnant patients who require hospitalization, care in a facility that can conduct close maternal and fetal monitoring is preferable. Fetal and uterine contraction monitoring, individualized delivery planning, and team-based case with multispecialty consultation are recommended.

For most pregnancies complicated by COVID-19, the panel said that timing of delivery should be dictated by obstetric indications. Timing of delivery need not be altered for patients who recover from COVID-19 early in pregnancy. To avoid virus transmission to the neonate, postponing delivery (barring medical indications for it) in women with COVID-19 in the third trimester is reasonable until test results for the virus are negative or quarantine restrictions are lifted. After delivery, newborns should be temporarily separated from mothers who have COVID-19 or are persons under investigation for SARS-CoV-2, to minimize the chance of transmission to via respiratory droplets. Breastfeeding is recommended by ACOG, and the Centers for Disease Control and Prevention has issued interim guidance on it in women with COVID-19.   

Dr. Brenna Hughes, MD, a maternal-fetal medicine specialist at Duke Health in Durhan, N.C., served on the panel. Her research expertise is infectious diseases in pregnancy. Dr. Hughes, along with Dr. Sarah Dotters-Katz, authored the article 

“COVID-19: The pathogen that will define the decade,”

The National Institutes of Health has released a comprehensive set of guidelines for the treatment of COVID-19, which includes recommendations for the care of pregnant women.

NIH panel releases COVID-19 treatment recommendations

In a new letter, researchers from Wuhan Children’s Hospital in Wuhan, China, have provided insights on early-onset SARS-CoV-2 infection in neonates. The 

In their hospital, the authors treated 33 neonates born to mothers with COVID-19. Their account describes outcomes in three of the neonates who also were diagnosed with the virus. Data included were collected from January 2020 to February 2020.


	Born at 40 weeks’ gestation to a mother with COVID-19 pneumonia, the infant in Case 1 was lethargic and had a fever on Day 2 of life. Chest x-ray showed pneumonia but all lab tests other than for procalcitonin were normal. Nasopharyngeal and anal swabs were positive for SARS-CoV-2 on Days 2 and 4 but negative on Day 6.

Also born to a mother with confirmed COVID-19 pneumonia, the infant in Case 2 had lethargy, vomiting and fever. Chest x-ray showed pneumonia and lab tests showed leukocytosis, lymphocytopenia, and an elevated creatine kinase-MB fraction. As with the infant in Case 1, nasopharyngeal and anal swabs were positive for SARS-CoV-2 on Days 2 and 4 but negative on Day 6.

The infant in Case 3 required resuscitation after cesarean at 31 weeks, 2 days for fetal distress and maternal COVID-19 pneumonia. He was treated with noninvasive ventilation, caffeine, and antibiotics for neonatal respiratory distress syndrome and pneumonia, which resolved on Day 14 of life. Antibiotics also were administered for suspected sepsis. On Days 2 and 4, nasopharyngeal and anal swabs were positive for SARS-CoVo-2 and negative on Day 7. 


	The authors described symptoms in all 33 infants-including the three infected neonates-as “mild” and their outcomes as “favorable.” They speculated of the most seriously ill neonate that he “may have been symptomatic from prematurity, asphyxia, and sepsis, rather than SARS-CoV-2 infection.” 


	The researchers concluded that “it is crucial to screen pregnant women and implement strict infection control measures, quarantine of infected mothers, and close monitoring of neonates at risk of COVID-19.” 

In a new letter, researchers from Wuhan Children’s Hospital in Wuhan, China, have provided insights on early-onset SARS-CoV-2 infection in neonates