Lindsey Carr

Bacterial vaginosis during pregnancy may lead to adverse outcomes, such as preterm birth, preterm delivery, and spontaneous abortion, according to results from a meta-analysis.

Researchers conducted a meta-analysis to delve deeper into the connection between bacterial vaginosis in early pregnancy and preterm birth. From November 2018 to March 2020, they searched PubMed, Cochrane, Google Scholar, and LILAC for data relating to bacterial vaginosis and preterm birth. They only included studies that were published from 2008 to 2018 and those that offered statistical data. They excluded studies that only consisted of conceptual and qualitative data. The search ultimately led to data from 20,894 women across 11 studies.

Researchers then evaluated the findings of each study, extracting various outcomes and conclusions. They combined the results—risk ratios (RR) and odds ratios (OR)—for deeper analysis. For women with bacterial vaginosis during pregnancy, the combined odds of preterm birth or preterm delivery was 2.79 (2.29-3.41).

Through their evaluation, they found that preterm birth was more than 2 times as likely in pregnant women with bacterial vaginosis than those without the infection (OR= 2.79; 95% CI, 2.29 to 3.41). Bacterial vaginosis was also found to be a greater risk factor for preterm delivery in late pregnancy, increasing the odds 4-fold.

Researchers also examined the conclusions of each study, ultimately identifying bacterial vaginosis in early pregnancy as a significant risk factor for preterm delivery and spontaneous abortion. They also found that the administration of clindamycin at <22 weeks’ gestation significantly reduced the risk for preterm birth.

Reference
Mohanty T, Doke PP, Khuroo SR. Effect of bacterial vaginosis on preterm birth: a meta-analysis [published online ahead of print, 2022 Oct 17]. 

. 2022;10.1007/s00404-022-06817-5. doi:10.1007/s00404-022-06817-5

Articles

Bacterial vaginosis during pregnancy may lead to increased risks for preterm birth, preterm delivery, and spontaneous abortion, according to new research in the Archives of Gynecology and Obstetrics.

Bacterial vaginosis during pregnancy may heighten risk of preterm birth, pregnancy loss

A US Food and Drug Administration (FDA) advisory panel has voted 14 to 1 to withdraw 17α-hydroxyprogesterone caproate (Makena; Covis Pharma) for the prevention of preterm birth from the market.

Panelists agreed with the 2020 decision by the FDA that deemed the injectable drug ineffective, citing evidence from the confirmatory trial, the PROLONG study.

The study included 1700 patients and showed that Makena did not have a statistically significant effect on preterm births before 35 weeks gestation (relative risk [RR] 0.95, 95% CI 0.71-1.26) or a neonatal composite index that included outcomes such as death, respiratory distress syndrome, bronchopulmonary dysplasia, and sepsis, among others (RR 1.05, 95% CI 0.68-1.61).

The FDA’s briefing materials note that the benefit-risk calculation for Makena was not favorable, as the medication is ineffective and carries risks for adverse events like blood clots or depression.

“If we allow Makena to remain on the market, it implies the FDA looked at a large study, found no benefit and yet allowed this drug to stay on the market," said Margery Gass, MD, an ob-gyn at Cleveland Clinic and one of the FDA advisory panelists. “I think that’s a bad precedent.”

Is it expected that Robert Califf, MD, FDA commissioner, will make a final decision on the withdrawal of the drug within the next few months. This would be the first time the FDA formally pulled a drug from the market following approval based on early data if Califf follows through with the advisory panel’s advice.

The injectable drug was approved for pregnant women with a history of at least 1 spontaneous preterm birth. Initially, the FDA approved Makena in 2011 to reduce the risk of preterm birth before 37 weeks of pregnancy among women who had a history of spontaneous preterm birth. The drug was under accelerated approval, which allows the agency to expedite the approval process based on a surrogate endpoint thought to predict clinical benefit.

The initial approval was based on clinical trial results, during which women received a 250-mcg injection of Makena and had a significantly lower risk of delivering before 37 weeks compared with the placebo group. However, since the risk reduction in preterm births did not signify a direct clinical benefit to babies born prematurely, the FDA required a post-marketing confirmatory trial.

This article was published by our sister publication Contemporary OB/GYN.

FDA panel backs removal of unproven pregnancy drug. October 19, 2022. Accessed October 19, 2022. 

https://news.yahoo.com/fda-panel-backs-removal-unproven-150245703.html

Carr L.FDA plans to remove hydroxyprogesterone caproate approval. 

. October 17, 2022. Accessed October 19, 2022. https://www.contemporaryobgyn.net/view/fda-plans-to-remove-hydroxyprogesterone-caproate-approval

An advisory panel for the US Food and Drug Administration voted 14-1 to withdraw 17α-hydroxyprogesterone caproate (Makena; Covis Pharma) from the market.

FDA votes to withdraw approval of premature birth prevention drug

Under California Law, children under 8 years must be properly buckled. Children aged 8 and older are permitted to use a seat belt if it fits properly. However, research suggests 30.4% of 4- to 7-year-old children are unrestrained or in a seat belt. From 2018 to 2020, this has led to 5 fatalities and 218 injured children under 8 years of age in Orange County, California.

For the Clinic in the Park research project, researchers targeted low-income families, 85% of which identified as Hispanic or Latino. They set up neighborhood distribution hubs, where they distributed the booster seat in a bag, educational materials, and a liability waiver. Educational materials included a self-guided, online 15-minute HIPAA-compliant educational module in both English and Spanish. Content included information on age and size-appropriate protection devices and current California state laws. Participants also completed a 3-month follow-up survey online.

From June 2021 to December 2021, 3 virtual training workshops were held. Eleven organizations participated as distribution sites, which included family resource centers, school districts, law enforcement, and community-based organizations. In total, 125 booster seats were distributed to children 5 to 11 years of age.

According to the results, the reasons the child needed a booster seat varied from the fact that they outgrew the car seat (10%), the booster seat was damaged in a crash or purchased secondhand (16%), the booster seat was needed for a second vehicle (6%), or the child did not have a booster seat and were only using the vehicle seat belt (68%).

The 3-month follow-up electronic survey included 80% of respondents (100/125). Of those, 99% reported that children were using the booster seat, 98% stated that the seat belt fit better with a booster seat, and 100% agreed that children may need to ride in a booster seat until 10 to 12 years of age.

The researchers concluded that the virtual platform was a success—it was cost-saving, convenient, and efficient. It also eliminated access barriers and could be used as a model for bicycle helmets and water safety for parent education.

Malone E, Valdez A, Murray S, Bhalla J, et al. Poster. Boosters in a Bag: A Pandemic Innovation. Presented at: American Academy of Pediatrics National Conference & Exhibition. Anaheim, California. October 7 to October 11, 2022.

At the American Academy of Pediatrics National Conference & Exhibition, Phyllis Agran, MD, MPH; Erin Malone, MPH; Al Valdez, PhD; Sandra Murray, MD; Jaya Bhalla; Emma Course; Lauren Tabios, MPH; and Sara Brown, PhD, discussed how the research project Clinic in the Park offered booster seats to low-income families during the COVID-19 pandemic.

Booster seats in a bag: A pandemic success

The approval was granted to GlaxoSmithKline Biologicals.

According to Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, babies are at highest risk for getting pertussis and having serious related complications. This vaccine, tetanus toxoid, reduced diptheria toxoid and acellular pertussis vaccine, adsorbed [Tdap] (Boostrix) was first approved by the FDA in 2005 as a single dose for booster immunization against tetanus, diphtheria and pertussis in individuals aged 10 to 18. It was then also approved to include use in individuals aged 19 and older, and to include use of an additional dose 9 or more years after the initial dose of a Tdap vaccine. Apparently, the FDA’s approval has always included its use during pregnancy to protect the vaccinated individual. Today’s approval, however, specifically approves its use in pregnancy to prevent pertussis in infants under 2 years of age. Since 2012, the Centers for Disease Control and Prevention (CDC) have recommended the use of Tdap vaccines during the third trimester of pregnancy.

The safety of the vaccine during the third trimester of pregnancy was assessed in a randomized, placebo-controlled study with a non-US formulation. The FDA considered the safety data with the non-US formulation relevant because it contains the same components as the US formulation, except the non-US formulation contains more aluminum per dose. The study included 680 pregnant individuals, of whom 340 received the non-US formulation and of whom, 340 received saline placebo.

The rates of side effects were the same among both groups—during pregnancy and after childbirth. The study did not find any vaccine-related adverse effects on pregnancy or on the fetus.

The most common side effects in previous studies were pain, redness at injection site, headache, fatigue and gastrointestinal symptoms.

Office. FDA Approves Vaccine for Use During Third Trimester of Pregnancy to Prevent Whooping Cough in Infants Younger Than Two Months of Age. U.S. Food and Drug Administration. Published 2022. Accessed October 7, 2022. https://www.fda.gov/news-events/press-announcements/fda-approves-vaccine-use-during-third-trimester-pregnancy-prevent-whooping-cough-infants-younger-two

The US Food & Drug Administration approved tetanus toxoid, reduced diptheria toxoid and acellular pertussis vaccine, adsorbed [Tdap] (Boostrix, GSK) today for immunization during the third trimester of pregnancy to prevent pertussis—or whooping cough—in infants under 2 months of age. 

Whooping cough vaccine approved for use during third trimester

Updated Case-finding Guidance: Monkeypox Outbreak—United States, 2022

Monkeypox can be transmitted to the fetus during pregnancy or to the newborn through close contact during and after birth. Spontaneous pregnancy loss and stillbirth, and preterm delivery, have been reported in confirmed cases.

Monkeypox is similar to smallpox (Variola virus) but seems to be less severe in its manifestations and resulting illnesses during pregnancy, including hemorrhagic complications and death. Variola virus infection during pregnancy has been reported to cause pregnancy loss, stillbirth, preterm birth, and congenital infection.

The signs and symptoms of monkeypox infection in pregnancy appear like those of nonpregnant people, including prodromal symptoms such as fever, headache, lymphadenopathy, malaise, sore throat and cough, and rash.

The cause of fever may be difficult to identify until the rash appears.

It is important to differentiate a monkeypox diagnosis from dermatoses of pregnancy, including pruritic urticarial papules and plaques of pregnancy.

Monkeypox lesions can mimic the appearance of other infections. Patients with rashes that appear to be more common infections, such as varicella zoster or sexually transmitted infections (STIs), need to be evaluated for a characteristic monkeypox rash (IMAGES). Providers should also consider diagnostic testing, especially if epidemiologic risk factors for monkeypox virus infection are present. The Centers for Disease Control and Prevention (CDC) recommends a broad approach to testing as simultaneous infections of monkeypox virus and STIs have been reported.

Providers should prioritize currently or recently pregnant and breastfeeding people with monkeypox infection for medical treatment before non-pregnant individuals, as the likely increased risk of severe disease, fetal transmission during pregnancy, and severe newborn infection via close contact during and after birth.

At the time of this article’s publication, there is not yet a treatment approved specifically for monkeypox infections. However, antivirals developed for use in patients with smallpox may be beneficial.

If treatment is indicated, tecovirimat—also known as TPOXX—should be considered as the first-line antiviral for pregnant, recently pregnant, or breastfeeding people. Tecovirimat is a US Food and Drug Administration (FDA)-approved antiviral medication for the treatment of smallpox in children and adults. It is expected to have antiviral activity against monkeypox and is FDA-authorized for this indication under an expanded access protocol.

The information regarding the effects of tecovirimat on fetal and reproductive development is limited to animal studies, in which subject animals were given a dose that was 23 times higher than the recommended human dosage. No specific fetal effects were noted, but it is unclear whether it prevents congenital monkeypox.

While tecovirimat was present in subject animals’ breast milk, it is unknown if the levels are sufficient for treating a breastfeeding child with monkeypox infection. If indicated, breastfeeding children with monkeypox infection should be treated independently.

While they are considered alternative antiviral therapies for treating monkeypox infection, animal studies have shown evidence of teratogenicity so they should not be used to treat people in their first trimester of pregnancy. Their presence in breastmilk is also unknown, so it should also be avoided in breastfeeding people in case of serious adverse reactions in the breastfeeding infant.

Vaccinia Immune Globulin Intravenous (VIVIG)

Researchers have not yet conducted animal reproduction studies with VIVIG, so there is little data on whether it can cause fetal harm during pregnancy, or on a person’s future fertility. However, immune globolins have been used during pregnancy for many years without any apparent negative reproductive side effects. Providers should evaluate the risks and benefits of VIVIG for each individual patient and exercise caution when administering to a breastfeeding person, as it may be excreted in breast milk.

Live, nonreplicating viral vaccine licensed for the prevention of smallpox and monkeypox infection.

Vaccine-associated risks in pregnancy are unknown, but animal studies indicated no evidence of harm to a developing fetus.

Due to its nonreplicating quality, it should not present a risk of transmission to breastfed infants, making it the vaccine of choice for both pregnant and breastfeeding people.

Replicating viral vaccine licensed for smallpox prevention. Contraindicated in pregnant and breastfeeding people due to risk of pregnancy loss, congenital defects, and fetal-infant vaccinia virus infection.

Pre- and post-exposure prophylaxis should be offered when indicated to pregnant or breastfeeding people.

As with any treatment, shared decision-making should be used when discussing the risks and benefits with patients.

Direct contact between a patient in isolation for monkeypox and their newborn is not advised. Separating the monkeypox-infected person from their newborn is the best way to prevent transmission, and full-time rooming-in is not recommended during the infectious period. Providers should counsel the patient on the transmission risk and potential consequences for severe disease in newborns. If the patient chooses to have infant contact during their infectious period, the following precautions should be taken:

Infant should be fully clothed or swaddled, and after contact occurs, the clothing or blanket should be replaced.

Patient should always wear gloves and a fresh gown, covering all visible skin below the neck.

Soiled linens should be removed from the area.

The patient should wear a medical mask or other well-fitting source control during the visit.

Discharge planning should consider a patient’s isolation period duration, ability to strictly adhere to isolation recommendations and availability of alternate caregivers.

Breastfeeding should also be delayed until the isolation period has concluded.

This article originally appeared on Contemporary OB/GYN®.

CDC. Clinical Considerations for Monkeypox in People Who are Pregnant or Breastfeeding. Centers for Disease Control and Prevention. Published July 18, 2022. Accessed July 26, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/pregnancy.html

What we know about monkeypox in pregnancy, including treatment recommendations, vaccination, and postpartum care.

Clinical considerations for monkeypox in pregnancy

Prolonged levels of maternal stress and postnatal depression in pregnant women during the COVID-19 pandemic may hinder structural development in key regions of the fetal brain, according to research in 

Researchers at the Developing Brain Institute in Washington, DC saw a unique opportunity during the pandemic—to investigate the short- and long-term impacts of prenatal stress on early brain development. The findings may lead to a deeper understanding of early childhood development and provide insight into factors relating to cognitive- and health-related issues later in life.

“Understanding how contemporary stressors may influence fetal brain development during pregnancy has major implications for basic science and informing public policy initiatives,” said Catherine Limperopoulos, PhD, chief and director of the Developing Brain Institute at Children’s National and the study’s senior author.

Limperopoulos and her research team used magnetic resonance imaging (MRI) scans, advanced image processing techniques, artificial intelligence, and 3-dimensional brain mapping to observe fetal brain tissue volumes and development activity in 2 groups of pregnant women.

The initial research began in March 2014 and continued until February 2020, when 137 healthy pregnant women were enrolled in a longitudinal study of normative fetal brain development in low-risk patients, all with normal prenatal history. During the visit, mothers underwent MRI scans and reported their levels of distress using 4 validated stress, anxiety, and depression scales.

To evaluate pregnancies during the pandemic, the research team then enrolled a second group of 65 women—all with no known exposure to COVID-19—to compare to the previous group. The second group of women also underwent MRI scans and recorded their stress levels each time. All 202 women were between 16.7 to 39.1 gestational weeks when 274 fetal brain scans were taken.

Stress and depression scores in the pandemic group were significantly higher than those in the pre-pandemic group and correlated directly to impaired fetal brain growth, with evidence of decreased amounts of fetal white matter, hippocampal, and cerebellar volumes, and delayed development of fetal brain folds. They also showed lower brain surface area, gyrification, and sulcal depth than the pre-pandemic fetal brain data.

Among 173 pregnant women with available maternal distress measures, 27.6% (n=34) of the prepandemic[LL1] group and 52 (n=26) in the pandemic group showed elevated levels of psychological distress. Higher levels of anxiety and stress, researchers found, were linked to smaller hippocampus and cerebellar volumes.

The median gestational age at the time of MRI was 30.2 weeks (range from 16.7 to 39.1) in the prepandemic[LL2] group and 30.8 weeks (range from 17 to 38.4) in the pandemic group. The median maternal age was 34.1 years old (range from 17 to 51 years). At birth, the median gestational age was 39.6 weeks (range: 31.0 to 41.9), and the median birth weight was 3.36 kg (range: 1.02 to 4.70).

These findings present an opportunity for ob-gyns and prenatal care providers to counsel patients on the importance of mental health during and after pregnancy. More research is needed, according to the research team, to understand the potential long-term neurodevelopmental consequences of altered fetal brain development in pandemic-era pregnancies.

Originally published on our sister brand, 

Proofpoint Isolation. Urlisolation.com. Published 2022. Accessed May 26, 2022. 

https://urlisolation.com/browser?clickId=5F38A541-6A1E-46E0-B4D7-74C9C426FEED&traceToken=1653583718%3Bcnmc_hosted%3Bhttps%3A%2Fwww.nature.com%2Farticles%2Fs&url=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs43856-022-00111-w

GLOBE. Pandemic-related stressors in pregnant women may impact their babies before they’re born. Bluefield Daily Telegraph. Published May 26, 2022. Accessed May 26, 2022. 

https://www.bdtonline.com/news/nation_world/pandemic-related-stressors-in-pregnant-women-may-impact-their-babies-before-they-re-born/article_68121a19-9420-5250-a2ad-8947d3261b1a.html

Research from the Developing Brain Institute found maternal psychological distress during the COVID-19 pandemic had disrupted critical processes of fetal brain development.