Incidence of still births halved after Seasonal Trivalent Influenza Vaccination During Pregnancy: First Population-Based Retrospective Cohort Study.

The Obstetric Practice and Immunization Expert Work Group of the American College of Obstetricians and Gynecologists (ACOG) updated the committee opinion that all pregnant women should receive influenza vaccination back in 2014. World Health Organizations and CDC guidelines recommend seasonal influenza vaccinations(inactivated influenza vaccine ) for pregnant women in any trimester. However, the live attenuated vaccine is not recommended for pregnant women but can be used safely during the postnatal period.

Pregnancy puts women at increased risk pneumonia and acute respiratory illnesses because of lowered immunity. Antenatal Infections are also linked to fetal mortality and preterm labor. But, in spite of it only 50% of women get themselves immunized due to safety concerns for the fetus.

Recent research shows that there are other maternal and fetal benefits of seasonal influenza vaccination, other than just preventing the flu. A Canadian study by published in Canadian Medical Association Journal has shown that Influenza Vaccination in pregnancy reduces the odds of having a preterm delivery or delivery of a low-birth-weight baby compared with pregnant women who did not get the vaccine.

A recent Population based retrospective study by published online on March 30, 2016 in the journal of Clinical Infectious Diseases  have shown that women in western Australia who received the vaccine have half the risk of stillbirths as compared to women who do not receive the shot.

The lead author Annette K. Regan, MPH, from the School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, and Western Australia Department of Health, Shenton Park said in a news release “During the 2009 H1N1 pandemic, we saw a similar reduction in stillbirths following vaccination,” she added that “Our results are particularly exciting since they show we can get the same protection during seasonal epidemics, which occur every winter. Unfortunately, we know that about 40 percent of pregnant women go unvaccinated, missing out on these benefits.”

The researchers in Australia analyzed midwives’ data retrospectively. A total of 58,008 women delivered during the winter flu season in the year 2012 and 2013 in Western Australia. Out of which 5076 women received the influenza vaccine, and 377 stillbirths occurred. After adjusting for confounders (maternal smoking, indigenous status, and propensity for vaccination) the risk of stillbirth among vaccinated mothers was 51 percent lower than the risk among women who had not been vaccinated.

The observed rate of stillbirths also increased around the time of Influenza virus circulation, suggesting a link between the virus and stillbirths.

The authors call for further research to look into causes of decrease in still birth rates following Influenza vaccination.

"Given the growing body of evidence supporting the health benefits to mother and infant, concerted efforts are needed to improve seasonal influenza vaccine coverage among pregnant women," the researchers conclude.

The study limitations were being retrospective, depending upon data reporting by healthcare workers and generalizability of findings to women in developing countries.

The study also has wider implications on global public health level as vaccination against Influenza is an attainable step to avert stillbirths. In 2015, an estimated 2·6 million (uncertainty range 2·4–3·0 million) babies were stillborn, with 70% of infant death around the time of birth.

References:

http://www.thelancet.com/pdfs/journals/langlo/PIIS2214-109X%2815%2900275-2.pdf

http://www.eurekalert.org/pub_releases/2016-03/idso-siv032916.php

http://cid.oxfordjournals.org/content/early/2016/03/10/cid.ciw082.abstract

Uterine stem cells deficiency linked to Recurrent Pregnancy Loss (RPL).

Stem cells have the potential to treat a myriad of diseases and have acted as a powerful tool to treat many life threatening diseases. Researchers have opened up a new avenue in stem cell therapy by tying stem cell deficiency in endometrium to recurrent pregnancy loss.

According to a recent paper published in February issue of Stem cells by Lucas E S et al researchers postulated that stem cell deficiency in the endometrial tissue and accelerated stromal aging is responsible for RPL by limiting the endometrial capacity to decidualize. Most miscarriages are sporadic and are due to chromosomal aberration in the conceptus, but RPL is a distinct entity.  In about 50% of RPL, the etiology is not defined. It is estimated that roughly 5% of women suffer from 2 clinical miscarriage and 1% ending up with 3 or more losses. While many factors seems to play role in RPL, the underlying endometrial pathology is not yet explored.

It is indicated that RPL is associated with impaired differentiation of endometrial stromal cells (HESCs) into specialized decidual cells. The differentiation termed as decidualization, predicts the end of implantation window and confers endometrium the ability to recognize, respond to and eliminate implanting compromised embryos, theory of natural selection. The theory suggests that it is the response of the decidualized endometrium to embryonic signals, which decides the future implantation and development of the  embryo or its rapid demise through menstruation-like shedding. Current evidence suggests that it is the abnormal decidualization which causes the loss of selectivity leading to implantation without further progress leading to pregnancy loss. So, the endometrium acts as a ‘biosensor’ detecting the embryo derived signal and deciding the fate of the embryo.

It is already known that decidualization of the endometrium in not dependent on embryo. It happens in post ovulatory phase of every cycle due to increase in progesterone levels and cAMP. It is because of cyclic activation of mesenchymal stem cells which differentiate into stromal cells in regenerating endometrium.

The authors hypothesized that defect in cyclic regeneration of endometrium in RPL patients is impacted due to defect in DNA methylation status of human endometrial stromal cells (HESCs).

A total of 183 endometrial biopsies were taken from patients with  normal women and those with RPL, except 8 random samples, all other were timed between 6 and 10 days after the preovulatory luteinizing hormone surge.  HESCs were isolated from the samples and cultured in laboratory. They were further tested for epigenetic markers for recurrent pregnancy loss.

It was seen that endometrial lining in patients with RPL showed loss of plasticity, with included increased senescence, deficiency and limited capacity to differentiate. Epigentic signature was lacking in women who experienced RPL as compared to their normal counterparts.

The endometrium also had decreased number of stem cells that had limited capacity to renew the endometrium, resulting in aging. Aging cells mount an inflammatory response that is enough for implantation but not for development and sustaining the embryo.

In an interview with medscape  Dr. Brosens said “"We also found that the greater the number of miscarriages a woman had experienced...the more depleted the lining was."

"Cultured cells from women who had had three or more consecutive miscarriages showed that aging cells in the lining of the womb don't have the ability to prepare adequately for pregnancy," Dr. Brosens notes.

He futher explained hat medicine usually regards recurrent miscarriage as being associated with an underlying disease, and normal practice is to investigate clotting abnormalities, hormonal imbalances, or immune responses. In the United States, patients are referred to specialist care after two consecutive losses; patients are referred after three losses in the United Kingdom. "It is often stated that a cause for recurrent miscarriage can be found in 50% of patients. However, for every woman with an apparent known 'cause' of miscarriage, there will be 50 to 100 women who have the same disorder but do not experience miscarriage. So current tests completely lack specificity."

With sporadic miscarriages, the majorities are caused by chromosomal abnormalities in the fetus, but with recurrent miscarriages, the majority involves normal fetuses. The more miscarriages a woman has, the greater the likelihood pregnancy loss involves a fetus with normal chromosomes. "Also, as the number of miscarriages increases, there is a higher chance of recurrent miscarriage," Dr. Brosens added.

According to Dr. Brosens, the real challenge lies in translating these findings into something clinically meaningful. He believes that this could further lead to development of some sort of screening tests, eventually ending up with some sort of treatment for women at risk. "The abnormalities we have identified all precede pregnancy, so it is possible to test the uterine lining for these markers and help predict if a patient is at risk of recurrent miscarriages."

He also pointed that stem cells in the uterine lining were highly dynamic and active pool, that are undergoing  cyclic shedding and regeneration, so intermittently the defects in the uterine lining could undergo self-repair, changing from an unsupportive environment to a supportive one. This explains why many women have a successful pregnancy even after recurrent miscarriages.

The authors concluded that “These findings open up new avenues to screen women prior to pregnancy for the risk of miscarriage and point to the potential of cell-based therapies in the prevention of RPL.”

References:

Lucas, E. S., Dyer, N. P., Murakami, K., Hou Lee, Y., Chan, Y.-W., Grimaldi, G., Muter, J., Brighton, P. J., Moore, J. D., Patel, G., Chan, J. K.Y., Takeda, S., Lam, E. W.-F., Quenby, S., Ott, S. and Brosens, J. J. (2016), Loss of Endometrial Plasticity in Recurrent Pregnancy Loss. STEM CELLS, 34: 346–356. doi: 10.1002/stem.2222

http://www.ncbi.nlm.nih.gov/pubmed/22835448

http://www.ncbi.nlm.nih.gov/pubmed/1975862

http://www.ncbi.nlm.nih.gov/pubmed/20847090

FDA announces a proposal to ban most powdered medical gloves in USA.

In a press release on March 21, 2016 US Food and Drug Administration (FDA) announced a proposal to ban most powdered medical gloves in USA. The ban includes powdered surgeon’s gloves, powdered patient examination gloves and absorbable powder for lubricating a surgeon’s glove. Both synthetic gloves and natural rubber latex (NRL) are covered in the ban, only powdered radiographic examination gloves are exempt.

A ban was only option to FDA as the risks associated with the use of powdered gloves cannot be corrected through new or updated labeling.

“This ban is about protecting patients and health care professionals from a danger they might not even be aware of,” said Jeffrey Shuren, M.D., director of FDA’s Center for Devices and Radiological Health. “We take bans very seriously and only take this action when we feel it’s necessary to protect the public health.”

Surgical gloves made a room in doctor’s armamentarium in the year 1889, and have played an important role in protecting both patients and health care personnel in medical field since than. Various types of powder lubricants have been used so that they can be donned easily. The first was powder made from Lycopodium spores (club moss spores) and later replaced by talcum powder (chemically hydrous magnesium silicate). Both of these were replaced by modified cornstarch as they were recognized to cause wound granulomas and adhesion formation.  Cornstarch is currently the most commonly used type of absorbable glove powder.

Before proposing the ban, FDA considered all available scientific evidence in disease causation due to powder which included a through review of literature. FDA has also received several public petitions from 1997 to 2011, requesting a ban due to multiple health issues in doctors and healthcare workers.

The level and type of risks due to use of powdered gloves vary according to the composition of gloves (synthetic versus NRL) and its intended use (surgeon’s glove versus patient examination glove). It is known that powdered synthetic patient examination gloves present less risk than powdered NRL surgeon’s gloves.

The identified risks of powdered gloves according to composition and intended use are:

1) Risks of Absorbable Powder for Lubricating a Surgeon's Glove.

This powder, often referred to as Absorbable Dusting Powder or ADP, has been shown to cause acute severe airway inflammation, granulomas, and adhesions. When used on NRL gloves, powder has the ability to adhere to latex allergenic proteins that, when aerosolized and inhaled, present significant risks to patients, including inflammatory responses, hypersensitivity reactions, and allergic reactions. Additionally, the latex sensitive individuals experience cutaneous reactions upon skin exposure to the latex allergenic proteins adherent to the powder.

2) Risks of Powdered Natural Rubber Latex Gloves.

The powder used to lubricate these gloves bind to the natural rubber latex protein, causing latex aerosol which causes allergic and inflammatory responses to NRL. Allergic reactions include asthma, allergic rhinitis, conjunctivitis, and dyspnea.

3) Risks of Powdered Synthetic Surgeon’s Gloves.

These gloves do not pose the risk of allergic reaction due to aerosolized powder, but exposes individuals to powder by inhalation leading to airway inflammation. Additionally surgeries and invasive examinations deposits the powder could then results in granuloma formation in any exposed site, as well as peritoneal and other tissues adhesions. Additional studies show that powder may promote infection in wounds, which can lead to wound healing complications.

4) Risks of Powdered Synthetic Patient Examination Gloves.

The patient examination gloves does not expose the patient’s internal organs  to powder but the internal tissue  are exposed  during procedures such as oral, vaginal, gynecological, and rectal examinations. In female patients the reproductive tracts is exposed to powder leading to tubal adhesions and infertility in animal and human studies.

Over the years organizations such the American Academy of Allergy, Asthma, and Immunology(ACAAI), the National Institute for Occupational Safety and Health (NIOSH), the American College of Surgeons (ACS), and the American Nurses Association have all issued statements against the use of powdered gloves. CDC also joined the team, issuing a statement on NRL sensitization and recommending that non powdered rubber latex gloves would be more efficient.

Moreover, health care systems such as the Cleveland Clinic network of nine hospitals, the Johns Hopkins Hospital and University of Virginia Healthcare systems have all restricted or banned the use of powdered NRL gloves in their systems. In Europe, Germany and the United Kingdom have also taken steps against use of powdered NRL gloves.

The FDA published a request for comments in its notice to include the public in Federal decision making.  Comments will be accepted for 90 days from the date of publication. The full notice and the way to post comments can be viewed here.

FDA further proposes that the ban will not incur any additional economical or environmental burden. The proposed rule is expected to provide a positive net benefits range between $26.6 million and $29.3 million due to reduced adverse effects.

It further added that the policy will also not affect the medical practice as several non powdered alternatives are already available in the market.

References:

https://s3.amazonaws.com/public-inspection.federalregister.gov/2016-06360.pdf

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm491466.htm

https://www.regulations.gov/#!documentDetail;D=FDA-2011-N-0027-0001