Showing posts with label Brazil. Show all posts
Showing posts with label Brazil. Show all posts

Saturday, December 8, 2018

First live birth following a uterine transplant from a deceased donor


A Brazilian woman becomes the first person to successfully give birth to a healthy baby after receiving a uterine transplant from a deceased donor. This comes after a history of previous 10 unsuccessful attempts at live birth after deceased donor transplants in the United States, the Czech Republic, and Turkey.

This is a milestone in the history of uterine transplants as it opens the path forward for achieving successful pregnancies without the need of live donor and donor surgery. The details of the case were published by the Lancet on December 4, 2018, accompanied by an editorial.

Dr. Dani Ejzenberg, PhD, the lead author and researcher from the Department of Obstetrics and Gynecology, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, said in a press release by Lancet, "The use of deceased donors could greatly broaden access to this treatment, and our results provide proof-of-concept for a new option for women with uterine infertility."

Ejzenberg and colleagues report that the 32-year old woman was born without a uterus because of congenital uterine agenesis, also called as Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, which affects 1 in 4500 women.

The woman received uterus in September 2016 after 10.5-hour surgery from a 45-year old multiparous woman who died of subarachnoid hemorrhage. After the transplant, the woman was discharged on the 8th postoperative day with immunosuppression achieved and maintained with prednisolone and thymoglobulin and continued via tacrolimus and mycophenalate mofetil (MMF) when at five months post-transplant, azathioprine replaced MMF.

The woman got her first period 37 days after transplant and after that continued to have regular cycles every 26–32 days.  Pregnancy occurred following single embryo-transfer after seven months from cryopreserved blastocyst from a successful in-vitro fertilization four months before the transplant surgery.

The pregnancy progressed uneventfully and was monitored by ultrasound and Doppler flow velocity waveforms of uterine arteries, fetal umbilical, or middle cerebral arteries.

A healthy, female baby weighing 2550 g was delivered by elective cesarean section at 36 weeks on December 15, 2017. At the time of writing the article, the baby is healthy and developing normally.

The uterus was also removed at the time of cesarean section, and immunosuppressive therapy stopped.

Cesar Diaz-Garcia, MD, Nuffield Department of Women's and Reproductive Health, University of Oxford, UK, and Antonio Pellicer, MD, PhD, Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Spain, writes in an accompanying editorial, "In a context in which the scarcity of human data is still the norm, [the report] reveals a breakthrough in the field of uterus transplantation."

The first uterine transplant from a living donor took place in Sweden in 2013, followed by first live-birth after transplant in 2015. Since then, 11 more births have taken place worldwide, albeit all from live donor transplant.

However, uteri from living donors are limited because the person has to a relative of the recipient, thereby, limiting the option for women with uterine factor infertility. If uterine transplant after dead donor becomes successful, uteri will not be in short supply as people are more willing to donate organs after death than when they are alive.

The authors agree that many potential issues need to be addressed before deceased donor transplant becomes a norm. These include standardization of operative procedures, immunosuppressive therapy before and during pregnancy, criteria for rejection if it happens, and long-term outcome of the baby delivered after transplant.



Wednesday, October 24, 2018

Global cesarean section rates almost double since the turn of the century


Globally, the cesarean section rate has almost doubled since 2000, with wide geographical variations based on economic prosperity. The rate is unprecedently high, reaching almost 60% in some parts of Latin America and as low as 5% in southern Africa. The intervention is often overused unnecessarily in some parts of the world and denied to mothers in the area where it is needed the most. The linear increases in rates make it highly unlikely that it will be reversed soon.

The considerable variation in C-section rates indicates that the increase is not backed by scientific evidence, as evident by a whopping 6·2 million unnecessary caesareans performed each year, half of which are done in Brazil and China.

Lancet launched a three-part series on optimizing the cesarean section rates at the World Congress of Gynecology and Obstetrics (FIGO) on Oct 18. Simultaneously, the World Health Organization (WHO) also published guidelines on October 11 to reduce the incidence of unnecessary cesarean sections. 



The WHO guidance is unique because it includes the first ever non-clinical interventions to decrease the rising cesarean rates. The guidance consists of 3 sets of separate recommendations targeted at women, healthcare professionals, and health organization and systems.

Those addressed at women, stress the importance of health education to allay fear of childbirth and misconceptions. The WHO guidance states, comprehensive health education, including tailored information and support about childbirth fear, pain relief, and the advantages and disadvantages of cesarean sections, should be provided to all women.

Providers guidance is crucial in a sense it includes a mandatory second opinion for cesarean section indication, audit and timely feedback in good resource settings to bring down the cesarean rates. Another significant recommendation is the equal remuneration for the vaginal birth and cesarean deliveries.

The guidance also acknowledges other barriers towards practicing evidence-based medicines such as cultural beliefs, litigations, increased surgical skills of younger providers with decreasing confidence in conducting difficult vaginal births.

As the part of the Lancet series, the editorial by Wiklund and colleagues highlights the importance of investing in midwives and midwives-led care in bringing down the global cesarean section rate. Trained midwives can provide continuous and watchful support during labor, creating an atmosphere of trust that may calm the patients resulting in more natural births.

The series further analyzed the significant trends of cesarean section in Brazil and China. Both are emerging economies with the highest cesarean section rates seen in wealthier, educated women in private clinics as compared to less well-educated women (54.4% of births versus 19.4%). Wealthier women are 6 times more likely to have surgical delivery as compared to women from a low socioeconomic background.

FIGO also issued a position paper on how to curb the recent cesarean section epidemic. Gerard Visser, MD, from the University Medical Centre, Utrecht, the Netherlands, and chair of FIGO's Committee on Safe Motherhood and Newborn Health, and colleagues note, “Worldwide there is an alarming increase in C-section rates. The medical profession on its own cannot reverse this trend.

Drivers for the increasing C-section rates can vary between countries and include a loss of medical skills to confidently and competently attend a (potentially tricky) vaginal delivery, as well as medico-legal issues."

In the position paper, FIGO calls upon governmental bodies, UN partners, professional organizations, women's groups, and other stakeholders to join hands to bring down the global cesarean section rates.

The six recommendations by FIGO includes:

  • Educating the women about benefits and harm of operative delivery
  • Matching the rates of surgical and vaginal deliveries, especially in private practice
  • Making mandatory for hospitals to publish their Cesarean section rates
  • Ensuring that all hospitals adopt a uniform classification system for CS
  • Reinvesting the money saved from lower cesarean section to improve the infrastructure
  • Increasing access to skilled care, fetal monitoring and assisted births in low-income, rural areas

The authors further note that the only aspect that has consistently resulted in a significant reduction in CS rates has been an altered reimbursement model for doctors and hospitals that favor vaginal delivery. This has been shown in Portugal following wide dissemination of information on the increased risks of CS, as well as in governmental hospitals in Iran and in a large hospital setting in Shanghai.


Comments

Editorial

Profile


Thursday, April 14, 2016

CDC Confirms the link between Zika infection and microcephaly.



Zika has been linked to microcephaly since Brazil reported a sudden increase in number of infants born with microcephaly in September 2015, but causation was not established. CDC today made an important announcement after careful review of all the possible evidence that Zika virus is a cause of microcephaly and other severe fetal brain defects.

The study is published online in the New England Journal of  Medicine today.

“This study marks a turning point in the Zika outbreak.  It is now clear that the virus causes microcephaly.  We are also launching further studies to determine whether children who have microcephaly born to mothers infected by the Zika virus is the tip of the iceberg of what we could see in damaging effects on the brain and other developmental problems,” said Tom Frieden, M.D., M.P.H., director of the CDC. “We’ve now confirmed what mounting evidence has suggested, affirming our early guidance to pregnant women and their partners to take steps to avoid Zika infection and to health care professionals who are talking to patients every day. We are working to do everything possible to protect the American public.”

The investigators examined the causality evidence in light of Shepard’s criterias, which is set of rules that must be satisfied before labeling  an agent being ‘ teratogenic’  and causing  congenital malformations. According to the Shepard’s criterias, causality is established when either criteria 1, 3, and 4 (rare exposure–rare defect approach) or criteria 1, 2, and 3 (epidemiologic approach) are fulfilled.

So, the relationship between Zika infection and microcephaly was termed casual under the rare exposure–rare defect approach as criteria 1, 3 and 4 were fulfilled:

  1. Proven exposure must occur at a critical time during prenatal exposure: The microcephaly and other anomalies occur when the exposure occurs during first trimester or early second trimester. 
  2. Careful delineation of clinical cases with the finding of a specific defect or syndrome: Infants with Zika infection do have a typical pattern which includes severe microcephaly, intracranial calcifications, and other brain anomalies, sometimes accompanied by eye findings, redundant scalp skin, arthrogryposis, and clubfoot which led the scientist to coin a term “Congenital Zika Syndrome.”
  3. Rare exposure and a rare defect: This criterion was met because microcephaly is a rare defect with an incidence of 6 infants per 10,000 liveborn infants in the United States and infection in travelers who spent a limited amount of time in Brazil with active infection, constitute rare exposure for the patients.


Also supportive of causation is lack of alternative explanation for sudden increase in microcephaly cases in Brazil, French Polynesia and Colombia.

But, proving the causation is not enough in the fight against Zika infection. Many key questions are yet to be answered that have important implications.

CDC's director, Tom Frieden, MD said “We are launching further studies to determine whether children who have microcephaly born to mothers infected by the Zika virus is the tip of the iceberg of what we could see in damaging effects on the brain and other developmental problems," in a statement.

In addition to this researchers are also interested in knowing relative and absolute risk of infection and malformation. At present 1% to 29% of babies are born with microcephaly of all the mothers infected with the virus. They are also looking at other factors that modify the risk and severity of infections, such as gestational week at infection, additional morbidities and co-viral infection like Dengue fever.

CDC has not changed the travel warning or guidelines related to Zika infection after this publication.

Mark S. DeFrancesco, MD, MBA, President of the American College of Obstetricians and Gynecologists (ACOG), released the following statement regarding the U.S. Centers for Disease and Control and Prevention (CDC) paper addressing Zika virus “The message of the CDC paper underscores the importance of ongoing research into this outbreak. We once again encourage Congress to act swiftly to pass emergency funding to enhance our public health preparedness and enable America’s researchers to lead the charge in the development of a vaccine or treatment for this virus. Ongoing support for Zika virus research will protect American families and, indeed, families around the world."

References:
http://www.nejm.org/doi/full/10.1056/NEJMsr1604338?query=featured_home&
http://www.acog.org/About-ACOG/News-Room/Statements/2016/ACOG-Statement-on-the-CDC-Update-on-Zika-Virus
http://www.cdc.gov/media/releases/2016/s0413-zika-microcephaly.html

Tuesday, March 8, 2016

Maternal ZIKA virus infection linked to fetal and placental malformations, apart from Microcephaly.



The World Health Organization has declared the Zika virus an international public health emergency, with a prediction of about four million people being infected at the end of the year.

WHO has issued a travel warning for pregnant women advising them not to travel to areas with continuing outbreaks of Zika virus due to the potential risk of birth defects.

Sexual transmission appears to be more common than previously thought of. "Pregnant women whose sexual partners live in or travel to areas with Zika virus outbreaks should ensure safe sexual practices or abstain from sex for the duration of their pregnancy," the WHO said, based on advice from its Emergency Committee of independent experts.

According to a preliminary report of case series  from Rio de Janeiro, Brazil, published online March 4 issue of the New England Journal of Medicine, ZIKA is also linked to fetal death, placental insufficiency, IUGR and Nervous system malformation.

Dr. Patrícia Brasil, MD, the principal investigator of the study  “our findings provide further support for a link between maternal ZIKV infection and fetal and placental abnormalities that is not unlike that of other viruses that are known to cause congenital infections characterized by intrauterine growth restriction and placental insufficiency.”

In September, 2015 researchers in Brazil identified dengue like fever, which was later identified as ZIKV. In the same month the ZIKV was linked to microcepahy, cases in Brazil rocketed to 3,500 from 147, the average for the same time last year (2014).

The link was first detected when Brazilian health authorities found traces of the Zika virus in a deceased infant born with microcephaly or in amniotic fluid of mothers delivering microcephalic infants.

In the present study, the researchers enrolled pregnant women of any gestation, who presented with a rash that had developed within the previous 5 days. Out of 88 women, 72 (82%) women tested positive ZIKV in blood and/or urine by reverse-transcriptase polymerase chain reaction assays. The researchers followed the women prospectively with clinical examinations and serial ultrasound. All the study participants were generally healthy with no h/o congenital malformations.

Clinically the women presented with a macular or maculopapular rash, pruritus (94%) arthalgia (65%), conjuntival redness (58%). Fever was not a significant symptom with only one third of women reporting it.

All the ZIKV negative as well as positive women had ultrasound. USG showed abnormalities in 12 of ZIKV positive women while those women who are negative showed normal USG.  Sonographically detected abnormalities include:
  • intrauterine growth restriction, with or without accompanying microcephaly(5)
  • cerebral calcification (4)
  • CNS alterations (n = 2)
  • Oligohydramnios and anhydramnios (2)
  • Abnormal arterial flow in the cerebral or umbilical arteries(4)
  • additional malformations, including agenesis of the vermis, Blake’s pouch cyst, and potentially a club foot, in addition to cerebral calcifications, intrauterine growth restriction, and microcephaly(1)

Abnormalities were present in fetuses of women irrespective of there gestational age at ZIKV infection, although those women infected in first trimester show signs of insult during embryogenesis. CNS abnormalities seen in fetuses infected as late as 27 weeks.

Six live births and two still births occurred during the follow up and confirmed the Sonography findings.

The authors suggest that “many aspects of ZIKV infection are similar to those of rubella, particularly rash, arthralgias, pruritus, and lymphadenopathy in the mother without high fever.” But, it is worrisome that there is no population immunity for ZIKV as compared to rubella U.S. pandemic of 1959–1965, when only 17.5% of women of childbearing age lacked rubella antibodies.

In summary the study findings provide support to the hypothesis of link between maternal ZIKV infection and fetal and placental abnormalities. The women infected with ZIKV should be followed up closely with serial ultrasonography to evaluate for signs of placental insufficiency, given the risks of fetal death and intrauterine growth restriction.

References:
http://www.nejm.org/doi/full/10.1056/NEJMoa1602412?query=featured_home#t=articleDiscussion

 

Wednesday, February 3, 2016

All about Zika virus infection.



Zika Virus was first isolated from rhesus monkeys  in Zika forest in Uganda in 1947, but was barely in news till now as it did not cause outbreak in humans.

The Zika virus is a flavivirus, part of the same family as yellow fever, West Nile, chikungunya and dengue. But unlike some of those viruses, there is no vaccine to prevent Zika or medicine to treat the infection.

The incubation period of Zika virus disease is not clear, but is likely to be a few days. The symptoms are similar to other arbovirus infections such as dengue, and include fever, skin rashes, conjunctivitis, muscle and joint pain, malaise, and headache. These symptoms are usually mild and last for 2-7 days. But, majority of patients with this infection have no or very little symptoms, causing it very difficult to track. They can, however, still transmit the disease if they are bitten by a mosquito that then bites someone else.

Transmission
The Vector for Zika is  Aedes mosquitoes (which usually bite during the morning and late afternoon/evening hours. On Tuesday CDC reported the first sexually transmitted case of Zika virus in Dallas, Texas.  Previously, there have been only two documented cases linking Zika to sex and isolated cases of spread through blood transfusion.
In addition, the CDC says there have been documented cases of virus transmission during labor( vertical transmission ) , blood transfusion, and laboratory exposure. While Zika has been found in breast milk, it's not yet confirmed it can be passed to the baby through nursing.

Diagnosis
According to CDC- During the first week of illness, Zika virus disease can often be diagnosed by performing reverse transcriptase-polymerase chain reaction (RT-PCR) on serum. Serology assays can also be used to detect Zika virus-specific IgM and neutralizing antibodies, which typically develop toward the end of the first week of illness. Plaque-reduction neutralization testing (PRNT) can be performed to measure virus-specific neutralizing antibodies to confirm primary flavivirus infections and differentiate from other viral illnesses.


World Health Organization Director-General Margaret Chan declared the current outbreak as  a public health emergency on February 1, 2016, with 24 countries involved from South and Central America and the Caribbean involved in the outbreak.

Courtesy: Vox.com


Zika is commanding attention worldwide because of connection between the virus and microcephaly.


According to CDC, in the past four months, microcephaly cases in Brazil rocketed to 3,500 from 147, the average for the same time last year (2014).  About 46 babies have died due to birth defects.

The link was first detected when Brazilian health authorities found traces of the Zika virus in a deceased infant born with microcephaly or in amniotic fluid of mothers delivering microcephalic infants.

The first confirmed cases of ZIKV infection in Brazil were reported in May 2015.

Transmission of the virus in Brazil is likely to have started several months before because the disease is new and mild, and could have been unrecognised or misdiagnosed, as dengue and chikungunya epidemics were ongoing.

Microcephaly caused due to any infection is usually caused by transplacental infections occurring early in pregnancy and is only detected during the second half of pregnancy or after birth.

The observed six months delay between the recognition of the transmission of ZIKV in May 2015, and the detection of an increase in microcephaly in November 2015, is therefore compatible with a temporal association between the two events.

Currently there is only ecological evidence of an association between the two events, due to sudden epidemic of microcephalic babies born and clustered around a specific time period. Researchers are still working to confirm the link — could it be something else that's causing the microcephaly?

On 13 January 2016, the Brazil Ministry of Health reported the detection of Zika virus genome, through the RT-PCR technique in four cases of congenital malformation in the state of Rio Grande do Norte. The cases correspond to two miscarriages and two full-term newborns (37 and 42 weeks respectively) who died in the first 24 hours of life. Tissue samples from both newborns were also positive for Zika virus by immunohistochemistry

Obstetrical providers should obtain a travel history from all pregnant women and use recent travel history to guide decisions about testing.  Testing is not indicated for pregnant women without a travel history to an area with Zika virus transmission.

Courtesy: Vox.com


Diagnosis in pregnant patients.
Zika virus RT-PCR can also be performed on amniotic fluid.  Other testing that can performed includes the following: 1) histopathologic examination and immunohistochemical staining of the placenta and umbilical cord, 2) Zika virus testing of frozen placental tissue and cord tissue, and 3) IgM and neutralizing antibody testing of cord blood.

Amniocentesis should be offered to pregnant women with recent travel to an area with Zika virus transmission, reporting 2 or more symptoms within two weeks of travel and a positive or inconclusive maternal serum test.  For pregnant women with recent travel to an area with Zika virus transmission and ultrasound findings of microcephaly or intracranial calcifications, amniocentesis may also be considered.

A positive Zika virus RT-PCR result from amniotic fluid would be suggestive of intrauterine infection.  This information would be useful for pregnant women and their healthcare providers to assist in determining clinical management (e.g., antepartum testing, delivery planning).  A negative Zika virus RT-PCR result from amniotic fluid may prompt a work up for other causes of microcephaly (e.g., other infections, genetic disorders).

There is currently no cure for the Zika virus. A number of institutions are scrambling to develop a vaccine, but it could take up to five years, as health experts called for new incentives for drug companies.

Meanwhile, American women who are pregnant have been advised to stay out of countries where the Zika virus is circulating. The CDC recommends consulting your doctor before your trip and following steps to prevent mosquito bites during the trip.



References:
http://www.paho.org/hq/index.php?%20option=com_topics&view=article&id=427&Itemid=41484&lang=en

Sunday, January 17, 2016

Microcephaly in Brazil potentially linked to the Zika virus epidemic says European Center for Disease Control (ECDC).





photo by CDC PHIL, Aedes Mosquito


 
New European Center for Disease Control ( ECDC) risk assessment is currently evaluating a possible link between the observed increase of congenital microcephaly in Brazil and Zika virus (ZIKV) infection.

Until recent months Zika virus was not widely associated with microcephaly.

According to CDC, in the past four months, microcephaly cases in Brazil rocketed to 3,500 from 147, the average for the same time last year (2014).  About 46 babies have died due to birth defects.

The link was first detected when Brazilian health authorities found traces of the Zika virus in a deceased infant born with microcephaly or in amniotic fluid of mothers delivering microcephalic infants.

The first confirmed cases of ZIKV infection in Brazil were reported in May 2015.

Transmission of the virus in Brazil is likely to have started several months before because the disease is new and mild, and could have been unrecognised or misdiagnosed, as dengue and chikungunya epidemics were ongoing.

Microcephaly caused due to any infection is usually caused by transplacental infections occurring early in pregnancy and is only detected during the second half of pregnancy or after birth.

The observed six months delay between the recognition of the transmission of ZIKV in May 2015, and the detection of an increase in microcephaly in November 2015, is therefore compatible with a temporal association between the two events.

Currently there is only ecological evidence of an association between the two events, due to sudden epidemic of microcephalic babies born and clustered around a specific time period.

A possible causative association cannot be ruled out but further investigations and studies are needed to understand the association and the possible role of other factors, states the ECDC risk assessment.

In November the Brazilian Ministry of Health declared a public health emergency in relation to an unusual increase in the number of children born with microcephaly in 2015.

In addition to Brazil's findings, French Polynesian health authorities have also reported an unusual increase in autoimmune and central nervous system malformations in babies born during a Zika virus outbreak on the islands from 2014 to 2015. (73 cases, 42 of them being Guillain-Barré Syndrome, in a population of about 270 000). 

CDC map illustrates areas affected or possibly affected by the spread of Zika virus


Zika virus disease is a mosquito-borne viral disease caused by Zika virus (ZIKV), a flavivirus from the Flaviviridae family and is primarily transmitted through the bite of infected Aedes mosquitoes.

The virus was first identified in 1947 in the Zika forest in Uganda in the rhesus Macaque population and have two main lineages, the African lineage and the Asian lineage.

Prenatal or perinatal complications of ZIKV infections have not been described in the literature. There is some evidence that perinatal transmission can occur, most probably transplacental or during the delivery of a viraemic mother. However, materno-foetal transmission has been demonstrated for several other Flaviviruses (dengue, West Nile fever).

Some other Flavivirus infections are known to have the potential to cause premature birth, congenital defects and microcephaly.

The most common symptoms of Zika virus disease are fever, rash, joint pain, and conjunctivitis (red eyes). The illness is usually mild with symptoms lasting from several days to a week.

Meanwhile, Brazilian officials are also reporting neurologic complications in other Zika virus patients, primarily Guillain-Barre syndrome, which has also been seen in French Polynesian patients who had suspected infections. "Although neither even establishes a causal relation with Zika virus, the hypothesis cannot be ruled out," says a health official in Brazil.

In conclusion, a causative association between microcephaly in newborns and ZIKV infection during pregnancy is plausible, but not enough evidence is available yet to confirm or refute it. Many studies are needed before a definite conclusion can be reached.

There is no vaccine to prevent infection or medicine to treat Zika virus.

Meanwhile, CDC issues a travel advisory to pregnant women  to consider postponing travel to areas where Zika virus transmission is ongoing.




References: