29 January 2016

FEATURE: Fetal Anomaly, Screening and Abortion



The Zika virus: what it is and what it causes

The Zika virus was first recognized in Uganda in the Zika forest in the 1940s. Zika is a subtropical virus transmitted by the Aedes aegypti and Aedes albopictus mosquitoes, part of a group of diseases known as arboviruses, short for arthropod-borne viruses. Though it causes fever, rash and joint pain, it was not considered a menace until a connection between microcephaly and Zika was discovered in Brazil. Microcephaly is a rare neurological condition which causes abnormal smallness of the head. Sometimes only detected at birth, microcephaly usually is the result of the brain developing abnormally in the womb or not growing as it should after birth. It has several other causes, including genetic defects or rubella or cytomegalovirus in the mother during pregnancy.

Virologists say Zika has already reached "epidemic" proportions in El Salvador, where doctors were able to isolate the virus in some children suffering from microcephaly. An estimated 1.5 million people have been infected in Brazil, possibly leading to the recent growth in the suspected number of cases to 3,893 since authorities began investigating the surge in October, according to health ministry officials. The Health Ministry said most of the babies had been born with microcephaly in the country's poorest regions. Pernambuco, the first state to detect the problem, has had about 35% of all cases nationally. In October 2015, the Central Health Ministry decreed a National Public Health Emergency, set up a task force and sent a report to PAHO.

The Zika virus was first detected in May of 2015 in Bahia  and spread rapidly throughout the northeastern region. Soon afterwards, French Polynesian authorities also reported that they faced a Zika outbreak in 2013 with some microcephaly cases.

Mosquito that carries Zika virus
Photo James Gathany/AP

Local transmission of Zika virus has been found in 14 Western Hemisphere countries and territories: Brazil, Colombia, El Salvador, French Guiana, Guatemala, Haiti, Honduras, Martinique, Mexico, Panama, Puerto Rico, Paraguay, Suriname and Venezuela.  There have been recent reports from an additional six countries as well.

Many fetuses with the condition are miscarried, and many others die during birth or shortly after. Those who survive tend to suffer from developmental and health problems. Microcephaly has several other causes, including genetic defects or  rubella or  cytomegalovirus in the mother during pregnancy. There is no vaccine for Zika, but the National Institute of Allergy and Infectious Diseases has been working on one for the past month. Dr. Stanley Plotkin, a leading vaccine inventor, said a Zika vaccine "should not be extremely difficult to make" because the disease is closely related to  yellow fever  and Japanese encephalitis, for which there are effective vaccines.

This month, a British biotech company, Oxitec, said tests they began in April 2015 have shown that releasing genetically modified sterile male mosquitoes succeeded in reducing a variety of disease-transmitting mosquito larvae by 82% by year's end. The tests were carried out in the city of Piracicaba, in the province of São Paolo. The city's health department confirmed the tests and results. Joseph Conlon, a technical adviser for the American Mosquito Control Association, called the results "novel and potentially efficacious". Conlon said the procedure was not 100% effective, but if allowed to proceed to full measure, it would "reduce the mosquito population below disease transmission levels with minimal effect on the environment". He added that the Aedes aegypti were "notoriously difficult to control by conventional spray methods such as truck or aerial sprays".

Warnings against mosquito bites, against travelling to affected regions and above all against getting pregnant - even for up to the next 2 years - are being issued in more than one affected country.


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Tags: Latin America, fetal anomaly, Zika virus


Zika and microcephaly: can we learn from history?

from: Anthropology Now

by Ilana Löwy, a senior researcher at INSERM (Institut National de la Santé et de la Recherche Scientifique), CERMES 3, Paris. Trained as a biologist with a PhD in immunology, she then retrained as a historian of science and medicine. She is currently studying the history of birth defects and prenatal diagnosis in a comparative perspective.

Brazil is facing an epidemic of a severe birth defect: microcephaly (abnormally small head size), a condition linked with important neurological impairments and developmental delays. Not all children born with an abnormally small circumference of the head suffer from these problems, but many do. The microcephaly epidemic has been linked to an infection with the zika virus, transmitted by the mosquito Aedes aegypti.  [1] The latest epidemiological bulletin of the Brazilian Ministry of Health, dated January 5, 2016, reported 3,174 suspected cases. [2] Nearly all the cases of microcephaly were observed in the Northeast of Brazil, especially in the states of Pernambuco, Paraiba and Bahia. The Brazilian Ministry of Health declared the microcephaly outbreak a sanitary emergency, and advised women in the most affected regions to postpone pregnancies. The Health Ministry instructed hospitals with microcephaly cases to send samples of blood from newborns diagnosed with this condition, together with samples of placenta tissue (if available) and maternal blood, to a virology laboratory. There was no mention of the possibility of a prenatal diagnosis of microcephaly or of maternal and fetal infection with the zika virus - for a very clear reason.

It is possible to diagnose suspected microcephaly during an ultrasound examination in the third trimester of pregnancy, although the diagnosis is more difficult in borderline cases. It is also possible to verify whether a pregnant woman who lives in an affected region and suffers from a suspicious "fever" (often accompanied by a typical rash) is infected with zika, and if that is the case, to perform amniocentesis to check if the fetus is infected too. The question, however, is to what end? Finding out that a pregnant woman is at risk of giving birth to a child with microcephaly will only increase her anguish. There is no treatment which can prevent an abnormal development of the fetal brain, and since Brazilian laws do not allow abortion for a fetal indication with the sole exception of anencephaly (the absence of a brain), she cannot elect to interrupt the pregnancy.

The Brazilian government focuses its efforts to stop the microcephaly epidemic on fighting the spread of zika infections, undoubtedly an important goal, but difficult to achieve rapidly. In the meantime, Brazilian specialists such as Maria Angela Rocha, a pediatrician from Para Thomaz Gollop, a fetal medicine expert from São Paolo, who was interviewed by Folha de São Paolo, December 1st, 2015 and the virologist Pedro Vasconcelos (interviewed by O Globo, December 5th, 2015) have expressed their despair and feeling of impotence when observing the rapid progress of cases of microcephaly. As Dr Vasconcelos put it, "We have our feet and hands tied down". [3]

It is important to examine the accuracy of this statement, and whether physicians' inaction is the only possible answer to the mounting numbers of children born with severe neurological impairment in Brazil. There is important historical precedent: doctors' reaction to infection with rubella (German measles). A woman infected with the rubella virus in the first trimester of pregnancy is at high risk of giving birth to a child with severe fetal malformations. The rubella virus attacks the fetal central neural system and can induce numerous fetal malformations: blindness, deafness (and not infrequently a combination of both), neurological problems and microcephaly. It is impossible to predict the extent of such malformations: some children born to infected mothers are healthy, some have sensory impairment(s) but no additional health problems, some have severe neurological and cognitive problems. Many women who contracted rubella early in pregnancy and were aware of links between this disease and a risk of fetal malformations wished to terminate the pregnancy. In the 1940s, '50s and '60s, abortion was criminalized in Western Europe; doctors who performed abortions risked prison and the loss of their medical licenses. In spite of these legal restrictions, numerous British and French doctors provided abortions to pregnant women infected with rubella. [4]

Not all physicians in the UK and France believed that rubella infection during the first trimester of pregnancy justified abortion. Physicians held different opinions about abortion for fetal impairment; they also had divergent evaluations of the risk of birth defects linked to rubella infection. Animated debate among physicians had limited practical consequences, however. In the 1950s and '60s, British and French women infected with rubella early in pregnancy who were aware of the risk of fetal malformations and wanted abortions were nearly always able to find practitioners willing to brave legal interdictions, either in private practice or, in the great majority of cases, in public hospitals and clinics. In a widely debated paper on rubella and abortion published March 14, 1959 in the British Medical Journal, the pioneer of medical genetics, Julia Bell of University College, London, stated that "now the facts of the situation have accumulated so that one can state without doubt that rubella in the early weeks of pregnancy is such a menace to the normal development of the fetus that it constitutes a risk one cannot allow to be taken for the unborn child." Abortion, Bell explained - 10 years before the legalization of abortion in the UK - had become the generally recognized treatment for the risk of fetal malformation induced by infection with the rubella virus: "to such an extent has this become routine treatment that maybe we can no longer hope to get measure of the risk involved or discover what proportion of such occurrences can be expected to result in a normally developed child". [5]

In the mid-20th century, experts who argued that women who contracted rubella early in pregnancy should be allowed to elect abortion spoke about a risk of suffering for the child and the family, not the certainty of such suffering. People with severe impairments could live happy and fulfilling lives; their families need not face distress and could find unexpected joy in raising an impaired child, especially with support from the larger society. Nevertheless, the concern that the birth of a severely impaired child may be a source of distress and difficulty for the child's mother and other members of her family is no less valid in 2015 than it was in 1959. Only a pregnant woman, many doctors believed in the mid-20th century, could decide whether she was ready and capable of caring for a special needs child, not infrequently for life.

Brazilian women today are not legally entitled to make such decisions, and in this area like many others, poor women have more circumscribed choices than affluent ones. And the number of newborns born with microcephaly is steadily increasing. Some experts fear that the epidemic of neurological impairments might be more severe than current evaluations suggest. These are based exclusively on measuring the circumference of the newborn's cranium, but children born to infected mothers can have a normal head size and still suffer brain lesions which will induce neurological and cognitive difficulties.

Microcephaly is scary. As reported in an article published by BBC Brazil on December 15, 2015, pregnant women in rural zones of Pernambuco say they are terrified by what they know about the zika epidemic and its consequences.  [6] Brazilian doctors have no answer to their fears. Public health experts are predicting 15,000 cases of microcephaly - and possibly up to 50,000 zika-induced birth defects-before the end of 2016.  [7] When asked about the possibility that women will be allowed to abort fetuses at risk of birth defects induced by zika, the answer is: "Abortion is a crime."

In another time and place, physicians who, like their Brazilian colleagues today, worked in countries that criminalized abortion, had a different attitude. In a letter to the British Medical Journal dated April 25, 1959, British obstetrician Bevis Brock of St. Bartholomew's Hospital, London explained there is a widespread agreement that "when a pregnant mother, having had rubella, is aware of the risks and is prepared to face them, then no one would try to persuade her to accept termination. But if she feels unable to face the appalling anxiety of a pregnancy overshadowed by fear of a blind or deaf child, then it requires strong convictions to refuse this request". [8]

One must wonder whether Brazilian doctors' unwillingness to consider interventions beyond the strict limits of the law reflects such strong convictions, or is influenced also by the fact that the majority of women at high risk of giving birth to children with microcephaly live in poor, often neglected areas.

Tags: Brazil, antenatal screening, fetal anomaly, zika virus, abortion



Non-invasive prenatal testing for Down's syndrome: a briefing

by Jane Fisher, Director, Antenatal Results and Choices (ARC), a UK charity providing non-directive information and support  to parents through prenatal screening and its consequences.

Where Down's syndrome (DS) screening is offered prenatally, the recommended test is usually what is known as 'combined screening'. This includes an ultrasound scan to measure a pocket of fluid at the back of the fetal neck. The detection rate is between 85-90% with a screen positive rate of 3-4%. 'Screen positive' refers to those women who get a result that represents a chance of the baby having DS that falls within a certain threshold (this is a 1 in 150 chance or higher in the UK). Most of these women will not have an affected pregnancy because the screening test is not very precise. This means a significant proportion will opt for diagnostic testing (which puts the pregnancy at risk), and a number of miscarriages will occur when there was no chromosomal problem.

It is important to note that in public health prenatal settings, DS screening is 'offered' rather than performed as routine. Uptake rates vary internationally; in the UK, between 65-70% of pregnant women choose to be screened. Combined screening can be performed between 10-14+1 gestational weeks. For women who fall outside this window, biochemical screening is usually offered (with a lower detection rate) from 14-20 weeks.

At present, thousands of women will be classed as 'screen positive' and offered invasive testing. Very few of these women will actually have a baby with Down's syndrome, so many will have had a small but always significant risk of miscarriage.

In the UK, of those women who have diagnostic testing for DS and are told their pregnancy is affected, 90% decide to terminate the pregnancy.[1]  While this percentage is not uniform internationally, we know the majority of women terminate after a positive diagnosis.

Non-invasive prenatal testing (NIPT)
Advances through research into prenatal cell-free fetal DNA testing (commonly known as NIPT) has led to a more accurate method for assessing the probability of Down's syndrome. It can be done from 10 weeks' gestation onwards and involves a maternal blood test (though a scan should always be performed beforehand to check the gestational age of the fetus and whether it is a singleton or multiple pregnancy). The sample is sent to a lab and cell free maternal and fetal DNA is extracted from the serum for the analysis. For more information on the science see www.rapid.nhs.uk. It is now clear from published evidence that it is a very accurate screening test with a detection rate of around 99%.[3]  Because there is a very small false positive rate, it  remains a screening test for DS and women are advised to have a diagnostic test for a conclusive result.

NIPT has been available in private health care settings since 2012 (at an average cost of US$ 500). It has been marketed by different biotechnical companies with brand names such as Harmony, Nifty, MaterniT21, Verifi and Panorama. Millions of women have taken up private testing and it is proving a very lucrative business for the companies involved.

NIPT is also starting to be implemented into public health prenatal screening programmes (an announcement on its introduction into the English National Health Service was made on 15 January 2016) as the evidence suggests it will both improve detection and, importantly, reduce the 'screen positive' rate - meaning far fewer women will undergo invasive diagnostic tests. This will significantly reduce the number of procedure-related miscarriages.  International professional bodies recommend that NIPT is offered as a contingent screen (i.e. to women who are 'screen positive' from conventional screening or at higher risk of having a baby with DS for other reasons such as maternal age or previous affected pregnancy), and the consensus is that diagnostic testing is required for definitive confirmation.[4] 

What are the ethical concerns?
Advocates for those living with Down's syndrome and anti-choice campaigners have been vocal in suggesting that NIPT represents 'eugenics through the back door' and will lead to an eradication of people with Down's syndrome.[5]  They believe there will be more terminations because there will be more prenatal diagnoses and women will feel compelled to have the testing because it is risk free.

In fact, their argument is not so much about the new technology, but more that expectant parents are making what they consider ill-informed choices when they terminate the pregnancy after a positive diagnosis. They assert that the information about the condition provided to parents is overly negative and based on a medical rather than social model of disability.[6]  There is a fear that DS screening will become completely routinized and that health professionals will be less likely to caution women about potential outcomes, given that fewer women will have to consider invasive 'risky' testing.[7,8] 

Many campaigners do not believe Down's syndrome is a serious disability because treatments for associated health issues have improved and mainstream education in many countries makes more provision for children with learning disability. There is an international campaign to problematize prenatal screening and claim it is eugenic in purpose.  In the US, moves have been made to restrict abortion on the grounds of Down's syndrome,[9]  and these tactics are likely to be taken up elsewhere. Campaigners use compelling images of cute children with Down's syndrome
[10] and point to the achievements of those who are at the higher end of what is a spectrum condition.[11] It is a strategy that plays well in the media but leads to those who make the decision to terminate the pregnancy feel judged and stigmatised.

Are there valid concerns?
The simple answer is no. NIPT for Down's syndrome is a positive development because it will lead to fewer risky invasive tests and thus fewer procedure-related miscarriages. At the moment we have the inequity that only women who can pay have access to more effective testing. Of course we need to ensure that women and couples are properly counselled before testing and enabled to make individualised choices at all stages.

We cannot be sure how exactly the implementation of NIPT into current public health screening programmes will affect the termination rate. Two research studies in the UK have found that some women who would previously not have opted for DS screening decided to go for it when NIPT was included because they wished to be informed prenatally, knowing they would not terminate, but did not want to have diagnostic procedures that carried a risk. Those that had a positive NIPT used the result to prepare themselves for having a baby with Down's syndrome.
A Dutch study came to similar conclusions. [14]  So as well as reducing fetal losses, the introduction of NIPT could also expand choice for women. 

As ever, we can trust women and couples to make the decisions that are right for them in their individual circumstances regarding prenatal testing. At ARC we know this happens now, and there is no reason to think it will change.

[References available on request]

Tags: UK, antenatal screening, fetal anomaly, Down's syndrome, abortion