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Women and Gender Studies, Italian Style Veronica Pravadelli UNIVERSITY ROMA TRE In March 2009 the University of Roma Tre hosted the conference 'Gendering the Academy: Italian Experiences and Experiments', sponsored and organized by the European Journal of Women's Studies via Paola Bono, professor at Roma Tre and associate editor of the journal. The conference focused on the teaching and research on women and gender as well as on the status of the female academic population in Italian universities. It aimed at detailing the 'national specificity' of such experiences in relation to other international contexts. One can indeed argue that there is such a thing as an 'Italian style' in gender studies and that it can be grasped and framed within a cultural, historical and generational perspective. Starting from the conference's premises I would like to present the main contours of these experiences.

It has often been claimed that the peculiarity of Italian feminism resides in its dual nature, namely its mobile position between theory and practice, academic research and politics. In their impressive anthology of Italian feminist writings, in 1991 Paola Bono and Sandra Kemp claimed that the most distinctive feature of Italian feminism is its non-institutional basis, a result of 'the importance of politics for Italian feminism, reflecting the strongly political character of Italian society in general'. In this fashion 'Italian feminism helps bridge an uncomfortable inconsistency between feminism's theoretical refusal to countenance "master narratives" and the political ascendancy of certain canonical texts in France, Britain and America' which rapidly became 'classic feminist texts'. While in these countries feminist theory has become increasingly institutionalized, some have started to blame its supposed results, the 'rift between the theoretical and the personal, writing and life'. On the other hand, so far 'there have been no "women's studies" . . . in Italian universities'. Instead of trying to institutionalize these issues, in Italy feminist scholars 'manage to carve out a space in the curriculum as it is' (Bono and Kemp, 1991: 2-3; on this topic see also [START_REF] Lauretis | The Essence of a Triangle or, Taking the Risk of Essentialism Seriously: Feminist Theory in Italy, the US, and Britain[END_REF]. Such a position has been the dominant one in Italian feminism: that is, in Italy the lack of institutionalization of women's studies has been consciously decided by feminists. The antiinstitutional thrust of Italian feminism has been pursued by relentless separatist strategies. However, a younger generation of female academics, 'around 40', mainly educated abroad, has recently developed. As we see, such a generation supports a different view on these matters. In order to grasp the specificity of the Italian context it is first necessary to dwell on its historical development.

In the 1970s western feminists, not simply Italians, debated their status vis-a-vis any institutional context, especially academia. At that time many believed, on both sides of the Atlantic, that the radical thrust of feminist thought could not develop simply within the institutional arena of the university. Moving in and out of academia and of the women's movement defined the very nature of feminism in any western country. In the heyday of 'the personal is the political', feminists working in academia were also active in feminist groups and engaged in the battles for women's rights. The convergence between theory and practice can also be tested at another level: feminist academics worked alongside non-academics in different social contexts and cultural practices. To give just a couple of examples drawn from my specific area of research, we can think of the peculiar convergence of women's cinema and feminist film theory in the 1970s and early 1980s. In those days, filmmakers, academics, cultural critics and activists regularly met at film festivals, at screenings in colleges and artistic venues to discuss, to be brief, the politics and aesthetics of women's experimental cinema [START_REF] Rich | Chick Flicks: Theories and Memories of the Feminist Film Movement[END_REF]. It is important to stress that such debates always involved theoretical concerns to the extent that, for example, many films included a discussion of feminist (and) psychoanalytic theory or a visual representation of psychoanalytic processes. E. Ann Kaplan coined the term 'avant-garde theory-film' for works in which 'theory is worked into the text as an integral part of its form' (Kaplan, 1983: 142). A similar convergence between politics and theory is at the heart of Laura Mulvey's seminal piece 'Visual Pleasure and Narrative Cinema' [START_REF] Mulvey | Visual Pleasure and Narrative Cinema[END_REF]. While Mulvey was not an academic when she wrote the piece, but became one later, we should first of all recall that the strength of her essay resides in its unparalleled fusion of a militant rhetoric with an extremely sophisticated theoretical apparatus. Interestingly, in a recent reassessment, Mandy Merck has interpreted the piece as a political manifesto in the tradition of Futurism and Surrealism [START_REF] Merck | Mulvey's Manifesto[END_REF]. And Mulvey was both a theorist and an avant-garde filmmaker. I have brought up these two examples in relation to British and American feminism in order to suggest that the alliance between theory and practice, in the early stages of feminism, was an essential feature of western secondwave feminism. At the time the primary tenets of the debate were clearly theoretical, in the sense that there was no gap between theory and politics. To put it more clearly, the alliance between theory and practice, institutional and non-institutional contexts, was the historical specificity of 1970s feminism.

In this light, the experience of Italian feminism was totally congruent with that of other western countries. As in other national contexts, Italian academics have been teaching 'women's issues' in many disciplines since the mid-1970s. The international and cosmopolitan thrust of 1970s feminism can also be appreciated if one looks at the reception and translation of important works into Italian. The interdisciplinary journal dwf.donnawomanfemme, founded in 1975, has been for many years the most important feminist journal. Dwf has pursued a consistent politics of translation. It readily translated the two most quoted feminist essays of the 1970s, Gayle Rubin's 'The Traffic in Women ' (1975/1976) and Mulvey's 'Visual Pleasure andNarrative Cinema' (1975/1978). The journal also translated Adrienne Rich's 'Compulsory Heterosexuality and Lesbian Existence' (1980/1981) as well as essays by feminist sociologists and historians such as Linda Gordon, Ruth Milkman and others. Book-length studies were translated with a similar eagerness: we may think of the early Kate Millet's Sexual Politics (1969/1971) and Shulamith Firestone's The Dialectic of Sex (1970/1971), Juliet Mitchell's Psychoanalysis and Feminism (1974/1976), Adrienne Rich's Of Woman Born (1976/1977), and of the Boston Women's Collective's Our Body, Ourselves (1974Ourselves ( /1974)), which was the first of some 20 translations around the world (Davis, 2007: 214-16). The major exponents of French feminist thought were also made available to the Italian audience: consider Luce Irigaray's Speculum (1975/1976) and Ce sexe qui n'est pas un (1977/1978), and Monique Wittig's Le Corps lesbien (1973/1977). In the following decade we should recall at least Joan Scott's fundamental essay 'Gender: A Useful Category of Historical Analysis ' (1986/1987), which spurred a lively debate among Italian women historians.

While the impact of Italian feminism abroad cannot be compared to American, British and French thought, we should at least recall the important contribution to the international debate made by major thinkers such as Teresa de Lauretis and Rosi Braidotti. Educated in the Department of Semiotics at the University of Bologna, directed by Umberto Eco, de Lauretis moved to the US and became, in the 1980s, one of the leading feminist cultural theorists. One can safely argue that her first major book in English, Alice Doesn't: Semiotics, Feminism, Cinema (de [START_REF] Lauretis | Alice Doesn't: Semiotics, Feminism, Cinema[END_REF], combines in an original fashion the Italian and the American intellectual contexts she was part of.

While British and American feminist thought has developed evenly in most disciplines of the human and the social sciences, in Italy feminist scholarship has not flourished consistently. Italian feminist thought has produced a massive corpus of scholarship in history, philosophy, psychoanalysis, literary studies and sociology. Important contributions have been made in other disciplines, for example, anthropology, film and media studies. Yet, in these and other fields feminist work has been more sporadic. In order to capture the status of recent and current trends, I believe it is necessary to map out the basic tenets of the 'Italian tradition' in feminist scholarship (Di Cori and Barazzetti, 2001;Kemp and Bono, 1993). I think that the most original work has been produced mainly in the fields of history and philosophy. For this and other reasons, which can only partially be addressed here, I limit myself to detail briefly the research done in these two disciplines.

From a national and international perspective, I believe we can safely argue that the most famous experience of Italian feminism is the 'theory of sexual difference' associated with the Milan Women's Bookstore Collective, the group Diotima and the work of philosophers Luisa Muraro and Adriana Cavarero. Sharing Luce Irigaray's assumption that western philosophy had negated women a place in the Symbolic order, through a severe separatist practice known as 'autocoscienza', Italian theorists devised a conceptual framework aiming at attaining a consciousness of self as sexed subjects. Teresa de Lauretis has suggested that although this practice was adapted from North American feminism, because Italy is not only more pervasively gender-segregated but 'more thoroughly politicized than the United States', the impact of this practice was perhaps more significant for the development of feminist theory in Italy than in the US (de [START_REF] Lauretis | The Practice of Sexual Difference and Feminist Thought in Italy: An Introductory Essay[END_REF]. Like their French counterparts, Italian feminists argued against equality and for difference by building a rhetorical and conceptual apparatus that conjured up notions such as female genealogy and maternal symbolic order. The theory and practice of Italian sexual difference is built around two phases. While the separatism of female groups first produces a collective female subject different from men, in the second phase a relational practice among women establishes and recognizes differences among women. Therefore, 'the signifier Woman gives way to a female symbolic order that links each individual self to other women according to the practice of entrustment and difference' (Cavarero, 2002: 98; see also [START_REF] Cavarero | Towards a Theory of Sexual Difference[END_REF]. In this fashion Italian feminists recuperate the figure of the mother in a totally different way vis-a-vis the psychoanalytic uses of international feminism. Luisa Muraro's notion of the symbolic mother is central: for Muraro the mother-daughter relation is the basis for the construction of female subjectivity. For the daughter the mother is the source both of material and symbolic life, since she fuses on her own body the traditional binary opposition between mother/body and father/language [START_REF] Muraro | L'ordine simbolico della madre[END_REF]. Thus conceived, the mother-daughter relation is the most important and radical example of entrustment (affidamento), in which 'one woman gives her trust or entrusts herself symbolically to another woman, who thus becomes her guide, mentor, or point of reference -in short, the figure of symbolic mediation between her and the world' (de Lauretis, 1990: 8-9). Read in conjunction with French theorists of sexual difference, this project has influenced enormously scholars working in literary and film studies. The most popular paradigm, to be brief, is a consideration of literature and artistic creation as the 'writing of the body' via a formal practice known as 'female language' (on cinema and female language, see Detassis and Grignaffini, 1981;[START_REF] Pravadelli | Performance, Rewriting, Identity. Chantal Akerman's Postmodern Cinema[END_REF].

While theorists of sexual difference have dominated the discipline of philosophy, women historians have pursued different lines of investigation. If the relation to the feminist movement has led researchers to take women as their object of study, in order to 'make women visible', from a methodological perspective Italian women's history has positioned itself in the tradition of microhistory, especially in relation to the 16th and 17th centuries. As we know, in all areas of research feminists have had to investigate the past in order to bring to light the work done by women. This strategy is obviously more evident in history. As Annarita Buttafuoco has stated, 'Historiography is that "technique" which is prompted by its specific status to devote itself to dissipating amnesia and cultivating memory. However, it too acts in a selective manner, leaving some experiences in limbo, and bringing others to light, according to the personal and social "point of view" which orientates the researcher' (Buttafuoco, 1993: 172). The relation between women, religion and the church is one of the most popular areas of research. Female historians have studied the lives of nuns, saints, and mystics in the medieval and the modern period along the following lines: women's critical stance towards institutions, women's material life and culture and female agency [START_REF] Scaraffia | Women and Faith: Catholic Religious Life in Italy from Late Antiquity to the Present[END_REF][START_REF] Zarri | Recinti. Donne, clausura e matrimonio nella prima età moderna[END_REF]. Feminist philosophers such as Luisa Muraro have similarly approached the topic from a theological perspective [START_REF] Muraro | Guglielma e Maifreda. Storia di un'eresia femminista[END_REF]. The study of the legal system in relation to ownership has led to investigate different status of women and men vis-a-vis such matters. As in other countries, women historians have researched extensively on such fundamental issues as marriage, work and motherhood (Rossi-Doria, 2003). While other areas and topics have been investigated, what interests me at this juncture is another level of the debate. Women historians have been particularly sensitive to reflect on the paradigms of their research and to recognize the validity of foreign contributions as well as their own pitfalls. Simonetta Soldani has pointed out, for example, how works done abroad on totalitarianism have allowed Italians to deal in a less monolithic fashion with such binary terms as public/private, fascism/anti-fascism. She has also lamented the paucity of works in the realm of material culture and in the 'history of everyday life'. Finally, Soldani has called for the transition to 'the cultural turn' in the study of contemporary Italian history [START_REF] Soldani | L'incerto profilo degli studi di storia contemporanea[END_REF]. Commenting on the status of gender studies in American history, Raffaella Baritono and Elisabetta Vezzosi have made further suggestions: they claim that Italian women's history 'should start to rebuild the networks among women in a transnational context' by looking at how similar historical episodes have been experienced by women in different national contexts. They also point to the necessity, for Italian scholars, to broaden their areas of enquiry by working more thoroughly, for example, on the construction of masculinity [START_REF] Baritono | Gli studi di storia americana tra Italia e Stati Uniti[END_REF].

It seems to me that it is precisely along these lines that a new generation of scholars is moving. The theory of sexual difference has been fundamental to the development of feminist thought and subjectivity. Its method and practice were congruent with the historical moment, namely, they were fit to rescue women from the position of the object and promote the construction of woman as subject. The present historical moment calls us to a different approach. In many disciplines of the human and the social sciences, a generation of gender scholars 'around 40' is thriving with new ideas and strong passions. These women (and a few men) have often been educated abroad, especially in the US, but also in England or France. They are part of a cosmopolitan academic milieu, a transnational gender studies approach that has slowly shaped up; for this reason, they often feel closer to certain foreign experiences than to the Italian feminist tradition. Their work is integrated within their specific disciplines since no women's studies programme exists in Italy. Yet, the study of gender is approached from a cultural and historical perspective in the attempt to preserve the specificity of 'local' contexts and experiences. The convergence between gender, cultural and historical perspectives is, to my mind, the most viable approach for understanding the status of women and gender in different cultural and/or national contexts. But it is also, for Italian gender scholars, the only way to affect their fields of enquiry and to rescue gender from the marginal position it has always had in Italian academia.

European Journal of Women's Studies 17(1)


1 Defending biomedical authority and regulating the womb as social space:

Prenatal testing in the Polish press

In 1998-9, a bill to introduce provisions into the Polish criminal code and law on the medical profession 'for the protection of the conceived child from experiments interfering with its development' i was debated in the Polish Sejm (lower house of Parliament) and Senate (upper house). Proposed by MP Antoni Szymański of the right-wing political grouping AWS (Solidarity Election Action), this amendment aimed to strengthen the legal protection of the health and life of the 'unborn child'. In particular, the bill proposed access to prenatal testing, specifically, amniocentesis ii , be legally permissible in only three cases: when a sibling was 'genetically burdened'; when there was suspicion of a genetic disease which could be treated in the mother's womb and when there was suspicion of the heavy disability of the foetus. The bill included pre-natal tests within the provisions of law relating to medical 'experiments', and excluded access to tests for women aged 35 or over, customarily defined as 'high risk'. Developed without consultation with medical professionals, and accompanied by considerable comment and analysis as well as opinion polling on the issue, this controversial bill passed its second reading in the right-wing dominated Sejm. It was referred to the Senate for amendment, traditionally sympathetic to the 'pro-life' position.

However, after consultation with the medical community, the Senate Committees rejected the majority of the bill's provisions. The Sejm accepted the Senate's position, and no limits on access to pre-natal testing were introduced into law. This paper offers an analysis of the ways in which the meaning of prenatal testing was constructed and communicated through newspaper coverage of this legislative initiative.

The medical profession plays a considerable role in mediating women's access to reproductive healthcare services whilst biomedicine 'holds a status analogous to the that of the established Church in the medieval period' (Ettorre, 2002: 19).

However, the terms of this legislative initiative around amniocentesis significantly challenged Polish biomedical knowledge and authority, with the usually silent medical community commenting publicly and vociferously on the bill and politicians unusually muted in their public response.

Although the technology of prenatal testing diffuses geographically, the culture of medical ethics does not similarly diffuse [START_REF] Rapp | Testing women, testing the foetus: The social impact of amniocentesis in America[END_REF]. How the medical ethics governing the relationship between medical professionals and women patients is described, problematised and understood varies according to cultural context. In the course of amniocentesis debates, and reproductive debates in general, 'biomedical discourses transform women's wombs into highly managed social spaces -sites of discourses about 'good' genes, women-as-foetal-incubators, 'good enough' foetal bodies and disability' (Ettorre, 2002: 21).

The majority of studies examine pre-natal testing in geographical areas where abortion is (relatively) easy to access and unpoliticised. Few studies analyse the social meaning and significance of prenatal testing where (legal) abortion is very difficult to obtain, and where debate around prenatal testing is 'high key' and politicised. The relationship between the politicisation of abortion and the politicisation of prenatal testing thus remains poorly understood.

Pre-natal testing in pregnancy and foetal healthcare

The routinisation of pre-natal diagnosis has accompanied the medical professionalisation of pregnancy through which the pregnant body has been increasingly constructed, regulated and disciplined through medical knowledge and management. Across the industrialised world, pregnant women are routinely screened for foetal abnormalities. After screening pregnancies are identified as being 'high' or 'low' risk, with women in high-risk groups referred for additional testing through prenatal diagnosis (ultrasound, amniocentesis, chorionic villus sampling or genetic tests) to ascertain whether the foetus carries the suspected abnormality. Performed at between 16 to 18 weeks gestation in conjunction with ultrasound, to diagnose Down's syndrome, blood type, metabolic and neural problems, amniocentesis iii is an invasive procedure which 'involves the insertion of a long thin needle into the pregnant woman's abdomen to withdraw a sample of amniotic fluid, which is then cultured for genetic diagnosis' (Farquhar, 1996: 174). Prenatal testing operates in the language of risks and probabilities: it is risk that has legitimated the widespread diffusion of ultrasound and amniocentesis, as well as the motivation for women to undergo these procedures [START_REF] Mitchell | Baby's first picture: Ultrasound and the politics of fetal subjects Toronto & London[END_REF]. In particular, advanced maternal age is linked to increased risk since 'a higher percentage of women over thirty-five give birth to Down's syndrome babies than women under thirty-five' (Ettorre, 2002: 24). However, prenatal testing cannot eliminate disability: only 10-20% of disabled people have congenital conditions, most of which would not be picked up by screening (Shakespeare, 2006).

The routinisation of prenatal technologies has had specific consequences for women's health care and experiences of pregnancy. Reproductive technology can be both liberating or socially controlling, depending on each particular woman's life experiences and context, while the experience of pre-natal testing is itself socially differentiated [START_REF] Rapp | Testing women, testing the foetus: The social impact of amniocentesis in America[END_REF]. Prenatal testing has institutionalised anxieties about potential foetal impairment, normalising and valorising non-disabled children, whilst simultaneously burdening women who do not produce non-disabled children with the the discourse of shame, of a flaw, mistake or wrongdoing. Moreover, the routinisation of pre-natal technology has enabled the erosion of women's reproductive autonomy, often making women into 'objects of medical care rather than subjects with agency and rational decision-making powers' (Ettorre, 2002: 20). However, debate remains as to the degree to which women experience prenatal technologies as universally oppressive: women are not simply or only victim to prenatal technologies: they 'accept, invoke, and adapt these technologies' for their own use (Farquhar: 1996: 172). Moreover, women can obtain pleasure as well as 'anxiety, frustration, uncertainty, and sadness' from viewing their foetus through ultrasound (Mitchell, 2001: 184).

As part of the routine medical surveillance of pregnancy, its character, quality and progress is now diagnosed and described in relationship with a doctor. The angle of vision centres on the foetus, and women's bodies disappear, whilst the foetus emerges as a 'social person' in its own right [START_REF] Draper | It was a real good show": the ultrasound scan, fathers and the power of visual knowledge[END_REF]. Moreover, the foetus has become both a patient in its own right, 'treated' and monitored during the pregnancy and a rights-bearing entity, which Bordo calls a 'supersubject' (Bordo, 1993:71). For example, Mitchell notes how ultrasound 'is sometimes used as a window onto an endangered fetal self or onto a woman whose body or behaviour must be corrected' (Mitchell, 2001: 175). Thus as Ettorre notes, the development of reproductive technologies 'are shaping new values for the standards of reproduction -values to which all pregnant women are told they should conform' in the genetics moral order (Ettorre, 2002: 19).

Both feminists and those writing from a disability studies perspective have much critiqued the stated aim of prenatal screening to offer reproductive 'choices'.

Rothman has argued that 'taking the least-awful choice… is experienced as being trapped, caught' while as Ettorre notes, 'choosing' selective abortion may be 'shaped by docility and pain' (Rothman, 1986: 181;Ettorre: 2002: 40). Others have been concerned that prenatal testing diminishes women's choices, since termination following a specific diagnosis is socially expected (Parens & Asch, 1999). Rapp meanwhile notes that in the USA pre-natal counselling minimises differences between women across racial, ethnic, religious and class backgrounds since 'the pregnant woman is counselled as if her choices were individual, unconstrained by larger constellations of kinship and community' (Rapp, 1999: 58). Furthermore, the experience of undergoing amniocentesis is experienced by women not just as a choice but also as a burden because reproductive responsibilities are distributed unequally (ibid). Both those writing from a feminist and disability rights perspective have shifted from examining the individual/ised 'choices' women make, towards examining the social contexts within which such decisions are made [START_REF] Mclaughlin | Screening networks: Shared agendas in feminist and disability movement challenges to antenatal screening and abortion[END_REF].

Selective abortion asks pregnant women to experience 'tentative' pregnancies which cannot be confirmed until the foetus has been pronounced healthy and 'normal' (Rothman, 1986). Given that few of the disorders identified through prenatal testing are curable, most foetuses with abnormalities are terminated: prenatal testing is only possible 'when enrolled by and through legal access to abortion' (Rapp, 1999:33). These are among the most socially acceptable abortions in the USA, UK and Polish contexts. They require that pregnant women play a 'gatekeeper role,' making moral and social judgments about 'who is fit to be born' (ibid.). However, given that prenatal screening aims to 'to reduce the numbers of children born with disabilities', commentators have noted its connectedness to eugenics as well as the possibility that it logically discriminates against disabled people, either directly or indirectly (Santalahti et al, 2001: 112; see also [START_REF] Sharp | Feminism, Disability and Abortion: Irreconcilable Differences?[END_REF]. What remains central to both feminist and disability rights positions is that the meaning of choice must be questioned, and the contexts which shape selective abortion decisions must be explored [START_REF] Mclaughlin | Screening networks: Shared agendas in feminist and disability movement challenges to antenatal screening and abortion[END_REF].

Reproductive politics and healthcare in Poland

Despite having real and material effects on women's lives, postcommunist abortion debates across East Central Europe are debates about the nature of democracy and the character of the nation-state (Gal and Kligman, 2000: 30). In the Polish context, which has been marked by the influence of the Roman Catholic Church, the terms of abortion debate have addressed the proper shape of the postcommunist nation-state, gendered citizens, civil society and the legitimacy of political authority (reference; reference; reference). Reproductive politics continues to inform the Polish political agenda, closely reported by the press and wider media. Abortion law has changed three times in Poland since 1989 iv with access restricted in 1993 to allow for abortions in four situations: irreparable damage to the foetus; endangerment to the health or life of the pregnant woman; or if pregnancy resulted from rape or incest. Abortion law was liberalised in 1996 to allow for abortions on social grounds. With the liberalised law found 'unconstitutional' by the Constitutional Court, the 1993 'anti-abortion' law was re-introduced in 1997. It remains extremely difficult to obtain an abortion legally with doctors often refusing to refer women on grounds of 'conscience' (reference). Despite the operation of a restrictive law by European standards, pro-life movements are also still very much mobilised and campaign to further restrict access to abortion.

With the exception of debate around the use of the 'conscience clause ' in 1997 (reference), and in contrast to abortion debate in the UK and USA, medical professionals have been rarely visible as 'subjects' of and 'authorities' on, abortion debate in the Polish context (reference). In the early nineties gynaecologists were stigmatised and 'isolated within the medical community', constructed as financial beneficiaries of liberal abortion law and complicit with the 'annihilation' of the Polish nation under state socialism when abortion was available on demand [START_REF] Nowicka | Ethical Considerations on Anti-Abortion Law, Poland: Safe Abortion: A WHO Technical Consultation, To develop technical and policy guidance for healthy systems[END_REF]. In this context it is unsurprising that medical professionals have, by and large, been unwilling to speak in favour of abortion liberalisation. Meanwhile, the rights of pregnant women to receive healthcare is seen as a lesser right and of lower value than the right to life of a foetus (or 'conceived child') in Poland by both the medical and the legal establishment. This is manifest explicitly in the pro-life 1991 Code of Medical Ethics, which states that foetal genetic defects are not considered sufficient justification for an abortion and the 1997 Constitutional ruling which states: 'the need to limit the rights of the pregnant woman' v .

Although the 1993 'anti-abortion' law is designed to ensure free access to information and prenatal tests, in practice access is seriously restricted. Doctors refuse to send patients for tests even in the case of clear medical indications either because of a lack of knowledge, the high cost of the tests, or because prenatal tests are associated with abortion [START_REF] Nowicka | Reproductive Rights in Poland: The effects of the antiabortion law[END_REF]. Moreover, a doctor's decision cannot be appealed by a patient, but can only be challenged through the courts. Disciplinary proceedings by the medical chambers are relatively weak [START_REF] Bodnar | Analysis of court cases concerning the lack of availability of services for terminating pregnancy in Poland[END_REF] and the doctor-patient relationship is characterised by poor communication and hierarchalism. Additionally, within the ob/gyn community the majority view towards prenatal testing was conservative, with 'emotional rather than scientific arguments' predominating and, in common with Polish abortion debate, the 'language used is extremely ideologized' (Domaradzka, 2008: 66).

Pre-natal testing in the Polish press

I have chosen to focus on press coverage of prenatal testing since the pluralistic, free market Polish media has played a central role in Polish reproductive politics (Zielińska, 2000). The popular media is a key forum through which 'contemporary anxieties about reproduction' are raised, at once both disseminating information and 'recruit[ing] subjects' identifications with users or providers' (Farquhar, 1996: 3). In analysing broadsheet coverage of the prenatal testing debate, this paper analyses a key site through which the social meaning and consequences of prenatal testing in the Polish context is articulated and contested, at a moment in which the future of prenatal testing seems uncertain and biomedical authority and knowledge is being challenged in the Polish Parliament. This contributes to the understanding of prenatal practices, and prenatal politics, as both globalised and localised [START_REF] Rapp | Testing women, testing the foetus: The social impact of amniocentesis in America[END_REF]. This paper proceeds from the understanding that newspaper reportage constructs as well as reflects social reality, that it is 'both partial and ideological' (reference). Using a critical discourse analysis methodology, this paper analyses the values explicit in the coverage of prenatal testing. In this debate, the medical community appear as key commentators and meaning-makers where earlier debate is almost exclusively focused on the party political dimension of abortion.

Thus this paper investigates how journalists and expert commentators, specifically including experts in reproductive genetics as well as the medical community more widely, 'articulate, construct and reproduce their positions of authority' as 'interpreters of genetic knowledge' in their role as 'educators, surveillors and storytellers' (Ettorre: 2002: 124). In particular, it poses the questions: who are 'legitimate' authorities on pre-natal testing and what kinds of professional identities are constructed by, and for, the medical profession? Second, the paper examines the relationship between foetus, pregnant woman and doctor. Mitchell notes that ultrasound, and I would contend, other forms of prenatal testing, do not simply distance or separate pregnant and foetus, rather 'it comes to be seen as vital to the process of reconnecting the two, and as a site for instructing women about their "proper" relationship to this new individual' [START_REF] Mitchell | Baby's first picture: Ultrasound and the politics of fetal subjects Toronto & London[END_REF]. Thus, the paper poses the questions, first, what meanings purposes, benefits and/or risks are attributed to pre-natal testing, for the foetus, and for the pregnant woman, and what role is assigned to the medical professional in mediating between woman and foetus?

This paper examines coverage of pre-natal testing in the most widely read opinion-forming national broadsheet: Gazeta Wyborcza (centre-left). Originally part of the Solidarity movement, Gazeta Wyborcza is now part owned by the US media company Cox Communications. It has the highest circulation of any nontabloid newspaper at around 600,000, representing about 17 per cent of the dailies readership market vi . Given its political outlook, this newspaper covered the amniocentesis debate in the most detail, soliciting a variety of (critical) expert opinions, offering numerous opinion pieces on the topic and reporting the issue in depth over a number of weeks. In contrast, coverage in Rzeczpospolita, the other leading opinion-forming national broadsheet, had few articles on the issue and limited non-news content. What this coverage cannot capture however is the response in the right wing, pro-Catholic and pro-life press, or the tabloid press, which is likely to have treated the issue both in less depth, and in a more sensationalist manner.

From November 1997 to October 1999, a total of thirty-two articles are devoted to coverage of pre-natal testing in Gazeta Wyborcza vii . Coverage is most intense during the legislation's passage through the Sejm and Senate with twenty-six articles in this period. Pre-natal testing is front-page news three times, with extended weekend reports after each stage of the legislative process. As well as featuring as national news items, the issue is also reported in relation to scientific issues, three times as theme of the day (where expert opinion is solicited), twice in the women's supplement Wysokie Obcasy, once in the Health section, and once as a letter. It more rarely appears in the opinion sections, and is usually raised in relation to the progress of the bill through the Polish Parliament.

Various constituencies are mobilised to comment on the issue. This includes individuals drawn from the medical community, most commonly high-profile geneticists (for example, directors of research institutes), psychologists, ob/gyn specialists, together with academic institutions such as the Polish Academy of Sciences; Parliamentary Deputies and Senators, particularly those most allied to the legislative initiative, or those most likely to oppose it; women's and feminist groups, including the Liga Kobiet and the Federation for Women and Family Planning; the legal community; disabled groups; and lastly, public opinion. There is consistent slippage between the following terms in the coverage: woman and mother; foetus and conceived child; mother and parents, evidencing the pro-life capture of the terms of debate.

Defending biomedical authority and knowledge

Throughout the coverage of the pre-natal testing debate, the Sejm is described both in opinion articles and by expert commentators, as over-reaching its remit, particularly since it has attempted to legislate on matters in which it is not expert. In particular, it is described as not competent to decide on the issue without medical consultation [START_REF] Borkowska | In respect for the law. Controversy regarding pre-natal tests[END_REF]Gazeta Wyborcza, 19-20/6/1999a). In an opinion piece, Deputies are described as not possessing the relevant qualities and characteristics to understand the issue, being unable to appreciate the human dimension of pre-natal testing in a comparable manner to medical professionals, because 'they are unable to identify with the situation of people touched with genetic problems' [START_REF] Martens | The alphabet of Krzysztof Marten. On the stiffness of thinking[END_REF].

Meanwhile, the authority and status of the Sejm is brought into question: 'Stop rummaging around with pre-natal tests, leave this to the calmness of medical ethics, and apply its main principle: above all, do not do harm!' (Gazeta Wyborcza, 22/06/1999). This opinion piece suggests that politicians supporting the bill neglected their primary responsibilities while acting in grubby selfinterest, contra doctors' responsibility to act in their patients' best interests.

Further, the bill is reported to 'undermine society's trust in medical expertise' by Izabela Jaruga-Nowacka, spokesperson of the League of Women and Vice-President of the Labour Union (Boratyn, 02-03/6/1999), who oppose the legislative initiative. Given that a 'storm of protest' against the bill by relevant and eminent professional associations is reported in great detail (Gazeta Wyborcza, 09/7/1999b), the amniocentesis bill is clearly interpreted as an attack on the medical profession, and on the status of scientific knowledge and authority itself.

The reduction of access to prenatal tests solicited in the amniocentesis bill is identified throughout the coverage as the next logical step to reduce numbers of legal abortions by the ongoing and active pro-life movement, which had recently been successful in overturning the 1996 liberalisation of abortion amendment using the Constitutional Court. Typical of coverage at other times where abortion debate comes to the fore, several Deputies associated with liberalisation attempts label the debate 'ideological' or 'without practical meaning' (Gazeta Wyborcza, 19-20/6/1999). Here, in common with many commentators, reference is made to the influence of the Roman Catholic Church in determining abortion policy (Kramer, 2005;Kulczycki, 1995;[START_REF] Millard | Women in Poland: the impact of post-communist transformation 1989-1994[END_REF][START_REF] Titkow | Polish women in politics: an introduction to the status of[END_REF]. However, contrary to previous media coverage of abortion and related issues, during coverage of the amniocentesis debate, most expert opinion and commentary derives from the medical community rather than politicians and lawyers, while Church spokespersons are conspicuous by their absence.

The amniocentesis bill is also itself repeatedly denounced as inappropriate and unnecessary in terms of improving healthcare. The bill's authors reportedly claim that that the formal criteria for determining access to tests use the same criteria as doctors employ (Gazeta Wyborcza, 22-23/5/1999a), that the bill simply formalises procedures in law and therefore does no harm. However, the bill is described throughout the coverage as removing responsibility for prenatal tests from doctors: hence the point is repeatedly made that only doctors have the right to decide who should have access to pre-natal tests (Borkowska, 22-23/5/1999; Mossakowksi, 02-03/6/1999; Gazeta Wyborcza, 27/5/1999).

The consequences for reproductive healthcare

Several articles note that genetics clinics are already largely empty (Kozerawska, 23/02/1999), that access to pre-natal tests is already very difficult because of doctors and women being ignorant and little money available (Cichocka, 10-11/7/1999). The bill is thus also criticised for making obstetricians and gynaecologists even more unwilling to refer women for pre-natal tests (Gazeta Wyborcza, 11/6/1999; Gazeta Wyborcza, 19-20/6/1999; Gazeta Wyborcza, 22/06/1999), as doctors might incur some risk when referring high-risk women for pre-natal tests (Gazeta Wyborcza, 09/7/1999b).

Many Polish doctors have utilised the so-called 'conscience clause' to refuse to refer women for an abortion even though they are ethically obliged to. The point is frequently made throughout the coverage, both by medical experts and in opinion pieces, that denying access to prenatal tests offers scope for 'manipulation' or an 'alibi' [START_REF] Martens | The alphabet of Krzysztof Marten. The various colours of hypocrisy[END_REF] or, as one geneticist puts it, a 'pretext' (Gazeta Wyborcza, 09/7/1999b) to justify deployment of the 'conscience clause'. One opinion piece notes:

A certain part of the medical community rejects the referral of patients for pre-natal tests, even in obvious cases… The majority of Deputies who voted for this fatal liberalisation, are perfectly aware of this. [START_REF] Martens | The alphabet of Krzysztof Marten. On the stiffness of thinking[END_REF] The point being made here is that Deputies are acting in collusion with the vocal and active pro-life section of the medical community to give justification and authority for the 'conscience clause' (reference), and further undermine legal access to abortion for foetal impairment. Thus the bill not only potentially criminalizes doctors, but also further erodes the public image of prenatal tests in the eyes of ob/gyn doctors and potential patients, when such services are already vulnerable, poorly supported and poorly understood.

The potential consequences for medical professionals if the bill is passed are thus differentiated by medical specialisation: ob/gyn doctors may be subject to the force of the law for illegally referring a patient, while geneticists will continue to have ever emptier clinics, and ever fewer patients. One pro-life gynaecologist, founder for the Society for Responsible Parenthood and member of the Catholic Doctors' Association, asserts that defending pre-natal tests and amniocentesis lies in the interest of geneticists as 'they depend on the acquisition of material for research' (Boratyn, 02-03/6/1999). Thus geneticists are argued to be acting in their own self-interest, defending their research projects rather than their patients' interests. However, such a critical viewpoint is encountered only very rarely in the coverage. Additionally, critiques of prenatal testing are only offered by those identified either with the amniocentesis bill or the pro-life movement more generally, while feminist challenges to the form of biomedical authority enshrined in reproductive genetics, for example, are not visible, given the pressing need to protect women's reproductive healthcare options. In such a precarious context, the benefits of pre-natal testing are consistently affirmed.

Mapping the relationships between foetus, pregnant woman and doctor

Given that the issue of abortion is politicised and remains extremely controversial, the point made repeatedly by those in support of pre-natal testing and particularly geneticists, is that they 'save children and prevent abortion' (Boratyn, 02-03/6/1999), aiming not to 'destroy' disabled foetuses but to ensure that they are born into an optimum situation for treatment and care (Gazeta Wyborcza, 04/6/1999). Prenatal tests are described as being as in the foetus' best interests, providing or facilitating better foetal healthcare, described rather as 'care and rehabilitation' for the foetus or baby (Kozerawska, 23/02/1999).

The tests are described as preventative medicine, not 'experiments' [START_REF] Mossakowski | Pre-natal testing is not an experiment[END_REF]Gazeta Wyborcza, 18/6/1999), enabling corrective 'treatment' (Kozerawska, 23/02/1999;Gazeta Wyborcza, 24/5/1999).

The majority of medical opinions solicited in the coverage describe prenatal tests as either 'making safe the life of a newborn touched by a genetic defect' or even 'protecting conceived life', hardly medical terminology [START_REF] Borkowska | In respect for the law. Controversy regarding pre-natal tests[END_REF]. This echoes Domaradzka's findings that in common with Polish abortion debate generally, the language which the Polish ob/gyn community use to talk about prenatal testing is, ideologised and uses emotional language rather than medical terminology (2008).

As I have found elsewhere in relation to the attempt to liberalise abortion law in 1996, abortions are hierarchised according to reason, with abortions on grounds of foetal abnormality cited as 'better reason' for termination than for example, abortion on social grounds viii . Doctor Romauld Dębski, head of a Gynaecological-Obstetric Clinic in Warsaw, for example, states starkly: 'I am against the termination of pregnancy on social grounds. That is murder for money. However, pre-natal tests are conducted in order to state whether the foetus is healthy' (Boratyn, 02-03/6/1999). It is important to note timing here: the amniocentesis debate follows the Sejm ratification of the Constitutional Tribunal Ruling that the liberalisation of abortion on social grounds is unconstitutional. In this context, it seems politically expedient to distance pre-natal tests from what is now an illegal activity for which doctors can be prosecuted.

As well as facilitating better foetal healthcare, the importance of prenatal tests is also signalled as enabling women to have better knowledge and information [START_REF] Mossakowski | Pre-natal testing is not an experiment[END_REF][START_REF] Martens | The alphabet of Krzysztof Marten. On the stiffness of thinking[END_REF]) 'to make one of the most important decisions' in life [START_REF] Borkowska | In respect for the law. Controversy regarding pre-natal tests[END_REF]. Pre-natal tests are described as relieving stress (Kozerawska, 23/02/1999), allowing women to prepare psychologically for giving birth to a disabled child (Mossakowski, 02-03/6/1999; Martens, 05-06/6/1999) and providing psychological tranquillity (Gazeta Wyborcza, 26/5/1999). Limiting tests is characterised as acting against 'aware motherhood' [START_REF] Borkowska | In respect for the law. Controversy regarding pre-natal tests[END_REF], while the bill is argued to discriminate against the poor who cannot pay for tests privately [START_REF] Martens | The alphabet of Krzysztof Marten. On the stiffness of thinking[END_REF]. The widespread take-up of prenatal tests globally (Boratyn, 02-03/6/1999) 'all over the civilised world' (Gazeta Wyborcza, 26/5/1999) is counter posed with recognition that in the (non-civilised) Polish context, access to pre-natal tests is often refused by medical professionals even when a pregnancy is defined as high risk.

The statistical risk of Down's and other genetic defects increasing with age is noted (Kozerwaska, 23/02/1999). Other reasons for genetic conditions are erased, with women's age, and their lack of enthusiasm for having children early consistently advanced as the sole reason for 'defects'. Here, then, not only is it that women's bodies are at fault for causing defects, but women are even biologically 'punished' for choosing to have a family later in life. Women's agency is thus described as ultimately constrained by their biology. Meanwhile, a protesting psychologist notes that limiting women's access to pre-natal tests 'is interference by the state in the private life of the family' [START_REF] Borkowska | In respect for the law. Controversy regarding pre-natal tests[END_REF]. The irony here, of course, is that through the restrictive 'antiabortion law' the Polish state already interferes in the private life of the family: limiting pre-natal tests, had it been successful, would only have continued a pattern already well established.

The mover of the bill reports that the bill's purpose is to reduce the incidence of abortions, as, he argues, pre-natal tests have a eugenic purpose ix (Boratyn, 02-03/6/1999). These assertions are repeatedly countered throughout the coverage, both in opinion pieces, by medical opinion and opposition Deputies.

First, alongside coverage which describes pre-natal testing as a modern procedure involving cutting-edge technology and techniques, pre-natal tests are also naturalised, de-technologised, and described as simply an extension (and an improvement) of the pregnant woman's body's function. A special report on prenatal tests explains:

From the moment of fertilisation until three months a spontaneous miscarriage can occur. The woman's body recognises a fault in the pregnancy and makes the decision for untimely/premature birth. The older the woman, the more difficult for nature to diagnose the defect. Pre-natal tests in this way help. (Boratyn, 02-03/06/1999) Thus the pre-natal test performs a 'corrective function' in recognising a 'defective' foetus where women's aging bodies are themselves constructed as faulty and defective. The language used here, of faults and defects and corrections, echoes the findings of [START_REF] Mitchell | Baby's first picture: Ultrasound and the politics of fetal subjects Toronto & London[END_REF] and [START_REF] Ettorre | Reproductive genetics, gender and the body London & New York[END_REF] that the language of reproductive genetics is not neutral, but is rather shaping a new moral order where values for the standards of reproduction are being defined through biomedical knowledge and authority. In this passage, it is women's aging bodies which are defined as defective, not-good-enough foetal-incubators.

Tests, so geneticists inform us, are conducted only 'where benefits exceed the risks' (Czech, 15/10/1999) whilst the financial 'cost' of tests is characterised as incomparable to the 'cost' of giving birth to a disabled child [START_REF] Borkowska | In respect for the law. Controversy regarding pre-natal tests[END_REF]. Here economic labels and relationships are assigned to foetuses, with defective foetuses described 'as prospective, burdensome human beings with a price tag on their heads as well as defective products' (Ettorre: 2002: 21).

Meanwhile, the decision to bring up a disabled child is characterised as being women's responsibility, and a heavy responsibility to bear at that (Borkowska, 22-23/05/1999).

There is only one article, a lengthy special report, which refers to disabled rights.

Here we learn that disabled organisations are in favour of the tests (Boratyn, 02-03/6/1999) and we learn a little about the position of the disabled in Polish society.

For example, we learn from one mother who is expecting a child with Down's and making the decision whether or not to terminate the pregnancy, that the disabled can expect 'mercy' but not much of a 'future' in Polish society (ibid.), while the President of the Association for People with Mental Disabilities states that the situation of families with disabled children is 'tragic' as the state provides no extra benefits for the disabled. So the reportage notes that whilst abortions on medical grounds are resisted by the pro-life lobby, no adequate help is allocated to families who do in fact proceed with a pregnancy where a genetic defect is identified or suspected.

Foetal safety is continually affirmed, with amniocentesis described as 'relatively safe' [START_REF] Borkowska | In respect for the law. Controversy regarding pre-natal tests[END_REF] for the foetus. Meanwhile, geneticists and the majority of other medical commentators argue that only two to three per cent of tested patients in the high-risk category in fact show abnormalities [START_REF] Borkowska | In respect for the law. Controversy regarding pre-natal tests[END_REF]. Risk becomes no risk; abnormalities become 'normal'. 'Their happiness can't be described,' states one geneticist (Kozerawska, 23/02/1999).

It is left to the special report to document the 'seconds of joy destroyed by a dark stain' when a defect is discovered (Boratyn, 02-03/6/1999). Whilst very rarely, the voices of women who have had pre-natal tests do emerge from the coverage, the taken-for-granted positive estimation of the tests precludes a more detailed analysis of the real costs and dilemmas pre-natal testing poses for women.

In common with coverage of the deployment of the conscience clause by medical professionals in 1997 (reference), in this coverage of debate around pre-natal testing the (gendered) character of the doctor/patient relationship becomes apparent. A heroic masculinised narrative emerges from the coverage, whereby tests are characterised as being 'for women's benefit', and designed to 'help women' (Boratyn, 02-03/6/1999), as if they were helpless dependants, rescued from ignorance by the paternalistic medical protagonist. A rather patronising tone towards women suffuses reported medical opinion; geneticists talk of 'dissuading' women (as if children) from tests when there is no need (Gazeta Wyborcza, 22-23/5/1999a); else describing Polish women as either 'wise enough' to agree to tests despite the tone of the pre-natal testing debate or else 'scared' to agree to have tests (Gazeta Wyborcza, 22-23/5/1999a).

Not only are the benefits of pre-natal tests, both for the foetus, and for women, outlined in detail, but also their measured use, and professional behaviour of the medical community, is consistently emphasised in the coverage. The opinion that prenatal tests are neither over-used nor abused is pervasive throughout, even expressed by the bill's mover himself. The point is made repeatedly that tests are selective [START_REF] Borkowska | In respect for the law. Controversy regarding pre-natal tests[END_REF], that they are only given to a pre-identified high risk group (ibid.; Gazeta Wyborcza, 22-23/5/1999a), and never available 'on demand' (Czech, 15/10/1999;Gazeta Wyborcza, 22-23/5/1999a), with the medical profession operating within the law. This last phrase distances the practice of pre-natal tests from the availability of abortion without restriction and seems to indicate that it is not pregnant women who decide or request to have tests, but rather doctors who 'instruct' women to have them.

Conclusion

As with other moments in Polish abortion debate, in press coverage of the attempt to restrict access to pre-natal tests, public opinion is marshalled against the bill and the competence and authority of the Sejm is brought into question.

However, the party political dimension of debate is muted here. In its stead, press coverage shows a significant mobilisation of the medical community in defence of biomedical knowledge, the practice of medicine and in defence of the legal status quo. Throughout the coverage, the meaning of debate is defined in biomedical terms, constructed and contested by medical expertise, which is sometimes divergent, but nonetheless claims the pre-eminence of medical opinion both as primary definer of the meaning of pre-natal tests and as chief regulator of their accessibility to women.

Why then does the medical profession mobilise in defence of women's access to pre-natal tests when there is no comparable mobilisation in defence of liberal abortion law in 1989-1993, or the liberalised abortion law in 1997? I would argue that the medical community, and in particular geneticists, mobilise against the bill because they see it as reflective of a pro-life initiative building upon the success of the 1997 Constitutional Tribunal Ruling, which in eroding access to abortion, and politicising prenatal tests, impacts negatively upon their professional status. The motivation may thus lie less in a defence of patient interests than in a defence of medical status and authority.

Given that the meaning of prenatal testing is defined in biomedical terms, with little exploration of the social context in which prenatal testing occurs, the (socially differentiated) meaning of the tests for women, or for the disabled community, is rarely considered. There are few opportunities to hear the voice of disabled people and throughout the coverage a rather patronising and paternalist tone is expressed towards women patients by expert medical commentators, whilst women's rights to access pre-natal tests are always described as contingent upon doctors' approval. As with previous coverage around the invocation of the conscience clause in 1997, women's rights as patients hardly feature, while the form of healthcare defended by those supporting prenatal tests is explicitly foetal-centred, rather than shaped by the needs and interests of pregnant women.

Moreover, the language used by medical commentators slips from foetus to 'conceived child', suggesting that the pro-life language of Polish abortion debate, is not only shaping the terms of debate in Polish reproductive politics generally, but is also shaping biomedical knowledge and the form of intervention it can make into Polish reproductive politics. In other words, when the function and purpose of prenatal testing is described as a logical extension of the 'pro-life' desire to safeguard and protect foetal life, it is clear that the status and authority of biomedical knowledge can only be defended by using language and definitions already captured by the Polish pro-life lobby. Thus the terms of the amniocentesis debate, and the social meaning of prenatal testing, is in the Polish context fundamentally shaped by the terms of the abortion debate.

  Gazeta Wyborcza (04/6/1999) 'About tests'.GazetaWyborcza (11/6/1999) 'Senate Committee on pre-natal tests. Limitations are not necessary'. Gazeta Wyborcza (18/06/1999) 'In the Senate on pre-natal tests. Conditions and traps'. Gazeta Wyborcza (19-20/6/1999) 'Pre-natal tests. The Senate puts Away'.Gazeta Wyborcza (22/06/1999a) 'They rejected the amendments because they think about the law. Behind the scenes of the Senate decision on the matter of pre-natal tests.' Gazeta Wyborcza (22/06/1999b) 'Pre-natal ping pong'. Gazeta Wyborcza (09/7/1999a) 'CBOS on pre-natal tests. Everybody should have this right'. Gazeta Wyborcza (09/7/1999b) 'The Sejm has decided. Pre-natal tests -yes'. Ghai, Anita & Johri, Rachana (2008) 'Prenatal diagnosis: Where do we draw the line?' Indian Journal of Gender Studies 15(2): 291-316 Kozerawska, Małgorzata (23/02/1999) 'Geneticists wait for patients. Spying on chromosomes', Gazeta Wyborcza. (1995) 'Abortion policy in postcommunist Europe: The conflict in Poland', Population and Development Review 21(3): 471-505.

women in Poland ',M. (ed.) ii Pregnant women in Poland defined as high risk are referred for genetic counselling, and if necessary, techniques of pre-natal diagnosis, including amniocentesis. There is no comparable mass AFP screening programme for Down's and other genetic conditions as in the UK. In 1999, the number of women being referred for pre-natal diagnosis at this time did not total more than a few thousand.

iii Estimates of miscarriage resulting from the procedure ranging from 0.5% to 1%.


M.D Fabrizio ; Fabrizi
email: fabrizi@policlinico.mi.it

Vivek Dixit

Ph.D Paul Martin

Piergiorgio Messa

The impact of diabetes mellitus on the immunological response to hepatitis B virus vaccine in dialysis patients: Meta-analysis of clinical trials

Keywords: Hepatitis B Virus, Vaccine, Diabetes mellitus, Dialysis, Meta-analysis

published or not. The documents may come

The impact of diabetes mellitus on the immunological response to hepatitis B virus vaccine in dialysis patients:

Meta-analysis of clinical trials

Introduction

The frequency of hepatitis B virus (HBV) infection, as detected by persistent positivity for hepatitis B surface antigen in serum, is low but not negligible among patients with chronic kidney disease (CKD) on maintenance dialysis in the industrialized world [1]. In 2002, the Centers for Disease Control and Prevention (CDC, Atlanta, GA, US) has reported that the prevalence of HBsAg seropositivity among dialysis patients was 0.9% in the US [2]. Also, outbreaks of HBV infection in haemodialysis (HD) units continue to occur [START_REF] Thompson | Nonhospital health care-associated hepatitis B and C virus transmission: United States, 1998-2008[END_REF]. Prevalence and incidence rates of HBV infection remain much higher within dialysis units in less-developed countries [START_REF] Burdick | Patterns of hepatitis B prevalence and seroconversion in hemodialysis units from three continents: the DOPPS[END_REF]. It is well known that patients undergoing long-term dialysis have a lower response to HBV vaccine compared with the non-uraemic population: the number of patients who develop protective antibody (anti-HBs) against HBV surface antigen (HBsAg) is lower, the antibody titers of those who mount an antibody response are reduced and decline faster over time [START_REF] Rangel | for the Advisory Committee on Immunzation Practices and the American Academy of Pediatrics. Vaccine recommendations for patients on chronic dialysis[END_REF].

Diabetic patients have a compromised immune system and their immunological response to HBV vaccine is less optimal than non-diabetic individuals [START_REF] Pozzilli | Reduced protection against hepatitis B virus following vaccination in patients with type 1 (insulin-dependent) diabetes[END_REF]; nevertheless, the influence of this metabolic disease on seroprotection rate after HBV vaccination is not well investigated in chronic dialysis patients. A few studies on HBV vaccination of patients with CKD and diabetes mellitus have been published and preliminary results have been given [START_REF] Alavian | The effect of diabetes mellitus on immunological response to hepatitis B virus vaccine in individuals with chronic kidney disease: A meta-analysis of clinical trials[END_REF].

The goal of this study was to investigate the available evidence on the relationship between diabetes mellitus and immune response to HBV vaccination in long-term dialysis population by performing a systematic review of the literature with a meta-analysis of clinical studies.

Material and Methods

Search strategy and data extraction

We performed electronic searches of the National Library of Medicine's MEDLINE database, Current Contents, and manual searches of selected speciality journals to identify all pertinent literature. It has previously demonstrated that an electronic search alone may not sensitive enough.

Four MEDLINE database engines (Ovid, PubMed, Embase and GratefulMed) were used. The key words 'hepatitis B', 'vaccine', 'diabetes mellitus', 'dialysis', and 'chronic kidney disease' were used. Reference lists from qualitative topic reviews and published clinical trials were also searched.

Our search was limited to human studies that involved individuals aged >19 years published in the English literature. All articles were identified by a search from 1980 to November 2010. Data extraction was conducted independently by two investigators (F.F., V.D.) and consensus was achieved for all data. Studies were compared to eliminate duplicate reports for the same patients, which included contact with investigators when necessary. Eligibility and exclusion criteria were prespecified.

Criteria for inclusion

We included studies evaluating only patients undergoing maintenance hemodialysis [HD] and peritoneal dialysis [PD]. Studies restricted to students, military recruits or other cohorts that involved subjects <19 years of age were excluded. Many studies have identified an effect of diabetes mellitus on response rate to HBV vaccine. However, only studies that (i) specified either a relative risk and a measure of variance for vaccine response among dialysis patients with diabetes mellitus, compared with non-diabetic individuals, or (ii) presented data in a form that could be used to construct a 2x2 contingency table were considered for final inclusion. Both randomizedcontrolled trials and observational studies were considered eligible for inclusion in the analysis. We included trials using plasma-derived or recombinant DNA hepatitis B vaccine. Patients who The decision as to inclusion or exclusion of clinical trials was not related to results. All dose schedules and routes of administration were included, as long as they involved primary vaccination regimens and not booster doses only.

Ineligible studies

Studies were excluded if they reported inadequate data on measures of response, or included individuals with positive serology for HBsAg, antibodies to HBsAg (HBsAb) or human immunodeficiency virus (HIV). Trials that were only published as abstracts or as interim reports were excluded; letters and review articles were not considered for this analysis. Trials that involved renal transplant recipients or patients with kidney failure at pre-dialysis stage were excluded.

End-points of interest

We compared the seroprotection rate after completion of HBV vaccination schedule in patients with diabetes mellitus versus non-diabetic patients. Patients vaccinated against HBV are considered immune if protective titres of anti-HBs antibody can be demonstrated after completion of vaccination. The level of antibody production that defines seroprotection was 10 IU/mL across the studies. These definitions were consistent with standards published in the scientific literature.

Statistical methods

In all studies included in this analysis, data from patients who did not complete the vaccination schedule were excluded from the final analysis; thus, analysis was made by per-protocol (PP), not by intention-to-treat (ITT). A summary estimate of the odds ratio (OR) for seroresponse after vaccination among diabetic versus non-diabetic patients was generated by use of a random-effects approach, as described by DerSimonian and Laird [8]. The Cochrane's Q test was used for quantifying the heterogeneity [START_REF] Petitti | Approaches to heterogeneity in meta-analysis[END_REF]; the I 2 index-the percentage of total variation across studies due to heterogeneity rather than chance [START_REF] Higgins | Measuring inconsistencies in metaanalysis[END_REF], was also used. The Galbraith plot was made to assess the heterogeneity and precision of single studies [START_REF] Galbraith | A note on graphical presentation of estimated odds ratios from several clinical trials[END_REF]. Pooled ORs were calculated in the subgroups of clinical trials as sensitivity analyses. The publication bias assessment (PBA), i.e., the number of void or negative trials necessary to render the meta-analysis meaningless, was made according to the Klein formula [START_REF] Klein | Total parenteral nutrition and cancer clinical trial[END_REF]. The publication bias was also measured by the test of funnel plot asymmetry. The 5% significance levels were used for alpha risk. Every estimate was given with its 95% Confidence Intervals (95% CI).

Results

Literature review

Our electronic and manual searches identified 143 manuscripts which were selected for full text review. One hundred and thirty-one (92%) studies were excluded because they did not fulfil the inclusion criteria. A list of the 143 bibliographic references is available from the authors on request.

Twelve (8%) papers [START_REF] Waite | Successful vaccination with intradermal hepatitis B vaccine in hemodialysis patients previously nonresponsive to intramuscular hepatitis B vaccine[END_REF][START_REF] Fabrizi | Recombinant hepatitis B vaccine use in chronic hemodialysis patients[END_REF][START_REF] Mettang | Low dose intradermal versus intramuscular hepatitis B vaccination in patients with end-stage renal failure[END_REF][START_REF] Jha | Granulocyte macrophage colony stimulating factor induced seroprotection in end stage renal failure patients to hepatitis B in vaccine non responders[END_REF][START_REF] Eardley | Efficacy of the accelerated hepatitis B vaccination schedule used in haemodialysis patients post-exposure to virus: a single-centre experience[END_REF][18][START_REF] Elwell | Factors associated with long-term antibody production induced by hepatitis B vaccine in patients undergoing haemodialysis: A retrospective cohort study[END_REF][START_REF] Liu | A comparison of responsiveness to hepatitis B vaccination in patients on hemodialysis and peritoneal dialysis[END_REF][START_REF] Chow | Antibody response to hepatitis B vaccine in endstage renal disease patients[END_REF][START_REF] Ocak | The evaluation of immune responses to hepatitis B vaccination in diabetic and non-diabetic haemodialysis patients and the use of tetanus toxoid[END_REF][START_REF] Afsar | Antibody response following hepatitis B vaccination in dialysis patients: Does depression and life quality matter ?[END_REF][START_REF] Chow | Extra-high dose hepatitis B vaccination does not confer longer serological protection in peritoneal diaalysis patients: a randomized controlled trial[END_REF], representing a total of 1002 unique patients, were included in our meta-analysis. There was a 100% concordance between reviewers with respect to final inclusion and exclusion of studies reviewed based on the predefined inclusion and exclusion criteria.

Patient characteristics

Some salient demographic characteristics of subjects enrolled in the included clinical trials are shown in Table 1. Many (six of 12, 50%) studies were from centres in developed world (western Europe and North America). There were two (17%) controlled randomized clinical trials (RCTs), and one clinical controlled trial (CCT). Nine were cohort studies, three (20%) having retrospective design.

As listed in Table 2, recombinant HBV vaccine was used in all clinical studies. Intramuscular administration of HBV vaccine was used in the majority of patients (984, 98.2%). The mean age of subject cohorts ranged from 43 to 66 years (Table 3). The gender distribution ranged from 35% to 64% male. All clinical studies included patients on maintenance dialysis; 917 (92%) and 85 (8%) underwent regular HD and PD, respectively. All PD patients received continuous ambulatory peritoneal dialysis (CAPD). shown in the Galbraith plot (Figure 1); it provides information on the heterogeneity between trials.

It also reports the effect of treatment, the precision and the effect of each single trial included in the meta-analysis.

Despite the test for heterogeneity was not significant, we explored some of the possible sources of study heterogeneity. As reported in Table 4, no heterogeneity was found in stratified analyses.

Discussion

The impaired efficacy of HBV vaccine in dialysis population has been attributed to numerous factors notably immune compromise because of uraemia, older age [START_REF] Fabrizi | Meta-analysis: The effect of age on immunological response to hepatitis B vaccine in end-stage renal disease[END_REF], male gender, nutritional status [START_REF] Fernandez | Response to the hepatitis B virus vaccine in haemodialysis patients: influence of malnutrition and its importance as a risk factor for morbidity and mortality[END_REF], serological positivity for human immunodeficiency virus (HIV) [START_REF] Ahuja | Hepatitis B vaccination in human immunodeficiency virus-infected adults receiving haemodialysis[END_REF] or hepatitis C (HCV) infection [START_REF] Navarro | Antibody level after hepatitis B vaccination in haemodialysis patients: influence of hepatitis C virus infection[END_REF], blood transfusion history, and possession of the major histocompatibility complex aplotype HLA-B [START_REF] Pol | Genetic basis of nonresponse to hepatitis B vaccine in hemodialysis patients[END_REF]. In addition, the failure to complete a full course of HBV vaccination may cause a poor active immunization [START_REF] Jibani | Hepatitis B immunization in UK renal units: failure to put policy into practice[END_REF]. Diabetic nephropathy is the most common cause of chronic kidney disease and diabetic patients with normal renal function show a lower seroprotection rate than non-diabetic patients after HBV vaccination [START_REF] Pozzilli | Reduced protection against hepatitis B virus following vaccination in patients with type 1 (insulin-dependent) diabetes[END_REF]. The link between diabetes mellitus and the poor and non-persistent immunological response to HBV vaccine in dialysis population remains controversial.

Our meta-analysis determined that patients with diabetes mellitus show a lower seroprotection rate to HBV vaccine than non-diabetic patients in dialysis population. These results were very robust as no heterogeneity occurred in primary analysis; also, the analysis in various subgroups yielded only minimal changes on the effect size. This phenomenon is biologically plausible as numerous changes in cellular and humoral immune responses have been described in non-uraemic patients with diabetes mellitus. As an example, the presence of DR3 and DR7 human leukocyte antigen (HLA) alleles in diabetic individuals has been implicated in this impaired immunological response [START_REF] Alper | Genetic prediction of nonresponse to hepatitis B vaccine[END_REF].

Our findings are consistent with data from other sources. The analysis of the FMCNA database (14546 patients with end stage renal disease who received HBV recombinant DNA vaccine) revealed that the OR of seroprotection rate of HBV vaccine in DM versus non-DM patients with CKD was 0.83 (95% CI, 0.77; 0.89), P=0.002 [START_REF] Lacson | Antibody response to Engerix-B and Recombivax-HB hepatitis B vaccination in end stage renal disease[END_REF]. A lower response rate after HBV vaccination in diabetic versus non-diabetic patients with CKD at pre-dialysis stage has been found in at least two surveys [START_REF] Daroza | Stage of chronic kidney disease predicts seroconversion after hepatitis B immunization: earlier is better[END_REF][START_REF] Morais | Intradermal hepatitis B vaccination in patients with advanced chronic renal failure: immunogenicity and follow-up[END_REF].

This meta-analysis is potentially limited in a number of ways. First, as with all meta-analyses, this study has the potential limitation of publication bias. Negative trials are less likely to be published- we postulated that the authors who found a statistical association between diabetes mellitus and response rate to HBV vaccine would likely be to comment on such a finding in published manuscripts, whereas investigators who failed to find such an association would be less likely to give any comment. This is of particular concern, given that the evaluation of vaccine response according to diabetes mellitus was not a primary objective of most studies (eleven of 12, 92%) included in our analysis. To limit the possible effect of publication bias, we used several strategies for identifying studies to include published and unpublished studies. Inclusion criteria, established a priori, were chosen to increase the likelihood that high-quality studies would be included. Secondly, there was in our studies incomplete information about nutritional status, HIV/HCV infection, serum haemoglobin concentration, erythropoietin use or adequacy of dialysis. However, the link between these parameters and seroresponse to HBV vaccine is still controversial in dialysis population. In their multiple logistic regression model, Chin et al. [18] found that DM was a significant and independent predictor of failure to seroconvert after vaccination against HBV (OR, 3.4; 95% CI, 1.3-9.0; P=0.01). Finally, we have made mostly a meta-analysis of observational studies and it is clear that a meta-analysis of randomized clinical trials is provided with better accuracy and reliability. The low heterogeneity found in primary and stratified analyses, the absence of publication bias and the good number (n=1002) of patients available for our analysis strengthen our data.

Various approaches have been suggested in order to improve the response rate to hepatitis B vaccine in dialysis population including increased vaccine doses [START_REF] Fabrizi | Recombinant hepatitis B vaccine use in chronic hemodialysis patients[END_REF] or shots; recent evidence has shown efficacy and safety of intradermal administration of recombinant vaccine towards HBV [START_REF] Edey | Review article: hepatitis B and dialysis[END_REF][START_REF] Ono | Complete seroconversion by low dose intradermal injection of recombinant hepatitis B vaccine in hemodialysis patients[END_REF][START_REF] Marangi | Hepatitis B virus infection in chronic uraemia: long-term follow-up of a two-step integrated protocol of vaccination[END_REF] in dialysis population. HBV vaccine has been given to uraemic patients not yet requiring regular dialysis [START_REF] Daroza | Stage of chronic kidney disease predicts seroconversion after hepatitis B immunization: earlier is better[END_REF][START_REF] Morais | Intradermal hepatitis B vaccination in patients with advanced chronic renal failure: immunogenicity and follow-up[END_REF]. Numerous vaccine adjuvants have been recommended, such as interferon, interleukin, and erythropoietin, among others. The Centers for Disease Control (CDC) [START_REF] Centers For | Recommendations for preventing transmission of infections among chronic haemodialysis patients[END_REF] currently recommend that dialysis patients receive by intramuscular route double doses (20 mcg x2) at 0, 1, 2, and 6 months with regular monitoring of antibody levels to ensure that antibody

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Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

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RESULTS

Study selection 17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

8-9

Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

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Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).

8-9

Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.

8-9

Synthesis of results 21 Present results of each meta-analysis done, including confidence intervals and measures of consistency.

8-9

Risk of bias across studies 22 Present results of any assessment of risk of bias across studies (see Item 15).

8-9

Additional analysis 23 Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]).

8-9

DISCUSSION

Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).

10-12

Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

  schedule (naïve patients) or those who had failed to respond to prior vaccine schedule (nonresponder patients) against HBV vaccine were enrolled.

  outcome A significant decrease in response rates among patients with diabetes mellitus vs. non-diabetic patients was found; the pooled OR was=0.52 (95% CI 0.38-0.71), P=0.001 according to a random effects model. No significant heterogeneity occurred (P=0.295). The publication bias assessment (PBA) was 41. The test of funnel plot asymmetry was not significant [alpha=0.53; 95% CI, -2.98; 4.05 (P=0.77)]. The comparison between patients with DM and non-diabetic patients has been

  the protective level of 10 mIU/mL. There is no evidence that the various approaches to improve HBV vaccination response rates have an effect in diabetics on dialysis. Studies on vaccination schedules with adapted vaccine doses or shots, intradermal administration of recombinant vaccine or use of vaccine adjuvants are under way among dialysis patients with diabetes mellitus.

F

Figure 1 .

 1 Figure 1.Response rate to HB vaccine: diabetic versus non-diabetic patients(Galbraith plot)

10 - 12 Conclusions 26 12 FUNDINGFunding 27

 1012261227 Provide a general interpretation of the results in the context of other evidence, and implications for future research.10-Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.

13 From:

 13 Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(6): e1000097. doi:10.1371/journal.pmed1000097

Table 4 .

 4 Pooled Odds Ratio (OR) of failure to respond to vaccine (diabetic vs. non-diabetic patients) in various subgroups of interest

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Acknowledgement

Declaration of personal interests: None. Declaration of funding interests: The authors' work is supported in part by the grant 'Project Glomerulonephritis'; in memory of Pippo Neglia.

Authors (reference number)

Country

Patients, n

Publication Year

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Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

5-6

Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

5-6

Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

5-6

Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

5-6

Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

5-6

Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

5-6

Risk of bias in individual studies

12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

6-7

Summary measures 13 State the principal summary measures (e.g., risk ratio, difference in means).

6-7

Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I

2

) for each meta-analysis.

6-7

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