MD Alexis Genthon
email: alexis.genthon@gmail.com

Thibault Chiarabini

Pierre Baylac

Nadia Valin

Tomas Urbina

Jérome Pacanowski

Arsène Mekinian

Eolia Brissot

Fella

Fella M ' Hammedi-Bouzina

Simona Lapusan

Mohamad Mohty

Karine Lacombe

Patrick Ingiliz

Severe COVID-19 infection in a patient with paroxysmal nocturnal hemoglobinuria on eculizumab therapy

Keywords: PNH, COVID-19, SARS-CoV-2, pre-exposure prophylaxis, tocilizumab, eculizumab

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

The course of the COVID-19 infection has been better understood since the first identification of a novel beta-coronavirus (SARS-CoV-2) in early January 2020 in Wuhan, China [START_REF] Zhou | Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study[END_REF]. Some individuals will develop after the first "viral phase", as a predictor of a severe outcome, a second "immunological" phase that appears to be mediated by strong complement activation and can lead to a state of thrombotic microvascular injury [START_REF] Magro | Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases[END_REF]. Several antiviral or immune -modulatory drugs have been used in clinical trials or as experimental therapy in COVID-19 patients all over the world. Among the latter are several biologicals such as interleukine 6 (IL-6) antagonists (tocilizumab) [START_REF] Somers | Tocilizumab for treatment of mechanically ventilated patients with COVID-19[END_REF][START_REF] Guaraldi | Tocilizumab in patients with severe COVID-19: a retrospective cohort study[END_REF] and IL-6 receptor antagonists (sarilumab) or TNFalpha-antagonists [START_REF] Alijotas-Reig | Immunomodulatory therapy for the management of severe COVID-19. Beyond the anti-viral therapy: A comprehensive review[END_REF]. A beneficial effect from the off-label use of the complement antagonist eculizumab has been reported in patients with severe [START_REF] Diurno | Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience[END_REF] or critical [START_REF] Laurence | Anti-complement C5 therapy with eculizumab in three cases of critical COVID-19[END_REF] COVID-19 infections and in combination with ruxolitinib in 7 patients in a controlled study [START_REF] Giudice | Combination of Ruxolitinib and Eculizumab for Treatment of Severe SARS-CoV-2-Related Acute Respiratory Distress Syndrome: A Controlled Study[END_REF]. Eculizumab is a monoclonal antibody currently approved for the treatment of paroxysmal nocturnal hematuria (PNH) and some other conditions. It specifically binds to complement C5, thereby inhibiting its cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b-9 [START_REF] Thomas | Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv[END_REF]. It is hypothesized that treatment with eculizumab could improve outcome by reducing immune-mediated lung injury during the course of COVID-19 pneumoniae. Eculizumab is currently used as an investigational and experimental [START_REF] Diurno | Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience[END_REF] agent to treat COVID-19 but its efficacy is yet to be proven. Here, we report a case of patient who received eculizumab to treat underlying PNH while he became infected with SARS-CoV-2.

A 45-year old man was referred to our emergency department in Saint-Antoine Hospital, Paris, France with a 3-day history of dry cough, myalgia, and diarrhea (figure 1). He also reported anosmia. He had been diagnosed with PNH when he was 18 years old. The patient had no history of thrombosis and had been treated with eculizumab since 2008 at the dose of 1200 mg every 12 days with partial response.

He was obese with a body mass index of 42.6 kg/m² and had obstructive sleep apnea.

Three days before his referral, he had come to our outpatient department to receive his eculizumab infusion. A few hours later, he developed myalgia and fever. The The SARS-CoV-2 PCR was finally negative on day 31 and the patient was discharged from the ICU. Hemoglobin was stable at 95 g/L with no sign of hemolysis.

A new chest computed tomography imaging was performed on June 24 showed disappearance of ground-glass opacities.

We here report the case of a male individual treated for PNH by repeated eculizumab infusions since 2008 that developed a severe SARS-CoV-2 infection, while his treatment was pursued. Although being on a stable eculizumab regimen for PNH, we saw an increased hemolysis during the COVID-19 infection, as it has been described

with other viral infections. While the induction of auto-immune hemolytic anemia has been described in COVID-19, the underlying pathomechanism in our case was most likely complement activation. Eculizumab is not suspected to have the potential to prevent SARS-CoV-infection, and likewise, in our case, the administration did not serve him as pre-exposure prophylaxis. Few agents such as hydroxychloroquine have been suggested for pre-and post-exposure prophylaxis in COVID-19 but have not proven efficacy yet [START_REF] Boulware | A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19[END_REF]. Biologicals, such as eculizumab, may not be suitable due to their deleterious impact on the immune response and even facilitate infection.

However, eculizumab is investigated in clinical trials such as the SOLID C-19 trial (NCT number: 04288713) or the CORIMMUNO-ECU trial (NCT number: 04346797)

for the treatment of moderate to severe pneumonia related to COVID-19.

Eculizumab is an inhibitor of the complement factor C5. The complement system plays a crucial role in the host defense system against bacterial, fungal, or viral infections. It is further related to a pro-inflammatory state associated with ARDS in SARS-CoV-infection [START_REF] Gralinski | Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis[END_REF], and its inhibition may therefore lead to a favorable disease outcome. In mice with MERS and acute respiratory failure high concentrations of C5 have been detected and blockage of C5a led to a reduced alveolar macrophage infiltration [START_REF] Jiang | Blockade of the C5a-C5aR axis alleviates lung damage in hDPP4 -transgenic mice infected with MERS-CoV[END_REF].

Our patient developed a severe course requiring mechanical ventilation despite repeated administration of 1200mg i.v. eculizumab at day 1 and 10 of COVID-19 related symptoms, and the drug did not seem to have an effect on the course of the disease. Several risk factors for severe outcomes have been identified in COVID-19 patients, such as arterial hypertension, diabetes mellitus, coronary heart disease, age [START_REF] Zhou | Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study[END_REF], or obesity. Our patient was hypertensive and had a BMI of 42.6 kg/m2, and this may explain the severity of his disease, and these factors may outweigh the beneficial effect of a complement C5 blockade. Interestingly, this very high-risk patient experienced no thrombotic complication. The i.v. administration of the IL-6 receptor antagonist tocilizumab was followed by a remarkable decrease in inflammatory blood markers such as C-reactive protein or lactate dehydrogenase, while his IL-6 levels remained strongly elevated. It is noteworthy that both C-reactive protein and lactate dehydrogenase levels abruptly rose 14 days after infusion.

Tocilizumab is currently evaluated in randomized-controlled trials to treat the cytokine-release syndrome associated to COVID-19 [START_REF] Moore | Cytokine release syndrome in severe COVID-19[END_REF], and reduced risk of mechanical ventilation or death have been reported [START_REF] Somers | Tocilizumab for treatment of mechanically ventilated patients with COVID-19[END_REF][START_REF] Guaraldi | Tocilizumab in patients with severe COVID-19: a retrospective cohort study[END_REF].

For eculizumab as for tocilizumab, the accurate dose in COVID-19 ARDS is unknown. In the CORIMMUNO-ECU trial, much higher doses of eculizumab are administered (1200mg i.v. at day 1, 4, and 8, then again at day 15, 18, and 22), as pharmacokinetics are likely to differ in the septic state. Considering the high body weight of our patient, he was potentially underdosed to reach drug levels that may be sufficient to induce sufficient complement blockade.

Although tocilizumab was associated with a transient decrease in inflammatory biomarkers, further reports are needed to identify whether this anti-IL6 receptor agent

  patient was started on antibiotic treatment with amoxicillin/clavulanate and ciprofloxacin with no improvement and was then referred to the hospital. Physical examination revealed a blood pressure of 156/81 mmHg, a pulse of 104 beats per minute, a body temperature of 37.2°C, respiratory rate of 18 breaths per minute, and oxygen saturation of 100% while the patient was breathing ambient air. Chest radiography revealed interstitial lung infiltrates. A posterior nasopharyngeal swab was tested positive for SARS-CoV-2 nucleic acid by RT-PCR. Laboratory findings revealed macrocytic anemia with hemolysis: hemoglobin: 89 g/L, MCV: 110 µ3, reticulocytes: 272 G/L (11.3 %), LDH: not measurable due to hemolysis, haptoglobin <0.01 g/L, total bilirubin: 63 µmol/L and conjugated bilirubin: 28 µmol/L (figure2).The antibiotic treatment was stopped and a hydroxychloroquine treatment was started outside of clinical trial (200 mg TID). Seven days after the first symptoms, the patient developed a severe hypoxemic syndrome with PaO2 of 68 mmHg. Oxygen supplementation delivered by nasal cannula at 6 liters per minute was started. A chest computed tomography imaging was performed and showed bilateral groundglass opacities. An association of ritonavir and lopinavir, based on in vitro efficacy on SARS-CoV and middle-east respiratory syndrome (MERS) viruses available at this time[START_REF] -W. Chan | Treatment With Lopinavir/Ritonavir or Interferon-β1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset[END_REF][START_REF] De Wilde | Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture[END_REF] , as well as venous thromboembolism prevention by enoxaparin 6000 IU OD was added. The eculizumab treatment was continued at the dose of 1200 mg on day 7, day 19, and day 29 of the hospitalization. The patient's condition continued to worsen and he developed a fever of 40ºC. Laboratory findings showed an inflammatory syndrome with C-reactive protein: 204.2 mg/L (<5 mg/L) and interleukin-6 at 68.1pg/mL (<12.5 pg/mL). The decision was made to stop lopinavir/ritonavir and hydroxychloroquine and to administer i.v. tocilizumab (8 mg per kg). He was transferred to the ICU on day 10 since first symptoms. A second line of antibiotics, cefotaxime and azithromycin was also administered. On day 12, he developed an acute respiratory distress syndrome (ARDS) with a PaO2/FiO2 ratio of 78 and was placed under lung-protective mechanical ventilation with neuromuscular blockade. Three sessions of prone positioning were required before respiratory parameters gradually improved and fever ultimately disappeared. A percutaneous tracheostomy was performed after 25 days of mechanical ventilation to facilitate weaning.

  or eculizumab itself could have modified the course of the severe Sars-Cov2 infection for this overweight individual with PNH.In conclusion, we may speculate that eculizumab administered in a classical schedule for PNH did not contribute, in our case, to control a severe course of COVID-19 ARDS in an overweight individual. Tocilizumab may have played a role in reversing the course of the disease. Controlled studies are needed and awaited to understand the benefit and eventually the optimal administration of immunomodulating drugs during Sars-Cov2 infections.

Figures  Figure 1 .

 1 Figures

Acknowledgments

AG, TC, PI and KL wrote the manuscript. PB, FM, SL, TC, PI, AM, KL and AG contributed to the acquisition and analysis of the data. TU, JP, AM, EB and MM contributed and revised the manuscript. All authors approved the submitted and final version.

Conflicts of


Loyal Deborah

AURIACOMBE, Marc, SERRE, Fuschia, CALCAGNI Anne-Laure Sutter

Nicolas & Rascle

STIGMA ATTACHED TO SMOKING PREGNANT WOMEN Stigma Attached to Smoking Pregnant Women: A Qualitative Insight in the General French Population

Introduction. Cigarette consumption during pregnancy has major health consequences for women and unborn children. The stigma of smoking during pregnancy might hinder mothers-to-be's access to adequate healthcare and smoking cessation, especially in disadvantaged groups. This qualitative study was designed to describe extensively the public stigma associated with smoking during pregnancy. Method. Participants were French adults recruited from the general population through social networks (N=100). They were asked to answer three pairs of open-ended questions regarding cognitions, emotions and behaviours elicited in the general population by pregnant smoking women. An inductive thematic analysis was performed and inter-judge agreement was computed on 30% of the corpus analysed deductively. Finally, independence (chi-square) between themes and gender, education, parenthood and smoking status was tested. Results. Themes (n=25) were defined regarding cognitions (n=9, e.g., irresponsible, thoughtless and unmindful, etc.), emotions (n=8, e.g., anger, disgust, etc.) and behaviours (n=8, e.g., inform and persuade, moralise and blame, etc.). Global interjudge agreement was strong (κ=0.8). No difference was observed in themes according to gender, parental status or education, indicating a heterogenous awareness of stigma. However, some differences were observed according to smoking status (χ2 = 69.59, p = 0.02) (e.g., non-smokers more frequently stressed immorality).

Conclusion.

The stigma associated with smoking during pregnancy includes various components that might be measured and targeted in interventions to improve access to adequate healthcare and smoking cessation in this specific population.

Implications. This qualitative study explores the stigma that the general French population attaches to pregnant women who smoke. Themes regarding cognitions (e.g., irresponsible, thoughtless and unmindful, etc.), emotions (e.g., anger, disgust, etc.) and behaviours (e.g., inform and persuade, moralise and blame, etc.) were identified. These themes could guide further research regarding scale development and anti-stigma interventions to support smoking cessation.

Introduction.

In 2016, 32.9% of French adults were smokers. This is higher than in the USA (21.9%), Spain (29.4%), Belgium (28.3%), Ireland (24.4%), Portugal (23.2%), Norway (20.2%), and Europe (28.7%). [START_REF] Who | World Health Statistics data visualizations dashboard | Tobacco smoking[END_REF] Smoking has wellknown and serious health consequences, such as the development of cancer, cardiovascular and respiratory diseases and the impairment of reproductive functions. [START_REF] Onor | Clinical Effects of Cigarette Smoking: Epidemiologic Impact and Review of Pharmacotherapy Options[END_REF] Worldwide, smoking is associated with the death of 6 million people annually. [START_REF] Who | Global report: mortality attributable to tobacco[END_REF] During the past 50 years, in industrialised countries, social attitudes towards smokers have undergone a strong shift. Cigarette smoking is no longer regarded as a glamorous, upper-class activity. [START_REF] Chapman | Markers of the denormalisation of smoking and the tobacco industry[END_REF] Numerous authors have suggested that although tobacco-control policies are required and efficient, they might accidentally enhance the stigma of smoking. [START_REF] Bayer | Tobacco Control, Stigma, and Public Health: Rethinking the Relations[END_REF][START_REF] Bell | Smoking, stigma and tobacco "denormalization": Further reflections on the use of stigma as a public health tool. A commentary on Social Science & Medicine's Stigma, Prejudice, Discrimination and Health Special Issue (67: 3)[END_REF] Stigma is an "attribute that is deeply discrediting" and reduces someone "from a whole and usual person to a tainted, discounted one". [START_REF] Goffman | Stigma: Notes on the Management of Spoiled Identity[END_REF] Stigma can be attached to physical appearance (obesity, infirmity) deviant behaviours or conditions (mental illness, addiction, unemployment) or membership of a particular community (ethnic or religious groups). [START_REF] Goffman | Stigma: Notes on the Management of Spoiled Identity[END_REF] Cognitions ("They are dangerous") are at the core of stigma and can trigger both emotional ("I am scared of them") and behavioural reactions ("I avoid them"). [START_REF] Bos | Stigma: Advances in Theory and Research[END_REF] Today, health has become an important value and is widely regarded as being mainly dependent on the individual's behaviour. [START_REF] Blue | Theories of practice and public health: understanding (un)healthy practices[END_REF] As a consequence, smokers are subjected to moral condemnation for damaging their health and shortening their life expectancy. They are described as being selfish, thoughtless and undereducated. [START_REF] Chapman | Markers of the denormalisation of smoking and the tobacco industry[END_REF][START_REF] Seiter | Nonsmokers' Perceptions of Cigarette Smokers' Credibility, Likeability, Attractiveness, Considerateness, Cleanliness, and Healthiness[END_REF] Smokers are also subjected to social rejection and are regarded as undesirable housemates, [START_REF] Chapman | Markers of the denormalisation of smoking and the tobacco industry[END_REF] bad employees [START_REF] Chapman | Markers of the denormalisation of smoking and the tobacco industry[END_REF][START_REF] Roulin | Smoking as a Job Killer: Reactions to Smokers in Personnel Selection[END_REF] and unattractive love interests. [START_REF] Chapman | Markers of the denormalisation of smoking and the tobacco industry[END_REF][START_REF] Chapman | Smoking status of 132,176 people advertising on a dating website. Are smokers more "desperate and dateless[END_REF] Smokers themselves perceive this social disapproval [START_REF] Stuber | Smoking and the emergence of a stigmatized social status[END_REF] in family members, coworkers, healthcare providers and even strangers. [START_REF] Evans-Polce | The Downside of Tobacco Control? Smoking and Self-Stigma: A systematic review[END_REF] Whereas smoking has diminished in French men from 1980 (51.5%) to 2012 (34.4%), it has increased substantially in French women over the same period (18.8%-27.7%). [START_REF] Thomas | épidémie de tabagisme : état des lieux[END_REF] Pregnancy is often regarded as an opportunity to promote smoking cessation. However, 14.2% of pregnant French women smoke. This is higher than the prevalence reported in Sweden (5.4%), Switzerland (5.5%) and the United Kingdom (6.9%). [START_REF] Smedberg | Characteristics of women who continue smoking during pregnancy: a cross-sectional study of pregnant women and new mothers in 15 European countries[END_REF] In addition to the well-known risks that smoking poses to women's health [START_REF] Onor | Clinical Effects of Cigarette Smoking: Epidemiologic Impact and Review of Pharmacotherapy Options[END_REF] , tobacco consumption during pregnancy is associated with many health risks for the pregnancy and the unborn child. [START_REF] Mund | Smoking and Pregnancy -A Review on the First Major Environmental Risk Factor of the Unborn[END_REF] These risks include ectopic pregnancy, placenta insufficiency, spontaneous abortion, stillbirths, neonatal deaths, preterm birth, intrauterine growth retardation and birth defects. [START_REF] Mund | Smoking and Pregnancy -A Review on the First Major Environmental Risk Factor of the Unborn[END_REF][START_REF] Einarson | Smoking in pregnancy and lactation: a review of risks and cessation strategies[END_REF][START_REF] Hackshaw | Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls[END_REF] The societal expectation is that a pregnant woman will promote her health and protect her unborn child. [START_REF] Lee | Risk, Health and Parenting Culture[END_REF] Moreover, a sense of public ownership of a pregnant woman's body serves to justify the formation and expression of judgments and commentaries about their health behaviour that would be considered socially inappropriate for other people. [START_REF] Oaks | Smoking and Pregnancy: The Politics of Fetal Protection[END_REF] Thus, pregnant smokers might experience an even greater degree of stigma than other smokers. Scholars have observed that pregnant smoking women were rated more negatively (selfish and ignorant) than women who were smokers but not pregnant. [START_REF] Wigginton | Stigma and hostility towards pregnant smokers: does individuating information reduce the effect?[END_REF] Smoking women were also regarded as bad mothers. [START_REF] Wigginton | Stigma and hostility towards pregnant smokers: does individuating information reduce the effect?[END_REF] Most women who smoked while pregnant experienced strong negative social attitudes and reported feeling guilty, shameful and miserable. [START_REF] Flemming | Smoking in pregnancy: a systematic review of qualitative research of women who commence pregnancy as smokers[END_REF] Many report unpleasant social experiences, such as receiving harsh criticism from family, friends, coworkers and health professionals [START_REF] Flemming | Smoking in pregnancy: a systematic review of qualitative research of women who commence pregnancy as smokers[END_REF] .

While many researchers have studied the reasons that pregnant women keep smoking, little research has focused on the ways in which people perceive and respond to smoking pregnant women. Smoking stigma, especially in pregnant women, is an understudied topic, and of the studies that have been conducted, few are quantitative. [START_REF] Evans-Polce | The Downside of Tobacco Control? Smoking and Self-Stigma: A systematic review[END_REF] However, extensively describing the stigma associated with smoking during pregnancy might be helpful to support smoking cessation. It is well established that self-stigma is associated with poor mental health in various stigmatised situations (mental illness, non-heterosexual orientation, etc.). [START_REF] Mak | Meta-analysis of stigma and mental health[END_REF] Self-stigma is also a welldocumented barrier to healthcare-seeking behaviour and adherence to treatment. [START_REF] Stangl | The Health Stigma and Discrimination Framework: a global, crosscutting framework to inform research, intervention development, and policy on health-related stigmas[END_REF] Smoking self-stigma has been associated with the desire to stop smoking but also with negative consequences (anxiety, depression, guilt, low self-esteem and defensiveness, etc.), which then act to prevent smoking cessation. [START_REF] Evans-Polce | The Downside of Tobacco Control? Smoking and Self-Stigma: A systematic review[END_REF] More recently, it has been observed that stigma was associated with lower intention to stop smoking in people with low levels of selfefficacy and low income. [START_REF] Kim | Does Stigmatization Motivate People to Quit Smoking? Examining the Effect of Stigmatizing Anti-Smoking Campaigns on Cessation Intention[END_REF] In an experimental study, it was also observed that stereotype threat (situation in which a person is concerned about being judged or treated negatively on the basis of stereotypes [START_REF] Spencer | Stereotype Threat[END_REF] ) facilitates the inability to delay cigarette consumption. [START_REF] Cortland | The ironic effects of stigmatizing smoking: combining stereotype threat theory with behavioral pharmacology[END_REF] Stigma can also lead some smokers (8%-13%) to hide their smoking behaviour from healthcare providers. [START_REF] Curry | Nondisclosure of Smoking Status to Health Care Providers Among Current and Former Smokers in the United States[END_REF] It is especially noteworthy in pregnant smoking women, who underreport or hide their smoking behaviour (22.9%) more than non-pregnant women do (9.2%). [START_REF] Dietz | Estimates of Nondisclosure of Cigarette Smoking Among Pregnant and Nonpregnant Women of Reproductive Age in the United States[END_REF] Thus, stigma potentially prevents access to adequate healthcare for pregnant women who smoke, because of its association with distress and non-disclosure of their smoking status. Moreover, stigma has been shown to impact on the behaviour of healthcare providers dealing with mental health and substance-use disorders. [START_REF] Ungar | Theoretical and Practical Considerations for Combating Mental Illness Stigma in Health Care[END_REF][START_REF] Van Boekel | Stigma among health professionals towards patients with substance use disorders and its consequences for healthcare delivery: Systematic review[END_REF] Professionals who hold stigmatising attitudes towards people with substance-use disorders are less engaged and have a more taskoriented approach in healthcare provision, resulting in lower levels of personal involvement and empathy. [START_REF] Van Boekel | Stigma among health professionals towards patients with substance use disorders and its consequences for healthcare delivery: Systematic review[END_REF] Although no studies have focused specifically on the reduction of the stigma of smoking, a large corpus of literature, especially in the field of mental health, shows that it is possible to reduce stigma in the general population [START_REF] Heijnders | The fight against stigma: An overview of stigma-reduction strategies and interventions[END_REF][START_REF] Corrigan | Challenging the public stigma of mental illness: a meta-analysis of outcome studies[END_REF] , among healthcare providers [START_REF] Stubbs | Reducing mental illness stigma in health care students and professionals: a review of the literature[END_REF] and in the victims of stigma themselves. [START_REF] Mittal | Empirical Studies of Self-Stigma Reduction Strategies: A Critical Review of the Literature[END_REF] However, to develop interventions aimed at reducing the stigma of smoking during pregnancy, it is necessary to have an adequate tool to assess it. Currently, no tool has been designed to measure the stigma of smoking during pregnancy. Two scales are used to assess the stigma of smoking in general, but these have been derived from measures of mental health stigma. [START_REF] Stuber | Smoking and the emergence of a stigmatized social status[END_REF][START_REF] Brown-Johnson | Validity and Reliability of the Internalized Stigma of Smoking Inventory: An Exploration of Shame, Isolation, and Discrimination in Smokers with Mental Health Diagnoses[END_REF] Boateng et al. strongly recommend the use of qualitative inductive methods to identify relevant themes and to generate adequate items from the responses of individuals. [START_REF] Boateng | Best Practices for Developing and Validating Scales for Health, Social, and Behavioral Research: A Primer[END_REF] For that reason, the Pregnant Smoker Stigma Scale (P3S) study was designed to build a scale assessing the stigma associated with smoking during pregnancy in both the general population (public stigma) and pregnant smoking women (self-stigma). The first step in this study was to describe this stigma in the general population. This description will guide the subsequent scale construction. The aim of this paper is to document this first step.

Method.

Procedure and Participants.

Participants were French adults recruited from the general population through social media (Facebook).

They had to be resident in France and older than 18. A brief presentation of the study was posted on various community groups of residents of and students in French cities (Anglet, Angouleme, Biarritz, Bordeaux, Bayonne, Caen, Cannes, La Rochelle, Lille, Lyon, Marseille, Montpellier, Nancy, Nantes, Nice, Paris, Poitiers, Reims, Rennes, Rouen, Strasbourg, Toulon and Toulouse). Participants were automatically directed to the questionnaire hosted at LimeSurvey (https://www.limesurvey.org/). All participants received written information and signed an informed consent form. All procedures were performed in accordance with the 1964 Declaration of Helsinki and its subsequent amendments. This study was approved by an institutional review board (IRB00003888, IORG0003254, FWA00005831).

Assessment.

Cognitions are at the core of stigma and can trigger both emotional and behavioural reactions. [START_REF] Bos | Stigma: Advances in Theory and Research[END_REF] Therefore, three pairs of open-ended questions were formulated by consensus of the research team members and used to explore cognitions, emotions and behaviours elicited by pregnant smoking women (Table 1). To avoid social desirability bias which is commonly observed in online data collection, 39 these questions were formulated to ask what 'most people' think, feel and do. Next, participants were requested to provide a range of personal characteristics (age, gender, marital and parental status, education and employment) and to indicate their smoking status.

Analyses.

Our approach is in line with grounded theory. [START_REF] Tie | Grounded theory research: A design framework for novice researchers[END_REF] After an initial screening of the data, a thematic analysis [START_REF] Braun | Using thematic analysis in psychology[END_REF] was performed, taking an inductive approach. Thereafter, a thematic guide was constructed. The coding order was randomly selected. This analysis was performed by a research team member with significant experience in qualitative data analyses (DL, health psychologist, PhD, female, former smoker). Our sample size is bigger than what is usually observed in qualitative research and is sufficient to ensure data saturation. [START_REF] Vasileiou | Characterising and justifying sample size sufficiency in interview-based studies: systematic analysis of qualitative health research over a 15-year period[END_REF] Themes that were deemed too small (n<5) to be significant in the context of stigma were excluded. Per definition, stigma is supposed to be widely shared and well known among members of a culture. [START_REF] Major | The Social Psychology of Stigma[END_REF] To ensure reliability, another researcher with significant experience in qualitative data analyses (NC, health psychologist, PhD, male, former smoker) performed an independent deductive thematic analysis using the thematic guide on 30% of data randomly selected. An inter-judge agreement was computed. Cohen's kappa coefficient indicates the level of agreement that might be weak (≥.40) moderate (≥.60), strong (≥.80), or very strong (≥.90). Finally, chi-square test for independence was performed to explore whether the themes differed according to gender, education, parenthood and smoking status. Thematic analysis and inter-judge agreement were performed with Nvivo 12 software. Descriptive statistics and chi-square were computed with RStudio software (version 1.2.5033).

Results.

Participant characteristics are presented in Table 2 (N=100 The average age of participants was 31 (M=30.92, SD=11.97, range = 18-63 years). Women constituted 60% of the participants and men 40%. Nearly half of the participants were smokers (46%), while 33% were non-smokers and 21% were former smokers. One third of the participants had children (33%).

Regarding the qualitative data production, participants generated content that was nearly 50 words long (M=49.17, SD=49. 19). There was no significant difference in the number of words generated according to gender, education, parental status or smoking status. Themes (n=25) were defined regarding cognitions (n=9, irresponsible, thoughtless and unmindful, selfish, immoral, neglectful, dangerous, bad mother, addicted, stupid), emotions (n=8, anger, disgust, sadness and pity, incomprehension, shock, disregard, fear and worries, discomfort) and behaviours (n=8, inform and persuade, moralise and blame, judge and disapprove, criticise and reproach, reprimand and aggress, support and understand, no reaction, avoid and reject). Themes and quotes are presented in Table 3. Smaller themes that were mentioned less than five times were not presented but only mentioned as table notes. Cohen's kappa indicated a strong level of agreement for the coding as a whole (κ =.8) and each theme (κ>.6) except for "support and understand" (κ=0.24) and "avoid and reject" (κ=0.39) (see Table 3). Independence (chi-square) between the themes and various variables (gender, parenthood, smoking status and education) was tested. No difference was observed according to gender (χ2 = 25.27, p = .37), parenthood (χ2 = 32.36, p = 0.11) or education (χ2 = 56.04, p = 0.20). Some differences were observed regarding smoking status (χ2 = 69.59, p = 0.02). Standardised residuals were observed to check for meaningful associations (≥2) (Table 4). Non-smokers more frequently emphasised immorality and lack of reaction themes, while smokers less frequently emphasised the addiction theme. The "sadness and pity" theme was more frequent in non-smokers than in smokers.

Discussion.

The P3S study was designed to build a scale that assessed the stigma associated with smoking during pregnancy in both the general population (public stigma) and pregnant smoking women (internalisation leading to self-stigma). This study's first step was to describe this stigma in the general population, in order to guide the scale construction thereafter. Indeed, to decide which themes and items should be included in the development of a scale, qualitative inductive methods are strongly advised. [START_REF] Boateng | Best Practices for Developing and Validating Scales for Health, Social, and Behavioral Research: A Primer[END_REF] Such analyses guide item generation and formulation as closely as possible to the speech of participants [START_REF] Boateng | Best Practices for Developing and Validating Scales for Health, Social, and Behavioral Research: A Primer[END_REF] . The aim of this paper is to document this first step.

As mentioned, French adults recruited from the general population through Facebook were asked what "most people" think, feel and do when they encounter pregnant women who smoke. Our analysis identified 25 themes regarding cognitions (n=9), emotions (n=8) and behaviours (n=8) that are elicited by pregnant smoking women in the general population.

First, cognitions regarding women who smoke while pregnant need to be understood within the broader framework of the contemporary risk society. [START_REF] Hookway | Risk, morality and emotion: social media responses to pregnant women who smoke[END_REF] In modern Western societies, individual risk management has become a moral imperative, [START_REF] Blue | Theories of practice and public health: understanding (un)healthy practices[END_REF] one that is especially imbued in the 'good mothering' mandate. [START_REF] Lee | Risk, Health and Parenting Culture[END_REF][START_REF] Lupton | The best thing for the baby': Mothers' concepts and experiences related to promoting their infants' health and development[END_REF][START_REF] Douglas | The Mommy Myth: The Idealization of Motherhood and How It Has Undermined All Women[END_REF][START_REF] Hays | The Cultural Contradictions of Motherhood[END_REF] The failure to protect oneself against risk is construed as a moral violation of the responsible, civilised and ordered middleclass body. [START_REF] Reich | Neoliberal Mothering and Vaccine Refusal: Imagined Gated Communities and the Privilege of Choice[END_REF] Themes in our analysis reflected how women who smoke during their pregnancy were considered to have failed this moral imperative. They were portrayed as thoughtless and unmindful because they ignore risks and do not manage them adequately ("She acts rashly and does not weigh up the risks.'). Such women are even labelled dangerous because they deliberately expose their unborn child to health risks ("She poisons her baby"). They are also portrayed as neglectful ("She cares little about her child's health and is negligent with him") and selfish mothers ("She values her pleasure over the smooth growth of the foetus") who do not care about their unborn child and its health. It is in conflict with the very definition of mothering as a "set of activities and relationships involved in nurturing and caring for people". [START_REF] Glenn | Social constructions of mothering: A thematic overview[END_REF] Mothers are also supposed to be highly selfless, because "the very definition of good mothering includes the willingness to give up things so that your children can have things" [START_REF] Hays | The Cultural Contradictions of Motherhood[END_REF] . Moreover, women who smoke during their pregnancy were portrayed as immoral. This perception is expressed in simple statements ("I think it's wrong") but also in highly pejorative terms ("It's a shame", "She's a whore", "She is not worthy of being a mother"). The observation was made earlier that unhealthy behaviour (e.g. overeating, lack of exercise, etc.) are thought to be associated with a lack of morality. [START_REF] Hoverd | Immoral Bodies: The Implicit Association Between Moral Discourse and the Body[END_REF] Moreover, morality is an important aspect of the motherhood mandate. [START_REF] Hays | The Cultural Contradictions of Motherhood[END_REF] It is important to note that immorality has been associated with disgust and behavioural avoidance [START_REF] Tapp | The essence of crime: Contagious transmission from those who have committed moral transgressions[END_REF] , two themes that emerged from our analyses. Some participants mentioned that smoking when pregnant was an addiction issue. However, this was not a frequent theme when compared to the themes of being irresponsible, thoughtless, unmindful and selfish.

Viewing smoking during pregnancy as an addiction issue is probably factually accurate, and this view lacks the moral condemnation that this transgression evokes in most people. Unexpectedly, some participants (n=2) commented that women who smoke while pregnant might also be consuming alcohol ("Maybe she also drinks").

This was not a frequent comment, but it might have important implications given the stigma that is also attached to alcohol consumption during pregnancy. [START_REF] Corrigan | Stakeholder perspectives on the stigma of fetal alcohol spectrum disorder[END_REF] Thus, a woman who smokes during pregnancy might be regarded through the lens of multiple stigmatising behaviours. [START_REF] Turan | Challenges and opportunities in examining and addressing intersectional stigma and health[END_REF] Finally, women smoking during their pregnancy are portrayed as bad mothers. This has been described previously in the literature and is not surprising. [START_REF] Wigginton | Stigma and hostility towards pregnant smokers: does individuating information reduce the effect?[END_REF][START_REF] Hookway | Risk, morality and emotion: social media responses to pregnant women who smoke[END_REF] Nevertheless, this remains an important finding because being a good mother is central to the identity of most mothers [START_REF] Crenner | Rôles familiaux et identité[END_REF] . Being labelled and labelling oneself as a bad mother could cause depressive symptoms in mothers-tobe who smoke and prevent them from successfully giving up smoking. [START_REF] Scott | Depressive symptoms predict smoking status among pregnant women[END_REF] It is of interest to note that previous studies have found some of the emotions reported in this study to be similarly elicited by groups that are low in competence. These emotional responses are triggered by groups that are either high in warmth (e.g. feeling pity for disabled or elderly people) or low in warmth (e.g. feeling disregard for poor or homeless people). [START_REF] Fiske | A model of (often mixed) stereotype content: Competence and warmth respectively follow from perceived status and competition[END_REF] This correspondence is notable, because it indicates that pregnant smokers might be at the receiving end of both contemptuous and paternalistic prejudice. [START_REF] Fiske | A model of (often mixed) stereotype content: Competence and warmth respectively follow from perceived status and competition[END_REF] This double prejudice possibly stems from the fact that pregnant smokers generate ambivalent feelings because they combine a positive feature (being pregnant) and a negative one (smoking). This double prejudice could also be related to the complex attitude that many people have towards those who struggle with addiction. They are often framed either as criminals who should be held morally responsible for their behaviour (contemptuous prejudice) or as victims of a disease (paternalistic prejudice). [START_REF] Heather | Is Addiction a Brain Disease or a Moral Failing? A: Neither[END_REF] However, it is important to note that participants mentioned feeling sadness and pity for both the mother and the baby (e.g., "sad for her and her child") but sometimes for the unborn child only (e.g., "sadness for the baby, who is endangered"). Anger has also been associated with lowwarmth groups such as poor or homeless people. [START_REF] Cuddy | The BIAS map: behaviors from intergroup affect and stereotypes[END_REF] This emotion is usually associated with the perception of a violation of social norms and threat to the group's moral standing [START_REF] Cottrell | Different emotional reactions to different groups: a sociofunctional threat-based approach to "prejudice[END_REF][START_REF] Dubreuil | Punitive emotions and norm violations[END_REF] . However, anger might also be precipitated by disgust. [START_REF] Tapp | The essence of crime: Contagious transmission from those who have committed moral transgressions[END_REF][START_REF] Cottrell | Different emotional reactions to different groups: a sociofunctional threat-based approach to "prejudice[END_REF] As mentioned above, disgust is frequently mentioned in our analysis and has been associated with perceptions of immorality and a threat being posed to group values. [START_REF] Tapp | The essence of crime: Contagious transmission from those who have committed moral transgressions[END_REF][START_REF] Cottrell | Different emotional reactions to different groups: a sociofunctional threat-based approach to "prejudice[END_REF] Anger and disgust are also described as manifestations of a moral outrage. [START_REF] Hookway | Risk, morality and emotion: social media responses to pregnant women who smoke[END_REF] Indeed, pregnant smokers challenge the dominant view of the ideal, selfless mother who rationally screens for and avoids various risks to protect her precious and innocent unborn child. This discrepancy or cognitive dissonance could enforce discomfort [START_REF] Harmon-Jones | An introduction to cognitive dissonance theory and an overview of current perspectives on the theory[END_REF] and consequent behaviours of rejection or avoidance of pregnant smokers.

Regarding behaviours, one might assume that they can easily be divided into two main descriptive categories, namely harmful behaviours (moralise and blame, judge and disapprove, criticise and reproach, reprimand and aggress, avoid and reject) and facilitative behaviours (inform and persuade, support and understand). [START_REF] Cuddy | The BIAS map: behaviors from intergroup affect and stereotypes[END_REF] However, the matter is more complex than that. First, information and persuasion can certainly be seen as well-meaning behaviour by people who are genuinely concerned about the health of their loved one. However, receiving advice about one's smoking may unfortunately trigger reactance in some smokers and pregnant smokers. [START_REF] Rosenberg | A 50-year review of psychological reactance theory: Do not read this article[END_REF] Obviously, the manner in which such information is imparted plays a role. The aggressive, unsolicited and commanding provision of information is not equivalent to a benevolent and mutual discussion about tobacco use. Secondly, harmful behaviours can be divided into active or punitive harm (criticise and reproach, reprimand and aggress, etc.) and passive harm (avoid and reject). [START_REF] Cuddy | The BIAS map: behaviors from intergroup affect and stereotypes[END_REF] While active harm might be associated with disregard only, passive harm might be associated with both disregard and pity. [START_REF] Cuddy | The BIAS map: behaviors from intergroup affect and stereotypes[END_REF] Similarly, emotions such as disregard and disgust could feed into indirect and collective forms of punishment, such as mockery and exclusion. [START_REF] Dubreuil | Punitive emotions and norm violations[END_REF] . Our results regarding active harm (criticise and reproach, reprimand and aggress) are in accordance with the findings of previous qualitative studies that many pregnant women who smoke report unpleasant social experiences. [START_REF] Flemming | Smoking in pregnancy: a systematic review of qualitative research of women who commence pregnancy as smokers[END_REF] Moreover, results regarding avoidance and rejection are in accordance with the literature, which shows that smokers are seen as undesirable persons. [START_REF] Chapman | Markers of the denormalisation of smoking and the tobacco industry[END_REF][START_REF] Roulin | Smoking as a Job Killer: Reactions to Smokers in Personnel Selection[END_REF][START_REF] Chapman | Smoking status of 132,176 people advertising on a dating website. Are smokers more "desperate and dateless[END_REF][START_REF] Peretti-Watel | Cigarette smoking as a stigma: evidence from France[END_REF] It is especially important when considering that social network and support work in favour of both good postnatal mental health [START_REF] O'hara | Postpartum Depression: What We Know[END_REF] and smoking cessation. [START_REF] Glanz | Health Behavior and Health Education: Theory, Research, and Practice[END_REF] Generally, our results support the idea that smoking during pregnancy is mostly seen as reprehensible [START_REF] Oaks | Smoking and Pregnancy: The Politics of Fetal Protection[END_REF][START_REF] Hookway | Risk, morality and emotion: social media responses to pregnant women who smoke[END_REF] and that this view motivates various punitive behaviours. Other scholars have previously indicated that smoking during pregnancy and around young children could even be viewed by some as a form of child abuse and calls for punitive legislation and policies. [START_REF] Bell | Medicine, morality and mothering: public health discourses on foetal alcohol exposure, smoking around children and childhood overnutrition[END_REF][START_REF] Goldstein | Is Exposure to Secondhand Smoke Child Abuse? Yes[END_REF] Finally, the test of independence between themes and various variables (gender, education, smoking status and parental status) found no major differences between participants with diverse personal characteristics. This finding confirms, as expected, that the awareness of the stigma attached to smoking during pregnancy is widespread. [START_REF] Major | The Social Psychology of Stigma[END_REF] However, some differences were observed in line with smoking status. First, non-smokers reported more frequently lack of reaction. This difference in response might stem from the fact that smokers and former smokers are more aware of smoking eliciting negative reactions because they have experienced such responses in various contexts. [START_REF] Stuber | Smoking and the emergence of a stigmatized social status[END_REF][START_REF] Evans-Polce | The Downside of Tobacco Control? Smoking and Self-Stigma: A systematic review[END_REF] . Differences in the responses relating to immorality, addiction, and sadness and pity seem to indicate a stronger awareness of these notions in non-smokers. Those differences are difficult to interpret given that participants were asked to report on what "most people think, feel and do" (e.g., "The common opinion is to criticise them for their selfishness"). However, some participants were clearly expressing their personal point of view (e.g., "I would not hesitate to tell her what I thinkthat it's a shame not to want the best for your baby's health."). The difference in responses in line with smoking status could be explained by the fact that non-smokers endorse harsh attitudes more strongly.

This study documents extensively the stigma that is attached to women who smoke when pregnant. The next step in the study will be to develop a new scale, the P3S, to quantify this stigma. The P3S items will be written as closely as possible to participants' speech to assess each theme. Providing researchers with a scale to assess the stigma of smoking when pregnant could spark new research efforts to better understand this stigma and its impact. This would enable the design of innovative interventions to decrease the stigma.

This study has some limitations, which should be acknowledged. First, this study examines the stigma of smoking when pregnant in French society. While some core cognitions, emotions and behaviours might be shared by certain countries, others might not. This difference could be the result of a range of variables, such as the strictness of tobacco control measures, family policy (social programs, laws, and public directives regarding family) or gender ideology. It would be of value to conduct studies similar to this one in countries with stricter (Ireland, United Kingdom, Norway) or more lenient (Luxembourg Romania, Latvia) tobacco control policies. [START_REF] Joossens | The Tobacco Control Scale: a new scale to measure country activity[END_REF] Secondly, this study relies on online recruitment and data collection. Research about online recruitment and data collection is still scarce, but the field offers promising research opportunities. [START_REF] King | Social media recruitment and online data collection: A beginner's guide and best practices for accessing low-prevalence and hard-to-reach populations[END_REF] The internet and social media offer a cost-effective way to quickly recruit a large number of participants. However, issues have been raised regarding the representativeness of samples recruited online. Internet users are known to be younger, wealthier and more educated than non-users. [START_REF] Skitka | The internet as psychological laboratory[END_REF] Moreover, our recruitment method through various Facebook community groups of residents of and students in major French cities might over-represent younger people who live in urban areas. Thirdly, this qualitative online data collection method does not provide an opportunity for in-depth investigation, as would be the case in face-to-face interviews. However, while the obtained written information was brief (50 words on average), our sample size was larger than those usually observed in qualitative research. [START_REF] Vasileiou | Characterising and justifying sample size sufficiency in interview-based studies: systematic analysis of qualitative health research over a 15-year period[END_REF] Fourthly, it is crucial to bear in mind that our questions did not investigate the participant's personal opinion.

They were asked about what 'most people' think, feel and do. This formulation was chosen to deal with social desirability bias, an issue that is commonly observed in online data collection. [START_REF] Dodou | Social desirability is the same in offline, online, and paper surveys: A meta-analysis[END_REF] Consequently, this study does not provide evidence regarding how widespread those negatives views are or if participants agreed with them.

Nevertheless, as researchers we assert that the first step to effectively assess stigma is to describe it through such qualitative methods. Finally, we have chosen to exclude themes that were deemed too small (n<5) to be significant. After all, stigma is per definition widely shared and well known among members of a culture. [START_REF] Major | The Social Psychology of Stigma[END_REF] However, the decision to incorporate quantitative cut-offs in qualitative analyses is controversial. [START_REF] Elliott | Thinking about the Coding Process in Qualitative Data Analysis[END_REF] For this reason smaller themes are nonetheless presented for information (Table 3) and would lend themselves to further research. Judge and Disapprove 28 3.18 .76 "They allow themselves to judge", "by disapproving", "Some people will judge her"

Criticize and Reproach 23 4.02 .80 "They may make disparaging remarks or reproach her directly", "Allow themselves to tell her openly what she should and shouldn't do" Reprimand and Aggress 12 1.10 .82 "People can be aggressive", "People may behave badly and reprimand this woman".

"Being severe by reprimanding her", "Clashes may happen", "Verbally belittle her" Support and Understand 9 1.50 .24 "Do not blame her", "Others will be sympathetic and seek to understand why she continues to smoke", "The companion can stop at the same time to support her" No Reaction 8 1.03 .63 "They don't say anything because it's very sensitive to talk about it", "It is not the role of friends or colleagues to interfere", "They remain passive" Avoid and Reject 5 0.41 .39 "Can be kept out of the way or avoided", "Some react with disgust and move away from the person", "I couldn't meet here anymore because I found it so horrible" Note. a Number of occurrences of the theme in the corpus. b Percentage covered by the theme in the whole corpus. c Cohen's Kappa indicating inter-judge agreement obtained on 30% of the corpus. Themes that were dropped out (N<5) are: unstable, lack of will, social outcast, childish, disappointment, to frighten her, to gaze at her and to criticise her behind her back .

Table 1 .

 1 Stigma Questions

Cognitions

What do most people think of a pregnant woman who smokes?

How would most people describe a pregnant woman who smokes?

Emotions a How does most people feel when they see a pregnant woman smoking?

What emotions do most people feel when they see a pregnant woman smoking?

Behaviors b How do some people (friends, family, colleagues, doctors...) behave with a pregnant woman who smokes?

How do some people (friends, family, colleagues, doctors...) react to a pregnant woman who smokes? Note. a . Help displayed. "Emotions are for example: joy, fear, anger, sadness, disgust, surprise, shame…" b . Help displayed. "If you can, provide examples"

Table 2 .

 2 Participants Characteristics. Advise her not to smoke because it is dangerous for her and her baby", "They would probably try to convince her to stop by informing her of the risks to the child" Moralise and Blame 35 5.26 .87 "Moralists", "They try to make her feel guilty", "By lecturing her"

	Variables	M(SD) or %
	Age	30.92 (11.97)
	Gender
	Female	60%
	Male	40%
	Marital Status
	Single	33%
	Couple	34%
	Married	31%
	Widowed	2%
	Number of Children
	0	68%
	1	11%
	2	13%
	≥ 3	8%
	Age of the Youngest Child a	11.47 (9.36)
	Education Level
	≤ High School Diploma	24%
	≤ Bachelor Degree	35%
	≤ Master Degree	37%
	≤ PhD	4%
	Employment
	Students	31%
	Working	58%
	Unemployed/At Home	9%
	Retired	2%
	Skill Level
	Students	31%
	Low Qualification	31%
	Medium Qualification	10%

Table 4 .

 4 Standardised residuals regarding independence (chi-

	square) between themes and smoking status
		Non-smokers N=33	Former Smokers N=21	Smokers N=46
	Cognitions
	Irresponsible	0.07	0.61	-0.53
	Thoughtless and Unmindful	1.33	-0.59	-0.85
	Selfish	-1.36	-0.81	1.95
	Immoral	2.01	-1.48	-0.84
	Neglectful	-1.38	-0.64	1.84
	Dangerous	-1.88	1.12	0.99
	Bad Mother	0.53	0.55	-0.94
	Addicted	1.11	1.68	-2.36
	Stupid	0.07	1.34	-1.09
	Emotions
	Anger	-0.68	0.50	0.28
	Disgust	-0.26	1.38	-0.79
	Sadness and Pity	2.15	0.05	-2.14
	Incomprehension	1.00	-0.18	-0.84
	Shock	-1.68	1.70	0.36
	Disregard	-1.28	-0.62	1.73
	Fear and Worries	-1.01	0.39	0.69
	Discomfort	1.73	-1.67	-0.42
	Behaviours
	Inform and Persuade	1.62	-0.71	-1.04

Funding.

This study is funded by the French National Institute of Cancer (TABAC-2020-019).

Data availability statement

Data available on request.

Declaration of Interest.

The authors declare that they have no conflict of interest. .87 .86 "A pregnant woman who smokes is irresponsible", "A woman who is aware that she is pregnant is irresponsible to smoke", "She is not a reasonable woman" Thoughtless and Unmindful 33 4.73 .83 "Most people would describe her as unmindful", "She acts rashly and does not weigh up the risks", "A pregnant woman who smokes can be described as unaware of the dangers" Selfish 31 1.94 .94 "The common opinion is to criticise them for their selfishness", "Totally egocentric", "She privileges her pleasure over the smooth growth of the foetus" Immoral 25 2.67 .99 "It's a shame", "She's a whore", "Contrary to the morals of most people", "She is not worthy to be a mother", "I think it's wrong" Neglectful 20 2.88 .66 "She doesn't pay enough attention to her baby's health", "She cares little about her child's health and is negligent with him", "She doesn't respect her health and that of her child" … Dangerous 18 3.71 .80 "She puts her child in danger", "She poisons her baby" Bad Mother 15 1.94 .63 "Bad mother", "who will not be a good mother", "future bad mother"