Camille Pouchieu
email: c.pouchieu@uren.smbh.univ-paris13.fr

Rachel Levy

Céline Faure

Valentina A Andreeva

Pilar Galan

Serge Hercberg

Mathilde Touvier

Rachel Le ´vy

Ce ´line Faure

Socioeconomic, lifestyle and dietary factors associated with dietary supplement use during pregnancy

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

Introduction

Pregnancy is a physiologically-specific period during which the needs for some nutrients increase. While the nutrient requirements of the general population can be met by an adequate diet, risk of suboptimal micronutrient intake is common during pregnancy [START_REF] Blumfield | A systematic review and meta-analysis of micronutrient intakes during pregnancy in developed countries[END_REF] and supplements might be useful to meet dietary requirements for specific key nutrients. In France as in several other countries, 0.4 mg/day of folic acid is recommended before the conception, at the beginning of pregnancy to reduce the risk of neural tube defects (NTD), and also later during pregnancy, to prevent megaloblastic anemia in the mother [START_REF] Martin | The ''apports nutritionnels conseille ´s (ANC)'' for the French population[END_REF][START_REF] Lassi | Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes[END_REF][START_REF] Mcnally | Periconceptional folic acid supplementation in a nationally representative sample of mothers[END_REF][START_REF] Nilsen | Patterns and predictors of folic acid supplement use among pregnant women: the Norwegian Mother and Child Cohort Study[END_REF][START_REF] Vandevijvere | Determinants of folate status in pregnant women: results from a national cross-sectional survey in Belgium[END_REF][START_REF] Candito | Nutritional and genetic determinants of vitamin B and homocysteine metabolisms in neural tube defects: A multicenter case-control study[END_REF]. The 2011 incidence of NTD in France was estimated at 1.0 case per 1000 births [START_REF] Eurocat | Prevalence Tables[END_REF], while upwards of 200 cases per year could be prevented by improving folic acid intake [START_REF]Enrichissement de la farine en vitamines B en France: proposition d'un programme-pilote[END_REF]. This has led some countries to proceed with large-scale dietary folic acid fortification programmes [START_REF] Castillo-Lancellotti | Impact of folic acid fortification of flour on neural tube defects: a systematic review[END_REF]. The prevalence of anemia in developed countries (due to iron deficiency in 2/3 of the cases) is estimated at around 5% before pregnancy and is tripled during pregnancy [START_REF] Schlienger | Dietary supplements during pregnancy: a review[END_REF]. Anemia is a risk factor for preterm delivery, low birth weight and cognitive impairment in the infant [START_REF] Milman | Iron in Pregnancy -How Do We Secure an Appropriate Iron Status in the Mother and Child?[END_REF][START_REF] Alwan | Dietary iron intake during early pregnancy and birth outcomes in a cohort of British women[END_REF]. Vitamin D deficiency has been associated with the risk of pre-eclampsia, gestational diabetes, preterm delivery, low birth weight, and low fetal bone mineral content [START_REF] Li | Suboptimal vitamin D levels in pregnant women despite supplement use[END_REF]. Iodine deficiency is associated with maternal and fetal goiter, cretinism, intellectual impairments, neonatal hypothyroidism, increased risk of miscarriage and infant mortality [START_REF] Stagnaro-Green | Iodine Supplementation during Pregnancy and Lactation[END_REF]. Thus, folic acid, iron, vitamin D and iodine supplementation at moderate doses is recommended for pregnant women at risk of deficiency. In contrast, other systematic supplementation is not necessary in the absence of specific pathological situations and some supplements should even be avoided [START_REF] Autorite ´de Sante | Recommandations professionnelles[END_REF]. Excessive intake of retinol [START_REF] Schnorr | The effects of vitamin A supplementation to rats during gestation and lactation upon redox parameters: Increased oxidative stress and redox modulation in mothers and their offspring[END_REF] or vitamin E [START_REF] Smedts | High maternal vitamin E intake by diet or supplements is associated with congenital heart defects in the offspring[END_REF], for example, may have serious deleterious effects on fetal development. According to the Developmental Origins of Health and Disease (DOHaD) concept [START_REF] Barouki | Developmental origins of non-communicable disease: Implications for research and public health[END_REF], exposure to nutritional factors in utero is likely to have major health consequences in later life, notably through epigenetic mechanisms [START_REF] Steegers-Theunissen | Periconceptional Maternal Folic Acid Use of 400 mg per Day Is Related to Increased Methylation of the IGF2 Gene in the Very Young Child[END_REF][START_REF] Jaddoe | Fetal nutritional origins of adult diseases: challenges for epidemiological research[END_REF].

Despite being of major public health concern, little information is available regarding dietary supplement (DS) use in pregnant women worldwide [START_REF] Mcnally | Periconceptional folic acid supplementation in a nationally representative sample of mothers[END_REF][START_REF] Picciano | Use of dietary supplements by pregnant and lactating women in North America[END_REF][START_REF] Branum | Dietary Supplement Use and Folate Status during Pregnancy in the United States[END_REF][START_REF] Haugen | Dietary Supplements Contribute Substantially to the Total Nutrient Intake in Pregnant Norwegian Women[END_REF][START_REF] Tarrant | Maternal and infant nutritional supplementation practices in Ireland: implications for clinicians and policymakers[END_REF][START_REF] Jensen | Sources and Determinants of Vitamin D Intake in Danish Pregnant Women[END_REF]. Some studies conducted in various countries have suggested that DS use may be more frequent in older [START_REF] Haugen | Dietary Supplements Contribute Substantially to the Total Nutrient Intake in Pregnant Norwegian Women[END_REF][START_REF] Sullivan | Multivitamin use in pregnant and nonpregnant women: results from the Behavioral Risk Factor Surveillance System[END_REF][START_REF] Arkkola | Dietary intake and use of dietary supplements in relation to demographic variables among pregnant Finnish women[END_REF], well-educated [START_REF] Haugen | Dietary Supplements Contribute Substantially to the Total Nutrient Intake in Pregnant Norwegian Women[END_REF][START_REF] Tarrant | Maternal and infant nutritional supplementation practices in Ireland: implications for clinicians and policymakers[END_REF][START_REF] Sullivan | Multivitamin use in pregnant and nonpregnant women: results from the Behavioral Risk Factor Surveillance System[END_REF][START_REF] Arkkola | Dietary intake and use of dietary supplements in relation to demographic variables among pregnant Finnish women[END_REF], non-smoking and primiparous women [START_REF] Haugen | Dietary Supplements Contribute Substantially to the Total Nutrient Intake in Pregnant Norwegian Women[END_REF]. However, information is lacking about differences in nutrient intake from food between pregnant DS users and non-users. If DS use is indeed associated with different sociodemographic, economic, lifestyle, and dietary factors, an accurate assessment of these associations is necessary in order to better target the nutritional recommendations regarding pregnant women's supplementation with specific nutrients.

Our objectives were: 1) to investigate the demographic, socioeconomic, lifestyle and dietary correlates of overall and folic acid DS use in pregnant women included in the NutriNet-Sante ćohort study; and 2) to assess the role of physicians in the motives for DS purchases and the proportion of self-medicating users.

Methods

Study population

Worldwide, the NutriNet-Sante ´study is the first large-scale population-based prospective cohort study that is exclusively Internet-based. It aims at elucidating the relationships between nutrition and chronic disease risk, as well as defining the determinants of eating behaviour [START_REF] Hercberg | The Nutrinet-Sante ´Study: a web-based prospective study on the relationship between nutrition and health and determinants of dietary patterns and nutritional status[END_REF]. It was launched in France in May 2009. Adults ($18 y) living in France and having access to the Internet are recruited via mass-media campaigns. The study was approved by the Institutional Review Board of the French Institute for Health and Medical Research (IRB Inserm nu0000388FWA00005831) and the ''Commission Nationale de l'Informatique et des Liberte ´s'' (CNIL nu908450 and nu909216). Written informed consent was obtained from all subjects.

Data collection

Participants fill in self-administered web-based questionnaires at baseline and then regularly during the follow-up. Several of the baseline questionnaires were tested and compared against traditional assessment methods (paper questionnaires or interviews by a dietitian) [START_REF] Touvier | Comparison between web-based and paper versions of a self-administered anthropometric questionnaire[END_REF][START_REF] Touvier | Comparison between an interactive web-based self-administered 24 h dietary record and an interview by a dietitian for large-scale epidemiological studies[END_REF][START_REF] Vergnaud | Agreement between web-based and paper versions of a socio-demographic questionnaire in the NutriNet-Sante study[END_REF]. In the NutriNet-Sante ´study, 60388 women had completed the DS questionnaire.

Pregnancy data. At baseline and regularly over the followup, data on current pregnancy and due date were collected through health status questionnaires.

Dietary supplement use. The questionnaire regarding DS use was administered two months after baseline in the entire cohort. In our study, we considered as DS both regular DS and medicinal supplements mainly composed of vitamins and minerals, which are treated as pharmaceutical products in France.

Participants were asked if they were currently taking any supplement at least 3 days a week. They were also asked to specify the type of DS using a list of 34 different nutrients and substances. They had to refer to the nutritional information on the packaging of the DS that they were currently taking. Circumstances of DS purchase (notably role of physicians versus selfmedication) were also reported. Demographic, socioeconomic, lifestyle and behavioural data. At baseline, self-administered questionnaires were used to collect data on demographic, socioeconomic and lifestyle characteristics, including age, geographical region, marital status, number of children, educational level, socioprofessional category, and income.

Dietary data. Each year, the participants are asked to complete three non-consecutive self-administered web-based 24 h dietary records, the days for which are randomly assigned during a two-week period (two days during the week and one day during the weekend). All foods and beverages consumed at breakfast, lunch, dinner and at all other occasions are recorded. For foods with potentially high nutrient variability, participants are also asked to provide the brand name. The participants are asked to estimate the portion size for each reported food and beverage item using validated photographs [START_REF] Hercberg | SU.VI.MAX Portions alimentaires manuel-photos pour l'estimation des quantite[END_REF]. Daily dietary intakes of energy and nutrients are then calculated using the NutriNet-Sante food composition table, which includes more than 2500 different foods.

Knowledge of official nutritional recommendations as provided in the French National Nutrition and Health Programme (PNNS) was also assessed. Finally, a specific questionnaire was used to assess the opinion and behaviour of women as regards organic food.

Statistical analyses

All women who entered the cohort before September 2012 and had completed the DS questionnaire while pregnant were included in the present study (n = 903).

We estimated the proportion of DS users overall and according to the trimester of pregnancy. Types of DS as well as circumstances of purchase were also described.

DS users (overall and specifically regarding folic acid) and nonusers were compared by age-adjusted unconditional logistic regression analyses, regarding their sociodemographic characteristics (age, geographical region, marital status, number of children, education, income, and socioprofessional category), knowledge of official nutritional recommendations and organic food consumption. Odds ratios (OR) and 95% confidence intervals (CI) were calculated.

The mean daily intake of dietary micro-and macro-nutrients was compared via logistic regression between DS users and nonusers after adjustment for age, number of 24 h records and energy intake. Only women who provided at least one dietary record during their pregnancy and who were normo-energy reporters according to the Goldberg criteria [START_REF] Black | Critical evaluation of energy intake using the Goldberg cut-off for energy intake:basal metabolic rate. A practical guide to its calculation, use and limitations[END_REF] were included in this part of the analysis.

A P-value,0.05 was considered significant in all statistical tests. All tests were two-sided. Analyses were carried out with SAS software (Release 9.1, SAS Institute Inc., Cary, NC, USA).

Results

Among the 903 pregnant women included in this study, 31% were in the 1 st trimester of pregnancy, 36% in the 2 nd , and 33% in the 3 rd at the time of the DS questionnaire completion. Sociodemographic characteristics of the study population are presented in Table 1. The average age of the participants was 31.764.07 years. A high proportion of pregnant women (64.9%) used DS at least three days a week. The corresponding proportion among the non-pregnant women of childbearing age in the cohort was only 29.1% (data not shown). The proportion of DS users increased significantly with the trimester of pregnancy (58.0%, 62.2% and 74.5% in the first, second and third trimester, respectively).

Demographic, socioeconomic and behavioural correlates of overall and folic acid dietary supplement use

As compared with non-users (Table 1), pregnant women who used DS were more likely to be older, to live in the Paris From the French National Nutrition and Health Programme. Determined by multiple correspondence analysis of data from a questionnaire on organic food consumption (5 clusters defined by the first 3 discriminant axes).

Because of missing values, the proportions of subjects were calculated with 483 supplement users and 266 non-users. doi:10.1371/journal.pone.0070733.t001

metropolitan area, to have had no biological children, to have a higher income, and to occupy an executive/high-skilled position (compared to manual workers and low-skilled staff). The same correlates were statistically significant specifically for folic acid supplement use (P = 0.02 for age, 0.01 for geographical region, 0.0001 for number of children, 0.001 for income, and 0.007 for socioprofessional category, data not tabulated).

Overall and specific DS use according to the trimester of pregnancy

The three substances most commonly reported were folic acid, iron and magnesium (Table 2). About half of the women used folic acid in the 1 st trimester. The proportion of iron users tripled from the 1 st to the 3 rd trimester. 15.5% of women reported taking vitamin D supplements on a regular/daily basis (information about single-dose use was not available). The proportion of vitamin D users during pregnancy was respectively 16.9%, 14.8%, 15.4% and 9.8% in women who delivered during the spring, summer, fall and winter, respectively (data not shown). The proportion of pregnant women using iodine DS reached 25.6% in the 2 nd trimester. Retinol supplement use reached 5.8% during the last trimester of pregnancy. Vitamin E supplements were used by 29.0% of women in the 2 nd trimester. About 11% of the women reported taking herbal supplements.

Circumstances of dietary supplement purchase

37 women were excluded from these analyses because of missing data. A very high proportion of pregnant women (86.7%) reported taking DS with a medical prescription or following physician advice (Table 3). The proportion of users of prescribed DS increased significantly from 67% in the 1 st trimester to 76% in the 3 rd trimester. 18.6% of pregnant women reported taking their supplements following advice of a pharmacist.

Dietary intake associated with DS use

Among the 903 pregnant women included in this study, 74% (n = 666) provided dietary data during their pregnancy and were normo-reporters; thus they were included in the following analyses. Most of those participants (73%) provided three 24 h dietary records, 17% provided 2 dietary records and only 10% provided only 1 record. DS users had significantly higher dietary intakes of most vitamins and minerals (i.e. thiamin, riboflavin, vitamin B6, folic acid, beta-carotene, vitamin E, iron, magnesium and potassium) (Table 4). DS users had slightly lower intakes of vitamin D than did DS non-users. Regarding folic acid intake from food, only 181 (27%) pregnant women reached the recommended dose of 0.4 mg/day and this proportion was significantly higher in folic acid supplement users than in non-users (33% vs. 23%; P = 0.002, data not tabulated).

Discussion

The present study highlighted demographic, socioeconomic and lifestyle disparities associated with DS use. Users of DS in general and of folic acid in particular were slightly older and belonged to higher socioeconomic classes, consistent with reports from other developed countries [START_REF] Branum | Dietary Supplement Use and Folate Status during Pregnancy in the United States[END_REF][START_REF] Haugen | Dietary Supplements Contribute Substantially to the Total Nutrient Intake in Pregnant Norwegian Women[END_REF][START_REF] Sullivan | Multivitamin use in pregnant and nonpregnant women: results from the Behavioral Risk Factor Surveillance System[END_REF][START_REF] Arkkola | Dietary intake and use of dietary supplements in relation to demographic variables among pregnant Finnish women[END_REF][START_REF] Woude | Periconceptional folic acid use: Still room to improve[END_REF][START_REF] Forster | The use of folic acid and other vitamins before and during pregnancy in a group of women in Melbourne, Australia[END_REF]. Demographic and socioeconomic disparities associated with nutritional behaviour during pregnancy are of major public health importance as they are the precursors of socioeconomic inequalities regarding the health status of the next generation [START_REF] Hanson | Early life opportunities for prevention of diabetes in low and middle income countries[END_REF]. While some medicinal supplements recommended during pregnancy were partly reimbursed by social security/assistance programmes, the extra cost to the patient may deter DS purchases in low-income households.

Besides, women with low income likely visit physicians less often and are might be less aware of nutritional recommendations compared to their more affluent counterparts.

The fact that women who already had children took fewer DS in general and folic acid in particular is also of major concern and has been observed in other countries [START_REF] Mcnally | Periconceptional folic acid supplementation in a nationally representative sample of mothers[END_REF][START_REF] Arkkola | Dietary intake and use of dietary supplements in relation to demographic variables among pregnant Finnish women[END_REF][START_REF] Forster | The use of folic acid and other vitamins before and during pregnancy in a group of women in Melbourne, Australia[END_REF]. This may be related to the fact that women who have already been pregnant in the past have fewer physician consultations in early pregnancy and/or are less compliant with the physician's recommendations.

Disparities between pregnant DS users and non-users also appeared as regards nutritional intake from food. Indeed, DS users had significantly higher dietary intakes of most vitamins and minerals, as previously reported in pregnant women [START_REF] Haugen | Dietary Supplements Contribute Substantially to the Total Nutrient Intake in Pregnant Norwegian Women[END_REF] and in the general adult population [START_REF] Pouchieu | Socio-demographic, lifestyle and dietary correlates of dietary supplement use in a large sample of French adults: results from the Nutrinet-Sante ´cohort study[END_REF]. A recent study in the Netherlands showed an inverse association between a Mediterranean diet rich in fruit, vegetables, fish, legumes and cereals and the risk of spina bifida in the offspring [START_REF] Vujkovic | The maternal Mediterranean dietary pattern is associated with a reduced risk of spina bifida in the offspring[END_REF]. Thus, diet quality during pregnancy is of major public health importance. Our results highlight a combination of two risk factors (a poorer diet and an absence of supplementation for key nutrients) that may act synergically to increase the risk of disease in the foetus.

Whereas medical prescription or advice represented about 55% of DS use in the general NutriNet-Sante ´study [START_REF] Pouchieu | Socio-demographic, lifestyle and dietary correlates of dietary supplement use in a large sample of French adults: results from the Nutrinet-Sante ´cohort study[END_REF], this proportion was much higher in pregnant women (86.7%), while self-medication with DS was still reported by about 15% of the pregnant women. This proportion was much lower than those documented in Australian and US studies [START_REF] Forster | The use of folic acid and other vitamins before and during pregnancy in a group of women in Melbourne, Australia[END_REF][START_REF] Tsui | A survey of dietary supplement use during pregnancy at an academic medical center[END_REF]. To our knowledge, such data have not been published for other European countries. In our study, 18.6% of DS users reported taking their supplements following advice of a pharmacist. It has been suggested that some pharmacists might be ill-equipped to counsel pregnant women about these products, and an ethical issue stemming from the profit-motive may occur [START_REF] Boon | The Ethics of Dietary Supplements and Natural Health Products in Pharmacy Practice: A Systematic Documentary Analysis[END_REF].

During pregnancy, the nutritional requirements for several key nutrients (folic acid, iron, vitamin D and iodine in particular) increase, hence, supplemental intake under medical supervision may be beneficial. In our study, only 27% of pregnant women reached the recommended folate intake of 0.4 mg/day with food only. In turn, folic acid was the most frequently used nutrient in DS in our study. The proportion of folic acid users was higher than that observed in the 2010 French perinatal survey (40% took folic acid supplements during pregnancy and 24% before and/or at the time of conception [START_REF]Ministe `re de l'Emploi du Travail et de la Sante ´[END_REF]) but much lower than in other developed countries [START_REF] Mcnally | Periconceptional folic acid supplementation in a nationally representative sample of mothers[END_REF][START_REF] Branum | Dietary Supplement Use and Folate Status during Pregnancy in the United States[END_REF][START_REF] Forster | The use of folic acid and other vitamins before and during pregnancy in a group of women in Melbourne, Australia[END_REF][START_REF] Barbour | Uptake of folic acid supplements before and during pregnancy: focus group analysis of women's views and experiences[END_REF][START_REF] Roy | Dietary supplement use and iron, zinc and folate intake in pregnant women in London, Ontario[END_REF]. The potential harm of systematic folic acid supplementation has been questioned, but a recent metaanalysis of 13 trials showed that folic acid supplementation did not increase cancer risk at any site [START_REF] Vollset | Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50000 individuals[END_REF]. One of the issues regarding folic acid supplementation is that unplanned pregnancies possibly miss the critical period during which supplementation would be beneficial. [START_REF] Castillo-Lancellotti | Impact of folic acid fortification of flour on neural tube defects: a systematic review[END_REF][START_REF] Berry | Folic Acid Working Group (2010) Fortification of flour with folic acid[END_REF] Iron requirements increase during pregnancy, especially over the last trimester [START_REF] Martin | The ''apports nutritionnels conseille ´s (ANC)'' for the French population[END_REF][START_REF] Milman | Iron in Pregnancy -How Do We Secure an Appropriate Iron Status in the Mother and Child?[END_REF]. The current recommendation is to prescribe iron supplementation if women are at risk of insufficiency [START_REF] Autorite ´de Sante | Recommandations professionnelles[END_REF]. This is consistent with our results: iron was the second most frequently used supplemental nutrient, and its use tripled between the first and the last trimester, reaching 64% of users. However, this proportion is lower than in other developed countries [START_REF] Branum | Dietary Supplement Use and Folate Status during Pregnancy in the United States[END_REF][START_REF] Arkkola | Dietary intake and use of dietary supplements in relation to demographic variables among pregnant Finnish women[END_REF][START_REF] Knudsen | Iron supplement use among Danish pregnant women[END_REF].

Next, the current practice in France is to prescribe a single dose of 100 000 IU of vitamin D at the sixth month of pregnancy notably when the last trimester would take place in the winter [START_REF] Autorite ´de Sante | Recommandations professionnelles[END_REF]. However, our DS questionnaire (designed for the general population) did not capture information about the use of singledose vitamin D medication. Nonetheless, our study provides important data on regular vitamin D supplement use, which concerned 15.5% of pregnant women.

The World Health Organization recommends a dose of 250 mg/d of iodine for pregnant women if access to iodized salt cannot be guaranteed [START_REF]Reaching Optimal Iodine Nutrition in Pregnant and Lactating Women and Young Children[END_REF]. In France, no systematic iodine supplementation is practiced [START_REF] Autorite ´de Sante | Recommandations professionnelles[END_REF]. In our study, the proportion of pregnant women using iodine supplementation reached 25.6% among those who were in their second trimester of pregnancy, as also observed in the US [START_REF] Stagnaro-Green | Iodine Supplementation during Pregnancy and Lactation[END_REF].

In contrast, several arguments encourage caution regarding supplement use as self-medication during pregnancy. They pertain to the potential toxicity associated with overdose of some nutrients or bioactive compounds and the potential deleterious effects of some herbal supplements, alone or when combined with certain medications [START_REF] Tsui | A survey of dietary supplement use during pregnancy at an academic medical center[END_REF][START_REF] Buehler | Interactions of herbal products with conventional medicines and potential impact on pregnancy[END_REF]. Excessive retinol intake is associated with increased risk of teratogenicity [START_REF] Schnorr | The effects of vitamin A supplementation to rats during gestation and lactation upon redox parameters: Increased oxidative stress and redox modulation in mothers and their offspring[END_REF][START_REF]Tolerable Upper Intake levels For Vitamins and Minerals by the Scientific Panel on Dietetic Products, Nutrition and Allegies (NDA) and Scientific Committee on Food (SCF)[END_REF] and retinol supplementation during pregnancy is not recommended. In our study, 5.8% of pregnant women used retinol supplements during the third trimester. A recent study showed that high maternal dietary and supplemental intake of vitamin E (.14.9 mg/day) was associated with a nine-fold increased risk of coronary heart disease in the offspring [START_REF] Smedts | High maternal vitamin E intake by diet or supplements is associated with congenital heart defects in the offspring[END_REF]. Thus, vitamin E DS use during pregnancy is of major concern. In our study, mean intake of vitamin E from food was 12 mg/day and nearly 30% of women used vitamin E supplements during the second trimester of pregnancy. 11% of the pregnant women used herbal supplements and only two women in this study took phyto-oestrogen supplementation.

To our knowledge, this epidemiologic study is the first which examined DS use and its correlates in French pregnant women. Its strengths include a substantial number of subjects, detailed evaluation of socioeconomic and lifestyle factors associated with DS use and detailed information on dietary intake.

Several limitations should be acknowledged. Caution is needed when extrapolating our results to pregnant women in general as this study was based on a sample of volunteers involved in an Internet-based cohort study on nutrition and health. Compared to pregnant women in the general French population, those participating in our study were older, better educated, and belonged to higher socioprofessional categories [START_REF]Ministe `re de l'Emploi du Travail et de la Sante ´[END_REF]. However, the direction of bias is predictable and suggests that supplement use in French pregnant women is probably slightly lower than what is observed in the present study. In addition, the major objective of this work was to investigate the associations between DS use and several individual-level correlates. Thus, the diversity of the sample (rather than its representativeness) is regarded the important parameter. Besides, this study included about 8% of women from lower socioprofessional categories (a population group that is usually difficult to reach), allowing us to perform between-class comparisons. Second, no information was available regarding folic acid and other DS use before pregnancy, while this period is critical regarding NTD prevention. Third, the distinction between medically-assisted versus spontaneous and planned versus unplanned pregnancies could not be made in this study while these factors may influence DS use [START_REF] Timmermans | Determinants of folic acid use in early pregnancy in a multi-ethnic urban population in The Netherlands: The Generation R study[END_REF]. Fourth, longitudinal follow-up of DS use during pregnancy was not available in this study (women were divided according to trimester groups in a cross-sectional manner). Fifth, although three dietary records are appropriate to adequately estimate energy intake [START_REF] Ma | Number of 24-Hour Diet Recalls Needed to Estimate Energy Intake[END_REF], they may not capture all of the variability of dietary intake during the entire pregnancy. Next, the nutrient doses from the DS were not quantified. Finally, no information was available regarding biomarkers of nutritional status or ethnicity in this study, since a specific authorization is required in France to collect such sensitive data.

Conclusion

This study provides new and detailed information on DS use and its correlates during pregnancy, highlighting socioeconomic differences in that dietary behaviour. In particular, women from lower socioeconomic classes were less likely to benefit from folic acid supplementation. 15% of pregnant women relied on selfmedication. Even in this relatively well-educated and well-off population, folic acid supplementation at the beginning of pregnancy remained insufficient (only 50%), whereas only 27% of women reached the recommended 0.4 mg/day with food intake. In contrast, irrelevant supplementation practices have been identified (notably for retinol and vitamin E). It appears necessary to increase awareness among health professionals regarding the importance of recommending use of the right nutrient at the right moment (not only for the first but also for subsequent pregnancies; pre-and post-conception), while avoiding unnecessary (and even potentially hazardous) supplementation, with special attention paid to the lower socioeconomic strata. In pregnant women who provided at least one dietary record during their pregnancy.

2 DS users were defined as the subjects who used dietary supplement(s) at least 3 days a week at the time of completion of the dietary supplement questionnaire.

3 Unconditional logistic regression analyses adjusted for age, number of 24 h records and energy intake. doi:10.1371/journal.pone.0070733.t004

4

 4

5

 5

Table 1 .

 1 Demographic, socioeconomic and lifestyle correlates of dietary supplement use in pregnant women of the NutriNet-Sante ´cohort study.

	All Pregnant	Supplement	Supplement	Age adjusted logistic
	women		Non-Users		Users 1		regression analyses
	(n = 903)		(n = 317)		(n = 586)
	n	%	n	%	n	%	O R	P 2

2

P for linear trend (with adjustment for age, number of children, income, and knowledge of nutritional recommendations) or overall P (for all other variables).

3

Values are n % for all variables except for age where values are mean SD.

Table 2 .

 2 Overall and specific dietary supplement use in pregnant women of the NutriNet-Sante ´cohort study, according to the trimester of pregnancy1 . defined as the subjects who used dietary supplement(s) at least 3 days a week at the time of the DS questionnaire.Comparison of overall and specific DS use among pregnant women according to the trimester of pregnancy by unconditional logistic regression analysis adjusted for age.

		All pregnant		1 st		2nd		3 rd
		women		trimester		trimester		trimester
		(n = 903)		(n = 281)		(n = 328)		(n = 294)
		n	%	n	%	n	%	n	%	P 2
	Overall supplement use	586	64.9	163	58.0	204	62.2	219	74.5	0.0001
	Specific supplement use 3
	Folic acid	406	45.0	141	50.2	144	43.9	121	41.2	0.07
	Iron	380	42.1	52	18.5	140	42.7	188	63.9	,0.0001
	Magnesium	289	32.0	57	20.3	111	33.8	121	41.2	,0.0001
	Vitamin B6	240	26.6	48	17.1	105	32.0	87	29.6	,0.0001
	Thiamin	233	25.8	49	17.4	105	32.0	79	26.9	0.0002
	Riboflavin	229	25.4	46	16.4	103	31.4	80	27.2	,0.0001
	Vitamin E	205	22.7	39	13.9	95	29.0	71	24.1	,0.0001
	Vitamin B12	197	21.8	46	16.4	83	25.3	68	23.1	0.02
	Zinc	187	20.7	41	14.6	83	25.3	63	21.4	0.004
	Vitamin B8	182	20.2	38	13.5	79	24.1	65	22.1	0.004
	Iodine	182	20.2	37	13.2	84	25.6	61	20.7	0.0007
	Pantothenic acid	165	18.3	42	14.9	70	21.3	53	18.0	0.07
	Other minerals 4	148	16.4	31	11.0	64	19.5	53	18.0	0.01
	Vitamin D	140	15.5	35	12.5	60	18.3	45	15.3	0.1
	Vitamin C	142	15.7	23	8.2	68	20.7	51	17.3	0.0001
	Niacin	134	14.8	37	13.2	51	15.5	46	15.6	0.6
	v3 fatty acids	99	11.0	20	7.1	47	14.3	32	10.9	0.02
	Calcium	92	10.2	17	6.0	36	11.0	39	13.3	0.02
	Other herbal supplement	72	8.0	20	7.1	26	7.9	26	8.8	0.97
	Selenium	69	7.6	8	2.8	33	10.1	28	9.5	0.003
	Retinol	41	4.5	6	2.1	18	5.5	17	5.8	0.08
	Phosphorus	27	3.0	8	2.8	10	3.0	9	3.1	0.98
	Evening primrose, borage, or cod liver oil	18	2.0	4	1.4	11	3.4	3	1.0	0.1
	Beta-carotene	11	1.2	1	0.4	5	1.5	5	1.7	0.3
	Fluoride	11	1.2	3	1.1	3	0.9	5	1.7	0.7
	Acerola, guarana or cranberry supplement	10	1.1	3	1.1	5	1.5	2	0.7	0.6
	Vitamin K	6	0.7	2	0.7	3	0.9	1	0.3	0.7
	Fiber	4	0.4	3	1.1	1	0.3	0	0.0	0.6
	Ginseng	3	0.3	2	0.7	0	0.0	1	0.3	0.8
	Amino acids/proteins	3	0.3	1	0.4	1	0.3	1	0.3	0.99
	Phytoestrogens	2	0.2	2	0.7	0	0.0	0	0.0	0.99
	Lutein	1	0.1	0	0.0	0	0.0	1	0.3	-

1

DS users were 2

Table 3 .

 3 Motives for dietary supplement purchase in pregnant women of the NutriNet-Sante ´cohort study. DS users were defined as the subjects who used dietary supplement(s) at least 3 days a week at the time of the dietary supplement questionnaire. Data regarding circumstances of dietary supplement use were available for 94% of supplement users (i.e. 549 women out of 586).

	Pregnant women who

PLOS ONE | www.plosone.org

August 2013 | Volume 8 | Issue 8 | e70733

Nutrients and other substances were consumed alone or in combination in the same DS.

Potassium, copper, lithium, manganese, chromium, and others. doi:10.1371/journal.pone.0070733.t002

Several answers possible. doi:10.1371/journal.pone.0070733.t003

Acknowledgments

The authors thank Gwenael Monot, Paul Flanzy, Mohand Ait Oufella, Yasmina Chelghoum, and Than Duong Van (computer scientists), Florence Charpentier (dietitian), Anne-Sylvie Monot-Berroyer (communication assistant), Nathalie Arnault, Ve ´ronique Gourlet, Fabien Szabo, Laurent Bourhis, and Stephen Besseau (statisticians), and Rachida Mehroug (logistics assistant) for their technical contribution to the NutriNet-Sante ´study.

The NutriNet-Sante ´cohort study is funded by the following public institutions: Ministe `re de la Sante ´, Institut de Veille Sanitaire (InVS), Institut National de la Pre ´vention et de l'Education pour la Sante ´(INPES), Fondation pour la Recherche Me ´dicale (FRM), Institut National de la Sante ´et de la Recherche Me ´dicale, Institut National de la Recherche Agronomique (INRA), Conservatoire National des Arts et Me ´tiers (CNAM) and Paris 13 University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author Contributions


T Fournier
email: tristan.fournier@univ-tlse2.fr

E Bruckert

S Czernichow

A Paulmyer

J P Poulain

The THEMA study: a sociodemographic survey of hypercholesterolaemic individuals

Keywords: compliance, diet, France, hypercholesterolaemia, medication, sociodemographic

Background: Hypercholesterolaemia is estimated to affect 20% of the population, although little sociodemographic information is available on affected individuals. The present study aimed to gather relevant information and investigate social determinants of dietary compliance. Methods: A telephone survey was carried out on a representative population sample. Quotas were applied for gender, geography and degree of urbanisation. Individuals were eligible if they were hypercholesterolaemic, and were being followed by a doctor. Sociodemographic, socioeconomic and health data were collected, as well as information about the individuals' perception of the disease, their relationship and beliefs surrounding food, and their food behaviour (shopping, cooking, eating-out, deviation from prescribed diet). The association between compliance with diet and medication was investigated. Results: Overall, 802 individuals were included, representing 8% of those contacted, as opposed to the expected 20%. Mean (SD) age was 60 (14.2) years, with 51% of individuals living as a couple; 48% had a good level of physical activity; 44% considered that the hypercholesterolaemia was inherited; 31% felt that the disease was normal beyond the age of 45 years. The functional and convivial aspects of eating were of more importance than that of health maintenance. Cheese was particularly likely to be eaten in dietary lapses. Of a subgroup of 729 individuals, 476 (65%) took medication; of these 476 individuals, 51% complied with dietary recommendations (P < 0.05).

Conclusions:

The key factors associated with dietary compliance in hypercholesterolaemic individuals were identified: age, sex, the perceptions of hypercholesterolaemia, and the sociocultural aspects of food. By contrast to general assumptions, both dietary and medicinal measures are practised fairly well by a large proportion of these individuals.

Introduction

Hypercholesterolaemia is a serious illness, of which the long-term effects are one of the major causes of cardiovascular disease [START_REF] Mcqueen | Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case control study[END_REF]The Emerging Risk Factors Collaboration, 2009). As such, it places an enormous burden upon health, social work and research budgets in developed countries. However, it is a disease that can be easily detected by simple blood testing, and in which sufferers can take active life-style measures to help themselves. These measures usually initially involve changes being made to the patient's diet and level of physical activity before lipid-lowering medication is used [START_REF] Grundy | Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines[END_REF]AFSSAPS, 2005).

Twenty percent of the French population is estimated to have hypercholesterolaemia [START_REF] Ferrieres | Trends in plasma lipids, lipoproteins and dyslipidaemias in French adults, 1996-2007[END_REF], although limited sociodemographic and socioeconomic data exist for this group. A qualitative sociological study [START_REF] Fournier | Les de ´terminants sociaux du non-suivi des re ´gimes alimentaires. Le cas des patients hypercholeste ´role ´miques[END_REF]) concentrated on determining the reasons given by a small sample of French hypercholesterolaemic patients for not following their recommended lipid-lowering diet. Four main reasons were found: the patients' food pattern and cultural experience; their relationship with healthcare professionals; their perception of the risks associated with hypercholesterolaemia; and the social context of the eating situation. Certain foods, such as cheese, butter and processed meat (charcuterie) were identified as being particularly difficult to reduce.

Over and above the strong regional and traditional dietary habits, the French attitude to food also gives great weight to the pleasurable aspect of eating [START_REF] Rozin | Attitudes to food and the role of food in life in the U.S.A., Japan, Flemish Belgium and France: possible implications for the diet-health debate[END_REF][START_REF] Pettinger | Psychosocial influences on food choice in Southern France and Central England[END_REF], with the quality of product being considered of more importance than the quantity. It has been suggested that this attitude towards pleasure could have as much an influence on diet-dependent health as the actual dietary components [START_REF] Rozin | Attitudes to food and the role of food in life in the U.S.A., Japan, Flemish Belgium and France: possible implications for the diet-health debate[END_REF]. This could be one explanation for the 'French paradox' (i.e. for the fact that, although the average French diet has a relatively high fat level compared to the average American diet, the French have lower levels of cardiovascular disease) [START_REF] Richard | Coronary risk factors. The French paradox[END_REF][START_REF] Rozin | Attitudes to food and the role of food in life in the U.S.A., Japan, Flemish Belgium and France: possible implications for the diet-health debate[END_REF]. This possibility underlines the importance of having an overall understanding of how individual patients relate to eating, and dietary behaviour in general.

The THEMA (Typologie d'Hypercholeste ´role ´miques et Etude de leurs Mode `les Alimentaires -Typology of hypercholesterolaemic people and study of their eating patterns) survey was developed with the aim of collecting sociodemographic and socioeconomic data from a representative sample of French hypercholesterolaemic individuals, and investigating possible social determinants of the lack of dietary compliance. The present part of the THEMA study aimed to document aspects of individuals' eating patterns, their attitudes towards food and their disease, and how often they were in contact with a doctor.

Materials and methods

Subject selection

Because a survey base did not exist, a nonrandom quota survey method was used. A private polling institute, the BVA company (Viroflay, France), conducted out anonymised telephone questionnaires on a sample of individuals representative of the French population. Because it is estimated that approximately 20% of the French population has a cholesterol level higher than that recommended [START_REF] Ferrieres | Trends in plasma lipids, lipoproteins and dyslipidaemias in French adults, 1996-2007[END_REF], a 20% inclusion rate was aimed for. Quotas were applied for sex, region of residence and size of urban area, as well as whether the individual took lipid-lowering medication or not. Although the vast majority of patients being treated were given statins, no specific questions were asked regarding the type of treatment (resin, fibrate, statin or other), nor the dosage prescribed to the patients. No specific dietetic prescription was given to the patients in the present study and they only received the advice given by the general practitioner according to the French guidelines, which include mainly a reduction in saturated fats at the same time as maintaining an adequate intake of mono-and polyunsaturated fats. According to French law regulating clinical research (Loi Huriet), this survey did not require any particular ethical committee or data protection board approval.

The questionnaire was designed as an extension of qualitative sociological research that had been carried out previously. It comprised 58 closed and multiple choice questions and consisted of standard questions used in sociology to describe population sociodemographics [START_REF] Desrosieres | The Politics of Large Numbers: A History of Statistical Reasoning[END_REF], as well as questions that were used in other studies [START_REF] Poulain | The contemporary diet in France: 'De-structuration' or from commensalism to 'vagabond feeding[END_REF][START_REF] Rozin | Attitudes towards large numbers of choices in the food domain: a cross-cultural study of five countries in Europe and the USA[END_REF]. To check whether the questions were both comprehensible and discriminatory, they were pretested on 20 individuals (who were not included in the final sample). Finally, the overall questionnaire was validated by the multidisciplinary team involved in the present study. The questionnaire was planned to take an average of 25 min to complete. The BVA interviewers were trained in its use by one of the authors; this training comprised of one half-day spent reading through the questionnaire, testing it using a computer assistance system, and in the simulation of the possible responses to the multiple choice questions.

Telephone contact was made between 17.00 h and 19.00 h, from Mondays to Fridays, during March 2008. Individuals who had raised cholesterol and were receiving dietary advice from their doctor were included.

Eligible, consenting individuals were invited to answer further questions on several subjects, as outlined below.

Sociodemographic questions

Sociodemographic information included sex, age, living situation, level of education and socioprofessional category. Socioprofessional categories were based on the French National Institute of Statistics and Economic Studies (INSEE) groups (INSEE, 2008).

Health factors

Individuals were questioned about lipid-lowering medication intake, how long they had been aware of being hypercholesterolaemic, the presence of cardiovascular risk factors (smoking, hypertension, diabetes, family history of cardiovascular disease, personal cardiovascular incident), weight and height, and physical activity. Physical activity was assessed by two questions about walking and the frequency of taking part in a sporting activity: (1) 'Do you walk more than 30 min a day?' and (2) 'Do you take part in a sporting activity at least one time a week?'.

Disease management

Questions were asked on the following issues: to whom individuals gave the most confidence in the management of the disease; the information sources used; what they considered to be the best method of protecting against cardiovascular risk; and the frequency of medical consultation for the problem.

Behaviour and attitudes surrounding food and eating

Individuals chose two out of five preset responses to the question 'What does eating represent mainly for you?'. The possible responses were: (1) being with family or friends; (2) a pleasurable activity for myself; (3) a way of maintaining health and protecting myself against illness; (4) a way of expressing my ethical, political and ecological convictions; and (5) a necessary function. For analysis, these were classified as: (1) convivial, (2) hedonistic, (3) prudent, (4) political and (5) functional.

Individuals were also questioned about factors affecting food consumption, changes that would be made to food choices if more money was available, frequency of cooking and shopping for food, frequency of eating outside of the home and, if so, in what circumstances.

Adherence to a lipid-lowering diet

The following issues were treated: foods that individuals considered should be avoided or favoured; situations where deviation from a prescribed diet occurred; how the individual dealt with diet deviation; reasons for difficulty in following the diet; types of unrecommended food eaten; and cheese consumption.

Because a self-reported following of diet is likely to be biased, a separate 'compliance with diet' variable was built, using four variables: whether the individual followed a lipid-lowering diet; his/her amount of diet infringement; the difficulties encountered in adhering to the diet; and his/her hypothetical responses to a cheese-eating situation. Results were classified into compliance or noncompliance with the diet, and crossed with medication intake.

Statistical analysis

Data were excluded from individuals aged <18 years. Results are given as percentages and the mean. Categorical data were analysed using the chi-squared test. Statistical analysis was performed using spss, version 14.0 (SPSS Inc., Chicago, IL, USA). P < 0.05 was considered statistically significant.

Results

Construction of the sample

The questionnaire was answered by 802 individuals, representing an 8% inclusion rate from a total of 9599 valid telephone calls. The survey aimed to focus on French hypercholesterolaemic people who managed their disorder by dietary adjustment alone, and it was intended to include two-thirds of individuals using dietary control measures alone. However, because of recruitment difficulties, the quota of individuals taking lipid-lowering medication was increased; in the end, these individuals accounted for two-thirds of inclusions.

Sociodemographic characteristics

The mean (SD) age was 60 (14.2) years, with most individuals living as a couple. Thirty percent had only completed basic obligatory schooling, although 45% were, or had been, in the middle socioprofessional category. Fifty percent of individuals were retired (Table 1 and Fig. 1).

Health factors

Lipid-lowering medication intake varied according to age (30% in people aged <45 years; 60% between 46 and 55 years; 71% between 56 and 65 years; 78% between 66 and 75 years; and 80% >76 years). Forty-one percent of individuals had known about their hypercholesterolaemia for over 10 years; 46% for between 1 and 10 years; and 11% for <1 year. Fifty-seven percent of individuals did not know their cholesterol level.

A family history of cardiovascular disease and hypertension were the most reported classical cardiovascular risk factors; the majority of individuals had a good physical activity level (Table 2). Forty-four percent of individuals considered the disease to be a family trait, with lifestyle also being considered responsible in a quarter of cases; almost one-third of individuals classified hypercholesterolaemia as normal beyond the age of 45 years (Table 3).

Disease management

The majority of individuals had confidence in the medical profession for management of the disease and relied on them as an information source (Table 4). Two-thirds of individuals considered themselves to be the person with the most important role to play in disease management; the close circle, when it existed, had a variably helpful role to play (Table 5).

Behaviour and attitudes surrounding food and eating

The response of 'a way of expressing my ethical, political and ecological convictions' to the question 'What does eating represent mainly for you?' was almost nil, and it was therefore removed from the analysis. In the valid combined responses (n = 742), the combination given most frequently was 'necessary function' (first) with 'being with family or friends' (second). When the order given for the responses was ignored, 'being with family or friends' had the largest number of responses (57.1%), followed by 'necessary function' (55.4%), then 'a pleasurable activity for myself' (45.2%) and 'a way of maintaining health and protecting myself against illness' (42.1%). On analysing the first responses alone, four eating profiles were defined: the functional eater (41%), the convivial eater (21.5%), the hedonistic eater (20%) and the prudent eater (17.5%). 'The taste' was the most important reason behind choice of food; economic factors were of lesser importance (Table 6). Some 48.4% of the respondents declared themselves unwilling to change their diet even if they had more money (n = 802).

With regard to cooking frequency (n = 798), the majority (42.4%) of individuals cooked at every meal; 25.9% cooked at least one meal per day; 12.5% cooked several meals per week; 5.0% cooked for special occasions; and 14.2% never cooked.

For food shopping (n = 801), 71.7% shopped one or two times per week; 10.5% shopped several times per month; 8.4% shopped every day; 2.9% shopped less often than several times per month; and 6.6% never shopped.

As for eating outside of the home (n = 799), 44.8% never did so; 34.0% did so one or two times per week; and 21.2% did so three times or more each week. Of those individuals that ate meals outside the home (n = 396), 34.8% did this with friends; 31.6% ate in a restaurant; 19.4% in an institutional setting (e.g. the work canteen); and 14.1% ate home-prepared food at the workplace.

Adherence to a lipid-lowering diet

Individuals considered that fatty or red meats, processed meat and butter were the foods to avoid most if hypercholesterolaemic; vegetables, fruit and fish were considered to be the foods to favour (Table 7). Dietary deviation occurred mainly during meals at friends and at home; in the majority of cases, this was dealt with by eating more lightly at later meals (Table 8). The two most important reasons why following the medically prescribed dietary rules is difficult (n = 802) were 'tastes and eating habits' (40.8%) and 'being invited out' (24.4%); however, 50.9% of the individuals considered that their doctor's advice was quite easy to follow. Cheese, processed meat and cakes were the foods most likely to be eaten in dietary lapses. Moreover, cheese, cakes and snacks were particularly likely to be eaten despite their low initial ranking as food groups to be avoided (Table 9). No significant difference regarding dietary behaviours was found between urban and rural people.

For cheese consumption in those that liked it (n = 729), 43.8% continued to eat it without taking medical advice into account; 47.9% ate it occasionally (e.g. when invited out); and 8.4% did not eat it any more (even if invited out).

Using a hypothetical cheese-eating situation in the 'compliance with diet variable' meant that statistically, 'n' was reduced to 729. This was constructed with four variables, and excluded those who did not like cheese (see Materials and methods). Individuals classified themselves as good (11%), pretty good (35%), pretty poor (39%) and poor (15%) regarding diet compliance; this was collapsed into 46% compliance and 54% noncompliance. A significant association was found between compliance with diet and use of lipid-lowering medication (Table 10). In addition, compliance with diet was neither correlated with gender, nor area of residence.

Discussion

This survey is the first large-scale detailed sociodemographic and socioeconomic study of the French hypercholesterolaemic population (defined by a total cholesterol level above 2 g L )1 -5.13 mm, according to the French guidelines). Within the limitations imposed by the survey type, it provides a useful insight into this population group.

The initial difficulties with recruitment, and the final inclusion level of only 8% as opposed to the intended 20%, could indicate that a section of the French population is unaware of being hypercholesterolaemic. This speculated unaware hypercholesterolaemic population may reside in males aged <45 years old: blood testing is infrequent in this population group. In addition, hypercholesterolaemic individuals who are aware of their disease, but who have not yet been prescribed medication, may not consider themselves to be truly hypercholesterolaemic and, as a result, may have declined to answer the survey. The same could be true of individuals aged >45 years who consider that it is normal to have hypercholesterolaemia from middle-age onwards. Furthermore, as with any survey, there is also the possibility of selfexclusion occurring as a result of a lack of time or interest, or other personal factors.

The wide discrepancy between the expected level of recruitment and the actual level achieved may also have resulted from differences between the design of the present study and that of the reference used [START_REF] Ferrieres | Trends in plasma lipids, lipoproteins and dyslipidaemias in French adults, 1996-2007[END_REF]. [START_REF] Ferrieres | Trends in plasma lipids, lipoproteins and dyslipidaemias in French adults, 1996-2007[END_REF] investigated trends in dyslipidaemias by carrying out a representative survey of the general population in three French cities. However, a narrower age range for inclusion was imposed (35-64 years) and blood testing was carried out. These major differences in design make comparison between the results more difficult. First, it can be assumed that the level of unknown hypercholesterolaemia is higher in younger adults, thus reducing the percentage of self-reporting in the present study. Second, because blood testing is a far more accurate method of assessing hypercholesterolaemia than is self-reporting, [START_REF] Ferrieres | Trends in plasma lipids, lipoproteins and dyslipidaemias in French adults, 1996-2007[END_REF] probably detected a more reliable frequency. However, an important selection bias may have existed in that study because the participants were required to be available for a questionnaire, physical examination and blood testing.

In terms of gender, the present sample was representative of the French population (INSEE, 2008). However, as expected when selecting hypercholesterolaemic individuals, the mean age of participants was above that of the general population (INSEE, 2008). Perhaps as a reflection of this older population, and the generally higher level of being overweight and obesity in hypercholesterolaemic people [START_REF] Denke | Excess body weight. An under-recognized contributor to high blood cholesterol levels in white American men[END_REF][START_REF] Denke | Excess body weight. An under-recognized contributor to dyslipidemia in white American women[END_REF], the mean body mass index (BMI) was higher [START_REF] Charles | Monitoring the obesity epidemic in France: the Obepi surveys 1997-2006[END_REF].

Although the overall sample education level appears low, this is probably a result of the older population not having required tertiary education certification to progress in their work in the 1970s and 1980s. Indeed, compared to the overall French population (INSEE, 2008), when divided into age groups, the education level of the individuals in the sample was high. This could be considered as unexpected because a high level of consumption of fatty foods has often been found especially in the lower social levels [START_REF] Corbeau | L'imaginaire du gras associe ´a `divers types de consommation de gras et les perceptions de leurs qualite ´s[END_REF][START_REF] Bruckert | Blood lipid and lipoprotein levels: relationships with educational level and region of residence in the French SU.VI.MAX study[END_REF][START_REF] Czernichow | Intake of added oils and fats among middle-aged French adults: relationships with educational level and region of residence[END_REF]. This may indicate that the speculated unaware hypercholesterolaemic population resides not only in under males aged <45 years, but also in less educated people in general.

The French census only records the socioprofessional category of the household head; in the present study, however, not only family heads, but also spouses, other family members, people who lived in shared accommodation, etc. were interviewed. It was thus impossible to choose who should be considered as the 'official' head of the household.

A quarter of the sample perceived their hypercholesterolaemia to be worrying, and 52% were frightened to some extent by the associated risks. However, 57% of individuals did not know their cholesterol level, 31% considered the disease to be normal beyond the age of 45 years, and 22% considered it to be invisible. In addition, 46% were not frightened or not really frightened by the associated risks. These combined results may indicate that a substantial number of hypercholesterolaemic individuals have a tendency to consider the disease as trivial.

In terms of behaviour and attitudes surrounding food and eating, the strong preference given for communal eating is not unexpected [START_REF] Rozin | Attitudes towards large numbers of choices in the food domain: a cross-cultural study of five countries in Europe and the USA[END_REF]; of more interest is the lesser emphasis given to the pleasurable aspects of food, and the strong 'functional' response. This may be a result of the older sample population placing more emphasis on family and friendship ties than personal gratification.

The older population might also explain the fact that 14% of the sample never cooked and 7% never shopped for food. One could expect that, because 50% of the sample was retired and 51% were living as a couple, certain individuals would not be involved in food preparation at any level. The results showing that 'the taste' is the major factor involved in food choice are entirely in line with previous studies [START_REF] Rozin | Attitudes to food and the role of food in life in the U.S.A., Japan, Flemish Belgium and France: possible implications for the diet-health debate[END_REF][START_REF] Pettinger | Psychosocial influences on food choice in Southern France and Central England[END_REF]; this has been shown to be a very distinct French characteristic, in comparison with, for example, the American population.

The lack of response to the option of eating mainly representing ethical, political and ecological convictions is probably a reflection of French cultural attitudes to food. It is unsurprising because the lack of interest in expressing such convictions via dietary choice in French people has already been reported [START_REF] Pettinger | Psychosocial influences on food choice in Southern France and Central England[END_REF].

The results for compliance with diet are of particular interest. As was noted in the initial sociological study [START_REF] Fournier | Les de ´terminants sociaux du non-suivi des re ´gimes alimentaires. Le cas des patients hypercholeste ´role ´miques[END_REF], convivial circumstances, such as meals with friends and festive occasions, can make dietary compliance difficult. Faced with a food that they liked but which they were recommended to restrict, 44% of the cheese-liking subgroup (n = 729) continued to eat it. In addition, in the 'compliance with diet' variable, 54% admitted that they did not comply with the recommended lipid-lowering diet. This could be an indication of pleasure (or habit) over-riding prudence. Of those that generally did comply with dietary recommendations, more individuals took lipid-lowering medication than not. This finding is important because it is often assumed that patients on medication have a tendency to relax their vigilance concerning their diet, relying on the drug to take care of the cholesterol problem. In terms of medical and dietetic practice, this could mean that a change in expectation from the healthcare practitioner (with more encouragement being given to the patient to persist with simultaneous dietary and pharmaceutical measures) would result in better management of blood cholesterol.

Before the present study began, no other French data of this type had been produced. However, in 2008, the From The Heart study [START_REF] Hobbs | The From The Heart study: a global survey of patient understanding of cholesterol management and cardiovascular risk, and physician-patient communication[END_REF] reported the findings from their intercontinental survey of cholesterol management. This survey had a similar method to the present one (i.e. a telephone survey with quotas applied), and it reported the demographic details of 200 French hypercholesterolaemic patients. In the From The Heart study, 52% of French hypercholesterolaemic patients stated that they were 'not concerned about being diagnosed with high cholesterol'. This directly supports the suggestion made in the present study that a large proportion of patients have a tendency to consider hypercholesterolaemia as a trivial disease.

Despite an extensive literature search being made, only one other study reporting specific details about compliance or not with both diet and medication in hypercholesterolaemia was found. In the Women's Health Initiative [START_REF] Hsia | Compliance with National Cholesterol Education Program dietary and lifestyle guidelines among older women with self-reported hypercholesterolemia. The Women's Health Initiative[END_REF], comprising a cross-sectional study of 91 627 post-menopausal American women, it was found that those women who had hypercholesterolaemia and needed lipid-lowering medication, and those who had high low-density lipoprotein cholesterol levels, were more likely to comply with dietary and lifestyle recommendations than women who did not have hypercholesterolaemia. It was suggested that being aware of high cholesterol was associated with lifestyle changes. This partly supports the results reported in the present study, although there are great cultural differences between the populations. In hypercholesterolaemia, factors affecting adherence to medical recommendations can include a poor understanding of the disease and cardiovascular risk factors [START_REF] Hobbs | The From The Heart study: a global survey of patient understanding of cholesterol management and cardiovascular risk, and physician-patient communication[END_REF]; IQ, complicated drug regimes, depression, anxiety [START_REF] Stilley | Psychological and cognitive function: predictors of adherence with cholesterol lowering treatment[END_REF]; and misunderstandings in doctor/patient communication, caused by the use of medical jargon and inadequate responses to questions [START_REF] Durack-Bown | Patients' and physicians' perceptions and experience of hypercholesterolaemia: a qualitative study[END_REF]. In the light of the present findings, these factors could be usefully studied in the future in the context of both diet and medication.

This survey has several limitations. First, the nonrandom quota method has inherent bias [START_REF] Fourrier-Reglat | Initiation aux me ´thodes de sondage, application a `la pharmaco-e ´pide ´miologie[END_REF]. Second, patient self-reporting always carries the risk of under-or over-estimations being made [START_REF] Drummond | Effectiveness of dietary advice given by community dietitians to men with elevated blood cholesterol in a clinical setting: a pilot study[END_REF]; it is unlikely that self-reported height and weight, for example, give an accurate BMI [START_REF] Yannakoulia | Correlates of BMI misreporting among apparently healthy individuals: the ATTICA study[END_REF]. Third, no post-survey check was carried out. Finally, the self-selection of individuals who considered themselves to be hypercholesterolaemic could have resulted in the inclusion of more severely affected and more motivated people, thus biasing the results. However, by using an anonymised telephone survey, the bias introduced in surveys carried out in person by healthcare professionals (during which patients may be more tempted to give answers that they think the professional would like to hear) was reduced.

There are several clinical implications resulting from this study. First, because the perception of risk linked to hypercholesterolaemia was low in a proportion of individuals already diagnosed with the disease, doctors and dieticians could be advised to place greater emphasis on educating existing patients about the serious long-term cardiovascular effects of the illness, and to continue encouraging them to persist with treatment. The finding that compliance with both dietary and medicinal measures was already practised by a large percentage of individuals can be used to support patients in their efforts to follow recommendations. Second, because it appears that a significant proportion of the population could be unaware of being affected, measures may be required to raise awareness and encourage screening in more at-risk individuals, particularly younger men. However, because the initial treatment involves dietary alterations, once hypercholesterolaemia is diagnosed, the healthcare professional needs to determine the individual patient's overall attitude to food, lifestyle and social situation to be able to give appropriate dietary advice that will actually be followed. This may involve taking the time to discern the patient's perception of risk associated with hypercholesterolaemia, their degree of confidence in what the professional says, their attitudes towards eating in a social context, their eating habits, and their economic situation. Depending on the country-specific and/or the individual cultural context, this would also involve being sensitive to the conviviality and pleasure surrounding eating behaviour, as well as the emphasis placed on taste.

In conclusion, the present survey provides extensive and detailed information on sociodemographic characteristics, disease perception, and dietary beliefs and practices in a large sample of hypercholesterolaemic individuals. It has shown that, contrary to general expectations, a substantial number of individuals comply simultaneously with dietary and pharmaceutical recommendations. These findings have direct implications for the management of hypercholesterolaemia.

Table 1

 1 Sociodemographic characteristics

	n (%)

*Quotas were applied. Lower: independent farmer, self-employed craftsperson or artisan, independent shopkeeper or tradesperson, salaried service staff, factory or agricultural worker. Middle: intermediate salaried professional and paramedical professional, primary school teacher or similar, salaried employee. Upper: business owner (self-employed and with more than 10 employees), self-employed professional (except paramedical professionals), teacher (high-school and university), salaried scientist, upper level manager. Inactive: student, disabled person, houseperson.

Table 2

 2 Classical cardiovascular risk factors, body mass index (BMI)

	and physical activity
		n (%)
	CV risk factors (n = 802)*
	Family history of CV disease	326 (41.5)
	Hypertension	283 (35.3)
	Smoking	147 (18.3)
	Diabetes	96 (12.0)
	Previous CV incident	94 (11.7)
	BMI (kg m )2 ) à (n = 783)
	<18.5	14 (1.8)
	18.5-24.9	344 (43.9)
	25-29.9	302 (38.6)
	30+	123 (15.7)
	Physical activity § (n = 802)
	Very good level	192 (23.9)
	Good level	383 (47.8)
	Poor level	227 (28.3)
	CV, cardiovascular.
	*Each factor was enquired about individually.
	n = 786.

à When BMI and physical activity were taken into account, 30.7% of individuals had two other classical CV risk factors; mean BMI was 25.9 kg m )2 . § Very good level: walking over 30 min daily and taking part in a sporting activity at least once a week; good level: walking over 30 min daily or taking part in a sporting activity at least once a week; poor level: walking <30 min daily and not taking part in a sporting activity at least once a week.

Table 3

 3

	Aetiology, perception of disease, and fear of cholesterol-
	associated risks
		n (%)
	Aetiology of disease, according to individual
	(n = 802)
	Family trait	351 (43.8)
	Lifestyle	171 (21.3)
	Disturbance in metabolism	108 (13.5)
	Did not know	56 (7.0)
	Unexplained	42 (5.2)
	Poor quality food	41 (5.1)
	Other medication	26 (3.2)
	Lack of information	7 (0.9)
	Perception of disease (n = 802)
	Normal after 45 years of age	251 (31.3)
	Worrying	193 (24.1)
	Invisible	173 (21.6)
	Restricting	149 (18.6)
	Did not know	36 (4.5)
	Fear of cholesterol-associated risks (n = 802)
	Quite frightened	338 (42.1)
	Not really frightened	184 (22.9)
	Not at all frightened	182 (22.7)
	Very frightened	83 (10.3)
	Did not know	15 (1.9)

ª 2011 The Authors Journal of Human Nutrition and Dietetics ª 2011 The British Dietetic Association Ltd. 2011 J Hum Nutr Diet, 24, pp. 572-581

Table 4

 4 Person to whom confidence in disease management was given, information sources used, beliefs concerning protection against cardiovascular risks, and frequency of medical consultation

	n (%)

Table 5

 5 Influence and role of people in management of the disease

	n (%)

Table 7

 7 Foods classified as to be avoided or favoured*

	n (%)

*The patients were asked two questions: (1) 'Name three foods which should, in your opinion, be avoided when someone has a too high level of cholesterol?'; (2) 'Name three foods which should, in your opinion, be eaten regularly when someone has a too high level of cholesterol?'. Each food was enquired about individually.

Table 8

 8 Dietary deviation and ease of following recommended diet One hundred and thirty-two individuals were not included (101 claimed to never deviate from the prescribed diet, and 31 did not know how often they deviated from diet).

	n (%)

*

Table 9

 9 Foods eaten during dietary deviation compared with foods individuals believed should be avoided*

		n (%)
		Foods eaten during	Foods considered
		dietary deviations	'to be avoided'
		(n = 670)	(n = 802)
	Cheese	337 (50.3)	211 (26.3)
	Processed meat	262 (39.1)	354 (44.1)
	(charcuterie)
	Cakes	221 (33.0)	88 (11.0)
	Dish with rich sauce	188 (28.1)	83 (10.3)
	Fatty meat, red meat	161 (24.0)	455 (56.7)
	Alcohol (wines	154 (23.0)	74 (9.2)
	and other alcohols)
	Snacks	140 (20.9)	13 (1.6)
	Butter	118 (17.6)	312 (38.9)
	Egg	118 (17.6)	150 (18.7)
	Other	52 (7.8)	201 (25.1)
	Did not know	6 (0.9)	7 (0.9)
	*Each food was enquired about separately.
	One hundred and thirty-two individuals were not included (101
	claimed to never deviate from the prescribed diet, and 31 did not
	know how often they deviated from diet).

ª 2011 The Authors Journal of Human Nutrition and Dietetics ª 2011 The British Dietetic Association Ltd. 2011 J Hum Nutr Diet, 24, pp. 572-581

Table 10

 10 Association between compliance with diet and lipid-lowering medication

			Did not take
		Took lipid-lowering	lipid-lowering
		medication (%)	medication (%)	P
	(n = 729)	476 (65)	253 (35)	<0.05
	Complied	244 (51)	89 (35)
	with diet
	Did not comply	232 (49)	164 (65)
	with diet

Journal of Human Nutrition and Dietetics ª 2011 The British Dietetic Association Ltd. 2011 J Hum Nutr Diet, 24, pp. 572-581

ª 2011 The Authors

ª 2011 The Authors Journal of Human Nutrition and Dietetics ª 2011 The British Dietetic Association Ltd. 2011 J Hum Nutr Diet, 24, pp. 572-581

Acknowledgments

The authors thank the individuals who participated in the survey. Catriona Holmes (Paris), provided medical writing services.

Conflict of interests, source of funding and authorship

TF and JPP declares having received honoraria from Unilever. EB declares having received honoraria from Unilever and Danone. AP is employed by Unilever, France. The THEMA study was commissioned by the New French Society for Atherosclerosis (la Nouvelle Socie ´te ´Franc ¸aise d'Athe ´roscle ´rose), and funded by Unilever France. TF, EB, SC, AP and JPP contributed to the planning of the study, the supervision of the questionnaire design, and the analysis of the data. TF supervised the data collection and analysis. All authors contributed to the preparation of the manuscript. All authors critically reviewed the manuscript and approved the final version submitted for publication.