Ingo Frommholz
email: ifrommholz@acm.org

Philipp Mayr
email: philipp.mayr@gesis.org

Guillaume Cabanac
email: guillaume.cabanac@univ-tlse3.fr

Suzan Verberne
email: s.verberne@liacs.leidenuniv.nl

Bibliometric-enhanced Information Retrieval: 11th International BIR Workshop

Keywords: Academic Search, Information Retrieval, Digital Libraries, Bibliometrics, Scientometrics

The Bibliometric-enhanced Information Retrieval (BIR) workshop series at ECIR tackles issues related to academic search, at the intersection of Information Retrieval, Natural Language Processing and Bibliometrics. BIR is a hot topic investigated by both academia and the industry. In this overview paper, we summarize the 11th iteration of the workshop and present the workshop topics for 2021.

Motivation and Relevance to ECIR

Bibliometric-enhanced IR is a hot topic with growing recognition in the information retrieval as well as the scientometrics community in recent years. This is motivated by the exploding number of scholarly publications and the need to satisfy scholars' specific information needs to find relevant research contribution for their own work. As a very recent example, the COVID-19 crisis and the large number of scientific publications triggered by it has made the effective and efficient scholarly search for and discovery of high-quality publications, for instance in pre-print repositories to ensure the quick dissemination of crucial research results, a priority. Bibliometric-enhanced information retrieval tries to provide solutions to the peculiar needs of scholars to keep on top of the research in their respective fields, utilising the wide range of suitable relevance signals that come with academic scientific publications, such as keywords provided by authors, topics extracted from the full-texts, co-authorship networks, citation networks, and various classification schemes of science. Bibliometric-enhanced IR systems must deal with the multifaceted nature of scientific information by searching for or recommending academic papers, patents, venues (i.e., conferences or journals), authors, experts (e.g., peer reviewers), references (to be cited to support an argument), and datasets.

The purpose of the BIR workshop series founded in 2014 [START_REF] Mayr | Bibliometric-Enhanced Information Retrieval[END_REF] is to tackle these challenges by tightening up the link between IR and Bibliometrics. We strive to bring the 'retrievalists' and 'citationists' [START_REF] White | Visualizing a discipline: An author co-citation analysis of Information Science, 1972-1995[END_REF] active in both academia and industry together. The success of past BIR events (Tab. 1) evidences that BIR@ECIR is a much needed scientific event for the different communities involved to meet and join forces to push the knowledge boundaries of IR applied to literature search and recommendation.

Objectives and Topics

The call for papers for the 2021 workshop (the 11th BIR edition) addressed current research issues regarding 3 aspects of the search/recommendation process:

1. User needs and behaviour regarding scientific information, such as:

-Finding relevant papers/authors for a literature review.

-Measuring the degree of plagiarism in a paper.

-Identifying expert reviewers for a given submission.

-Flagging predatory conferences and journals.

-Information seeking behaviour and HCI in academic search. 2. Mining the scientific literature, such as:

-Information extraction, text mining and parsing of scholarly literature.

-Natural language processing (e.g., citation contexts).

-Discourse modelling and argument mining. 3. Academic search/recommendation systems, such as:

-Modelling the multifaceted nature of scientific information.

-Building test collections for reproducible BIR.

-System support for literature search and recommendation.

At the time of writing, three keynote speakers accepted our invitation to give an invited talk during the workshop: Ludo Waltman, Lucy Lu Wang and Jimmy Lin. Jimmy Lin is a professor and the David R. Cheriton Chair in the David R. Cheriton School of Computer Science at the University of Waterloo, Canada. His main work is at the intersection of information retrieval, natural language processing, databases and data management. He has spearheaded the development of a search engine that provides access to over 45,000 scholarly articles about COVID-19 in the Allen Institute for AI's CORD-19 research dataset.

Ludo

Target Audience

The target audience of the BIR workshops are researchers and practitioners, junior and senior, from Scientometrics as well as Information Retrieval and Natural Language Processing. These could be IR/NLP researchers interested in potential new application areas for their work as well as researchers and practitioners working with bibliometric data and interested in how IR/NLP methods can make use of such data. The 10th anniversary edition in 2020 ran online with an audience peaking at 97 online participants [START_REF] Cabanac | Report on the 10th Anniversary Workshop on Bibliometric-enhanced Information Retrieval (BIR 2020)[END_REF]. In December 2020, we published our third special issue emerging from the past BIR workshops [START_REF] Cabanac | Scholarly literature mining with Information Retrieval and Natural Language Processing: Preface[END_REF].

Peer Review Process and Workshop Format

Our peer review process is supported by Easychair. Each submission is assigned to 2 to 3 reviewers, preferably at least one expert in IR and one expert in Bibliometrics or NLP. The programme committee for 2021 consists of peer reviewers from all participating communities. Accepted papers are either long papers (15minute talks) or short papers (5-minute talks). Two interactive sessions close the morning and afternoon sessions with posters and demos, allowing attendees to discuss the latest developments in the field and opportunities (e.g., shared tasks such as CL-SciSumm). These interactive sessions serve as ice-breakers, sparking interesting discussions that, in non-pandemic times, usually continue during lunch and the cocktail party. The sessions are also an opportunity for our speakers to further discuss their work. As a follow-up of the workshop, the co-chairs will write a report summing up the main themes and discussions to SIGIR Forum [1, for instance] and BCS Informer6 , as a way to advertise our research topics as widely as possible among the IR community.

Next Steps

Research on scholarly document processing has for many years been scattered across multiple venues such as ACL, SIGIR, JCDL, CIKM, LREC, NAACL, KDD, and others. Our next strategic step is the Second Workshop on Scholarly Document Processing (SDP)7 that will be held in June 2021 in conjunction with the 2021 Conference of the North American Chapter of the Association for Computational Linguistics (NAACL). This workshop and initiative will be organized by a diverse group of researchers (organizers from BIR, BIRNDL, Workshop on Mining Scientific Publications/WOSP and Big Scholar) which have expertise in NLP, ML, Text Summarization/Mining, Computational Linguistics, Discourse Processing, IR, and others.

Table 1 .

 1 Overview of the BIR workshop series and CEUR proceedings

	Year	Conference	Venue		Papers	Proceedings
	2014	ECIR	Amsterdam,	NL	6	Vol-1143
	2015	ECIR	Vienna,	AT	6	Vol-1344
	2016	ECIR	Padua,	IT	8	Vol-1567
	2016	JCDL	Newark,	US	10 + 10 a	Vol-1610
	2017	ECIR	Aberdeen,	UK	12	Vol-1823
	2017	SIGIR	Tokyo,	JP	11	Vol-1888
	2018	ECIR	Grenoble,	FR	9	Vol-2080
	2019	ECIR	Cologne,	DE	14	Vol-2345
	2019	SIGIR	Paris,	FR	16 + 10 b	Vol-2414
	2020	ECIR	Lisbon (Online), PT	9	Vol-2591
	2021	ECIR	Lucca (Online), IT	TBA	TBA
	a with CL-SciSumm 2016 Shared Task; b with CL-SciSumm 2019 Shared Task

  Waltman is professor and deputy director at the Centre for Science and Technology Studies (CWTS) at Leiden University. He leads the Quantitative Science Studies (QSS) research group at CWTS, which does research in the fields of bibliometrics and scientometrics. Ludo is coordinator of the CWTS Leiden Ranking, a bibliometric ranking of major universities worldwide. Lucy Lu Wang is a postdoctoral investigator at the Allen Institute for AI (AI2) in the Semantic Scholar research group. Lucy works in the areas of knowledge representation and biomedical ontologies, natural language processing applications for biomedical and scientific text, open access, and meta-science. She is one of the authors of the Covid-19 open research dataset (CORD-19).

BIR 2020 appeared in https://irsg.bcs.org/informer/category/spring-2020/

https://sdproc.org/2021/

Acknowledgement The organizers wish to thank all those who contributed to this workshop series: the researchers who contributed papers, the many reviewers who generously offered their time and expertise, and the participants of the BIR and BIRNDL workshops. Since 2016, we maintain the Bibliometric-enhanced-IR Bibliography that collects scientific papers which appear in collaboration with the BIR/BIRNDL organizers.


Peggy Drouillet
email: drouillet<peggy.drouillet@inserm.fr

Anne Forhan

Blandine De Lauzon-Guillain

Olivier Thiébaugeorges

Valérie Goua

Guillaume Magnin

Michel Schweitzer

Monique Kaminski

Pierre Ducimetière

Marie-Aline Charles

Olivier Thi

Val Rie Goua

Pierre Ducimeti

postnatal determinants of the child s development and health) '

Keywords: Adolescent, Adult, Birth Weight, Body Height, Diet, Fatty Acids, administration & dosage, Fatty Acids, Omega-3, administration & dosage, Fatty Acids, Unsaturated, administration & dosage, Female, Fetal Development, physiology, France, Humans, Infant, Newborn, Maternal Nutritional Physiological Phenomena, Middle Aged, Overweight, metabolism, Pregnancy, Pregnancy Complications, metabolism, Prenatal Exposure Delayed Effects, Prospective Studies, Regression Analysis, Seafood, Social Class

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.

Maternal fatty acid intake and fetal growth: evidence for an association in overweight women. The 'EDEN mother-child' cohort (study of pre-and early postnatal determinants of the child's development and health).

Maternal fatty acid intake and fetal growth: evidence for an association in overweight women. The EDEN mother-child cohort (study of pre-and early

INTRODUCTION

An adequate amount of dietary fat is essential for health, particularly for pregnancy and lactation. Essential fatty acids (EFA) play a major role during pregnancy. They provide the precursors for prostaglandins and leucotrienes and are present mainly in highly specialized membranes (retina and synapses). The consumption of EFA is deemed important for normal growth and development in infants. The interest in EFA in relation to pregnancy stemmed from both epidemiological observations and intervention studies , . They showed 1 -7 longer gestation, larger babies and in some cases, reduced numbers of pregnancy complications such as intrauterine growth retardation, pregnancy-induced hypertension, pre-delivery, in association with higher marine FA (long-chain polyunsaturated fatty acid (LC-PUFA) or n-3 FA), fish or fish oil intake.

Several mechanisms have been suggested for explaining these associations. The first one is a delayed spontaneous delivery, resulting from altered balance between the prostaglandins involved in the initiation of the labour , . The second one is an increased fetal 10 11 growth rate, resulting from improved placental blood flow due to lowered thromboxane/prostacyclin ratio and blood viscosity . 12 4 Moreover, marine fat could reduce the risk of pre-term delivery , and of intrauterine growth retardation . 13 14 15 However results in the literature are not consistent. Indeed, in one study, Olsen et al. could not detect any association between on 16

the one hand the length of gestation, birthweight and length and on the other hand the intake of n-3 FA in the second trimester of pregnancy, whether intake was quantified by a validated questionnaire or biochemical measurements. More importantly, an other randomised control trial in pregnant women failed to detect effects of n-3 and n-6FA supplementation on gestational length, birthweight and length, head circumference or placental weight . Nevertheless, several studies in both animals and humans have shown that 17

deficiency of dietary n-3 PUFA are associated with biochemical changes in the brain and with disturbances in vision and other neurological parameters . The most vulnerable period of neural development is during embryonic and fetal growth. EFAs, especially 18 docosahexaenoic acid (DHA), are required for fetal brain, nervous system and retinal growth in late pregnancy. The maternal plasma concentration of individual FA, and hence the composition of the maternal diet, may have large effects on LC-PUFA delivery to the foetus.

In the EDEN mother-child cohort study, we previously reported that a difference in pre-pregnancy fish and shells consumption from

" "
less than five to more than nine times per month was associated with a difference in birthweight of 5.0 (from 3,248 g to 3,412 g; p % = 0.0006), in overweight women only . The mother s fat store is relevant to the maternal hormonal responses and to the nourishment of the 19

'
embryo and fetus during pregnancy, and provides the basis for subsequent fat storage and utilization during pregnancy , . We 20 21 hypothesised that the association between fish intake and fetal growth may be related to differences in the fatty acid contents of fat stored and was enhanced in overweight women because of a greater availability from fat stored.

Objectives

The aim of the present analysis was, therefore, to study the relationship between FA intake before and during pregnancy and fetal growth in the same French population and to evaluate whether it is a possible mediator of the observed association with fish intake in overweight women . 19

MATERIAL AND METHODS

Population and study design

Pregnant women seen for a prenatal visit at the departments of Obstetrics and Gynaecology of the University Hospitals of Nancy and Poitiers before 24 weeks of amenorrhea (WA) were invited to participate. Enrolment started in February 2003 in Poitiers and September 2003 in Nancy, it lasted 27 months in each center and ended up with the inclusion of 2,002 women. Exclusion criteria were twin pregnancies, known diabetes before pregnancy, not being able to speak and read French, planned moving away from the region. Among women who fulfilled these inclusion criteria, 55 agreed to participate. The study was approved by the Ethic Committee of the Bic tre

% ê

Hospital. Written consents were obtained from the mother for herself at inclusion and for her newborn child after delivery.

At a visit performed between 24 28 WA by midwives research assistants, maternal height was measured with a wall Seca 206 stadiometer (Hamburg, Germany) to the nearest 0.2 cm and maternal weight was measured using electronic Terraillon SL 351 scales (Hanson Ltd, UK) to the nearest 0.1 kg. Skinfolds were measured using a commercial Harpenden caliper (Chasmor Ltd, London, UK) three times in the following order: tricipital (posterior aspect of the arm, at midpoint between the acromion and the olecranon), bicipital (anterior aspect of the arm, at midpoint between the acromion and the olecranon), subscapular (1 cm below the lower angle at the scapula) and supra-iliac (1 cm over the iliac crest, at the midaxillary line). After a five minute rest, three measures of systolic and diastolic blood pressures were performed at two-minute intervals with an Omron M4I device (Omron Healthcare Europe, Hoofddorp, The Netherlands).

Women came to the examination in a fasting state and received a 50 g glucose oral load.

22

. The questionnaire used in the EDEN study is very close to that of the FLVS study with the addition of some questions for a more 23 specific assessment of the intake of foods rich in folates, n-3 FA and vitamin A and of fish and trophallergic foods. It inquires about the intake of 137 different foods or food groups with a 7-item scale ranking from never to more than once a day.

The first-trimester FFQ (completed at recruitment, on average 15 WG) concerned the usual diet during the year prior to pregnancy; the second FFQ (completed in the first few days following delivery) was related to food intake during the last three months of pregnancy. To compute energy and nutrient intakes, we multiplied, for each food, the intake frequency by the nutrient composition for a portion size.

Portion size were determined using pictures for 12 food types (meats, French fries, pastas, vegetables, cakes, cheese ) on a three level … scale or were standard portions for the French adult population . We then summed contributions across all foods to obtain average daily 24 total intake of energy and intake of various macro-and micronutrients. Food composition was obtained from the SU.VI.MAX. nutrient composition database , which is based on a French nutrient composition database and US department of Agriculture publications and 25 26 is continually incremented by other published sources and personal communications from laboratories and manufacturers . Energy 27 -29 and nutrient intake was not estimated when more than 3 items of the FFQ were missing. Moreover, women with estimated total energy intake under 4,186.8 kJ/day (1,000 kcal/day) or over 20,934 kJ/day (5,000 kcal/day) were not included in the analyses. N-3 FA included linolenic acid, docohexaenoic acid (DHA), docosapentaenoic acid and eicosapentaenoic acid (EPA). The FFQ gave also information on type of oil used for cooking or seasoning.

Variable description and statistical analyses

Mean consumptions of total lipid and different FAs (saturated (SFA), mono-unsaturated (MUFA) and poly-unsaturated (PUFA), as well as n-3 and n-6 FA), in grams per day were compared between centers by Student s t test. Relationships with the socio-demographic ' characteristics of women were studied by multiple linear regressions adjusted for center and mother s age (in years).

'

We studied relationships between lipid consumption and fetal growth using the nutrient density method, i.e. we used the relative percentage of contribution of lipid intake to total energy intake, the relative percentage of contribution of SFA, MUFA or PUFA to total lipid intake or the relative percentage of contribution of n-3FA to total PUFA intake. Multiple linear regressions adjusted for different set of confounding variables (centre, mother s age and height, smoking habits, parity, gestational age, newborn s sex, BMI, and delay between ' '

birth and anthropometric measures) were performed to study these relationships.

As we had additional information on the type of fat used for cooking or seasoning, we used it to study whether this source of FA was associated with our outcome variables. We defined a four level variable from the answers to three questions asking for the type of oil used for cooking or seasoning. The first level corresponds to women who used with no preference any type of fat, the second level corresponds to women who used more often saturated fat (butter, hard margarine), the third level corresponds to women who used more often fat rich in n-6 FA (sunflower oil, corn oil) and the last level corresponds to women who used more often fat rich in n-9 FA (olive oil, groundnut oil). Only 3 women consumed preferentially fat rich in n-3 FA (colza oil), so they were classified in the 4 others groups according to the other type of fat they used. We tested whether the type of fat used for cooking or seasoning variable modified the relationships between

" "
FA intakes and fetal growth.

Separate analyses were performed for intake prior to and during the last three months of pregnancy. Interaction terms between FA consumption and center, gestational length, BMI (continuous then categorical variable), average cigarettes per day smoked during pregnancy and educational level were tested. Significant interaction was found for BMI (p<0.05), therefore analyses were stratified according to overweight status (BMI<25 vs. 25 kg/m ). Several additional adjustments for educational level and maternal health

RESULTS

Subjects characteristics

Analyses included the 1,446 women who completed the two FFQs and for whom nutrients intake could be evaluated (67 were not included because of at least one missing FFQ and 374 because nutrient intake could not be estimated: 285 because more than three items of the FFQ were missing, 50 because total energy intake was under 4,186.8 kJ/day and 39 over 20,934 kJ/day. Also, newborns for whom delay between birth and anthropometric measures spaced from more than seven days were not included (n 9). The main characteristics of = included women (and their newborn), compared to the 450 excluded women, are shown in . Excluded women had less often Table 1 reached a university level and were more often single than included women. The percentage of newborn transfer to reanimation or a neonatal unit was higher for excluded women. Mean birthweight was significantly lower for offspring of excluded women compared to the others (3,224 vs. 3,295 g). Mean maternal age was 29 years in both groups (range 17 45). For included women, mean pBMI was 23 kg/m -2 , 9.5 of women had a pBMI < 18.5 kg/m , 17.5 were overweight and 7.7 were obese. Overweight women had less often reached a

% 2 % %
university level and were less often single than non-overweight women ( ). Mean birth weight and length were significantly lower Table 2 for offspring of non-overweight women compared to the others (3,269 vs. 3,362 g and 49.4 vs 50.0 cm respectively).

The average intake of energy, proteins, carbohydrates, lipids and different families of FA (SFA, MUFA and PUFA) prior to and in the last three months of pregnancy are given in . Intakes were normally distributed except alcohol consumption. Significantly higher Table 3 total energy intake and percent of fat in total energy intake (with and without taking into account alcohol in total energy intake) were observed at the end of pregnancy compared to before pregnancy (9,948 vs. 9,596 kJ/day, 39 vs. [START_REF] Innis | Transport mechanisms for long-chain polyunsaturated fatty acids in the human placenta[END_REF] for the part of n-3 FA in total PUFA which decreased in overweight women. There was no significant difference in estimated total fat and FA intake according to maternal overweight status.

Relationships between maternal fat and FA intakes prior to pregnancy and socio-demographics characteristics of women

Differences in consumptions were observed between centers for MUFA, PUFA and n-3FA, as well as the part of PUFA in total lipid intake with higher intakes in Nancy, but there was no difference for the part of n-3FA in total PUFA intake. Total fat and FA intake (SFA, MUFA, PUFA) did not change significantly with age but n-3FA consumption increased by 0. intake of total lipid and the different types of FA was observed according to income level, marital status or smoking status during pregnancy. The same relationships were observed for intake during the last three months of pregnancy.

Fatty acid intakes and fetal growth

There was no relationship between the part of lipid in total energy intake before pregnancy and newborn anthropometric measures in the whole sample of women ( ). The same results were found for the part of SFA, MUFA and PUFA in total lipid intake, as well as Table 4 the part of n-3 or n-6 FA in total PUFA intake before and in the last three months of pregnancy. However, maternal overweight before pregnancy modified the relationship between FA intake and most outcome parameters (for instance p<0.04 for birthweight). Interaction were also significant for BMI as a categorical variable, so we decided to conduct the analyses separately for women < and 25 kg/m , ≥ 2 which separate overweight and obese women from the others.

In overweight women (n 366), no association was found between the part of lipid in total energy intake and fetal growth when = adjusted for centre, mother s age and height, smoking habits, parity, gestational age, newborn s sex and delay between birth and ' ' anthropometric measures ( ). A substitution of pre-pregnancy lipid intake of 6.2 (1 SD) to other macronutrients was associated Table 5 % with a 25g lighter birthweight (p 0.27) and 7 mm smaller head circumference (p 0.25). In models also adjusted for total energy intake, = = results were unchanged (Data not shown). Same results were found for lipid intake during the last trimester of pregnancy. No significant association was observed with the different FA families even when models were adjusted for total lipid intake (see for PUFA/lipid in table

). Results were unchanged when adjusted for educational level. 5

To study the relationships between n-3FA consumption and fetal growth, we first used a regression model adjusted for center, mother s ' age and height, smoking habits, parity, gestational age, newborn s sex and delay between birth and anthropometric measures (

). A ' Table 6 substitution of 0.3 (1 SD) of the part of n-3FA in total lipid intake to other macronutrients before pregnancy was related to an average % increase in birthweight of 87g (p 0.002), length of 28mm (p 0.02), head circumference of 18mm (p 0.02), arm and wrist circumferences

= = =
of 16 and 13mm respectively (p<0.007) and sum of skinfolds of 0.3mm (p 0.01) (Model 1). Further adjustment on total lipid intake shows = that fetal growth was strongly associated with a greater contribution of n-3FA to total lipid intake (Model 2).

Similar results were found for the part of n-3FA in total PUFA intake. A substitution of 2.4 (1 SD) of this intake to other type of % PUFA before pregnancy was related to an average increase in birthweight of 60g (p 0.01), head circumference of 13mm (p 0.04), arm and

= =
wrist circumferences of 14 and 9mm respectively (p<0.006) and sum of skinfolds of 0.2 mm (p 0.03). Further adjustment on total PUFA = intake shows that fetal growth was more strongly associated with a higher contribution of n-3FA to total PUFA intake (Model 4). Results were unchanged when adjusted for educational level (Model 5). Relationships with n-3FA intake during the last trimester of pregnancy were weaker and not significant ( ). Table 6 After further adjustment for systolic or diastolic arterial pressure, fasting glucose and triglycerides (at 6 month of pregnancy) these th associations remained unchanged. Before pregnancy, a substitution of 2.4 of n-3FA to other PUFA was related to an increase in % birthweight of 41g to 51g, depending on the adjustments (0.03 p 0.09). For n-3FA intake during pregnancy, the range of variation was ≤ ≤ 26g to 36g and was not significant (data not shown).

The type of fat used for cooking or seasoning was not associated with newborn anthropometric measures (Data not shown). Moreover, previous associations found between total n-3FA intake estimated by the FFQ and the newborn anthropometric measures were unchanged when we took into account the type of fat used for cooking or seasoning (data not shown).

Correlation coefficients between number of fish and shells consumptions per week and PUFA intake ( PUFA/energy intake) was % 0.12 for intake before pregnancy and 0.06 for intake in the last three months of pregnancy (p<0.04). Correlation was very strong for n-3FA/PUFA (r 0.38 and r 0.35 for intakes prior to and during pregnancy respectively, p<0.0001). Moreover, fish and shells consumption

= =
explained more than 32 of the variability in n-3FA intake. When average monthly fish and shells consumption before pregnancy was % added to the model, the relationship with n-3FA in total PUFA intake was reduced to no significant level. Relationship with fish and shells consumption remained significantly associated with fetal growth.

There were too few obese women to be studied separately, but excluding obese women from the analyses did not change the associations found in women with a BMI 25 kg/m .

≥ 2
No statistically significant associations were found with placental weight and length of gestation.

No statistically significant associations were found in non overweight women, as shown in for the association between Figure 1 birthweight and the part of n-3FA in total PUFA intake divided into tertiles.

DISCUSSION

In this French cohort, increased proportion of n-3FA in total PUFA intake before pregnancy, and to a lesser extent of intake during the last three months of pregnancy, was not associated with fetal growth in the total sample of women. However, in overweight women, it was associated with increased fetal growth, appreciated by birthweight, head, arm and wrist circumferences and skinfolds. Several epidemiologic studies conducted in Northern countries with usual high mean fish and shells intake as well as marine n-3FA by pregnant women found an association with an increased birthweight either due to an increase in length of gestation or an increase in fetal growth rate but without considering the maternal BMI status , . 5 30 -32 Although pBMI may be affected by recall bias, we did not consider BMI estimated using measured weight during pregnancy as an accurate measure of maternal nutritional status. It is affected by plasma volume expansion related to pregnancy and fetal and placental weight. However for 1042 women who had a first visit before 15 WA, we found similar results when using measured BMI, i.e. significant interaction with maternal overweight and positive association with maternal n-3/PUFA intake and fetal growth.

In our study, the women excluded from the dietary analysis were different from included women for some characteristics such as educational level. It may be related to a greater ability of educated women to average intake frequency and to concentrate on a long series of questions. Nevertheless, adjustment for educational level had no effect on our results. Even if it is not possible to exclude possible recall bias in the report of consumptions before pregnancy, FFQ appears to be the only way to evaluate nutrient intakes before pregnancy in our study.

The percentage of overweight and obese could appear low but was similar to the general population of French women. In France, albeit the prevalence is notably lower than in the USA, the frequency of obesity has nearly doubled between 1997 and 2006. In women 20-39 years old, it increased from 5.2 to 11 during this period .

% % 33
Furthermore, evaluation of nutrient intakes with a food frequency questionnaire has some limits. This may have altered our observed differences in food intake and therefore our ability to detect differences between groups. For example, the estimation of PUFA intake with the FFQ did not included the type of fat and oils used for cooking or seasoning. In order to take into account differences in type of fat used for cooking or seasoning, we studied whether using predominantly (or not) SFA or fat rich in n-6 or n-9FA, was associated with fetal growth and found no specific association.

Several previously published studies have demonstrated a heavier placenta and a longer gestation among women who consumed more n-3 FA but we did not observed these associations in our study. Because of the imprecision in the gestational age assessment, however, 34 the effect of FA consumption on the prolongation of the intrauterine growth period may be difficult to detect. Another explanation would be that this effect requires higher n-3 FA intake than that observed in our study. In an intervention study by Olsen et al. , , the level of 4 13 n-3 FA intake was higher than in our study (6.1g/day for the intervention group vs. 2.7 g/day in the control group, whereas in our study the estimated mean intake was 1.2g/day).

There was no significant association between birth anthropometry and FA intakes in non-overweight women. Associations found in subgroups need to be considered with caution because of likely more false positive results. However there may be some rationale for such a selective effect in overweight women.

Overweight women have a higher fat mass. Differences in FA intake are associated with variations in the composition of FA stored in the adipose tissue. In fact, several studies showed that FA composition of the diet could influence FA composition of the adipose tissue.

Arterburn

showed that tissue contents in EPA and DHA increase in response to supplementation with theses FA, which means et al. [START_REF] Arterburn | Distribution, interconversion, and dose response of n-3 fatty acids in humans[END_REF] n-3FA in tissue increase with their presence in diet. Katan estimated that EPA levels in adipose tissue reflected intake over a et al. [START_REF] Katan | Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: an 18-month controlled study[END_REF] period of months and even years for DHA. Correlations between n-3 FA in total fat intake estimated by FFQ and n-3 FA in total fat % % measured in adipose tissue ranked from 0.38 to 0.42 in another study . Therefore, overweight women may have an enhanced ability to 37

release FA from adipose tissue to sustain fetal growth. We previously suggested that the specific relationship between fish and shells or n-3 FA intake and fetal growth in overweight women illustrates a special role of stored FA in the adipose tissue. This is reinforced by the fact that fish and shells as well as n-3FA consumption before pregnancy is more strongly associated with fetal growth than consumption during the last three months of pregnancy, as also observed by Olsen et al. . The storage of LC-PUFA and the balance of the n-3 and n- 6 16 families in maternal adipose tissue are of great importance since they represent a pool of FA, which can be used via placenta s transfer to ' supply the developing foetus , . There is evidence that the placenta itself may play a role in initiating the mobilisation of fatty acid 38 39 from the maternal adipose tissue in response to fetal needs . 40

In our study, significant relationships were observed between n-3FA intake and fetal growth when adjusted for PUFA intake. This result shows the importance of the balance n-3/n-6 which seems more essential than the absolute intake of n-3FA. There is a competition between the two FA families for entry and release from cellular phospholipids, as well as for the enzymes that catalyse their conversion to produce, for instance, arachidonic acid-derived eicosano des, such as the prostaglandins (PGF and PGE ) , . The balance plays a ï 2 α 2 10 41 major role in the availability of n-3 FA for the developing foetus. The concomitant intake of n-6 FA may explain part of the discrepancies in the literature about fish or n-3 FA consumption and fetal growth. All of the n-6 and n-3 FA accumulated by the foetus are derived by transfer across the placenta, which is provided with a specific system to ensure this function. The substrate of the placenta is provided by the maternal diet and the high rate of mobilization from maternal adipose stores and the mother adapts her metabolism to support the continuous draining of substrates by the fetus .

-44

Fish and shells intake removed the association between the contributions of n-3FA/PUFA on fetal growth in our study whereas the type of fat used for cooking or seasoning which is another major source of PUFA was not associated with fetal growth and did not removed this association. Fish and shells is indeed the main source of the variation of n-3FA/PUFA in our sample of French women . 19

These results consolidate the hypothesis of an effect of the n-3FA from fish and shells, in particular EPA and DHA, which are mainly present in fish and shells.

In conclusion, our study finds a relationship between the ratio of maternal n-3FA/PUFA intake and fetal growth in the French population, which is specific to overweight women. We suggest that the enrichment in long chain n-3 FA in the maternal adipose tissue stored before conception is a possible mediator of this relationship. The fact that the ratio n-3/n-6 appears more strongly related to fetal growth than the absolute intake of n-3FA may explain some of the discrepancies in the literature concerning the association of fish and shells intake and fetal growth. However, because our results stem from a subgroup analysis, replication is needed before firm conclusion can be made.

Ackowledgements:

We are indebted to the participating families, to the midwife research assistants (L Douhaud, S Bedel, B Lortholary, S Gabriel, M Rogeon, M Malinbaum) for data collection and to P Lavoine for checking, coding and data entry. We acknowledge all the funding sources for the EDEN for Research (ANR).

Footnotes:

Conflicts of interest and contribution of each author to the manuscript

There is no conflict of interest. Peggy Drouillet performed the study s analysis and wrote the paper. Anne Forhan was in charge of the

≥ 2 variables

 2 (systolic or diastolic arterial pressure, fasting plasma glucose) were also made.All analyses were performed with SAS version 9.1 (Cary, N.C., USA).

'Figure 1

 1 Figure 1Adjusted mean birthweight and of n-3 fatty acid intake in total polyunsaturated fatty acid intake ( n-3 FA/PUFA) before † % %

  Gestational age at delivery (determined from the date of the last menstrual period and early ultrasound assessment), newborn admission to a reanimation or neonatal unit, birth weight and length, placental weight (in Poitiers only) were extracted from clinical records. In the two obstetric departments, electronic Seca scales (Hamburg, Germany: Seca 737 in Nancy and Seca 335 in Poitiers) were used to measure infant weight and wooden somatometer (Testut, B thune, France) to measure infant length.

	circumference, measured at the largest occipitofrontal circumference. Skinfolds were measured in triplicate using a commercial Holtain
	caliper (Chasmor Ltd, London, UK)) in the following order: tricipital skinfold, measured at the same level as the midarm circumference;
	subscapular skinfold, measured at the lower angle of the scapula.
		é
	Dietary assessment
		Mothers completed two food frequency questionnaires (FFQs) similar to the questionnaire developed for the French population in the
	Fleurbaix-Laventie Ville Sant Study (FLVS) . This food frequency questionnaire has been validated against a series of 24 hour recalls é
		Glucose concentrations were measured on fasting
	and one hour after the glucose challenge. Weight before pregnancy, educational level and smoking habits during pregnancy were obtained
	by interview. Prepregnancy body mass index (pBMI) was computed as reported weight (kg)/measured height squared (m ). According to 2
	references of the International Obesity Task Force, overweight was defined as a BMI of 25 kg/m or more and obesity as a BMI of 30 kg/m 2
	2	and above. Average number of cigarettes consumed per day during pregnancy was computed.
		A second visit was performed for newborns by the same research assistants on average 1.8 days after delivery. Mother s weight and

  and 39.2 vs. 38.7 respectively,

	%	%
	p<0.001). Nevertheless, the part of PUFA in total lipid intake increased by 0.4 during pregnancy (p<0.0001); as well as the part of n-3

%

FA in total PUFA intake which decreased by 0.1 (p 0.08). Same trends were observed in non-overweight or overweight women, except % =

Table 1

 1 5.58 9.65 /2 : 9.65 11.38 /3 : 11.38 24.97 Means (SE) adjusted for centre, mother s age and height, smoking habits, Parity, † ' gestational age, newborn s sex and delay between birth and anthropometric measures Maternal and neonatal characteristics of the cohort (n 1896)

	-	[	[	-	[	[	-	] %

' = Mean (standard deviation) or % Included (n 1446) = Non included (n 450) * p<0.05 Δ of transfer in reanimation or neonatal unit %

Table 2

 2 Maternal and neonatal characteristics of included women according to their BMI

Mean (standard deviation) or % BMI<25kg/m (n 1055) 2 = BMI 25kg/m (n 364)

			≥	2	=
	Age (years)	29.1 (4.8)	29.5 (5.0)
	Height (m) *	1.64 (0.06)	1.63 (0.07)
	Prepregnant BMI (kg/m ) 2 *	21.1 (2.0)	29.1 (4.2)
	University Level *	60%	47%
	Parous *	52%	61%
	Unmarried	8%	5%
	Smoke during pregnancy	26%	23%
	Gestational length (weeks)	39.3 (1.6)	39.3 (1.8)
	Birth weight (g) *	3,269 (479)	3,362 (528)
	Birth length (cm) *	49.4 (2.3)	50.0 (2.5)
	Ponderal Index (kg/m3) *	27.1 (2.8)	26.8 (3.0)
	Transfer Δ	5.4%	8.2%

* p<0.05 Δ of transfer in reanimation or neonatal unit %

[START_REF] Andersen | Diet, pre-eclampsia, and intrauterine growth retardation[END_REF]

[START_REF] Andersen | Diet, pre-eclampsia, and intrauterine growth retardation[END_REF]

[START_REF] Andersen | Diet, pre-eclampsia, and intrauterine growth retardation[END_REF]

[START_REF] Andersen | Diet, pre-eclampsia, and intrauterine growth retardation[END_REF]

[START_REF] Andersen | Diet, pre-eclampsia, and intrauterine growth retardation[END_REF]

[START_REF] Andersen | Diet, pre-eclampsia, and intrauterine growth retardation[END_REF]

[START_REF] Andersen | Diet, pre-eclampsia, and intrauterine growth retardation[END_REF]

[START_REF] Andersen | Diet, pre-eclampsia, and intrauterine growth retardation[END_REF]

[START_REF] Andersen | Diet, pre-eclampsia, and intrauterine growth retardation[END_REF]