En cas de cotutelle internationale, mettre ici le Logo de l’établissement de préparation de la thèse logo de l’établissement de préparation de la (UPSud, HEC, UVSQ, UEVE, ENS Paris-Saclay, thèse (UPSud, HEC, UVSQ, UEVE, ENS Paris- Polytechnique, IOGS, …). Ou, le cas échéant, logo de l’établissement co-délivrant le doctorat en Saclay, Polytechnique, IOGS,v …) cotutelle internationale de thèse (Cadre à enlever) (Cadre à enlever) v Maternal diet during pregnancy and early growth: focus on diet quality and food chemicals 2018SACLS014 : exposure NNT Thèse de doctorat de l'Université Paris-Saclay préparée à l’Université Paris Sud École doctorale n°570 Santé Publique EDSP Spécialité de doctorat: Santé publique – épidémiologie Thèse présentée et soutenue à Villejuif, le 16 janvier 2018, par Manik Kadawathagedara Composition du Jury : Mme M-C. Boutron-Ruault Directrice de recherche, INSERM (U 1018) Présidente Mme K. Castetbon Professeure, Université Libre Bruxelles Rapportrice Mme I. Momas Professeure, Université Paris V Rapportrice Mme M. Vrijheid Professeure, IS Global Barcelonne Rapportrice Mme C. Philippat Chargée de Recherche, INSERM (U 1209) Examinatrice M. J-F. Huneau Professeur, Agro Paris Tech (U 914) Examinateur Mme B. de Lauzon-Guillain Chargée de Recherche, INSERM (U 1153) Directrice de thèse En cas de cotutelle internationale, mettre ici le Logo de l’établissement de préparation de la thèse logo de l’établissement de préparation de la (UPSud, HEC, UVSQ, UEVE, ENS Paris-Saclay, thèse (UPSud, HEC, UVSQ, UEVE, ENS Paris- Polytechnique, IOGS, …). Ou, le cas échéant, logo de l’établissement co-délivrant le doctorat en Saclay, Polytechnique, IOGS,v …) cotutelle internationale de thèse (Cadre à enlever) (Cadre à enlever) v Maternal diet during pregnancy and early growth: focus on diet quality and food chemicals 2018SACLS014 : exposure NNT Thèse de doctorat de l'Université Paris-Saclay préparée à l’Université Paris Sud École doctorale n°570 Santé Publique EDSP Spécialité de doctorat: Santé publique – épidémiologie Thèse présentée et soutenue à Villejuif, le 16 janvier 2018, par Manik Kadawathagedara Composition du Jury : Mme M-C. Boutron-Ruault Directrice de recherche, INSERM (U 1018) Présidente Mme K. Castetbon Professeure, Université Libre Bruxelles Rapportrice Mme I. Momas Professeure, Université Paris V Rapportrice Mme M. Vrijheid Professeure, IS Global Barcelonne Rapportrice Mme C. Philippat Chargée de Recherche, INSERM (U 1209) Examinatrice M. J-F. Huneau Professeur, Agro Paris Tech (U 914) Examinateur Mme B. de Lauzon-Guillain Chargée de Recherche, INSERM (U 1153) Directrice de thèse L'amitié double les joies et réduit de moitié les peines. Francis Bacon Acknowledgment I want to thank many people who led me to achieve this thesis and helped me through their sharing, support, advice and friendship. First, I would like to thank Blandine de Lauzon-Guillain, my supervisor. Thank you for your encouragements, guidance, help, availability, support and trust during these 3 years. I would like to thank Jérémie Botton, who gave me the opportunity to work on this topic and on the COCTELL project. You both gave me the opportunity and supported me to carry out all the new ideas that I had, such as getting involved in the doctoral network and going to Norway for a research stay. I would like to thank Eleni Papadopoulou, Margareta Haugen and Anne Lise Brantsaeter from the Norwegian Institute of Public Health for your comments, friendship, time and hospitality during my stay in Norway. I would like to thank all the committee members. Thanks to Professor Marie-Christine Boutron-Ruault who accepted to be the president of the committee, Professor Martine Vrijhied, Professor Isabelle Momas and Professor Katia Castetbon principle referees. Thanks to Professor Jean-François Huneau and Doctor Claire Philippat who accepted to be examiners of my thesis. I am grateful for being able to benefit from their expertise. I would like to thank all the institutions that funded this thesis: the region Ile-de-France for my doctoral grant (CORDDIM), the French National Agency for Research that funded the COCTELL project, the Aurora program and Open Health Institute that helped with the expenses related to my doctoral stay in Norway. I would like to thank all the members of the COCTELL project for their implications, contributions, comments and fruitful discussion on this complex topic: Veronique Sirot, Thiéma Traoré, Amélie Crépet, Marion Hulin, Marie Aline Charles, Barbara Heude, Blandine de Lauzon- Guillain, Anne Forhan and Jérémie Botton the leader of the project. I would like to thank Fanny Rancière, Eleni Papadopoulou and Maria Pipi for their time in reading and commenting this manuscript. I would like to thank the doctoral school “Ecole Doctorale de Santé Publique” (ED570) and its director Jean Bouyer, Audrey Bourgeois and Fabienne Renoirt the secretaries, for their kindness and helpfulness. I would like to thank all the members of the student’s association (Astrid Coste, Catherine Tcheandjieu, Soumaya Ben-Khedher, Lucie Fournier, Fanny Artaud, Lucile Malard, Emmanuel Wiernick, Jean Kaboré and Pauline Scherdel) for the good energy and fun times that we had organizing the “Journée de l’Ecole Doctorale” and all the other activities. This thesis was prepared as part of the Doctoral Network in Public Health led by the EHESP. I would like to thank the doctoral network that supported me financially for my stay in Norway and for giving me the opportunity to attend many interesting seminars and to meet other doctoral students from a wide range of public health disciplines. I had the chance to co-organize a successful seminar on “Perinatal Environment and Child’s Health: importance of nutrition”. Thank you to all the doctoral students involved in this great project: Julie Boudet-berquier, Alice Brochard, Maxime Jeanjean, Romana Haneef, Maud Peltier and Eve Reynaud. I would like to thank all the members of the ORCHAD team for their contribution, guidance and help during this thesis. I will start of course with Anne Forhan and Edith Lesieux-Potier the foundation of this team. Edith thank you for your friendship, kindness and administrative help. Anne without you 7 Acknowledgment I wouldn’t be here: thank you for your patience and all the time spend to teach me SAS and for our sincere discussions. Thanks to Patricia Dargent and Cécilia Saldanha-Gomes for your engagement and support. Thanks to all the new PHD students and new engineer for their friendship, youthful happiness and kindness: Camille Davisse-Paturet (thank you for your kindness and willingness to help anyone), Morgane Ballon (thank you for your craziness and happiness), Déborah Walter (thank you for you joyfulness), Luisa Murcia, Marion Taine, Morgane Leguern, Marion Lecorguillé, Julie de Chefdebien and Céline Sardano. Thanks to the older team members with whom we shared so much: musical experiences, concerts, drinks, amazing talks, laughter, trips but most of all support and friendship you all made this thesis feasible and bearable I will never be able to thank you as much you all deserve! I was lucky to meet great friends in this difficult experience. Sophie Carles, thank for your unconditional support, sincere talks and your sense of humour; Pauline Scherdel, my favourite roommate, Vive Radio Bonheur! Fanny Rancière, thank you for your kindness and support; Eve Reynaud my little sis, thank you for being who you are and your unlimited kindness towards everyone; Yves Koudou, thank you for your joyfulness, amazing jokes ;) and our musical moments; Wen Lun Yuan, thank you for your friendship; Fabienne Lesueur, thank you to be so passionate and Jonathan Bernard thank you for your happiness. I would like to thank as well the amazing colleagues from NIPH: Somrutai Poothong, Ida Caspersen, Marianne Abel, Eleni Papadopoulou, Margareta Haugen, Anne Lise Brantsaeter and all department of Environmental exposures and epidemiology that made me feel home in Norway, shared their love of this amazing country and gave me a taste of the Norwegian culture. Sans vous, les amis je ne serais surement pas allée jusqu’au bout merci pour votre soutien dans les moments difficiles et d’avoir été là pour partager les moments joyeux ! Aux amis d’enfance, Alexis Morelle (merci de m’avoir initiée au running, un exutoire indispensable pour les journées difficiles de fin de thèse), Jones Dauphin, Elisa Revest, Marie Cerceau, Myriam Bou-saha et Ananda Henri-Biabaud merci d’avoir toujours été là et de l’être encore! Aux sages-femmes qui m’accompagnent depuis toujours, pour vos encouragements et tous nos moments passés ensemble depuis les pré-fa de la route de Grenoble à aujourd’hui merci pour tout : Claire Roman, Charlotte Clech, Emmanuelle Nabet, Elodie Buffet, Sylvain Fréhel, Audrey Randell, Elisabeth Joulakian et Marielle Bouqueau. My dear Londoners midwives, Maria Pipi, Sara Longoni, Jennifer Mittelsdaedt, Mariso Coéffé, Geraldine Wurm and Katerine Sorensen I am so grateful that we manage to keep in touch and still be there for every big steps in each other’s life. Mes chères collègues de la Maternité des Lilas, merci de partager l’amour de ce métier à la fois si difficile, intense et magnifique. Nous partageons des moments heureux comme des moments tragiques et vous m’avez donné la force de continuer malgré l’adversité. Merci particulièrement à Clémence Laisné-Baron, Clémentine Morel-Duclos, Zina Hebbache, Cécile Vitré, Carole Borye, Aurore Camier et Cécile Vernier de m’accompagner au quotidien. Merci à Tonia Ray et Marie Carmantrant pour votre amitié. Merci à Camille Millerand. Aux familles Gandoin, Wimille et Chambon merci pour votre soutien, vos encouragements et votre générosité sans limite. Merci de m’avoir accueillie dans votre famille pendant 10 ans. Merci à Guillaume Gandoin pour ton soutien. Merci à mes parents et mes sœurs, Saumya et Dayanthie, pour leurs accompagnements et soutiens. 8 Summary Introduction Maternal diet is the only prenatal source of nutrients and the major source for non-nutrients (such as chemicals) and can influence foetal growth and offspring’s long-term health.