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Maternal reproductive history, fertility treatments and folic acid supplementation in the risk of childhood acute leukemia: the ESTELLE Study

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Abstract

Purpose

To investigate the potential involvement of fertility treatments and other conditions of becoming pregnant (infertility, getting pregnant on birth control, maternal history of fetal loss) and folic acid supplements in the etiology of childhood leukemia (CL).

Methods

The ESTELLE study included 747 cases of CL [636 cases of acute lymphoblastic leukemia (ALL) and 100 of acute myeloblastic leukemia (AML)] diagnosed in France in 2010–2011 and 1,421 population controls frequency-matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to mothers. The odds ratios (OR) and their 95 % confidence intervals were estimated using unconditional regression models adjusted for potential confounders.

Results

CL was not associated with difficulty in becoming pregnant [OR 0.9 (0.7–1.2)], in vitro fertilisation [OR 0.6 (0.3–1.5)] or the use of any fertility treatment [OR 0.8 (0.5–1.1)] for the index pregnancy. CL was not significantly associated with becoming pregnant on contraception [OR 1.2 (0.8–1.8)], but a positive association was observed for third generation oral contraception [OR 4.3 (1.2–16.2)]; however, the result is based on small numbers. Folic acid supplementation during pregnancy was not associated with CL, but an inverse borderline association was observed for supplementation initiated in the 3 months preceding pregnancy [OR 0.7 (0.5–1.0)]. In addition, maternal histories of stillbirth and miscarriage were associated with ALL [OR 2.6 (1.1–5.9)] and AML [OR 1.8 (1.1–2.8)], respectively.

Conclusions

The findings do not suggest that infertility and fertility treatments are risk factors for CL. They suggest that maternal histories of stillbirth and miscarriage may be more frequent among mothers of CL cases and that folic acid supplementation during preconception may reduce the risk of CL.

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Abbreviations

AL:

Acute leukemia

ALL:

Acute lymphocytic leukemia

AML:

Acute myeloblastic leukemia

AI:

Artificial insemination

ART:

Assisted reproductive technologies

CL:

Childhood acute leukemia

COCs:

Combined oral contraceptives

CATI:

Computer-assisted telephone interviewing

GIFT:

Gamete intrafallopian transfer

ICSI:

Intracytoplasmic sperm injection

IVF:

In vitro fertilization

NRCH:

National Registry of Childhood Hematopoietic Malignancies

NRST:

National Registry of Childhood Solid Tumors

OR:

Odds ratios

ZIFT:

Zygote intrafallopian transfer

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Acknowledgments

The authors are grateful to: Noureddine Balegroune, Sofiène Ben salha and the team of clinical research associates who contributed to the recruitment of the cases; Laure Faure and the staff of the French National Registry of Childhood Blood Malignancies, who contributed to case detection and verification; Christophe David and the team of interviewers (Institut IPSOS), who recruited the controls and interviewed the cases and controls. The authors would like to thank all of the Société Française de lutte contre les Cancers de l’Enfant et de l’Adolescent (SFCE) principal investigators: André Baruchel (Hôpital Saint-Louis/Hôpital Robert Debré, Paris), Claire Berger (Centre Hospitalier Universitaire, Saint-Etienne), Christophe Bergeron (Centre Léon Bérard, Lyon), Gerard Michel (Hôpital La Timone, Marseille), Yves Bertrand (Hôpital Debrousse, Lyon), Pascal Chastagner (Centre Hospitalier Universitaire, Nancy), Patrick Boutard (Centre Hospitalier Régional Universitaire, Caen), Gérard Couillault (Hôpital d’Enfants, Dijon), Christophe Piguet (Centre Hospitalier Régional Universitaire, Limoges), Anne-Sophie Defachelles (Centre Oscar Lambret, Lille), François Demeocq (Hôpital Hôtel-Dieu, Clermont-Ferrand), Alain Fischer (Hôpital des Enfants Malades, Paris), Virginie Gandemer (Centre Hospitalier Universitaire – Hôpital Sud, Rennes), Dominique Valteau-Couanet (Institut Gustave Roussy, Villejuif), Philippe Colombat (Centre Gatien de Clocheville, Tours), Frederic Millot (Centre Hospitalier Universitaire Jean Bernard, Poitiers), Guy Leverger (Hôpital Armand-Trousseau, Paris), Patrick Lutz (Hôpital de Hautepierre, Strasbourg), Nicolas Sirvent (Hôpital Arnaud de Villeneuve, Montpellier), Xavier Rialland (Hôpital Mère et Enfants, Nantes), Martine Münzer (American Memorial Hospital, Reims), Brigitte Nelken (Hôpital Jeanne de Flandre, Lille), François Doz (Institut Curie, Paris), Brigitte Pautard (Centre Hospitalier Universitaire, Amiens), Yves Perel (Hôpital Pellegrin Tripode, Bordeaux), Alain Pierre-Kahn (Hôpital Enfants Malades, Paris), Emmanuel Plouvier (Centre Hospitalier Régional, Besançon), Xavier Rialland (Centre Hospitalier Universitaire, Angers), Alain Robert (Hôpital des Enfants, Toulouse), Hervé Rubie (Hôpital des Enfants, Toulouse), Nicolas Sirvent (L’Archet, Nice), Marilyne Poiree (Fondation Lenval, Nice), Jean-Pierre Vannier (Hôpital Charles Nicolle, Rouen), Dominique Plantaz (Centre Hospitalier Universitaire, Grenoble), Philippe le moine (Hôpital Morvan, Brest) and Christian Sainte Rose (Centre Hospitalier Universitaire Necker, Paris). The authors would like also to thank all of the Lebanese university. This work was supported by grants from the Ligue Nationale Contre le Cancer (LNCC), the Agence Nationale de Sécurité Sanitaire de l’alimentation, de l’Environnement et du Travail (ANSES), the Institut National du Cancer (INCa) and the association Enfants et santé.

Conflict of interest

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Environmental Epidemiology of Cancers, INSERM, Villejuif, France

    Roula Ajrouche, Jérémie Rudant, Laurent Orsi, Denis Hémon & Jacqueline Clavel

  2. Department of Environmental Epidemiology of Cancers, Research Centre for Epidemiology and Population Health, Paris-Sud University, Villejuif, France

    Roula Ajrouche, Jérémie Rudant, Laurent Orsi, Denis Hémon & Jacqueline Clavel

  3. RNHE - National Registry of Childhood Hematopoietic Malignancies, Villejuif, France

    Jérémie Rudant & Jacqueline Clavel

  4. Service onco-hématologie pédiatrique, AP-HP, Hôpital Armand Trousseau, Paris, France

    Arnaud Petit

  5. Université Paris 6 Pierre et Marie Curie, Paris, France

    Arnaud Petit

  6. Service hématologie pédiatrique, AP-HP, Hôpital Robert Debré, Paris, France

    André Baruchel

  7. Université Paris 7, Paris, France

    André Baruchel

  8. Service hématologie pédiatrique, Hôpital Jeanne de Flandre, CHRU, Lille, France

    Brigitte Nelken

  9. Service oncologie pédiatrique, Hôpital des Enfants, Toulouse, France

    Marlène Pasquet

  10. Service hémato-oncologie pédiatrique, AP-HM, Hôpital la Timone, Marseille, France

    Gérard Michel

  11. Bureau d’Etude Clinique, Institut d’Hématologie et d’Oncologie Pédiatrique, Lyon, France

    Christophe Bergeron

  12. Service onco-hématologie pédiatrique, Hôpital Pellegrin Tripode, Bordeaux, France

    Stéphane Ducassou

  13. Unité onco-hématologie pédiatrique, CHU Hôpital Sud, Rennes, France

    Virginie Gandemer

  14. Service de pédiatrie 3, Hôpital de Hautepierre, Strasbourg, France

    Patrick Lutz

  15. Service hémato-oncologie pédiatrique, Hôpital Arnaud de Villeneuve, Montpellier, France

    Laure Saumet

  16. Unité d’onco-hématologie pédiatrique, Hôpital Mère-Enfant, CHU-Nantes, Nantes, France

    Xavier Rialland

  17. Unité d’oncologie pédiatrique, CHU d’Angers, Angers, France

    Xavier Rialland

Authors
  1. Roula Ajrouche
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  2. Jérémie Rudant
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  3. Laurent Orsi
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  4. Arnaud Petit
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  5. André Baruchel
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  6. Brigitte Nelken
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  7. Marlène Pasquet
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  8. Gérard Michel
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  9. Christophe Bergeron
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  10. Stéphane Ducassou
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  11. Virginie Gandemer
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  12. Patrick Lutz
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  13. Laure Saumet
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  14. Xavier Rialland
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  15. Denis Hémon
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  16. Jacqueline Clavel
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Correspondence to Roula Ajrouche.

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Ajrouche, R., Rudant, J., Orsi, L. et al. Maternal reproductive history, fertility treatments and folic acid supplementation in the risk of childhood acute leukemia: the ESTELLE Study. Cancer Causes Control 25, 1283–1293 (2014). https://doi.org/10.1007/s10552-014-0429-8

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  • DOI: https://doi.org/10.1007/s10552-014-0429-8

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