Fertility treatments, congenital malformations, fetal loss, and childhood acute leukemia: The ESCALE study (SFCE)

Authors

  • Jérémie Rudant MD, PhD,

    Corresponding author
    1. Department of Environmental Epidemiology of Cancers, INSERM, Villejuif, France
    2. Department of Environmental Epidemiology of Cancers, Paris-Sud University, Research Center in Epidemiology and Population Health, Villejuif, France
    3. RNHE - National Registry of Childhood Hematopoietic Malignancies, Villejuif, France
    • U1018 Inserm CESP – Environmental Epidemiology of Cancer Unit, 16 Avenue Paul Vaillant-Couturier, 94807 Villejuif Cedex, France.===

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  • Alicia Amigou,

    1. Department of Environmental Epidemiology of Cancers, INSERM, Villejuif, France
    2. Department of Environmental Epidemiology of Cancers, Paris-Sud University, Research Center in Epidemiology and Population Health, Villejuif, France
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  • Laurent Orsi PhD,

    1. Department of Environmental Epidemiology of Cancers, INSERM, Villejuif, France
    2. Department of Environmental Epidemiology of Cancers, Paris-Sud University, Research Center in Epidemiology and Population Health, Villejuif, France
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  • Thomas Althaus MD,

    1. Department of Environmental Epidemiology of Cancers, INSERM, Villejuif, France
    2. Department of Environmental Epidemiology of Cancers, Paris-Sud University, Research Center in Epidemiology and Population Health, Villejuif, France
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  • Guy Leverger MD, PhD,

    1. AP-HP, Hôpital Armand Trousseau, Paris, France
    2. Université Paris 6 Pierre et Marie Curie, Paris, France
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  • André Baruchel MD, PhD,

    1. AP-HP, Hôpital Robert Debré, Paris, France
    2. Université Paris 7, Paris, France
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  • Yves Bertrand MD, PhD,

    1. Institut d'Hémato-Oncologie Pédiatrique, Lyon, France
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  • Brigitte Nelken MD, PhD,

    1. Hôpital Jeanne de Flandre, CHRU, Lille, France
    2. Université Lille Nord de France, Lille, France
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  • Geneviève Plat MD, PhD,

    1. Hôpital des Enfants, Toulouse, France
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  • Gérard Michel MD, PhD,

    1. AP-HM, Hôpital la Timone, Marseille, France
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  • Nicolas Sirvent MD, PhD,

    1. Hôpital Arnaud de Villeneuve, Montpellier, France
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  • Pascal Chastagner MD, PhD,

    1. Hôpital d'enfants, CHU de Nancy, Vandoeuvre, France
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  • Stéphane Ducassou MD, PhD,

    1. Hôpital Pellegrin Tripode, Bordeaux, France
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  • Xavier Rialland MD, PhD,

    1. Hôpital Mère-Enfant, CHU-Nantes, France
    2. CHU d'Angers, Angers, France
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  • Denis Hémon PhD,

    1. Department of Environmental Epidemiology of Cancers, INSERM, Villejuif, France
    2. Department of Environmental Epidemiology of Cancers, Paris-Sud University, Research Center in Epidemiology and Population Health, Villejuif, France
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  • Jacqueline Clavel MD, PhD

    1. Department of Environmental Epidemiology of Cancers, INSERM, Villejuif, France
    2. Department of Environmental Epidemiology of Cancers, Paris-Sud University, Research Center in Epidemiology and Population Health, Villejuif, France
    3. RNHE - National Registry of Childhood Hematopoietic Malignancies, Villejuif, France
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  • Conflict of interest: Nothing to declare.

Abstract

Background

This study investigated the relationships between childhood acute leukemia (AL) and selective maternal and birth characteristics, including congenital malformations and the use of fertility treatment, for which the literature remains scarce.

Procedure

The national registry-based case–control study ESCALE was carried out in France in 2003–2004. Population controls were frequency matched with cases on age and gender. Data were obtained from structured telephone questionnaires. Odds ratios (OR) and their 95% confidence intervals were estimated using unconditional regression models adjusted for potential confounders.

Results

In all, 764 cases of AL (648 lymphoblastic AL (acute lymphoblastic leukemia, ALL) and 101 myeloblastic AL) and 1,681 controls were included. The AL cases' mothers reported congenital malformations more frequently than the controls' mothers (OR = 1.5 [1.0–2.4]). ALL was significantly associated with the use of fertility treatment for the index pregnancy (OR = 1.9 [1.3–2.8]). In particular, ALL was associated with ovulation induction only (OR = 2.6 [1.6–4.3]), but not with in vitro fertilization (IVF, OR = 1.0 [0.4–2.3]) or artificial insemination (OR = 1.3 [0.5–3.9]). A positive association was also observed for the difficulty of becoming pregnant without fertility treatment (OR = 1.5 [1.0–2.1]). AL was positively associated with a history of voluntary abortion (OR = 1.4 [1.1–1.8]) but not with a history of spontaneous (OR = 0.8 [0.7–1.0]) or therapeutic (OR = 0.7 [0.5–1.1]) abortion.

Conclusion

The results suggest that subfertility in itself and ovulation induction may be associated with ALL, and support a positive association with congenital malformations. The links with the various types of fertility drugs and the underlying causes of infertility need to be investigated further. Pediatr Blood Cancer 2013;60:301–308. © 2012 Wiley Periodicals, Inc.

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