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History of Maternal Fetal Loss and Childhood Leukaemia Risk in Subsequent Offspring: Differentials by Miscarriage or Stillbirth History and Disease Subtype.
Paediatr Perinat Epidemiol. 2015 Sep; 29(5):453-61.PP

Abstract

BACKGROUND

Despite the putative intrauterine origins of childhood (0-14 years) leukaemia, it is complex to assess the impact of perinatal factors on disease onset. Results on the association of maternal history of fetal loss (miscarriage/stillbirth) with specific disease subtypes in the subsequent offspring are in conflict. We sought to investigate whether miscarriage and stillbirth may have different impacts on the risk of acute lymphoblastic leukaemia (ALL) and of its main immunophenotypes (B-cell and T-cell ALL), as contrasted to acute myeloid leukaemia (AML).

METHODS

One thousand ninety-nine ALL incidents (957 B-ALL) and 131 AML cases along with 1:1 age and gender-matched controls derived from the Nationwide Registry for Childhood Hematological Malignancies and Brain Tumors (1996-2013) were studied. Multivariable regression models were used to assess the roles of previous miscarriage(s) and stillbirth(s) on ALL (overall, B-, T-ALL) and AML, controlling for potential confounders.

RESULTS

Statistically significant exposure and disease subtype-specific associations of previous miscarriage(s) exclusively with AML [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.00, 2.81] and stillbirth(s) with ALL [OR 4.82, 95% CI 1.63, 14.24] and B-ALL particularly, emerged.

CONCLUSION

Differential pathophysiological pathways pertaining to genetic polymorphisms or cytogenetic aberrations are likely to create hostile environments leading either to fetal loss or the development of specific leukaemia subtypes in subsequent offspring, notably distinct associations of maternal miscarriage history confined to AML and stillbirth history confined to ALL (specifically B-ALL). If confirmed and further supported by studies revealing underlying mechanisms, these results may shed light on the divergent leukemogenesis processes.

Authors+Show Affiliations

Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece.Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece.Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece.Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece.Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece.Department of Pediatric Hematology-Oncology, 'Pan. & Agl. Kyriakou' Children's Hospital, Athens, Greece.2nd Department of Pediatrics, Aristotelion University of Thessaloniki, AHEPA General Hospital, Thessaloniki, Greece.Department of Pediatric Hematology and Oncology, Hippokration Hospital, Thessaloniki, Greece.Department of Pediatric Haematology-Oncology, 'Aghia Sophia' Children's Hospital, Athens, Greece.Department of Pediatric Hematology and Oncology, Hippokration Hospital, Thessaloniki, Greece.Department of Pediatric Hematology-Oncology, University Hospital of Heraklion, Heraklion, Greece.Haematology-Oncology Unit, First Department of Pediatrics, Athens University Medical School, 'Aghia Sophia' Children's Hospital, Athens, Greece.Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece.Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26174857

Citation

Karalexi, M A., et al. "History of Maternal Fetal Loss and Childhood Leukaemia Risk in Subsequent Offspring: Differentials By Miscarriage or Stillbirth History and Disease Subtype." Paediatric and Perinatal Epidemiology, vol. 29, no. 5, 2015, pp. 453-61.
Karalexi MA, Skalkidou A, Thomopoulos TP, et al. History of Maternal Fetal Loss and Childhood Leukaemia Risk in Subsequent Offspring: Differentials by Miscarriage or Stillbirth History and Disease Subtype. Paediatr Perinat Epidemiol. 2015;29(5):453-61.
Karalexi, M. A., Skalkidou, A., Thomopoulos, T. P., Belechri, M., Biniaris-Georgallis, S. I., Bouka, E., Baka, M., Hatzipantelis, E., Kourti, M., Polychronopoulou, S., Sidi, V., Stiakaki, E., Moschovi, M., Dessypris, N., & Petridou, E. T. (2015). History of Maternal Fetal Loss and Childhood Leukaemia Risk in Subsequent Offspring: Differentials by Miscarriage or Stillbirth History and Disease Subtype. Paediatric and Perinatal Epidemiology, 29(5), 453-61. https://doi.org/10.1111/ppe.12207
Karalexi MA, et al. History of Maternal Fetal Loss and Childhood Leukaemia Risk in Subsequent Offspring: Differentials By Miscarriage or Stillbirth History and Disease Subtype. Paediatr Perinat Epidemiol. 2015;29(5):453-61. PubMed PMID: 26174857.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - History of Maternal Fetal Loss and Childhood Leukaemia Risk in Subsequent Offspring: Differentials by Miscarriage or Stillbirth History and Disease Subtype. AU - Karalexi,M A, AU - Skalkidou,A, AU - Thomopoulos,T P, AU - Belechri,M, AU - Biniaris-Georgallis,S-I, AU - Bouka,E, AU - Baka,M, AU - Hatzipantelis,E, AU - Kourti,M, AU - Polychronopoulou,S, AU - Sidi,V, AU - Stiakaki,E, AU - Moschovi,M, AU - Dessypris,N, AU - Petridou,E Th, Y1 - 2015/07/14/ PY - 2015/7/16/entrez PY - 2015/7/16/pubmed PY - 2016/6/9/medline KW - acute lymphoblastic leukaemia KW - acute myeloid leukaemia KW - child KW - fetal loss KW - miscarriage KW - stillbirth SP - 453 EP - 61 JF - Paediatric and perinatal epidemiology JO - Paediatr Perinat Epidemiol VL - 29 IS - 5 N2 - BACKGROUND: Despite the putative intrauterine origins of childhood (0-14 years) leukaemia, it is complex to assess the impact of perinatal factors on disease onset. Results on the association of maternal history of fetal loss (miscarriage/stillbirth) with specific disease subtypes in the subsequent offspring are in conflict. We sought to investigate whether miscarriage and stillbirth may have different impacts on the risk of acute lymphoblastic leukaemia (ALL) and of its main immunophenotypes (B-cell and T-cell ALL), as contrasted to acute myeloid leukaemia (AML). METHODS: One thousand ninety-nine ALL incidents (957 B-ALL) and 131 AML cases along with 1:1 age and gender-matched controls derived from the Nationwide Registry for Childhood Hematological Malignancies and Brain Tumors (1996-2013) were studied. Multivariable regression models were used to assess the roles of previous miscarriage(s) and stillbirth(s) on ALL (overall, B-, T-ALL) and AML, controlling for potential confounders. RESULTS: Statistically significant exposure and disease subtype-specific associations of previous miscarriage(s) exclusively with AML [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.00, 2.81] and stillbirth(s) with ALL [OR 4.82, 95% CI 1.63, 14.24] and B-ALL particularly, emerged. CONCLUSION: Differential pathophysiological pathways pertaining to genetic polymorphisms or cytogenetic aberrations are likely to create hostile environments leading either to fetal loss or the development of specific leukaemia subtypes in subsequent offspring, notably distinct associations of maternal miscarriage history confined to AML and stillbirth history confined to ALL (specifically B-ALL). If confirmed and further supported by studies revealing underlying mechanisms, these results may shed light on the divergent leukemogenesis processes. SN - 1365-3016 UR - https://www.unboundmedicine.com/medline/citation/26174857/History_of_Maternal_Fetal_Loss_and_Childhood_Leukaemia_Risk_in_Subsequent_Offspring:_Differentials_by_Miscarriage_or_Stillbirth_History_and_Disease_Subtype_ L2 - https://doi.org/10.1111/ppe.12207 DB - PRIME DP - Unbound Medicine ER -