Prelabor cesarean delivery and early-onset acute childhood leukemia risk

Abstract

The long-term impact of cesarean delivery (CD) on the health of the offspring is being explored methodically. We sought to investigate the effect of birth by (a) prelabor and (b) during-labor CD on the risk of early-onset (≤3 years) acute lymphoblastic leukemia (ALL), specifically of its prevailing precursor B (B-ALL) subtype. A total of 1099 incident cases of ALL (957 B-ALL), 131 of acute myeloid leukemia (AML), and their 1 : 1 age-matched and sex-matched controls, derived from the Nationwide Registry for Childhood Hematological Malignancies (1996-2013), were analyzed using multivariate regression models. A null association was found between prelabor and/or during labor CD and either ALL (B-ALL) or AML in the 0-14 age range. By contrast, birth by CD increased significantly the risk of early-onset ALL [odds ratioCD (ORCD)=1.57, 95% confidence interval (CI): 1.10-2.24] mainly on account of prelabor CD (ORprelaborCD=1.66, 95% CI: 1.13-2.43). The respective figures were even higher for the early-onset precursor B-ALL (ORCD=1.66, 95% CI: 1.15-2.40 and ORprelaborCD=1.79, 95% CI: 1.21-2.66), whereas no association emerged for early-onset AML. Prelabor CD, which deprives exposure of the fetus/infant to the presumably beneficial effect of stress hormones released in both vaginal labor and during labor CD, was associated exclusively with an increased risk of early-onset ALL, particularly the precursor B-ALL subtype. If confirmed, these adverse long-term outcomes of CD may point to re-evaluation of prelabor CD practices and prompt scientific discussion on the best ways to simulate the effects of vaginal delivery, such as a precesarean induction of labor.

Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC)

“…One study distinguished between emergency and prelabour caesarean delivery and reported null associations for caesarean delivery overall and for prelabour caesarean delivery in children diagnosed at age 0-14 years, but reported moderate positive associations for children aged 0-3 years between ALL—particularly B-cell ALL—and both all-caesarean deliveries and prelabour caesarean delivery. 19 By contrast, no association was identified with emergency caesarean delivery. 19 Finally, one study investigated common ALL and reported a positive association between this subtype and caesarean delivery, especially in Hispanic people.…”

“…19 By contrast, no association was identified with emergency caesarean delivery. 19 Finally, one study investigated common ALL and reported a positive association between this subtype and caesarean delivery, especially in Hispanic people. 20 Our findings suggest that prelabour caesarean delivery increases risk of ALL.…”

“…We also did analyses restricted to children aged 0-3 years to replicate the analyses from the Greek study. 19 Separately, we stratified analyses by child's ethnic origin within ALL cases overall and then restricted analysis to children aged 2-5 years with ALL to replicate analyses from the California study. 20 For stratification by ethnic origin, we used data from the four US-based studies because these contained the most detailed data for ethnic origin.…”

“…18 Furthermore, two studies have done subgroup analyses and shown raised effect estimates when stratifying by disease subtypes or type of caesarean delivery. In what was, to our knowledge, the first study to investigate the role of prelabour caesarean delivery in childhood leukaemia, investigators showed an increased risk of overall ALL and precursor B-cell ALL in children aged 0–3 years after prelabour caesarean delivery, 19 whereas another study reported increased risk of common ALL (defined as ALL with expression of CD10 and CD19 surface antigens and diagnosis occurring between age 2 and 5.9 years), particularly in Hispanic people, after caesarean delivery. 20 …”

History of Maternal Fetal Loss and Childhood Leukaemia Risk in Subsequent Offspring: Differentials by Miscarriage or Stillbirth History and Disease Subtype

“…During the period 1996–2013, 1496 confirmed incident leukaemia cases aged 0–14 years old were notified by the network of Nationwide Registry for Childhood Hematological Malignancies and Brain Tumors (NARECHEM‐BT) collaborators in all six paediatric haematology‐oncology departments across Greece. Details on the NARECHEM‐BT case–control study have been described elsewhere . In the course of the study, interviews with the guardians of 192 children were not conducted for short intervals in two of the collaborating departments due to purely administrative reasons that are not likely to bias the results.…”