Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study

Abstract

In a historical cohort study of all singleton live births in Northern Ireland from 1971 -86 (n=434 933) associations between early life factors and childhood acute lymphoblastic leukaemia were investigated. Multivariable analyses showed a positive association between high paternal age (535 years) and acute lymphoblastic leukaemia (relative risk=1.49; 95% confidence interval (CI)=0.96 -2.31) but no association with maternal age. High birth weight (53500 g) was positively associated with acute lymphoblastic leukaemia (relative risk=1.66; 95% CI=1.18 -2.33). Children of mothers with a previous miscarriage or increased gestation (540 weeks) had reduced risks of ALL (respective relative risks=0.49; 95% CI=0.29 -0.80, and 0.67; 95% CI=0.48 -0.94). Children born into more crowded households (51 person per room) had substantially lower risks than children born into less crowded homes with also some evidence of a lower risk for children born into homes with three adults (relative risks=0.56; 95% CI=0.35 -0.91 and 0.58; 95% CI=0.21 -1.61 respectively). These findings indicate that several early life factors, including living conditions in childhood and maternal miscarriage history, influence risk of acute lymphoblastic leukaemia in childhood.

Pre- and Post- birth Causes of Acute Lymphoblastic Leukemia

“…In the present study, there was no meaningful relationship between the birth order and ALL in children, which was similar to the findings of other studies (23)(24)(25). However, some studies have reported a rise in the birth order (26,27) and some others reported a decrease in the birth order (28) as a risk factor for the incidence of ALL in children.…”

Birth weight, maternal weight and childhood leukaemia

“…In addition, risk increased 14% with each 1000 g increase in birth weight. While some studies have been negative (Robison et al, 1987;Kaye et al, 1991;Savitz and Ananth, 1994;Dockerty et al, 1999;Thompson et al, 2001;Ma et al, 2005), the majority of studies support a weak to moderate increased risk of ALL among children who had heavier birth weights (Buckley et al, 1994;Cnattingius et al, 1995;Ross et al, 1997;Westergaard et al, 1997;Yeazel et al, 1997;Smulevich et al, 1999;Suminoe et al, 1999;Murray et al, 2002;Okcu et al, 2002;Reynolds et al, 2002;Shu et al, 2002), including some studies published since the metaanalysis (Hjalgrim et al, 2004;Jourdan-Da Silva et al, 2004;Lee et al, 2004;Paltiel et al, 2004). Our findings with respect to birth weight are consistent with previous studies.…”

“…A few earlier studies published in the 1960s or early 1970s suggested a weak increased risk of leukaemia or leukaemia death among offspring born to older mothers in the United States (Manning and Carroll, 1957;MacMahon and Newill, 1962;Stark and Mantel, 1969;Fasal et al, 1971). Since then, however, most studies of maternal age and the risk of leukaemia in the offspring have been negative or have shown weak, nonsignificant elevated risk with older maternal age (Salonen and Saxen, 1975;Kneale and Stewart, 1976;Shaw et al, 1984;Steensel-Moll et al, 1985;McKinney et al, 1987McKinney et al, , 1999Shu et al, 1988Shu et al, , 1994Shu et al, , 1999Zack et al, 1991;Cnattingius et al, 1995;Petridou et al, 1997;Roman et al, 1997;Ross et al, 1997;Westergaard et al, 1997;Dockerty et al, 1999;Thompson et al, 2001;Murray et al, 2002;Okcu et al, 2002;Jourdan-Da Silva et al, 2004). A handful of studies have resulted in statistically significant increased risk ratios in the order of 1.5 -2.0 for ALL or all leukaemias among children born to women older than age 35 years at delivery (Kaye et al, 1991;Buckley et al, 1994;Hemminki et al, 1999;Mogren et al, 1999;Dockerty et al, 2001;Reynolds et al, 2002;Shu et al, 2002;Jourdan-Da Silva et al, 2004).…”

The effects of advanced paternal age on fertility

“…For example, childhood leukemia carries a risk of 1 : 25 000 within the general population; however, with APA the rate increases to 1 : 17 000, with a relative risk of 1.5. 75 An increase in non-Hodgkins lymphoma has been documented in cases of APA, independent of maternal age. 76,77 Similarly, Yip et al 78 examined pediatric central nervous system tumors and found the risk of developing them to be 1 : 21 000 in the offspring of fathers with APA compared with that of the general population risk of 1 : 36 000.…”