Maternal supplementation with folic acid and other vitamins and risk of leukemia in offspring: a Childhood Leukemia International Consortium study.

Background: Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemias (ALL) and 17% acute myeloid leukemias (AML). The early onset of the disease is suggestive of genetic predisposition and critical exposures occurring before birth. Maternal prenatal supplementation with folic acid and other vitamins, known to maintain DNA integrity and limit oxidative stress, could play a role in the prevention of childhood leukemia. However, reduced risks of childhood ALL following prenatal supplementation have been reported inconsistently. As for childhood AML, a rarer subtype, little is known regarding the effect of prenatal vitamins. Methods: We pooled original data on socio-demographic characteristics and maternal intake of folic acid, vitamins, and alcohol from 12 case-control studies (1980-2012) participating in CLIC (clic.berkeley.edu). The standardized data included the use of any vitamins, and use of folic acid, given anytime (before and/or during pregnancy) or during a specific period. The pooled analyses included 6,970 cases of ALL, 585 cases of AML, and 19,617 controls. Subgroup analyses were undertaken for vitamin type, period of use, and leukemia subtype. Logistic regression was used to estimate the odds ratios (OR) and 95 % confidence interval (CI), adjusted for age, sex, ethnicity, and other confounders including parental education, and study center. Results: Maternal intake of vitamins and folic acid anytime prenatally was associated with reduced risks of childhood ALL and AML. For ALL, the ORs for vitamin and folic acid intake during pregnancy specifically were 0.78 (95% CI: 0.71-0.85) and 0.82 (95% CI: 0.72-0.94), respectively, and 0.85 (95% CI: 0.64-1.13) and 0.52 (95% CI: 0.31-0.88), respectively, for AML. The observed reduction in ALL risk associated with prenatal vitamin intake was stronger in households where parents had no formal education or a primary education (OR=0.68, 95% CI: 0.56-0.83) and a secondary education (OR=0.75, 95% CI: 0.66-0.85), compared to those with a tertiary education (OR=0.96, 95% CI: 0.86-1.09). A similar trend across education levels was reported for maternal folic acid intake. The association between childhood ALL and maternal vitamin and folic acid intake also appeared stronger among women who did not consume alcohol. Conclusions: Our analyses based on the largest number of childhood ALL and AML cases to date suggest that maternal vitamin and folic acid intake reduces the risk of acute childhood leukemias. The risk seems modified by surrogate markers of nutritional status such as socio-economic status and alcohol consumption. Alternatively, participant selection, recall, access to prenatal care, or genetic susceptibility may vary in low vs. high income populations, therefore possibly contributing to this observation. Citation Format: Catherine Metayer, Elizabeth Milne, John D. Dockerty, Jacqueline Clavel, Maria S. Pombo-de-Oliveira, Catharina Wesseling, Logan G. Spector, Joachim Schüz, Eleni Petridou, Sameera Ezzat, Bruce K. Armstrong, Jérémie Rudant, Sergio Koifman, Peter Kaatsch, Maria Moschovi, Wafaa Rashed, Steve Selvin, Kathryn McCauley, Alice Y. Kang, Rayjean J. Hung, Patricia A. Buffler, Claire Infante-Rivard. Maternal supplementation with folic acid and other vitamins before and during pregnancy and risk of leukemia in the offspring: A childhood leukemia international consortium (CLIC) study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-31. doi:10.1158/1538-7445.AM2013-LB-31 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.

Introduction: Recent meta-analyses have reported modest but significant associations between birth by cesarean delivery (CD) and subsequent risk of immune-related disorders. An association of CD with childhood leukemia has not been established, although two recent case-control studies showed an increased risk of acute lymphoblastic leukemia (ALL) among young children born by CD, and elective CD (E-CD) in particular. Methods: We pooled data from 12 case-control studies in the Childhood Leukemia International Consortium. We analyzed CD overall and according to indications that likely resulted in E-CD (multiple birth and previous CD). Odds ratios (OR) and 95% confidence intervals (CIs) for risk of ALL and acute myeloid leukemia (AML) were estimated using multivariable logistic regression, adjusting for child's birth weight, sex, age, ethnicity, parental education, maternal age, and study center. Results: Delivery method was known for 8017 ALL cases, 659 AML cases, and 21273 controls. Among three studies with information on indication for CD, data were available for 3677 ALL cases, 114 AML cases, and 3929 controls. The association between CD and ALL (pooled OR: 1.06 [95% CI: 0.99, 1.14]) was not statistically significant, whereas birth by E-CD was associated with an increased risk of ALL (pooled OR: 1.27 [95% CI: 1.06, 1.52]). Subgroup analysis by immunophenotype revealed an association between E-CD and B-ALL (pooled OR: 1.28 [95% CI: 1.04, 1.57]), but not T-ALL. Pooled ORs for AML were 1.02 (95% CI: 0.82, 1.27) for overall CD and 1.39 (95% CI: 0.76, 2.53) for E-CD. Conclusions: Findings derived from a pooled analysis of data from several countries suggest a higher risk of childhood ALL following E-CD. More comprehensive assessment of the indications for E-CD in consortia studies will allow investigators to further explore the potential for confounding by indication. If this association is causal, maladaptive immune activation due to lack of stress response before birth and differential colonization of the microbiome in children born by E-CD should be considered as potential mechanisms. Risk of childhood leukemia associated with cesarean delivery overall and elective cesarean deliveryCesarean delivery (all indications)Pre-labor elective cesarean deliveryNumber of studiesExposed controlsExposed casesOR (95% CI)Number of studiesExposed controlsExposed casesOR (95% CI)Overall12340419241.06 (0.99, 1.14)32513081.27 (1.06, 1.52)ALL12340417491.06 (0.99, 1.14)32512901.27 (1.06, 1.52)AML824781221.02 (0.82, 1.27)1126161.39 (0.76, 2.53)ImmunophenotypeB-cell9313212201.07 (0.99, 1.16)22241961.28 (1.04, 1.57)T-cell931321300.95 (0.77, 1.18)2224241.18 (0.75, 1.88)Age012251561.08 (0.73, 1.60)36102.89 (0.93, 8.89)1-512221212261.05 (0.96, 1.15)31711921.22 (0.98, 1.53)6-10126693481.09 (0.93, 1.28)350591.34 (0.90, 2.01)11-14112721190.97 (0.74, 1.26)324291.25 (0.70, 2.24)Year of birth1970-1979464551.06 (0.70, 1.60)29111.13 (0.46, 2.80)1980-198997235351.01 (0.88, 1.15)31021221.30 (0.99, 1.72)1990-19991215296671.06 (0.95, 1.19)362741.32 (0.92, 1.90)2000-2009810524741.14 (0.98, 1.33)173781.14 (0.78, 1.65)2010-2013336181.93 (0.57, 6.51)1551.81 (0.16, 20.4)Gestational ageEarly preterm11126451.19 (0.67, 2.11)3650.58 (0.10, 3.24)Late preterm112581281.13 (0.84, 1.52)313151.56 (0.61, 3.98)Early term116943481.11 (0.93, 1.32)364851.27 (0.87, 1.86)Full term1113196331.01 (0.90, 1.14)31001311.31 (0.99, 1.72)Late term105482571.02 (0.86, 1.22)3760.95 (0.31, 2.90) Citation Format: Erin Marcotte, Thomas Thomopoulos, Jacqueline Clavel, John Dockerty, Sameera Ezzat, Stephen S. Francis, Claire Infante-Rivard, Corrado Magnani, Catherine Metayer, Ana Maria Mora, Beth A. Mueller, Wafaa M. Rashed, Michael E. Scheurer, Joachim Schuz, Catharina Wesseling, Alkistis Skalkidou, Eleni Petridou, Logan Spector. Cesarean delivery and risk of childhood leukemia: findings from the Childhood Leukemia International Consortium (CLIC). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-194. doi:10.1158/1538-7445.AM2015-LB-194

The Australian Study of Causes of Acute Lymphoblastic Leukemia in Children (Aus-ALL) was designed to test the hypothesis, raised by a previous Western Australian study, that maternal folic acid supplementation during pregnancy might reduce the risk of childhood acute lymphoblastic leukemia (ALL). Aus-ALL was a national, population-based, multicenter case-control study that prospectively recruited 416 cases and 1,361 controls between 2003 and 2007. Detailed information was collected about maternal use of folic acid and other vitamin supplements before and during the index pregnancy. Data were analyzed using logistic regression, adjusting for matching factors and potential confounders. A meta-analysis with the results of previous studies of folic acid supplementation was also conducted. We found weak evidence of a protective effect of maternal folate supplementation before pregnancy against risk of childhood ALL, but no evidence for a protective effect of its use during pregnancy. A meta-analysis including this and 2 other studies, but not the study that raised the hypothesis, also found little evidence that folate supplementation during pregnancy protects against ALL: the summary odds ratios (ORs) for folate supplementation were 1.06 [95% confidence interval (CI): 0.77-1.48] with reference to no folate supplementation and 1.02 (95% CI: 0.86-1.20) with reference to no vitamin supplementation. For vitamin supplementation in general, the summary OR from a meta-analysis of 5 studies-including Aus-ALL-was 0.83 (95% CI: 0.73-0.94). Vitamin supplementation in pregnancy may protect against childhood ALL, but this effect is unlikely to be large or, if real, specifically due to folate.

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

Objective:Tobacco smoke contains carcinogens known to damage somatic and germ cells. In this study, we investigated the effect of tobacco smoking on the risk of childhood acute lymphoblastic leukemia (ALL) and myeloid leukemia (AML).Methods:Information about tobacco smoking exposures of the mother before, during, and after pregnancy was collected via PubMed, Embase, and Web of Science databases through November 5, 2018. We performed to evaluate the association between smoking exposure and the risk of childhood ALL and AML. Study selection, data abstraction, and quality assessment were performed by 2 independent reviewers. Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs).Results:Nineteen case–control studies of childhood leukemia (age < 15 years) conducted in 9 countries from 1974 to 2018. Maternal smoking exposures did not a significant association with childhood ALL (OR = 1.004, 95% CI 0.953–1.058, P = .881) and AML (OR = 0.92, 95% CI 0.815–1.038, P = .177) during exposure time windows. However, there was an association with paternal smoking and ALL (OR = 1.15, 95% CI 1.038–1.275, P = .007). Paternal smoking in AML showed there was no association with smoking exposures and childhood AML (OR = 1.133, 95% CI 0.943–1.362, P = .181). Next, maternal daily cigarettes consumption showed no associations with ALL (OR = 1.08, 95% CI 1.000–1.168, P = .051) during pregnancy. No association with maternal daily smoking and AML (OR = 0.909, 95% CI 0.682–1.211, P = .514). Paternal daily cigarettes consumption was associated with increased risks of childhood ALL (OR = 1.200, 95% CI 1.112–1.302, P = .000). The higher consumption of paternal smoking (more than 10 per day) was significantly related to childhood ALL. Paternal daily smoking consumption also was related to AML (OR = 1.242, 95% CI 1.031–1.496, P = .022).Conclusion:Maternal smoking before, during, or after pregnancy was not associated with childhood ALL or AML. However, paternal smoking was related to a significantly elevated risk of childhood ALL during pregnancy, but not for AML. Maternal daily smoking consumption was not associated with ALL or AML during pregnancy. The higher consumption of paternal smoking were, the higher the risk of childhood ALL or AML.

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Several studies suggest that maternal folic acid supplementation before or during pregnancy protects against childhood acute lymphoblastic leukemia (ALL). We investigated associations between ALL risk and folate pathway gene polymorphisms, and their modification by maternal folic acid supplements, in a population-based case–control study (2003–2007).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; All Australian pediatric oncology centers provided cases; controls were recruited by national random digit dialing. Data from 392 cases and 535 controls were included. Seven folate pathway gene polymorphisms (&lt;i&gt;MTHFR&lt;/i&gt; 677C&gt;T, &lt;i&gt;MTHFR&lt;/i&gt; 1298A&gt;C, &lt;i&gt;MTRR&lt;/i&gt; 66A&gt;G, &lt;i&gt;MTR&lt;/i&gt; 2756 A&gt;G, &lt;i&gt;MTR&lt;/i&gt; 5049 C&gt;A, &lt;i&gt;CBS&lt;/i&gt; 844 Ins68, and &lt;i&gt;CBS&lt;/i&gt; 2199 T&gt;C) were genotyped in children and their parents. Information on prepregnancy maternal folic acid supplement use was collected. ORs were estimated with unconditional logistic regression adjusted for frequency-matched variables and potential confounders. Case–parent trios were also analyzed.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; There was some evidence of a reduced risk of ALL among children who had, or whose father had, the &lt;i&gt;MTRR&lt;/i&gt; 66GG genotype: ORs 0.60 [95% confidence interval (CI) 0.39–0.91] and 0.64 (95% CI, 0.40–1.03), respectively. The ORs for paternal &lt;i&gt;MTHFR&lt;/i&gt; 677CT and TT genotypes were 1.41 (95% CI, 1.02–1.93) and 1.81 (95% CI, 1.06–3.07). ORs varied little by maternal folic acid supplementation.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Some folate pathway gene polymorphisms in the child or a parent may influence ALL risk. While biologically plausible, underlying mechanisms for these associations need further elucidation.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Impact:&lt;/b&gt; Folate pathway polymorphisms may be related to risk of childhood ALL, but larger studies are needed for conclusive results. &lt;i&gt;Cancer Epidemiol Biomarkers Prev; 24(1); 48–56. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Several studies suggest that maternal folic acid supplementation before or during pregnancy protects against childhood acute lymphoblastic leukemia (ALL). We investigated associations between ALL risk and folate pathway gene polymorphisms, and their modification by maternal folic acid supplements, in a population-based case–control study (2003–2007).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; All Australian pediatric oncology centers provided cases; controls were recruited by national random digit dialing. Data from 392 cases and 535 controls were included. Seven folate pathway gene polymorphisms (&lt;i&gt;MTHFR&lt;/i&gt; 677C&gt;T, &lt;i&gt;MTHFR&lt;/i&gt; 1298A&gt;C, &lt;i&gt;MTRR&lt;/i&gt; 66A&gt;G, &lt;i&gt;MTR&lt;/i&gt; 2756 A&gt;G, &lt;i&gt;MTR&lt;/i&gt; 5049 C&gt;A, &lt;i&gt;CBS&lt;/i&gt; 844 Ins68, and &lt;i&gt;CBS&lt;/i&gt; 2199 T&gt;C) were genotyped in children and their parents. Information on prepregnancy maternal folic acid supplement use was collected. ORs were estimated with unconditional logistic regression adjusted for frequency-matched variables and potential confounders. Case–parent trios were also analyzed.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; There was some evidence of a reduced risk of ALL among children who had, or whose father had, the &lt;i&gt;MTRR&lt;/i&gt; 66GG genotype: ORs 0.60 [95% confidence interval (CI) 0.39–0.91] and 0.64 (95% CI, 0.40–1.03), respectively. The ORs for paternal &lt;i&gt;MTHFR&lt;/i&gt; 677CT and TT genotypes were 1.41 (95% CI, 1.02–1.93) and 1.81 (95% CI, 1.06–3.07). ORs varied little by maternal folic acid supplementation.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Some folate pathway gene polymorphisms in the child or a parent may influence ALL risk. While biologically plausible, underlying mechanisms for these associations need further elucidation.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Impact:&lt;/b&gt; Folate pathway polymorphisms may be related to risk of childhood ALL, but larger studies are needed for conclusive results. &lt;i&gt;Cancer Epidemiol Biomarkers Prev; 24(1); 48–56. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;

Several studies suggest that maternal folic acid supplementation before or during pregnancy protects against childhood acute lymphoblastic leukemia (ALL). We investigated associations between ALL risk and folate pathway gene polymorphisms, and their modification by maternal folic acid supplements, in a population-based case-control study (2003-2007). All Australian pediatric oncology centers provided cases; controls were recruited by national random digit dialing. Data from 392 cases and 535 controls were included. Seven folate pathway gene polymorphisms (MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756 A>G, MTR 5049 C>A, CBS 844 Ins68, and CBS 2199 T>C) were genotyped in children and their parents. Information on prepregnancy maternal folic acid supplement use was collected. ORs were estimated with unconditional logistic regression adjusted for frequency-matched variables and potential confounders. Case-parent trios were also analyzed. There was some evidence of a reduced risk of ALL among children who had, or whose father had, the MTRR 66GG genotype: ORs 0.60 [95% confidence interval (CI) 0.39-0.91] and 0.64 (95% CI, 0.40-1.03), respectively. The ORs for paternal MTHFR 677CT and TT genotypes were 1.41 (95% CI, 1.02-1.93) and 1.81 (95% CI, 1.06-3.07). ORs varied little by maternal folic acid supplementation. Some folate pathway gene polymorphisms in the child or a parent may influence ALL risk. While biologically plausible, underlying mechanisms for these associations need further elucidation. Folate pathway polymorphisms may be related to risk of childhood ALL, but larger studies are needed for conclusive results.

Surrogate measures of infectious exposures have been consistently associated with lower childhood acute lymphoblastic leukemia (ALL) risk. However, recent reports have suggested that physician-diagnosed early-life infections increase ALL risk, thereby raising the possibility that stronger responses to infections might promote risk. We examined whether medically diagnosed infections were related to childhood ALL risk in an integrated health-care system in the United States. Cases of ALL (n=435) diagnosed between 1994-2014 among children aged 0-14 years, along with matched controls (n=2,170), were identified at Kaiser Permanente Northern California. Conditional logistic regression was used to estimate risk of ALL associated with history of infections during first year of life and across the lifetime (up to diagnosis). History of infection during first year of life was not associated with ALL risk (odds ratio (OR)=0.85, 95% confidence interval (CI): 0.60, 1.21). However, infections with at least 1 medication prescribed (i.e., more "severe" infections) were inversely associated with risk (OR=0.42, 95% CI: 0.20, 0.88). Similar associations were observed when the exposure window was expanded to include medication-prescribed infections throughout the subjects' lifetime (OR=0.52, 95% CI: 0.32, 0.85).

It has been suggested that parental occupational paint exposure around the time of conception or pregnancy increases the risk of childhood leukemia in the offspring. We obtained individual level data from 13 case-control studies participating in the Childhood Leukemia International Consortium. Occupational data were harmonized to a compatible format. Meta-analyses of study-specific odds ratios (ORs) were undertaken, as well as pooled analyses of individual data using unconditional logistic regression. Using individual data from fathers of 8,185 cases and 14,210 controls, the pooled OR for paternal exposure around conception and risk of acute lymphoblastic leukemia (ALL) was 0.93 [95% confidence interval (CI) 0.76, 1.14]. Analysis of data from 8,156 ALL case mothers and 14,568 control mothers produced a pooled OR of 0.81 (95% CI 0.39, 1.68) for exposure during pregnancy. For acute myeloid leukemia (AML), the pooled ORs for paternal and maternal exposure were 0.96 (95% CI 0.65, 1.41) and 1.31 (95% CI 0.38, 4.47), respectively, based on data from 1,231 case and 11,392 control fathers and 1,329 case and 12,141 control mothers. Heterogeneity among the individual studies ranged from low to modest. Null findings for paternal exposure for both ALL and AML are consistent with previous reports. Despite the large sample size, results for maternal exposure to paints in pregnancy were based on small numbers of exposed. Overall, we found no evidence that parental occupational exposure to paints increases the risk of leukemia in the offspring, but further data on home exposure are needed.

It has been suggested that home paint exposure increases the risk of childhood acute lymphoblastic leukemia (ALL). We obtained individual level data from eight case-control studies participating in the Childhood Leukemia International Consortium. All studies had home paint exposure data (sometimes including lacquers and varnishes) for the pregnancy period with additional data for the 1-3-month period before conception in five, the year before conception in two, and the period after birth in four studies, respectively. Cytogenetic subtype data were available for some studies. Data were harmonized to a compatible format. Pooled analyses of individual data were undertaken using unconditional logistic regression. Based on 3,002 cases and 3,836 controls, the pooled odds ratio (OR) for home paint exposure in the 1-3 months before conception and risk of ALL was 1.54 [95% confidence interval (CI) 1.28, 1.85], while based on 1,160 cases and 1,641 controls for exposure in the year before conception, it was 1.00 (95% CI 0.86, 1.17). For exposure during pregnancy, using 4,382 cases and 5,747 controls, the pooled OR was 1.14 (95% CI 1.04, 1.25), and for exposure after birth, the OR was 1.22 (95% CI 1.07, 1.39), based on data from 1,962 cases and 2,973 controls. The risk was greater for certain cytogenetic subtypes and if someone other than the parents did the painting. Home paint exposure shortly before conception, during pregnancy, and/or after birth appeared to increase the risk of childhood ALL. It may be prudent to limit exposure during these periods.

ObjectiveTo ascertain whether there was an association between parental occupational exposure to pesticides and increased risk of acute lymphoblastic leukaemia (ALL) in the offspring.MethodA population-based case–control study of childhood ALL...

Parental tobacco smoking and risk of childhood leukemia in Costa Rica: A population-based case-control study

Genetic polymorphisms in the promoter regions of FAS, FASL and CASP8 involved in the apoptotic signaling pathway are thought to be associated with susceptibility to cancer. We hypothesized that these functional genetic variants might be associated with the risk of childhood acute lymphoblastic leukemia (ALL). A case–control study in a Chinese population with 361 cases of ALL and 519 controls was performed to evaluate the association between FAS, FASL and CASP8 variants and risk of childhood ALL. Individuals with FAS − 1377AG had an odds ratio (OR) of 0.72 for the risk of ALL compared to − 1377GG and the variant FASL − 844CC was associated with a statistically significantly decreased risk of childhood ALL (OR = 0.38). Furthermore, combined genotypes with 5–8 protective alleles were associated with a significantly decreased risk of childhood ALL compared with those with 0–4 variants, and this decreased risk was more pronounced among the subgroups of age < 6 years, female, parental never-drinking status and never house-painting. Our results provide evidence that FAS–FASL–CASP8 polymorphisms contributed to a reduced risk of childhood ALL in our population. Larger studies are warranted to validate our findings.

In addition to biological factors, maternal exposures during pregnancy can contribute to leukemogenesis in offspring. We conducted a population-based cohort study in Sweden to investigate the association between risk of acute lymphoblastic leukemia (ALL) in offspring and maternal anthropometrics during pregnancy. A total of 2,961,435 live-born singletons during 1983–2018 were followed from birth to ALL diagnosis, end of age 18, or end of 2018. 1388 children were diagnosed with ALL (55.6% boys). We observed an increased risk of ALL among daughters of overweight/obese mothers in early pregnancy [Body mass index (BMI) ≥ 25 kg/m2; Standardized incidence ratio (SIR) = 1.4, 95% CI: 1.2–1.6] compared with the risk in daughters of mothers with normal BMI. This association was not found in their sons (SIR = 1.0, 95% CI: 0.9–1.1). Similar results were found for the association between ALL and maternal BMI before delivery. We did not find an association between low or high gestational weight gain (GWG) and risk of ALL (both SIRs = 1.0) in male/female offspring. These suggest that maternal overweight/obesity are important risk factors for childhood ALL in daughters, whereas GWG is not associated with risk of ALL. Further research on this mother-daughter association may shed light on a possible sex hormone/chromosome-related etiology of ALL.