TABLE 2.
Evidence examining the relationship between never versus ever feeding human milk and childhood leukemia1
| Article, study design (study/cohort name when applicable), country |
Notable sample characteristics | Never vs. ever feeding human milk exposures2 |
Significant associations with childhood leukemia |
Nonsignificant associations with childhood leukemia |
|---|---|---|---|---|
| Ajrouche 2015 (15) Case control (ESTELLE) France |
N = 617 ALL cases, 1225 controls Baseline: 1–14 y Race/ethnicity NR |
Ever BF vs. never BF | ALL: OR 0.80 (95% CI: 0.66, 0.99) | None |
| BF <6 mo vs. never BF | None | ALL: OR 0.81 (95% CI: 0.65, 1.02) | ||
| BF ≥6 mo vs. never BF | None | ALL: OR 0.78 (95% CI: 0.59, 1.04) | ||
| Beral 2001 (16) Case control (UKCCS) UK |
N = 1637 leukemia cases (134 in the subsample age 1 y, 890 in the subsample ages 2–5 y, 613 in the subsample ≥6 y, 1401 in the ALL subsample), 6964 controls Baseline: 1–14 y Race/ethnicity NR Sex NR |
Ever BF vs. never BF | None | Leukemia: OR 0.89 (95% CI: 0.80, 1.00), P = 0.06 Leukemia in subsample age 1 y: OR 0.76 (95% CI: 0.51, 1.12) Leukemia in subsample ages 2–5 y: OR 0.95 (95% CI: 0.81, 1.11) Leukemia in subsample ages ≥6 y: OR 0.85 (95% CI: 0.70, 1.02) ALL subsample: OR 0.91 (95% CI: 0.81, 1.04) |
| BF <1 mo vs. never BF | None | Leukemia: OR 0.96 (95% CI: 0.81, 1.14) ALL subsample: OR 0.98 (95% CI: 0.82, 1.17) |
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| BF 1–6 mo vs. never BF | None | Leukemia: OR 0.88 (95% CI: 0.77, 1.02) ALL subsample: OR 0.90 (95% CI: 0.77, 1.04) |
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| BF ≥7 mo vs. never BF | None | Leukemia: OR 0.85 (95% CI: 0.73, 1.00) ALL subsample: OR 0.89 (95% CI: 0.75, 1.05) |
||
| Davis 1988 (17) Case control US |
N = 52 ALL cases, 181 controls Baseline: 1.5–15 y Race/ethnicity NR |
Artificial feeding vs. BF > 6 mo | None | ALL: OR 1.46 (95% CI: 0.68, 3.14) |
| Dockerty 1999 (18) Case control New Zealand |
N = 95 ALL cases, 303 controls Baseline: 0–14 y Race/ethnicity: 88.7% non-Maori 11.3% Maori Sex NR |
BF vs. no BF |
None |
ALL: OR 0.98 (95% CI: 0.39, 2.47) |
| BF 2 d to 6 mo vs. no BF | None | ALL: OR 1.24 (95% CI: 0.47, 3.23) | ||
| BF > 6 mo to 1 y vs. no BF | None | ALL: OR 0.82 (95% CI: 0.29, 2.27) | ||
| BF > 1 y vs. no BF | None | ALL: OR 0.47 (95% CI: 0.15, 1.43) | ||
| Greenop 2015 (19) Case control (Australian Study of the Causes of Acute Lymphoblastic Leukaemia) Australia |
N = 314 ALL cases, 663 controls Baseline: 0–14 y Race/ethnicity: 77% European Ethnicity 17.5% ≥50% European 2.7% ≥50% Non-European 2.8% Indeterminate |
BF vs. no BF |
ALL: OR 0.52 (95% CI: 0.32, 0.84) |
None |
| BF <3 mo vs. no BF | ALL: OR 0.49 (95% CI: 0.28, 0.86) | None | ||
| BF ≥3 to <6 mo vs. no BF | None | ALL: OR 0.62 (95% CI: 0.34, 1.12) | ||
| BF ≥6 mo vs. no BF | ALL: OR 0.51 (95% CI: 0.30, 0.84) | None | ||
| EBF <3 mo vs. no BF | ALL: OR 0.50 (95% CI: 0.29, 0.84) | None | ||
| EBF ≥3 to <6 mo vs. no BF | ALL: OR 0.52 (95% CI: 0.31, 0.87) | None | ||
| EBF ≥6 mo vs. no BF | ALL: OR 0.55 (95% CI: 0.31, 0.99) | None | ||
| Infante-Rivard 2000 (20) Case control Canada |
N = 491 ALL cases (249 in the subsample age <4 y, 242 in the subsample age ≥4 y), 491 controls Baseline: 0–9 y Race/ethnicity NR |
BF ≤3 mo vs. no BF | ALL: OR 0.68 (95% CI: 0.49, 0.95) | ALL in subsample age <4 y: OR 0.62 (95% CI: 0.37, 1.03) ALL in subsample age ≥4 y: OR 0.78 (95% CI: 0.50, 1.23) |
| BF >3 mo vs. no BF | ALL: OR 0.67 (95% CI: 0.47, 0.94) | ALL in subsample age <4 y: OR 0.63 (95% CI: 0.39, 1.03) ALL in subsample age ≥4 y: OR 0.68 (95% CI: 0.41, 1.14) |
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| BF 1–6 mo vs. no BF | ALL in subsample age <4 y: OR 0.61 (95% CI: 0.39, 0.95) | ALL in subsample age ≥4 y: OR 0.72 (95% CI: 0.48, 1.09) | ||
| BF >6 mo vs. no BF | None | ALL in subsample age <4 y: OR 0.68 (95% CI: 0.36, 1.28) ALL in subsample age ≥4 y: OR 0.83 (95% CI: 0.42, 1.63) |
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| Jourdan-Da Silva 2004 (21) Case control France |
N = 393 ALL cases, 221 leukemia cases age 2–6 y, 199 leukemia cases 6–15 y, 530 controls |
BF vs. no BF | None | ALL: OR 1.1 (95% CI: 0.9, 1.5) Leukemia age 2–6 y: OR 1.0 (95% CI: 0.7, 1.5) Leukemia age 6–15 y: OR 1.4 (95% CI: 0.9, 2.0) |
| Baseline: 1–14 y Race/ethnicity NR |
BF <3 mo vs. BF 0 mo | None | ALL: OR 1.2 (95% CI: 0.8, 1.7) Leukemia age 2–6 y: OR 0.8 (95% CI: 0.5, 1.3) Leukemia age 6–15 y: OR 1.7 (95% CI: 1.0, 2.9) |
|
| BF 3–6 mo vs. BF 0 mo | None | ALL: OR 1.1 (95% CI: 0.7, 1.6) | ||
| BF >6 mo vs. BF 0 mo | None | ALL: OR 1.4 (95% CI: 0.8, 2.5) | ||
| BF ≥3 mo vs. never BF | None | Leukemia age 2–6 y: OR 1.4 (95% CI: 0.8, 2.2) Leukemia age 6–15 y: OR 1.0 (95% CI: 0.6, 1.6) |
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| Kwan 2005 (22) Case control (NCCLS) US |
N = 305 ALL cases (183 in the subsample age 2–5 y), 398 controls Baseline: 1–14 y |
Ever BF vs. never BF | None | ALL: OR 0.99 (95% CI: 0.64, 1.55) ALL in the subsample age 2–5 y: OR 1.49 (95% CI: 0.83, 2.65) |
| Race/ethnicity: 37.7% Hispanic 50% Non-Hispanic White |
BF ≤3 mo vs. never BF | None | ALL: OR 1.14 (95% CI: 0.68, 1.91) ALL in the subsample age 2–5 y: OR 1.67 (95% CI: 0.85, 3.28) |
|
| 2.8% Non-Hispanic Black 9.3% other |
BF 4–6 mo vs. never BF | None | ALL: OR 0.84 (95% CI: 0.48, 1.47) ALL in the subsample age 2–5 y: OR 1.07 (95% CI: 0.50, 2.25) |
|
| BF 7–12 mo vs. never BF | None | ALL: OR 0.88 (95% CI: 0.51, 1.53) ALL in the subsample age 2–5 y: OR 1.29 (95% CI: 0.63, 2.67) |
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| BF ≥13 mo vs. never BF | None | ALL: OR 1.08 (95% CI: 0.61, 1.92) ALL in the subsample age 2–5 y: OR 1.87 (95% CI: 0.88, 3.95) |
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| EBF ≤3 mo vs. FF only | None | ALL: OR 1.06 (95% CI: 0.65, 1.71) ALL in the subsample age 2–5 y: OR 1.75 (95% CI: 0.91, 3.34) |
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| EBF 4–6 mo vs. FF only | None | ALL: OR 0.97 (95% CI: 0.55, 1.71) ALL in the subsample age 2–5 y: OR 1.32 (95% CI: 0.63, 2.77) |
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| EBF 7–12 mo vs. FF only | None | ALL: OR 0.98 (95% CI: 0.55, 1.75) ALL in the subsample age 2–5 y: OR 1.14 (95% CI: 0.53, 2.44) |
||
| EBF ≥13 mo vs. FF only | None | ALL: OR 0.86 (95% CI: 0.38, 1.92) ALL in the subsample age 2–5 y: OR 2.04 (95% CI: 0.69, 6.07) |
||
| MacArthur 2008 (23) Case control (CCCLS) Canada |
N = 399 leukemia cases (351 in subsample with ALL), 399 controls Baseline: 0–14 y Race/ethnicity: 81.9% Caucasian 2.7% Asian 15.4% other |
BF vs. no BF at 0–3 mo | None | Leukemia: OR 1.26 (95% CI: 0.89, 1.79) ALL subsample: OR 1.33 (95% CI: 0.93, 1.91) |
| McKinney 1987 (24) Case control (IRESCC) UK |
N = 171 leukemia cases, 342 controls Baseline: 0–14 y Race/ethnicity: ∼93% White European ∼7% Indian/Pakistani/West Indian/Other |
BF vs. not BF | None | Leukemia: NS (RR <2 and nonsignificant statistical test; data NR) |
| McKinney 1999 (25) Case control (UKCCS) UK |
N = 144 leukemia cases (124 in the subsample with ALL), 271 controls Baseline: 3 mo to 14 y Race/ethnicity NR Sex NR |
Initially BF vs. not initially BF | None | Leukemia: OR 0.96 (95% CI: 0.62, 1.49) ALL subsample: OR 0.92 (95% CI: 0.58, 1.47) |
| Murray 2002 (26) Retrospective cohort (Northern Ireland Child Health System Cohort) UK |
N = 434,933 Baseline: 0–15 y Race/ethnicity NR |
BF vs. no BF | None | ALL: RR 0.98 (95% CI: 0.68, 1.42) |
| Perrillat 2002 (14) Case control France |
N = 247 leukemia cases, 237 controls Baseline: 2–15 y Race/ethnicity: 84.5% Caucasian 7% North African 1.6% Caribbean 1.4% African 1.4% Asian/Middle Eastern 4% mixed/others |
BF <6 mo vs. no BF |
None |
Leukemia: OR 1.1 (95% CI: 0.7, 1.7) |
| BF ≥6 mo vs. no BF | Leukemia: OR 0.5 (95% CI: 0.2, 1.0)3 | None | ||
| Perrillat 2002 (27) Case control |
N = 247 leukemia cases (219 in the subsample with ALL), 237 controls |
Any BF duration vs. never BF | None | Leukemia: OR 0.8 (95% CI: 0.6, 1.2) ALL subsample: OR 0.8 (95% CI: 0.6, 1.2) |
| France | Baseline: 2–15 y Race/ethnicity: 84.5% Caucasian 7% North African 1.6% Caribbean 1.4% African 1.4% Asian/Middle Eastern 4% mixed/others |
BF <3 mo vs. never BF |
None |
Leukemia: OR 1.0 (95% CI: 0.6, 1.7) ALL subsample: OR 1.0 (95% CI: 0.6, 1.6) |
| BF 3–5 mo vs. never BF | None | Leukemia: OR 1.3 (95% CI: 0.8, 2.3) ALL subsample: OR 1.3 (95% CI: 0.8, 2.4) |
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| BF 6–11 mo vs. never BF | Leukemia: OR 0.4 (95% CI: 0.2, 1.0)3 | ALL subsample: OR 0.5 (95% CI: 0.2, 1.1) | ||
| BF ≥12 mo vs. never BF | None | Leukemia: OR 0.6 (95% CI: 0.2, 2.7) ALL subsample: OR 0.5 (95% CI: 0.1, 2.5) |
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| Petridou 1997 (28) Case control Greece |
N = 153 leukemia cases, 300 controls Baseline: 0–14 y Race/ethnicity NR |
BF vs. no BF | None | Leukemia: OR 0.85 (95% CI: 0.52, 1.41) |
| Rudant 2010 (29) |
N = 634 ALL cases, 1494 controls | BF vs. no BF | None | ALL: OR 1.0 (95% CI: 0.8, 1.2) |
| Case control (ESCALE) |
Baseline: 1–14 y | BF <6 mo vs. no BF | None | ALL: OR 1.1 (95% CI: 0.9, 1.4) |
| France | Race/ethnicity NR | BF ≥6 mo vs. no BF | ALL: OR 0.7 (95% CI: 0.5, 1.0), P < 0.05 | None |
| BF ≤2 mo vs. no BF | None | ALL: OR 1.3 (95% CI: 1.0, 1.6) | ||
| BF 3–5 mo vs. no BF | None | ALL: OR 0.9 (95% CI: 0.7, 1.2) | ||
| BF 6–11 mo vs. no BF | None | ALL: OR 0.7 (95% CI: 0.5, 1.1) | ||
| BF ≥12 mo vs. no BF | None | ALL: OR 0.6 (95% CI: 0.3, 1.0) | ||
| Shu 1995 (30) Case control China |
N = 159 leukemia cases (99 in subsample age ≤5 y, 60 in subsample age >5 y, 108 in subsample with ALL), 159 controls Baseline: 1–14 y Race/ethnicity: NR Sex NR |
Ever BF vs. never BF | None | Leukemia: OR 1.14 (95% CI: 0.7,1.9) Leukemia in subsample age ≤5 y: OR 1.48 (95% CI: 0.8, 2.8) Leukemia in subsample age >5 y: OR 0.76 (95% CI: 0.3, 2.0) ALL subsample: OR 1.12 (95% CI: 0.6, 2.1) |
| BF 1–6 mo vs. never BF | None | Leukemia: OR 1.20 (95% CI: 0.6, 2.3) Leukemia in subsample age ≤5 y: OR 1.54 (95% CI: 0.7, 3.4) Leukemia in subsample age >5 y: OR 0.82 (95% CI: 0.2, 2.9) ALL subsample: OR 1.10 (95% CI: 0.5, 2.5) |
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| BF >6 mo vs. never BF | None | Leukemia: OR 1.11 (95% CI: 0.6,1.9) Leukemia in subsample age ≤5 y: OR 1.44 (95% CI: 0.7, 2.9) Leukemia in subsample age >5 y: OR 0.74 (95% CI: 0.3–2.0) ALL subsample: OR 1.12 (95% CI: 0.6, 2.2) |
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| Urayama 2012 (31) Case control (NCCLS) US |
N = 507 ALL cases (231 in the Non-Hispanic White subsample, 276 in the Hispanic subsample), 762 controls Baseline: 1–14 y Race/ethnicity: 47.0% Non-Hispanic White 53% Hispanic |
BF vs. no BF | None | ALL: OR 0.88 (95% CI: 0.62, 1.23) ALL in non-Hispanic white subsample: OR 0.97 (95% CI: 0.55, 1.69) ALL in Hispanic subsample: OR 0.89 (95% CI: 0.57, 1.38) |
| van Steensel-Moll 1986 (32) Case control (Dutch Childhood Leukemia Study) Netherlands |
N = 516 ALL cases, 500 controls Baseline: 0–14 y Race/ethnicity NR Sex NR |
BF vs. no BF | None | ALL: RR 1.1 (95% CI: 0.8, 1.4) |
1ALL, acute lymphoblastic leukemia; BF, breastfeeding/breastfed; CCCLS, Cross-Canada Childhood Leukemia Study; EBF, exclusive breastfeeding/exclusively breastfed; ESCALE, Etude Sur les Cancers et les Leucémies de l'Enfant; ESTELLE, Etude Sur les Tumeurs Embryonnaires; Leucémies et Lymphomes de l'Enfant; FF, formula fed/formula feeding; IRESCC, Inter-Regional Epidemiological Study of Childhood Cancer; NCCLS, Northern California Childhood Leukemia Study; NR, not reported; RR, relative risk; UKCCS, UK Childhood Cancer Study.
2Exposures, as defined by the authors of the studies included in the body of evidence, which address never compared with ever feeding human milk or vice versa.
3Although the CI includes the null, the authors indicated the association was significant.