Gestational age and childhood leukemia: A meta-analysis of epidemiologic studies

Figures & data

Figure 1. Flow chart of study selection.

Table 1. Characteristics of studies on the association between gestational age and risk of leukemia.

Study	Country	Study period	Age range	Study design	Sources of data for cases’ gestational age	Adjusting factors	Leukemia type	Gestational age, weeks	Case/control	NOS score
Savitz et al. [10]	Denver	1976–1983	<15	Case–control	Biologic mothers	Mother’s smoking, year of diagnosis, and wire code	ALL	<37	4/12	6
								37–40	50/155
								≥41	14/41
Murray et al. [11]	Northern Ireland	1975–1997	<16	Cohort	Cancer registries	Sex, Down’s syndrome and age of diagnosis	ALL	<38	19/36297	7
								38–39	98/255229
								≥40	70/139679
Hjalgrim et al. [12]	Denmark, Sweden, Norway, and Iceland	1984–1999	<14	Case–control	Acute leukemia database	Birth weight, birth order and parental age	Childhood leukemia	≤37	212/970	7
								38–41	1678/8320
								≥42	207/909
							ALL	≤37	186/846
								38–41	1454/7184
								≥42	177/797
							AML	≤37	26/124
								38–41	224/1136
								≥42	30/112
Jourdan-Da et al. [15]	France	1995–1998	<15	Case–control	Questionnaire	Gender, age at diagnosis, region of residence at diagnosis	Childhood leukemia	<37	46/45	7
								37–40	345/448
								≥41	39/52
							ALL	<37	41/45
								37–40	300/448
								≥41	32/52
							AML	<37	5/45
								37–40	45/448
								≥41	7/52
Podvin et al. [21]	Washington	1981–2003	<20	Case–control	Birth records	Maternal age	Childhood leukemia	<37	42/437	7
								37–42	508/5053
								≥43	17/226
McLaughlin et al. [16]	New York	1985–2001	≤9	Case–control	Cancer registry	Birth year, gender, race and ethnicity, maternal age, gestational age and birth weight	Childhood leukemia	≤37	130/1134	7
								38–41	729/6505
								≥42	185/1801
							ALL	≤37	109/1134
								38–41	628/6505
								≥42	156/1801
							AML	≤37	21/1134
								38–41	101/6505
								≥42	29/1801
Dorak et al. [22]	England	1968–1992	≤14	Case–control	Birth records	Unadjusted analysis	Childhood leukemia	≤37	23/101	6
								38–42	188/962
							ALL	≤37	18/85
								38–42	169/864
Johnson et al. [13]	Minnesota	1976–2004	<14	Case–control	Birth records	Unadjusted analysis	ALL	<37	43/657	6
								37–42	446/6938
								>42	28/311
Sprehe et al. [17]	Texas	1995–2003	<5	Case–control	Birth records	Unadjusted analysis	Childhood leukemia	<37	83/1301	6
								37–41	661/9408
								≥42	99/1574
							ALL	<37	65/1301
								37–41	523/9408
								≥42	81/1574
							AML	<37	15/1301
								37–41	88/9408
								≥42	13/1574
Oksuzyan et al. [18]	California	1988–2008	<16	Case–control	Cancer registry	Birth weight, birth order, mother’s age, father’s education, child’s race, and payment source for delivery	Leukemia	<37	608/539	7
								37–42	4414/4430
								>42	455/473
							ALL	<37	466/441
								37–42	3629/3602
								>42	376/385
							AML	<37	120/87
								37–42	619/657
								>42	62/60
Roman et al. [19]	U.S.A., U.K. and Germany	1989–1996	<15	Case–control	Cancer registry	Unadjusted analysis	ALL	<37	218/639	6
								37–40	2642/7880
								>40	1037/3224
Crump et al. [14]	Swedish	1973–2010	<38	Cohort	Birth registry	Birth year, sex, fetal growth, parental country of birth, and family history of ALL in a parent or sibling	Childhood leukemia	<37	125/206373	7
								37–41	1920/3064287
								≥42	230/298358
							ALL	<37	111/206276
								37–41	1657/3062893
								≥42	192/298204
Crump et al. [23]	Swedish	1973–2010	<38	Cohort	Birth registry	Birth year, sex, season of birth, fetal growth, gestational age at birth and maternal education	AML	<37	14/206373	7
								37–41	263/3064287
								≥42	38/298358

Abbreviations: ALL: acute lymphocytic leukemia; AML: acute myeloid leukemia; NOS: Newcastle-Ottawa-Scale; U.K.: the United Kingdom; U.S.A.: United States of America.

Figure 2. Forest plot of the association between gestational age and childhood leukemia.

Figure 3. Forest plot of the association between gestational age and acute lymphocytic leukemia.

Figure 4. Forest plot of the association between gestational age and acute myeloid leukemia.

Table 2. Pooled association between gestational age and childhood leukemia.

Groups	No. of studies	I^2 (%)	P for heterogeneity test	Pooled OR (95% CI)	P for hypothesis test	P for Egger's test	P for Begg's test
Childhood leukemia associated with preterm birth	8	0.0	0.599	1.06 (0.98, 1.13)	0.132	0.787	0.902
Childhood leukemia associated with postterm birth	7	56.1	0.033	1.01 (0.90, 1.13)	0.834	0.296	0.548
ALL associated with preterm birth	11	0.0	0.924	1.04 (0.97, 1.11)	0.306	0.355	0.640
ALL associated with postterm birth	10	39.5	0.095	1.03 (0.95, 1.12)	0.464	0.292	0.474
AML associated with preterm birth	6	0.0	0.499	1.20 (1.00, 1.44)	0.050	0.203	0.707
AML associated with postterm birth	6	0.0	0.601	1.20 (1.00, 1.43)	0.049	0.262	0.133

Table 3. Subgroup analyses of the association between postterm age and childhood leukemia, acute lymphoblastic leukemia (ALL).

Factor	Level	Childhood leukemia associated with postterm birth				ALL associated with postterm birth
		No. of studies	I^2 (%)	P for heterogeneity test	Pooled OR (95% CI)	No. of studies	I^2 (%)	P for heterogeneity test	Pooled OR (95% CI)
Total		7	56.1	0.033	1.01 (0.90, 1.13)	10	39.5	0.095	1.03 (0.95, 1.12)
Study type	Case–control	6	8.0	0.365	0.97 (0.90, 1.06)	8	0.0	0.514	0.98 (0.92, 1,04)
	Cohort	1	–	–	1.23 (1.07, 1.41)	2	0.0	0.596	1.21 (1.06, 1.39)
Sample size	>1000	6	63.2	0.018	1.01 (0.90, 1.14)	8	52.4	0.040	1.04 (0.95, 1.14)
	<1000	1	–	–	0.97 (0.63, 1.51)	2	0.0	0.738	0.96 (0.65, 1.41)
Study region	Europe	3	0.0	0.502	1.17 (1.06, 1.30)	4	0.0	0.565	1.15 (1.04, 1.28)
	North America	4	0.0	0.762	0.93 (0.85, 1.02)	5	3.8	0.385	0.96 (0.87, 1.07)
	North America and Europe	–	–	–	–	1	–	–	0.96 (0.88, 1.04)
Child’s age	≤9	2	0.0	0.867	0.91 (0.79, 1.04)	2	0.0	0.839	0.91 (0.78, 1.05)
	9–16	3	9.5	0.331	1.03 (0.92, 1.15)	7	25.4	0.235	1.03 (0.94, 1.13)
	Other	2	71.7	0.060	1.02 (0.63, 1.64)	1	–	–	1.19 (1.02, 1.38)
Postterm age	≥40 or >40	–	–	–	–	2	72.3	0.058	1.08 (0.80, 1.45)
	≥41	1	–	–	0.97 (0.63, 1.51)	2	0.0	0.738	0.96 (0.65, 1.41)
	≥42 or >42	5	66.5	0.018	1.03 (0.91, 1.16)	6	49.6	0.078	1.04 (0.93, 1.16)
	≥43	1	–	–	0.75 (0.45, 1.24)	–	–	–	–

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