Birthweight and all-cause mortality after childhood and adolescent leukemia: a cohort of children with leukemia from Denmark, Norway, Sweden, and Washington State

Figures & data

Table 1. Characteristics of 7148 children and adolescents with leukemia from Denmark, Norway, Sweden, and Washington State, 1967–2015.

	Denmark 1973–2013		Norway 1967–2015		Sweden 1973–2011		Washington State 1974–2014		All
	N	%	N	%	N	%	N	%	N	%
Overall	1724	100	1871	100	2043	100	1510	100	7148	100
Type of leukemia
Myeloid	300	17.4	361	19.3	–	–	278	18.4	939	13.1
Lymphoid	1355	78.6	1369	73.2	2043	100	922	61.1	5689	79.6
Other	69	4.0	141	7.5	–	–	310	20.5	520	7.3
Diagnosis year
1967–1983	166	9.6	449	24.1	283	13.9	74	4.9	972	13.6
1984–1987	147	8.5	163	8.7	212	10.4	78	5.2	600	8.4
1988–1992	213	12.4	188	10.0	291	14.2	136	9.0	828	11.6
1993–2003	547	31.7	511	27.3	760	37.2	495	32.8	2313	32.4
2004–2007	247	14.3	188	10.0	239	11.7	225	14.9	899	12.6
2008–2015	404	23.4	372	19.9	258	12.6	502	33.2	1536	21.5
Sex
Male	953	55.3	1017	54.4	1131	55.4	823	54.5	3924	54.9
Female	771	44.7	854	45.6	912	44.6	687	45.5	3224	45.1
Age group at diagnosis
0–12 months	98	5.7	79	3.9	117	6.3	101	6.7	395	5.5
1–2	413	23.9	517	25.3	454	24.3	333	22.1	1717	24.1
3–8	765	44.4	977	47.8	788	42.1	642	42.5	3172	44.4
9–13	231	13.4	285	13.9	256	13.7	203	13.4	975	13.6
14–19	217	12.6	185	9.1	256	13.7	231	15.3	889	12.4
Median age at diagnosis (interquartile range)	4	(2;9)	4	(2;9)	4	(2;8)	4	(2;10)	4	(2;9)
Birthweight, g
<2500	75	4.4	69	3.7	86	4.2	99	6.6	329	4.6
2500–3999	1330	77.1	1376	73.5	1540	75.4	1181	78.2	5427	75.9
≥4000	310	18.0	425	22.7	409	20.0	222	14.7	1366	19.1
Missing	9	0.5	1	0.1	8	0.4	8	0.5	26	0.4
Median birthweight, g (interquartile range)	3500 (3100; 3850)		3600 (3220; 3950)		3570 (3210; 3900)		3486 (3118; 3827)		3530 (3160; 3890)
Gestational age, weeks
23–36	88	5.1	112	6.0	120	5.9	142	9.4	462	6.5
37–41	1293	75.0	1437	76.8	1717	84.0	1008	66.8	5455	76.3
42–44	117	6.8	204	10.9	197	9.6	111	7.4	629	8.8
Missing	226	13.1	118	6.3	9	0.4	249	16.5	602	8.4
Size for gestational age
Small	65	3.8	71	3.8	62	3.0	159	10.5	357	5.0
Appropriate	1379	80.0	1622	86.7	1831	89.6	1077	71.3	5909	82.7
Large	50	2.9	82	4.4	81	4.0	175	11.6	388	5.4
Missing	230	13.3	96	5.1	69	3.4	99	6.6	494	6.9
Birth length, cm
<50	248	14.4	568	30.4	609	29.8	–	–	1425	19.9
50–52	769	44.6	937	50.1	1046	51.2	–	–	2752	38.5
53	254	14.7	182	9.7	207	10.1	–	–	643	9.0
54–62	429	24.9	137	7.3	166	8.1	–	–	732	10.2
Missing	24	1.4	47	2.5	15	0.7	1510	100	1596	22.3
Ponderal index, kg/m^3
<24	620	36.0	130	6.9	158	7.7	–	–	908	12.7
24–30	1043	60.5	1349	72.1	1548	75.8	–	–	3940	55.1
≥30	37	2.1	345	18.4	319	15.6	–	–	701	9.8
Missing	24	1.4	47	2.5	18	0.9	1510	100	1599	22.4
Down’s syndrome	45	2.6	64	3.4	47	2.3	24	1.6	180	2.5
Other malformations	46	2.7	55	2.9	8	0.4	18	1.2	127	1.8

Gestational age available from 1978 in Denmark.

Birth length not available for Washington State.

Diagnosis year group defined according to NOPHO guideline changes in 1984, 1988, 1993, 2004, and 2008.

Table 2. Cumulative proportion of deaths in 7148 children and adolescents with leukemia from Denmark, Norway, Sweden, and Washington State, 1967–2015.

	Five-year all-cause mortality risk, % (95% CI)
Overall	23.2 (22.6, 23.8)
Sex
Male	23.7 (22.9, 24.5)
Female	22.5 (21.6, 23.3)
Age group at diagnosis
0–12 months	49.0 (46.1, 52.0)
1–2 years	20.0 (18.9, 21.2)
3–8 years	18.1 (17.3, 18.9)
9–13 years	25.0 (23.4, 26.7)
14–19 years	34.1 (32.2, 36.0)
Birthweight, g
<2500	26.9 (21.5, 33.2)
2500–3999	24.2 (22.9, 25.6)
≥4000	19.4 (17.0, 22.2)
Gestational age, weeks
23–36	25.3 (22.9, 27.8)
37–41	22.4 (21.8, 23.1)
42–44	22.9 (21.1, 24.9)
Size for gestational age
Small	26.9 (24.2, 29.9)
Appropriate	22.4 (21.7, 23.0)
Large	22.0 (19.6, 24.7)
Birth length, cm
<50	25.2 (23.9, 26.6)
50–52	23.8 (22.8, 24.7)
53	23.0 (21.2, 25.0)
54–62	21.4 (19.7, 23.2)
Ponderal index, kg/m^3
<24	26.0 (24.3, 27.7)
24–30	23.6 (22.9, 24.4)
≥30	21.4 (19.7, 23.2)
Down’s syndrome
No	22.9 (22.3, 23.5)
Yes	33.0 (29.1, 37.3)
Other malformations
No	23.1 (22.5, 23.7)
Yes	24.5 (20.3, 29.4)
Leukemia subtype
Myeloid	45.05 (43.1, 47.0)
Lymphiod	19.0 (18.4, 19.7)
Other	31.9 (29.0, 34.9)
Year of diagnosis
1967–1983	43.1 (41.4, 45.0)
1984–1987	26.9 (24.9, 29.0)
1988–1992	25.9 (24.2, 27.6)
1993–2003	20.0 (19.0, 20.9)
2004–2007	13.8 (12.6, 15.2)
2008–2015	15.3 (14.1, 16.6)

Diagnosis year group defined according to NOPHO guideline changes in 1984, 1988, 1993, 2004, and 2008.

Table 3. Five-year all-cause mortality risk by birthweight categories, size for gestational age, and Ponderal index in 7148 children and adolescents with leukemia from Denmark, Norway, Sweden, and Washington State, 1967–2015.

	5-year mortality
	Number of deaths	Total years of follow-up	Crude rate (95% CI)	Hazard rate ratio (95% CI)^a
Birthweight (g)
<2500	74 (22.5%)	1204	6.1 (4.8, 7.7)	1.1 (0.9, 1.4)
2500–3999	1160 (21.4%)	20,590	5.6 (5.3, 6.0)	1
≥4000	306 (22.4%)	5328	5.7 (5.1, 6.4)	1.0 (0.9, 1.2)
Size for gestational age
Small	87 (24.4%)	1204	7.2 (5.8, 8.9)	1.2 (0.9, 1.5)
Appropriate	1235 (20.9%)	22,742	5.4 (5.1, 5.7)	1
Large	76 (19.6%)	1424	5.3 (4.2, 6.7)	1.1 (0.9, 1.4)
Ponderal index
<24	231 (25.4%)	3565	6.5 (5.7, 7.4)	1.1 (0.9, 1.2)
24–30	909 (23.1%)	15,815	5.7 (5.4, 6.1)	1
>30	146 (20.8%)	2892	5.0 (4.3, 5.9)	1.0 (0.8, 1.2)

^aAdjusted for sex, diagnosis year, country, the presence of Down’s syndrome, other malformations, and type of leukemia.

Diagnosis year group defined according to NOPHO guideline changes in 1984, 1988, 1993, 2004, and 2008.

Table 4. Five-year all-cause mortality risk by birthweight categories and stratified by age at leukemia diagnosis in 7148 children and adolescents with leukemia from Denmark, Norway, Sweden, and Washington State, 1967–2015.

Age at leukemia diagnosis and child birthweight (g)	5-year mortality
	Number of deaths	Total years of follow-up	Crude rate (95% CI)	Hazard rate ratio (95% CI)^a
0–12 months
<2500	7 (46.7%)	31	22.7 (9.1, 46.7)	1.5 (0.7, 3.2)
2500–3999	148 (47.6%)	815	18.2 (15.4, 21.3)	1
≥4000	30 (44.1%)	200	15.0 (10.1, 21.4)	0.9 (0.6, 1.4)
1–2 years
<2500	19 (23.8%)	306	6.2 (3.7, 9.7)	1.6 (1.0, 2.6)
2500–3999	247 (18.8%)	5125	4.8 (4.2, 5.5)	1
≥4000	58 (18.4%)	1292	4.5 (3.4, 5.8)	0.9 (0.7, 1.2)
3–8 years
<2500	21 (15.4%)	527	4.0 (2.5, 6.1)	1.0 (0.6, 1.5)
2500–3999	387 (16.2%)	9650	4.0 (3.6, 4.4)	1
≥4000	123 (19.2%)	2581	4.8 (4.0, 5.7)	1.2 (0.9, 1.4)
9–13 years
<2500	13 (24.5%)	195	6.7 (3.6, 11.4)	1.0 (0.6, 1.8)
2500–3999	168 (23.0%)	2744	6.1 (5.2, 7.1)	1
≥4000	43 (23.1%)	716	6.0 (4.3, 8.1)	1.0 (0.7, 1.4)
14–19 years
<2500	14 (31.1%)	145	9.6 (5.3, 16.2)	1.2 (0.7, 2.1)
2500–3999	210 (30.5%)	2255	9.3 (8.1, 10.7)	1
≥4000	52 (33.5%)	539	9.6 (7.2, 12.7)	1.1 (0.8, 1.5)

^aAdjusted for sex, diagnosis year, country, the presence of Down’s syndrome, other malformations, and type of leukemia.

Data availability

Data sharing is not allowed according to Danish, Norwegian, Swedish law. Our own approvals to use the data sources for the current study do not allow us to distribute or make patient data directly available to other parties. Interested researchers may apply for Danish data access through the Research Service at the Danish Health Data Authority (e-mail: [email protected]; phone: [phone]). Up-to-date information on data access is available online (http://sundhedsdatastyrelsen.dk/da/forskerservice). Access to data from the Danish Health Data Authority requires approval from the Danish Data Protection Agency (https://www.datatilsynet.dk/english/legislation/). Similar options are available for data from the other countries.