. 2023 Aug 14;46(10):1839–1847. doi: 10.2337/dc23-0417

Table 2.

Timing of introduction of selected complementary foods and risk of developing IA by HLA genotype or by use of probiotics during the first 52 weeks of life

	HLA genotype						Use of probiotics during the first 52 weeks^***
Timing of first food exposure (months) and outcome	n	Affected, n	Other than HLA DR3/4 HR (95% CI), P^*	n	Affected, n	HLA DR3/4 HR (95% CI), P^*	n	Affected, n	No probiotic exposure before 52 weeks of age HR (95% CI), P^**	n	Affected, n	Probiotic exposure before or at 52 weeks of age HR (95% CI), P^**
Any solid foods
Any IA
<4	1,840	145	0.93 (0.66, 1.30), 0.656	1,192	159	1.31 (0.90, 1.91), 0.153	2,367	234	1.20 (0.88, 1.62), 0.245	665	70	0.91 (0.57, 1.44), 0.678
4 to <6	2,393	243	1.09 (0.78, 1.50), 0.620	1,528	219	1.31 (0.91, 1.89), 0.151	3,070	364	1.31 (0.98, 1.76), 0.069	851	98	0.91 (0.59, 1.42), 0.688
≥6	495	48	1	322	36	1	621	55	1	196	29	1
Interaction P	0.209						0.154
IAA-first
<4	1,840	56	0.96 (0.54, 1.69), 0.880	1,192	60	1.78 (0.90, 3.53), 0.098	2,367	88	1.45 (0.85, 2.46), 0.174	665	28	0.90 (0.42, 1.93), 0.777
4 to <6	2,393	92	1.13 (0.65, 1.94), 0.670	1,528	76	1.70 (0.86, 3.34), 0.126	3,070	131	1.55 (0.92, 2.60), 0.101	851	38	0.90 (0.43, 1.87), 0.769
≥6	495	17	1	322	10	1	621	17	1	196	10	1
Interaction P	0.290						0.396
GADA-first
<4	1,840	55	0.84 (0.48, 1.46), 0.543	1,192	68	1.09 (0.64, 1.86), 0.754	2,367	94	0.93 (0.60, 1.44), 0.749	665	29	1.17 (0.53, 2.59), 0.692
4 to <6	2,393	118	1.28 (0.76, 2.15), 0.350	1,528	101	1.12 (0.66, 1.89), 0.667	3,070	174	1.22 (0.80, 1.86), 0.358	851	43	1.22 (0.57, 2.60), 0.609
≥6	495	18	1	322	18	1	621	27	1	196	9	1
Interaction P	0.307						0.732
Multiple autoantibodies
<4	1,840	69	0.86 (0.54, 1.38), 0.531	1,192	99	1.28 (0.81, 2.03), 0.289	2,367	122	1.29 (0.85, 1.95), 0.234	665	46	0.77 (0.45, 1.34), 0.358
4 to <6	2,393	129	1.14 (0.73, 1.76), 0.572	1,528	142	1.37 (0.87, 2.14), 0.172	3,070	212	1.61 (1.08, 2.41), 0.020	851	59	0.73 (0.43, 1.23), 0.234
≥6	495	27	1	322	24	1	621	29	1	196	22	1
Interaction P	0.236						0.028
Cereals (24 missing)
Any IA
<4	1,101	81	0.86 (0.63, 1.19), 0.371	762	89	1.03 (0.74, 1.45), 0.844	1,501	135	1.06 (0.80, 1.40), 0.689	362	35	0.76 (0.48, 1.19), 0.224
4 to <6	2,807	273	1.01 (0.78, 1.32), 0.927	1,744	262	1.22 (0.91, 1.63), 0.184	3,585	428	1.25 (0.98, 1.59), 0.072	966	107	0.84 (0.59, 1.20), 0.335
≥6	805	82	1	527	62	1	952	89	1	380	55	1
Interaction P	0.447						0.051
IAA-first
<4	1,101	32	0.88 (0.52, 1.47), 0.617	762	33	1.26 (0.71, 2.25), 0.435	1,501	49	1.05 (0.67, 1.66), 0.820	362	16	1.02 (0.50, 2.07), 0.960
4 to <6	2,807	101	0.96 (0.63, 1.48), 0.858	1,744	94	1.50 (0.90, 2.52), 0.121	3,585	154	1.24 (0.84, 1.85), 0.277	966	41	0.96 (0.53, 1.73), 0.891
≥6	805	32	1	527	19	1	952	33	1	380	18	1
Interaction P	0.402						0.522
GADA-first
<4	1,101	31	0.79 (0.47, 1.32), 0.364	762	34	0.89 (0.53, 1.50), 0.252	1,501	52	0.93 (0.61, 1.44), 0.756	362	13	0.69 (0.33, 1.43), 0.315
4 to <6	2,807	130	1.16 (0.76, 1.77), 0.502	1,744	125	1.29 (0.83, 2.00), 0.697	3,585	207	1.38 (0.96, 1.99), 0.085	966	48	0.94 (0.53, 1.66), 0.832
≥6	805	30	1	527	27	1	952	37	1	380	20	1
Interaction P	0.957						0.368
Multiple autoantibodies
<4	1,101	40	0.82 (0.52, 1.27), 0.371	762	53	0.91 (0.60, 1.38), 0.660	1,501	70	0.95 (0.66, 1.37), 0.782	362	23	0.76 (0.44, 1.33), 0.337
4 to <6	2,807	137	0.97 (0.68, 1.39), 0.877	1,744	169	1.21 (0.85, 1.72), 0.298	3,585	238	1.24 (0.90, 1.69), 0.184	966	68	0.84 (0.54, 1.29), 0.420
≥6	805	48	1	527	43	1	952	55	1	380	36	1
Interaction P	0.430						0.240
Gluten-containing cereals (134 missing)
Any IA
<4	294	14	0.49 (0.28, 0.84), 0.010	213	22	0.81 (0.52, 1.27), 0.359	410	31	0.68 (0.46, 0.99), 0.042	97	5	0.52 (0.21, 1.28), 0.155
4 to <6	1,624	162	0.97 (0.77, 1.21), 0.765	1,057	160	1.01 (0.80, 1.27), 0.918	2,116	254	0.95 (0.79, 1.14), 0.580	565	68	1.13 (0.82, 1.56), 0.454
≥6	2,723	259	1	1,725	230	1	3,421	365	1	1,027	124	1
Interaction P	0.397						0.636
IAA-first
<4	294	7	0.65 (0.295, 1.43), 0.281	213	7	0.73 (0.33, 1.62), 0.442	410	14	0.84 (0.47, 1.48), 0.539	97	0	–
4 to <6	1,624	58	0.88 (0.61, 1.28), 0.509	1,057	52	0.92 (0.63, 1.36), 0.670	2,116	83	0.84 (0.61, 1.14), 0.255	565	27	1.15 (0.70, 1.91), 0.578
≥6	2,723	100	1	1,725	86	1	3,421	138	1	1,027	48	1
Interaction P	0.992						0.798
GADA-first
<4	294	4	0.33 (0.12, 0.90), 0.030	213	9	0.73 (0.36, 1.47), 0.377	410	10	0.51 (0.26, 0.98), 0.042	97	3	0.67 (0.20, 2.21), 0.505
4 to <6	1,624	82	1.18 (0.84, 1.66), 0.330	1,057	75	1.04 (0.74, 1.46), 0.823	2,116	128	1.12 (0.86, 1.48), 0.404	565	29	1.09 (0.65, 1.82), 0.748
≥6	2,723	105	1	1,725	102	1	3,421	158	1	1,027	49	1
Interaction P	0.319						0.804
Multiple autoantibodies
<4	294	3	0.19 (0.06, 0.59), 0.004	213	12	0.76 (0.41, 1.38), 0.365	410	12	0.46 (0.25, 0.83), 0.010	97	3	0.52 (0.16, 1.67), 0.271
4 to <6	1,624	74	0.78 (0.57, 1.07), 0.127	1,057	106	1.16 (0.87, 1.53), 0.317	2,116	136	0.91 (0.71, 1.16), 0.429	565	44	1.16 (0.78, 1.72), 0.465
≥6	2,723	147	1	1,725	147	1	3,421	214	1	1,027	80	1
Interaction P	0.063						0.916
Nongluten-containing cereals (29 missing)
Any IA
<4	1,029	79	0.89 (0.65, 1.23), 0.486	712	83	0.99 (0.71, 1.38), 0.948	1,415	128	1.01 (0.77, 1.32), 0.946	326	34	0.83 (0.53, 1.31), 0.418
4 to <6	2,830	270	0.98 (0.75, 1.27), 0.870	1,759	261	1.15 (0.87, 1.53), 0.323	3,601	424	1.17 (0.93, 1.47), 0.192	988	107	0.84 (0.59, 1.19), 0.326
≥6	850	87	1	561	69	1	1,018	100	1	393	56	1
Interaction P	0.523						0.092
IAA-first
<4	1,029	28	0.90 (0.54, 1.50), 0.675	712	35	1.08 (0.61, 1.89), 0.796	1,415	31	0.91 (0.59, 1.42), 0.696	326	32	1.19 (0.58, 2.43), 0.927
4 to <6	2,830	99	0.93 (0.61, 1.41), 0.723	1,759	107	1.29 (0.79, 2.08), 0.307	3,601	100	1.09 (0.75, 1.58), 0.648	988	106	0.97 (0.54, 1.76), 0.773
≥6	850	28	1	561	26	1	1,018	34	1	393	20	1
Interaction P	0.586						0.475
GADA-first
<4	1,029	30	0.80 (0.48, 1.35), 0.406	712	32	0.93 (0.55, 1.56), 0.776	1,415	50	0.94 (0.62, 1.45), 0.788	326	12	0.72 (0.34, 1.52), 0.386
4 to <6	2,830	129	1.12 (0.74, 1.69), 0.595	1,759	126	1.34 (0.87, 2.07), 0.186	3,601	206	1.35 (0.95, 1.93), 0.095	988	49	0.98 (0.56, 1.73), 0.943
≥6	850	32	1	561	28	1	1,018	40	1	393	20	1
Interaction P	0.888						0.451
Multiple autoantibodies
<4	1,029	40	0.91 (0.58, 1.41), 0.660	712	49	0.88 (0.58, 1.33), 0.543	1,415	67	0.96 (0.67, 1.39), 0.844	326	22	0.81 (0.46, 1.42), 0.456
4 to <6	2,830	136	0.99 (0.69, 1.41), 0.936	1,759	169	1.17 (0.83, 1.65), 0.376	3,601	237	1.23 (0.91, 1.66), 0.188	988	68	0.82 (0.53, 1.27), 0.380
≥6	850	49	1	561	47	1	1,018	59	1	393	37	1
Interaction P	0.480						0.213
Fruits and berries (37 missing)
Any IA
<4	1,053	69	0.69 (0.51, 0.94), 0.017	690	84	1.03 (0.77, 1.39), 0.835	1,341	116	0.85 (0.67, 1.09), 0.199	402	37	0.83 (0.53, 1.30), 0.413
4 to <6	2,481	248	0.96 (0.76, 1.22), 0.751	1,584	230	1.09 (0.85, 1.40), 0.514	3,124	367	1.03 (0.85, 1.25), 0.759	941	111	1.00 (0.69, 1.44), 0.987
≥6	1,169	118	1	756	98	1	1,566	167	1	359	49	1
Interaction P	0.120						0.617
IAA-first
<4	1,053	26	0.76 (0.46, 1.28), 0.303	690	32	1.12 (0.68, 1.83), 0.665	1,341	32	0.96 (0.64, 1.44), 0.843	402	14	0.81 (0.38, 1.71), 0.575
4 to <6	2,481	101	1.19 (0.80, 1.77), 0.397	1,584	89	1.12 (0.73, 1.72), 0.603	3,124	80	1.16 (0.83, 1.62), 0.375	941	45	1.11 (0.60, 2.05), 0.746
≥6	1,169	38	1	756	33	1	1,566	33	1	359	16	1
Interaction P	0.290						0.880
GADA-first
<4	1,053	29	0.61 (0.38, 0.96), 0.034	690	33	0.95 (0.60, 1.51), 0.834	1,341	46	0.70 (0.49, 1.02), 0.061	402	16	1.01 (0.50, 2.07), 0.970
4 to <6	2,481	106	0.83 (0.59, 1.18), 0.303	1,584	10	1.20 (0.82, 1.75), 0.348	3,124	169	0.98 (0.74, 1.30), 0.865	941	47	1.12 (0.62, 2.03), 0.710
≥6	1,169	56	1	756	43	1	1,566	81	1	359	18	1
Interaction P	0.283						0.772
Multiple autoantibodies
<4	1,053	30	0.54 (0.34, 0.84), 0.006	690	57	1.08 (0.75, 1.56), 0.682	1,341	64	0.84 (0.61, 1.17), 0.305	402	23	0.69 (0.40, 1.21), 0.198
4 to <6	2,481	127	0.90 (0.65, 1.25), 0.533	1,584	144	1.09 (0.80, 1.49), 0.602	3,124	202	1.04 (0.80, 1.35), 0.756	941	69	0.86 (0.55, 1.34), 0.504
≥6	1,169	67	1	756	64	1	1,566	96	1	359	35	1
Interaction P	0.035						0.507
Egg (470 missing)
Any IA
≤9	3,098	286	0.99 (0.80, 1.23), 0.947	2,020	282	1.00 (0.80, 1.24), 0.974	4,082	445	0.94 (0.79, 1.12), 0.515	1,036	123	1.16 (0.85, 1.58), 0.350
>9	1,353	450	1	886	126	1	1,663	192	1	576	69	1
Interaction P	0.801						0.466
IAA-first
≤9	3,098	107	0.93 (0.66, 1.31), 0.682	2,020	97	0.96 (0.67, 1.37), 0.811	4,082	166	1.09 (0.81, 1.47), 0.554	1,036	38	0.63 (0.40, 1.01), 0.053
>9	1,353	54	1	886	47	1	1,663	64	1	576	37	1
Interaction P	0.911						0.038
GADA-first
≤9	3,098	130	1.02 (0.74, 1.42), 0.898	2,020	132	1.08 (0.78, 1.50), 0.651	4,082	200	0.86 (0.67, 1.11), 0.245	1,036	62	2.26 (1.29, 3.97), 0.004
>9	1,353	55	1	886	53	1	1,663	91	1	576	17	1
Interaction P	0.904						0.004
Multiple autoantibodies
≤9	3,098	135	0.83 (0.63, 1.11), 0.210	2,020	176	0.95 (0.72, 1.23), 0.677	4,082	236	0.85 (0.68, 1.06), 0.153	1,036	75	1.01 (0.6, 1.48), 0.942
>9	1,353	81	1	886	86	1	1,663	119	1	576	48	1
Interaction P	0.321						0.475

Boldface indicates significance at P < 0.05.

Adjusted for country, first-degree family member with type 1 diabetes status, sex of the child, and probiotic exposure during the 1st year of life (52 weeks).

^**

Adjusted for country, first-degree family member with type 1 diabetes status, sex of the child, and high-risk genotype (HLA DR3/4).

^***

When the timing of first probiotic exposure was studied in categories <26 weeks, and ≥26 weeks, or none, slightly stronger associations were found, but they did not affect the interpretation of the results.