Extended Data, Table 8. Group differences in developmental trajectories and cross-sectional volumes by age: Males Only.

The primary analysis of brain volume trajectories included only those male and female study participants, with three completed visits (6-12-24 months), to best depict longitudinal trajectories over time. Separate analyses on males and females are likely to be inadequately powered due to small subsample size (males = 13, females = 2) and therefore provide inconclusive results. With that caveat, we provide the results of our male-only three group analysis for total brain volume. We do not see any group differences in the first year (6-12 months). The HR-ASD males show a pattern of TBV brain enlargement by the end of the second year, compared to the LR and HR-neg groups. Key: LR = low risk, HR-neg = High Risk negative, HR-ASD = High Risk with Autism, 1^st Year = 6-12 month period, 2^nd Year = 12-24 month period, Pairwise Group Comparison (p<.05), SE = standard error, LSM = least square means, Unit of brain volume measures for trajectory and cross-sectional analyses is mm³. Unit for surface area is mm², and for cortical thickness is mm. Slope is represented as change/months. Sample for piecewise linear model included subjects with complete data at all three visits (6m, 12m, 24m).

		LR(a) (N=28)		HR-neg(b) (N=51)		HR-ASD(c) (N=13)		Overall Group Comparison			Pairwise Group Contrast
Measure	Trajectory	Slope	SE	Slope	SE	Slope	SE	df1, df2	F	P
Total brain volume	1st Year	21559	1683	24038	1124	18633	4522	2, 106	1.25	0.29
	2nd Year	10398	896	9396	450	16255	3057	2, 106	2.83	0.06	c>b
Surface Area	1st Year	1020	105	1070	75	1421	153	2, 177	2.56	0.08	c>(a,b)
	2nd Year	858	47	891	37	921	80	2, 177	0.29	0.75
Cortical Thickness	1st Year	-0.020	0.004	-0.021	0.003	-0.025	0.006	2, 177	0.19	0.83
	2nd Year	-0.026	0.002	-0.023	0.002	-0.026	0.004	2, 177	0.41	0.67
Cross-Sectional	Visit age	LSM	SE	LSM	SE	LSM	SE	df1,df2	F	P
Total brain volume	6 months	718589	16333	727226	9585	762604	42125	2, 106	0.49	0.62
	12 months	847944	20012	871452	11539	874399	52450	2, 106	0.53	0.59
	24 months	972725	21498	984204	12307	1069460	57570	2, 106	1.24	0.29
Surface area	6 months	53167	660	54885	473	54463	939	2, 177	2.32	0.10
	12 months	59287	781	61307	588	62990	1170	2, 177	4.01	0.02	c>a
	24 months	69582	886	72001	667	74036	1354	2, 177	4.42	0.01	c>a
Cortical thickness	6 months	6.04	0.05	5.99	0.033	6.09	0.067	2, 177	1.10	0.33
	12 months	5.92	0.045	5.86	0.034	5.95	0.07	2, 177	0.81	0.45
	24 months	5.61	0.035	5.58	0.026	5.63	0.05	2, 177	0.37	0.69