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Table 1.

Subject Characteristics and Cognitive Test Scores.

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Fig 1.

Inter-site reliability of (A) brain volume and (B) head circumference measurements from 8 adult subjects, scanned twice each at all four sites. For both brain volume and head circumference measurements, within-subject variability was much lower than between subject variability (as reflected by ICCs of 0.994 and 0.995, respectively) suggesting that data can be combined across scanners for these measures without obvious bias.

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Fig 1 Expand

Fig 2.

Head circumference increased with age for both males (blue) and females (red) in both groups (A, B), and HC was lower in PAE than controls for males but not females (C). Brain volume did not change with age in either group (D,E), and was consistently reduced in PAE relative to controls for both males and females (F). IQ standard scores did not change with age in either group (G, H), and were again lower in the PAE group (I). Sex differences within groups were larger in the control group for both head circumference (C) and brain volume (F). ns = non-significant.

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Fig 2 Expand

Fig 3.

(A) Head circumference (HC) standard deviation distributions showing a shift towards the number of participants with higher normed HC in controls and lower normed HC in PAE subjects, albeit with substantial overlap between groups. (B) Z score distribution for total brain volume is left- shifted in the PAE group (grey curve) relative to controls (black curve). PAE distribution curves for brain lobe volumes show similar leftward shifts towards negative Z scores. (C) Likewise, IQ score profile is right-shifted in the control group compared to PAE (C), peaking above the population norm of 100 in controls, and below in the PAE group.

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Fig 3 Expand

Fig 4.

Brain volume Z scores and normed head circumference (HC) standard deviations are shown to positively correlate in both the control (A) and prenatal alcohol exposure (PAE) groups (B).

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Fig 5.

Age-standardized IQ versus normed head circumference standard deviation, showing non-significant relationships in both the control (A) and PAE groups (B), despite significant correlations between brain volume Z score and normed HC SD in this subset of participants (C,D). Likewise, there does not appear to be any systematic pattern/grouping of IQ in controls (C) or PAE (D) again demonstrating that those with the smallest normed HC and brain volume did not show consistently lower IQ scores.

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Fig 5 Expand

Fig 6.

When only including the 14 PAE participants below the clinical cutoff for microcephaly (HC ≤ 3rd percentile, A–column 1), it is notable that 10 (~70%) of the subjects have brain volumes below the 3rd percentile.

Similarly, ~80% of the subjects with HC ≤ 10th percentile have brain volumes under the 10th percentile (A–column 2). Conversely, among the PAE participants with total brain volume ≤ 3rd (n = 14, B–column 1) or 10th percentile (n = 22, B—column 2), 55–65% of subjects have HC in the ‘normal’ range from the 11th-99th percentiles, suggesting a disconnect between small brain volumes and head circumference. Note that the category of ≤ 10th percentile on the x-axis of A and B includes subjects who are ≤ 3rd percentile (to match cutoffs used in various diagnostic guidelines), while colour divisions within each bar are non-overlapping.

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Fig 6 Expand