Alteration of fractional anisotropy in preterm-born individuals: a systematic review and meta-analysis

Figures & data

Figure 1. Search strategy used. DTI, diffusion tensor; FA, fractional anisotropy, ROI, region of interest; TBSS, tract-based spatial statistical.

Table 1. Demographic and clinical characteristics of subjects in the 17 PT-TBSS studies included in the systematic review.

Author	Year	Participants, n (males)		Age, year		Gestational age, week		Birth weight, g		Full IQ
		PT	HC	PT	HC	PT	HC	PT	HC	PT	HC
Vangberg et al.	2006	34 (16)	47 (18)	15.2	15.5	29.3	39.5	1218	3670	NA	NA
Skranes et al.	2007	34 (16)	47 (18)	15.2	15.5	29.3	39.5	NA	NA	77.9	94.7
Anjari et al.	2007	26 (15)	6 (4)	TEA	NB	28.9	39.7	1084	3300	NA	NA
Rose et al. (1)	2008	12 (5)	10 (3)	TEA	NB	26.9	39.5	1022	3353	NA	NA
Rose et al. (2)	2008	11 (6)	10 (3)	TEA	NB	30.9	39.5	1530	3353	NA	NA
Nagy et al.	2009	74 (23)	69 (16)	14.9	14.3	28.54	39.72	1069.54	3530	NA	NA
Allin et al.	2011	80 (41)	41 (27)	19.2	18.6	28.9	40.2	1263.6	3317.9	95.5	106.3
Eikenes et al.	2011	49 (20)	59 (22)	20.2	20.3	29.2	39.7	NA	NA	NA	NA
Feldman et al. (site1)	2012	25 (12)	40 (18)	12.6	13	28.6	NA	1209	NA	NA	NA
Feldman et al. (site2)	2012	33 (16)	23 (9)	12.6	12.8	29.6	NA	1349	NA	NA	NA
Loe et al.	2013	25 (12)	20 (10)	12.7	12.9	28.6	39.3	1191	3171	109	113
Lee et al.	2013	18 (9)	18 (9)	1.24	1.22	30.2	39.3	1520	3056	NA	NA
Salvan et al.	2014	21 (11)	10 (4)	20.85	20	28.24	39.33	1244.95	3145	99.86	108.9
Padilla et al.	2014	20 (11)	20 (10)	1	1	30.04	39.82	1531.15	3272	NA	NA
Alexandrou et al.	2014	58 (33)	14 (5)	TEA	NB	25.53	38.76	NA	3580	NA	NA
Kelly et al.	2016	193 (92)	83 (49)	TEA	NB	34.4	39.7	2171	3587	NA	NA
Kelly et al.	2016	145 (71)	33 (16)	7.5	7.6	27.5	38.9	974	3244	99.1	109.5
Saunavaara et al. (with FGR)	2017	43 (24)	21 (11)	9	9	28.8	39.4	1269	3356	NA	NA
Saunavaara et al. (without FGR)	2017	13 (6)	21 (11)	9	9	28.4	39.4	808	3356	NA	NA
Young et al.	2018	31 (18)	28 (13)	4.2	4.6	28.62	NA	NA	NA	NA	NA

Note: PT, preterm; HC, healthy control; TBSS, tract-based spatial statistical; IQ, intelligence quotient; HC, healthy control; NA, not available; TEA, term equivalent age; and NB, newborn.

Table 2. The main research results in the 17 PT-TBSS studies included in the systematic review.

Author	year	MRI Telsa	Statistical threshold	coordinate system	diffusion directions	Major findings (PT relative to HC)
Vangberg et al.	2006	1.5	FWE	MNI	6	reduced FA values in the CC, IC and superior fasciculus
Skranes et al.	2007	1.5	FWE	NA	6	reduced FA values in the IC, EC, CC and superior, middle superior and inferior fasciculus.
Anjari et al.	2007	3	Uncorrected	NA		dreduced FA values in genu of the CC, CS
Rose et al. (1)	2008	1.5	multiple comparisons	NA	NA	reduced FA in the genu, splenium of the CC, EC
Rose et al. (2)	2008	1.5	multiple comparisons	NA	NA	reduced FA in posterior commissural tracts of the CR
Nagy et al.	2009	1.5	multiple comparisons	NA	30	reduced FA in external capsule, posterior body, isthmus, CC
Allin et al.	2011	1.5	multiple comparison	MNI	uniform	reduced FA in CC, bilateral SLF and left superior CR, increased FA in bilateral IFOF and bilateral anterior CR
Eikenes et al.	2011	1.5	TFCE	MNI	12	reduced FA in the cerebellar peduncle, CSTt, uncinate fasciculus, SLF, cingulum
Feldman et al. (site1)	2012	3	multiple comparisons	MNI	30	no significant group difference in FA value at either site
Feldman et al. (site2)	2012	3	multiple comparisons.	MNI	30	no significant group difference in FA value at either site
Loe et al.	2013	3	TFCE	MNI	30	no significant group difference in FA value at either site
Lee et al.	2013	1.5	FWE/TFCE	NA	NA	In subgroup A (<1 year old), reduced FA in the CS, IC, EC, crus of the fornix, ILF, ILOF, and CC. In subgroup B (1 to 2 years old), reduced FA in the CS, ILOF, and CC In subgroup C (>2 years old), reduced FA in the CS and genu of CC
Salvan et al.	2014	1.5	FWE	MNI	uniform	reduced FA in left hippocampal, fornix, splenium of the CC, ILF and IFOF
Padilla et al.	2014	3	FWE	MNI	30	reduced FA in the CC increased FA in the anterior CR
Alexandrou et al.	2014	1.5	multiple comparisons	NA	15	reduced FA bilaterally in the frontal WM, CR, CS, genu and splenium of the CC, ILF and the left EC
Kelly et al. (3.9)	2016	3	FWE/TFCE	NA	45	reduced FA in the cerebral peduncle, IFOF, posterior thalamic, uncinate fasciculus, CC, cingulum, EC, IC, fornix, SLF and CR
Kelly et al. (4.5)	2016	3	FWE/TFCE	NA	45	reduced FA was in the right cingulum, right ILF, right IFOF, right uncinate fasciculus, right anterior thalamic radiation and EC
Saunavaara et al. (without FGR)	2017	1.5	FWE	NA	40	no significant differences between the two groups
Saunavaara et al. (with FGR)	2017	1.5	FWE	NA	40	reduced FA values in forceps major, forceps minor, bilaterally anterior thalamic radiation, CST, cingulum, IFOF, ILF, SLF and uncinate fasciculus
Young et al.	2018	3	multiple comparisons	NA	6	reduced FA values in the lateral frontal, middle and superior temporal, cingulate, precuneus and lateral occipital regions

Note: PT, preterm; TBSS, tract-based spatial statistics; MRI, magnetic resonance imaging; HC, healthy control; FEW, familywise error correction; MNI, Montreal Neurological Institute;; FA, fractional anisotropy; CC, corpus callosum; IC, internal capsule; NA, not available; EC, external capsule; CS, centrum semiovale; WM, white matter; CR, corona radiata; IFOF, inferior fronto-occipital fasciculus; SLF, superior longitudinal fasciculus; CST, corticospinal tract; TFCE, threshold-free cluster enhancement; and ILF, inferior longitudinal fasciculus.

Figure 2. Four clusters with decreased FA were identified in PT compared with HC: the corpus callosm, bilateral thalamus and the left superior longitudinal fasciculus II. FA, fractional anisotropy; PT, preterm; HC, healthy control. CC, corpus callosm; L, left; R, right; SLF, superior longitudinal fasciculus.

Table 3. Regional differences in FA values between PT and HC subjects identified by the present meta-analyses (voxelwise p < 0.005 and FWHM 20 mm).

WM Tract	Voxels, n	MNI Coordinates (peak voxel)			SDM z value	P, uncorrected	Cluster breakdown (voxels, n)
		x	y	z
PT < HC
Corpus callosum	336	18	−44	10	−2.271	∼0	Corpus callosum (336)
Left thalamus	157	−10	−30	6	−1.674	0.000441551	Left thalamus (120)
							Left anterior thalamic projections (37)
Right thalamus	146	12	−30	8	−2.458	∼0	Right thalamus (110)
							Right hippocampus, BA 27 (22)
							Right anterior thalamic projections (14)
Left superior longitudinal fasciculus II	107	−34	054	24	−1.412	0.001545429	Left superior longitudinal fasciculus II (75)
							Left inferior network, inferior fronto-occipital fasciculus (32)

Note: FA, fractional anisotropy; PT, preterm; HC, healthy control; FWHM, full width at half maximum; WM, white matter; MNI, Montreal Neurological Institute; SDM, seed-based d mapping; and BA, Brodmann area.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.