Regional Differences in Gamma-Aminobutyric Acid and Glutamate Concentrations in the Healthy Newborn Brain

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Fig 1.
Voxel locations of ROIs: cerebellum (A), right basal ganglia (B), and right frontal lobe (C).
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Fig 2.
Composite ¹H-MR spectroscopy PRESS OFF and J-DIFF spectra for all 3 ROIs. Composite spectra from the 3 ROI voxels show the mean (solid line) and SD (shaded area) of all spectra included in the analysis. The spectra were acquired on a 3T scanner with TE = 68 ms, TR = 2000 ms, number of signal averages = 256, and the editing pulses at 1.9 and 7.5 ppm. RBG indicates right basal ganglia; RF, right frontal lobe.
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Fig 3.
Temporal trajectories of metabolites with postmenstrual age. R indicates right.

Table 1:

Baseline clinical parameters (n = 58)^{^a}

Clinical Parameters
GA at birth (wk)	39.1 (SD, 1.3)
Birth weight (g)	3278 (SD, 464)
Female sex	28 (48%)
Race
African American	8 (15%)
White	35 (65%)
Others	11 (20%)
Singleton gestation	60 (100%)
Apgar score at 5 min (in median)	9 (9)
Vaginal delivery	31 (57%)
Maternal age (yr)	35.4 (SD, 5.6)
PMA at MR imaging (wk)	43.1 (SD, 2.4)
Postnatal age at MR imaging (wk)	3.9 (SD, 2.1)

Table 2:

Regional difference in metabolite concentrations adjusted for PMA^{^a}

	Cerebellum	Right Basal Ganglia	Right Frontal Lobe	Pair-Wise Comparisons (P Value)
	Cerebellum	Right Basal Ganglia	Right Frontal Lobe	C vs RBG	C vs RF	RBG vs RF
Metabolites
GABA+	2.56 (SD, 0.1)	2.25 (SD, 0.1)	1.63 (SD, 0.1)	↑.04	↑<.001	↑<.001
Glx	5.95 (SD, 0.2)	5.68 (SD, 0.3)	4.33 (SD, 0.3)	NS	↑<.001	↑<.001
NAA	3.84 (SD, 0.1)	6.72 (SD, 0.2)	4.31 (SD, 0.2)	↓<.001	↓.05	↑<.001
Cr	6.67 (SD, 0.1)	6.72 (SD, 0.2)	3.64 (SD, 0.2)	NS	↑<.001	↑<.001
Cho	3.08 (SD, 0.1)	2.33 (SD, 0.1)	1.88 (SD, 0.1)	↑<.001	↑<.001	↑<.001
Glu	3.80 (SD, 0.2)	3.78 (SD, 0.2)	3.07 (SD, 0.2)	NS	↑.006	↑.02
Gln	2.55 (SD, 0.1)	1.95 (SD, 0.2)	1.72 (SD, 0.2)	↑.005	↑<.001	NS
GSH	1.89 (SD, 0.1)	1.23 (SD, 0.1)	1.05 (SD, 0.1)	↑<.001	↑<.001	NS
mIns	8.02 (SD, 0.3)	5.10 (SD, 0.3)	6.05 (SD, 0.3)	↑<.001	↑<.001	↓.017
Metabolite ratios
GABA+/Cho	0.85 (SD, 0.4)	0.97 (SD, 0.0)	0.86 (SD, 0.4)	↑.03	NS	NS
Glx/Cho	1.97 (SD, 0.1)	2.53 (SD, 0.1)	2.26 (SD, 0.1)	↓<.001	↓.004	↑.026
NAA/Cho	1.31 (SD, 0.0)	3.00 (SD, 0.1)	2.34 (SD, 0.0)	↓<.001	↓<.001	↑<.001
Cr/Cho	2.18 (SD, 0.0)	2.96 (SD, 0.1)	1.96 (SD, 0.0)	↓<.001	↑<.001	↑<.001
GABA+/Glx	0.45 (SD, 0.2)	0.39 (SD, 0.0)	0.41 (SD, 0.2)	NS	NS	NS

Note:—↑ indicates higher than; ↓, lower than; C, cerebellum; RBG, right basal ganglia; RF, right frontal lobe; GLN, glutamine.
↵a Metabolites are marginal means (SD, standard error, in international units) adjusted for PMA. Metabolites are the following: n = 38 for the cerebellum, n = 30 for the right basal ganglia, and n = 38 for the right frontal lobe. Metabolite ratios are the following: cerebellum (n = 51), right basal ganglia (n = 36), and left frontal lobe (n = 48).

Table 3:

Association of PMA and postnatal age with metabolites adjusted for clinical factors^{^a}

	Age Parameter	Cerebellum (β, P Value)	Right Basal Ganglia (β, P Value)	Right Frontal Lobe (β, P Value)
Metabolite
GABA+	Model 1^{^b}: PMA (wk)	0.02, NS	0.02, NS	0.06, .11
GABA+	Model 2^{^c}: postnatal age (wk)	–0.01, NS	0.10, NS	0.09, NS
Glx	PMA	0.25, .09	0.22, .003	0.3, .005
Glx	Postnatal age	0.03, NS	0.15, .13	0.14, NS
Cr	PMA	0.29, .002	0.11, .11	0.20, <.001
Cr	Postnatal age	0.15, NS	0.06, NS	0.14, .06
Cho	PMA	0.06, .095	0.02, NS	0.05, .016
Cho	Postnatal age	0.03, NS	0.01, NS	0.03, NS
NAA	PMA	0.22, .002	0.23, <.001	0.36, <.001
NAA	Postnatal age	0.14, .11	0.17, .06	0.27, .007
Metabolite ratios
Glx/Cho	PMA	0.02, NS	0.10, .003	0.09, .02
Glx/Cho	Postnatal age	–0.02, NS	0.08, .038	0.06, NS
GABA+/Cho	PMA	–0.01, NS	0.02, NS	0.02, NS
GABA+/Cho	Postnatal age	-0.02, NS	0.02, NS	0.03, .10
NAA Cho	PMA	0.05, .001	0.13, <.001	0.13, <.001
NAA Cho	Postnatal age	0.04, .04	0.08, .002	0.10, <.001
Cr/Cho	PMA	0.05, <.001	0.05, .12	0.06, <.001
Cr/Cho	Postnatal age	0.02, .14	0.06, .13	0.05, .015
GABA+/Glx	PMA	–0.02, NS	–0.02, .11	–0.01, NS
GABA+/Glx	Postnatal age (wk)	0.00, NS	–0.01, NS	0.00, NS

↵a Metabolites are the following: n = 38 for the cerebellum, n = 30 for the right basal ganglia, and n = 38 for the right frontal lobe. Metabolite ratios were the following: cerebellum (n = 51), right basal ganglia (n = 36), and left frontal lobe (n = 48).
↵b Linear regression model 1: adjusted for PMA, sex, and mode of delivery.
↵c Linear regression model 2: adjusted for postnatal age, gestational age, sex, and mode of delivery.