. Author manuscript; available in PMC: 2024 Mar 4.

Published in final edited form as: FASEB J. 2021 Dec;35(12):e22063. doi: 10.1096/fj.202101401RR

TABLE 5.

Plasma choline metabolite enrichments and enrichment ratios for the control and intervention groups at Visit 2 through delivery¹

Variables	Visit 2 (gestation week 20–24)			Visit 3 (gestation week 28–32)			Delivery
Variables	Control	Intervention	p-Value	Control	Intervention	p-Value	Control	Intervention	p-Value
Enrichment %
d9-Choline	1.87^a [1.59, 2.19]	1.85^a [1.67, 2.05]	.87	2.73^a [1.93, 3.85]	2.08^a [1.73, 2.48]	.38	2.13^a [1.81, 2.50]	1.81^a [1.19, 2.76]	.06
d3-Choline	0.56^a [0.47, 0.64]	0.74^a [0.63, 0.85]	.01	0.74^b [0.64, 0.85]	0.86^b [0.73, 0.98]	.13	0.87^c [0.74, 0.99]	0.92^b [0.75, 1.08]	.60
d9-Betaine	2.45^a [2.06, 2.92]	2.77^a [2.47, 3.11]	.14	3.28^a [2.47, 4.35]	2.70^a [2.20, 3.32]	.37	2.57^a [2.18, 3.01]	3.32^a [1.61, 4.14]	.25
d3-Betaine	0.49^a [0.41, 0.57]	0.62^a [0.52, 0.72]	.11	0.65^a,b [0.57, 0.74]	0.75^a [0.66, 0.84]	.11	0.76^b [0.66, 0.86]	0.79^a [0.66, 0.92]	.73
d6-Dimethylglycine	9.63^a [6.71, 12.6]	11.0^a [9.53, 12.5]	.37	10.2^a [8.29, 12.1]	10.0^a [8.29, 11.7]	.87	8.80^a [7.57, 10.0]	8.68^a [6.69, 10.7]	.91
d3-Dimethylglycine	0.45^a [0.33, 0.58]	0.48^a [0.37, 0.59]	.70	0.63^b [0.48, 0.77]	0.66^b [0.53, 0.80]	.69	0.67^b [0.49, 0.84]	0.75^b [0.56, 0.94]	.51
d9-TMAO	1.00^a [0.67, 1.50]	8.59^a [6.38, 11.6]	<.0001	1.05^a [0.78, 1.42]	9.87^b [4.15, 23.5]	<.0001	1.29^a [0.94, 1.78]	21.5^a,b [3.06, 150]	.10
d3-TMAO²	1.10^a [0.00, 2.46]	2.06^a,b [0.00, 4.22]	.42	0.28^a [0.17, 0.38]	1.96^a [0.24, 3.68]	.046	0.36^a [0.17, 0.55]	0.19^b [0.05, 0.34]	.15
d9-PC	1.27^a [1.15, 1.38]	1.20^a [1.06, 1.33]	.39	1.45^a [1.25, 1.65]	1.15^a [0.95, 1.35]	.03	1.33^a [1.12, 1.53]	1.03^a [0.81, 1.26]	.06
d3-PC	0.67^a [0.59, 0.77]	0.95^a [0.81, 1.13]	.002	0.79^b [0.68, 0.92]	1.00^a [0.82, 1.23]	.07	0.88^a,b [0.76, 1.03]	1.04^a [0.76, 1.44]	.77
d9-Sphingomyelin	1.40^a [1.21, 1.58]	1.37^a [1.11, 1.62]	.85	1.62^a [1.40, 1.85]	1.33^a [1.13, 1.53]	.04	1.55^a [1.33, 1.76]	1.20^a [0.95, 1.46]	.04
d9-LysoPC	1.29^a [1.21, 1.39]	1.23^a [1.09, 1.40]	.33	1.49^a [1.37, 1.63]	1.26^a [0.98, 1.62]	.046	1.36^a [1.16, 1.59]	1.18^a [0.88, 1.60]	.15
Enrichment ratios
d9-Betaine:d9-Choline	1.33^a [1.18, 1.47]	1.50^a [1.40, 1.60]	.04	1.27^a [1.17, 1.38]	1.30^b [1.18, 1.42]	.71	1.21^a [1.17, 1.25]	1.36^a,b [1.28, 1.45]	.002
d9-Betaine:d9-PC	1.90^a [1.72, 2.09]	2.35^a [2.16, 2.55]	.001	2.20^a [1.79, 2.69]	2.49^a [2.13, 2.91]	.20	1.94^a [1.79, 2.11]	3.28^a [1.81, 5.96]	.60
d9-PC:d9-Choline	0.71^a [0.64, 0.78]	0.65^a [0.61, 0.68]	.11	0.68^a [0.52, 0.90]	0.58^a [0.46, 0.74]	.41	0.64^a [0.58, 0.70]	0.88^a [0.51, 1.51]	.95
d9-Sphingomyelin:d9-PC	1.10^a [0.99, 1.21]	1.13^a [1.00, 1.26]	.70	1.14^a [1.01, 1.27]	1.22^a [1.04, 1.41]	.43	1.18^a [1.08, 1.29]	1.15^a [0.94, 1.36]	.75
d6-Dimethylglycine:d9-Betaine	3.83^a [3.50, 4.18]	4.00^a [3.70, 4.31]	.40	3.55^a [2.93, 4.30]	3.75^a [3.39, 4.14]	.35	3.53^a [3.18, 3.92]	8.39^a [2.33, 30.2]	.45
d3-PC:d9-PC	0.53^a [0.48, 0.58]	0.79^a [0.72, 0.87]	<.0001	0.55^a [0.50, 0.60]	0.91^b [0.81, 1.03]	<.0001	0.68^b [0.61, 0.75]	1.04^c [0.91, 1.19]	<.0001
d3-Choline:d3-PC	0.82^a [0.78, 0.87]	0.78^a [0.76, 0.81]	.14	0.94^b [0.89, 1.00]	0.88^b [0.80, 0.97]	.17	0.99^a,b [0.94, 1.04]	1.26^a,b [0.75, 2.11]	.73
d3-Betaine:d3-Choline	0.88^a [0.85, 0.92]	0.83^a [0.81, 0.86]	.01	0.89^a [0.85, 0.92]	0.89^a [0.84, 0.94]	.92	0.89^a [0.84, 0.93]	0.89^a [0.83, 0.95]	.95

Abbreviations: PC, phosphatidylcholine; TMAO, trimethylamine N-oxide.

Values are Mean [95% CI]. The intervention group (n = 15) received 550 mg of choline from choline chloride (500 mg unlabeled choline + 50 mg deuterium-labeled d9-choline), while the control group (n = 15) received 25 mg of d9-choline only. Repeated measures mixed models with random intercepts and slopes and heterogenous autoregressive covariance structures were employed followed by the Tukey-Kramer post-hoc test. A time × intervention interaction term was used to obtain p-value for the intervention effect at each time point. Superscript letters within a row indicate significant difference (p < .05) among visits within each group.

Lower limit of the confidence intervals for visit 2 were negative and thus reported as zero.