Metabolomics profiling of maternal and umbilical cord blood in normoglycemia macrosomia

Figures & data

Table 1. Baseline characteristics and clinical information in the macrosomia and control groups.

Variables	Control (n = 20)	Macrosomia (n = 20)	p value
Maternal age (years)	30.0 ± 3.97	28.6 ± 3.78	0.260
Maternal height (kg)	160.4 ± 4.51	159.2 ± 4.04	0.421
Maternal weight (kg)	70.5 ± 9.88	73.9 ± 7.93	0.235
BMI (kg/m2)	27.4 ± 3.88	29.1 ± 3.30	0.136
Pregnancy weight gain (kg)	11.3 ± 3.96	19.6 ± 4.11	< 0.001
Gravidity	3.30 ± 2.49	2.40 ± 1.43	0.170
Parity	1.70 ± 0.66	1.80 ± 0.62	0.622
History of GDM
No	14 (70.0%)	15 (75.0%)	0.723
Yes	6 (30.0%)	5 (35.0%)
Cesarean
No	13 (65.0%)	11 (55.0%)	0.519
Yes	7 (35.0%)	9 (45.0%)
Obesity
No	13 (65.0%)	9 (45.0%)	0.204
Yes	7 (35.0%)	11 (55.0%)
Alb (g/L)	34.0 ± 3.39	33.3 ± 2.73	0.470
Hb (g/L)	115.2 ± 12.7	121.1 ± 12.7	0.150
Gestational age (weeks)	38.1 ± 2.29	40.3 ± 0.97	< 0.001
Newborn birth weight (g)	3284 ± 254.7	4291 ± 301.2	< 0.001
Newborn sex
Boy	10(50.0%)	9(45.0%)	0.752
Girl	10(50.0%)	11 (55.0%)

Data are n (%): means ± SD; BMI: body mass index; GDM: gestational diabetes mellitus; Alb: albumin; Hb: hemoglobin.

Figure 1. The classification and percentage of metabolites.

Figure 2. Metabolite profile of the macrosomia group vs. the control group about maternal serum samples. (a) Results of PCA analysis. (b) Results of OPLS-DA model. (c)Permutation test of OPLS-DA model.

Figure 3. Metabolite profile of the macrosomia group vs. the control group about umbilical cord serum samples. (a) Results of PCA analysis. (b) Results of OPLS-DA model. (c) Permutation test of OPLS-DA model.

Figure 4. Differential metabolites in maternal serum samples. (a) Volcano plot based on univariate analysis. (b) Volcano plot of OPLS-DA model. (c) Classification of differential metabolites.

Figure 5. Differential metabolites in umbilical cord serum samples. (a) Volcano plot based on univariate analysis. (b) Volcano plot of OPLS-DA model. (c) Classification of differential metabolites.

Table 2. Differential metabolites of lipids and lipid-like molecules in maternal serum (μmol/L).

Metabolite	Class	Median		p value	FDR	log2FC	VIP
		Control	Macrosomia
Docosahexaenoic acid	VLCFA	8.85	16.5	0.001	0.018	0.903	1.914
Docosapentaenoic acid (22n-3)	VLCFA	2.87	8.14	0.004	0.038	1.503	1.785
Docosapentaenoic acid (22n-6)	VLCFA	0.57	1.66	<0.001	0.016	1.528	2.084
Adrenic acid	VLCFA	2.15	5.15	0.001	0.019	1.259	1.973
Eicosapentaenoic acid	LCFA	0.43	0.65	0.020	0.090	0.604	1.596
10Z-Heptadecenoic acid	LCFA	1.19	2.25	0.001	0.018	0.905	1.97
9E-tetradecenoic acid	LCFA	0.15	0.40	0.008	0.051	1.372	1.745
Myristoleic acid	LCFA	0.42	1.31	0.001	0.017	1.657	1.86
Ricinoleic acid	LCFA	0.18	0.28	0.004	0.038	0.761	1.716
Tridecanoic acid	LCFA	0.17	0.24	0.004	0.038	0.508	1.716
12-Hydroxystearic acid	LCFA	0.13	0.16	0.004	0.040	0.322	1.415
Palmitelaidic acid	LCFA	0.86	2.51	<0.001	0.016	1.131	2.095
Pentadecanoic acid	LCFA	0.71	0.96	0.001	0.018	0.44	1.746
Arachidonic acid	LCFA	16.0	37.1	<0.001	0.014	1.211	1.945
Myristic acid	LCFA	5.30	9.50	0.001	0.017	0.843	2.119
Palmitoleic acid	LCFA	16.9	43.2	0.001	0.018	1.351	1.999
Dihomo-gamma-linolenic acid	LCFA	0.59	1.17	0.003	0.032	0.98	2.023
Oleic acid	LCFA	557.2	892.7	0.004	0.038	0.641	1.895
10Z-Nonadecenoic acid	LCFA	1.66	2.81	0.001	0.018	0.73	1.926
gamma-Linolenic acid	LCFA	1.36	2.77	0.014	0.076	1.033	1.819
Linoleic acid	LCFA	502.4	715.0	0.016	0.081	0.562	1.78
alpha-Linolenic acid	LCFA	10.0	20.4	0.033	0.120	1.02	1.724
Nonanoic acid	MCFA	1.89	2.04	0.036	0.130	0.123	1.199
2-Methylhexanoic acid	MCFA	0.009	0.013	0.003	0.033	0.481	1.27
Decanoic acid	MCFA	1.41	2.47	0.007	0.048	0.806	1.444
5Z-Dodecenoic acid	MCFA	0.27	0.53	0.002	0.027	0.966	1.796
Dodecanoic acid	MCFA	1.40	2.45	0.005	0.040	0.807	1.339
Isovaleric acid	MBFA	0.46	0.55	<0.001	0.002	−0.714	1.992
Isovalerylcarnitine	AC	0.04	0.02	0.018	0.085	−0.791	1.809
Propionylcarnitine	AC	0.29	0.20	0.024	0.101	−0.376	1.681
Dodecanoylcarnitine	AC	0.02	0.04	0.029	0.115	0.89	1.417
Tetradecanoylcarnitine	AC	0.01	0.02	0.007	0.046	0.815	1.398

VLCFA: very long-chain fatty acids; LCFA: long-chain fatty acids; MCFA: medium-chain fatty acids; MBFA: methyl-branched fatty acids; AC: acyl-carnitines; FDR: false discovery rate; FC: fold change; VIP: variable importance in projection.

Table 3. Differential metabolites of lipids and lipid-like molecules in umbilical cord serum (μmol/L).

Metabolite	Class	Median		P value	FDR	log2FC	VIP
		control	macrosomia
Adipic acid	MCFA	0.63	0.77	0.028	0.230	0.294	1.38
2-Methylhexanoic acid	MCFA	0.011	0.016	<0.001	0.022	0.533	1.588
12-Hydroxystearic acid	LCFA	0.13	0.17	0.004	0.095	0.319	1.339
Citramalic acid	HFA	0.17	0.21	0.049	0.311	0.31	1.354
Valeric acid	SCFA	0.53	0.67	0.004	0.095	0.34	2.171
Isocaproic acid	MBFA	4.13	6.09	0.026	0.223	0.561	1.569
Tauro-Chenodeoxycholic Acid	BA	1.07	0.67	0.013	0.141	−0.683	1.903
Glycochenodeoxycholicacid	BA	0.42	0.26	0.005	0.095	−0.695	1.739
Tetradecanoylcarnitine	AC	0.012	0.015	0.046	0.311	0.334	1.491
Acetylcarnitine	AC	4.84	5.75	0.043	0.311	0.247	1.188
Adipoylcarnitine	AC	0.011	0.017	0.003	0.095	0.685	1.565

MCFA: medium-chain fatty acids; LCFA: long-chain fatty acids; HFA hydroxy fatty acids; SCFA: straight-chain fatty acids; MBFA: methyl-branched fatty acids; BA: bile acids; AC: acyl-carnitines; FDR: false discovery rate; FC: fold change; VIP: variable importance in projection.

Table 4. Maternal to umbilical cord serum unsaturated fatty acids differences between control and macrosomia subjects.

Unsaturated fatty acids	Gradient Maternal-to-Umbilical cord		p value	FDR
	control	macrosomia
Eicosapentaenoic acid	−0.03 ± 0.89	−0.85 ± 0.86	0.005	0.019
Docosahexaenoic acid	0.46 ± 0.71	−0.29 ± 0.70	0.002	0.019
Docosapentaenoic acid (22n-3)	−0.34 ± 1.04	−1.29 ± 0.83	0.003	0.019
Docosapentaenoic acid (22n-6)	0.35 ± 0.74	−0.42 ± 0.88	0.005	0.019
Adrenic acid	−0.09 ± 0.70	−0.71 ± 0.76	0.012	0.030
Oleic acid	−0.95 ± 0.93	−1.45 ± 0.73	0.065	0.078
10Z-Nonadecenoic acid	−1.43 ± 0.91	−1.72 ± 0.65	0.239	0.239
Arachidonic acid	0.59 ± 0.50	−0.06 ± 0.75	0.003	0.019
Dihomo-gamma-linolenic acid	0.11 ± 0.60	−0.45 ± 0.75	0.013	0.030
Palmitoleic acid	−0.57 ± 1.15	−1.44 ± 0.97	0.013	0.030
Palmitelaidic acid	−0.13 ± 1.40	−1.17 ± 1.20	0.016	0.030
10Z-Heptadecenoic acid	−1.01 ± 1.19	−1.65 ± 0.79	0.051	0.075
alpha-Linolenic acid	−1.22 ± 1.32	−1.97 ± 1.15	0.064	0.078
Linoleic acid	−0.93 ± 0.97	−1.46 ± 0.80	0.066	0.078
gamma-Linolenic acid	−0.55 ± 1.14	−1.34 ± 0.90	0.019	0.030
Myristoleic acid	−0.28 ± 1.23	−1.23 ± 1.21	0.018	0.030
9E-tetradecenoic acid	−0.15 ± 1.16	−0.71 ± 1.43	0.182	0.192
Ricinoleic acid	−0.68 ± 1.03	−1.50 ± 1.06	0.018	0.030
5Z-Dodecenoic acid	0.11 ± 1.08	−0.47 ± 1.10	0.100	0.1116

Gradient maternal-to-umbilical cord calculated as [ln (umbilical cord/maternal serum)] ; Data are means ± SD; FDR: false discovery rate.

Figure 6. Common differential metabolites in maternal and umbilical cord serum (μmol/L). (a) lactic acid (b) Aconitic acid (c) Citric acid (d) Isocitric acid (e) 2-Methylhexanoic acid (f)12-Hydroxystearic acid.

* p < 0.05

Figure 7. Metabolite set enrichment analysis. (a) The pathways in maternal serum. (b) The pathways in in umbilical cord serum.

The statistically significant pathways were marked with names.

Table 5. Results of correlation analysis between common metabolites and clinical parameters.

Metabolite		MA		BMI		PWG		GA		Parity
		r	p value	R	p value	r	p value	r	p value	r	p value
MS	2-Methylhexanoic acid	−0.019	0.908	0.144	0.374	0.364	0.021	0.194	0.230	0.131	0.420
	12-Hydroxystearic acid	−0.337	0.033	−0.094	0.565	0.286	0.074	0.103	0.526	0.146	0.367
	Isocitric acid	−0.155	0.339	0.237	0.140	0.595	<0.001	0.182	0.262	0.148	0.362
	Aconitic acid	−0.103	0.527	0.284	0.075	0.537	<0.001	0.195	0.229	0.096	0.557
	Lactic acid	−0.071	0.661	0.05	0.758	0.351	0.026	0.062	0.706	0.100	0.540
	Citric acid	−0.134	0.409	0.235	0.145	0.465	0.003	0.136	0.404	0.115	0.478
UCS	2-Methylhexanoic acid	−0.059	0.718	0.127	0.434	0.521	0.001	0.370	0.019	0.120	0.460
	12-Hydroxystearic acid	0.062	0.702	0.182	0.262	0.276	0.085	0.454	0.003	−0.102	0.531
	Isocitric acid	−0.161	0.320	0.085	0.600	0.307	0.054	0.226	0.162	0.163	0.316
	Aconitic acid	−0.167	0.303	−0.014	0.934	0.301	0.059	0.232	0.150	0.185	0.253
	Lactic acid	−0.156	0.335	−0.169	0.297	0.294	0.065	0.306	0.055	0.112	0.490
	Citric acid	−0.17	0.294	0.021	0.898	0.272	0.090	0.213	0.186	0.184	0.255

MS: maternal serum; UCS: umbilical cord serum; MA: maternal age; BMI: body mass index; PWG: pregnancy weight gain; GA: gestational age.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.