Table 2. Median concentrations (IQR) of profiled compounds relative to creatinine concentration at the three visits, and patient-wise fold-change between visits.
| Median concentrationa (IQR) [mM/mM Creatinine] | Rel. individual FCa (t-test p-value) | ||||
| Compound | Visit V1b (<20 wk) | Visit V2b (28 wk) | Visit V3b (3 mo p.p.) | V1 → V2 | V2 → V3 |
| Ureac,d | 2.5 (1.9–3.3) | 2.4 (1.9–3.1) | 2.6 (2–3.3) | −1.01 (0.64) | 1.07 (0.0025) |
| Unknown multiplet, 0.55 ppmx,d | 2.3 (1.9–2.9) | 4.9 (4.1–5.9) | 1.7 (1.3–2.2) | 2.12 (7e-200) | −2.88 (2.7e-194) |
| Unknown multiplet, 0.62 ppmx,d | 4.2 (3.4–5.3) | 9.4 (7.9–11) | 1.8 (1.4–2.3) | 2.2 (1.4e-219) | −5.14 (2.8e-283) |
| Unknown multiplet, 0.78 ppmx,e | 0.2 (0.091–0.34) | 1.2 (0.92–1.6) | 0.026 (0–0.084) | 6.11 (1.4e-151) | −21.8 (1e-125) |
| Unknown multiplet, 0.90 ppmx,e | 0.28 (0–1.1) | 2.6 (1.3–4.4) | 0 (0–0.3) | 3.42 (1.1e-42) | −4.35 (8e-24) |
| Unknown doublet, 0.75 ppmx,e | 0.047 (0.0085–0.15) | 0.04 (0.006–0.13) | 0.055 (0.01–0.17) | −1.12 (0.22) | 1.45 (0.00027) |
| Valine | 0.0059 (0.004–0.008) | 0.006 (0.004–0.008) | 0.0041 (0.003–0.006) | −1.02 (0.29) | −1.45 (2.5e-34) |
| Leucine | 0.004 (0.003–0.005) | 0.0045 (0.003–0.006) | 0.0025 (0.002–0.004) | 1.12 (2.1e-11) | −1.83 (8.2e-89) |
| Unknown doublet, 1.08 ppmx | 3.5 (2.3–5) | 5.4 (3.6–8.1) | 2.1 (1.4–3.1) | 1.61 (5.9e-68) | −2.63 (1.4e-106) |
| Unknown doublet, 1.11 ppmx | 11 (7.5–16) | 19 (14–25) | 2.9 (1.9–4.4) | 1.78 (3.1e-114) | −6.66 (1.2e-231) |
| 3-Aminoisobutyratee | 0.0098 (0.004–0.022) | 0.011 (0.0041–0.024) | 0.008 (0.003–0.019) | 1.08 (0.14) | −1.28 (0.00018) |
| Unknown doublet, 1.24 ppmx,e | 2.9 (2.2–4) | 4.4 (3–6.2) | 3.2 (2.3–4.5) | 1.43 (1.6e-38) | −1.33 (2.8e-20) |
| Unknown doublet, 1.26 ppmx,e | 1.3 (0.78–1.9) | 1.9 (1.3–2.8) | 0.88 (0.41–1.4) | 1.55 (1.2e-40) | −2.31 (6.2e-65) |
| 3-Hydroxyisovaleratee | 0.0092 (0.007–0.012) | 0.011 (0.0084–0.014) | 0.0054 (0.004–0.007) | 1.2 (5.8e-28) | −2.1 (7.9e-145) |
| 2-Hydroxyisobutyrate | 0.0071 (0.006–0.008) | 0.0076 (0.006–0.009) | 0.0054 (0.004–0.006) | 1.11 (1.0e-14) | −1.44 (2.5e-87) |
| comb. Lactate/Threoninex | 29 (20–43) | 56 (39–83) | 8.7 (5.8–13) | 1.89 (1.6e-89) | −6.3 (2.6e-202) |
| Alanine | 0.04 (0.029–0.054) | 0.065 (0.046–0.09) | 0.02 (0.015–0.028) | 1.62 (1.7e-84) | −3.22 (1.5e-191) |
| Lysinee | 0.02 (0.011–0.034) | 0.016 (0.009–0.026) | 0.0093 (0.005–0.016) | −1.26 (4.7e-08) | −1.64 (6.8e-23) |
| Acetaminophen metabolitesx,e | 9.3 (6.5–14) | 10 (6.7–14) | 5.8 (3.5–9.4) | 1.04 (0.27) | −1.56 (1.1e-14) |
| Acetone | 0.003 (0.002–0.005) | 0.004 (0.003–0.006) | 0.003 (0.002–0.005) | 1.1 (0.38) | −1.09 (0.49) |
| N-Acetylglutamine | 0.055 (0.04–0.08) | 0.048 (0.03–0.07) | 0.07 (0.045–0.09) | −1.29 (1.5e-13) | 1.6 (5.6e-34) |
| Unknown singlet, 2.35 ppmx | 17 (9.4–28) | 16 (8.1–26) | 21 (11–31) | −1.13 (0.00072) | 1.3 (3.7e-11) |
| Citrate | 0.24 (0.18–0.3) | 0.25 (0.18–0.32) | 0.15 (0.1–0.21) | 1.03 (0.077) | −1.64 (2.7e-56) |
| Dimethylamine | 0.041 (0.037–0.046) | 0.047 (0.043–0.052) | 0.042 (0.038–0.048) | 1.14 (1.9e-18) | −1.08 (1.8e-06) |
| Unknown singlet, 2.78 ppmx | 3 (2.4–3.9) | 2.9 (2.4–3.9) | 3.6 (2.9–4.8) | −1.01 (0.68) | 1.26 (6.8e-17) |
| Trimethylamine N-oxide | 0.038 (0.025–0.064) | 0.037 (0.022–0.064) | 0.041 (0.027–0.073) | −1.12 (0.019) | 1.22 (0.00055) |
| Glycine | 0.24 (0.17–0.36) | 0.32 (0.23–0.45) | 0.11 (0.056–0.18) | 1.32 (3.9e-41) | −3.06 (6.6e-118) |
| Creatine | 0.079 (0.033–0.15) | 0.086 (0.042–0.16) | 0.05 (0.021–0.13) | 1.16 (0.00022) | −1.56 (2.7e-17) |
| Creatininef [abs. mM] | 10 (7.3–14) | 8.5 (6.3–12) | 12 (8.8–16) | −1.19 (8.6e-13) | 1.33 (1.5e-25) |
| Trigonelline | 0.011 (0.0066–0.018) | 0.012 (0.0068–0.023) | 0.014 (0.0073–0.027) | 1.11 (0.017) | 1.14 (0.012) |
| Lactose | 0.04 (0.025–0.06) | 0.1 (0.073–0.14) | 0.24 (0.14–0.39) | 2.47 (6.4e-122) | 2.11 (2.8e-51) |
| 1-Methylnicotinamide | 0.009 (0.007–0.012) | 0.013 (0.0093–0.017) | 0.0053 (0.003–0.008) | 1.41 (4.3e-42) | −2.58 (5.4e-111) |
| Unknown singlet, 4.51 ppmx,e | 0 (0–0.062) | 0 (0–0.25) | 0 (0–0.17) | 1.1 (0.66) | −1.41 (0.14) |
| Ascorbatee | 0.006 (0.004–0.011) | 0.01 (0.006–0.016) | 0.006 (0.004–0.011) | 1.58 (9.6e-14) | −1.47 (6.9e-10) |
| Glucose | 0.1 (0.079–0.13) | 0.14 (0.11–0.18) | 0.079 (0.064–0.11) | 1.39 (6.3e-35) | −1.77 (2.3e-64) |
| Acetaminophen glucuronidee | 0.033 (0.023–0.046) | 0.039 (0.028–0.053) | 0.029 (0.022–0.043) | 1.18 (3.9e-08) | −1.18 (1.3e-05) |
| Unknown multiplet, 5.02 ppmx,e | 0.89 (0.43–1.8) | 0.93 (0.46–1.8) | 1 (0.54–1.9) | 1.07 (0.18) | 1.12 (0.044) |
| Unknown doublet, 5.08 ppmx,e | 0.089 (0–0.26) | 0.084 (0–0.29) | 0.12 (0–0.29) | −1.02 (0.8) | 1.02 (0.87) |
| Unknown doublet, 5.20 ppmx | 1.8 (1.3–2.5) | 2.5 (1.9–3.6) | 1.2 (0.86–1.7) | 1.38 (6.3e-34) | −2.1 (1.2e-75) |
| Sugar doublets, 5.23 ppmx | 7.8 (6.1–10) | 16 (12–20) | 22 (15–33) | 1.98 (4.6e-120) | 1.27 (3.9e-11) |
| Unknown doublet, 5.30 ppmx,e | 0.53 (0.34–0.81) | 1.2 (0.71–1.7) | 0.66 (0.47–0.93) | 1.99 (7.6e-78) | −1.61 (1.1e-45) |
| Unknown doublet, 5.42 ppmx,e | 0.29 (0.077–0.83) | 0.52 (0.18–1.2) | 0.42 (0.12–1.1) | 1.56 (3.3e-07) | −1.12 (0.22) |
| 1,6-Anhydroglucosee | 0.003 (0.001–0.006) | 0.005 (0.002–0.01) | 0.003 (0.002–0.007) | 1.64 (1.1e-14) | −1.4 (2.3e-08) |
| Unknown doublet, 6.58 ppmx,e | 0.015 (0–0.17) | 0.013 (0–0.18) | 0.027 (0–0.22) | 1.0 (0.99) | 1.08 (0.59) |
| 4-Hydroxyphenylacetate | 0.009 (0.007–0.01) | 0.01 (0.08–0.014) | 0.01 (0.08–0.014) | 1.07 (0.028) | −1.01 (0.72) |
| Tyrosine | 0.012 (0.008–0.016) | 0.013 (0.0092–0.019) | 0.0051 (0.003–0.008) | 1.16 (1e-12) | −2.9 (1.2e-91) |
| N-Phenylacetylglycineg | 0.074 (0.047–0.11) | 0.065 (0.038–0.099) | 0.09 (0.054–0.13) | −1.15 (0.00018) | 1.37 (3e-14) |
| Acetaminophen sulfatee | 0.03 (0.023–0.039) | 0.033 (0.025–0.042) | 0.03 (0.023–0.04) | 1.09 (0.00011) | −1.01 (0.72) |
| Hippurate | 0.21 (0.13–0.32) | 0.22 (0.14–0.33) | 0.23 (0.14–0.36) | 1.02 (0.49) | 1.01 (0.68) |
| Histidine regiong | 0.058 (0.052–0.065) | 0.068 (0.061–0.075) | 0.053 (0.048–0.06) | 1.17 (1.2e-76) | −1.26 (6.3e-101) |
| Formate | 0.035 (0.026–0.052) | 0.052 (0.038–0.073) | 0.016 (0.011–0.025) | 1.51 (1.9e-59) | −3.28 (3.4e-147) |
a
While the median (IQR) values are reported on their natural scale, all parametric statistical tests were carried out using the log-transformed, normally distributed variables.
b
Visit V1: gestational week 8–20; V2: gestational week 26–30; V3∶10–16 weeks post partum.
c
Urea is affected by NMR water suppression.
d
Broader spectral signal; measured before subtracting BXR baseline.
e
Compound very dilute to undetectable in a substantial number of samples; reported concentration may represent noise.
f
Concentration of creatinine is reported as absolute mM before normalization.
g
No conclusive identification, quantified as stated.
x
Concentrations of unidentified signals in arbitrary units, but nonetheless individually normalized to creatinine.