Table 2.
Crude and adjusted ORs of GDM associated with quartile groups of plasma AAs at 10–14 and 15–26 GW in the NICHD Fetal Growth Studies–Singleton Cohort
| 10–14 GW | 15–26 GW | |||
|---|---|---|---|---|
| AAs and quartile groups | Crude OR | Adjusted OR* | Crude OR | Adjusted OR |
| Glycine | ||||
| Q2 vs. Q1 (reference) | 0.42 (0.21, 0.84) | 0.44 (0.21, 0.95) | 0.58 (0.29, 1.15) | 0.66 (0.31, 1.40) |
| Q3 vs. Q1 | 0.29 (0.14, 0.61) | 0.39 (0.17, 0.90) | 0.31 (0.15, 0.65) | 0.35 (0.15, 0.81) |
| Q4 vs. Q1 | 0.19 (0.09, 0.43) | 0.25 (0.10, 0.62) | 0.17 (0.07, 0.41) | 0.18 (0.07, 0.51) |
| P-trend† | <0.001 | 0.004 | <0.001 | <0.001 |
| FDR critical P value† | 0.002 | 0.0025** | ||
| Alanine | ||||
| Q2 vs. Q1 (reference) | 1.50 (0.68, 3.31) | 1.92 (0.79, 4.65) | 1.22 (0.57, 2.60) | 1.10 (0.45, 2.67) |
| Q3 vs. Q1 | 2.24 (1.07, 4.70) | 2.78 (1.19, 6.46) | 1.36 (0.62, 3.01) | 1.46 (0.56, 3.77) |
| Q4 vs. Q1 | 2.67 (1.28, 5.57) | 3.32 (1.43, 7.74) | 2.50 (0.18, 5.29) | 3.59 (1.48, 8.72) |
| P-trend | 0.005 | 0.005 | 0.01 | 0.002 |
| FDR critical P value | 0.004 | 0.0075** | ||
| Aspartic acid | ||||
| Q2 vs. Q1 (reference) | 1.05 (0.49, 2.26) | 1.17 (0.49, 2.81) | 2.15 (1.04, 4.44) | 2.83 (1.20, 6.66) |
| Q3 vs. Q1 | 1.69 (0.80, 3.56) | 1.63 (0.69, 3.84) | 1.28 (0.54, 3.01) | 1.76 (0.66, 4.70) |
| Q4 vs. Q1 | 2.19 (1.10, 4.36) | 2.40 (1.07, 5.39) | 3.59 (1.41, 9.16) | 3.62 (1.26, 10.30) |
| P-trend | 0.008 | 0.01 | 0.02 | 0.05 |
| FDR critical P value | 0.006 | |||
| Asparagine | ||||
| Q2 vs. Q1 (reference) | 0.97 (0.52, 1.81) | 0.88 (0.44, 1.75) | 0.54 (0.23, 1.24) | 0.51 (0.18, 1.43) |
| Q3 vs. Q1 | 0.63 (0.32, 1.24) | 0.69 (0.32, 1.45) | 0.45 (0.17, 1.19) | 0.51 (0.16, 1.67) |
| Q4 vs. Q1 | 0.51 (0.25, 1.06) | 0.49 (0.21, 1.15) | 0.39 (0.15, 1.03) | 0.52 (0.16, 1.75) |
| P-trend | 0.05 | 0.09 | 0.08 | 0.40 |
| Arginine | ||||
| Q2 vs. Q1 (reference) | 1.10 (0.55, 2.20) | 1.14 (0.52, 2.48) | 0.45 (0.18, 1.13) | 0.28 (0.10, 0.83) |
| Q3 vs. Q1 | 1.22 (0.62, 2.38) | 1.24 (0.58, 2.64) | 1.43 (0.68, 2.97) | 1.01 (0.43, 2.33) |
| Q4 vs. Q1 | 1.66 (0.84, 3.29) | 1.75 (0.81, 3.75) | 2.06 (1.01, 4.21) | 1.32 (0.59, 2.98) |
| P-trend | 0.12 | 0.14 | 0.07 | 0.15 |
| Glutamine | ||||
| Q2 vs. Q1 (reference) | 1.09 (0.56, 2.11) | 0.91 (0.43, 1.93) | 0.46 (0.19, 1.10) | 0.62 (0.23, 1.68) |
| Q3 vs. Q1 | 1.06 (0.49, 2.28) | 1.27 (0.52, 3.11) | 0.83 (0.20, 3.40) | 0.98 (0.22, 4.26) |
| Q4 vs. Q1 | 0.90 (0.39, 2.07) | 1.00 (0.38, 2.60) | 0.34 (0.07, 1.56) | 0.31 (0.06, 1.52) |
| P-trend | 0.89 | 0.91 | 0.05 | 0.10 |
| Glutamic acid | ||||
| Q2 vs. Q1 (reference) | 1.06 (0.52,2.15) | 0.86 (0.39, 1.89) | 3.09 (1.26, 7.62) | 3.89 (1.34, 11.30) |
| Q3 vs. Q1 | 1.78 (0.81, 3.93) | 1.62 (0.67, 3.90) | 4.70 (1.15, 19.2) | 4.04 (0.87, 19.0) |
| Q4 vs. Q1 | 2.66 (1.07, 6.59) | 2.45 (0.89, 6.67) | 7.20 (1.60, 32.3) | 5.15 (1.00, 26.5) |
| P-trend | 0.02 | 0.04 | 0.04 | 0.17 |
| FDR critical P value | 0.008 | |||
| Threonine | ||||
| Q2 vs. Q1 (reference) | 1.14 (0.57, 2.32) | 0.93 (0.42, 2.07) | 1.19 (0.59, 2.42) | 0.95 (0.41, 2.20) |
| Q3 vs. Q1 | 1.15 (0.58, 2.29) | 0.83 (0.38, 1.82) | 1.30 (0.65, 2.62) | 1.13 (0.51, 2.50) |
| Q4 vs. Q1 | 1.85 (0.92, 3.71) | 1.61 (0.73, 3.56) | 1.36 (0.67, 2.77) | 1.09 (0.47, 2.54) |
| P-trend | 0.08 | 0.25 | 0.37 | 0.73 |
| Serine | ||||
| Q2 vs. Q1 (reference) | 0.72 (0.38, 1.34) | 0.74 (0.48, 0.60) | 0.79 (0.39, 1.61) | 0.97 (0.43, 2.18) |
| Q3 vs. Q1 | 0.54 (0.28, 1.04) | 0.48 (0.22, 1.03) | 0.76 (0.37, 1.55) | 0.83 (0.37, 1.87) |
| Q4 vs. Q1 | 0.51 (0.24, 1.05) | 0.60 (0.27, 1.38) | 1.01 (0.48, 2.13) | 1.20 (0.50, 2.89) |
| P-trend | 0.04 | 0.13 | 0.94 | 0.72 |
| Methionine | ||||
| Q2 vs. Q1 (reference) | 1.14 (0.58, 2.24) | 0.98 (0.45, 2.13) | 1.27 (0.57, 2.81) | 1.66 (0.66, 4.16) |
| Q3 vs. Q1 | 1.27 (0.67, 2.40) | 1.24 (0.62, 2.50) | 1.73 (0.76, 3.94) | 2.36 (0.92, 6.01) |
| Q4 vs. Q1 | 0.96 (0.49, 1.86) | 0.87 (0.40, 1.87) | 2.36 (1.01, 5.50) | 2.16 (0.84, 5.59) |
| P-trend | 0.85 | 0.79 | 0.03 | 0.11 |
| Histidine | ||||
| Q2 vs. Q1 (reference) | 1.25 (0.67, 2.34) | 1.82 (0.89, 3.73) | 1.26 (0.62, 2.55) | 1.08 (0.48, 2.42) |
| Q3 vs. Q1 | 0.77 (0.40, 1.50) | 0.71 (0.33, 1.54) | 1.10 (0.53, 2.25) | 0.95 (0.43, 2.09) |
| Q4 vs. Q1 | 0.63 (0.30, 1.31) | 0.68 (0.29, 1.58) | 0.58 (0.27, 1.27) | 0.44 (0.17, 1.11) |
| P-trend | 0.13 | 0.18 | 0.17 | 0.10 |
| Lysine | ||||
| Q2 vs. Q1 (reference) | 0.61 (0.30, 1.24) | 0.53 (0.25, 1.16) | 1.02 (0.49, 2.11) | 1.10 (0.49, 2.44) |
| Q3 vs. Q1 | 0.97 (0.50, 1.86) | 0.90 (0.43, 1.88) | 0.98 (0.48, 2.01) | 0.83 (0.38, 1.85) |
| Q4 vs. Q1 | 1.14 (0.58, 2.24) | 1.10 (0.51, 2.40) | 1.49 (0.76, 2.94) | 1.18 (0.54, 2.59) |
| P-trend | 0.44 | 0.49 | 0.2 | 0.76 |
| Proline | ||||
| Q2 vs. Q1 (reference) | 1.14 (0.59, 2.20) | 1.23 (0.60, 2.55) | 0.91 (0.42, 1.99) | 0.80 (0.33, 1.95) |
| Q3 vs. Q1 | 0.62 (0.30, 1.31) | 0.73 (0.33, 1.65) | 1.13 (0.55, 2.34) | 1.33 (0.58, 3.04) |
| Q4 vs. Q1 | 0.96 (0.50, 1.82) | 1.05 (0.50, 2.19) | 0.65 (0.30, 1.41) | 0.53 (0.22, 1.28) |
| P-trend | 0.66 | 0.87 | 0.37 | 0.30 |
| Valine | ||||
| Q2 vs. Q1 (reference) | 1.09 (0.54, 2.19) | 1.02 (0.47, 2.23) | 1.51 (0.70, 3.25) | 1.65 (0.66, 4.16) |
| Q3 vs. Q1 | 1.22 (0.58, 2.56) | 1.03 (0.44, 2.41) | 1.49 (0.71, 3.11) | 0.97 (0.39, 2.40) |
| Q4 vs. Q1 | 1.32 (0.67, 2.59) | 1.19 (0.56, 2.53) | 1.97 (0.97, 4.02) | 1.71 (0.72, 4.06) |
| P-trend | 0.40 | 0.63 | 0.07 | 0.39 |
| Leucine | ||||
| Q2 vs. Q1 (reference) | 1.42 (0.73, 2.78) | 1.45 (0.70, 3.01) | 0.72 (0.33, 1.58) | 0.72 (0.29, 1.78) |
| Q3 vs. Q1 | 1.07 (0.52, 2.19) | 0.91 (0.41, 2.02) | 1.01 (0.50, 2.07) | 0.79 (0.35, 1.79) |
| Q4 vs. Q1 | 1.16 (0.58, 2.30) | 1.13 (0.52, 2.43) | 1.66 (0.81, 3.41) | 1.30 (0.57, 2.99) |
| P-trend | 0.88 | 0.99 | 0.09 | 0.39 |
| Isoleucine | ||||
| Q2 vs. Q1 (reference) | 1.36 (0.67, 2.77) | 1.18 (0.54, 2.58) | 1.28 (0.58, 2.82) | 1.46 (0.59, 3.63) |
| Q3 vs. Q1 | 1.58 (0.77, 3.24) | 1.29 (0.58, 2.86) | 1.46 (0.67, 3.16) | 1.27 (0.51, 3.13) |
| Q4 vs. Q1 | 1.67 (0.83, 3.34) | 1.52 (0.69, 3.33) | 3.11 (1.14, 1.94) | 3.15 (1.29, 2.27) |
| P-trend | 0.17 | 0.30 | 0.002 | 0.01 |
| FDR critical P value | 0.01 | |||
| Phenylalanine | ||||
| Q2 vs. Q1 (reference) | 1.34 (0.66, 2.71) | 1.29 (0.59, 2.84) | 1.22 (0.56, 2.63) | 1.20 (0.50, 2.86) |
| Q3 vs. Q1 | 2.09 (1.03, 4.26) | 2.11 (0.97, 4.58) | 1.87 (0.87, 4.01) | 1.82 (0.76, 4.32) |
| Q4 vs. Q1 | 1.26 (0.62, 2.59) | 1.25 (0.56, 2.82) | 2.55 (1.20, 5.43) | 2.22 (0.95, 5.17) |
| P-trend | 0.48 | 0.52 | 0.008 | 0.04 |
| FDR critical P value | 0.015 | |||
| Tyrosine | ||||
| Q2 vs. Q1 (reference) | 1.82 (0.86, 3.84) | 1.27 (0.56, 2.90) | 0.86 (0.32, 2.29) | 0.66 (0.23, 1.94) |
| Q3 vs. Q1 | 2.23 (1.08, 4.60) | 2.00 (0.91, 4.37) | 1.60 (0.73, 3.50) | 1.16 (0.47, 2.83) |
| Q4 vs. Q1 | 2.34 (1.13, 4.85) | 1.72 (0.76, 3.86) | 3.75 (1.78, 7.89) | 2.78 (1.24, 7.21) |
| P-trend | 0.04 | 0.18 | <0.001 | 0.001 |
| FDR critical P value | 0.0025** | |||
| Taurine | ||||
| Q2 vs. Q1 (reference) | 0.50 (0.22, 1.12) | 0.42 (0.17, 1.06) | 1.52 (0.72, 3.23) | 1.50 (0.65, 3.44) |
| Q3 vs. Q1 | 0.93 (0.46, 1.89) | 0.89 (0.40, 1.98) | 1.43 (0.64, 3.15) | 1.57 (0.64, 3.86) |
| Q4 vs. Q1 | 1.41 (0.77, 2.58) | 1.36 (0.68, 2.71) | 1.65 (0.80, 3.40) | 1.51 (0.66, 3.46) |
| P-trend | 0.06 | 0.08 | 0.26 | 0.45 |
| Citrulline | ||||
| Q2 vs. Q1 (reference) | 0.71 (0.35, 1.42) | 0.75 (0.35, 1.61) | 0.82 (0.42, 1.63) | 0.70 (0.32, 1.53) |
| Q3 vs. Q1 | 0.86 (0.43, 1.74) | 0.86 (0.38, 1.95) | 0.70 (0.33, 1.48) | 0.52 (0.21, 1.25) |
| Q4 vs. Q1 | 1.18 (0.60, 2.30) | 1.33 (0.64, 2.78) | 1.17 (0.57, 2.40) | 1.13 (0.47, 2.73) |
| P-trend | 0.51 | 0.39 | 0.74 | 0.93 |
| Ornithine | ||||
| Q2 vs. Q1 (reference) | 0.89 (0.46, 1.73) | 0.66 (0.31, 1.40) | 0.58 (0.26, 1.29) | 0.60 (0.23, 1.54) |
| Q3 vs. Q1 | 1.04 (0.53, 2.06) | 0.89 (0.41, 1.95) | 1.76 (0.84, 3.68) | 1.70 (0.70, 4.13) |
| Q4 vs. Q1 | 1.30 (0.66, 2.56) | 1.04 (0.47, 2.28) | 1.21 (0.57, 2.56) | 1.02 (0.43, 2.44) |
| P-trend | 0.36 | 0.67 | 0.33 | 0.73 |
| Hydroxyproline | ||||
| Q2 vs. Q1 (reference) | 0.79 (0.39, 1.61) | 0.66 (0.30, 1.45) | 0.96 (0.46, 2.01) | 1.21 (0.49, 3.00) |
| Q3 vs. Q1 | 1.44 (0.71, 2.93) | 1.44 (0.64, 3.29) | 1.12 (0.56, 2.24) | 1.18 (0.53, 2.64) |
| Q4 vs. Q1 | 1.34 (0.66, 2.74) | 1.28 (0.56, 2.92) | 1.00 (0.48, 2.08) | 1.09 (0.46, 2.59) |
| P-trend | 0.32 | 0.36 | 0.90 | 0.91 |
| α-Aminobutyric acid | ||||
| Q2 vs. Q1 (reference) | 0.73 (0.37, 1.41) | 0.63 (0.30, 1.33) | 1.01 (0.47, 2.18) | 0.69 (0.28, 1.72) |
| Q3 vs. Q1 | 0.49 (0.23, 1.04) | 0.36 (0.15, 0.89) | 1.26 (0.62, 2.58) | 1.10 (0.48, 2.53) |
| Q4 vs. Q1 | 1.09 (0.56, 2.15) | 0.88 (0.41, 1.85) | 1.02 (0.48, 2.17) | 0.67 (0.28, 1.61) |
| P-trend | 0.75 | 0.78 | 0.87 | 0.58 |
| Cystine‡ | ||||
| T2 vs. T1 (reference) | 1.95 (0.88, 4.32) | 2.37 (0.97, 5.81) | 1.20 (0.52, 2.75) | 0.89 (0.34, 2.36) |
| T3 vs. T1 | 2.12 (0.81, 5.52) | 1.97 (0.66, 5.85) | 3.41 (1.21, 9.58) | 2.44 (0.79, 7.50) |
| P-trend | 0.12 | 0.20 | 0.02 | 0.12 |
| Grouped AAs | ||||
| Glutamine–to–glutamic acid ratio | ||||
| Q2 vs. Q1 (reference) | 0.61 (0.31, 1.20) | 0.57 (0.27,1.22) | 0.53 (0.24, 1.18) | 0.71 (0.28, 1.78) |
| Q3 vs. Q1 | 0.55 (0.25, 1.21) | 0.47 (0.19, 1.16) | 0.58 (0.16, 2.08) | 0.84 (0.20, 3.44) |
| Q4 vs. Q1 | 0.49 (0.20, 1.17) | 0.57 (0.21, 1.56) | 0.23 (0.05, 1.05) | 0.27 (0.05, 1.39) |
| P-trend | 0.17 | 0.43 | 0.02 | 0.03 |
| Summed BCAAs§ | ||||
| Q2 vs. Q1 (reference) | 1.14 (0.57, 2.30) | 1.10 (0.51, 2.38) | 1.39 (0.67, 2.88) | 1.41 (0.61, 3.26) |
| Q3 vs. Q1 | 1.33 (0.66, 2.69) | 1.09 (0.49, 2.40) | 0.63 (0.27, 1.48) | 0.46 (0.17, 1.23) |
| Q4 vs. Q1 | 1.33 (0.68, 2.59) | 1.15 (0.54, 2.47) | 2.23 (1.12, 4.42) | 1.89 (0.83, 4.28) |
| P-trend | 0.41 | 0.73 | 0.04 | 0.16 |
| Summed aromatic AAs‖ | ||||
| Q2 vs. Q1 (reference) | 2.97 (1.33, 6.66) | 2.32 (0.97, 5.57) | 2.66 (1.19, 3.52) | 3.46 (1.31, 9.13) |
| Q3 vs. Q1 | 3.35 (1.53, 7.30) | 3.33 (1.42, 7.81) | 1.33 (0.55, 3.23) | 1.12 (0.41, 3.11) |
| Q4 vs. Q1 | 2.31 (1.00, 5.34) | 1.83 (0.73, 4.62) | 3.04 (1.23, 7.52) | 3.30 (1.12, 9.71) |
| P-trend | 0.20 | 0.36 | 0.002 | 0.03 |
AA concentrations were measured as μmol/dL.
*
Models were adjusted for family history of diabetes (yes, no), nulliparity (yes, no), prepregnancy BMI (<25.0, 25.0–29.9, 30.0–34.9, and 35.0–44.9 kg/m2), maternal age (years), and GW at the time of blood draw.
†
Tests of linear trend were conducted by using the median value for each quartile and fitted as a continuous variable in the conditional logistic regression models. FDR was performed on the 24 individual plasma AAs. Individual AAs were ranked based on their P values for trend. Critical P value was calculated for individual AAs using the equation critical P value = (rank/total number of test) × FDR rate, with an FDR rate of 0.05 and compared with the P value. Significant AAs with P value < critical P value were considered statistically significant after the FDR adjustment and are marked with double asterisks.
‡
Tertiles instead of quartiles were modeled for cystine due to the large number of zero values (n = 96 at 10–14 GW and n = 129 at 15–26 GW).
§
BCAA: summed valine, leucine, and isoleucine.
‖
Aromatic AA: summed tyrosine and phenylalanine.