Table 2.
Risk of Oral Clefts by Type of Cleft and Quartiles of Maternal Biomarkers of Folate-Dependent One-Carbon Metabolism
| No. of mothersa
|
Adjustedb odds ratios and 95% confidence intervals
|
Combined
|
||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Controls | Isolated
|
Multiple congenital anomalies
|
Isolated
|
Multiple congenital anomalies
|
||||||
| CL/P | CP | CL/P | CP | CL/P | CP | CL/P | CP | CL/P = CP | ||
| Quartile of plasma folate (nmol/L) | ||||||||||
| Quartile 1 (≤36.7) | 99 | 67 | 30 | 8 | 4 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
| Quartile 2 (36.7–53.6) | 102 | 61 | 21 | 7 | 10 | 0.86 (0.54–1.36) | 0.67 (0.35–1.27) | 0.74 (0.24–2.24) | 1.91 (0.54–6.76) | 0.83 (0.56–1.25) |
| Quartile 3 (53.7–74.0) | 118 | 50 | 19 | 3 | 4 | 0.66 (0.42–1.05) | 0.54 (0.28–1.03) | 0.34 (0.09–1.33) | 0.84 (0.20–3.54) | 0.59 (0.39–0.89) |
| Quartile 4 (≥74.1) | 149 | 34 | 17 | 7 | 5 | 0.34 (0.21–0.56) | 0.35 (0.18–0.68) | 0.63 (0.21–1.85) | 0.45 (0.09–2.14) | 0.35 (0.23–0.53) |
| p-trend | p < 0.001 | p = 0.002 | p = 0.278 | p = 0.143 | p < 0.001 | |||||
| Quartile of erythrocyte folate (nmol/L) | ||||||||||
| Quartile 1 (≤1488) | 98 | 56 | 28 | 8 | 7 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
| Quartile 2 (1489–1878) | 112 | 53 | 25 | 7 | 9 | 0.83 (0.52–1.33) | 0.78 (0.42–1.46) | 0.92 (0.30–2.79) | 1.06 (0.33–3.36) | 0.82 (0.55–1.23) |
| Quartile 3 (1879–2486) | 132 | 50 | 17 | 4 | 5 | 0.65 (0.41–1.04) | 0.46 (0.23–0.90) | 0.48 (0.13–1.72) | 0.62 (0.18–2.13) | 0.56 (0.38–0.85) |
| Quartile 4 (≥2487) | 123 | 52 | 17 | 6 | 1 | 0.78 (0.48–1.25) | 0.49 (0.24–0.97) | 0.81 (0.25–2.63) | 0.12 (0.01–1.07) | 0.64 (0.42–0.97) |
| p-trend | p = 0.20 | p = 0.01 | p = 0.51 | p = 0.03 | p = 0.01 | |||||
| Quartile of Plasma pyridoxal-5′-phosphate (nmol/L) | ||||||||||
| Quartile 1 (≤26.0) | 112 | 60 | 21 | 12 | 5 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
| Quartile 2 (26.1–45.0) | 116 | 48 | 25 | 4 | 2 | 0.79 (0.50–1.27) | 1.23 (0.64–2.35) | 1.27 (0.44–3.63) | 0.39 (0.19–1.29) | 0.41 (0.76–2.17) |
| Quartile 3 (45.1–78.0) | 114 | 48 | 27 | 6 | 10 | 0.77 (0.48–1.24) | 1.26 (0.66–2.43) | 0.74 (0.22–2.47) | 0.57 (0.19–1.65) | 1.29 (0.38–4.35) |
| Quartile 4 (≥78.1) | 126 | 56 | 14 | 3 | 6 | 0.83 (0.52–1.31) | 0.57 (0.27–1.19) | 0.81 (0.26–2.53) | 0.25 (0.07–0.95) | 0.80 (0.22–2.94) |
| p-trend | p = 0.43 | p = 0.19 | p = 0.049 | p = 0.92 | p = 0.12 | |||||
| Quartile of plasma homocysteine (μmol/L) | ||||||||||
| Quartile 1 (≤3.2) | 114 | 49 | 22 | 5 | 9 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
| Quartile 2 (3.21–4.0) | 107 | 42 | 20 | 10 | 4 | 0.95 (0.58–1.56) | 1.05 (0.54–2.06) | 2.11 (0.67–6.68) | 0.58 (0.16–2.03) | 1.01 (0.67–1.54) |
| Quartile 3 (4.1–5.0) | 114 | 53 | 20 | 3 | 5 | 1.19 (0.74–1.93) | 1.03 (0.53–2.03) | 0.73 (0.17–3.22) | 0.43 (0.11–1.73) | 1.04 (0.69–1.57) |
| Quartile 4 (≥5.1) | 91 | 55 | 21 | 6 | 3 | 1.43 (0.88–2.33) | 1.30 (0.66–2.55) | 1.56 (0.45–5.38) | 0.44 (0.11–1.75) | 1.33 (0.87–2.03) |
| p-trend | p = 0.10 | p = 0.49 | p = 0.18 | p = 0.88 | p = 0.21 | |||||
All cases with known genetic syndromes or chromosomal abnormalities were excluded from the analyses.
a
The number of assays completed varies slightly because of limited availability of some sample aliquots.
b
Adjusted for maternal age, education, alcohol use, smoking, multivitamin use, and interval between delivery of the index child and maternal blood collection in logistic regression models.
CL/P, cleft lip with or without cleft palate; CP, cleft palate; I, isolated oral cleft (no other birth defects); M, with multiple birth defects.