Table 5.
Results of log binomial regression and associated performance analyses examining the association between second trimester serum biomarker pattern and severe preeclampsia
| Severe Preeclampsia
|
|||||||
|---|---|---|---|---|---|---|---|
| n (%)
|
Rate (1/x)
|
RR (95% CI)a
|
Sensitivity (%)
|
Specificity (%)
|
PPV (%)
|
NPV (%)
|
|
| Sample (n = 136,139) | 1,208 (0.9) | 112.7 | -- | ||||
| No abnormal biomarkersb (n = 93,228) | 666 (0.7) | 140.0 | Reference | ||||
| Any Early Onset Preeclampsia ‘at risk’ Quad Biomarkerc (n = 21,290) | 391 (1.8) | 54.5 | 2.7 (2.0, 3.6)d | 32.4 | 84.5 | 1.8 | 99.3 |
| One ‘at risk’ biomarker | |||||||
| High AFP (n = 5,270) | 67 (1.3) | 78.7 | 1.5 (0.7, 2.9) | 5.5 | 96.1 | 1.3 | 99.1 |
| High hCG (n = 3,902) | 35 (0.9) | 111.5 | 1.6 (0.8, 3.2) | 2.9 | 97.1 | 0.9 | 99.1 |
| High INH (n = 3,845) | 81 (2.1) | 47.5 | 2.7 (1.6, 4.7)d | 6.7 | 97.2 | 2.1 | 99.1 |
| Low uE3 (n = 4,471) | 47 (1.1) | 95.1 | 1.2 (0.5, 2.7) | 3.9 | 96.7 | 1.1 | 99.1 |
| Two ‘at risk’ biomarkers | |||||||
| High AFP and hCG (n = 470) | 10 (2.1) | 47.0 | 7.2 (2.7, 19.1)d | 0.8 | 99.7 | 2.1 | 99.1 |
| High AFP and INH (n = 424) | 21 (5.0) | 20.2 | 10.4 (4.4, 24.7)d | 1.7 | 99.7 | 5.0 | 99.1 |
| High hCG and INH (n = 1,526) | 52 (3.4) | 29.3 | 5.0 (2.7, 9.4)d | 4.3 | 98.9 | 3.4 | 99.1 |
| High AFP, Low uE3 (n = 144) | 2 (1.4) | 72.0 | 1.9 (0.5, 7.7)e | 0.2 | 99.9 | 1.4 | 99.1 |
| High hCG, Low uE3 (n = 290) | 4 (1.4) | 72.5 | 4.3 (1.1, 17.1)f | 0.3 | 99.8 | 1.4 | 99.1 |
| High INH, Low uE3 (n = 235) | 14 (6.0) | 16.8 | 3.5 (0.5, 23.2) | 1.2 | 99.8 | 6.0 | 99.1 |
| Three or more ‘at risk’ biomarkers | |||||||
| High AFP, hCG, and INH (n = 403) | 35 (8.7) | 11.5 | 15.8 (7.7, 32.5)d | 2.9 | 99.7 | 8.7 | 99.1 |
| High AFP, hCG and Low uE3 (n = 24) | 1 (4.2) | 24.0 | 5.8 (0.9, 39.8)e | 0.1 | 100.0 | 4.2 | 99.1 |
| High AFP, INH and Low uE3 (n = 38) | 5 (13.2) | 7.6 | 18.4 (8.1, 41.8)d,e | 0.4 | 100.0 | 13.2 | 99.1 |
| High hCG, INH and Low uE3 (n = 188) | 12 (6.4) | 15.7 | 13.0 (5.0, 33.7)d | 1.0 | 99.9 | 6.4 | 99.1 |
| High AFP, hCG, INH and Low uE3 (n = 60) | 5 (8.3) | 12.0 | 34.2 (9.9, 117.9)d | 0.4 | 100.0 | 8.3 | 99.1 |
PPV, positive predictive value; NPV, negative predictive value; AFP, alpha-fetoprotein; hCG, human choronic gonatotropin; uE3, unconjugated estriol; INH, inhibin-A; “High” biomarker = Multiple of the Median (MoM) ≥ 95th percentile; “Isolated” biomarker = all ‘at risk’other biomarker MoMs > 5th and < 95th percentile.
Unless otherwise indicated, binomial analyses included Hispanic and black race/ethnicity, maternal age ≤ 17 years, maternal age ≥ 35 years, weight at testing > 95th percentile and any diabetes (all dichotomized as yes versus no).
AFP, hCG, uE3 and INH MoMs all between the 5th and 95th percentile (AFP > 0.60, < 1.74; hCG > 0.42, < 2.35; uE3 >0.61, < 1.49; INH > 0.48, < 1.95). 21,621 pregnancies were not included who had neither ‘at risk’ biomarkers nor ‘no abnormal’ biomarkers.
Any high biomarker and/or low uE3 (all biomarkers found to be predictive in Table 2)
p < 0.001
Crude model (insufficient power to adjust for other factors listed in a).
p < 0.05