Table 3.
Results of log binomial regression and associated performance analyses examining the association between second trimester serum biomarker pattern and severe early onset preeclampsia
| Severe Early Onset Preeclampsia
|
|||||||
|---|---|---|---|---|---|---|---|
| n (%)
|
Rate (1/x)
|
RR (95% CI)a
|
Sensitivity (%)
|
Specificity (%)
|
PPV (%)
|
NPV (%)
|
|
| Sample (n = 136,139) | 319 (0.2) | 426.8 | -- | ||||
| No abnormal biomarkersb (n = 93,228) | 133 (0.1) | 701.0 | Reference | ||||
| Any Early Onset Preeclampsia ‘at risk’ Quad Biomarkerc (n = 21,290) | 160 (0.8) | 133.1 | 4.9 (3.3, 7.3)d | 50.2 | 84.4 | 0.8 | 99.9 |
| One ‘at risk’ biomarker | |||||||
| High AFP (n = 5,270) | 27 (0.5) | 195.2 | 1.7 (0.6, 4.7) | 8.5 | 96.1 | 0.5 | 99.8 |
| High hCG (n = 3,902) | 10 (0.3) | 390.2 | 2.3 (1.0, 5.5) | 3.1 | 97.1 | 0.3 | 99.8 |
| High INH (n = 3,845) | 29 (0.8) | 132.6 | 4.9 (2.5, 9.7)d | 9.1 | 97.2 | 0.8 | 99.8 |
| Low uE3 (n = 4,471) | 14 (0.3) | 319.4 | 0.4 (0.1, 3.2) | 4.4 | 96.7 | 0.3 | 99.8 |
| Two ‘at risk’ biomarkers | |||||||
| High AFP and hCG (n = 470) | 2 (0.4) | 235.0 | 6.5 (1.6, 26.9)e | 0.6 | 99.7 | 0.4 | 99.8 |
| High AFP and INH (n = 424) | 10 (2.4) | 42.4 | 25.0 (10.8, 57.9)d | 3.1 | 99.7 | 2.4 | 99.8 |
| High hCG and INH (n = 1,526) | 20 (1.3) | 76.3 | 10.0 (4.9, 20.3)d | 6.3 | 98.9 | 1.3 | 99.8 |
| High AFP, Low uE3 (n = 144) | 1 (0.7) | 144.0 | 12.8 (1.8, 90.5)e | 0.3 | 99.9 | 0.7 | 99.8 |
| High hCG, Low uE3 (n = 290) | 0 (0.0) | -- | -- | -- | -- | -- | -- |
| High INH, Low uE3 (n = 235) | 7 (3.0) | 33.6 | 21.9 (7.0, 68.8)d | 2.2 | 99.8 | 3.0 | 99.8 |
| Three or more ‘at risk’ biomarkers | |||||||
| High AFP, hCG, and INH (n = 403) | 28 (7.0) | 14.4 | 37.6 (17.4, 81.3)d | 8.8 | 99.7 | 6.9 | 99.8 |
| High AFP, hCG and Low uE3 (n = 24) | 0 (0.0) | -- | -- | -- | -- | -- | -- |
| High AFP, INH and Low uE3 (n = 38) | 4 (10.5) | 9.5 | 36.9 (5.6, 244.3)d | 1.3 | 100.0 | 10.5 | 99.8 |
| High hCG, INH and Low uE3 (n = 188) | 6 (3.2) | 31.3 | 27.4 (8.8, 85.5)d | 1.9 | 99.9 | 3.2 | 99.8 |
| High AFP, hCG, INH and Low uE3 (n = 60) | 2 (3.3) | 30.0 | 79.0 (21.3, 293.4)d | 0.6 | 100.0 | 3.3 | 99.8 |
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.
Binomial analyses included black race/ethnicity 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
p < 0.01