Table 4.
Results of log binomial regression and associated performance analyses examining the association between second trimester serum biomarker pattern and severe late onset preeclampsia
| Severe Late Onset Preeclampsia
|
|||||||
|---|---|---|---|---|---|---|---|
| n (%)
|
Rate (1/x)
|
RR (95% CI)a
|
Sensitivity (%)
|
Specificity (%)
|
PPV (%)
|
NPV (%)
|
|
| Sample (n = 136,139) | 889 (0.7) | 153.1 | -- | ||||
| No abnormal biomarkersb (n = 93,228) | 533 (0.6) | 174.9 | Reference | ||||
| Any Early Onset Preeclampsia ‘at risk’ Quad Biomarkerc (n = 21,290) | 231 (1.1) | 92.2 | 2.3 (1.6, 3.3)d | 26.0 | 84.4 | 1.1 | 99.4 |
| One ‘at risk’ biomarker | |||||||
| High AFP (n = 5,270) | 340 (0.8) | 135.1 | 1.3 (0.6, 2.9) | 4.5 | 96.1 | 0.8 | 99.4 |
| High hCG (n = 3,902) | 25 (0.6) | 156.1 | 1.6 (0.8, 3.5) | 2.8 | 97.1 | 0.6 | 99.3 |
| High INH (n = 3,845) | 52 (1.4) | 73.9 | 2.0 (1.0, 4.2) | 5.8 | 97.2 | 1.4 | 99.4 |
| Low uE3 (n = 4,471) | 33 (0.7) | 135.5 | 1.5 (0.7, 3.5) | 3.7 | 96.7 | 0.7 | 99.3 |
| Two ‘at risk’ biomarkers | |||||||
| High AFP and hCG (n = 470) | 8 (1.7) | 58.8 | 7.2 (2.3, 22.3)d | 0.9 | 99.7 | 1.7 | 99.4 |
| High AFP and INH (n = 424) | 11 (2.6) | 38.5 | 2.9 (0.4, 20.2) | 1.2 | 99.7 | 2.6 | 99.4 |
| High hCG and INH (n = 1,526) | 32 (2.1) | 50.9 | 3.3 (1.4, 8.1)e | 3.6 | 98.9 | 2.1 | 99.4 |
| High AFP, Low uE3 (n = 144) | 1 (0.7) | 144.0 | 1.2 (0.2, 8.6)f | 0.1 | 99.9 | 0.7 | 99.3 |
| High hCG, Low uE3 (n = 290) | 4 (1.4) | 72.5 | 5.6 (1.4, 22.4)g | 0.4 | 99.8 | 1.4 | 99.3 |
| High INH, Low uE3 (n = 235) | 7 (3.0) | 33.6 | 4.5 (0.6, 31.7) | 0.8 | 99.8 | 3.0 | 99.4 |
| Three or more ‘at risk’ biomarkers | |||||||
| High AFP, hCG, and INH (n = 403) | 7 (1.7) | 57.6 | 9.3 (3.0, 28.7)d | 0.8 | 99.7 | 1.7 | 99.4 |
| High AFP, hCG and Low uE3 (n = 24) | 1 (4.2) | 24.0 | 7.3 (1.1, 50.0)f,g | 0.1 | 100.0 | 4.2 | 99.3 |
| High AFP, INH and Low uE3 (n = 38) | 1 (2.6) | 38.0 | 5.2 (0.7, 35.5)f | 0.1 | 100.0 | 2.6 | 99.3 |
| High hCG, INH and Low uE3 (n = 188) | 6 (3.2) | 31.3 | 13.0 (4.3, 39.3)d | 0.7 | 99.9 | 3.2 | 99.4 |
| High AFP, hCG, INH and Low uE3 (n = 60) | 3 (5.0) | 20.0 | 44.8 (12.9, 155.1)d | 0.3 | 100.0 | 5.0 | 99.3 |
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 or 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
p < 0.01
Crude model (insufficient power to adjust for other factors listed in a).
p < 0.05