A New Model for Screening for Late-Onset Preeclampsia in the Third Trimester
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Patients
2.3. Study Variables
2.4. Procedure
2.5. Risk Assessment of Late-Onset Preeclampsia
- Maternal factors: date of birth (dd-mm-yyyy), ethnicity (White, Black, South Asian, East Asian or Mixed), height (cm), weight (kg), currently smoking (Yes/No), conception method (spontaneous, ovulation drugs or in vitro fertilization), family history of PE (Yes/No), and parity (Nulliparous or Parous); for multiparous women, additional data from the previous pregnancy were recorded, including history of preeclampsia (Yes/No), date of delivery (dd-mm-yyyy), and gestational age at delivery (weeks and days). Systemic conditions were also documented, including pregestational diabetes (Yes, type I or II)/No), chronic hypertension (Yes/No), personal history of PE (Yes/No), systemic lupus erythematosus (Yes/No), and antiphospholipid syndrome (Yes/No).
- Biophysical parameters: right uterine artery pulsatility index (PI), left uterine artery PI, MAP (mmHg), and date of measurement of biophysical parameters.
- Biochemical parameters: sFlt-1 (pg/mL) in the third trimester, PlGF (pg/mL) in the third trimester, and data from biochemical parameter measurements.
2.6. Diagnostic Criteria
2.7. Statistical Analysis
3. Results
3.1. The Characteristics of the Study Population
3.2. The Predictive Performance of the Fetal Medicine Foundation’s Third-Trimester Model for Late-Onset Preeclampsia
External Validation of the Fetal Medicine Foundation’s Third-Trimester Model in Our Population of Pregnant Women
3.3. Improvement of the Fetal Medicine Foundation’s Third-Trimester Model
3.3.1. Modification of the Cutoffs for Our Population of Pregnant Women
3.3.2. The Incorporation of Additional Variables Not Included in the Original Model
3.4. The Development of Our Own Predictive Model
- SD: Systemic disease (pregestational diabetes, chronic hypertension, a personal history of PE and/or FGR, antiphospholipid syndrome, and/or kidney disease) (0 = no; 1 = yes);
- GD: Gestational diabetes (0 = no; 1 = yes);
- ART: Assisted reproductive technology (0 = no; 1 = yes);
- GWG: Gestational weight gain (kg);
- RATIO: The sFlt-1/PlGF ratio in the third trimester;
- DBP: Diastolic blood pressure (mmHg) in the third trimester;
- AGE: Maternal age (years);
- BMI: Body mass index (kg/m2).
Predictive Indicators of Our Model According to Different Cutoffs
4. Discussion
4.1. A Comparative Analysis According to the Development of Late Preeclampsia and Its Absence
4.2. The Predictive Performance of the Fetal Medicine Foundation’s Third-Trimester Model for Late-Onset Preeclampsia
External Validation of the Fetal Medicine Foundation’s Third-Trimester Model in Our Population of Pregnant Women
4.3. Improvement of the Fetal Medicine Foundation’s Third-Trimester Model
4.3.1. Modification of the Cutoffs for Our Population of Pregnant Women
4.3.2. The Incorporation of Additional Variables Not Included in the Original Model
4.4. The Development of Our Own Predictive Model
Predictive Indicators of Our Model According to Different Cutoffs
4.5. Strengths and Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AIC | Akaike Information Criterion |
ASA | aspirin |
AUC | area under the curve |
BMI | body mass index |
CI | confidence interval |
CIs | confidence intervals |
DBP | diastolic blood pressure |
DR | detection rate |
FGR | fetal growth restriction |
FMF | Fetal Medicine Foundation |
FPR | false positive rate |
ISSHP | International Society for the Study of Hypertension in Pregnancy |
LR− | negative likelihood ratio |
LR+ | positive likelihood ratio |
MAP | mean arterial pressure |
MoM | multiples of the median |
NPV | negative predictive value |
PE | preeclampsia |
PI | pulsatility index |
PlGF | placental growth factor |
PPV | positive predictive value |
ROC | receiver operating characteristic |
SBP | systolic blood pressure |
Se | sensitivity |
SEGO | Spanish Society of Gynecology and Obstetrics |
sFlt-1 | soluble fms-like tyrosine kinase-1 |
Sp | specificity |
UtA-PI | uterine artery pulsatility index |
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No Late PE (n= 1534) | Late PE (n= 46) | p-Value | |
---|---|---|---|
Maternal characteristics | |||
Demographic and epidemiological data | |||
Maternal age in years | 32.01 ± 5.83 | 31.78 ± 6.52 | 0.838 |
Racial origin | |||
Caucasian | 1497 (97.59) | 46 (100) | 0.624 |
Other | 37 (2.41) | 0 (0.0) | |
Maternal body mass index, kg/m2 | 25.20 ± 4.87 | 28.35 ± 6.75 | 0.002 |
Smoking | 171 (11.15) | 3 (6.52) | 0.472 |
Family history of PE | 40 (2.61) | 3 (6.52) | 0.127 |
Parity (number of previous deliveries) | |||
None | 790 (51.50) | 33 (71.74) | 0.032 |
One | 521 (33.96) | 12 (26.09) | |
Two | 163 (10.63) | 1 (2.17) | |
Three or more | 60 (3.91) | 0 (0) | |
Maternal comorbidities | |||
Chronic hypertension | 29 (1.89) | 2 (4.34) | 0.227 |
Previous PE and/or FGR | 39 (2.54) | 6 (13.04) | 0.002 |
Systemic disease | 77 (5.02) | 9 (19.57) | 0.001 |
Clinical pregnancy data | |||
Assisted reproduction | |||
NO | 1447 (94.33) | 39 (84.78) | 0.017 |
SI | 87 (5.67) | 7 (15.22) | |
Gestational weight gain (kg) | 11.31 ± 3.87 | 11.97 ± 6.45 | 0.843 |
Aspirin intake | 39 (2.54) | 9 (19.57) | <0.001 |
Biophysical markers | |||
SBP (mmHg) | |||
1st T | 117.51 ± 11.50 | 123.61 ± 10.89 | 0.001 |
2nd T | 112.52 ± 9.47 | 124.89 ± 9.00 | <0.001 |
3rd T | 116.65 ± 11.01 | 132.87 ± 14.76 | <0.001 |
DBP (mmHg) | |||
1st T | 73.93 ± 8.70 | 78.52 ± 8.89 | 0.001 |
2nd T | 71.84 ± 8.48 | 77.63 ± 6.42 | <0.001 |
3rd T | 75.60 ± 7.94 | 87.30 ± 8.37 | <0.001 |
MAP (mmHg) | |||
1st T | 88.46 ± 8.52 | 93.55 ± 8.27 | <0.001 |
2nd T | 85.40 ± 7.74 | 93.38 ± 6.46 | <0.001 |
3rd T | 89.28 ± 7.93 | 102.49 ± 9.46 | <0.001 |
Uterine artery PI median | |||
1st T | 1.38 ± 0.49 | 1.47 ± 0.52 | 0.284 |
2nd T | 0.93 ± 0.23 | 1.08 ± 0.38 | 0.004 |
3rd T | 0.69 ± 0.18 | 0.80 ± 0.28 | 0.011 |
Biochemical markers | |||
PlGF (pg/mL) 1st T | 33.39 ± 16.01 | 25.54 ± 10.40 | <0.001 |
sFlt-1 (pg/mL) 3rd T | 1333.68 ± 1444.25 | 3630.76 ± 5379.09 | <0.001 |
PlGF (pg/mL) 3rd T | 437.54 ± 344.07 | 156.05 ± 95.06 | <0.001 |
sFlt-1/PlGF 3rd T | 9.54 ± 13.69 | 53.70 ± 64.55 | <0.001 |
Obstetric outcomes | |||
Gestational diabetes | 152 (9.91) | 14 (30.43) | <0.001 |
FGR | 33 (2.15) | 5 (10.87) | 0.004 |
Perinatal outcomes | |||
Birth weight (g) | 3304.40 ± 420.58 | 2973.15 ± 575.75 | <0.001 |
Low birth weight | 320 (20.86) | 21 (45.65) | <0.001 |
Birth weight percentile | 34.52 ± 26.31 | 28.15 ± 29.27 | 0.015 |
Estimate and 95% CI | |
---|---|
Sensitivity (%) | 32.6 (19.1–46.1) |
Specificity (%) | 98.6 (98.0–99.2) |
PPV (%) | 41.7 (25.6–57.8) |
NPV (%) | 98.0 (97.3–98.7) |
FPR (%) | 1.3 |
Positive LR | 23.286 (12.855–42.181) |
Negative LR | 0.684 (0.559–0.836) |
Cutoff | ≥1/100 | ≥1/150 | ≥1/200 |
---|---|---|---|
Sensitivity (%) | 60.9 (46.8–75.0) | 60.9 (46.8–75.0) | 63.0 (49.0–77.0) |
Specificity (%) | 94.6 (93.5–95.7) | 92.8 (91.5–94.1) | 91.4 (90.0–92.8) |
PPV (%) | 25.2 (17.1–33.3) | 20.1 (13.4–26.8) | 18.0 (12.1–23.9) |
NPV (%) | 98.8 (98.2–99.4) | 98.8 (98.2–99.4) | 98.8 (98.2–99.4) |
FPR (%) | 5.3 | 7.0 | 8.3 |
Positive LR | 11.278 (8.254–15.410) | 8.458 (6.311–11.336) | 3.326 (5.565–9.645) |
Negative LR | 0.413 (0.288–0.592) | 0.421 (0.293–0.604) | 0.405 (0.278–0.591) |
Crude Adjustment | Multivariate Adjustment with ASA | |
---|---|---|
AUC | 0.871 (0.813–0.929) | 0.872 (0.813–0.930) |
Cutoff | Se (%) | Sp (%) | FPR (%) | PPV (%) | PNV (%) | LR+ | LR− |
---|---|---|---|---|---|---|---|
0.05 | 76.1 | 91.6 | 8.2 | 21.3 | 99.2 | 9.0 | 0.261 |
0.10 | 69.6 | 96.0 | 3.9 | 34.0 | 99.1 | 17.4 | 0.317 |
0.15 | 54.3 | 97.5 | 2.5 | 39.1 | 98.6 | 21.7 | 0.469 |
0.20 | 45.7 | 98.4 | 1.5 | 46.7 | 98.4 | 28.5 | 0.552 |
0.25 | 45.7 | 98.7 | 1.3 | 51.2 | 98.4 | 35.1 | 0.550 |
0.30 | 43.5 | 99.2 | 0.8 | 60.6 | 98.3 | 54.3 | 0.570 |
0.35 | 41.3 | 99.5 | 0.5 | 70.4 | 98.3 | 82.6 | 0.590 |
0.40 | 39.1 | 99.5 | 0.4 | 72.0 | 98.2 | 78.2 | 0.612 |
0.45 | 39.1 | 99.6 | 0.4 | 75.0 | 98.2 | 97.7 | 0.611 |
0.50 | 37.0 | 99.7 | 0.3 | 81.0 | 98.1 | 123 | 0.632 |
0.55 | 34.8 | 99.9 | 0.1 | 88.9 | 98.1 | 348 | 0.653 |
0.60 | 30.4 | 99.9 | 0.1 | 87.5 | 98.0 | 304 | 0.697 |
0.65 | 26.1 | 99.9 | 0.1 | 92.3 | 97.8 | 261 | 0.740 |
0.70 | 23.9 | 99.9 | 0.1 | 91.7 | 97.8 | 239 | 0.762 |
0.75 | 21.7 | 99.9 | 0.1 | 90.9 | 97.7 | 217 | 0.784 |
0.80 | 17.4 | 99.9 | 0.1 | 88.9 | 97.6 | 174 | 0.827 |
0.85 | 13.0 | 99.9 | 0.1 | 85.7 | 97.5 | 130 | 0.871 |
0.90 | 13.0 | 99.9 | 0.1 | 85.7 | 97.5 | 130 | 0.871 |
0.95 | 10.9 | 99.9 | 0.1 | 83.3 | 97.4 | 109 | 0.892 |
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Jiménez-García, C.; Palacios-Marqués, A.M.; Quesada-Rico, J.A.; Baviera-Royo, P.; Pérez-Pascual, E.; Baldó-Estela, I.; García-Sousa, V. A New Model for Screening for Late-Onset Preeclampsia in the Third Trimester. J. Clin. Med. 2025, 14, 7185. https://doi.org/10.3390/jcm14207185
Jiménez-García C, Palacios-Marqués AM, Quesada-Rico JA, Baviera-Royo P, Pérez-Pascual E, Baldó-Estela I, García-Sousa V. A New Model for Screening for Late-Onset Preeclampsia in the Third Trimester. Journal of Clinical Medicine. 2025; 14(20):7185. https://doi.org/10.3390/jcm14207185
Chicago/Turabian StyleJiménez-García, Clara, Ana María Palacios-Marqués, José Antonio Quesada-Rico, Paloma Baviera-Royo, Encarnación Pérez-Pascual, Inmaculada Baldó-Estela, and Víctor García-Sousa. 2025. "A New Model for Screening for Late-Onset Preeclampsia in the Third Trimester" Journal of Clinical Medicine 14, no. 20: 7185. https://doi.org/10.3390/jcm14207185
APA StyleJiménez-García, C., Palacios-Marqués, A. M., Quesada-Rico, J. A., Baviera-Royo, P., Pérez-Pascual, E., Baldó-Estela, I., & García-Sousa, V. (2025). A New Model for Screening for Late-Onset Preeclampsia in the Third Trimester. Journal of Clinical Medicine, 14(20), 7185. https://doi.org/10.3390/jcm14207185