Pre-eclampsia is a multi-organ disorder of pregnancy characterised by new-onset hypertension (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg on two occasions at least 4 hours apart) at or after 20 weeks of gestation, with one or more features of organ dysfunction including proteinuria, renal impairment, thrombocytopaenia, liver dysfunction, pulmonary oedema, or uteroplacental dysfunction. It affects approximately 3-5% of pregnancies globally and is a leading cause of maternal and perinatal mortality. The Fetal Medicine Foundation (FMF) first-trimester screening algorithm combines maternal risk factors with three objective biomarkers — mean arterial pressure (MAP), uterine artery pulsatility index (UtA PI) measured by Doppler ultrasound, and placental growth factor (PlGF) in serum — to calculate an individualised risk of developing pre-eclampsia before 37 weeks (preterm PE) and before 34 weeks (early PE). A risk of 1:100 or greater for preterm pre-eclampsia at the 11-13+6 week combined screening visit identifies women who benefit from prophylactic low-dose aspirin (150 mg nightly from 11-14 weeks), which reduces preterm PE risk by approximately 62% in the high-risk group. PAPP-A (pregnancy-associated plasma protein-A) is an additional biochemical marker used in some algorithms. In established suspected pre-eclampsia, the sFlt-1/PlGF ratio is used to confirm or exclude the diagnosis and predict severity: a ratio below 38 has a high negative predictive value (rule-out); a ratio above 85 confirms significant disease.
FMF PE Risk = Combined algorithm: Maternal factors + MAP (mmHg) + UtA PI (Doppler) + PlGF (MoM) + PAPP-A (MoM); High risk ≥1:100 for preterm PE → aspirin 150mg nightly from 11-14 weeks; sFlt-1/PlGF ratio: <38=rule out, 38-85=intermediate, >85=confirm PE
- 1At the 11-13+6 week combined screening visit, collect maternal risk factors: age, BMI, ethnicity, smoking status, parity, conception method, family history of PE, personal history of PE, chronic hypertension, diabetes, SLE or antiphospholipid syndrome, and inter-pregnancy interval.
- 2Measure mean arterial pressure (MAP) bilaterally in both arms using a standardised protocol: MAP = diastolic BP + (systolic BP − diastolic BP)/3. Use the higher of the two arm measurements.
- 3Perform uterine artery Doppler at 11-13+6 weeks: measure the uterine artery pulsatility index (UtA PI) bilaterally by transvaginal or transabdominal Doppler. Impaired trophoblast invasion is reflected by elevated UtA PI (normal UtA PI <1.5).
- 4Measure serum PlGF (placental growth factor) — a placenta-derived angiogenic protein that is reduced in women who will develop pre-eclampsia. PlGF is converted to a multiple of the median (MoM) corrected for gestational age, weight, and ethnicity.
- 5Optional: measure PAPP-A, which is also reduced in pre-eclampsia. PAPP-A MoM is incorporated in extended algorithms.
- 6Enter all parameters into a validated Bayes theorem-based FMF algorithm (available via the FMF calculator or licensed software) to generate an individual risk for preterm PE (<37 weeks) and early PE (<34 weeks). A risk of ≥1:100 for preterm PE is the treatment threshold.
- 7Prescribe aspirin 150 mg orally at night from 11-14 weeks to all women at high risk (≥1:100 for preterm PE). Continue until 36 weeks gestation. Monitor blood pressure and urine protein at every antenatal visit.
No aspirin indicated; routine antenatal monitoring
Normal MAP, normal UtA PI, and adequate PlGF combine with a low-risk obstetric history to produce reassuringly low preterm PE risk. Standard antenatal monitoring is sufficient.
Aspirin 150mg nightly from 12 weeks; enhanced BP and urine monitoring from 20 weeks; USS growth surveillance
Multiple high-risk features (nulliparity, obesity, African ethnicity, elevated MAP, high UtA PI, low PlGF) produce a very high preterm PE risk. Early aspirin reduces this risk by ~62%.
High negative predictive value; outpatient management may be appropriate; recheck in 1 week
An sFlt-1/PlGF ratio below 38 has >99% negative predictive value for ruling out pre-eclampsia requiring delivery within 1 week, supporting safe continued outpatient management with close follow-up.
Admit; magnesium sulfate for seizure prophylaxis; consider delivery; liaise with neonatology
A ratio above 85 (or above 110 before 34 weeks in some guidelines) confirms significant pre-eclampsia and predicts high risk of adverse outcomes. Immediate assessment and likely delivery is indicated.
First-trimester combined PE screening at 11-13+6 weeks to identify women who benefit from prophylactic aspirin 150 mg., representing an important application area for the Preeclampsia Risk in professional and analytical contexts where accurate preeclampsia risk calculations directly support informed decision-making, strategic planning, and performance optimization
Confirming or ruling out pre-eclampsia in women presenting with hypertension or suspected PE symptoms using the sFlt-1/PlGF ratio., representing an important application area for the Preeclampsia Risk in professional and analytical contexts where accurate preeclampsia risk calculations directly support informed decision-making, strategic planning, and performance optimization
Guiding outpatient versus inpatient management decisions in women with borderline PE using the negative predictive value of sFlt-1/PlGF ratio <38., representing an important application area for the Preeclampsia Risk in professional and analytical contexts where accurate preeclampsia risk calculations directly support informed decision-making, strategic planning, and performance optimization
Academic researchers and university faculty use the Preeclampsia Risk for empirical studies, thesis research, and peer-reviewed publications requiring rigorous quantitative preeclampsia risk analysis across controlled experimental conditions and comparative studies
Health economics: targeted aspirin prescribing to high-risk women identified by biomarker screening is cost-effective compared to universal or risk factor-only based prescribing., representing an important application area for the Preeclampsia Risk in professional and analytical contexts where accurate preeclampsia risk calculations directly support informed decision-making, strategic planning, and performance optimization
Chronic Hypertension
{'title': 'Chronic Hypertension', 'body': 'Women with chronic hypertension are at significantly elevated risk of superimposed pre-eclampsia (incidence approximately 25%). They should receive aspirin from 12 weeks regardless of first-trimester screening result. Differentiating superimposed PE from worsening chronic hypertension can be challenging; the sFlt-1/PlGF ratio is particularly useful in this context.'}
Antiphospholipid Syndrome
In the Preeclampsia Risk, this scenario requires additional caution when interpreting preeclampsia risk results. The standard formula may not fully account for all factors present in this edge case, and supplementary analysis or expert consultation may be warranted. Professional best practice involves documenting assumptions, running sensitivity analyses, and cross-referencing results with alternative methods when preeclampsia risk calculations fall into non-standard territory.
Twin Pregnancy
{'title': 'Twin Pregnancy', 'body': 'Multiple pregnancy independently increases PE risk, particularly in monochorionic twins with twin-to-twin transfusion syndrome. First-trimester screening algorithms for twins differ from singleton algorithms. PlGF MoM values are lower in twin pregnancies, and different thresholds apply. Many guidelines recommend aspirin for all twin pregnancies regardless of screening result.'}
IVF Pregnancy
{'title': 'IVF Pregnancy', 'body': 'IVF pregnancies have elevated PE risk, particularly those conceived with donated oocytes (egg donation), where immunological mismatch between donor genetics and maternal tolerance is thought to increase susceptibility. Aspirin is generally recommended from 12 weeks for all egg donation pregnancies. PAPP-A may be artifactually elevated in IVF pregnancies, reducing its discriminatory value.'}
| Ratio | Interpretation | Clinical Action |
|---|---|---|
| <38 | Rules out PE (high NPV for 1 week) | Outpatient management; recheck in 1 week |
| 38-85 | Intermediate — monitor closely | Admit or intensify monitoring; twice-weekly recheck |
| >85 (>34 weeks) | Confirms significant PE | Admit; consider delivery; magnesium sulfate |
| >110 (<34 weeks) | Confirms significant PE (preterm threshold) | Specialist management; corticosteroids; delivery planning |
What is the ASPRE trial and what did it show?
The ASPRE (Aspirin for Evidence-Based Preeclampsia Prevention) trial, published in NEJM in 2017, randomised high-risk women identified by FMF first-trimester screening to aspirin 150 mg nightly or placebo from 11-14 weeks. Aspirin reduced preterm pre-eclampsia (<37 weeks) by 62% in the high-risk group. This landmark trial established first-trimester screening-guided aspirin as the standard of care in many countries.
What dose of aspirin is recommended and when should it be taken?
The evidence-based dose is 150 mg (or 100-162 mg where 150 mg is unavailable) taken at night (bedtime). Night-time dosing exploits the nocturnal peak in thromboxane production and maximises trophoblast invasion during the night. Aspirin should be started before 16 weeks (ideally 11-14 weeks) and continued until 36 weeks gestation.
What is PlGF and why is it reduced in pre-eclampsia?
Placental growth factor (PlGF) is a member of the VEGF family produced by trophoblast cells and is essential for normal placentation. In women who will develop pre-eclampsia, inadequate trophoblast invasion leads to placental ischaemia, which reduces PlGF secretion and stimulates excess production of sFlt-1 (a decoy receptor that sequesters PlGF and VEGF). Low PlGF in the first trimester reflects early impaired placentation.
What is the sFlt-1/PlGF ratio used for?
The sFlt-1/PlGF ratio is used to confirm or rule out pre-eclampsia in women who present with suspected PE (hypertension, proteinuria, or symptoms) after 20 weeks. A ratio <38 rules out pre-eclampsia requiring delivery in the next week with high sensitivity. A ratio >85 (or >110 before 34 weeks in some thresholds) confirms significant disease requiring escalated management.
Does aspirin prevent all pre-eclampsia?
No. Aspirin is highly effective for preventing preterm pre-eclampsia (<37 weeks) in the identified high-risk group (62% relative risk reduction). Its effect on term pre-eclampsia is much smaller. It does not eliminate risk entirely — women on prophylactic aspirin still require blood pressure monitoring and proteinuria testing at every antenatal visit.
Who should receive first-trimester PE screening?
FMF combined first-trimester PE screening with biomarkers is recommended for all pregnant women at 11-13+6 weeks. This is the approach taken in the UK, many European countries, and increasingly internationally. In contrast, NICE UK currently recommends risk factor-based assessment rather than biomarker-based screening, though this is under active review. This is particularly important in the context of preeclampsia risk calculations, where accuracy directly impacts decision-making. Professionals across multiple industries rely on precise preeclampsia risk computations to validate assumptions, optimize processes, and ensure compliance with applicable standards. Understanding the underlying methodology helps users interpret results correctly and identify when additional analysis may be warranted.
What are the risk factors for pre-eclampsia?
High-risk factors (any one triggers aspirin in NICE guidelines): previous PE, chronic hypertension, diabetes, kidney disease, autoimmune disease (SLE, antiphospholipid syndrome). Moderate-risk factors (two or more needed): first pregnancy, age ≥40, BMI ≥35, family history of PE, multi-fetal pregnancy, inter-pregnancy interval >10 years. This is particularly important in the context of preeclampsia risk calculations, where accuracy directly impacts decision-making. Professionals across multiple industries rely on precise preeclampsia risk computations to validate assumptions, optimize processes, and ensure compliance with applicable standards. Understanding the underlying methodology helps users interpret results correctly and identify when additional analysis may be warranted.
Can pre-eclampsia be managed at home?
Mild pre-eclampsia with well-controlled BP, no severe features, and an sFlt-1/PlGF ratio below 38 may be managed on an outpatient basis with close monitoring (twice-weekly BP checks, weekly blood tests, fetal growth surveillance). Severe features (systolic BP ≥160, platelet count <100, creatinine >97, severe symptoms) require admission and often delivery.
Pro Tip
In first-trimester PE screening, PlGF and UtA PI are the most powerful discriminators for preterm PE. A PlGF MoM below 0.4 combined with elevated UtA PI above 2.0 should heighten clinical suspicion even if the algorithm-generated risk falls just below the 1:100 threshold — consider prescribing aspirin based on clinical gestalt in borderline cases.
Did you know?
The link between aspirin and pre-eclampsia was first suggested in 1985 by John Crandon and colleagues, who observed that women regularly taking low-dose aspirin for other medical conditions appeared to have lower rates of hypertensive complications. The subsequent decades of randomised trials, culminating in the ASPRE trial, confirmed that early high-dose aspirin reduces preterm PE by over 60% in high-risk women — making first-trimester risk stratification one of the most impactful preventive interventions in modern obstetrics.
References
- ›Rolnik DL et al. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia (ASPRE). NEJM 2017.
- ›Zeisler H et al. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. NEJM 2016.
- ›NICE Guideline NG133 — Hypertension in pregnancy: diagnosis and management. 2019 (updated 2023).
- ›O'Gorman N et al. Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks' gestation. Am J Obstet Gynecol 2016.
- ›ISSHP Classification, Diagnosis, and Management of Hypertensive Disorders of Pregnancy. Pregnancy Hypertens 2018.