Background
Methods
Population
Predictors
Candidate predictor | Women with early onset pre-eclampsia
n = 954 Mean (SD) or n (%) | Number of women with missing data
n (%) |
---|---|---|
Maternal characteristics | ||
Maternal age (years), mean (SD) | 30.2 (6.1) | 2 (0.2%) |
Gestational age at diagnosis (weeks), mean (SD) | 30.5 (2.9) | – |
Number of fetuses in pregnancya
| ||
Singleton | 866 (91%) | |
Twins | 83 (9%) | – |
Triplets | 5 (1%) | |
Parity | – | |
0 | 551 (58%) | |
1 | 207 (22%) | |
2 | 109 (11%) | |
3 | 55 (6%) | |
4 | 20 (2%) | |
5 – 9 | 12 (1%) | |
History | ||
Medical historyb
| 1 (0.1%) | |
None | 601 (63%) | |
At least one condition | 251 (26%) | |
Two or more conditions | 101 (11%) | |
Chronic hypertension | 139 (15%) | 10 (1.0%) |
Renal disease | 30 (3%) | 10 (1.0%) |
Previous history of pre-eclampsia | 169 (43%) | 558b
|
Autoimmune disease | 18 (2%) | 32 (3.4%) |
Diabetes mellitus | 109 (11%) | 6 (0.6%) |
Symptoms | ||
Symptoms of headache and/or visual disturbance | 382 (41%) | 28 (2.9%) |
Symptoms of epigastric pain, nausea and/or vomiting | 202 (22%) | 47 (4.9%) |
Symptoms of chest pain and/or breathlessness | 60 (7%) | 126 (13.2%) |
Bedside examination and tests | ||
Systolic blood pressure (mmHg), mean (SD) | 159 (19) | 5 (0.5%) |
Diastolic blood pressure (mmHg), mean (SD) | 99 (12) | 5 (0.5%) |
Clonus | 95 (17%) | 403 (42.2%) |
Exaggerated tendon reflexes | 147 (24%) | 353 (37%) |
Oxygen saturation by pulse oximetry (%), mean (SD) | 98 (2) | 521 (54.6%) |
Oxygen saturation: abnormal (< 94%) | 4 (1%) | 521 (54.6%) |
Urine dipstick | ||
None/Trace | 39 (4%) | |
1+ | 170 (18%) | |
2+ | 314 (34%) | 19 (2%) |
3+ | 306 (33%) | |
≥ 4 | 106 (11%) | |
Laboratory tests | ||
Haemoglobin (g/L), mean (SD) | 11.9 (1.3) | 37 (3.9%) |
Platelet count (× 109/L), mean (SD) | 226 (78) | 41 (4.3%) |
Alanine transaminase (U/L), mean (SD) | 31.0 (71.0) | 75 (7.9%) |
Serum uric acid (μmol/L), mean (SD) | 0.6 (2.7) | 165 (17.3%) |
Serum urea (mmol/L), mean (SD) | 4.6 (4.4) | 70 (7.3%) |
Serum creatinine (μmol/L), mean (SD) | 61.0 (17.8) | 38 (4%) |
Urine PCR (mg/mmol), mean (SD) | 273 (492) | 109 (11.4%) |
Treatment provided | ||
Any anti-hypertensive therapyc
| 753 (79%) | 6 (0.6%) |
Oral anti-hypertensive therapy | 734 (77%) | 6 (0.6%) |
Parenteral anti-hypertensive therapy | 111 (12%) | 6 (0.6%) |
Parenteral magnesium sulfated
| 144 (15%) | 6 (0.6%) |
Outcomes
Sample size
Datasets for external validation
Data analysis
Model development
Internal validation and adjustment for over-optimism
External validation
Prediction of secondary (adverse perinatal) outcomes
Results
Characteristics of women in the PREP study
Outcomes
Model development
PREP-S model: risks at various time points
Box 1: Full PREP prognostic models to calculate the risk of adverse maternal outcomes in women with early onset pre-eclampsia
a. Risk at various time points from diagnosis until 34 weeks’ gestation using the survival model (PREP-S) S(t) = S0 (t)§ ^exp ((β1*X1 + ⋯ + βn*Xn)) S(t) = S0(t)^exp(– 0.031*maternal age + 1.514*((Log(GA at diagnosis/10))–2 – 0.8345136) + 5.707*((Log(GA at diagnosis/10))–2* ln(log(GA at diagnosis/10)) – 0.0652155) + 0.122 (exaggerated tendon reflexes) – 0.169 (one pre-existing medical condition) – 0.384 (two or more pre-existing medical conditions) + 0.016*systolic blood pressure + 0.797 (oxygen saturation < 94% on air) – 0.002*platelet count + 0.126*log(alanine amino transferase) + 0.605*log(serum urea)2 – 0.144*log(serum urea)3 + 0.265*log(serum creatinine) + 0.080*log(protein creatinine ratio) + 0.176 (baseline treatment with any antihypertensive) + 1.066 (baseline treatment with magnesium sulfate)) § S
0
(t) – baseline survival adjusted for optimism at time t S
0
(48 hrs) = 0.99142, S
0
(72 hrs) = 0.98542, S
0
(1 week) = 0.96492, S
0
(1 month) = 0.87377
b. Overall risk by postnatal discharge using the logistic model (PREP-L) Probability (maternal adverse outcome) = exp(X)/(1 + exp(X)), Where X = – 1.507– 0.020*maternal age + 12.052*(log (gestational age))3 – 39.90241) – 7.930*((log (gestational age))3*log(log (gestational age) – 49.08188) – 0.330 (if one pre-existing medical condition) – 0.579 (if two or more pre-existing medical conditions) + 0.146*log (urine protein creatinine ratio) – 0.951*(log (serum urea)–1) – 0.004*platelet count + 0.024*systolic blood pressure + 0.409 (baseline treatment with antihypertensive) + 1.252 (baseline treatment with magnesium sulfate) Predictor value is 1 when present and 0 when absent
|
PREP-L model: risk by postnatal discharge
Model performance | Development cohort | External cohorts | |
---|---|---|---|
PREP | PIERS | PETRA | |
PREP-S model | N = 946 | N = 339 | |
C-statistic (95% CI) | – | ||
At 48 hours | 0.84 (0.81–0.87)b
| 0.75 (0.69–0.81)a
| |
At 1 week | 0.79 (0.76–0.81)b
| 0.72 (0.68–0.76)a
| |
Overall | 0.75 (0.73–0.78)b,c
| 0.71 (0.67–0.75)a
| |
Calibration slope (95% CI) | – | ||
At 48 hours | 1 | 0.80 (0.62–0.99) | |
At 1 week | 1 | 0.75 (0.61–0.89) | |
Overall | 1 | 0.67 (0.56–0.79) | |
PREP-L model | N = 946 | N = 437 | N = 211 |
C-statistic (95% CI) | 0.82 (0.80, 0.84)b,d
| 0.81 (0.77–0.85)a
| 0.75 (0.64–0.86)a
|
Calibration slope (95% CI) | 1 | 0.93 (0.72–1.13) | 0.90 (0.48–1.32) |
External validation of PREP models
PREP-S model performance in external datasets
Risk stratification (No. of women) | Time | External validation in PIERS cohort | ||
---|---|---|---|---|
Observed survival probability
\( \left(\overline{S}(t)\right) \)
| Predicted survival probability (Ŝ(t)) | Ratio \( \left(\overline{S}(t)\right)/\left(\widehat{S}(t)\right) \)
| ||
≤ 15th (n = 59) | 48 hours | 0.91 | 0.95 | 0.96 |
1 week | 0.81 | 0.79 | 1.0 | |
> 15th–50th (n = 70) | 48 hours | 0.88 | 0.89 | 1.0 |
1 week | 0.62 | 0.60 | 1.0 | |
> 50th –85th (n = 123) | 48 hours | 0.90 | 0.70 | 1.3 |
1 week | 0.40 | 0.23 | 1.7 | |
> 85th (n = 87) | 48 hours | 0.46 | 0.28 | 1.6 |
1 week | 0.14 | 0.02 | 7.0 |