01.12.2017 | Research article | Ausgabe 1/2017 Open Access

Prediction of complications in early-onset pre-eclampsia (PREP): development and external multinational validation of prognostic models
- Zeitschrift:
- BMC Medicine > Ausgabe 1/2017
Electronic supplementary material
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 pregnancy
a
|
||
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 history
b
|
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%)
|
558
b
|
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 (× 10
9/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 therapy
c
|
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 sulfate
d
|
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) = S
0 (t)
§ ^exp ((β
1*X
1 + ⋯ + β
n*X
n)) S
(t) = S
0(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
|