Persisting risk factors for preeclampsia among high-risk pregnancies already using prophylactic aspirin: a multi-country retrospective investigation

Figures & data

Table 1. Aspirin Dose and Preeclampsia (n = 660).

Aspirin dose	Yes	No	Total
	Preeclampsia
High dose	33 (5.00)	79 (11.97)	112 (16.97)
Low dose	99 (15.00)	449 (68.03)	548 (83.03)
Total	132 (20.00)	528 (80.00)	660 (100)
	Preterm preeclampisa
High dose	19 (2.88)	93 (14.09)	112 (16.97)
Low dose	41 (6.21)	507 (76.82)	548 (83.03)
Total	60 (9.09)	600 (90.91)	660 (100)

NB: Percentages are total percentages all divided by 660.

Table 2. Demographic and pregnancy characteristics of high-risk pregnancies taking aspirin (n = 660).

Variables	Total N (%)
Aspirin
Low dose (≤81 mg per day)	548 (83.03)
High dose (>81 mg per day)	112 (16.97)
Preexisting Risk Factors for Preeclampsia
Chronic hypertension	194 (29.39)
Any diabetes	75 (11.36)
Type 1 diabetes	42 (6.36)
Type 2 diabetes	33 (5.00)
History of preeclampsia	292 (44.24)
BMI ≥35	249 (37.73)
Twin pregnancy	79 (11.97)
Multiple risk factors^1	191 (28.94)
Number of risk factors
1	469 (71.06)
2	157 (23.79)
3	31 (4.70)
4+	<5
Most common combinations
Chronic hypertension and BMI ≥35	66 (10.00)
History of preeclampsia and BMI ≥35	62 (9.39)
Chronic hypertension and history of preeclampsia	57 (8.64)
Demographic
Country:
Canada	311 (47.12)
Australia	91 (13.79)
United Kingdom	243 (36.82)
Jamaica/Argentina	15 (2.27)
Ethnicity:
Indigenous/Aboriginal	<5
White	548 (83.03)
Black	44 (6.67)
Asian	28 (4.24)
Latino/Hispanic	13 (1.97)
Indian/South Asian	20 (3.03)
Declined to answer	<5
Maternal age (years):
<20	6 (0.91)
20–29	194 (29.39)
30–34	244 (36.97)
≥35	216 (32.73)
Median age (med, IQR)	32 (29.00–35.50)
Marital status:
Single	63 (9.55)
Married/common law	587 (88.94)
Divorced/separated	10 (1.52)
Maternal education level:
High school and below	153 (23.18)
College/university not completed	126 (19.09)
College/university completed	381 (57.73)
Maternal BMI (kg/m^2):
Median BMI (med, IQR)	31.25 (25.00–37.80)
<18.5	8 (1.21)
18.5–24	156 (23.64)
25–29	137 (20.76)
30–34	110 (16.67)
≥35	249 (37.73)
Obstetrical factors
Parity:
Nulliparous (0)	182 (27.58)
Parous (≥1)	478 (72.42)
Smoking during pregnancy:
Yes	38 (5.76)
No	581 (88.03)
Quit during pregnancy	41 (6.21)
Alcohol intake during pregnancy:
Yes	10 (1.52)
No	497 (75.3)
Quit during pregnancy	153 (23.18)
Prescriptions and supplements
Folic acid supplementation:
Low dose (1 mg/day)	320 (48.48)
High dose (4 mg/day)	340 (51.52)
Calcium supplement	123 (18.64)
Birth outcomes
Preeclampsia	132 (20.00)
Preterm preeclampsia (<37 weeks gestation)	60 (9.09)
Preterm birth (<37 weeks gestation)	151 (22.88)

¹All combinations are available in Appendix 2.

Table 3. Bivariable and Multivariable log binomial regression models for factors associated with preeclampsia among those treated with prophylactic aspirin (n = 660).

	Development of Preeclampsia		Bivariable Log Binomial Regression		Multivariable Log Binomial Regression^a
Variables	Yes N = 132 n(%)	No N = 528 n(%)	RR (95% CI)	p-values	ARR (95% CI)	p-value
Preexisting Risk Factors for Preeclampsia
Chronic Hypertension	50 (37.88)	144 (27.27)	1.46 (1.07–1.99)	.016	1.92 (1.37–2.69)	<.001
Diabetes	12 (9.09)	63 (11.93)	0.78 (0.45–1.34)	.369	1.24 (0.72–2.11)	.212
History of Preeclampsia	77 (58.33)	215 (40.72)	1.76 (1.29–2.41)	<.001	2.42 (1.74–3.38)	<.001
BMI ≥35	47 (35.61)	201 (38.07)	0.92 (0.66–1.26)	.602	1.26 (0.93–1.69)	.135
Twin Pregnancy	21 (15.91)	58 (10.98)	1.39 (0.93–2.08)	.108	2.62 (1.68–4.11)	<.001
Aspirin dose (high vs low)	33 (5.00)	79 (11.97)	1.63 (1.16–2.29)	.005	1.17 (0.44–3.12)	.756
Age ≥35	38 (28.79)	178 (33.71)	0.83 (0.59–1.16)	.285	0.80 (0.57–1.11)	.184
Country
Canada	60 (45.45)	251(47.54)	(ref)	–	–	–
Australia	27 (20.45)	64 (12.12)	2.02 (0.93–4.37)	.036	1.36 (0.66–2.79)	.402
United Kingdom	40 (30.30)	203 (38.45)	1.80 (1.18–2.76)	.072	0.96 (0.47–1.92)	.904
Jamaica/Argentina	5 (3.79)	10 (1.89)	1.12 (0.51–2.45)	.771	1.42 (0.94–2.16)	.100

^aMultivariable model is built based on 5 risk factors (chronic hypertension, diabetes, history or preeclampsia, BMI ≥35, twin pregnancy) adjusted for aspirin dose, age and country site.

Table 4. Bivariable and Multivariable log binomial regression models for factors associated with preterm preeclampsia among those treated with prophylactic aspirin (n = 660).

	Development of Preterm Preeclampsia		Bivariable Log Binomial Regression		Multivariable Log Binomial Regression
Variables	Yes N = 60 n(%)	No N = 600 n(%)	RR (95% CI)	p-values	ARR (95% CI)	p-value
Preexisting Risk Factors for Preeclampsia
Chronic Hypertension	22 (36.67)	172 (28.67)	1.39 (0.84–2.28)	.194	2.18 (1.28–3.72)	.004
Diabetes	7 (11.67)	68 (11.33)	1.03 (0.48–2.18)	.938
History of Preeclampsia	35 (58.33)	257 (42.83)	1.76 (1.08–2.88)	.023	2.75 (1.62–4.67)	<.001
BMI ≥35	18 (30.00)	230 (38.33)	0.71 (0.42–1.21)	.208
Twin Pregnancy	13 (21.67)	66 (11.00)	2.03 (1.15–3.59)	.014	4.10 (2.15–7.82)	<.001
Aspirin dose (high vs low)	19 (2.88)	93 (14.09)	2.27 (1.36–3.76)	.002
Age ≥35	16 (26.67)	200 (33.33)	0.75 (0.43–1.29)	.298
Country
Canada	27 (45.00)	284 (47.33)	(ref)
Australia	15 (25.00)	76 (12.67)	1.89 (1.05–3.41)	.032
United Kingdom	17 (28.33)	226 (37.67)	0.81 (0.44–1.44)	.468
Jamaica/Argentina	<5	14 (2.33)	0.77 (0.11–5.27)	.788

^aMultivariable model did not converge, the variables were reviewed, and the final model included factors to minimize the Akaike Information Criteria (AIC) of the mode.

Data availability statement

With a data sharing agreement, de-identified data, the data dictionary, and ethics protocol are available.