Pulsatility index in combination with biomarkers or mean arterial pressure for the prediction of pre-eclampsia: Systematic literature review and meta-analysis

Figures & data

Figure 1. Flow diagram of study selection.

Table I. Summary of studies included in the meta-analysis.

Reference number	First author (publication year)	Study design	Patients	Time of testing (trimester)	Number of patients	Maternal age (years)^a	BMI (kg/m^2)^a	Gestational age at delivery (weeks)^a	Infant birth weight (g)^a
20	Akolekar (2013)	Cohort	Pre-eclampsia	1st (11–13 wk)	1426	NA	NA	NA	NA
			Early-onset pre-eclampsia (< 34 wk)		214	NA	NA	NA	NA
			Control		57458	NA	NA	NA	NA
21	Odibo (2011)	Cohort	Pre-eclampsia	1st (11–14 wk)	42	30.2 (6.4)	34.0 (8.9)	35.4 (4.1)	2581.6 (867.3)
			Early-onset pre-eclampsia (< 34 wk)		12
			Control		410	31.6 (5.6)	28.0 (7.2)	38.2 (3.8)	3265.7 (692.6)
22	Yu (2011)	Case-control	Pre-eclampsia	PGF, activin A, inhibin A: 1st (12–16 wk); PI: 2nd (22–24 wk)	31	28.17 (3.22)	21.65 (2.67)	36.02 (2.14)	2765 (576.72)
			Control		93	29.67 (3.71)	20.43 (2.42)	38.52 (1.44)	3243.55 (324.23)
23	Foidart (2010)	Case-control	Early-onset pre-eclampsia (< 34 wk)	1st (11–13 wk)	30	31.7 (25.4, 36.8)^d	27.8 (23.7, 32.4)^d	31.6 (28.7, 32.6)^d	1300 (900, 1600)^d
			Late-onset pre-eclampsia (≥ 34 wk)		60	31.5 (26.2, 36.7)^d	28.2 (24.0, 33.5)^d	38.3 (37.2, 39.9)^d	2800 (2300, 3300)^d
			Unaffected		180	32.5 (29.2, 36.7)^d	24.8 (22.6, 28.1)^d	39.7 (38.9, 40.7)^d	3500 (3200, 3700)^d
24	Poon (2010)	Cohort	Early-onset pre-eclampsia (< 34 wk)	1st (11–13 wk)	37	NA	NA	NA	NA
			Late-onset pre-eclampsia (≥ 34 wk)		128	NA	NA	NA	NA
			Unaffected		8061	NA	NA	NA	NA
25	Poon (2010)	Case-control	Early-onset pre-eclampsia (< 34 wk)	1st (11–13 wk)	26	32.7 (27.4, 38.7)d	27.2 (23.7, 32.0)d	NA	NA
			Late-onset pre-eclampsia (≥ 34 wk)		90	31.5 (26.3, 36.30)	27.1 (23.8, 33.4)	NA	NA
			Unaffected		201	32.1 (28.7, 35.5)	25.1 (22.9, 28.7)	NA	NA
26	Poon (2009)	Cohort	Pre-eclampsia	1st (11–13 wk)	156	NA	NA	NA	NA
			Early-onset pre-eclampsia (< 34 wk)		32	31.6 (17, 49)^c	27.6 (18.7, 38.1)^c	NA	NA
			Late-onset pre-eclampsia (≥ 34 wk)		124	32.0 (17, 44)^c	27.4 (18.9, 46.4)^c	NA	NA
			Unaffected		7895	32.3 (16, 49)^c	24.5 (15.3, 59.2)^c	NA	NA
27	Akolekar (2008)	Case-control	Early-onset pre-eclampsia (< 34 wk)	1st (11–13 wk)	29	32.7 (17, 49)^c	NA	NA	NA
			Late-onset pre-eclampsia (≥ 34 wk)		98	31.5 (18, 44)^c	NA	NA	NA
			Control		609	32.7 (16, 45)^c	NA	NA	NA
28	Crispi (2008)	Nested case-control	Early-onset pre-eclampsia (< 32 wk)	2nd (24 wk)	19	29 (5)	29 (7)	29 (25, 33)^d	998 (323)
			Late-onset pre-eclampsia (≥ 32 wk)		19	32 (5)	27 (6)	37 (34, 40)^d	2345 (479)
			Control		76	32 (5)	26 (4)	39 (36, 42)^d	3182 (571)
29	Spencer (2008)	Nested case-control	Pre-eclampsia	PAPP-A, activin A, inhibin A: 1st (11–13 wk); PI: 2nd (22–24 wk)	64	29	NA	36.2	2025
			Control		240	30	NA	NA	NA
30	Spencer (2007)	Nested case-control	Pre-eclampsia	2nd (22–24 wk)	12	NA	NA	NA	NA
			Early-onset pre-eclampsia (< 34 wk)		5	NA	NA	NA	NA
			Late-onset pre-eclampsia (≥ 34 wk)		7	NA	NA	NA	NA
			Control		73	NA	NA	NA	NA
31	Spencer (2007)	Nested case-control	Pre-eclampsia	PAPP, PP13: 1st (11–13 wk); PI: 2nd (22–24 wk)	88	29.5 (5.9)	27.1 (6.2)	36.2	2025
			Early-onset pre-eclampsia (< 34 wk)		44	28.9 (6.3)	27.2 (5.4)	30.9	1361
			Late-onset pre-eclampsia (≥ 34 wk)		44	NA	NA	NA	NA
			Control		446	30.2 (4.8)	25.4 (5.1)	39.1	3418
32	Spencer (2006)	Case-control	Pre-eclampsia	2nd (22–24 wk)	24	NA	NA	NA	NA
			Control		144	NA	NA	NA	NA
33	Nicolaides (2006)	Nested case-control	Pre-eclampsia	1st (11–13 wk)	10	32.7 (26.6–39.0)^b	NA	NA	NA
			Control		423	30.1 (15.0–44.5)^b	NA	NA	NA
34	Spencer (2005)	NA	Pre-eclampsia	PAPP: 1st (11–13 wk); PI: 2nd (22–24 wk)	64	29 (17, 44)^c	NA	NA	NA
			Normal		3999	30 (16, 47)^c	NA	NA	NA

Data expressed as ^amean ± standard deviation; ^bmean (range); ^cmedian (range); ^dmedian (IQR).

NA = no data available; PAPP-A = pregnancy-associated plasma protein A; PGF = placental growth factor; PI = pulsatility index; PP13 = placental protein 13.

Table II. Summary of outcomes.

Reference	First author (year)	Patients	Sensitivity	Specificity	Area under the curve (AUC)^a
	PI + PAPP-A
21	Odibo (2011)	Pre-eclampsia	45%	90%	0.77 (0.63, 0.81)
		Early-onset pre-eclampsia	58%	90%	0.80 (0.66, 0.98)
23	Foidart (2010)	Early-onset pre-eclampsia	83.3 (65.3, 94.3)^a	90%	0.923 (0.878, 0.955)
		Late-onset pre-eclampsia	NA	NA	NA
24	Poon (2010)	Early-onset pre-eclampsia	81.1 (64.8, 92.0)^a	90%	0.925 (0.919, 0.930)
26	Poon (2009)	Pre-eclampsia	35.90%	90%	0.675 (0.665, 0.685)
		Early-onset pre-eclampsia	59.40%	90%	0.852 (0.844, 0.860)
		Late-onset pre-eclampsia	NA	NA	NA
27	Akolekar (2008)	Early-onset pre-eclampsia	72.4 (52.8, 87.2)^a	90%	0.907 (0.882, 0.929)
		Late-onset pre-eclampsia	NA	NA	NA
29	Spencer (2008)	Pre-eclampsia	62%	95%	NA
31	Spencer (2007)	Pre-eclampsia	76%	80%	0.82 (0.76, 0.90)
		Early-onset pre-eclampsia	76%	80%	0.86 (0.77, 0.94)
		Late-onset pre-eclampsia	70%	80%	0.81 (0.72, 0.90)
34	Spencer (2005)	Pre-eclampsia	62.1%	95%	0.853
	PI + Activin A
22	Yu (2011)	Pre-eclampsia	77%	80%	0.852 (0.766, 0.939)
29	Spencer (2008)	Pre-eclampsia	63%	95%	NA
32	Spencer (2006)	Pre-eclampsia	75%	90%	0.935
	PI + Inhibin A
22	Yu (2011)	Pre-eclampsia	63%	80%	0.813 (0.726, 0.900)
29	Spencer (2008)	Pre-eclampsia	68%	95%	NA
32	Spencer (2006)	Pre-eclampsia	75%	90%	0.913
	PI + PGF
22	Yu (2011)	Pre-eclampsia	80%	80%	0.880 (0.794, 0.920)
23	Foidart (2010)	Early-onset pre-eclampsia	85.2 (66.3, 95.7)^a	90%	0.945 (0.904, 0.972)
		Late-onset pre-eclampsia	NA	NA	NA
20	Akolekar (2008)	Early-onset pre-eclampsia	89.7 (72.6, 97.7)^a	90%	0.941 (0.889, 0.994)
		Late-onset pre-eclampsia	49.0 (38.7, 59.3)^a	90%	0.817 (0.773, 0.861)
28	Crispi (2008)	Early-onset pre-eclampsia	89.5%	90%	0.974 (0.944, 1.000)
		Late-onset pre-eclampsia	10.5%	80%	0.620 (0.508, 0.733)
	PI + PP13
21	Odibo (2011)	Pre-eclampsia	45%	90%	0.75 (0.62, 0.82)
		Early-onset pre-eclampsia	68%	90%	0.86 (0.69, 1.00
30	Spencer (2007)	Pre-eclampsia	75%	80%	0.80 (0.65, 0.94)
		Early-onset pre-eclampsia	100%	80%	0.93 (0.88, 0.99)
		Late-onset pre-eclampsia	29%	80%	0.62 (0.4, 0.84)
31	Spencer (2007)	Pre-eclampsia	74%	80%	0.84 (0.78, 0.90)
		Early-onset pre-eclampsia	79%	80%	0.90 (0.84, 0.96)
		Late-onset pre-eclampsia	70%	80%	0.79 (0.69, 0.88)
33	Nicolaides (2006)	Pre-eclampsia	90 (55, 100)^a	90%	NA
	PI + MAP
24	Poon (2010)	Early-onset pre-eclampsia	87.5 (54.0, 99.5)^a	90%	0.933 (0.892, 0.962)
		Late-onset pre-eclampsia	57.0 (27.5, 80.0)^a	90%	0.835 (0.787, 0.876)
20	Akolekar (2013)	Pre-eclampsia	56.6%	90%	NA
		Early-onset pre-eclampsia	89.7%	90%	NA
24	Poon (2010)	Early-onset pre-eclampsia	89.2 (74.6, 96.9)^a	90%	0.954 (0.919, 0.989)
		Late-onset pre-eclampsia	57.0 (48.0, 65.7)^a	90%	0.863 (0.855, 0.870)

MAP = mean arterial pressure; NA = no data available; PAPP-A = pregnancy-associated plasma protein A; PGF = placental growth factor; PI = pulsatility index; PP13 = placental protein 13.

^aData expressed as mean (95% confidence interval).

Figure 3. QUADAS-2 quality assessment results with respect to (A) rating and (B) proportion of included studies with low, high, or unclear risk of bias.

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