Table 1.

General characteristics of the included studies in the meta-analyses. GH: gestational hypertension; SGA: small for gestational age. PTB: preterm birth. The outcomes used were in line with the definitions from International Society for the study of Hypertension (ISSHP) [9].

Study	Year	GA of Test (Weeks)	Biomarker (s)	Outcome	Study Design A	Low/High Risk	Location	n (Total)	n (PE)	Level of Evidence
Anderson et al. [10]	2011	11–16	α-1-microglobulin and fetal hemoglobin	PE	Nested case control (in prospective study) 1	LR	UK	96	60	3b
Akolekar et al. [11]	2008	11–14	PlGF, PAPP-A	EOPE, LOPE, GH	Nested case-control (in trisomy 21 screening cohort) 2	LR + HR	UK	824	127	3b
Akolekar et al. [12]	2013	11–14	PlGF, PAPP-A	PE	Prospective cohort (in screening)	LR + HR	UK	58,703	1245	1b
Audibert et al. [13]	2010	11–13	PAPP-A, ADAM-12, PlGF, hCG, inhibin-A, PP-13, protein-A, inhibin-A	PE, EOPE, LOPE, GH	Prospective cohort (trisomy 21 screening cohort) 3	LR + HR	Canada	893	40	1b
Bills et al. [14]	2009	First trimester	VEGF(165)b, sFLT, sEng	PE, EOPE, LOPE	Case-control 4	LR + HR	UK	70	25	3b
Bosio et al. [15]	2001	10–14	P-selectin	PE, GH	Nested case-control (in longitudinal cohort) 5	LR + HR	Ireland	70	20	3b
Boucoiran et al. (1) [16]	2013	12–18	PlGF, sFlt-1, inhibin A	PE, GH, SGA	Prospective cohort (nested in RCT) 6	LR + HR	Canada	793	34	1b
Boucoiran et al. (2) [17]	2013	11-14 and 18-22	PlGF, PP-13, ADAM-12	EOPE, LOPE, GH	Prospective cohort (trisomy 21 screening cohort) 7	LR + HR	Canada	893	40	1b
Brameld et al. [18]	2008	12 + 3	PAPP-A, free-hCG	PE	Retrospective cohort (trisomy 21 screening cohort) 8	LR	Australia	22,125	660	2b
Chafetz et al. [19]	2007	9–12	PP-13	PE, PTB, SGA	Nested case control in prospective cohort (MOMS-study) 9	LR	USA	425	47	3b
Cohen et al. [20]	2014	10–13	PAPP-A, α fetoprotein, free β-hCG	PE	Nested case control (retrospective cohort) 10	LR + HR	USA	2199	148	3b
Cowans et al. [21]	2011	11–14	PP-13	EOPE, LOPE	Nested case control (in cohort of trisomy screening) 11	HR	UK	234	37	3b
Deurloo et al. [22]	2013	9–14	ADAM-12, PP-13	PE, GH, SGA	Nested case control (in cohort of trisomy screening 12	LR + HR	The Netherlands	220	17	3b
Dugoff et al. [23]	2004	10–14	PAPP-A	PE, PTB, SGA	Prospective study (FASTER trial, trisomy screening cohort) 13	LR	USA	34,271	764	1b
Giguere et al. [24]	2014	10–18	PlGF, sFlt, PAPP-A, inhibin-A	PE	Nested case-control (in prospective cohort) 14	LR	Canada	648	216	3b
Goetzinger et al. [25]	2013	11–14	ADAM-12, PAPP-A	PE, EOPE, LOPE	Prospective cohort 15	LR + HR	USA	578	54	1b
Gonen et al. [26]	2008	6–10	PP-13	PE, GH	Prospective cohort 16	LR + HR	Israel	1239	20	1b
Ghosh et al. [27]	2013	11–14	PlGF	EOPE	Prospective study (screening antenatal care) 17	LR + HR	India	1206	9	1b
Hedley et al. [28]	2010	10–14	PAPP-A, free leptin index	PE	Nested case control (in First Trimester Screening Study) 18	LR	Denmark	415	126	3b
Kang et al. [29]	2008	11 and 16	PAPP-A, AFP, uE3, hCG, inhibin-A	PE	Retrospective cohort (trisomy 21 screening cohort) 19	LR + HR	Korea	3076	32	2b
Kenny et al. [30]	2014	14–16	Multiple	PE, EOPE, preterm and term PE	Prospective cohort 20	LR	Australia/UK/Ireland	5623	278	1b
Khalil et al. [31]	2010	11–14	PP-13	PE, EOPE, PE + SGA	Nested case-control (in antenatal clinic cohort) 21	HR	UK	252	42	3b
Kuc et al. [32]	2013	9–14	PAPP-A, free -hCG, ADAM-12, PlGF	EOPE, LOPE	Nested case control (in screening cohort) 22	LR + HR	The Netherlands	667	167	3b
Kusanovic et al. [33]	2009	6–15	PlGF, soluble endoglin, sVEGFR-1	EOPE, LOPE	Prospective cohort 23	LR	Chile	1622	62	3b
Myatt et al. [34]	2012	9–13	ADAM-12, PAPP-A, PP-13, sFLT, endoglin	PE	Nested case control (in cohort of RCT) 24	LR	USA	683	174	2b
Myers et al. [35]	2013	14–16	PlGF, soluble endoglin, sFLT-1	preterm PE (<37 week)	Prospective cohort 25	LR	Australia/UK/Ireland	235	47	1b
Nicolaides et al. [36]	2006	11–14	PP-13	EOPE	Nested case control (in screening cohort) 26	LR + HR	UK	433	10	3b
Odibo et al. [37]	2011	11–14	PP13, PAPP-A	PE, EOPE	Prospective cohort (trisomy 21 screening cohort) 27	LR + HR	USA	452	42	1b
Park et al. [38]	2014	11–14	PAPP-A, PlGF, inhibin-A, sFLT	LOPE	Prospective cohort 28	LR	Korea	262	8	1b
Poon et al. (1) [39]	2009	11–14	PAPP-A	PE, EOPE, LOPE	Prospective cohort (trisomy 21 screening cohort) 29	LR + HR	UK	8051	156	1b
Poon et al. (2) [40]	2009	11–14	PAPP-A, MMP-9, TNF-R1	EOPE, LOPE, GH, SGA, PTB	Nested case-control (in trisomy 21 screening cohort) 30	LR + HR	UK	1138	128	3b
Roes et al. [41]	2004	6–15	Inhibin-A	PE	Case control 31	LR	The Netherlands	55	19	3b
Schneuer et al. [42]	2012	11–13	PP-13	PE, EOPE, LOPE, SGA	Prospective cohort (trisomy 21 screening cohort) 32	LR + HR	Australia	2678	71	1b
Spencer et al. [43]	2006	11–14	PP-13, PAPP-A	PE, EOPE, LOPE	Nested case-control (in trisomy 21 screening cohort) 33	LR	UK	534	88	3b
Spencer et al. [44]	2008	11–14	Inhibin-A and activin-A	PE, EOPE, LOPE	Nested case-control (in trisomy 21 screening cohort) 34	LR	UK	304	64	3b
Tidwell et al. [45]	2001	5–15	PlGF	EOPE, LOPE	Case control 35	LR	Taiwan	39	14	3b
Thilaganathan et al. [46]	2010	14.7 (CO), 16.3 (PE)	cystatin-C, CRP	PE	Nested case-control (in antenatal clinic cohort) 36	LR	UK	170	45	3b
Xu et al. [47]	2014	First trimester	Chemerin	PE	Prospective cohort (antenatal care)37	LR	China	518	41	1b
Youssef et al. [48]	2011	11–14	PAPP-A, PlGF, sFlt-1, P-selectin, NGAL	LOPE	Prospective cohort 38	LR + HR	Italy	528	13	1b
Yu et al. [49]	2011	12–16	PlGF, inhibin-A, activin-A	PE	Nested case-control (in antenatal clinic cohort) 39	LR	China	124	31	3b
Zong et al. [50]	2012	13–16	Htr-A1 (High-Temperature Requirement A1)	PE	Prospective cohort (clinical cohort) 40	LR	China	1396	100	1b

^A Characteristics of the study population are mentioned below; ¹ Exclusion criteria diabetes, prepregnancy hypertension and premature delivery; ² Controls: did not develop any pregnancy complications and resulted in the live birth of phenotypically normal neonates; ³ Exclusion: multiparous, multiple gestation, major fetal chromosomal/structural anomaly; ⁴ Exclusion: pregnancy induced hypertension, fetal growth restriction, intrauterine death, preterm birth (PTB); ⁵ Controls: normal obstetric outcome. Matched for body mass index (BMI); ⁶ Exclusion: vitamin C and/or vitamin E supplements, history of major medical complications, major fetal defects, repeated spontaneous abortion, use of an illicit drug or warfarin treatment during the current pregnancy; ⁷ Inclusion: nulliparous women with singleton pregnancies without major fetal chromosomal or structural anomaly; ⁸ Exclusion: Women who had a previous fetus with a chromosomal abnormality and women with insulin-dependent diabetes mellitus; ⁹ Exclusion: AIDS or hepatitis, cases of major fetal anomaly, fetal death and women with placenta previa, placenta accrete, or placental abruption; ¹⁰ General population, singleton pregnancies; ¹¹ A priori high risk pregnancies; ¹² General population; ¹³ Inclusion: singleton pregnancy, exclusion: diabetes and chromosomal abnormalities; ¹⁴ Exclusion: chronic hepatic or renal diseases, pregnancies with major fetal abnormalities and those ending in termination, miscarriage or fetal death <24 weeks; ¹⁵ Exclusion : known aneuploidy and major congenital malformations; ¹⁶ Exclusion: miscarriages; ¹⁷ Exclusion: congenital abnormalities or medication use; ¹⁸ Randomly selected controls; ¹⁹ Exclusion: multifetal gestation, diabetes, chromosomal or structural abnormalities; ²⁰ Exclusion: increased risk factors of PE, SGA or PTB, known major fetal anomaly or abnormal karyotype, intervention that may modify pregnancy outcome such as treatment with aspirin or progesterone; ²¹ Inclusion: history of PE in a previous pregnancy, chronic hypertension, chronic renal disease, antiphospholipid syndrome, systemic lupus erythematosus, pregestational diabetes mellitus, obesity (BMI ≥ 30 kg/m²). Exclusion: multiple pregnancy, cases of major fetal anomaly, miscarriage or fetal death, HIV or hepatitis, placenta previa or placental abruption; ²² Exclusion: multiple pregnancy, delivery <24 weeks, chromosomal abnormalities; ²³ Inclusion: pregnancies in which a single live fetus was delivered after 37 complete weeks of gestation with birth weight above the 10th centile and without fetal anomalies; ²⁴ Inclusion: nulliparous, low risk women; ²⁵ Exclusion: increased risk of PE, SGA or PTB, known major fetal anomaly or abnormal karyotype, intervention that may modify pregnancy outcome such as treatment with aspirin or progesterone; ²⁶ Gestational age matched controls; ²⁷ Inclusion : singleton pregnancies. Exclusion: spontaneous miscarriage prior to 20 weeks, loss to follow-up or fetal anomalies diagnosed in the second trimester; ²⁸ Exclusion: high risk pregnancies; ²⁹ Definition controls: randomly selected women without reported pregnancy-associated hypertension; ³⁰ Definition controls: had blood collected and stored on the same day, which did not develop any pregnancy complications and resulted in the live birth of phenotypically normal neonates; ³¹ Unknown in- and exclusion criteria; ³² Inclusion: singleton pregnancies; ^33,34 Gestational age matched controls; ³⁵ Exclusion: multiparity, chronic hypertension, diabetes, multiple gestation, connective tissue disorder, any long-term use of medicine other than prenatal vitamins, and miscarriage before viability; ³⁶ Exclusion: diabetes, connective tissue disease, renal disorders, essential hypertension; ³⁷ Exclusion: previous systemic disorders or drug use, chronic hypertension, diabetes, renal disorders, recent or present fever or infectious disease, malignancies, autoimmune diseases and multiple pregnancies; ³⁸ Exclusion: early-onset PE, multiple gestations, pregnancies with fetal chromosomal or major structural anomaly, miscarriages; ³⁹ Unknown inclusion/exclusion criteria; ⁴⁰ Exclusion: cases showing intrahepatic cholestasis of pregnancy, abortion, peripartum cardiomyopathy, and other complications. PlGF: Placental growth factor; PAPP-A: Pregnancy associated plasma protein A; ADAM-12: A disintegrin and metalloprotease 12; CRP: C-reactive protein; hCG: human chorionic gonadotropin; PP-13: Placental protein 13; VEGF: Vascular endothelial growth factor; sFLT: Soluble fms-like tyrosine kinase-1; sEng: Soluble endoglin; sVEGR-1: Soluble endothelial growth factor-1; uE3: Oestradiol; MMP-9: Matrix metallopeptidase 9; TNF-R1: Tumor-necrosis factor receptor-1; NGAL: Neutrophil gelatinase-associated lipocalin; (1): publication 1 by same author in same year; (2): publication 2 by same author in same year.