False-Positive Maternal Serum Screens in the Second Trimester as Markers of Placentally Mediated Complications Later in Pregnancy: A Systematic Review and Meta-Analysis

Table 1

Characteristics of eligible studies.

Study	Design	Setting	Study period	Exclusions	Cases	Controls	Test & cut-off	Outcomes
Dungan (1994) [47]	Prospective cohort (matched)	Tennessee, USA (regional medical centre screening database)	Jan 1990 to Dec 1991	Multiples,  y	False-pos DS screen	Screen Neg (matched by age, race, parity, and bleeding)	Triple marker (15-20 wk GA) ≥1 : 270 at midgest	IUFD, , PET, major anomalies
Pergament (1995) [25]	Retrospective cohort (matched)	Illinois, USA (large teaching hospital)	Jul 1990 to Jun 1991	Multiples,  y	False-pos DS screen	Screen Neg (matched by age, race, sample date, DM)	Triple marker (15-20 wk GA) ≥1 : 250 at midgest	PTB, PPROM, abruption, PET, , IUFD, APOs
Milunsky (1996) [48]	Retrospective cohort (matched)	Massachusetts, USA (university teaching hospital)	1992 to 1994	Multiples, DM	Abn lytes plus screen Pos for DS	Normal lytes plus screen Neg for DS (matched by age, GA, and race)	Abnormal analyte levels +/- triple marker (15-24 wk GA) ≥1 : 270 at midgest	LBW, IUFD, NND, anomalies, DS
Chapman (1997) [43]	Retrospective cohort	Alabama, USA (genetic database at university teaching hospital)	Aug 1988 to Feb 1995	y, anomalies, abn amnio	False-pos DS screen plus normal amnio	Screen Neg plus normal amnio	Double marker (15-20 wk GA) ≥1 : 190 at midgest	IUFD, PTB,
Hsieh (1997) [44]	Retrospective cohort adjusted analysis	Taipei, Taiwan (university hospital)	Jan 1994 to Feb 1996	y	False-pos DS screen	Screen Neg	Double marker (14-22 wk GA) ≥1 : 270 at midgest	PTB, postdates, , LGA, macrosomia, PET, PPH, PROM, abruption, anomalies, poly, oligo, IUFD
Ogle (2000) [45]	Retrospective cohort (matched)	London, UK (university teaching hospital)	22 mo period	Multiples, preg dating not done by us	False-pos DS screen	Screen Neg (matched by age and GA of testing)	Double marker (15-18 wk GA) ≥1 : 250 at term	IUFD, PTB, PET, IUGR, APOs
Spencer (2000) [49]	Retrospective cohort	UK (tertiary hospital prenatal screening program)	1995 to 1998	Multiples, anomalies, abn amnio, preg  wk GA	outcome	outcome	Triple marker (15-19 wk GA) >1 : 251 at midgest	PTB, SGA, IUGR, IUFD
Antsaklis (2001) [50]	Retrospective cohort (matched)	Athens, Greece (large teaching hospital)	Jan 1991 to Dec 1998	Multiples,  y	False-pos DS screen	Screen Neg (matched by age & GA at testing)	Triple marker (16-20 wk GA) ≥1 : 250 at midgest	Fetal death (total and by etiology)
Naylor (2001) [51]	Prospective cohort (matched)	California, USA (university teaching hospital)	Aug 1995 (start)	Non-Hispanics, multiples, HTN, DM, PMHx, anomalies	False-pos DS screen plus normal amnio	Screen Neg, matched	Triple marker (15-20 wk GA) ≥1 : 190 at midgest	PET, PTB, , IUFD, APOs
Summers (2003) [52]	Retrospective cohort (matched)	Canada (provincial genetic database)	Oct 1995 to Sep 1998	Multiples, DM, +NTD screens, anomalies	False-pos DS screen	Screen Neg (matched by age, ethnicity, test site, sample date)	Triple marker (15-20 wk GA) ≥1 : 385 at term	PIH, PET, APH, PROM, SGA, PTB, oligo, poly, IUFD, APOs
Sritippayawan (2005) [26]	Retrospective cohort (matched)	Bangkok, Thailand (university teaching hospital)	Mar 1998 to Aug 2002	Multiples, DM, anomalies, aneuploidy, missing info, POBHx or FamHx, +NTD or unknown screen	False-pos DS screen	Screen Neg (matched by age, parity, and date of testing)	Double marker (14-21 wk GA) ≥1 : 270 at midgest	PTB, LBW, SGA, PET, previa, IUFD, APOs
Xia (2006) [53]	Retrospective cohort	Shanghai, China (university teaching hospital)	Apr 2002 to Mar 2005	Multiples	False-pos DS screen	Screen Neg	Triple marker (13-21 wk GA) ≥1 : 384 at term	IUGR, BGI, NBI, OSB, IUFD, distress, APOs
Weintraub (2012) [54]	Retrospective cohort	Negev, Israel (university teaching hospital)	ᴓ	Abnormal levels of individual analytes	False-pos DS screen (normal lytes & amnio)	Screen Neg	Triple marker (15-20 wk GA) ≥1 : 380 at term	Abn lytes, amnio, GDM, poly, IUGR, PROM, PTB, postdates, IOL, augmentation, breech, FTP, distress, mec, mode, GA, BWt, gender, Apgars, LGA, AGA, SGA, cardiac anomalies, PPH
Rodrigues (2013) [46]	Retrospective cohort (matched)	Lisbon, Portugal (hospital database)	Mar 2003 to Aug 2007	Multiples	False-pos T1 or T2 double marker screen	Screen Neg (matched by age, GA at testing, and type of screen)	PN screening cohort of 4422 (T1 integrated or T1 serum integrated or T2 double marker) vs controls	PTB, IUGR, HDP
Godbole (2015)	Retrospective cohort	Pune, India (tertiary care private hospital)	2 years	Abnormal chx	“High risk” screen	“Low risk” screen	Triple marker () vs T1 double marker ()	PTB, LBW, oligo, CS, PIH, NICU admission, resp distress
Yazdani (2015) [55]	Retrospective cohort	Babol, Iran (university teaching hospital)	Mar 2012 to 2013	Chronic HTN, DM, renal dis, heart dis, thal, thyroid dis, multiples, family hx, pos amnio	False-pos DS screen	Screen Neg	Quad marker (14-18 wk GA)	Composite APO, anemia, mode of del, infertility, UTI, GDM, GHTN, PET, PTL, IUGR, poly, oligo, PROM, skin dis, abruption

Legend: abn = abnormal; AGA = appropriate for gestational age; amnio = amniocentesis; APH = antepartum hemorrhage; APO(s) = abnormal pregnancy outcome(s); BGI = basal ganglia injury; BWt = birthweight; chx = chromosome; CS = cesarean section; del = delivery; dis = disease; DM = diabetes mellitus; DS = Down syndrome; FamHx = family medical history; GA = gestational age; GDM = gestational diabetes; GHTN = gestational hypertension; HDP = hypertensive disorders of pregnancy; HTN = hypertension; IOL = induction of labour; IUFD = intrauterine fetal demise or stillbirth; IUGR = intrauterine growth restriction; LWB = low birthweight; LGA = large for gestational age; lytes = analytes; midgest = midgestation of pregnancy or “midpregnancy”; NBI = neonatal brain injury; Neg = negative; NND = neonatal death; oligo = oligohydramnios; OSB = open spina bifida; PET = preeclampsia; PIH = pregnancy-induced hypertension; PMHx = past medical history; POBHx = past obstetrical history; poly = polyhydramnios; pos = positive; preg = pregnancy; PPH = postpartum hemorrhage; PROM = premature rupture of membranes; PTB = preterm birth; PTL = preterm labour; resp = respiratory; SGA = small for gestational age; T1 = first-trimester; T2 = second-trimester; thal = thalassemia; US = ultrasound; UTI = urinary tract infection; +NTD screens = positive screen for neural tube defect; %ile = percentile; ?screen = unknown or missing screening results.