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. 2021 Nov 18;16(11):e0260115. doi: 10.1371/journal.pone.0260115

Table 2. Main characteristics of studies.

Study Method Sample Size Biofluid PG/Metabolite Relevant Findings
Karim 1968 [10] TLC and biological assay n = 42 NL, n = 10 TL plasma PGF2α, PGF1α, PGE1, PGE2 NL < LOD
PGF2α higher at delivery than 1st stage labour
Brummer 1972 [11] RIA n = 40 NL, n = 46 L serum PGF2α L>TNL
late pregnancy similar to nonpregnant
increased through 1st stage labour (early-late), then decreased in 2nd stage
Gutierrez-Cernosek & Levine 1972 [12] RIA n = 10 1st TM serum PGF2α peaked at 2nd TM, decreased to nonpregnant levels at term
n = 52 2nd TM
n = 54 3rd TM
n = 9 serial (14-40wks)
Brummer 1973 [13] unknown n = 13 1st TM serum PGF2α decreased in 2nd TM, plateaued in 3rd TM
n = 40 2nd TM
n = 75 3rd TM
Brummer & Craft 1973 [14] RIA n = 58 L serum PGF2α highest in 1st stage labour, decreased in 2nd stage and remained low
n = 7 serial L
Hertelendy et al 1973 [15] RIA n = 8 PTNL plasma PGE <32wks pregnant similar to nonpregnant
n = 32 L increased through 1st stage labour (early-late), then decreased in 2nd stage
Keirse & Turnbull 1973 [16] GC n = 12 TNL, n = 38 TL AF PGE2 TL>TNL
increased through 1st stage labour
PGE1 <LOD
Salmon & Army 1973 [17] RIA n = 57 AF PGF2α L>TNL
constant through 2nd and 3rd TM, rise after 36wks
spike during 1st stage labour
Challis et al 1974 [18] RIA n = 4 TNL, n = 9 TL plasma PGF TL>TNL (nonsignificant)
Green et al 1974 [19] GC-MS n = 2 TL plasma PGF2α no correlation with stage of labour
n = 5 term serial PGFM TL>TNL
increased through 1st stage labour
Hamberg 1974 [20] RIA? n = 3 serial (9-40wks) urine t-PGFM increased with GA, peaked at term
n = 8 TNL, n = 1TL TL>TNL
Hennam et al 1974 [21] RIA n = 13 1st TM plasma PGF2α levels lowest at 2nd TM compared to 1st and 3rd
n = 10 2nd TM L>3rd TM
n = 20 3rd TM
n = 99 L
Hibbard et al 1974 [22] RIA n = 42 TNL, n = 13 TL AF PGF2α TL>TNL
increased with GA after 36 weeks
n = 22 PTNL 64% <LOD
Hillier et al 1974 [23] RIA n = 11 TNL, n = 5 TL AF PGF2α TL>TNL
increased with labour stage
plasma no correlation with labour stage
Keirse et al 1974 [24] RIA and GC n = 20 TNL, n = 26 TL AF PGF TL>TNL
n = 8 PTNL TNL>PTNL
increased through 1st stage labour
MacDonald et al 1974 [25] RIA n = 6 NL, n = 6 L AF PGF2α L>NL
Singh & Zuspan 1974 [26] PC and TD n = 6 AF PGF2α, PGF1α, PGE1, PGE2 constant from 24-36wks, increase in labour
Hillier et al 1975 [27] RIA n = 13 TNL, n =? TL AF PGF increased with labour stage, peaked before delivery
n = 8 PTNL increased from 2nd TM to term
Johnson et al 1975 [28] RIA n = 38 NL, n = 8 L AF PGF2α L>NL
n = 11 PTNL 3rd TM > 2nd TM
n = 33 NL, n = 99 L plasma no difference between NL and L
n = 15 PTNL no pattern with labour
Pokoly & Jordan 1975 [29] RIA n = 6 TNL, n = 2 TL (CS) AF PGF TL>TNL for CS only
n = 4 TNL, n = 13 TL plasma no difference between NL and L
AF PGE TL>TNL (nonsignificant)
plasma no difference between NL and L
Dray & Frydman 1976 [30] RIA n = 24 NL, n = 37 L AF PGF2α L>NL
n = 19 PTNL higher in late 3rd TM than early 3rd TM
increased with labour stage
PGE2 L>TNL
<LOD before 24wks, increased to 36wks, then remained constant to term
increased with labour stage
PGE1 <LOD
Granstrom & Kindahl 1976 [31] RIA n = 1 term serial urine t-PGFM TL>TNL
late 3rd TM > nonpregnant
Keirse et al 1977 [32] RIA n = 40 TNL, n = 46 TL AF PGF, PGFM TL>TNL
increased through 1st stage labour
Kinoshita et al 1977 [33] RIA n = 7 TNL, n = 10 TL AF PGF2α TL>TNL
PGE1 no difference between TNL and TL
n = 10 TL, n = 10 TNL plasma PGF2α no difference between TNL and TL
n = 10 3rd TM serial no pattern with gestation in 3rd TM
PGE1 no difference between TNL and TL
no pattern with gestation in 3rd TM
no correlation with labour stage
TambyRaja et al 1977 [34] RIA n = 27 PTL AF PGF2α increased through 1st stage labour
Haning et al 1978 [35] RIA n = 4 TNL, n = 8 TL plasma PGFM TL>TNL
Mitchell et al 1978 [36] RIA n = 13 NL, n = 10 L plasma PGF, PGE L > NL
n = 7 PTL no correlation with stage of labour
PGFM L > NL
no difference with PTL and NL
increased with labour stage
Nieder & Augustin 1978 [37] RIA n = 34 AF PGF2α, PGE increased from 31wks to term, steeper after 36wks
plasma no correlation with GA
Zuckerman et al 1978 [38] RIA n = 5 L plasma PGF2α lower in 1st stage labour than 2nd or 3rd
peaked at delivery and at placental separation
Ghodaonkar et al 1979 [39] RIA n = 2 serial (20-40wks) plasma PGFM no pattern with gestation
n = 14 TL increased in 2nd and 3rd stages of labour
Mitchell et al 1979 [40] RIA n = 24 NL, n = 31 TL AF 6-keto-PGF1a TL>TNL
no correlation with GA or cervical dilation
Satoh et al 1979 [41] RIA n = 17 serial (8-39wks) AF PGFM TL>TNL
no pattern with gestation in 3rd TM
n = 8 TNL, n = 10 TL plasma TL>TNL
n = 53 PTNL no correlation with GA
increased with labour stage, peaked at delivery
n = 30 3rd TM serial urine t-PGFM L>NL
Lewis et al 1980 [42] GC-MS n = 6 1st TM plasma 6-keto-PGF1a 2nd-3rd TM > nonpregnant
n = 9 2nd-3rd TM
Dubin et al 1981 [43] RIA n = 39 serial (16-40wks) plasma PGFM TL>TNL
n = 17 PTD no correlation with GA
Sellers et al 1981 [44] RIA n = 13 TNL, n = 21 TL plasma PGFM TL>TNL
n = 12 PTNL, n = 22 PTL PTL>PTNL
no difference between PTNL and PTL
no difference between PTL who delivered term and preterm
increased with labour stage in PTL and TL
Ylikorkala et al 1981 [45] RIA n = 9 serial plasma 6-keto-PGF1a TL>TNL
increased with labour stage
Fuchs et al 1982 [46] RIA n = 14 TNL, n = 20 TL plasma PGFM TL>TNL
Fuchs et al 1982 [47] RIA n = 10 TNL, n = 14 TL plasma PGFM TNL>PTNL
n = 10 PTNL, n = 15 PTL PTL>PTNL
Mitchell et al 1982 [48] RIA n = 10 TNL, n = 10 TL plasma bicyclo-PGEM TL>TNL
n = 10 1st TM 1st TM > nonpregnant
n = 10 2nd TM decreased in 3rd TM until labour
n = 10 3rd TM
Sellers et al 1982 [49] RIA n = 10 TL plasma PGFM increased with labour stage, peaked 5min after delivery
Sharma et al 1982 [50] RIA n = 92 NL, n = 6 TL plasma PGF2α TL>NL
remained unchanged until 2wks before delivery, then increased
PGE2 no difference between TL and NL
remained unchanged until 2wks before delivery, then increased
Fuchs et al 1983 [51] RIA? n = 4 TNL, n = 17 L plasma PGFM TL>TNL
increased with labour stage
Nieder & Augustin 1983 [52] RIA n = 23 1st TM AF PGF, PGE unchanged from 9-34wks, increase at 35wks
n = 37 2nd TM
n = 103 3rd TM
Spitz et al 1983 [53] RIA n = 12 serial (10-40wks) plasma 6-keto-PGF1a decrease after 33wks
Husslein & Sinzinger 1984 [54] RIA n = 5 TNL, n = 5 TL plasma PGEM TL>TNL
n = 5 PTNL no correlation with labour stage
Nagata et al 1984 [55] RIA n = 6 term serial plasma PGF2α TL>TNL
PGE1, PGE2 no difference between NL and L
no correlation with labour stage
Reddi et al 1984 [56] RIA n = 10 TL AF PGF, PGFM increased through 1st stage labour
Sellers et al 1984 [57] RIA n = 14 TNL, n = 9 TL plasma PGFM TL>TNL
Yamaguchi & Mori 1984 [58] RIA n = 4 <20wks plasma PGFM L>NL
n = 3 20-30wks no correlation with GA
n = 16 30-40wks 6-keto-PGF1a L>NL (nonsignificant)
Brennecke et al 1985 [59] RIA n = 9 TNL, n = 27 TL plasma PGFM TL>TNL
n = 12 serial increased with labour stage
bicyclo-PGEM no difference between TNL and TL
no correlation with GA or labour stage
Ogino & Jimbo 1986 [60] RIA n = 5 24-28wks plasma PGF2α peak at 32-36wks
n = 4 28-32wks PGE2 lowest at 36-40wks
n = 7 32-36wks
n = 8 36-40wks
Weitz et al 1986 [61] RIA n = 6 PTL-TD plasma PGFM PTL>PTNL
n = 14 PTL-PTD higher in PTL who delivered PT than those who delivered term
n = 11 PTNL
Ylikorkala et al 1986 [62] RIA n = 8 TNL, n = 13 TL urine 6-keto-PGF1a increased with labour stage and with C-section
Berryman et al 1987 [63] RIA n = 23 L AF PGD2 increased through 1st stage labour
Nagata et al 1987 [64] RIA n = 9 TL plasma PGFM increased with labour stage (nonsignificant)
PGE1 low throughout labour
Nagata et al 1987 [65] RIA n = 7 serial plasma PGFM TL>TNL
decreased 2wks prior to labour
increased with labour stage
Romero et al 1987 [66] RIA n = 23 PTNL, n = 30 PTL AF PGF2α, PGE2 PTL>PTNL
Noort et al 1988 [67] RIA n = 12 1st TM urine 6-keto-PGF1a L>NL (nonsignificant)
n = 12 2nd TM
n = 12 3rd TM
n = 12 TL
Romero et al 1988 [68] RIA n = 32 PTL-TD n = 22 PTL-PTD AF PGE2 higher in PTL who did not respond to tocolysis than those who responded to tocolysis
Sahmay et al 1988 [69] RIA n = 8 TNL, n = 9 TL AF PGF2α no difference between TNL and TL
plasma TL>TNL
AF PGE no difference between TNL and TL
plasma TNL>TL
Noort et al 1989 [70] RIA n = 7 TL plasma PGFM increased with labour stage
6-keto-PGF1a no correlation with labour stage
Romero et al 1989 [71] RIA n = 25 PTL-TD AF PGF2α no difference between PTL who delivered term and preterm
n = 16 PTL-PTD PGFM, bicyclo-PGEM higher in PTL who delivered PT than those who responded to tocolysis
Yamamoto & Kitao 1989 [72] RIA n = 76 term serial plasma PGF2α TL>TNL
increased with labour stage and delivery
Mazor et al 1990 [73] RIA n = 10 PTL-TD AF PGF2α no difference between PTL who delivered term and preterm
n = 10 PTL-PTD PGE2 higher in PTL who delivered PT than those who delivered at term
Norman & Reddi 1990 [74] RIA n = 54 TL AF PGF2α, PGFM, PGE2 increased through 1st stage labour
Fairlie et al 1993 [75] RIA n = 20 TL plasma PGFM increased with labour stage
bicyclo-PGEM in nulliparous: rose after amniotomy but did not change with labour
in multiparous: rose with amniotomy then increased with labour stage
Hillier et al 1993 [76] RIA n = 50 PTL AF PGE2 high levels associated with PTD and delivery within 1wk of amniocentesis
Johnston et al 1993 [77] RIA n = 18 TNL, n = 28 TL plasma PGFM TL>TNL
rose following amniotomy, then remained constant until delivery
PGEM TL>TNL only in primigravid
rose 1–2 after amniotomy, then remained constant until delivery
MacDonald & Casey 1993 [78] RIA n = 50 TNL, n = 190 TL AF PGF2α TL>TNL (forebag and upper compartment)
increased with labour stage, then decreased at 3-5cm dilation
PGFM TL>TNL (forebag and upper compartment)
increased with labour stage, then leveled out at 4–5.5cm dilation until delivery
PGE2 TL>TNL (forebag)
no difference between TL and TNL in upper compartment
increased with labour stage, then leveled out at 4–5.5cm dilation until delivery
Romero et al 1993 [79] RIA n = 24 NL, n = 16 TL AF PGF2α, PGFM, PGE2, 6-keto-PGF1α TL>NL
Romero et al 1994 [80] RIA n = 82 TNL, n = 168 TL AF PGF2α, PGFM, PGE2, 6-keto-PGF1α TL>TNL
increased through 1st stage labour
Lindsay et al 1995 [81] ELISA n = 8 serial (1st-3rd TM) urine 2,3-dinor-6-keto-PGF1α no correlation with GA
pregnant >> nonpregnant
Romero et al 1996 [82] RIA n = 28 serial (n = 17 L) AF PGF2α, PGE2 TL>TNL
increased with GA at term
Ichikawa & Minami 1999 [83] RIA n = 30 serial urine PGF2α TL>NL
increased from 28-36wks
PGFM TL>NL
increased from 28-36wks and again at 2nd stage of labour
Mitchell et al 2005 [84] ELISA n = 24 TNL, n = 37 TL AF 9α,11β-PGF2 TL>TNL
n = 13 PTNL, n = 56 PTL PTNL>PTL
Lee et al 2008 [85] ELISA n = 68 TNL, n = 34 TL AF PGF2α TL>TNL
n = 65 PTNL no correlation with GA until 36wks, 25-fold increase at TNL
increased with labour stage
PGE2 no difference between TL and TNL
no correlation with GA until 36wks, 2-fold increase at TNL
Lee et al 2009 [86] ELISA n = 140 PPROM (n = 126 PTD) AF PGF2α high levels associated with low GA at delivery and PTD
Maddipati et al 2014 [87] LC-MS n = 10 TNL, n = 35 TL AF PGF2α, PGFM, PGE2, bicyclo-PGEM, PGA2, PGJ2 TL>TNL
n = 18 PTNL
19-OH-PGE2 no difference between TL and TNL
TNL>PTNL
Park et al 2016 [88] ELISA n = 132 PTL (n = 41 PTD) AF PGF2α high levels associated with low GA at delivery and PTD
Rosen et al 2019 [89] GC-NICI-MS n = 740 (n = 41 sPTD) urine PGF2α no difference in 3rd TM levels between term and preterm delivery
Eick et al 2020 [90] GC-NICI-MS n = 469 (n = 50 PTD) urine PGF2α levels at 20-24wks and 24-28wks higher in preterm than term group
associated with increased odds of PTB
Peiris et al 2020 [91] LC-MS n = 10 TNL, n = 28 TL AF PGF2α, PGFM, PGE2 TL>TNL
Takahashi et al 2021 [92] LC-MS n = 11 TNL, n = 10 TL AF PGE2, 15-keto-PGE2, PGEM, 19-OH-PGE2 TL>TNL

Abbreviations: TLC = thin layer chromatography, NL = no labour, TL = term labour, LOD = limit of detection, RIA = radioimmunoassay, L = labour, TM = trimester, PTNL = preterm no labour, GC = gas chromatography, AF = amniotic fluid, TNL = term no labour, GC-MS = gas chromatography-mass spectrometry, PGFM = 13,14-dihydro-15-keto-PGF2α, t-PGFM = 5α,7α-dihydroxy 11-keto tetranor-prostane 1,16-dioic acid, GA = gestational age, PC = paper chromatography, TD = transmission densitometry, CS = Caesarean section, PTL = preterm labour, PTD = preterm delivery, bicyclo-PGEM = 11-deoxy-13,14-dihydro-15-keto-11,16-bicyclo PGE2, PGEM = 13,14-dihydro-15-keto-PGE2, PTL-TD = preterm labour-term delivery, PTL-PTD = preterm labour-preterm delivery, PT = preterm, ELISA = enzyme-linked immunosorbent assay, PPROM = preterm premature rupture of membranes, LC-MS = liquid chromatography-mass spectrometry, NICI = negative ion chemical ionization, sPTD = spontaneous preterm delivery.