First-trimester placental protein 13 and placental growth factor: markers for identification of women destined to develop early-onset pre-eclampsia.
OBJECTIVE
To investigate the predictive value of maternal serum pregnancy-associated plasma protein A (PAPP-A), free β subunit of human chorionic gonadotrophin (fβ-hCG), placental protein 13 (PP13), placental growth factor (PlGF) and a desintegrin and metalloproteinase 12 (ADAM12), for first-trimester identification of early-onset pre-eclampsia.


METHODS
Nested case-control study.


METHODS
Routine first-trimester screening for trisomy 21 in the Netherlands.


METHODS
Eighty-eight women who developed pre-eclampsia or haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 34 weeks of gestation and 480 controls.


METHODS
PP13, PlGF and ADAM12 were measured in stored first-trimester serum, previously tested for PAPP-A and fβ-hCG. All marker levels were expressed in multiples of the gestation-specific normal median (MoMs). Model predicted detection rates for fixed false-positive rates were obtained for statistically significant markers alone and in combination.


METHODS
Development of pre-eclampsia or HELLP syndrome.


RESULTS
PP13 and PlGF were reduced in women with pre-eclampsia, with medians 0.68 MoM and 0.73 MoM respectively (P < 0.0001 for both). PAPP-A was reduced (median 0.82 MoM, P < 0.02) whereas ADAM12 and fβ-hCG did not differ between control women and those with pre-eclampsia. In pre-eclampsia complicated by a small-for-gestational-age fetus, all markers except fβ-hCG had lower values, compared with pregnancies involving fetuses of normal weight. The model-predicted pre-eclampsia detection rate for a combination of PP13 and PlGF was 44% and 54%, respectively, for a fixed 5% and 10% false-positive rate.


CONCLUSIONS
This study demonstrates that PP13 and PlGF in the first-trimester might be promising markers in risk assessment for early pre-eclampsia/HELLP syndrome but for an adequate screening test additional characteristics are necessary.
Wortelboer
E J
EJ
Department of Obstetrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands. E.Wortelboer@umcutrecht.nl
Koster
M P H
MP
Cuckle
H S
HS
Stoutenbeek
P H
PH
Schielen
P C J I
PC
Visser
G H A
GH
D051722:ADAM Proteins / Q000378:metabolism; D000072199:ADAM12 Protein; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000378:metabolism; D019483:Disintegrins / Q000378:metabolism; D042241:Early Diagnosis; D005260:Female; D037161:Galectins / Q000378:metabolism*; D017359:HELLP Syndrome / Q000175:diagnosis; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000175:diagnosis*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism*; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism; D011296:Prenatal Diagnosis / Q000379:methods*
D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D019483:Disintegrins; D037161:Galectins; C038195:LGALS13 protein, human; D008565:Membrane Proteins; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; D011266:Pregnancy-Associated Plasma Protein-A