Low levels of maternal serum PAPP-A in the first trimester and the risk of pre-eclampsia.
BACKGROUND
Low levels of pregnancy associated plasma protein-A (PAPP-A) have been previously shown to be associated with pregnancies that subsequently develop pre-eclampsia. The objective of this study was to establish the relative risk for pre-eclampsia at various PAPP-A levels as an aid to counselling and follow up of pregnancies.


METHODS
Maternal serum PAPP-A and free ss-human chorionic gonadotropin (ss-hCG) levels at 11 to 13 weeks of gestation from 224 singleton pregnancies that subsequently developed pre-eclampsia were compared to those from 47,770 normal singleton pregnancies resulting in live births after 37 weeks with birth weight greater than or equal to the 10th centile of normal for gestation. In all cases, the measured PAPP-A and free ss-hCG levels were expressed as multiple of the median (MoM). The association between metabolite levels and the incidence of pre-eclampsia was assessed by comparing the relative incidence at a number of MoM cut-offs and at various centiles. At various marker levels, the likelihood ratio for pre-eclampsia was also calculated.


RESULTS
In the pre-eclampsia group the median PAPP-A MoM was significantly reduced (0.772 MoM, p < 0.0001) whilst the median free beta-hCG MoM was not different from controls (0.981 MoM, p = 0.26). With decreasing levels of PAPP-A, the likelihood ratio for pre-eclampsia increased. At the 5th centile of normal (PAPP-A MoM 0.415) the odds ratio was increased 4-fold and at this cut-off 15% of cases of pre-eclampsia would be identified.


CONCLUSIONS
The graphical presentation of a likelihood ratio curve for pre-eclampsia at any PAPP-A MoM level is likely to be useful in counselling women with low levels of PAPP-A and a normal karyotype. Use of low levels of PAPP-A for selecting women for further follow-up with uterine artery Doppler may further improve the clinical discrimination.
Spencer
Kevin
K
Prenatal Screening Unit, Department of Clinical Biochemistry, King George Hospital, Goodmayes, Essex, UK. KevinSpencer1@aol.com
Cowans
Nicholas J
NJ
Nicolaides
Kypros H
KH
D000328:Adult; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D005260:Female; D005865:Gestational Age; D006801:Humans; D016017:Odds Ratio; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D012307:Risk Factors
D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A