PAPP-A2. Median values in normal pregnancy in first trimester and association to Small-For-Gestational-Age infants.

Young Bae Hansen1,*, Vibeke Myrhøj1, Finn Stener Jørgensen2, Claus Oxvig3, Steen Sørensen1

1Department of Clinical Biochemistry, 2Fetal Medicine Unit, Department of Gynecology and Obstetrics, Copenhagen University Hospital Hvidovre, Hvidovre, 3Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark

Introduction: Pregnancy-Associated Plasma Protein A2 (PAPP-A2) is a recently discovered protease that cleaves Insulin-Growth-Factor-Binding-Protein-5. Its molecular function suggests involvement in the Insulin-Growth-Factor system that is imperative in fetal growth and development.

Objectives: The objectives were to establish median values for singleton normal pregnancies at 8-14 gestational weeks (GW) and to investigate whether PAPP-A2 is associated with Small-For-Gestational-age (SGA) infants before and after stratification according to maternal hypertension and/or proteinuria.

Methods: This study was a retrospective study based on serum samples from pregnant women who were screened for chromosomal aneuploidy at Copenhagen University Hospital Hvidovre from 2004-2008. We included 985 normal and 170 SGA cases. PAPP-A2 was measured by ELISA from AnshLabs. We obtained a median curve for PAPP-A2 at 8-14 GW by stratifying the concentrations from normal cases according to gestational day. All concentrations were converted to Multiple of the Medians and adjusted for variables that influenced the measured concentrations. We stratified the SGA group as described above. Mann-Whitney U test was used for comparisons.






Median MoM  (IQR)

Number of cases (%)

Median MoM  (IQR)

Number of cases (%)

Normal or SGA

1.0 (0.8-1.26)

985 (100)

0.93 (0.75-1.3)

170 (100)


Blood pressure ±proteinuria



Essential hypertension

Gestational hypertension

Mild preeclampsia

Severe preeclampsia


1.0 (0.8-1.25)


1.04 (0.95-1.15)

1.07 (0.84-1.28)

1.04 (0.96-1.42)

0.95 (0.75-1.63)


936 (95.0)

1 (0.1)

6 (0.6)

12  (1.2)

25 (2.5)

5 (0.5)


0.91 (0.73-1.23)



1.02 (0.82-1.13)

1.3 (0.82-1.69)

1.56 (1.34-2.00)


151 (88.8)


1 (0.6)

4 (2.4)

6 (3.5)

8 (4.7)








Conclusion: Data for PAPP-A2 median in first trimester fitted a cubic model. There was no difference between the normal and SGA cases, but, at subgroup level we found marginal lower PAPP-A2 in the normotensive SGA group compared to the normotensive normal group.

Keywords: Biochemistry, Biomarker