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First trimester PAPP-A levels correlate with sFlt-1 levels longitudinally in pregnant women with and without preeclampsia

Aditi R Saxena1*, Ellen W Seely1, Janet W Rich-Edwards1, Louise E Wilkins-Haug2, S Ananth Karumanchi3 and Thomas F McElrath2

Author Affiliations

1 Department of Medicine, Brigham and Women’s Hospital, 221 Longwood Avenue, RFB-2, Boston, MA, 02115, USA

2 Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Boston, MA, USA

3 Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

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BMC Pregnancy and Childbirth 2013, 13:85  doi:10.1186/1471-2393-13-85

Published: 4 April 2013



First trimester Pregnancy Associated Plasma Protein A (PAPP-A) levels, routinely measured for aneuploidy screening, may predict development of preeclampsia. This study tests the hypothesis that first trimester PAPP-A levels correlate with soluble fms-like tyrosine kinase-1 (sFlt-1) levels, an angiogenic marker associated with preeclampsia, throughout pregnancy.


sFlt-1 levels were measured longitudinally in 427 women with singleton pregnancies in all three trimesters. First trimester PAPP-A and PAPP-A Multiples of Median (MOM) were measured. Student’s T and Wilcoxon tests compared preeclamptic and normal pregnancies. A linear mixed model assessed the relationship between log PAPP-A and serial log sFlt-1 levels.


PAPP-A and PAPP-A MOM levels were significantly lower in preeclamptic (n = 19), versus normal pregnancies (p = 0.02). Although mean third trimester sFlt-1 levels were significantly higher in preeclampsia (p = 0.002), first trimester sFlt-1 levels were lower in women who developed preeclampsia, compared with normal pregnancies (p = 0.03). PAPP-A levels correlated significantly with serial sFlt-1 levels. Importantly, low first trimester PAPP-A MOM predicted decreased odds of normal pregnancy (OR 0.2, p = 0.002).


Low first trimester PAPP-A levels suggests increased future risk of preeclampsia and correlate with serial sFlt-1 levels throughout pregnancy. Furthermore, low first trimester PAPP-A status significantly predicted decreased odds of normal pregnancy.