Abstract
BackgroundFirst 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.MethodssFlt-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.ResultsPAPP-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).ConclusionsLow 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.
Highlights
First trimester Pregnancy Associated Plasma Protein A (PAPP-A) levels, routinely measured for aneuploidy screening, may predict development of preeclampsia
The rise in soluble fms-like tyrosine kinase-1 (sFlt-1) precedes the onset of clinical signs of preeclampsia [8]. As both PAPP-A and sFlt-1 may predict increased risk for preeclampsia, in this study we explore the relationship of 1st trimester PAPP-A levels, which are obtained routinely for clinical care, with serial levels of sFlt-1, a widely accepted marker of preeclampsia in research, and test the hypothesis that 1st trimester PAPP-A correlates with serial sFlt-1 levels throughout pregnancy
The relationship of first trimester PAPP-A to serial levels of placental growth factor (PlGF) and serial ratios of sFlt-1 to PlGF were explored, as studies have shown that PlGF is significantly lower in preeclampsia [9] and the ratio of sFlt-1/PlGF is significantly elevated in preeclampsia [10,11], prior to the onset of clinical signs
Summary
First trimester Pregnancy Associated Plasma Protein A (PAPP-A) levels, routinely measured for aneuploidy screening, may predict development of preeclampsia. Several markers have been evaluated regarding their ability to predict preeclampsia in the first trimester, prior to clinical onset of clinical signs. Pregnancy associated Plasma Protein A (PAPP-A) levels are measured in clinical practice for the 1st trimester aneuploidy screen, as low levels indicate addition, the relationship of first trimester PAPP-A to serial levels of placental growth factor (PlGF) and serial ratios of sFlt-1 to PlGF were explored, as studies have shown that PlGF is significantly lower in preeclampsia [9] and the ratio of sFlt-1/PlGF is significantly elevated in preeclampsia [10,11], prior to the onset of clinical signs
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