Use of first or second trimester serum markers, or both, to predict preeclampsia

• Longitudinal study of serum markers and preeclampsia (PE) in early pregnancy.
• Strongest association found for 2nd trimester markers and severe/early PE.
• Pregnancy-associated plasma protein-A (PAPP-A) strongest marker for PE.
• Placental like growth factor (PlGF) strongest late marker for severe/early PE.
• No markers were suitable for a between-trimester repeated measure.

ObjectivesPreeclampsia is a serious complication of pregnancy, threatening fetal and maternal health. The aim of our study is to examine the association between preeclampsia and biochemical markers, in matched first and second trimester maternal serum samples.Study designThis is a nested case/control study derived from the cohort of pregnancies delivering at Women & Infants Hospital. Cases were identified at a clinic or by hospital codes, and individually confirmed by record review. Stored samples were available from ‘integrated’ Down syndrome screening. Results were expressed as multiples of the median (MoM).Main outcome measuresPreeclampsia was classified as early/severe, late/severe, or mild based on professional guidelines. An additional adverse outcome group had only gestational hypertension.ResultsNinety-eight cases were each matched with five control pregnancies. Population distribution parameters and within and between trimester correlations were derived for cases and controls for six markers, as well as in case subgroups. The strongest associations were for early/severe preeclampsia with second trimester PAPP-A (rank sum test 2.30, p < 0.01); PlGF (2.60, p < 0.05) inhibin A (4.45, p < 0.05) and endoglin (4.25, p < 0.05). No strong associations were found for sVEGF-R and FLRG. Second trimester associations were stronger than those in the first (e.g., PAPP-A 2.45, p < 0.01). No between-trimester associations were found that would provide important improvements in prediction.ConclusionsThis matched analysis of the serum markers in early pregnancy allows for direct comparison of first and second trimester associations with preeclampsia. PAPP-A and PlGF are equally and highly predictive of early/severe preeclampsia.