First trimester maternal serum biochemical markers of aneuploidy in pregnancies with abnormally invasive placentation

Abstract

Objective To examine whether differences exist in routine first trimester maternal serum screening analyte measurements between normal pregnancies, placenta praevia and abnormally invasive placentation (AIP). Design Multidisciplinary audit.Setting Associated university teaching hospital with 9000 annual deliveries.Population Five hundred and sixteen pregnancies in total, including 344 normal controls, 17 with AIP and 155 placenta praevia cases.Methods Comparison of maternal serum free bhCG and PAPP-A MoMs distribution in pregnancies with abnormally invasive placentation, placenta praevia and normal controls, after correcting for known confounding factors between October 2005 and September 2013. Data from a previously published first trimester AIP and biochemistry study were combined with our study data and compared in the above way to complete the analysis.Main outcome measures Differences in first trimester maternal serum PAPP-A and free bhCG in AIP, placenta praevia, and normal pregnancies.Results Median free bhCG MoM in the control group was 1.04, and 1.08 (P = 0.859) in the placenta praevia group compared with 0.81 in the AIP group (P = 0.06). Median PAPP-A MoM was 1.01 in the control group and 1.05 (P = 0.83) in praevia, compared with 1.22 in AIP cases (0.16). The combined AIP dataset gave an overall PAPP-A median MoM of 1.40, and free bhCG of 0.85. Both markers showed a significantly different distribution from controls (PAPP-A P = 0.002 and free bhCG P = 0.031).Conclusions There may be differences between first trimester maternal serum biochemical markers between normal pregnancies and those complicated by abnormally invasive placentation. If upheld, this may provide useful information for the early identification of abnormally invasive placentation. More studies are required.

FIGO consensus guidelines on placenta accreta spectrum disorders: Prenatal diagnosis and screening,

“…Several placental and fetal hormones routinely used in the screening of Down syndrome have been found to have different concentrations in the serum of women with placenta previa accreta compared with those with a non‐accreta previa . At 11–12 weeks of pregnancy, human chorionic gonadotropin (hCG) and its free beta‐subunit (β‐hCG) are lower and pregnancy‐associated plasma protein A (PAPP‐A) is higher in the maternal serum of women with PAS disorders.…”

Placenta Accreta Spectrum: A Review of Pathology, Molecular Biology, and Biomarkers

“…The use of ultrasound and MRI in the diagnosis of PAS has been extensively reviewed elsewhere [ 2 , 55 , 56 ]. Several placental and fetal hormones routinely used in the screening for aneuploidy have been found to be differentially expressed in the serum of women with PAS compared with those with placenta previa [ 57 , 58 ]. More recently, there has been increasing interest in the role of cell-free fetal DNA (cffDNA) for screening and diagnosis of PAS.…”

“…This led to further studies into maternal serum AFP in the setting of a nonanomalous fetus, to investigate any association between elevated second trimester maternal serum AFP and PAS, all of which suggest that increased level of AFP are associated with PAS ( Table 1 ) [ 86 ]. Interestingly, Zelop et al showed that although AFP was elevated in approximately 45% of confirmed PAS cases, the negative controls did not have elevated levels suggesting this test may have a high negative predictive value [ 57 ].…”

Second‐trimester levels of fetoplacental hormones among women with placenta accreta spectrum disorders

“…α‐Fetoprotein (AFP) is synthesized by the secondary yolk sac and fetal liver. Levels of both hormones differ between women with placenta accreta spectrum (PAS) disorders and those with non‐accreta previa . Second‐trimester maternal serum levels of AFP are increased, and first‐trimester serum β‐hCG is decreased in women with PAS, compared with those with non‐accreta placenta previa.…”

“…Levels of both hormones differ between women with placenta accreta spectrum (PAS) disorders and those with non‐accreta previa . Second‐trimester maternal serum levels of AFP are increased, and first‐trimester serum β‐hCG is decreased in women with PAS, compared with those with non‐accreta placenta previa. An increased level of cell‐free β‐hCG mRNA has also been found in the plasma of women with PAS disorder .…”