Role of first-trimester free beta subunit of human chorionic gonadotropin (β-HCG) and pregnancy- associated plasma protein-A (PAPP-A) as markers for intrauterine fetal growth restriction

Intrauterine growth restriction (IUGR) is a major determinant of perinatal morbidity and mortality. Standard diagnostic methods like sonography are accurate, but they can not be employed as the screening tools. Lately, it has been proposed that there might be an association between IUGR and placental dysfunction; hormones such as human chorionic gonadotropin-beta subunit (β-HCG) and pregnancy-associated plasma protein-A (PAPP-A) may be good early indicators of unwanted outcomes. This study is aimed at evaluating the possible association of serum free β-HCG and PAPP-A levels in the first trimester with IUGR in chromosomaly normal pregnancies. In this cohort study, 1440 normal singleton pregnancies were evaluated in Tabriz Alzahra Teaching Hospital during a 17-month period. Serum free β-HCG and PAPP-A levels were measured in women at 10 to 14 weeks of pregnancy by enzyme linked immunosorbent assay (ELISA). All the women were followed up to determine the time of delivery and to be categorized as with or without IUGR. Serum free β-HCG and PAPP-A levels were compared between the groups. The rate of IUGR was 4.4%. The mean serum levels of free β-HCG and PAPP-A were 2.6±2.7 (range: 0.1 to 10.8, median: 0.9) M.O.M (multiples of the median) 2.4±2.6 (range: 0.1 to 8.9, median: 0.9) MoM, respectively. The median serum β-HCG was 1 and 0.9 MoM in cases with normal and IUGR pregnancies, respectively (p=0.587). The median serum PAPP-A was significantly lower in patients with IUGR (0.7 vs. 0.9 MoM; p=0.044). The optimal cut-off point for PAPPA was 0.79 MoM with sensitivity and specificity of 51 and 54%, respectively. This study showed that low level of serum PAPP-A but not β-HCG during the first trimester is associated with IUGR.