Eliminating first trimester markers: will replacing PAPP-A and βhCG miss women at risk for small for gestational age?

Objective: Placental analytes are traditionally used for aneuploidy screening, although may be replaced by cell-free fetal DNA. Abnormal analytes also identify women at risk for small for gestational age (SGA). We sought to quantify the proportion of women at risk for SGA by low pregnancy-associated plasma protein-A (PAPP-A) or beta hCG who would not otherwise be identified by maternal risk factors. Methods: We studied first-trimester PAPPA-A and bhCG from 658 euploid singleton pregnancies from a prospective longitudinal cohort. Analytes were standardized for gestational age in multiples of the median (MoM). SGA was defined as birthweight z-score <=-1.28. Maternal risk factors included chronic hypertension, pre-gestational diabetes and age >= 40. Results: Mean GA was 38.8 +/- 1.9 weeks; 6.8% had a SGA infant. Low PAPP-A and bhCG were identified in 48 (7.4%) and 9 (1.4%) of pregnancies, respectively, of whom 18.9% were SGA (OR 3.0, 95% CI 1.4-6.3). 88% did not have risk factors for SGA. Among women with no risk factors, low PAPP-A was a significant predictor of SGA (OR 3.3, 95% CI 1.5-7.4). Conclusion: Most women with abnormal analytes did not have risk factors for SGA. Eliminating PAPP-A and bhCG may present missed opportunities to identify women at risk for SGA.