Use of the combined first‐trimester screen result and low PAPP‐A to predict risk of adverse fetal outcomes

Abstract

ObjectivesTo investigate associations between combined first‐trimester screen result, pregnancy associated plasma protein‐A (PAPP‐A) level and adverse fetal outcomes in women.MethodsPregnancy outcomes for 10 273 women participating in a community based first‐trimester screening (FTS) programme in Western Australia were ascertained by record linkage to birth and birth defect databases. A first‐trimester risk cut‐off of ≥ 1 in 300 defined screen positive women.ResultsScreen positive pregnancies were more likely to have Down syndrome and birth defects (chromosomal or nonchromosomal) than screen negative pregnancies. When birth defects were excluded, screen positive pregnancies were at increased risk of pregnancy loss, low birth weight and preterm birth. Pregnancies with low PAPP‐A (⩽0.3 multiples of the median (MoM)) had higher risk of chromosomal abnormality, birth defect, preterm birth, low birth weight, or pregnancy loss, compared to those with PAPP‐A > 0.3 MoM. In pregnancies without birth defects, low PAPP‐A was a stronger predictor of preterm birth, low birth weight or pregnancy loss than a screen positive result.ConclusionsWomen with positive screen or low PAPP‐A were at increased risk for some adverse fetal outcomes. The sensitivity of these parameters was insufficient to support primary screening, but increased surveillance during pregnancy may be appropriate. Copyright © 2008 John Wiley & Sons, Ltd.

The Impact of First-Trimester Serum Free β-Human Chorionic Gonadotropin and Pregnancy-Associated Plasma Protein A on the Diagnosis of Fetal Growth Restriction and Small for Gestational Age Infant

“…1 As obtained by logistic regression equations including terms for SGA (n = 2,134) or FGR (n = 1,975) as outcome variables and PAPP-A, ␤-hCG, BMI <10th percentile and smoking at enrolment as dichotomous categorical variables. From a biologic point of view, PAPP-A plays a significant etiologic role in promoting fetal growth by breaking down IGF-binding proteins [6]. Given the heterogeneity of etiologic factors associated with FGR and the role of other proteins and hormones regulating fetal growth [6][7][8][9][10][11][12][13][14][15][16][17][18][19], it is likely that the activity of PAPP-A, although important, is only one of a number of factors regulating fetal growth processes.…”

“…Literature data suggest that first-trimester maternal serum concentrations of PAPP-A below the 10th percentile are associated with an OR of SGA between 2 and 5 [3][4][5][6]. Given our sample of 2,000, women our study had 90.2% power (␣ !…”

“…In previous studies on the predictive value of first-trimester biochemical screening, SGA at birth has been used as a proxy of intrauterine growth failure [3][4][5][6]8]. As reported in table 1, the likelihood of an SGA infant is between 2.4 and 2.8 times higher among women with first-trimester PAPP-A values below the 5th percentile than in controls with higher concentrations [1,3,4,9,10].…”

First trimester predictors of adverse pregnancy outcomes

“…Several studies have demonstrated an association between decreased first trimester PAPP-A concentrations and intrauterine growth restriction, 4-7 low birthweight, 7-10 preterm delivery, [4][5][6][9][10][11] stillbirth after 24 weeks gestation, 9,10,12 increased risk of miscarriage, pregnancy-induced hypertension and gestational diabetes. 4,5,9 Previous studies have also identified adverse obstetric outcomes associated with single markers such as increased fetal NT 13,14 and abnormal free β-hCG levels, 15 and among pregnancies identified at increased risk of Down syndrome, there was a greater risk of poor outcomes such as spontaneous abortion, placenta praevia, intrauterine fetal demise, pregnancy-induced hypertension and preterm labour.…”

Cornelia de Lange syndrome (CdLS): prenatal and autopsy findings

“…First trimester screening done in our Case 2 showed low PAPP-A. However, this finding is non-specific and has been associated with a number of conditions and adverse fetal outcomes including preterm birth, preeclampsia, low birth weight and pregnancy loss (Dugoff et al, 2004;Barrett et al, 2008). The cystic hygroma detected in our first case has been associated with a variety of conditions including aneuploidy, pregnancy loss and genetic syndromes such as Noonan syndrome (Malone et al, 2005).…”