Pregnancy outcome in the setting of extremely low first trimester PAPP-A levels


  • If Fergus Scott is unavailable, then send to Dr Andrew McLennan at the same address.

: Dr Fergus Scott, Sydney Ultrasound for Women, Level 3, 321 Kent Street, Sydney, NSW 2001, Australia. Email:


Background: Serum pregnancy-associated plasma protein-A (PAPP-A) is part of first trimester Down syndrome screening. Low levels have been associated with adverse outcome as well as chromosomal abnormality.

Aims: To assess the incidence of adverse outcome when PAPP-A levels are at or below 0.2 multiples of the median (MoM).

Methods: Data on consecutive patients attending a first trimester screening program were collected. Those with PAPP-A levels ≤ 0.2 MoM were divided into three groups: ≤ 0.1 MoM; 0.11–0.15 MoM; and 0.16–0.2 MoM.

Results: Screening 44 535 patients resulted in 197 with PAPP-A levels ≤ 0.2 MoM. The incidence of karyotypic abnormality increased with decreasing PAPP-A levels. In the absence of chromosome abnormality, pregnancy outcomes were defined as ‘normal’ in at least 30% and ‘good’ in at least 60%, with both percentages increasing as the PAPP-A level rose. The PAPP-A levels were significantly lower in the group with a poor outcome. The incidence of prematurity was similar in the three groups, but higher than the statewide average, while the incidence of extreme prematurity appeared to be related to reducing PAPP-A levels. The incidence of growth restriction in the three groups was similar, but was still double the incidence in the normal population.

Conclusion: If the PAPP-A level is ≤ 0.2 MoM and the karyotype is normal, there is an increased risk of adverse outcome. Even with PAPP-A below 0.1 MoM, a good outcome can be expected in 60% of cases. Careful morphological assessment is suggested and later monitoring of fetal growth and well-being.