# Low PAPP-A levels and their association with adverse perinatal outcomes in twin pregnancies

## TL;DR

This study explores how low levels of PAPP-A in early pregnancy are linked to complications in twin pregnancies, such as preterm birth.

## Contribution

The study investigates the association between first-trimester PAPP-A levels and adverse outcomes in twin pregnancies, an area with limited prior research.

## Key findings

- Low PAPP-A levels were associated with preterm birth in twin pregnancies.
- High PAPP-A levels were linked to hypertensive disorders of pregnancy.
- Using specific cut-off points for PAPP-A levels did not yield statistically significant associations with outcomes.

## Abstract

While in singleton pregnancies the maternal serum biomarkers used in the first-trimester screening for aneuploidies, particularly PAPP-A, may be, also, used as predictors of adverse perinatal outcomes, there is a scarcity of data regarding the association of first-trimester biomarkers with unfavorable pregnancy outcomes in twin pregnancies. The main purpose of our study was to evaluate the association of low PAPP-A levels in twin pregnancies with the subsequent development of perinatal complications.

454 twin pregnancies were recruited over a period of 11 years, and their data were analyzed retrospectively. First trimester assessment at 11 + 0–13 + 6 weeks included examination of fetal anatomy and markers of aneuploidy and measurement of the maternal serum concentration of PAPP-A and free b-hCG. The outcomes under investigation were preterm rupture of the membranes, preterm delivery earlier than 32, 34, and 36 weeks, gestational diabetes, hypertensive disease of the pregnancy (including pregnancy induced hypertension and pre-eclampsia), intrauterine demise, birth weight difference of more than 25% among the fetuses and composite adverse pregnancy outcome (which included preterm rupture of the membranes, preterm delivery earlier than < 36 weeks, hypertensive disease of the pregnancy, and gestational diabetes).

Low first-trimester PAPP-A levels were related with preterm birth, whereas high levels were associated with hypertensive disorders of pregnancy. When using specific cut-off points such as low PAPP-A MoM < 5th and < 10th centile or high PAPP-A MoM > 90th and 95th centile, these associations were not significant.

Low first-trimester PAPP-A levels were related with preterm birth, whereas high levels were associated with hypertensive disorders of pregnancy. When specific cut-off points were investigated, these associations were not statistically significant.

The online version contains supplementary material available at 10.1007/s00404-025-08299-7.