Low PAPP-A Levels and Growth in Twin Pregnancies

It is well established in the modern literature that newborns delivered from multiple gestations are more predisposed to low birthweight in comparison to their singleton equivalents. In this study, we sought to explore the potential of first-trimester biochemical (PAPP-A and free β-hCG) and biophysical indices (uterine artery Doppler) to predict low birthweight in one or both twins.

This is a retrospective cohort analysis of 400 twin viable pregnancies presenting for routine first-trimester assessment in four fetal medicine centers between 2014 and 2025. The examination included the recording of maternal demographic characteristics and medical history, the assessment of markers of aneuploidy and the fetal anatomy, the measurement of mean arterial pressure, the assessment of uterine arteries and the measurement of serum concentration of PAPP-A and free β-hCG. The evaluated outcomes included BW ≤ 3rd centile and BW ≤ 10th centile in one or both twins based on local population birthweight reference charts.

The study cohort consisted of 400 twin pregnancies. BW ≤ 3rd centile in one or both twins was reported in 1.5 and 3.8% of cases, respectively, and there was no association of BW ≤ 3rd centile with any of the studied parameters. BW ≤ 10th centile in one or both twins was reported in 14.8 and 9.8% of the cases, respectively. PAPP-A MoM values were significantly lower in cases complicated by BW ≤ 10th centile in one and in both twins, remaining statistically significant even after the appropriate multiple logistic regression. PAPP-A MoM demonstrated statistically significant but low prognostic value for BW ≤ 10th centile in either one or both twins.

Low PAPP-A levels were associated with BW ≤ 10th centile in one and both twins and its significant value as a risk marker was demonstrated. Higher PAPP-A MoM halves the risk of having at least one twin with low BW. Other maternal biophysical and biochemical indices did not seem to be predictive of low birthweight.