Association between first-trimester PAPP-A and large-for-gestational-age neonates in non-diabetic pregnancies: An...

To evaluate the predictive value of elevated first-trimester pregnancy-associated plasma protein-A (PAPP-A) for large-for-gestational-age (LGA) neonates in non-diabetic pregnancies, and to investigate its potential modifying effect on classical fetal-growth-restricting factors.

This retrospective cohort study analysed 563 normoglycaemic pregnancies, with strict exclusion of patients with gestational or pregestational diabetes. Participants were stratified by first-trimester PAPP-A percentile into high (>90th percentile, n = 73) and normal (≤90th percentile, n = 490) groups. Multivariate logistic regression models [categorical > 90th percentile and continuous multiples of the median (MoM)] were adjusted for maternal age, body mass index, weight gain, smoking status, and fetal gender. Main outcomes included birth weight, LGA (>4000 g), neonatal length, and neonatal intensive care unit admission rate.

High PAPP-A was significantly associated with higher mean birth weight (3388.2 ± 526.4 g vs 3193.1 ± 538.7 g; p = 0.004) and a 2.4-fold increase in the incidence of LGA (11.0% vs 4.5%; p = 0.044). PAPP-A MoM was positively correlated with neonatal crown-heel length (r = 0.132; p = 0.001). In the continuous multivariate model, every 1-unit increase in PAPP-A MoM was associated with a 1.82-fold increase [95% confidence interval (CI) 1.21-2.72; p = 0.003] in the risk of LGA. Receiver operating characteristic curve analysis showed an area under the curve of 0.665 (95% CI 0.566-0.762), with a high negative predictive value of 95.5% (95% CI 93.3-97.0%) but limited sensitivity (26.7%, 95% CI 14.2-44.4%) and positive predictive value (11.0%, 95% CI 5.7-20.2%). In exploratory subgroup analyses, high PAPP-A was associated with higher birth weight in the presence of factors such as advanced maternal age and limited weight gain.

In non-diabetic pregnancies, elevated first-trimester PAPP-A is an independent correlate of fetal overgrowth. As a potential marker of increased free insulin-like growth factor bioavailability, high PAPP-A may reflect an anabolic signal that warrants further investigation in multiparametric prediction models. Its clinical utility as a standalone screening tool is currently limited by low sensitivity and a positive predictive value; therefore, its role remains to be established in larger prospective trials.