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Correlation and predictive value of first-trimester serum markers (PAPP-A, Free β-hCG) for small-for-gestational-age
Fatemeh Nasiri-Amiri1, Shabnam Omidvar2, Nesa Asnafi1
1Infertility and Health Reproductive Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
Insights
First-trimester PAPP-A MoM shows promise as a predictor for small-for-gestational-age (SGA) births, offering early risk assessment. Free β-hCG MoM did not provide additional predictive value in this study.
Area of Science:
- Obstetrics and Gynecology
- Prenatal Diagnostics
- Biomarker Research
Background:
- First-trimester biomarkers can predict abnormal fetal growth, including small-for-gestational-age (SGA) and large-for-gestational-age (LGA) births.
- Maternal serum levels of PAPP-A and free β-hCG are assessed between 11 and 14 weeks of gestation.
Purpose of the Study:
- To evaluate the relationship and predictive capacity of maternal serum PAPP-A and free β-hCG levels for subsequent birth weight outcomes.
- To determine the utility of these biomarkers in predicting SGA and LGA.
- To assess the independent predictive value of PAPP-A and free β-hCG for birth weight.
Main Methods:
- Prospective cohort study of 162 singleton pregnancies in Babol, Iran.
- First-trimester screening included nuchal translucency and biochemical analysis (PAPP-A, free β-hCG MoM).
- Statistical analyses included correlation, regression, and ROC curve analysis.
Main Results:
- PAPP-A multiples of the median (MoM) showed a strong positive correlation with birth weight (ρ=0.711, p<0.001).
- PAPP-A MoM was an independent predictor of birth weight and the sole predictor for SGA (AUC: 0.949, sensitivity: 100%, specificity: 82.9%).
- Free β-hCG MoM had a modest correlation with birth weight and no independent predictive value for SGA or LGA.
Conclusions:
- First-trimester PAPP-A MoM is a promising independent marker for predicting the risk of SGA.
- Free β-hCG MoM did not offer significant additional predictive value in this cohort.
- Further external validation in larger, diverse populations is needed for clinical application of PAPP-A for SGA risk assessment.
Abstract:
The first trimester offers valuable biomarkers that can predict abnormal fetal growth, such as small-for-gestational-age (SGA) and large-for-gestational-age (LGA) births. This cohort study evaluates the relationship and predictive capacity of maternal serum levels of PAPP-A and free β-hCG measured between 11 and 14 weeks of gestation for subsequent birth weight outcomes. This prospective cohort study included pregnant women attending prenatal clinics at two hospitals in Babol, Iran, from March 2017 to March 2021. Participants underwent first-trimester combined screening, including nuchal translucency measurement and biochemical analysis of PAPP-A and free β-hCG, performed via standardized immunofluorescence. Data on maternal demographics, medical history, and pregnancy outcomes were collected from records, with follow-up until delivery. Inclusion criteria specified singleton, live, uncomplicated pregnancies, with exclusion of fetal anomalies. Although the estimated sample size was 124, a total of 200 women were recruited. Statistical analyses comprised descriptive statistics, correlation assessments, regression models, and receiver operating characteristic (ROC) curve analysis. Ethical approval and informed consent were obtained. Analysis of the 162 singleton pregnancies from the original 200 subjects showed that gestational age at delivery, PAPP-A multiples of the median (MoM), and free β-hCG MoM significantly differed (p < 0.05) among SGA, appropriate-for-gestational-age (AGA), and LGA pregnancies. Birth weight had a strong correlation with PAPP-A MoM (ρ = 0.711, p < 0.001) and a modest but significant correlation with free β-hCG MoM (ρ = 0.206, p = 0.008). In adjusted multivariable linear regression, both delivery before 37 weeks (β=-405.78, p < 0.001) and Loge(PAPP-A MoM) (β = 509.37, p < 0.001) were independent predictors of birth weight. Binary logistic LASSO regression found that Loge(PAPP-A MoM) was the only predictor for SGA (coefficient: -1.716). PAPP-A MoM effectively identified SGA infants (AUC: 0.949; optimal cut-off: 0.745 MoM) with a sensitivity of 100% and specificity of 82.9%. Internal validation of the model confirmed strong accuracy for predicting SGA. Because there were only four LGA cases (2.5%), findings for LGA are exploratory and need validation in larger groups. In this group of Iranian women, first-trimester PAPP-A MoM appeared promising as an independent marker related to the risk of SGA, indicating an inverse correlation with the chances of having an SGA infant. Free β-hCG MoM did not offer any additional independent predictive value in our cohort. Due to the limited number of cases (n = 4), reliable assessment of LGA prediction was not possible. These results imply that PAPP-A could be useful for early prenatal risk assessment for SGA; however, further external validation in larger and more diverse populations is required prior to clinical application. Future research should focus on incorporating PAPP-A into early prenatal screening models while considering the potential confounding effects of preterm delivery.