First-trimester maternal serum alpha-fetoprotein is not a good predictor for adverse pregnancy outcomes: a retrospective study of 3325 cases

Abstract

Background: It is well known that second-trimester maternal serum alpha-fetoprotein (MS-AFP) is a predictor for adverse pregnancy outcomes (APOs), such as preterm birth, stillbirth, preeclampsia and small for gestational age (SGA). However, it is unknown whether first-trimester MS-AFP is also predictive of APOs. Methods: We retrospectively reviewed the data on the first-trimester MS-AFP levels and pregnancy outcomes of 3325 singleton pregnant women. The cutoff value of 2.5 multiple of the median (MoM) was used to evaluate the risks of APOs regarding MS-AFP. The receiver operating characteristic (ROC) curves were used to evaluate the predictive efficiencies of MS-AFP to these disorders. Results: A total of 181 pregnancies resulted in preterm birth, 32 in stillbirth, 81 in preeclampsia, and 362 in SGA. Compared to women with MS-AFP < 2.5MoM, those with MS-AFP ≥ 2.5MoM had increased risks (odds ratio, 95% confidence interval) of preterm birth (2.53, 1.65~3.88), preeclampsia (3.05, 1.71~5.43) and SGA (1.90, 1.34~2.69), and had an earlier distribution of gestational weeks at delivery (P = 0.004) and a lower distribution of neonatal birth weights (P = 0.000), but the actual between-group differences were minuscule. The areas under ROC curves were 0.572 (P = 0.001), 0.579 (P = 0.015) and 0.565 (P = 0.000) for preterm birth, preeclampsia and SGA, respectively. Subdivisions for the disorders did not obviously improve the performances of MS-AFP. Conclusions: Elevated first-trimester MS-AFP is associated with increased risk of preterm birth, preeclampsia and SGA. However, the predictive efficiencies were low and it is not a good predictor for these APOs.

Clinical tools and biomarkers to predict preeclampsia

“…Second trimester AFP, produced primarily by the fetal liver, has also been robustly linked to adverse pregnancy outcomes including preeclampsia, 58 with a large retrospective study (n=3325) reporting first trimester elevations, but poor predictive performance. 59 When combined, a ratio of AFP/PAPP-A above 10 resulted in a relative risk for severe preeclampsia of 2.12, with slightly improved (although not significant) area under the ROC curve (of 0.60 À reflecting only modest predictive potential) compared to either biomarker alone. 57 We have also assessed the potential of combining placental biomarkers to improve prediction.…”

Analysis of the Effectiveness of First Trimester Nucal Translucence, Free Beta-Human Chorionic Gonadotropin, and Pregnancy-Related Plasma Protein-A in Prediction of Pregnancy Complications

“…Dieste-Pérez et alevaluated the relationship between first-trimester maternal serum free β-hCG and PAPP-A levels and pregnancy complications in 5297 pregnant women, 80 of whom were preeclamptic; PAPP-A and free β-hCG were significantly lower in the preeclamptic group than in the control group (Dieste-Pérez et al, 2022). It was found that 10% of preeclamptic pregnant women had PAPP-A levels below the 5th percentile and 7% of them had free β-hCG levels below the 5th percentile (Hu et al, 2020) Hendrix et al (2021 studied 8839 pregnant women, of whom 331 were preeclamptic. Similar to our study, the PAPP-A level was significantly lower in the preeclampsia group, whereas free β-hCG did not make a significant difference between the two groups.…”

Identifying biomarkers for prenatal diagnosis of neural tube defects based on “omics”

“…23,24 Moreover, the specificity of maternal serum AFP levels for NTD diagnosis can be disrupted by preeclampsia, placental damage, multiple births, or stillbirth. [25][26][27][28][29] In addition, maternal AFP seems to be sensitive to open NTDs, but not closed NTDs. 17 Thus, the diagnostic sensitivities and specificities of diverse NTD types are different, and maternal disease factors and improper fetal position that increase serum AFP levels can lead to misdiagnosis or missed diagnosis of NTDs.…”