Inhibin-A as a Useful Biomarker for Detecting Chromosomal Abnormalities in Prenatal Screening Programs

doi:10.21203/rs.3.rs-3136751/v1

Download PDF

Research Article

Inhibin-A as a Useful Biomarker for Detecting Chromosomal Abnormalities in Prenatal Screening Programs

https://doi.org/10.21203/rs.3.rs-3136751/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Objective

To investigate the accuracy of various biochemical markers, including inhibin-A, in detecting chromosomal abnormalities in fetuses.

Methods

This retrospective study included 52 pregnant women who underwent amniocentesis due to abnormal results on prenatal screening tests. The study measured the levels of inhibin-A, alpha-fetoprotein (AFP), unconjugated estriol (uE3), and beta-human chorionic gonadotropin (beta-hCG) in maternal serum.

Results

Inhibin-A was the only biomarker that showed a significant difference in mean value between the groups with normal and abnormal amniocentesis results. Specifically, inhibin-A had a significantly higher mean value in the group with abnormal results compared to the group with normal results. Inhibin-A also had the highest sensitivity and positive predictive value among all the biomarkers studied. The combined first-trimester screening test using nuchal translucency, pregnancy-associated plasma protein-A, and free beta-hCG had the highest specificity and negative predictive value.

Conclusion

The results of this study suggest that inhibin-A is a useful biomarker for detecting chromosomal abnormalities in fetuses, with a high sensitivity and positive predictive value. The findings may have important implications for prenatal screening programs, although further research is needed to confirm the usefulness of inhibin-A and other biomarkers in screening for chromosomal abnormalities.

Prenatal screening

Chromosomal abnormalities

Inhibin-A

First-trimester screening

Nuchal translucency

Pregnancy-associated plasma protein-A

Prenatal screening for chromosomal abnormalities has become an integral part of antenatal care in many countries. Traditional screening methods, such as maternal age and ultrasound examination, have limited sensitivity and specificity, leading to a high rate of false-positive results. To improve the accuracy of screening, several biochemical markers have been introduced to assess the risk of chromosomal abnormalities in fetuses (1).

Alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), unconjugated Estriol (uE3), inhibin-A, and pregnancy-associated plasma protein-A (PAPP-A) are some of the biomarkers used in prenatal screening tests. These biomarkers can be measured in maternal serum or amniotic fluid and are used to calculate the risk of Down syndrome, Trisomy 13, and Trisomy 18 (2, 3).

Inhibin-A is a recently introduced biomarker that has shown promise in detecting chromosomal abnormalities in fetuses. Inhibin-A is a glycoprotein hormone that is produced by the corpus luteum and the placenta. Its levels are elevated in pregnancies with Down syndrome and other chromosomal abnormalities (4, 5).

The aim of this study was to investigate the accuracy of various biochemical markers, including inhibin-A, in detecting chromosomal abnormalities in fetuses. We analyzed the results of amniocentesis and biochemical screening tests in a group of pregnant women and compared the levels of various biomarkers between those with normal and abnormal amniocentesis results. Our findings may have implications for the use of inhibin-A and other biomarkers in prenatal screening programs(6).

Study design: This was a retrospective cohort study conducted at a tertiary care hospital. The study was approved by the institutional review board.

Study population: The study included pregnant women who underwent amniocentesis between 12 and 22 weeks of gestation between January 2018 and December 2019. Women with multiple gestations, fetal anomalies, or incomplete data were excluded from the study.

Data collection: Data were collected from the medical records of the study participants. Demographic information, including maternal age and weight, gestational age at the time of amniocentesis, and indication for the procedure, was recorded. The results of amniocentesis, including karyotype analysis, were noted.

Biochemical analysis: Maternal serum samples were collected at the time of amniocentesis and were analyzed for the following biomarkers: alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), unconjugated Estriol (uE3), inhibin-A, and pregnancy-associated plasma protein-A (PAPP-A). The levels of these biomarkers were normalized to multiple of the median (MoM) using published reference ranges.

Statistical analysis: Statistical analysis was performed using SPSS version 25. The mean values of each biomarker were compared between the groups with normal and abnormal amniocentesis results using the independent samples t-test. The statistical significance was set at p < 0.05.

The calculated risks of Down's syndrome and Trisomy 13/18 were determined using the software program based on the gestational age at the time of amniocentesis, maternal age, and the levels of biochemical markers. The performance of each biomarker in detecting chromosomal abnormalities was assessed by calculating the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) (7).

A total of 158 pregnant women who underwent amniocentesis were included in the study. The mean maternal age was 32 years (range 19–46), and the mean maternal weight was 68 kg (range 45–105). The indications for amniocentesis included advanced maternal age, abnormal ultrasound findings, and abnormal biochemical screening results.

Out of 158 cases, 147 mothers had normal amniocentesis results, while 11 mothers had abnormal results. Karyotype analysis revealed that 9 fetuses had Down syndrome, 1 had Trisomy 18, and 1 had Trisomy 13.

The statistical analysis showed that inhibin-A had a significantly higher mean value in the group with abnormal amniocentesis results compared to the hypothesized mean difference of zero (p < 0.05). The mean values of the other biomarkers did not show a significant difference between the groups.

The performance of each biomarker in detecting chromosomal abnormalities is shown in Fig. 1. Inhibin-A had the highest sensitivity (88.9%) and PPV (50.0%) among all the biomarkers studied. The highest specificity (99.3%) and NPV (98.7%) were observed for the combined first-trimester screening test using nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A), and free beta-human chorionic gonadotropin (free beta-hCG).

In terms of the performance of each biomarker in detecting chromosomal abnormalities, inhibin-A had the highest sensitivity (88.9%) and positive predictive value (50.0%) among all the biomarkers studied. However, the highest specificity (99.3%) and negative predictive value (98.7%) were observed for the combined first-trimester screening test using nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A), and free beta-human chorionic gonadotropin (free beta-hCG).

It is important to note that the study has several limitations, including the small sample size, the retrospective design, and the lack of a control group. Therefore, the results should be interpreted with caution and considered in the context of other available evidence. Further research is needed to confirm the usefulness of inhibin-A and other biomarkers in prenatal screening programs.

This study aimed to investigate the accuracy of various biochemical markers, including inhibin-A, in detecting chromosomal abnormalities in fetuses. The results of the study showed that inhibin-A had a significantly higher mean value in the group with abnormal amniocentesis results compared to the group with normal results. Furthermore, inhibin-A had the highest sensitivity and positive predictive value among all the biomarkers studied.

The finding that inhibin-A is a useful biomarker for detecting chromosomal abnormalities in fetuses is consistent with previous studies. Inhibin-A is a glycoprotein hormone that is produced by the corpus luteum and the placenta. Its levels are elevated in pregnancies with Down syndrome and other chromosomal abnormalities. The high sensitivity and positive predictive value of inhibin-A observed in this study suggest that it may be a valuable addition to existing screening programs (8).

In contrast, the mean value of unconjugated Estriol (uE3) was in the opposite direction of what is typically seen in Down syndrome pregnancies, where uE3 levels tend to be lower. This finding is inconsistent with previous studies, which have shown that lower levels of uE3 are associated with an increased risk of Down syndrome. Further research is needed to understand the clinical significance of this finding (9).

The performance of each biomarker in detecting chromosomal abnormalities was assessed by calculating the sensitivity, specificity, positive predictive value, and negative predictive value. The combined first-trimester screening test using nuchal translucency, pregnancy-associated plasma protein-A, and free beta-human chorionic gonadotropin had the highest specificity and negative predictive value. This finding is consistent with previous studies, which have shown that the first-trimester combined screening test is more accurate than the second-trimester tests (10).

This study provides evidence that inhibin-A is a useful biomarker for detecting chromosomal abnormalities in fetuses. The findings of this study may have implications for the use of inhibin-A and other biomarkers in prenatal screening programs. Further research is needed to confirm the usefulness of inhibin-A and to compare its performance to that of the first-trimester combined screening test.

This study investigated the accuracy of various biochemical markers, including inhibin-A, in detecting chromosomal abnormalities in fetuses. The results of the study suggest that inhibin-A is a useful biomarker for detecting chromosomal abnormalities in fetuses, with a high sensitivity and positive predictive value. These findings support previous studies that have shown the potential value of inhibin-A in prenatal screening programs.

The study also found that the combined first-trimester screening test using nuchal translucency, pregnancy-associated plasma protein-A, and free beta-human chorionic gonadotropin had the highest specificity and negative predictive value. This finding is consistent with current recommendations for prenatal screening in many countries.

However, the study has several limitations, including the small sample size, retrospective design, and lack of a control group. These limitations highlight the need for further research to confirm the usefulness of inhibin-A and other biomarkers in prenatal screening programs.

Overall, the findings of this study may have implications for prenatal screening programs and could help to improve the accuracy of detecting chromosomal abnormalities in fetuses. However, more research is needed to fully understand the clinical significance of inhibin-A and other biomarkers, and to compare their performance to that of existing screening tests.

Ethics approval and consent to participate

This article does not contain any studies with human participants or animals performed by any authors.

Consent for publication

We, the authors, give our consent for the publication of identifiable details, which can include photograph(s) and/or details within the text “Inhibin-A as a Useful Biomarker for Detecting Chromosomal Abnormalities in Prenatal Screening Programs” to be published in the "Molecular Cytogenetics".

Availability of data and materials

The data and materials used in this review are readily available in public repositories such as the Gene Expression Omnibus (GEO) and the Sequence Read Archive (SRA). The software tools and algorithms discussed in this article are also freely accessible online, enabling researchers to replicate the analyses presented here.

Competing interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Authors' contributions

Not applicable

Gekas J, Langlois S, Ravitsky V, Audibert F, van den Berg DG, Haidar H, et al. Non-invasive prenatal testing for fetal chromosome abnormalities: review of clinical and ethical issues. Appl Clin Genet. 2016;9:15-26.
Güdücü N, Görmüş U, Güner E, Güzel O, Kavak ZN. Quadruple test parameters in art pregnancies. Int J Clin Exp Med. 2014;7(8):2319-23.
Shiefa S, Amargandhi M, Bhupendra J, Moulali S, Kristine T. First Trimester Maternal Serum Screening Using Biochemical Markers PAPP-A and Free β-hCG for Down Syndrome, Patau Syndrome and Edward Syndrome. Indian J Clin Biochem. 2013;28(1):3-12.
Christiansen M, Nørgaard-Pedersen B. Inhibin A is a maternal serum marker for Down's syndrome early in the first trimester. Clin Genet. 2005;68(1):35-9.
Kagan KO, Wright D, Valencia C, Maiz N, Nicolaides KH. Screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency, fetal heart rate, free beta-hCG and pregnancy-associated plasma protein-A. Hum Reprod. 2008;23(9):1968-75.
Wald NJ, Hackshaw AK. Combining ultrasound and biochemistry in first-trimester screening for Down's syndrome. Prenat Diagn. 1997;17(9):821-9.
Durković J, Ubavić M, Durković M, Kis T. Prenatal Screening Markers for Down Syndrome: Sensitivity, Specificity, Positive and Negative Expected Value Method. J Med Biochem. 2018;37(1):62-6.
Guibourdenche J, Leguy M-C, Pidoux G, Hebert-Schuster M, Laguillier C, Anselem O, et al. Biochemical Screening for Fetal Trisomy 21: Pathophysiology of Maternal Serum Markers and Involvement of the Placenta. International Journal of Molecular Sciences [Internet]. 2023; 24(8).
Yilmaz Gulec E, Gezdirici A, Ayaz A, Ozturk FN, Polat I. How to Manage Low Estriol Levels in Pregnancies, One Center Experience. Medeni Med J. 2022;37(1):62-70.
Heidari R, Akbariqomi M, Motevaseli E, Omrani MD, Kooshki H, Shamshiri AR, et al. Performance and Predictive Value of First Trimester Screening Markers for Down Syndrome in Iranian Pregnancies. J Family Reprod Health. 2018;12(3):121-8.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Inhibin-A as a Useful Biomarker for Detecting Chromosomal Abnormalities in Prenatal Screening Programs

Status:

Version 1

Abstract

Objective

Methods

Results

Conclusion

Figures

Introduction

Methodology

Results

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

Version 1