Executive Summary : | Biomarkers that allow for the early diagnosis of females at risk for pregnancy associated complications, ahead of appearance of any clinical symptoms, needs to be developed. We have recently published the findings of a pilot study conducted on a total of 139 pregnant females in first trimester of pregnancy [Keshari et al., 2022]. The study assessed the relationship between first-trimester ultrasound images and maternal blood biochemical indicators such as pregnancy-associated plasma protein-A (PAPP-A) and alpha fetoprotein (AFP). The fetal heart rate (HR), crown rump length (CRL), and nuchal translucency (NT) as well as the likelihood of developing fetal anomalies like neural tube defects (NTD), chronic heart disease (CHD), preeclampsia (PE), and gestational diabetes mellitus (GDM) were all correlated with the levels of PAPP-A and AFP. These findings interested us to further conduct a comprehensive study enrolling a larger sample size with employment of an array of blood biomarkers such as PAPP-A, AFP, Lamin A (LMNA), maternal serum sex hormone binding globulin (SHBG), and high-sensitive C-reactive protein (hs-CRP) to evaluate the correlation of these biomarkers with Fetal Ultrasound Scans in First- Trimester Low-Risk Noninvasive Prenatal-Tested Pregnant Women as well as evaluate their role as Prognostic Biomarkers for fetal outcomes in the North Indian population. Methodology The study will include 500 females in the age group of 21 and 35 years, in the first trimester of pregnancy, with a normal color duplex ultrasound screening for fetal NT between 11 ± 1 weeks, and without any history of an adverse pregnancy. Experimental methods Approximately 5 mL of venous blood will be drawn from each participant into separating gel vacuum tubes. Samples will be centrifuged at 3000 rpm for 15 minutes at 4 °C to collect the serum. Assessment of risk of fetal chromosomal abnormalities First the circulating cell-free fetal DNA (cfDNA) will be extracted from the maternal peripheral whole blood by commercially available cfDNA extraction kits. The risk of fetal chromosomal abnormalities will be assessed by by VeriSeq NIPT Solution v2 platform (Illumina, San Diego, CA, USA) for noninvasive prenatal testing (NIPT) assay. Analysis of blood biomarkers Levels of PAPP-A, AFP, LMNA, SHBG and Hs-CRP will be estimated by commercially available enzyme linked immunosorbent assay kits (ELISA kits). Correlation with ultrasonography findings Based on the ultrasonography findings, the correlation between the levels of biomarkers with the fetal NT thickness, FHR, and CRL along with the chances of occurrence of fetal anomalies such as NTD and CHD, PE, and GDM will be determined. Significance The studied maternal blood biomarkers may aid in the early detection of maternal and fetal anomalies. |