Background/Objectives: Non-invasive prenatal testing (NIPT) has become a widely used method for screening common fetal aneuploidies due to its high sensitivity and specificity compared to traditional screening methods. With various NIPT technologies available, such as whole-genome sequencing (WGS), single nucleotide polymorphisms (SNPs), microarray, and rolling circle amplification (RCA), understanding the accuracy and reliability of each method is critical for clinical decision-making. However, comprehensive evaluations comparing the performance of these NIPT methods, especially in terms of predictive values for trisomy detection, remain limited. A systematic review of the difference in accuracy of the different NIPT methods used for common aneuploidy screening. Methods: A systematic review of former clinical studies using different NIPT methods, such as whole-genome sequencing (WGS), a targeted method of single nucleotide polymorphisms (SNPs), microarray and rolling circle amplification (RCA). We collected data from the PubMed, Embase, Web of Science, Scopus, clinicaltrials.gov, and Cochrane library from the last 20 years, between 2003 January and 2023 October, without any language, search filter or publication type restrictions. Results: Two authors selected twenty articles including twenty-one studies to perform the systematic review. In these studies, altogether 92,164 pregnant women were tested by genomics-based non-invasive prenatal testing (NIPT). We extracted data on true positive, false positive, false negative, and true negative values from each study, and calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) from them. We collected data regarding trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13) detection from all studies. Conclusions: As a conclusion, for the detection of common fetal trisomies, different methods of NIPT perform similarly in terms of clinical sensitivity, specificity and NPV. However, the tests utilizing SNP and RCA had lower PPV values than other NIPT methods. Our research indicates all NIPT methods showed greater sensitivity for the detection of T21, above 97%, than traditional screening tests. For T18 detection, the targeted method with the microarray had a lower sensitivity compared to other tests. The SNP and the microarray-based test had high PPV, whilst the other tests, utilizing WGS, and the test with RCA had quite low PPV. Regarding T13 detection, all of the tests performed similarly in terms of clinical sensitivity, specificity, PPV, and NPV (with one exception—one of the tests using WGS had lower PPV). According to these results, there was no significant difference between the methods of NIPT, such as WGS, SNPs, microarray, and RCA, used to detect common trisomies, but the variation in PPV underlines the importance of invasive tests to derive positive NIPT results. We suggest that NIPT combined with US screening for structural abnormalities could further improve the utility of the non-invasive tests in pregnancy. This is the first independent systematic review into the efficacy of the different NIPT methods.

Phosphatidylinositol and its derivatives are essential components of cell membranes and play pivotal roles in growth signaling pathways. In the human primordial placenta, phosphatidylinositol synthesis is catalyzed by phosphatidylinositol synthase (PIS) and the phosphatidylinositol-exchange enzyme (IE), both of which require divalent cations. We investigated whether GTP-binding proteins modulate this biosynthetic process. Incorporation of [³H]inositol into phosphatidylinositol was measured in trophoblast tissue and microsomes from 8 to 10-week placentas. Our results demonstrate that Mn²⁺ strongly enhances phosphatidylinositol synthesis, and stimulation with AlF₄⁻ further increases incorporation rates by up to 2.5-fold. In contrast, Mg²⁺ combined with the non-hydrolyzable GTP analog GIDP elevated synthesis by 58%, whereas Mn²⁺ plus GIDP reduced incorporation by 30%. Complementary in silico protein–protein interaction analyses suggest that G-proteins may directly associate with inositol-exchange enzymes, providing a potential mechanism for the observed regulatory effects. These findings indicate that phosphatidylinositol synthesis is modulated in a manner consistent with G-protein involvement, with distinct effects depending on the prevailing enzymatic pathway. We propose that rapid trophoblast proliferation may involve feedback mechanisms mediated by distinct G-protein subtypes acting on early steps of the phosphatidylinositol cycle.