THE ROLE OF PRENATAL SCREENING IN THE DIAGNOSIS OF FETAL CHROMOSOMAL ABNORMALITIES

SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 239 THE ROLE OF PRENATAL SCREENING IN THE DIAGNOSIS OF FETAL CHROMOSOMAL ABNORMALITIES I.I. Nigmatulina Center for Maternal and Child Health Center for the Development of Professional Qualifications of Medical Workers https://doi.org/10.5281/zenodo.17541035 Abstract. The analysis of the diagnostic efficacy of the first-trimester combined prenatal screening program "Astraia Obstetrics" was conducted in pregnant women with high and average risk of developing chromosomal abnormalities. The sensitivity of "Astraia Obstetrics" was 96.06% with a specificity of 96.1% for high-risk women; for those with above-average risk, the sensitivity was 87.52% with a specificity of 88.4%. Keywords: first-trimester prenatal screening program "Astraia", sensitivity, specificity. Introduction. It has been extensively documented that congenital malformations (CM) occur in 5-5.5% of newborns, and they account for approximately 303,000 deaths annually within the first 4 weeks of life...” (World Health Organization. Congenital anomalies, 2016). Research is constantly being conducted worldwide to improve the effectiveness and informativeness of screening methods for diagnosing fetal congenital malformations (CM) and chromosomal abnormalities (CA) [1, 2, 3]. The most informative method for prenatal diagnosis of chromosomal abnormalities (CA) is currently fetal karyotyping following invasive intervention and collection of fetal material (ISUOG, Consensus Statement, 2019). The findings indicate that this invasive procedure can lead to pregnancy complications, including spontaneous abortion, in 1.0-5.0% of cases and is currently performed only based on indications obtained through combined prenatal screening of pregnant women (Fedorova N.I., 2016). Combined screening programs are used worldwide, for example: Astraia, a product of the Fetal Medicine Foundation, Institute of Fetal Medicine, UK. "Astraia Obstetrics" (Astraia software gmbH, Germany), developed with the support of the Fetal Medicine Foundation (FMF) (London, UK). According to the "Astraia Obstetrics" program, pregnant women with a risk of 1 ≤ 101 are considered low-risk, and those with a probability of 1 ≥ 100 are considered high-risk [4, 5, 7]. This program is constantly being improved. The main objective of our study was to evaluate the specificity, sensitivity, and effectiveness of the first-trimester combined prenatal screening program “Astraia Obstetrics” in pregnant women with high and average risk of developing fetal CA. Material and methods. Clinical observations were conducted at the “Aliev’s Family” Maternal and Child Diagnostic Center in Tashkent, where 46 pregnant women aged 26-38 years (average age – 32.8±3.89 years) at 11-13+6 days of gestation with a fetal crown-rump length (CRL) of 45-84 mm, who sought medical attention after receiving the results of comprehensive prenatal screening using the Astraia Obstetrics program. The study methods included instrumental examination methods (ultrasound with fetal fetometry and Doppler ultrasonography of the venous duct and tricuspid valve of the fetus), the results of the Astraia Obstetrics prenatal screening program, and statistical methods for processing the obtained study results. SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 240 Research results. It is important to emphasize that transabdominal ultrasound fetometry of the fetus at 1113+6 days of gestation in the studied pregnant women allowed us to identify various deviations from the norm for many indicators (Table 1). The average NT values of the fetuses of the pregnant women statistically significantly exceeded the norm (P≤0.05) and averaged 2.96±0.56 mm, which indirectly indicated the presence of CA in the fetuses of the studied pregnant women. We also assessed the incidence of NTD at 11-13+6 days of gestation. Deviations exceeding normal values were detected in 21 (45.65%) patients. In 12 (26.09%) women, there was no visualization of the nasal bone in the fetus, in 7 (15.22%) fetuses, tricuspid regurgitation was detected, which indicates the possible presence of congenital heart defects (CHD). The pulsatility index (PI) of blood flow in the venous duct above the norm was observed in 9 (19.57%) fetuses. It is known that for the nificationn of prenatal screening programs, it is customary to use the MoM value – the ratio of the obtained absolute value of the marker to the median [1,8,9], while it should be taken into account that a shift in the median of one marker by 10% of the risk increase increases the high-risk group by 1–2%, and a shift in the medians of several parameters results in a shift corresponding to the total changes in the medians of the parameters [6]. Fetal fetometry parameters in the studied patients are presented in Table 1. Table 1. Fetal fetometry parameters in the studied patients (M±σ) Indicators Patients under study Norm Fruit weight, g 28,6±4,9 11-52 Fetal heart rate (bpm) 149,4±24,1 136-168 Parietococcygeal length (CTL), mm 69,3±8,7 45-84 Biparietal size (BPR), mm 22,3±3,2 18-28 Head circumference (HC), mm 23,2±3,6 20-26 Femur length (FL), mm 11,4±1,8 7-16 Thickness of the collar space (TvP), mm 2,96±0,56 1,4-2,7 TVP above normal (abs. and %) 21 0 45,65 Nasal bone is visualized (abs. and %) 34 ≥96% 73,91 Nasal bone is visualized (abs. and %) 12 ≤2% 26,09 Tricuspid regurgitation is present (abs. and %) 7 ≤5% 15,22 No tricuspid regurgitation (abs. and %) 39 ≥95 84,78 Increase in PI in the venous duct (abs. and %) 9 19,57 Pulsatility index in the venous duct 1,34±0,23 ≤1,4 Pregnancy gestational age according to ultrasound (weeks) 11,9±1,9 Pregnancy period based on the first day of the last menstrual period (weeks) 12,6±1,8 The biochemical analysis of pregnancy-associated proteins in the blood serum of female patients participating in the combined prenatal screening programs in the first trimester of pregnancy revealed that the average concentration of PAPP-A was 0.67±0.11 mU/L (0.43±0.07 SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 241 MoM), while the β-hCG level was 156.3±20.6 ng/ml (2.18±0.4 MoM). Taking into account the serum concentrations of PAPP-A and β-hCG in the studied pregnant women and the results of ultrasound markers for the development of fetal CA, the study group was divided into two subgroups according to the risk level: high (≥1:100) and above average (1:101–1:1000) based on the results of the Astraia prenatal screening. Thus, the high-risk subgroup, based on the results of the comprehensive prenatal screening "Astraia Obstetrics", included 25 patients (54.35%) with an average risk of 1: 89.16 ± 6.37, and the above-average risk subgroup included 21 pregnant women (45.65%) with an average risk of 1: 658.37 ± 117.82. In the high-risk subgroups, all patients underwent invasive prenatal diagnosis (IPD) by amniocentesis with fetal karyotype determination (FISH). In the high-risk subgroup of the study group, based on the results of the Astraia Obstetrics comprehensive prenatal screening, 21 of 25 (84%) patients in the subgroup had high rates of fetal chromosomal abnormalities, with an average risk of 87.21±7.86. In the above-average risk subgroup, 20 of 21 (95.24%) pregnant women had high rates of fetal chromosomal abnormalities, with an average risk of 649.18±113.82. Table 2 presents the risk levels for fetal chromosomal abnormalities according to the Astraia program. Table 2. Risk levels for fetal chromosomal abnormalities according to the Astraia program Risk subgroup Quantity by "Astraia" Average risk (M±σ) Абс % High (≥1:100) total 25 54,35 1: 89,16±6,37 From these, high in SD 21 84,0 1: 87,21±7,86 From these, high in SE 3 12,0 1: 97,21±1,79 From these, high in SP 1 4,0 1: 96 From average (1:101–1:1000) total 21 45,65 1:658,37±117,82 From these, above average for SD 20 95,24 1:649,18±113,82 From these, above the SE average 1 4,76 1:676 It can be clearly observed that regarding Edwards' syndrome (ES), in the high-risk subgroup based on prenatal screening results, this CA accounted for 3 patients (12%) with an average risk of 1:97.21±1.79, while in the above-average risk group, there was 1 patient (4.76%) with a risk of 1:676. In the high-risk subgroup based on prenatal screening results, there was 1 pregnant woman (4%) with a risk of 1:96, while there were no such cases in the above-average risk group. Here is substantial evidence to suggest that we determined the risk levels for the Astraia prenatal screening program. The sensitivity of Astraia Obstetrics for high-risk cases was 96.06% with a specificity of 96.1%, i.e., The diagnostic accuracy for high-risk patients was 96.08%. For those with above-average risk, this prenatal screening program had a sensitivity of 87.52% and a specificity of 88.4%, meaning the diagnostic accuracy for those with above-average risk was 87.96%. These results necessitate the development of increasingly sophisticated prenatal diagnostic methods for screening the risk of developing fetal CAD, which will reduce the risk of complications for the mother and adverse effects on the fetus. SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 242 Table 3. Sensitivity, specificity, and accuracy of the Astraia program by risk group Methodology, group AUC AC Se 95% Cl Sp 95% Cl LR+ LRPV+ PVYouden index Р High risk of Astraia Obstetrics 0,91 2 <0,98 96,09 88,397,7 96,1 87,6 - 98,1 3,15 0,13 95, 62 95, 91 0,96 09 <0,00 1 Above average risk Astraia Obstetrics 0,84 0 <0,96 87,52 81,492,3 88,4 82,6 - 91,7 5,36 0,24 92, 36 93, 28 0,87 52 <0,01 Note: where: “AUC – area under the curve; AC – cutoff point; Se – sensitivity; 95% Cl – confidence interval for sensitivity; Sp – specificity; 95% Cl – confidence interval for specificity; LR+ – positive likelihood ratio; LR- – negative likelihood ratio; PV+ – positive predictive value; PV- – negative predictive value; p – statistical significance of the model; NPR – regression model indicator.” REFERENCES 1. Baranov V.S., Kashcheeva T.K., Kuznetsova T.V. New technologies and trends in the development of prenatal diagnostics // Journal of Obstetrics and Women's Diseases. 2016. 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