Evaluation of the incidence of anomaly in fetus and neonates of prenatal aneuploidy screening

Abstract

AimOur study aimed to investigate the frequency of anomalies and related maternal and neonatal outcomes in pregnant women who were admitted in our clinic in the last five years and underwent prenatal aneuploidy screening.MethodsThe prenatal fetal aneuploidy screening results of the pregnant women who participated in the study, the pregnant and maternal outcomes of the pregnant women who underwent amniocentesis according to these results, and the detection rates of chromosomal aneuploidy in infants were retrospectively analyzed.ResultsAccording to the first-trimester screening test, 22.4% of the cases (n = 121); According to the second-trimester screening test, 11.8% (n = 6) of the patients were found to be at high risk for chromosomal aneuploidy. Amniocentesis was recommended to 199 participating in the study, and 17.6% (n = 35) of these cases were accepted. Chromosomal aneuploidy was found in 1.8% (n = 3) of those who underwent amniocentesis. Two pregnancies with aneuploidy were terminated at the request of the families. The anxiety levels of the pregnant women who had prenatal screening tests were higher in the studies.ConclusionFetal aneuploidy screening tests may give false positive results at high rates, adversely affecting maternal anxiety and, thus, pregnancy outcomes. To increase the prenatal diagnosis rates cost-effectively, it is helpful to perform combined tests to increase the sensitivity or more sensitive tests are needed.

Keywords

Introduction

Considering that newborns with congenital anomalies cause problems for families and society, screening tests for chromosomal abnormalities are recommended for pregnant women in our country, as in many countries. The purpose of prenatal screening tests is to identify pregnant women with a high risk for chromosomal aneuploidy in the early weeks of pregnancy and to inform each pregnant woman by considering their current troubles and preferences.
Prenatal diagnosis can be made through invasive and non-invasive testing. The American Society of Obstetricians and Gynecologists and the Maternal-Fetal Medicine Association recommend that prenatal genetic screening tests be offered to all pregnant women, regardless of age or risk for chromosomal abnormality.¹
Screening tests from maternal blood, free human chorionic gonadotropin and pregnancy-associated protein A in the first trimester, a triple screening test (alpha-fetoprotein, free human chorionic gonadotropin and unconjugated protein A in the second trimester) estriol. The detection rate for Trisomy 21 with the first-trimester screening test varies between 82-87%, using a 5% positive screening rate depending on the laboratory.² The advantage of this test is that the test can be performed in the early stages of pregnancy (10-13 weeks of pregnancy).^3,4 Patients who agree to have a diagnostic test at 10-13 gestational weeks may be recommended chorionic villus sampling or amniocentesis from the 15th gestational week(26). It is known that the triple screening test (alpha-fetoprotein, human chorionic gonadotropin, estriol) performed during 16-18 gestational weeks has an accuracy rate of 60% with a false positive rate of 5%.^5,6 The most important expectation from screening tests is a high congenital anomaly detection rate and low false positivity. However, screening at an early gestational week allows for earlier prenatal diagnosis by calculating the possible increased risk earlier. With the detection of chromosomal anomalies by diagnostic tests, a termination option can be offered in the early weeks.
When the results of the screening tests are received, negative or positive results should be communicated to the family promptly. Even if the screening test result is negative or low-risk, the patient should be advised that an abnormality may still exist. In case of a high-risk outcome, the family should be informed about additional diagnostic testing options, if desired.^1,7
It is aimed to investigate whether diagnostic tests are performed and what their results are and to examine the contribution of prenatal screening tests to patients and physicians in a versatile way.

Materials and Methods

Among the pregnant women who applied to the Tekirdağ Namık Kemal University, Faculty of Medicine Health Practice and Research Hospital Gynecology and Obstetrics Polyclinic between 01.07.2017 and 01.07.2022, the pregnant women who were screened for fetal aneuploidy in a different clinic gave birth in a different clinic under the age of 18. This is a retrospective cross-sectional study in which a total of 542 pregnant women and their newborns were examined, excluding those with twin pregnancies, those whose screening results were not reported, and those whose screening results were not reported. Patient data and examination results were obtained through the hospital automation system, outpatient follow-up forms and phone calls. This data includes patients’ name, surname, age, comorbidities, smoking, weight, gravida, parity, abortion, number of living children, number of curettages, and family history were questioned. Pregnancy-associated protein A, human chorionic gonadotropin, nuchal translucency, estriol, alpha-fetoprotein test results, Trisomy 21 risk score, Trisomy 13 and Trisomy 18 risk score, neural tube defect risk score, according to results of double screening and triple screening. The pregnant women who underwent amniocentesis and their genetic influences, the week of the birth of the pregnant women who were born in our hospital, the birth weight of the newborn, the mode of delivery, the Apgar score of the newborn at birth, whether there was a need for neonatal intensive care after delivery, and the results of the neonates whose postpartum chromosomal analysis was performed from peripheral blood were recorded. In any of the prenatal screening tests, those with a cut-off value greater than 1/250 were considered high-risk, and those that were small were considered low-risk. Those with nuchal translucency greater than 2.5 mm were considered high-risk, and those with undersized nuchal translucency were deemed low-risk.Ethical ApprovalThe current study was approved by the ethics committee of Tekirdağ Namık Kemal University (Date: 26.07.2022, Decision No: 2022.145.07.12). The study was conducted in accordance with the Helsinki Declaration rules.Statistical AnalysisThe Number Cruncher Statistical System 2007 (Kaysville, Utah, USA) program was used for statistical analysis. Descriptive statistical methods (mean, standard deviation, median, frequency, percentage, minimum, maximum) were used while evaluating the study data. The conformity of the quantitative data to the normal distribution was tested with the Shapiro-Wilk test and graphical examinations. Independent groups t-test was used to compare two groups of normally distributed quantitative variables. Fisher’s exact test was used to compare qualitative data. Spearman correlation analysis was used to evaluate the relationships between quantitative variables. Statistical significance was accepted at P < .05.

Results

Our study was conducted with 542 cases, all women, who were admitted to our hospital between 01.07.2017 and 01.07.2022. The age of the study’s subjects ranged from 18 to 45, and the mean age was 28.91±5.37.
It was observed that 1.3% (n = 7) of the cases participating in the study had a family history. The chromosomal anomaly was found in 0.54% (n = 3) of the genetic results of the neonates.
When the dual screening test results of the subjects participating in the study were examined, 19.8% (n = 107) had an age-related risk, 4.1% (n = 22) had a T21 risk, and 0.6% (n = 3). T13-18 risk was observed in 0.6% (n = 3) of NT-related risk. It was determined that there was a risk in first-trimester screening test results in 22.4% (n = 121) of the cases.
The second-trimester screening test was performed in 9.4% (n = 51) of the cases in the study. In the test results of the cases, it was determined that 8.3% (n = 3) had an age-related risk, 3.1% (n = 1) had an NTD risk, and 4.2% (n = 2) had a T21 risk. T13-18 risk was not detected in any of the cases. It was determined that there was a risk in 11.8% (n = 6) of the issues due to the triple screening test. While chromosomal aneuploidy was detected in one of the neonates of three pregnant women who were found to be risky for fetal aneuploidy, according to NT, chromosomal aneuploidy was not detected in two neonates. Amniocentesis was recommended for 199 cases participating in the study. It was determined that 17.6% (n = 35) of the cases who were recommended to perform amniocentesis accepted the amniocentesis procedure, and 1.8% (n = 3) had positive test results. Two pregnancies with positive test results were terminated at the family’s request.
According to the double screening test results, no statistically significant difference was found between the chromosomal anomaly results of the cases (P > .05). Since only one of the three cases with chromosomal abnormality had a risk in the double screening test, the test’s sensitivity was 33.3%, and the specificity was 77.6%. Its positive predictive value was 82.6%, and its negative predictive value was 99.5%.
There was a very weak statistically significant correlation between the ß-hCG measurement values of the subjects and the 1st minute Apgar scores (r = 0.160; P = .022; P < .05) in the negative direction (As ß-hCG increases, Apgar score decreases). There was a very weak statistically significant correlation between the PAPP-A measurement values of the cases and the 1st minute Apgar scores (r = 0.160; P = .030; P < .05).
In addition, the weights of cases with high risk in the first-trimester screening test were statistically significantly higher than those without risk (P = .001; P < .01). The consequences of patients with increased risk in the first or second-trimester screening test were statistically significantly higher than those without risk (P = .001; P < .01). The risk rate in smokers’ first or second-trimester screening test was statistically significantly higher than that of non-smokers (P = .049; P < .05).

Discussion

Prenatal screening tests have been developed to detect fetal aneuploidies. These tests and their combinations applied in the first and second trimesters have different detection rates for chromosomal aneuploidies. Screening tests for chromosomal aneuploidies do not definitively tell whether the fetus is abnormal; instead, they can tell whether the fetus has a low or high probability of having the condition.⁸
According to Kaya et al., a risk group of 5.75% was determined according to the results of the second-trimester screening test in a study conducted on 1841 pregnant women.⁹ In their study, Atak et al. found a high risk of Down syndrome in 1.5% (n = 78) of those who underwent the first-trimester screening test and in 5.9% (n = 353) of those who experienced the second-trimester screening test.¹⁰ Similarly, in our study, the risk of Down syndrome was high in 4.1% (n = 22) of those who underwent the first-trimester screening test and 4.2% (n = 2) of those who experienced the second-trimester screening test. In addition, the high-risk rate for the anomaly in the first-trimester screening test was 22.4% (n = 121), and the high-risk rate in the second-trimester screening test was 11.8% (n = 6). In our study, only 51 cases also had the second-trimester screening test. Since the first-trimester screening test showed a risk in only one of the three cases with the chromosomal anomaly, the test’s sensitivity was 33.3%, and the specificity was 77.6%. Its positive predictive value was 82.6%, and its negative predictive value was 99.5%. It is known that there are differences in the sensitivity of screening tests. When the studies in the literature are examined, we see that prenatal screening tests recommend using contingency screening and fully integrated screening strategies that combine first and second-trimester screening tests to increase the rate of catching chromosomal aneuploidy.^11,12
Screening tests require a blood sample from the mother and a fetal ultrasonographic evaluation, so there is no increased risk of losing the pregnancy. Diagnostic testing for chromosomal abnormalities requires sampling fetal or placental fluid or tissue. There is a slight increase in the risk of losing the pregnancy (about 1/200 for chorionic villus sampling and 1/300-1/600 for amniocentesis).¹³ Chromosomal aneuploidy was detected in three of the patients who underwent amniocentesis. In two of them, the family terminated the pregnancy, and the fate of the third woman’s pregnancy is unknown since she continued her follow-up in an external center. The benefits of screening programs should be more pronounced than the adverse physical and psychological effects that may occur from participating in the screening program. It is essential to inform society adequately about the screening test, considering the anxiety that the screening tests may cause to pregnant women in our study, in which the rates of patients found to be at high risk as a result of screening tests are also examined. This is one of our study’s most critical clinical results.
When the literature is examined in detail, it has been shown in studies that although screening tests have benefits, the obtained risk estimation significantly increases the anxiety level of pregnant women.¹⁴ If an increased risk is detected in terms of chromosomal anomaly in the screening test, performing these screening tests in cases that will not go to the diagnostic test or terminate the pregnancy does not mean anything other than unnecessary cost and an increase in the anxiety rate in patients. Similar to our study, in the study of Kömül et al. concluded that it is essential that prenatal screening tests can be used more effectively by informing families about Down syndrome in detail. Thus, the expenditures made for screening tests for cases that do not want termination are used to solve the health problems of live-born Down syndrome cases, increase the quality of life, and reintegrate them into society. Kömül et al. stated that it will be more effective.¹⁵ Therefore, some studies stated that these high-risk cases should be followed carefully throughout pregnancy.^16,17 The idea that maternal serum pregnancy-associated protein A and human chorionic gonadotropin values may also be significant in predicting complications in the advancing gestational weeks, apart from determining the risk of chromosomal anomaly prompted researchers to conduct numerous studies on this subject.^18,19 In other studies, significant correlations were found between pregnancy complications such as gestational diabetes, low birth weight, high birth weight, intrauterine growth restriction and preterm labor, and maternal serum pregnancy-associated protein A and human chorionic gonadotropin values.^20,21 On the other hand, Morssink et al. also stated that first-trimester pregnancy-associated protein A and human chorionic gonadotropin values were not significantly associated with preterm labor.²² While examining the results of the cases in our study, we also investigated whether there is a relationship between pregnancy-associated protein A and human chorionic gonadotropin values of pregnant women who need admission to the neonatal intensive care unit for their babies. However, it did not detect a statistically significant association. In addition, there is no statistically significant relationship between the birth weight of newborns and pregnancy-associated protein A measurement values and human chorionic gonadotropin values in pregnant women (P > .05).
The body weights of the cases with risk in the first-trimester screening test were statistically significantly higher than those without risk (P = .001; P < .01). In addition, the risk rate in the double or triple screening test of smokers was statistically significantly higher than that of non-smokers (P = .049; P < .05). Our findings, in line with the literature, support that maternal body weight and smoking effectively increase the risk of chromosomal anomalies.²³ We think the relationship of some pregnancy-related biochemical markers with pregnancy complications and possible complications in the newborn in the postnatal period will be revealed in different studies, including more extensive case series.
In conclusion, the aim of prenatal diagnosis applications is not only to detect anomalies in fetal life but to terminate such pregnancies. To provide necessary counseling on many issues, such as ensuring the preparation of the required conditions for postnatal care and enabling prenatal treatment of the affected fetus. Screening tests for chromosomal aneuploidies do not definitively say whether the fetus is abnormal. They can only tell whether the fetus has a low or high probability of having this condition. Conversely, a diagnostic test can definitively tell if the fetus is abnormal. In this regard, it can be said that counseling for pregnant women is not sufficient. Accurate and effective prenatal screening tests are vital for adequate prenatal diagnosis. We emphasize the importance of these prenatal tests and reporting the patients correctly.

References

1. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics; Committee on Genetics; Society for Maternal-Fetal Medicine. Screening for fetal chromosomal abnormalities: ACOG Practice Bulletin. Obstet Gynecol. 2020;136(4). doi:10.1097/aog.0000000000004084
   Article · PubMed · Google Scholar
2. Srebniak MI, Joosten M, Knapen MF, et al. Frequency of submicroscopic chromosomal aberrations in pregnancies without increased risk for structural chromosomal abnormalities: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2018;51(4):445-452. doi:10.1002/uog.17533
   Article · PubMed · Google Scholar
3. 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 Edwards syndrome. Indian J Clin Biochem. 2013;28(1):3-12. doi:10.1007/s12291-012-0269-9
   Article · PubMed · Google Scholar
4. Guraya SS. The associations of nuchal translucency and fetal abnormalities: significance and implications. J Clin Diagn Res. 2013;7(5):936-941. doi:10.7860/jcdr/2013/5888.2989
   Article · PubMed · Google Scholar
5. Ergün P, Köken G, Coşar E, Şahin F, Arıöz D, Yılmazer M. Pregnancy womans measuring the level of knowledge for triple screen test and others during pregnancy. TAF Prev Med Bull. 2011;10(4):403-408.
   PubMed · Google Scholar
6. Malone FD, Canick JA, Ball RH, et al; First- and Second-Trimester Evaluation of Risk Research Consortium. First-trimester or second-trimester screening, or both, for Down syndrome. N Engl J Med. 2005;353(19):2001-2011. doi:10.1056/nejmoa043693
   Article · PubMed · Google Scholar
7. Yararbaş K, Ilgın-Ruhi H. Prenatal tanı. Turkiye Klinikleri J Med Sci. 2006;26.
   PubMed · Google Scholar
8. Practice Bulletin No. 163: screening for fetal aneuploidy. Obstet Gynecol. 2016;127(5). doi:10.1097/aog.0000000000001406
   Article · PubMed · Google Scholar
9. Kaya H, Cerci SS, Komek H, Yayla M, Alp MN, Oral D. Bölgemiz gebelerinde triple test ile prenatal tarama sonuçları ve sitogenetik değerlendirilmeleri. Perinatoloji Derg. 2004;12(1):38-42.
   PubMed · Google Scholar
10. Atak PG, Arpacı A, Seydal G. Adıyaman iline ait ikili ve üçlü prenatal tarama testlerinin medyan değerlerinin belirlenmesi. Turk J Biochem. 2014;39(2):231-237.
    PubMed · Google Scholar
11. Benn P, Wright D, Cuckle H. Practical strategies in contingent sequential screening for Down syndrome. Prenat Diagn. 2005;25(8):645-652. doi:10.1002/pd.1215
    Article · PubMed · Google Scholar
12. Platt LD, Greene N, Johnson A, et al; First-Trimester Maternal Serum Biochemistry and Fetal Nuchal Translucency Screening Study Group. Sequential pathways of testing after first-trimester screening for trisomy 21. Obstet Gynecol. 2004;104(4):661-666. doi:10.1097/01.aog.0000139832.79658.b9
    Article · PubMed · Google Scholar
13. Smidt-Jensen S, Permin M, Philip J. Sampling success and risk by transabdominal chorionic villus sampling, transcervical chorionic villus sampling, and amniocentesis: a randomized study. Ultrasound Obstet Gynecol. 1991;1(2):86-90.
    PubMed · Google Scholar
14. da Silva EC, Silva SV, Damião R, Fonseca EB, Garcia S, Lippi UG. Stress and anxiety in pregnant women exposed to ultrasound. J Matern Fetal Neonatal Med. 2012;25(3):295-298. doi:10.3109/14767058.2011.574299
    Article · PubMed · Google Scholar
15. Mürsel K, Kadıoğlu N, Özel Ş, Ustun YE. Down sendromu için gebelere yapılan prenatal tarama ve tanı testlerinin sonuçları: maliyet analizi. Ankara Med J. 2019;19(1):108-114.
    PubMed · Google Scholar
16. Yaron Y, Cherry M, Kramer RL, O’Brien JE, Hallak M, et al. Second-trimester maternal serum marker screening: maternal serum α-fetoprotein, β-human chorionic gonadotropin, estriol, and their various combinations as predictors of pregnancy outcome. Am J Obstet Gynecol. 1999;181(4):968-974. doi:10.1016/s0002-9378(99)70334-0
    Article · PubMed · Google Scholar
17. Tian W, Yuan Y, Yuan E, et al. Evaluation of the clinical utility of extended non-invasive prenatal testing in the detection of chromosomal aneuploidy and microdeletion/microduplication. Eur J Med Res. 2023;28(1):1-13.
    PubMed · Google Scholar
18. Kosinski P, Frühauf A, Lipa M, et al. Clinical consequences of maternal serum PAPP-A and free beta hCG levels above 2.0 multiple of median in the first trimester screening. Eur J Obstet Gynecol Reprod Biol. 2023;282:101-104. doi:10.1016/j.ejogrb.2023.01.016
    Article · PubMed · Google Scholar
19. Pihl K, Sørensen TL, Nørgaard-Pedersen B, et al. First-trimester combined screening for Down syndrome: prediction of low birth weight, small for gestational age, and pre-term delivery in a cohort of non-selected women. Prenat Diagn. 2008;28(3):247-253. doi:10.1002/pd.1946
    Article · PubMed · Google Scholar
20. Kavak ZN, Basgul A, Elter K, Uygur M, Gokaslan H. The efficacy of first-trimester PAPP-A and free beta hCG levels for predicting adverse pregnancy outcome. J Perinat Med. 2006;34(2):145-148.
    PubMed · Google Scholar
21. Gagnon A, Wilson RD; Society of Obstetricians and Gynaecologists of Canada Genetics Committee. Obstetrical complications associated with abnormal maternal serum markers analytes. J Obstet Gynaecol Can. 2008;30(10):918-932. doi:10.1016/s1701-2163(16)32973-5
    Article · PubMed · Google Scholar
22. da Fonseca EB, Damião R, Moreira DA. Preterm birth prevention. Best Pract Res Clin Obstet Gynaecol. 2020;69:40-49. doi:10.1016/j.bpobgyn.2020.09.003
    Article · PubMed · Google Scholar
23. Spencer K, Cowans NJ. Correction of first-trimester biochemical aneuploidy screening markers for smoking status: influence of gestational age, maternal ethnicity, and cigarette dosage. Prenat Diagn. 2013;33(2):116-123. doi:10.1002/pd.4017
    Article · PubMed · Google Scholar

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