Background: The aim of this study is to compare the efficacy of nuchal translucency (NT) measurement with laboratory screening tests in prenatal diagnosis of Down syndrome (DS) and neonatal outcomes. Materials and Methods: In this cross-sectional-descriptive study, data were collected from 260 pregnancy files. Ages of pregnant women were 20–34 year old who referred for prenatal care. NT was measured by ultrasound at 11–13 + 6 and quad marker tests at 15–18 gestational week. Data analysis was performed by SPSS 21 (IBM, USA) that was considered significant with P < 0.05. Result: Two-hundred and twenty-one pregnant women with average age of 26.6 ± 4.44 years were screened. Frequency of negative screening tests for DS was 188 pregnant women (88.7%) and 24 (11.3%) of them positive. Amniocentesis was performed for those who had positive screening test, but their NT measurement was <3.5 mm. All reports of amniocentesis were negative which was consistent with fetal NT ultrasonography reports, and all neonatal outcomes were normal after delivery follow-up. Conclusion: NT measurement and quad marker test cannot accurately predict the fetal health in the future; however, NT is more reliable than laboratory screening tests because it is more consistent with the results of amniocentesis. NT is also a safer and cheaper method than amniocentesis. Pregnant women tolerate an unfavorable psychological stress and high cost during amniocentesis. The suggested option is to assess the cell-free fetal DNA in pregnant blood instead of amniocentesis.
Keywords: Laboratory, neonatal outcomes, nuchal translucency, screening
Down syndrome (DS) is the most commonly identified genetic form of mental retardation and the leading cause of specific birth defects and medical conditions.
DS occurs in approximately 1 in every 800 live births. The risk of a fetus exhibiting DS increases with maternal age. It has been proved that a number of maternal serum markers are useful in screening of DS., Recent advances in screening have enabled the patients to be informed about the risk at a much earlier stage of pregnancy than has previously been possible.,,, The identification of DS during the first trimester offers significant advantages to the patients and clinicians, including greater privacy and easier and safer termination, if necessary. The nuchal translucency scan (NT scan) uses ultrasound to help to identify higher chances for chromosomal conditions including DS in a fetus, particularly for high-risk women. The NT scan is performed between 11.5 and 13 weeks and 6 days of gestation. As the ultrasound technology improved, the ability to provide more detailed fetal imaging and the differentiation of normal from pathologic NT structures became possible. First-trimester choices for screening include sonographic measurement of NT, serum screening of beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein A (PAPP-A) levels, and a combination of both serum and sonographic screening. Second-trimester choices include the quad test incorporating maternal serum AFP, β-hCG, unconjugated estriol, and diametric inhibin-A., Quad screening produces better results than triple screening; it has both lower false-positive rates and higher detection rates. It can be performed between 15 and 22 weeks of gestation. There are lots of evidence states that screening tests, sonographies, and also amniocentesis are more efficient and more valuable if they are used in the first trimester. Amniocentesis is the most extensively used fetal sampling technique for detection of chromosome abnormalities. The aim of this study was to detect the association between NT and neonatal outcome and the efficacy of NT measurement compared with laboratory screening tests in prenatal diagnosis of DS.
Study protocol was clarified, process of the study was explained to participants, and written consent was obtained from them. In this cross-sectional-descriptive study, data were gathered from 260 pregnancy files in Dr. Rasekh’s clinic during 2013–2014 in Jahrom, Iran.
The study group was aged between 20–38 years, and these women were referred for prenatal care. The study group was selected based on following characteristics: age, residence, education level, number of children, and no underlying medical disease.
Because of the incomplete information and also unwillingness of the patients to cooperate, 48 individuals were excluded from the study.
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Finally a total number of 212 patient files were stuudied
A total of ultimately 212 patient’s files were studied. NT was measured by ultrasound at 11–14 weeks of gestation. Quad marker test was performed at 15–18 weeks of gestation.
A fetal NT value of >3.5 was considered as DS. The quad marker test was performed by two accredited laboratories in Jahrom, Iran. The cutoff risk calculated for trisomy 21 was 1:250. It is expected that out of 250 women with similar results, one will have a trisomy 21 pregnancy and 249 will have a normal pregnancy. The doctors state that the screening tests cannot detect 100% of fetuses with DS. Maternal screenings will have some level of inherent false-negative and false-positive results, so they are not a good substitute for diagnostic tests. This finding is based on clinical information obtained from patients. Data management and analysis were performed using SPSS 21 (IBM, USA). Cases with P < 0.05 were considered significant.
A total number of 212 pregnant women referred to Dr. Rasekh’s clinic which randomly assigned to study groups. The average age of the women was 26.6 ± 4.44 years.
Screening test’s results
The frequency of negative and positive screening tests for DS was 188 persons (88.7%) and 24 persons (11.3%), respectively [Table 1]. Only 25% (six patients) of pregnant women with a positive screening test did amniocentesis.
Consequently, the result of amniocentesis was normal in all, without any cytogenetic abnormalities. All neonates also were normal at follow-up.
The remaining study groups were followed up by ultrasound and gave birth to normal neonates with a mean NT of 1.7 (maximum: 2.1 and minimum: 1.4), and the mean of apgar scores at birth was 9.
There was no association between the positive quadruple screening test and the birth of a neonate with DS (P = 0.06) [Table 2].
All NTs obtained by ultrasound were <3.5 (maximum: 2.8 and minimum: 1.2), and all the fetuses were born without any abnormality [Table 2].
The lowest percentages of the positive screening test results were found in patients who were 19–25 years (3%), and the highest percentage was in patients who had 35–40 years (71.4%). In this study, the largest age group was 25–35 year old.
The relation between the increased maternal age and a positive quadruple screening was considerable (P = 0.005) [Table 3] and [Table 4].
This is a hypothesis that the study group who has a normal NT screening test will have a normal neonate, and the group with abnormal screening test will not certainly have an abnormal neonate.
The cause of DS in neonates is meiotic nondisjunction of the 21st pair of chromosomes. Birth of a neonate with DS must be decreased by prevention and appropriate follow-up. In the present study, no significant association was found between positive quad screening test results and the birth of a neonate with DS or neonatal outcome, but NT by specificity of 100% was a great help to distinguish normal embryos, and it was more reliable than other identification tests. It is noteworthy that an expert sonographer also has an important role in measurement of NT.
The results of previous studies showed that false-positive rates in ultrasound and quad marker screening test were 5.4% and 6.2%, respectively, and their detection rates were similar to each other (94.6% for ultrasound and 94.8% for quad marker screening). Recent studies have confirmed the efficacy of combined first-trimester screening for DS based on maternal age, serum marker (hCG and PAPP-A), and ultrasound measurement of fetal NT., A previous study showed that a routine first-trimester NT measurement is effective for screening of fetal chromosomal abnormalities.,
Another studies have shown that the noninvasive prenatal tests would have missed a significant anomaly which would have been detected by ultrasound and NT.
In the present study, we found no significant relation between positive screening tests and the birth of neonates with DS, but NT is more reliable than laboratory screening tests.
Most false-positive results of the tests lead to pregnancy loss; however, there was no certain fetal abnormality. In two cases, the mothers with a positive quad marker test result agreed to do amniocentesis. During amniocentesis, rupture of membranous was happened, and the fetuses died after birth due to prematurity, while the amniocentesis report was normal chromosomes.
Pregnancy loss is one of the side effects of amniocentesis,, but false-positive results of laboratory reports in some cases lead to amniocentesis which could be resulted in abortion of normal fetuses.
Access to result of the amniocentesis has a long process which takes about 3–4 weeks. Waiting for this long time leads the mothers to a higher stress. On the other hand, amniocentesis is associated with a high cost and it is hard for some to afford it.
Laboratory’s weak points should be found and resolved to minimize the faults which can help pregnant women not to experience invasive and expensive intervention methods such as amniocentesis improvements in fetal screening test resulted in lower laboratory errors. NT measurement in the first-trimester ultrasound markers, first-trimester serum markers, and combinations of these screens are addressed.
We should say that it is better to recognized a more accurate and reliable screening test to detect trisomy.
Cell-free fetal DNA testing is a new screening test, which indicates high-risks women who are likely to have a fetus with DS (trisomy 21), Edward syndrome (trisomy 18), and Patau syndrome (trisomy 13).
In this test, blood sample of the women is taken after 10 weeks of pregnancy, and the relative amount of free fetal DNA in the mother’s blood is measured, and this test determines the risk of having a fetus with DS, Edward syndrome, and Patau syndrome based on the relative amount of DNA from chromosomes 21, 18, and 13.
The results are usually available within 2 weeks of the blood draw. Cell-free fetal DNA testing is regarded to detect >99% of all DS pregnancies and 98% of all trisomy 18 pregnancies. It detects about 65% of all trisomy 13 pregnancies.
The latest researches have shown that cfDNA testing for trisomy 21 has a higher sensitivity and positive predictive value and a lower false-positive rate comparing with standard screening by the measurement of NT and biochemical analyzes., This method can substantially reduce the need of invasive diagnostic procedures and attendant procedure-related fetal losses in women with positive screening test and abnormal NT.
CfDNA test is very expensive, and all of the patients are not able to afford it, so insurance companies can significantly contribute to reduce the costs.
In this study, a significant number of positive quad screening tests were found in pregnant women whom were >35 year old. Encouraging women not to be pregnant after the age of 35 and to do required screening tests can leads to a lower incidence of DS.
This research states that NT screening and quad marker test cannot accurately predict the status of the fetus in the future. Further study with an increased sample size can help to evaluate the specificity of the quad screening test. In comparison to the other screening tests, cell-free fetal DNA testing is a safer and more effective test to detect DS. Its further advantages are mentioned in following sentences. One of the benefits of this test is a faster access to the result, and it is also a noninvasive method. It results in reduction of trauma to the both mother and fetus, and it also decreases psychological damage to the mother.
We would like to thank Dr. Hooshmand for his insightful comments and encouragement.
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Conflicts of interest
There are no conflicts of interest.
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3], [Table 4]