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Online ISSN
1305-3124

Established
1993

Editors-in-Chief
​Cihat Şen, ​Nicola Volpe

Editors
Cecilia Villalain, Daniel Rolnik, M. Mar Gil

Managing Editors
Murat Yayla

Statistics Editor
Resul Arısoy

Examination of perinatal and postnatal outcomes of pregnant women who refuse the recommended invasive procedure for increased nuchal translucency

İlkin Seda Can Çağlayan, Vildan Kılıç

Article info

Examination of perinatal and postnatal outcomes of pregnant women who refuse the recommended invasive procedure for increased nuchal translucency. Perinatal Journal 2024;32(2):155-160 DOI: 10.59215/prn.24.0322010

Author(s) Information

İlkin Seda Can Çağlayan,
Vildan Kılıç

  1. Sivas Cumhuriyet University, Faculty of Medicine, Department of Gynecology and Obstetrics, Sivas, Türkiye
Correspondence

İlkin Seda Can Çağlayan, Sivas Cumhuriyet University, Faculty of Medicine, Department of Gynecology and Obstetrics, Sivas, Türkiye, [email protected]

Publication History

Manuscript Received: March 27, 2024

Manuscript Accepted: July 17, 2024

Earlyview Date: July 17, 2024

Publication date: July 27, 2024

Conflicts of Interest

No conflicts declared.

Objective
The aim of our study was to detect an increase in nuchal translucency (NT) measurement among our patients attending our clinic for 11-14 weeks of control and to examine the perinatal and postnatal outcomes of pregnant women who were recommended an invasive fetal procedure but refused it.
Methods
107 pregnant women between 11-14 weeks of gestation who were evaluated in our center from 2018 to 2021 and who rejected invasive procedures were included. Patients opting for follow-up and delivery at another facility were excluded from the study. The study groups were categorized into 3 groups based on NT values, regardless of gestational age: 1st Group 2.5-3.4 mm, 2nd Group 3.5-4.5 mm, and 3rd Group>4.5 mm. Fetal ultrasound scans were conducted during the antenatal period, with detailed examinations postnatally.
Results
Abnormal ultrasound findings were detected in 11.2% of fetuses, with a higher prevalence in groups exhibiting greater NT increases. While chromosomal anomaly was seen in 13% of all fetuses, Group 2 (NT 3.5-4.5mm) had the highest percentage (33.3%). The highest right and healthy birth rates were found in group 1 (91.8%), inversely proportional to the increase in NT.
Conclusion
Increased NT values ​​appear to be associated with increased rates of structural anomalies and adverse perinatal outcomes. Although chromosomal anomalies are associated with NT increase, a direct proportional relationship between the two remains undetermined.
Keywords

First trimester, nuchal translucency, perinatal outcome, decision-making, prenatal testing

Introduction
n the intrauterine period, the evaluation of fetal health is currently being performed by many methods, especially by ultrasound.[1] Fetal Nuchal Translucency (NT), which is measured with the help of ultrasound between 11-14th gestational weeks, is an effective test for screening first-trimester chromosomal anomalies when combined with serum markers and maternal age.[2] NT is the sonographic appearance of collected fluid under the skin behind the fetal neck in the first trimester of pregnancy, which refers to the hypoechoic region between the skin and soft tissues behind the cervical spine of the fetus.[3] In addition to chromosomal defects, increased NT thickness is also associated with an increased risk of various fetal malformations, genetic syndromes, and fetal mortality.[4-6] For this reason, it is important to examine increased NT even in genetic counseling and in fetuses that are shown to have a normal karyotype. However, not every increased NT should be interpreted as an anomaly.[7] NT is found to be increased in 4.4% of fetuses with normal karyotypes.[8] These fetuses have been reported to be at high risk for adverse pregnancy outcomes, structural abnormalities, particularly heart defects, genetic syndromes, and fetal losses.[5,9,10]
 Further prenatal testing is needed in fetuses that have increased NT. Prenatal diagnosis of fetal chromosomal abnormalities is the most common indication for invasive prenatal testing and is used for fetal and pregnancy management, and determining the method of delivery. Chorionic Villus Sampling (CVS), amniocentesis (AS), and cordocentesis (CS) are invasive diagnostic tests used to diagnose genetic or congenital diseases. These tests can detect the presence of chromosomal abnormalities in the fetus with an accuracy rate of almost 100%.[11,12] There is a risk of serious complications during invasive prenatal tests, such as abortion, bleeding, infection, pregnancy loss, amniotic leakage, clubfoot, talipes equinovarus, limb reduction defects, hemangiomas, and embolism.[13] It can be difficult to obtain maternal and paternal consent for the procedures due to the religious views of the couples, and the availability of treatment if a problem is detected. In our opinion being in a peripheral geographical area has negative effects on the approach to invasive procedures and many patients do not accept the procedure. In this case, the prenatal and postnatal outcomes of these pregnancies that reject invasive procedures become important to inform future patients. In our study, we aimed to present the perinatal and postnatal outcomes of women who declined prenatal invasive procedures in case of increased NT.
 
Methods
The present study included pregnant women who applied to the University hospital between January 1, 2018, and June 1, 2021, whose examinations showed increased nuchal thickness and rejected the recommended prenatal invasive procedure (CVS, AS, CS). Among the pregnant women who were included in the present study, those who gave birth or had an abortion outside the Sivas Cumhuriyet University Faculty of Medicine Obstetrics Clinic were excluded from the study because their newborn data were not available. Female patients who were between the ages of 18 and 40 were included in the present study. As a result of fetal NT scanning between 11-14 weeks, fetuses that had NT thickness of 2.5 mm and above were included in the study. All NT measurements were taken by the same physician following the standardized NT measurement techniques of the Fetal Medicine Foundation (FMF) (Guidelines of the Fetal Medicine Foundation, London, http://www.fetalmedicine.com). NT was measured in the mid-sagittal section with the fetal head in the neutral position. The ultrasound examination was performed  with the General Electrics Voluson E8 brand Ultrasonography Device (General Electric Medical Systems , Istanbul, Turkey) and the 2.7 MHz transabdominal curvilinear probe. The patients were dividedin three groups in the present study according to NT values, regardless of gestational ages (Group 1, NT: 2.5-3.4 mm, n=74; Group 2, NT: 3.5-4.5 mm, n=12; Group 3, NT: > 4.5 mm, n=21). First, the sociodemographic data (age, number of births, gestational weeks, disease history, medication used, etc.) of the pregnant women included in the present study were questioned. Then, ultrasound examinations were performed. The pregnant women who had multiple pregnancies and those who became pregnant by in vitro fertilization or intrauterine insemination were excluded from the study. Pregnancy outcomes were obtained from computerized records of hospital obstetric and gynecological admissions. In ongoing pregnancies, fetal structural anatomy screening was performed between 18-22nd gestational weeks, and fetal echocardiography was performed between 20-24th gestational weeks. The pediatrician examined all infants before being discharged from the unit. The results were recorded as miscarriage, termination of pregnancy, intrauterine death (IUMF), and live birth. Maternal age, parity, gestational age at NT measurement, NT values, fetal structural anomaly screening results, perinatal outcomes, percentage of living newborns with/without anomalies, gestational age at birth, birth weight between the groups, 5th-minute Apgar scores, and the final distribution of the structural anomalies were compared. The study protocol was approved by Sivas Cumhuriyet University, Non-Interventional Clinical Research Ethics Committee on 14.04.2021 (Decision No: 2021-04/20). All procedures that was performed in the study were in line with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki Principles and its later amendments or comparable ethical standards.
 Statistical analysis
The SPSS (Statistical Package for Social Sciences) for Windows 22.0 (IBM SPSS, USA) program was used for statistical analysis in evaluating the findings from the study. The Kolmogorov-Smirnov test was used for the conformity for normal distribution. The ANOVA and Tukey Tests were used if the data passed the normality test, and the Kruskal-Wallis test were used if the data did not pass the normality test. Descriptive measures were expressed as numbers and percentages for categorical variables, as the mean and standard deviation for numerical variables in normally distributed data, and as median and minimum-maximum in non-normally distributed data. The Chi-Square Test was used for the analysis of categorical variables and the statistical significance level was accepted as p < 0.05.
 
Results
A total of 107 women participated in the study. The demographic and clinical characteristics and perinatal outcomes of the participants are given in Table 1. Maternal age was statistically and significantly lower in Group 2 when compared to the other groups (p =0.017). A statistical significance was detected between the increased gravida and the NT being > 4.5 mm (p =0.003). In the obstetric history section given in Table 1, it was found that the participants in Group 2 and Group 3 did not have an extra negative history, and if the fetuses in Group 1 are included, a total of n = 87 (81.3%) did not have any bad obstetric history. A statistically significant difference was detected between the birth method, gender, weight, height, and need for intensive care of the infants (p < 0.001).
When the congenital and genetic anomalies in infants were evaluated according to NT groups, it was found that healthy and live birth rates decreased statistically and significantly, as NT measurement increased (p < 0.001) (Table 2). Interestingly, it was also found that genetic anomalies were statistically higher in infants in Group 2 (NT: 3.5-4.5 mm, n=12) than in the other groups (p< 0.001). Along with structural anomalies, Cystic hygroma was observed more frequently in Group 3 than in the other groups (p < 0.001). No fetus with cystic hygroma was found in Group 1 (NT: 2.5-3.4 mm, n=74), in which no structural anomaly was observed.
When the pregnancy outcomes of women who had pregnancies at an older age (≥35 years) were evaluated, it was found that older pregnancies did not cause a statistically significant difference, especially in NT thickness (p = 0.104) (Table 3). When the structural anomalies detected on ultrasound were questioned (cardiac anomaly, pelviectasis, short femur, hyperechoic bowel, megacystitis, hyperechoic cardiac focus, cystic hygroma) and previous negative obstetric stories (fetal anomaly history, abortion history, autism history, infection), were evaluated, it was found that there were statistically significant increases with advanced maternal age (n=8/18, 50%, n=4/18, 22.2%) (p =0.041, p< 0.001).. 
Discussion
In our study, we discovered that pregnant women with higher NT levels in their fetuses had an 11.2% (n = 12) rate of structural and chromosomal anomalies among all fetuses. This rate was highest in the group with NT>4.5 mm, at 38.1% (n = 8). The healthy live birth rate for all fetuses with increased NT was 78.5% (n = 84), with most of these fetuses having an NT measurement of 2.5-3.4 mm (n = 68, 91.8%). With advanced maternal age (≥ 35), the likelihood of structural and chromosomal anomalies and the need for infant intensive care in the postpartum period rise. In a recent study involving 85 patients with increased NT, chromosomal anomalies were found in 10.6% (n=9) of the patients, and fetal structural anomalies were found in 29.4% (n=25).[14]  In another study including 720 pregnant women with increased NT in their fetuses, the karyotype results of 523 fetuses were found to be normal. And 357 of these pregnancies (68.3%) resulted in live birth.[15]
 In the study that was conducted by Senat et al., which examined the pregnancy outcomes of fetuses that had increased Nuchal Translucency, 160 fetuses with NT of 4 mm and above were evaluated and abnormal karyotype was detected in 44.3% (n=70) of these fetuses.[16] Of the 55.7% with normal karyotypes, 74 % showed no abnormalities the follow-up ultrasound scan.[16] Our study detected abnormal karyotype (n=4) in 19% of 21 babies with NT over 4.5 mm (Group 3). Previous studies reported that the rates of structural abnormalities were high in fetuses with increased Nuchal Translucency.[5-6] In particular, the probability of these anomalies increased in frequency with the increased NT values.[17] The findings of the present study support the literature data. Group 3 appeared to be the group in which structural anomalies were most common (n=8, 38.1%), followed by the fetuses in Group 2 (n=4, 33.3%), while no structural anomalies were detected in Group 1.
In another study that examined the effects of increased Nuchal Translucency on adverse pregnancy outcomes in chromosomally normal fetuses, 16260 fetuses were examined and congenital malformation was detected in 772 (4.74%).[18] In the same study, the total adverse outcome (fetal loss or malformation) rate was found to be 2.7%, and the researchers found the rate in our study to be 21.5%. It was thought that the difference occurred because of the high number of patients in the first study. One of the important results of this study which was conducted by Westin et al. was that there were no relationships between increased NT and perinatal death, which the present study supports.[18] In our study, even though the intrauterine loss rate was highest in Group 3, with no statistically a significant relationship was found between the NT groups in this regard (p = 0.011).
The study followed up on 398 cases of fetuses with increased nuchal translucency (NT). In the group with NT ≥ 3.5mm, 3.7% (n=8) had morphological anomalies, 50.5% (n=103) had chromosomal anomalies, and maternal age was significantly higher in this group.[19] Among the live-born children, 70% (166/238) were healthy with no morphological or chromosomal abnormalities.[19] Our study found that structural anomalies and karyotype anomalies were higher in the group with advanced maternal age, and 78.5% (84/107) of live-born children were healthy.
In a study by Ozyuncu et al., NT increase grouping was adjusted as in our study and divided into 3 groups. In this study, normal ultrasonographic anatomy was found to be 47.5%, 7.7%, and 14.3% in groups 1, 2, and 3, respectively. Group 3 was found to have the lowest normal karyotype rate (44.6%). Higher frequencies of miscarriage and termination of pregnancy were observed in group 3 compared to group 1 (8.9% versus 4.9% and 66.1% versus 32.7%, respectively).[20] Similarly, in our study, the termination and intrauterine loss rate was highest in group 3 (19%, n = 4).
 In another study that included 393 patients and examined pregnancy outcomes in fetuses that had increased NT measurements, chromosomal anomalies were detected in 94 (66.1%) of 142 fetuses with NT measurements of 4.5 and above.[21] It was found in the present study that there were chromosomal anomalies in 4 of 21 patients (19%) with NT measurements above 4.5. It was thought that the difference occurred because of the number of patients in the study and the fact that 77 of the patients in the first study had an NT measurement of ≥ 6.5. In the same study, it was found that generally unfavorable pregnancy outcomes were detected in half of the cases with NT thickness >95th percentile, and similar results were found in the present study.
 In a study including 255 women examining increased fetal nuchal thickness in women with advanced maternal age, fetal NT was found to be ≥2.5 mm in 51 women. The incidence of chromosomal abnormalities in the NT increased group was 20.0% (9/45), and in the NT normal group was 0.5% (1/202).[22] The incidence of abnormal pregnancies and chromosomal abnormalities in women with advanced maternal age and NT thickening was higher than the incidence in normal NT.[22] In our study, we showed that structural anomalies and karyotype anomalies increase with advanced maternal age.
 The limitations of the present study were the low number of patients and the lack of long-term follow-up of infants after their births, especially in terms of detecting neurodevelopmental disorders and monitoring the progression of structural anomalies. The strength of the present study was that all the pregnant women were followed by one single physician and the measurements were made by one single physician. It’s crucial to communicate with patients who are hesitant about invasive procedures. It’s important to inform the family that a definitive diagnosis can only be obtained through invasive procedures. These procedures are essential for monitoring and managing the fetus during both the antenatal and postnatal periods.
Conclusion
In the present study was found that the fetuses in which increased NT measurements could be born alive and without structural defects in inverse proportion to the degree of NT thickness, but genetic anomalies could vary independently of the measurements, especially in the groups with NT of 3.5 and above.  The results are especially important for the management of couples whose infants are found to have increased NT and who refuse invasive procedures, and for informing patients about possible risks. 
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File/Dsecription
Table-1
Comparison of demographic features, clinical characteristics and perinatal outcomes between the NT groups.
Table-2
Comparison of fetuses in increased NT groups in terms of major congenitalanomalies and chromosomal defects
Table-3
The effect of advanced age pregnancy on NT values and pregnancy outcomes
Article's type
Original Article
Pages
155-160
Article info
Online publication date: July 17, 2024
Perinatal Journal 2024; 32 (2)
DOI
10.59215/prn.24.0322010
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