This study was done back in 1998.
Conflict of Interest Declaration
The author acknowledges no commercial affiliation or financial conflict of interest.
The author wishes to express his appreciation to Dr Ali Cadili, Dr. Essam Shaaban, Dr. S. Desilva, Dr Lqaporte a Radiologist at JPMC,, and Siti Arabiah Hamid for their help and guidance.
This project is dedicated to the memory of my beloved parents and brothers who were killed in Iraq.
The aim of the study was to confirm the relation between Nuchal translucency thickness and cardiac pathology; especially in restricted genetic pool communities. The measurement of nuchal translucency thickness is a part of the routine scan done for women in the first trimester of pregnancy.
Material and Methods:
8000 women were scanned by the same sonographer using 2D trans abdominal sonography in this longitudinal Prospective ultrasound exam review study from 1989 to 2006. The women’s mean age was 28 years. 25 percent of these women were over the age of 35 years. 90% of the women in this study practice close relatives marriages (restricted gene pools). A chromosomal analysis was performed on all patients over 35 years of age, and 98% of the high risk pregnancies which they have increased risk for aneuploidies due to maternal age and other factors. (n=600). This was a descriptive and Prospective study, the patients number was 8033, 33 patients declined to sign the consent form.
Results: From the high risk groups (over age of 35 years with abnormal karyotyping), 29 fetuses had nuchal translucency thickness (NT) values between 4.5 and 7.5 mm. The results were tabulated according to nuchal translucency thickness and cardiac anomalies.
Conclusions: The nuchal translucency proved to be an excellent marker of some fetal cardiac pathology in the first trimester. The nuchal translucency in this study shows an excellent relationship also between the NT and some cardiac pathology.
Keywords: Nuchal translucency (NT), Fetal Cardiac Anomalies, fetal ultrasound
Nuchal translucency thickness is the sonographic appearance of a subcutaneous collection of fluid behind the fetal neck in the first trimester. Nuchal translucency thickness is part of the routine sonography done in the 11 to 14 weeks gestation for most pregnant women (1) High resolution real-time sonography now permits the differentiation between nuchal translucency thickness (NT) and cystic hygroma of the fetal neck in the first trimester. (2) Nuchal translucency thickness has been indicated and used as useful marker for fetal Down syndrome. (3) Maternal age has proved to be a poor predicator of Down syndrome with a sensitivity ranging from 20 to 25 percent (4) . Triple screening lab tests may achieve up to a 65 percent detection rate for Down syndrome with a 5 percent false positive rate.(5) The best age to measure nuchal translucency thickness is between 9 to 14 weeks gestation.(6). Chromosomal anomalies were found in 28 percent of cases where the nuchal translucency thickness was greater than 2.5 mm. (7) Cardiac defects are responsible for 22 percent of perinatal deaths and more than 50 percent of childhood deaths due to congenital abnormalities. (7) Increased nuchal translucency thickness at 10 to 14 weeks of gestation is seen in about 70 to 80 percent of fetuses with chromosomal abnormalities; 40 to 60 percent of these fetuses have cardiac defects. (8) see figures (1 to 6).
Nuchal translucency scan is performed between the 11th and 14th week of gestation, because the accuracy is best in this period. The scan is obtained with the fetus in sagittal section and a neutral position of the fetal head (neither hyper flexed nor extended), either of which can influence the nuchal translucency thickness). The fetal image is enlarged to fill 75% of the screen, and the maximum thickness is measured, from inner-to-inner skin measurements. It is important to distinguish the nuchal translucency thickness from the underlying amniotic membrane. Normal thickness depends on the crown-rump length (CRL) of the fetus. Among those fetuses whose nuchal translucency thickness exceeds the normal values, there is a relatively high risk of significant anomalies to the fetus (2-7).
Material and Methods
This was a descriptive, Prospective, longitudinal and cohort study of 8000 consecutive cases of pregnant women who had routine sonography examinations in the first/second trimester. Written consent was obtained from each patient and the study was approved by the Clinical Committee of each hospital. These longitudinal studies were performed in Canada, Saudi Arabia, and Brunei from 1989 to 2006. Chromosomal analysis was performed on 25% of the high risk groups that identified by age 35 and over, and had a history of fetal malformations. The numbers of patients were 8033; Thirty three women did not consent to this study and refuse to participate.
Patients were considered to be at high risk for aneuploidies based on either advanced maternal age or positive biochemical screening results. There were no special criteria for the fetuses’ selection. This research was approved by the ethical committee of the Royal Jerudong Medical Center in Brunei under the supervision of the radiology manager in JPMC, Brunei-Darussalam. (Letter of approval will be provided upon request).
The sonogram were done from 11 to 14 weeks gestational for the high risk group, then at 18-20 gestational week for detail scan for both groups, and then a follow up for fetal anomalies at 26 and 32 weeks for the high risk group. Result of fetal wellbeing was collected after delivery of all patients.
Nuchal translucency thickness was measured prospectively from 11 to 14 weeks by the same sonographer using varieties of transducers frequencies ranging from 3.0 to 5.0 MHz, the sonographer were credentialed for the measurement of nuchal translucency thickness by the regional organization and following the SDMS standards. The sonographer did not measure the nuchal thickness but the Nuchal translucency from Inner-to-inner skin measurements. A variety of ultrasound machines were used including the ATL 3000 and Diasonic 1000 were used in Saudi Arabia and Brunei daru-alssalam, ATL 3000, 5000 and IU22 Philips models were used in USA and Canada.
The incidence of hypo-plastic ventricles was determined in this study based on pathological examination of the terminated fetuses, and postmortem results at 11 to 14 weeks gestation.
The sonographer examined the fetal neck in mid-sagittal plans with high resolution transducers. Different views of the fetal head were obtained to check for fetal head pathologies. The nuchal translucency thickness (NT) behind the occipital bone was measured in the true mid-sagittal plan, at least 3 measurements where obtained. The sonographer was very careful to measure the nuchal translucency thickness inner-to-inner and not to include the outer skin. These measurements were correlated with the fetal karyotype lab results, and after delivery of all fetuses, fetuses with anomalies was logged and compared favorably with the ultrasound examination for validity.
In the normal population ( who were defined by chromosomal analysis), mean nuchal translucency thickness measurement for each of the gestational weeks 11 to 14 weeks and maternal age were compared by one-way analysis of variance. 95 percent confidence intervals were also calculated.
Crown rump values that correlated with optimal NT measurement were 45 mm to 84 mm. When measuring the NT, the fetal neck and head were included in the image along with a good mid-sagittal section of the fetus.
The calipers were placed on the lines that define the NT translucency inner-to-inner. A pit falls might happen in the measurements when the sonographer incorrectly placed one of the callipers farther from the translucency lines, an image is included to show this pitfall (Figure 6). Although there were no strict guide lines back in 1989 regarding the Nuchal translucency (NT) many sonographers were lectured by scientists about the important of NT measurements Dr. Wald and Dr. Hackshaw were among the leading scientists in this field back in 1986 (21), and then followed by other scientists among them Dr. Nicolaides 1992. I was using the method in 1998 for a general interest. Fetal Medicine Foundation (FMF) standard were used in this study in later date after 1996.
A total of 8033 fetuses were scanned sonographically (including 600 fetuses in the high risk group for aneuploidies); 33 patients declined to participate in this study, the round number of 8000 fetuses were scanned in the first trimester as part of a routine evaluation. Five fetuses were identified with Trisomy 21 (Down syndrome) via amniocentesis in the high risk group. Only one case of Downs-syndrome had no cardiac pathology. The results were tabulated accordingly. (Just to be more informative you have to know that Trisomy 21 is not the cause of Down syndrome but it is Trisomy 22, doctors kept this mistake all these years so they dont disturb the public as it is published as 21 for many years until the DNA technology was advanced and they found it was Trisomy 22 and not 21.
There were 9 cases of left hypoplastic heart with nuchal translucency thickness of 2.9 mm – 3.0 mm and all were confirmed after the autopsy. In the chromosomally normal population, nuchal translucency thickness was less than 3.6 mm with mild cardiac pathologies, see tables (1-4).
29 cases had nuchal translucency thickness between 4.6 mm – 7.5 mm with various cardiac anomalies. There were 19 fetal demises; the pathology report showed verities of cardiac defects such as VSD, hypoplastic aortic arch, and imperforated aortic valve, all were confirmed in post-mortem examinations. 25 terminations of pregnancies were performed for no specific fetal anomalies; all were single females from Canada and wanted an abortion for personnel reasons.
A total of 1100 fetuses had nuchal translucency thickness measurements between 2.6 mm –3.5 mm.
46 fetuses had NT between 3.5 mm -4.5 mm, 13 fetuses had NT between 4.6 mm -5.5 mm, and 16 fetuses had NT between 5.5 mm -5.9 mm, see (table 1). Post mortem were done for 19 demise fetuses, see table (2. 13) fetuses with NT between 2.9 mm -3.6 mm had hypolastic left heart with 2 fetuses with VSD. The major cardiac anomalies were tabulated according to the NT and gestational age; see table (3, 4) & Figure (1).The incidence of hypoplastic ventricles in this study was 1.5/1000. A host of anomalies were also found among the chromosomally normal live birth fetuses. One of the fetuses had ectopia- cardis, 12 had VSD, one had ASD, 3 of these fetuses had Aortic atresia, 2 had tricuspid atresa, 3 had mitral Artesia, one had Bicuspid Artesia, and 6 were diagnosed with hypoplastic Aortic arch (table 3). In the majority of fetuses with major cardiac defects, the translucency resolved with advancing gestational age. Certainly, at 20 weeks of gestation, there was no evidence of heart failure.
I presented multiple tables and measurements in my research
PREGNANCY OUTCOME OF 800 CASES. 5694 NORMAL PREGNANCY, NORMAL NUCHAL TRANSLUCENCY THICKNESS.
1175 Chromosomally normal fetuses with thickened nuchal translucency thickness (edema) less than 6.0 mm
The incidence of hypo-plastic ventricle in large study was done in 2003 in the UK reported to be 2.04 PER 10.000 IN 2003, while in USA other studies reported incidence of 2.70 to 3.7 per 10.000 fetuses (19, 20). The incidence of hypo-plastic ventricle in this study was 1.5 per 1000. This remarkable difference may be related to the restricted gene pools of the studied communities (Lacrete-Alberta, Saskatoon-SK, Saudi Arabia-Alhasa region, Brunei daru-alssalam); all these populations are known to practice close marriages among them Mennonites, Hatorites, Mormons, the shiia Muslims in Alhasa region of Saudi Arabia and some Sunni Muslims in Malaysia and Brunei.
Nuchal translucency thickness is not a perfect marker of fetal anomalies since it is known to increase with gestational age. Therefore, the rate of false positive ultrasound examinations increase as the pregnancy advances.
In this study population, the overall prevalence of major cardiac defects (as determined by post mortem examination and live birth data) was correlated with ultrasonographic determination of nuchal translucency thickness.
The consequence of including data from terminations would be an overestimate of the true prevalence of cardiac defects in live births from a non-screened population therefore this is limitation in this study. This is because some of the antenatally diagnosed cardiac defects would have resulted in intrauterine deaths.
In this study, i opted to include the data from intrauterine deaths because such information is important both in terms of offering a possible explanation for the death and in defining the risk of recurrence.
A possible explanation for the relation between increased nuchal translucency thickness and anomalies of the heart and/or great arteries is the development of intrauterine heart failure. This is readily comprehensible when one considers the potential strain that these abnormalities impose on cardiac function at a stage of pregnancy when a high proportion of cardiac output is normally diverted to the head and neck.
In the majority of fetuses with major cardiac defects, the translucency resolved with advancing gestational age. Certainly, at 20 weeks of gestation, there was no evidence of heart failure. The involvement of a fetal cardiologist is needed when nuchal translucency thickness at 10-14 weeks is increased. Increased translucency is found in about 5 percent of the general population (13) .
Nuchal Translucency of ≥3.5 mm is found in only 1-2 percent of the general population (13), and about half of these cases are associated with chromosomal abnormalities or early intrauterine death.
Increased fetal nuchal translucency thickness at 10-14 weeks of gestational identifies a group of fetuses at high risk for aneuploidy and major caridac defects. In the case of aneuploidy, the sensitivity of screening by a combination of translucency and maternal age has been proven to be more than 80 percent accurate with a false positive rate of 5 percent. (13, 14)
A nuchal translucency thickness measurement of more than 6 mm was related to fetal heart anomalies in 19 cases of fetal demise. In these cases, VSD was the commonest anomaly followed by hypoplastic left heart and aortic arch.
Nuchal translucency thickness values of 2.9 to 4.0 mm were related to hypoplastic left heart, VSD and other heart anomalies in 14 terminated fetuses is shown in table 3 all obtained by using standard methodology. This seems to put the validity of the traditional cut off values of 3mm, 4mm, or 5 mm for the development of fetal anomalies into question. Whether this makes 2.9 mm nuchal translucency thickness a more appropriate cut off value for the development of fetal anomalies is unknown. Or whether this could be a technical error in the measurement?
What this does show, however, is that sonographers should be flexible in measuring and interpreting nuchal translucency thickness values in the context of rigid cut off guidelines. And that he or she must measure the NT in the correct mid-sagittal plan with the exact callipers placement IN to IN measurements’ and not away from the true nuchal thickness area as shown in this pitfall image’ (figure 6).
The likelihood of developing fetal cardiac anomalies increases with nuchal translucency thickness values of 3 to 4 mm. Visualization of the pulmonary trunk, and identification of pulmonary stenosis, seems to be more accurate when the nuchal translucency thickness value reaches 6 mm.
False negative sonographic results may indicate that sonographers do not pay much attention to fetal heart pathology this could be because it is sometimes difficult to adequately visualize fetal anomalies especially in obese mothers; ultrasonography is after all, an operator-dependent procedure. Therefore, the use of a magnified zooming view is important to assess for the presence of VSD or any major problem in the fetal heart. The sonographers must be trained to measure the NT.
The blood tests should not be the only factor in looking for fetal heart pathologies, as the nuchal translucency thickness can be thickened in both normal and abnormal chromosomal results.
There are several hypotheses regarding the patho-physiology of increased nuchal translucency thickness. Some of these possible mechanisms include cardiac dysfunction, venous congestion in the head and neck, lymphatic vessel hypoplasia, congenital infection, anemia, and hypopoteinemia. (14, 16)
The combination of abnormalities of lymph vessels and cardiovascular malformations may be attributed to impaired development of neural cysts cells which normally migrate from the embryonic veural tube and play a central role in development of the cardiovascular system. (14, 17)
This study added to the body of knowledge that some fetal cardiac pathology, such as left hypoplastic heart can be increased in the genetically restricted population who practice close family marriages. The researchers from UK and USA indicated that the incidences of hypoplastic left heart were between 2 to 3.7 per 10.000 fetuses (19, 20). This study showed that this incidence was 1.5 per 1000 and that is significant finding, it may be contributed by the restricted genetic pool communities in this study.
The ability to achieve a reliable measurement of NT is dependent upon appropriate training to measure the NT and also relies on a standardized technique to achieve uniformity of measurement.
The optimal training and gestational age for the NT measurement is between 11 to 14 weeks, the crown-rump length should be between 44 mm and 84 mm to achieve a reliable NT measurement.
Sonographers must use true mid-sagittal plan, measures the widest area in the NT, utilize the zooming and magnification knobs when measuring NT and use the electronic callipers if possible.
Sonographic screening for cardiac defects by measuring nuchal translucency thickness at 10 to 14 weeks gestation has been increasingly implemented to improve overall detection rates of fetal cardiac pathology.
The 5 mm cut off value for cardiac anomalies has been shown to be the best indicator of fetal anomalies. Values of 2.6 to 4.8 mm, on the other hand, have some false positive rates but increase the chance of detecting other anomalies such as Down syndrome. Increased risk of aneuploidy is highly possible when NT is 2.9 mm and higher, the interpreting physician should discuss with the patient the possibility of amniocentesis.
- Measurement of nuchal translucency thickness at 11-14 weeks of gestational is an effective method of screening for fetal cardiac defects.
- The prevalence of major defects of the heart and great arteries increases with increase NT
- Nuchal translucency thickness measurement should be viewed as an integral part, along with prenatal diagnosis and fetal karyotyping in prenatally managing pregnancies.
- Restricted genetic pool communities might have an increase in the incidence of NT and fetal cardiac pathologies specifically hypoplastic ventricles
– The fetous should occupy 50% of image.
– The image should be filled by the fetal head, neck, and upper thorax.
– Fetal spine in horizontal position and the margin of NT edges should be clear and this can be achieved by (decrease depth, narrow sector width, use magnification box-magnify then freeze.
– Fetus in mid-sagittal plan, tip of fetal nose seen in face area, 3rd and 4th ventricle seen in CNS.
– Stomach, Ribs, or Heart should not be seen in the image.
– Fetus head in neutral position if possible (not in hyper-flexion or hyper-extension).
– Fetus observed away from amnion, and avoid membrane shadows.
– Measure the widest space of the NT 3 time’s inner to inner lines perpendicular to the long axis of the fetus, and record the largest measurement.
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Steve Ramsey, PhD.