ORIGINAL RESEARCH ARTICLE |
https://doi.org/10.5005/jp-journals-10009-1943 |
Normal Nuchal Translucency with Septations at Crown-rump Length below 45 mm
1,6,7Department of Obstetrics and Gynecology, Miyake Clinic, Okayama, Japan; Department of Perinatology and Gynecology, Kagawa University Graduate School of Medicine, Kagawa, Japan
2-5Department of Obstetrics and Gynecology, Miyake Clinic, Okayama, Japan
8Department of Obstetrics and Gynecology, Faculty of Medicine, Sohag University, Sohag, Egypt
Corresponding Author: Toshiyuki Hata, Department of Obstetrics and Gynecology, Miyake Clinic, Okayama, Japan; Department of Perinatology and Gynecology, Kagawa University Graduate School of Medicine, Kagawa, Japan, Phone: +810878912174, e-mail: hata.toshiyuki@kagawa-u.ac.jp; toshi28@med.kagawa-u.ac.jp
Received on: 19 October 2022; Accepted on: 26 October 2022; Published on: 26 December 2022
ABSTRACT
Objective: To assess the clinical characteristics, pregnancy courses, and outcomes in fetuses showing normal nuchal translucency (NT) with septations at a crown-rump length (CRL) below 45 mm.
Materials and methods: During a 33-month period from July 2019 to March 2022, nine fetuses showing normal NT with septations (CRL: 22.3–43.3 mm) (NNTS group) and six cystic hygromas (CRL: 27.7–42.8 mm) (CH group) were identified at 9+1–11+2 weeks of gestation. Their clinical characteristics, pregnancy courses, and outcomes were investigated and compared between the groups.
Results: There were no significant differences in gestational age at examination, maternal age, parity, CRL, or prevalence of hydrops between NNTS and CH groups. There were significant differences in NT thickness between NNTS [1.66 (mean) ± 0.24 (standard deviation (SD)) mm] and CH [4.6 (mean) ± 0.93 (SD) mm] groups (p = 0.002). Good outcomes were noted in all cases (100%) in the NNTS group, whereas only two cases had healthy fetuses (33.3%) in the CH group (p = 0.004). In the NNTS group, seven fetuses (not determined in two fetuses) had normal ductus venous flow on first-trimester fetal ultrasound scan.
Conclusion: Normal NT with septations at CRL below 45 mm may not be an ominous sign, whereas CH at CRL below 45 mm may still be associated with poor fetal outcomes. However, the data and its interpretation in our study should be taken with some degree of caution because of the small number of subjects studied in both groups. Further studies involving a larger sample size of normal NT with septations at CRL below 45 mm would be needed to ascertain whether nuchal septations are a benign or an ominous sign in clinical practice.
How to cite this article: Hata T, Koyanagi A, Kawahara T, et al. Normal Nuchal Translucency with Septations at Crown-rump Length below 45 mm. Donald School J Ultrasound Obstet Gynecol 2022;16(4):278-281.
Source of support: Nil
Conflict of interest: None
Keywords: Cystic hygroma, Fetus, First trimester, Nuchal translucency, Pregnancy outcome, Septation
INTRODUCTION
Cystic hygroma diagnosed at a CRL below 45 mm leads to significantly lower rates of chromosomal abnormalities and a higher proportion of normal neonatal outcomes when compared with those at CRL of 45–84 mm.1 Grande et al.2 found that NT may also be a useful marker for the early detection of chromosomal abnormalities at 9–10 weeks of gestation (28–44 mm CRL). On the contrary, Mack et al.3 reported that visualization of NT septations at 11–14 weeks of gestation is a powerful marker for the detection of chromosomal abnormalities, independent of increased NT. The question raised here is whether normal NT with septations at CRL below 45 mm is a benign or an ominous marker. In this investigation, we assessed the clinical characteristics, pregnancy courses, and outcomes in fetuses showing normal NT with septations at CRL below 45 mm.
MATERIALS AND METHODS
During the 33-month period from July 2019 to March 2022, 2553 pregnancies were delivered at our clinic. Nine fetuses showing normal NT with septations (CRL: 22.3–43.3 mm) (NNTS group) (Fig. 1) and six cystic hygromas (CRL: 27.7–42.8 mm) (CH group) (Fig. 2) were identified using two-dimensional (2D) sonography (Voluson SWIFT, GE Healthcare, Zipf, Austria) with a transvaginal transducer (GE RIC5-9-RS, 3.8–9.3 MHz) at 9+1–11+2 weeks of gestation. All cases were singleton pregnancies. The upper reference value of NT was set at 1.95–2.38 mm at CRL below 45 mm.2 CH was defined as simultaneous visualization of increased NT and septations.4 2D sonography was performed to calculate gestational ages based on CRL measurements in the first trimester.5 Their clinical characteristics, pregnancy courses, and outcomes were investigated and compared between the groups. The study was conducted following approval by the Ethics Committee of Miyake Clinic, Okayama, Japan. All participants provided informed consent after a full explanation of the aim of the study.
Figs 1 A and B: Normal nuchal translucency (NT) with septations (large arrows) at 10 weeks of gestation. Small arrows indicate skin edema. (A) Transverse view; (B) Sagittal view. CRL, crown-rump length.
Figs 2 A and B: Cystic hygroma (arrows) at 10 weeks and 5 days of gestation. (A) Transverse view; (B) Sagittal view. CRL, crown-rump length; NT, nuchal translucency.
The unpaired t-test was used to assess differences in gestational age at examination, maternal age, CRL, and NT thickness. A comparison of the incidences of hydrops or good outcomes between the two groups was made using the Chi-square test. The Mann–Whitney U test was employed to examine differences in parity. Statistical software SPSS, version 28, for Windows (SPSS Inc., Chicago, IL, USA) was used for statistical analysis, with significance set at a p-value <0.05.
RESULTS
Clinical characteristics of subjects in the NNTS group are shown in Table 1. In the NNTS group, average NT was 1.66 mm (SD: 0.24 mm) at the initial scan. Four cases had hydrops (44.4%). Seven fetuses (not determined in two fetuses) showed normal ductus venous flow in the first-trimester fetal ultrasound scan (Table 1). NT at 11–13+6 weeks in seven fetuses (not determined in two fetuses) was also normal (Table 1). All pregnancies resulted in healthy neonates.
| Case | GA (weeks) | CRL (mm) | MA (years) | Para | NT (mm) | Hydrops | First-trimester scan | Additional findings | Genetic testing | Outcome | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NB | NT (mm) | TR | DVF | ||||||||||
| 1 | 10 | 35.3 | 32 | 0 | 1.9 | (+) | ND | 1.4 | ND | Normal | None | Not done | Healthy neonate |
| 2 | 9 + 1 | 22.7 | 32 | 2 | 1.5 | (+) | ND | ND | ND | ND | None | 46XY | Healthy neonate |
| 3 | 10 + 1 | 27.6 | 24 | 0 | 2 | (–) | (+) | 1.8 | (–) | Normal | None | Not done | Healthy neonate |
| 4 | 9 + 2 | 22.3 | 28 | 0 | 1.4 | (+) | ND | 1.6 | ND | Normal | None | Not done | Healthy neonate |
| 5 | 10 + 5 | 36.4 | 30 | 0 | 1.5 | (–) | ND | ND | ND | ND | None | Not done | Healthy neonate |
| 6 | 9 + 6 | 31 | 34 | 0 | 1.8 | (–) | ND | 1.1 | (–) | Normal | IVF-ET | Not done | Healthy neonate |
| 7 | 10 | 30.9 | 30 | 1 | 1.9 | (+) | (+) | 1.3 | (–) | Normal | None | Not done | Healthy neonate |
| 8 | 11 + 2 | 42.8 | 41 | 1 | 1.5 | (–) | ND | 1.5 | (–) | Normal | None | Not done | Healthy neonate |
| 9 | 11 + 2 | 43.3 | 30 | 0 | 1.4 | (–) | ND | 1.8 | ND | Normal | None | Not done | Healthy neonate |
First-trimester scan was done at 11–13+6 weeks of gestation
CRL, crown-rump length; DVF, Ductus venosus flow; FTET, Frozen-thawed embryo transfer; GA, Gestational age; MA, Maternal age; NB, Nasal bone; ND, Not determined; NT, Nuchal translucency; TR, Tricuspid regurgitation; TOP, termination of pregnancy
Clinical characteristics of subjects in the CH group are shown in Table 2. In the CH group, average NT was 4.6 mm (SD: 0.93 mm) at the initial scan. Four cases had hydrops (66.7%). NT at 11–13+6 weeks in four fetuses (not determined in two fetuses) ranged from 2.4 to 4.8 mm. Two fetuses (not determined in four fetuses) showed normal ductus venous flow in the first-trimester fetal ultrasound scan (Table 2). There was one case of trisomy 18 and one of trisomy 21. Four parents decided to terminate their pregnancies. In two out of four cases, parents decided to terminate their pregnancies after detailed explanations without genetic testing. Only two pregnancies resulted in healthy neonates.
| Case | GA (weeks) | CRL (mm) | MA (years) | Para | NT | Hydrops | First-trimester scan | Additional findings | Genetic testing | Outcome | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NB | NT (mm) | TR | DVF | ||||||||||
| 1 | 10 + 5 | 42.8 | 39 | 3 | 4.2 | (+) | (–) | ND | ND | Normal | None | Not done | TOP |
| 2 | 11 | 40.9 | 37 | 0 | 4.8 | (+) | ND | 4.8 | ND | ND | None | Trisomy 18 | TOP |
| 3 | 11 + 2 | 40.8 | 33 | 0 | 3.9 | (+) | ND | 3.9 | ND | ND | None | Trisomy 21 | TOP |
| 4 | 10 + 5 | 35.1 | 36 | 0 | 5.7 | (–) | ND | ND | ND | ND | FTET | Not done | Healthy neonate |
| 5 | 10 + 3 | 32.4 | 30 | 1 | 3.4 | (–) | (+) | 2.4 | (–) | Normal | FTET | Not done | Healthy neonate |
| 6 | 10 + 3 | 27.7 | 27 | 0 | 5.6 | (+) | Unclear | 4.6 | (+) | ND | None | Not done | TOP |
First-trimester scan was done at 11–13+6 weeks of gestation
CRL, crown-rump length; DVF, Ductus venosus flow; GA, Gestational age; IVF-ET, In vitro fertilization embryo transfer; MA, Maternal age; NB, Nasal bone; ND, Not determined; NT, Nuchal translucency; TR, Tricuspid regurgitation
There were no significant differences in gestational age at examination, maternal age, parity, CRL, or prevalence of hydrops between NNTS and CH groups (Table 3). There were significant differences in NT between NNTS [1.66 (mean) ± 0.24 (SD) mm] and CH [4.6 (mean) ± 0.93 (SD) mm] groups (p = 0.002) (Table 3). Good outcomes were noted in all cases (100%) in the NNTS group, whereas only two cases had healthy fetuses (33.3%) in the CH group (p = 0.004) (Table 3).
| Group | n | GA (weeks) | MA (y.o.) | Para | CRL (mm) | NT (mm) | Hydrops (%) | Good outcome (%) |
|---|---|---|---|---|---|---|---|---|
| Mean (SD) | Median (range) | Median (range) | Mean (SD) | Mean (SD) | ||||
| NNTS | 9 | 10.19 (0.78) | 30 (24–41) | 0 (0–2) | 32.48 (7.7) | 1.66 (0.24) | 4 (44.4) | 9 (100) |
| CH | 6 | 10.75 (0.35) | 34.5 (27–39) | 0 (0–3) | 36.62 (5.89) | 4.6 (0.93) | 4 (66.7) | 2 (33.3) |
| Significance | NS | NS | NS | NS | 0.002 | NS | 0.004 |
CRL, crown-rump length; GA, Gestational age; MA, Maternal age; NS, Not significant; NT, Nuchal translucency, SD, Standard deviation
DISCUSSION
Mack et al.3 reported that the prevalence of chromosomal abnormalities in fetuses with nuchal septations was significantly higher than that in fetuses with normal NT without septations or those with increased NT without septations at 11–14 weeks of gestation. These authors suggested that the sonographic identification of nuchal septations in the first trimester is a powerful risk factor for chromosomal abnormalities, independent of increased NT. The question raised here is whether nuchal septations at CRL below 45 mm (at 9–11 weeks of gestation) are a risk factor for an unfavorable pregnancy outcome, independent of NT measurements. In the present study, all pregnancies with normal NT with septations at CRL below 45 mm had favorable fetal outcomes, whereas only 33.3% of increased NT with septations had favorable fetal outcomes (p = 0.004). These results suggest that normal NT with septations at CRL below 45 mm may be a benign phenomenon, whereas increased NT with septations may be associated with unfavorable fetal outcomes. However, the data and its interpretation in our study should be taken with some degree of caution because of the small number of subjects studied in both groups. Further studies involving a larger sample size of normal NT with septations at CRL below 45 mm (at 9–11 weeks of gestation) would be needed to ascertain whether nuchal septations are a benign or an ominous sign in clinical practice.
Molina et al.6 reported that the capacity to note septations is dependent on the accuracy of the transverse plane of the fetal head and neck and on the “appropriate gain” settings of the ultrasound device. Regardless of this, they did not specify whether all fetuses were subjected to the same examination settings, with no settings reported to specifically visualize septations. Also, they failed to describe whether examinations were conducted with transabdominal or transvaginal approaches. In this investigation, we used the latest ultrasound machine with a high-resolution transvaginal probe for visualization of nuchal septations. Moreover, the max zoom-up function (about 3.4 times zooming) was used to observe septations. Therefore, normal NT with septations may be visualizable at CRL below 45 mm (at 9–11 weeks of gestation).
A limitation of this study was that chromosomal analyses were not performed in many cases (only 12 out of 15) although 11 pregnancies resulted in healthy neonates. Pan et al.7 reported that physicians have to be careful to counsel parents whose fetus shows a first-trimester CH, even with a normal array result and normal sonographic scans, suffering from rare genetic syndromes after birth. Another limitation was the small sample size with nuchal septations at CRL below 45 mm studied during the 33-month period, although 2553 pregnancies were delivered at our clinic. Such factors can result in a selection bias.
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