Prevalence and perinatal outcome of dichorionic and monochorionic twins with nuchal translucency above the 99th percentile and normal karyotype

Authors

  • A. Goncé,

    Corresponding author
    1. Department of Maternal-Fetal Medicine, Institut Clinic de Ginecologia, Obstetricia i Neonatologia, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
    • Department of Maternal-Fetal Medicine, Institut Clinic de Ginecologia, Obstetricia i Neonatologia, Hospital Clínic, University of Barcelona, Sabino de Arana 1, Barcelona 08028, Spain
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  • A. Borrell,

    1. Department of Maternal-Fetal Medicine, Institut Clinic de Ginecologia, Obstetricia i Neonatologia, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
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  • E. Meler,

    1. Department of Maternal-Fetal Medicine, Institut Clinic de Ginecologia, Obstetricia i Neonatologia, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
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  • M. Arigita,

    1. Department of Maternal-Fetal Medicine, Institut Clinic de Ginecologia, Obstetricia i Neonatologia, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
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  • J. M. Martínez,

    1. Department of Maternal-Fetal Medicine, Institut Clinic de Ginecologia, Obstetricia i Neonatologia, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
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  • F. Botet,

    1. Department of Neonatology, Institut Clinic de Ginecologia, Obstetricia i Neonatologia, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
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  • A. Sánchez,

    1. Biomedical Diagnosis Centre, Hospital Clinic-IDIBAPS, University of Barcelona and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain
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  • E. Gratacós

    1. Department of Maternal-Fetal Medicine, Institut Clinic de Ginecologia, Obstetricia i Neonatologia, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
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Abstract

Objective

To evaluate the prevalence of and perinatal outcome associated with increased nuchal translucency thickness (NT) > 99th percentile in dichorionic and monochorionic twins with normal karyotype.

Methods

Two hundred and six consecutive twin pregnancies (166 dichorionic and 40 monochorionic) underwent an NT scan during a 4-year period. In those with NT > 99th percentile and normal karyotype, we performed first- and second-trimester anomaly scans, fetal echocardiography at 14–16 and 20–22 weeks, maternal serology and, in monochorionic pregnancies, serial ultrasound examinations every other week. Perinatal outcome was recorded.

Results

There were 10 (4.95%) pregnancies in which one of the fetuses had NT > 99th percentile and normal karyotype, including five fetuses (1.5%) in dichorionic and five (6.25%) in monochorionic pregnancies. During the same period the prevalence of NT > 99th percentile and normal karyotype in singleton pregnancies studied in our center was 2.6%. Among the 10 twins affected, six (60%) were diagnosed with structural abnormalities (three dichorionic and three monochorionic), and two intrauterine fetal demises occurred (one dichorionic and one monochorionic). Thus, the perinatal outcome was normal in only two of the pregnancies, one dichorionic and one monochorionic.

Conclusions

The prevalence of NT > 99th percentile in dichorionic twins with a normal karyotype is similar to that in singletons. In monochorionic twins we confirmed previous studies reporting an increased prevalence compared with singletons. NT > 99th percentile with a normal karyotype in twins was associated with a high rate of fetal abnormalities and/or fetal demise (overall 80%) irrespective of chorionicity. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.

Introduction

It is well known that when an increased nuchal translucency thickness (NT) is observed in the first trimester in chromosomally normal fetuses there is an increased risk for structural abnormalities, mainly cardiac, genetic syndromes and fetal loss1. However, the prevalence and significance of increased NT in twin pregnancies has scarcely been investigated.

In monochorionic compared with dichorionic twin pregnancies, previous reports have described a higher prevalence of increased NT2. Earlier reports suggested an association between increased NT (> 95th percentile) in one fetus and subsequent development of twin–twin transfusion syndrome (TTTS)3, 4, but according to recent studies this association is controversial5, 6. In a recent series of monochorionic twins, a ≥ 20% discordance in NT was found to increase the risk of subsequent fetal demise or severe TTTS to more than 30%7. The prevalence and the perinatal outcome of dichorionic twins with increased NT and normal karyotype has not yet been reported.

The aim of this study was to investigate prevalence and perinatal outcome of twin pregnancies in which one or both fetuses had an increased NT > 99th percentile and a normal karyotype.

Methods

From October 2002 to September 2006, 206 consecutive first-trimester twin pregnancies with both fetuses alive at the 11 + 0 to 13 + 6-week scan were evaluated in our center, either for routine combined screening8 or referred due to an increased risk for chromosomal defects. All scans were performed by experienced sonographers certified by The Fetal Medicine Foundation in NT ultrasound, using high-resolution equipment (PowerVision 6000 (SSA-370), Toshiba Medical Systems; Acuson Aspen, Acuson Inc., Mountain View, CA, USA and Voluson 730 Expert. GE Healthcare, Milwaukee, WI, USA). Crown–rump length (CRL) was measured in each twin and NT was measured following The Fetal Medicine Foundation's guidelines9. Chorionicity was determined, the pregnancy being considered monochorionic in the presence of a single placenta and absent lambda sign, and dichorionic when the placentae were not adjacent or in a single placental plate and the lambda sign was present10. The intertwin discordance in CRL and NT was calculated as a percentage of the larger measurement: (CRL1 − CRL2/CRL1 × 100 and NT1 − NT2/NT1 × 100). As previously described8, chorionic villus sampling or amniocentesis for fetal karyotyping was offered if the estimated risk for Down syndrome in either fetus was ≥ 1/250 calculated by NT screening or by the combined test, when there was a structural abnormality and when the maternal age was > 37 years.

The objective of the study was to evaluate the prevalence and outcome of pregnancies in which one or both fetuses had an NT > 99th percentile, according to our reference ranges at the 11–14-week scan11, and a normal karyotype. These reference intervals were constructed following the methodology described by the National Committee for Clinical and Laboratory Standards (NCCLS)12 and Royston and Wright recommendations13. According to our center guidelines and similarly to singleton pregnancies with increased NT and normal karyotype, these women attended a specific antenatal clinic for an extensive follow-up. Antenatal investigations included first-trimester anomaly scan, fetal echocardiography at 14–16 weeks and 20–22 weeks, anomaly scan at 20–22 weeks and maternal serology including toxoplasmosis, cytomegalovirus and parvovirus B19 (IgG and IgM). In monochorionic pregnancies, serial scans were scheduled every other week to rule out TTTS. Postnatal follow-up until 2 years of age was obtained for survivors.

Data regarding perinatal outcome from all pregnancies were ascertained from delivery room records or by phone enquiry if the pregnancy was not followed up and delivered in our center. Statistical analysis was performed using the software package SPSS 14.0 (SPSS Inc., Chicago, IL, USA). 95% CIs were calculated for means. Student's t-test was used for comparisons between continuous variables.

Results

During the 4-year study period, 206 consecutive twin pregnancies were seen at our center (166 dichorionic and 40 monochorionic). In 12 of these, one of the pair of fetuses had NT > 99th percentile (Figure 1) and among them cytogenetic analysis revealed two unrelated dichorionic twins to have a chromosomal anomaly (Down syndrome and Turner syndrome). There were also two chromosomal anomalies diagnosed in the twins with NT ≤ 99th percentile, leaving 10 of 202 (4.95%) pregnancies with normal karyotype in which one of the fetuses had NT > 99th percentile (five dichorionic and five monochorionic, including four diamniotic and one monoamniotic). In all of them, the NT in the cotwin was < 99th percentile, but in one cotwin the NT was moderately increased (between 95th and 99th percentiles). The prevalence of twin fetuses with NT > 99th percentile and normal karyotype in dichorionic pregnancies was thus 1.5% (5/324 fetuses; 95%CI, 0.2–2.9%) and in monochorionic pregnancies it was 6.25% (5/80 fetuses; 95% CI, 0.9–11.6%). The prevalence of NT > 99th percentile and normal karyotype in singleton pregnancies studied in our center in the same period was 2.6% (171/6666 fetuses; 95% CI, 2.2–2.9%).

Figure 1.

Flow chart summarizing the twin study population. NT, nuchal translucency; TTTS, twin–twin transfusion syndrome.

Among twin pregnancies with NT > 99th percentile and normal karyotype, the mean maternal age was 33.4 (range, 27–39) years and the mean CRL was 60 (range, 45–84) mm. The pregnancy outcomes are shown in Table 1. An intertwin discordance of > 10% in CRL was observed in four (40%) of these pregnancies, all of which had a poor perinatal outcome; in three, the smaller twin was the one with an increased NT and in the fourth, the smaller twin had a nomal NT but was affected by exencephaly. Among the 10 cases with increased NT, the mean measurement was 5.2 (range, 4.1–7.1) mm in monochorionic and 3.8 (range, 3.1–5.0) mm in dichorionic fetuses, the difference being statistically non-significant. In all 10 pregnancies, the intertwin NT discordance was > 20%.

Table 1. Pregnancy data and outcome in dichorionic and monochorionic twin pregnancies with normal karyotype and one fetus with a nuchal translucency thickness > 99th percentile (Fetus 1)
MA (years)GA (weeks)Crown–rump length (CRL)Nuchal translucency thickness (NT)Fetal abnormalitiesOutcome
Fetus 1 (mm)Fetus 2 (mm)ΔCRL* (%)Fetus 1 (mm)Fetus 2 (mm)ΔNT (%)
  • *

    ΔCRL = CRL discordance as a percentage of the larger twin = CRL1 − CRL2/CRL1 × 100.

  • ΔNT = NT discordance as a percentage of the larger measurement = NT1 − NT2/NT1 × 100.

  • AVSD, atrioventricular septal defect; GA, gestational age; IUD, intrauterine demise; IUGR, intrauterine growth restriction; MA, maternal age; TOP, termination of pregnancy; VSD, ventricular septal defect.

Dichorionic pregnancy
2714.0848055.02.452Limb reduction & bilateral renal agenesis (both twins)TOP
3512.45566164.21.857Fanconi anemia syndromeSelective TOP
3613.1707573.42.041VSDBirth 40 weeks, survived
3512.24961203.12.132NoneIUD 17 weeks
3412.2615853.22.328NoneAlive & well
Monochorionic pregnancy
3512.16054104.81.275VACTERL associationSelective TOP, 20 weeks
3012.04757177.11.874Complex cardiac defect (truncus + AVSD), IUGRBirth 36 weeks, intervention, survived
3211.1454864.91.569Unilateral renal agenesis, hemivertebrae, hypoplastic thumbBirth 38 weeks, survived
3912.26149195.1  (Selective cotwin TOP for exencephaly at 17 weeks)IUD 35 weeks
3113.0716674.12.929NoneAlive & well

Regarding fetal outcome among the 10 with increased NT, there were six (60%) with structural abnormalities (three dichorionic and three monochorionic), all diagnosed before 22 weeks' gestation (Table 1). In addition, there were two intrauterine fetal demises, one in dichorionic and one in monochorionic twins. There was a normal fetal outcome with normal postnatal follow-up up to 2 years of age in only two pregnancies, one dichorionic and one monochorionic.

TTTS complicated four of the 40 (10%) monochorionic pregnancies but in none of the fetuses was the NT > 99th or > 95th percentile.

Discussion

This study provides evidence that the prevalence of increased NT in dichorionic twins (1.5%) is similar to that observed in singleton fetuses (2.6%), although both were above the 1% expected since the sample was obtained from a tertiary referral center. In chromosomally normal dichorionic twins, increased NT is likely to be due to an underlying mechanism similar to that in a singleton fetus, leading to a similar increased risk for adverse pregnancy outcome, although no specific data are available. However, in monochorionic twins, increased NT may also be produced by hemodynamic imbalances between the fetuses through the vascular anastomoses, which may result in severe early onset of TTTS3, 4. Previous studies in singleton pregnancies have reported that an increased NT in a fetus with normal karyotype was associated with a poor pregnancy outcome, the chances of which increased exponentially with increasing NT thickness, from 8% when NT ranged between the 95th and 99th percentiles to 80–85% when the NT was above 6.5 mm1, 14. While establishing our reference ranges for NT, we found the 99th percentile not to be a fixed value, as has been described by other groups1, 15, but to increase, from 2.27 mm at 45 mm CRL to 3.78 mm at 84 mm11.

In our series, twins with an NT > 99th percentile and normal karyotype had a 60% prevalence of fetal anomalies and a 20% risk of fetal demise, irrespective of chorionicity. Thus, although the relative rate of malformations is normally higher in monochorionic twins16, the presence of an NT > 99th percentile seems to represent a similarly increased risk for both monochorionic and dichorionic twins. It is well established that, compared with singleton pregnancies, structural malformations are more common in twin pregnancies, particularly monozygotic ones, in which each fetus has a two- to three-fold increased risk. This is basically due to the inherent risk of zygotic splitting and is also secondary to imbalances in placental sharing when the pregnancy is monochorionic16, 17. In the present study, there were three polymalformative disorders, including skeletal defects (two in a monochorionic and one in a dichorionic presumably monozygotic pregnancy because the cotwin showed the same defects) and two cardiac defects (one major abnormality in a monochorionic and one minor defect in a dichorionic fetus), also suggesting a higher rate of severe defects in monozygotic twins with increased NT.

It is well established that the rate of perinatal mortality in monochorionic twins is at least four-fold that in dichorionic ones, and this is likely to be due to the complications caused by placental vascular sharing18. The fetal demise of the dichorionic twin occurred at 17 weeks, concomitant with selective early growth delay, a condition already described in association with poor outcome19, 20. We found an intertwin CRL discordance > 10% in four pregnancies, and it was always associated with adverse fetal outcome (three severe fetal abnormalities and one fetal demise), in accordance with results from a previous study21. The fetal demise of the monochorionic twin occurred at 35 weeks in a pregnancy in which the exencephalic cotwin had been selectively terminated in the second trimester by cord occlusion. It has been shown that perinatal mortality is higher in monochorionic pregnancies in which at least one twin shows an NT > 95th percentile (30% vs. 7%)6 or when there is an intertwin NT discordance of > 20%7. In a recent series of 30 monochorionic pregnancies, poor perinatal outcome was observed in the five pregnancies in which one of the twins had an increased NT (> 95th percentile): one double fetal demise at 22 weeks, one case of TTTS and three extremely preterm deliveries. Nevertheless, prematurity was the only factor that showed a significant correlation with NT thickness22.

Increased NT in chromosomally normal twins is considered to be more common in monochorionic than in dichorionic pregnancies. It has been suggested that this sign might constitute an early manifestation of TTTS3, 4, but this notion has been questioned in more recent studies5, 6, 22. Therefore, it is suggested that this finding in a monochorionic twin should prompt a search for signs of TTTS. In the present study, NT > 99th percentile was four times more common among monochorionic compared with dichorionic twins (6.3% vs 1.5%), but this may have been due to the increased risk of structural defects in monozygotic twins rather than being an early sign of TTTS. Moreover, none of the four monochorionic pregnancies which developed TTTS showed an increased NT at the first-trimester scan. However, the small sample size prevented us from assessing the association between increased NT and TTTS.

In conclusion, this study provides prevalence rates for increased NT in multiple pregnancies, and suggests that twins with NT > 99th percentile and normal karyotype have a high rate of fetal structural anomalies and adverse perinatal outcome, irrespective of chorionicity.

Acknowledgements

M. Arigita and E. Meler were supported by Hospital Clinic research grants.

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