Department of Obstetrics and Gynecology, Assaf Harofe Medical Center, Zerifin (affiliated with Sackler Faculty of Medicine, Tel Aviv), 70300 Israel
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Abstract |
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Key words: multiplicity of higher order gestations/nuchal translucency/ultrasound
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Introduction |
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Since NT has evolved into a valuable marker for detecting the above-mentioned fetal abnormalities and complications, its importance is clear-cut with multiple pregnancies where biochemical screening is of limited value. Accordingly, it has been reported that in twin pregnancies, first trimester screening for chromosomal abnormalities is reliable and feasible (Pandya et al., 1995b). Furthermore, NT measurement may offer additional data about twin pathophysiology, such as underlying haemodynamic changes associated with early onset of twintwin transfusion syndrome (Sebire et al., 1997
).
The aim of the current study was to evaluate the feasibility of NT measurements in higher order multiple gestation, conceived by assisted reproduction, and to compare the measurements with those of a singleton gestation. We are unaware of any other similar report published in English.
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Materials and methods |
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A curvilinear abdominal transducer (HDI 3000; Advanced Technology Laboratories, Seattle, WA, USA) was used without a time limitation to generate a satisfactory image and an accurate NT measurement of each fetus. Demographic data and ultrasound findings, including the number of fetuses, CRL, NT and any obvious fetal malformations, were recorded into a computer database (Snijders et al., 1996, 1998
) at the time of scanning. The calculated risk of having a trisomy 21 newborn was based on maternal age and gestational age-related prevalence, multiplied by the likelihood ratio depending upon the deviation from normal in NT thickness for CRL (Snijders et al., 1996
, 1998
). Pregnancy outcome was obtained from the maternity units or from the patients themselves.
To examine a possible effect of multiplicity on NT thickness, the measurements of the study group were compared with those of spontaneous, singleton pregnancies. Thus, consecutive, singleton pregnancies were chosen as matched controls using similar CRL (±3 mm) as a criterion. The measurements were expressed as thickness in mm or as a multiple of medians (MOM). Since NT was log normally distributed the equation produced to calculate MOM of NT was based on the formula: Log10NT = 0.3599 + 0.0127 CRL 0.000058 CRL2 as previously reported (Nicolaides et al., 1998). The analysis included comparison of 5th, 50th and 95th centiles between each case in the study group and its matched control. It also included comparisons of mean NT thickness between each pregnancy and the study and control groups, and the maximal difference of NT thickness within each pregnancy with the maximal difference between its matched control. Paired Student's t-test was used for comparing matched controls, comparing means between the groups, and P < 0.05 was considered as statistically significant. Values were expressed as mean ± SD.
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Results |
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Of the study group of 24 patients, 18 completed uneventful pregnancies and deliveries, and there was one case of early neonatal death in this study group. Six patients aborted. In the current series, no abnormal karyotypes were detected prenatally and no traits were observed postnatally that warranted chromosomal analysis.
Table I shows that the study and control groups exhibited almost identical measurements for 5th and 95th centiles. Also, mean NT thickness expressed in mm or MOM were similar in both groups. While examining NT differences between wider and narrower thickness within each case of the study group and its corresponding control, it was found that the variation between siblings (study group) was smaller than that observed in non-siblings (control group) (0.43 ± 0.22 versus 0.72 ± 0.43 mm respectively). This difference was statistically significant (P < 0.01, paired Student's t-test).
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Discussion |
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Another critical problem in a higher order multiple gestation is the fetal reduction which recently has been introduced into the prenatal treatment armamentarium. This procedure's aim is to decrease feto-maternal complications related to premature contractions and deliveries among multiple pregnancies (Maymon et al., 1995), as well as to offer an alternative other than terminating the entire pregnancy to those women carrying either a higher number of fetuses than desired or an affected co-twin (Maymon et al., 1995
). Before feticide, a careful ultrasonographic assessment of the entire pregnancy is recommended to determine the actual number of living fetuses, their location, the placentation for monochorionic twins (Sepulveda et al., 1996
), presence of any visible fetal anomalies, or any fetal discordancy (Dickey et al., 1992
; Maymon et al., 1995
), as well as slower fetal heart rate (Achiron et al., 1991
). Those parameters may indicate an anomaly or poor prognosis for the survival of that fetus (Achiron et al., 1991
; Dickey et al., 1992
; Maymon et al., 1995
). In this context, a new challenge has been raised by the same authors (Berkowitz et al., 1993
), who reported that among 200 patients who underwent fetal reduction, six of the remaining fetuses had either anatomic (n = 4 cases) or chromosomal (n = 2 cases) abnormalities. Based on this, it seems important to offer pre-procedure, non-invasive genetic testing and a careful scanning, especially for those patients with a significantly increased risk of karyotypic abnormalities by virtue of their age (Berkowitz et al., 1993
). To overcome these problems, first trimester ultrasound screening with NT measurements seems to be a promising option.
It has been reported that in twin pregnancies, screening for trisomy 21 by measurement of fetal NT thickness and maternal age had a similar sensitivity to that found in singletons (Pandya et al., 1995b; Snijders et al., 1996
). However, ~9% of twins were screened as positive compared with 8% of singletons (Snijders et al., 1998
). Some authors believe that increased NT thickness is due to underlying haemodynamic changes associated with heart failure, and may be an early manifestation of twintwin transfusion syndrome among those monochorionic twins with increased NT thickness (Sebire et al., 1997
). Since in the current study there was only one case of monochorionic twins, the information provided by Sebire et al. (1997) cannot be validated.
Our study has carried this issue one step further. Contrary to others who have recently reported obtaining an NT thickness in only ~83% of the singletons (Haddow et al., 1998), we succeeded in measuring it in all of our cases. It is premature to draw any conclusions concerning the sensitivity and false-positive rate of the method, since our series is too small. Nevertheless, we have demonstrated that among these fetuses belonging to higher order multiple gestations, similar NT thickness measurements are exhibited compared with their matched, singleton controls. Moreover, the distribution of 5th, 50th and 95th centiles among the study group was comparable with that of the control group. This validates the practical use of the model of trisomy 21 risk assessment originally obtained in singleton pregnancies (Nicolaides et al., 1992
; Pandya et al., 1995a
; Snijders et al., 1996
, 1998
) among individuals of a higher order multiplicity.
We found that the difference between the NT thicknesses of siblings was significantly smaller than that observed in non-siblings. This unexpected finding deserves further explanation. It may be an incidental finding derived from our relatively small series, or it may indicate that NT thickness among normal fetuses is an inborn feature derived from genetic or other environmental factors. Thus, siblings possessing similar genetic inheritance or sharing the same uterus and blood supply exhibit closer NT thicknesses than do random, singleton fetuses.
Women who conceive after assisted reproduction methods are naturally wary of any invasive prenatal diagnostic procedure. Since they receive careful antenatal care early in their pregnancies, and maternal serum markers are less efficient for chromosomal screening in multiple pregnancies, it would seem reasonable to offer them ultrasound screening by NT measurement, which is presently the only available, efficient screening method.
In summary, the above methodology provides additional data for the identification of an abnormal fetus, thus lowering the probability of leaving an abnormal fetus after reducing a normal one (Berkowitz et al., 1993). Our highly selected study population provides evidence that NT thickness measurements are feasible for risk determination. We recommend that a programme of NT measurements should be favourably considered as part of routine antenatal care during the late first trimester in this group of patients.
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Acknowledgments |
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Notes |
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References |
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Submitted on October 19, 1998; accepted on April 16, 1999.