Volume 154, Issue 1 , Pages 27-30, January 2011
Non-syndromic malformations of the central nervous system in twin pregnancies: diagnostic and other clinical features of importance
Article Outline
- Abstract
- 1. Introduction
- 2. Materials and methods
- 3. Results
- 4. Comments
- Acknowledgements
- References
- Copyright
Abstract
Objective
The incidence of central nervous system malformations is higher among twins. Our aim was to summarize information about these malformations in twin pregnancies.
Study design
Based on a sample originating from the biggest genetic centre in Hungary between January 1990 and December 2008, we examined the data of 42 twin pregnancies associated with non-syndromic malformations of the central nervous system.
Results
The involvement of monozygotic fetuses and dizygotic ones of the same gender was found to be 62.5%. Usually only one of the fetuses was affected (57.1%), while the other one was healthy. The male-to-female ratio was 0.75. Identical and fraternal twins were found in 68.4% and 31.6% of the cases, respectively. In the pregnancies of our study the malformation was diagnosed before the 24th gestational week in 90% of the cases. Polyhydramnios (54.8%) was the most commonly associated non-central nervous system malformation.
Conclusion
Our findings suggest that, in addition to placentation and gestational age, the position of the affected fetus with relation to the uterine orifice is of great importance in determining whether selective abortion is an option in deciding about the outcome of pregnancies affected by craniospinal malformation.
Keywords: Twin pregnancy, Genetic counselling, Malformation of the central nervous system, Selective termination of pregnancy, Induced abortion
1. Introduction
Owing to the risk of possible complications twin pregnancies are regarded as obstetric pathological conditions [1]. Due to the spread of assisted reproductive techniques, the incidence of multiple pregnancies has significantly increased. Approximately two thirds of twins are fraternal (dizygotic, DZ). Their prevalence is 7–11/1000 deliveries, which increases in parallel with increasing maternal age. Fraternal twins are the result of simultaneous ovulation of two egg cells fertilized by two sperm cells. The prevalence of identical (monozygotic, MZ) twins is 3–3.5/1000 deliveries [2]. MZ twins result from the separation of the zygote at different stages of development. If, after division, the two cells of the zygote separate, two placentas, two chorions and amnions develop (diplacental, dichorionic, diamnionic placentation, DDD). If the separation is only partial, the two placentas unite to result in monoplacental, dichorionic and diamnionic placentation (MDD). If embryonic division begins prior to the development of the chorion, it leads to the development of two amnions within a single chorion (monoplacental, monochorionic, diamnionic placentation MMD), but when the process starts after the formation of the amnions, it results in a single amnion (monoplacental, monochorionic and monoamnionic placentation, MMM) [3].
Congenital malformations in twin pregnancies, especially monozygotic ones, have been widely known to occur more commonly than in singleton pregnancies; moreover those malformations usually affect one of the fetuses alone [4], [5]. There are several explanations for why the chances of genetic malformations in multiple pregnancies are higher [6]. Based on some studies, the risk of genetic disorders in twin pregnancies may be twice or three times as high as in singleton ones [7], [8], [9]. Certain malformations are associated with the process of twin formation itself (acardiacus, conjoined twins) [8], while the incidence of others exceeds the figures found in singleton pregnancies.
As in singleton pregnancies, craniospinal malformations appear to be the most common disorders in multiple pregnancies. In addition to neural tube defects, the prevalence of hydrocephalus is three times higher, while that of other central nervous system malformations is one and a half times higher in twin pregnancies [10]. Some publications report an even higher – as much as 10–15 times – increase in the prevalence of anencephaly [11].
In this paper we summarize the knowledge about the association of twinning and malformations of the central nervous system, based on a sample originating from the biggest genetic centre in Hungary, and we highlight the significance of sonography in decision-making about the fate of an affected twin pregnancy.
2. Materials and methods
We undertook a descriptive study of all the 42 twin pregnancies associated with malformation of the central nervous system diagnosed at the Genetic Counseling Unit of the 1st Department of Obstetrics and Gynecology of the Faculty of General Medicine at Semmelweis University in the period of 1st January 1990 and 31st December 2008. Cases in which a fetal central nervous system malformation occurred as part of a syndrome were excluded from the study.
Hydrocephalus, spina bifida, spina bifida plus hydrocephalus, anencephaly and holoprosencephaly were the malformations occurring in the 42 twin pregnancies examined [12], [13]. The fetopathological investigations were done at the Fetopathology Laboratory of the Department according to national and international protocols [14], [15], [16].
The computerized database containing the details of the individual cases served as the source of information. In addition to establishing the major demographic features, we had the opportunity to provide diagnostic details and a survey of the outcome of the pregnancies. We tried to pay special attention to the outcome because making a decision about the fate of twin pregnancies affected by malformation is one of the greatest challenges clinical genetics, and obstetrics and gynecology have to face. Together with providing the ultrasonographic diagnosis of the individual malformations we have attempted to reveal all the possible details of the associated non-central nervous system malformations as well.
For statistical analysis, differences between groups were evaluated with a 2-tailed Student's t test. For dichotomous parameters, the Fisher exact test was used. P
≤0.05 was considered statistically significant. For the sake of simplicity the condition ventriculomegaly/hydrocephalus will simply be referred to as ‘hydrocephalus’ in the rest of the text.
3. Results
Among the 2178 craniospinal malformations, 42 (1.92%) occurred in multiple (twin) pregnancies. Maternal median age was found to be 28±5.16 years.
Table 1 shows the distribution of the malformations in the examined twin pregnancies. Concerning the severity of the cases of hydrocephalus, in 11 pregnancies the diameter of the lateral ventricle was above 15mm (severe hydrocephalus), while in 3 cases it was 12–13mm (mild hydrocephalus). In the cases of spina bifida sacral localization occurred in 1 case, while the thoracolumbar or lumbar segment(s) were affected in the remaining 5 cases. In the 10 cases of associated spina bifida and hydrocephalus the diameter of the lateral ventricle was above 15mm. Both cases of encephalocele were occipital. In each case the fetopathological or neonatological examination confirmed the prenatal diagnosis.
Table 1. Distribution of central nervous system malformations in twin pregnancies in the study.
| Malformation | Number of cases (n) | Percentage (%) |
|---|---|---|
| Hydrocephalus | 14 | 33.34 |
| Spina bifida+hydrocephalus | 10 | 23.81 |
| Anencephaly | 8 | 19.04 |
| Spina bifida | 6 | 14.29 |
| Encephalocele | 2 | 4.76 |
| Holoprosencephaly | 2 | 4.76 |
| Total | 42 | 100 |
Table 2 shows the placentation in the examined cases. Sex was known in 38 cases. In 26 cases (68.42%) the fetuses were of the same sex, while in 12 cases (31.58%) they were of different sex. The summarized male-to-female ratio was 0.75.
Table 2. Placentation in twin pregnancies in the study.
| Placentation | Number of cases (n) | Percentage (%) |
|---|---|---|
| Diplacental, dichorionic, diamnionic (DDD) | 10 | 29.41 |
| Monoplacental, dichorionic, diamnionic (MDD) | 6 | 17.64 |
| Monoplacental, monochorionic, diamnionic (MMD) | 14 | 41.17 |
| Monoplacental, monochorionic, monoamnionic (MMM) | 4 | 11.76 |
| Total | 34 | 100 |
When we examined the effect of the individual malformations in the twin pregnancies we found that fetus A was affected in 24 cases (57.14%), and fetus B in 14 cases (33.34%). In 4 pregnancies both fetuses were affected by the same malformation (spina bifida with hydrocephalus). In 38 of the 42 cases (90.47%), the malformation(s) could be diagnosed before the 24th gestational week, and there were only 4 pregnancies (9.53%) with malformations diagnosed later than week 24.
As far as the outcome of the pregnancies was considered, abortion was induced in 30 cases (71.42%), while, with regard to the date of diagnosing the malformation, the pregnancy was terminated by induced premature delivery in 8 cases (19.04%). In 2 cases, the pregnancies were carried close to term and the mothers delivered a live, mature and healthy fetus A, together with the malformed fetus B in either case. In the remaining 2 cases (4.76%), fetuses B suffering from hydrocephalus were exposed to selective termination in the 22nd and 23rd gestational weeks (Table 3). In both cases, the intervention was possible due to the dichorionic placentation. These 2 pregnancies progressed uneventfully to the 37th and 39th gestational weeks and live, mature and healthy newborns were delivered.
Table 3. Outcome of twin pregnancies in the study.
| Outcome of pregnancy | Number of cases (n) | Percentage (%) |
|---|---|---|
| Induced abortion | 30 | 71.43 |
| Induced premature delivery | 8 | 19.05 |
| Delivery | 2 | 4.76 |
| Selective abortion | 2 | 4.76 |
| Total | 42 | 100 |
The pregnancies were terminated at a mean gestational age of 23.3 weeks (the 2 pregnancies terminated via selective abortion were considered as 4 individual cases).
In 30 pregnancies with specific malformations, one of the twins was unaffected (71.42%), but in 2 cases in which one fetus suffered from hydrocephalus the other one was affected by further malformation such as anencephaly or encephalocele.
The results of our study showed a relatively wide range of associated malformations apart from of the central nervous system. Among the 8 cases of anencephaly, polyhydramnios was also diagnosed in six instances, in addition to which diaphragmatic hernia, esophageal atresia, pyelectasis and intestinal malrotation were also found individually. In the 2 twin pregnancies complicated with encephalocele, no other malformations of the central nervous system could be found. In combined cases of hydrocephalus and spina bifida, polyhydramnios was the most commonly occurring other disorder (8 cases), in addition to which bifid ureter, pyelectasis and single umbilical artery are also worth mentioning. In 1 case in which both fetuses suffered from spina bifida, fetus A was also diagnosed with cheilognathopalatoschisis (cleft lip and palate). Facial dysmorphism and intestinal malrotation were found together with frequently occurring polyhydramnios in pregnancies in which hydrocephalus was diagnosed as the main malformation. In the 2 pregnancies in which both fetuses had hydrocephalus, no other anatomical malformation but polyhydramnios was confirmed. In 1 of the 2 cases of holoprosencephaly, an associated cardiac malformation (univentricular heart) was revealed and, in the same pregnancy, a possible chromosome aberration was also considered.
4. Comments
Regarding the prevalence of the malformations in question, in Windham's sample [17] anencephaly occurred in 53.5% of the cases, while spina bifida and encephalocele were close to each other in 21.5% and 25% of the cases. Comparing the two studies, it can be concluded that anencephaly was found at approximately the same rate.
The incidence of monochorionicity is approximately 25% in all twin pregnancies, but among twin pregnancies with fetal central nervous system malformations the incidence rate is higher. Sebire et al. [18] found that the association rate between monochorionicity and anencephaly is approximately 46%; in our sample the relevant finding stands at 33%. But if we examine the association rate between monochorionicity and all of the malformations of the central nervous system in the focus of our interest, we find the incidence rate just under 53%. Consequently, malformations of the central nervous system in multiple pregnancies are of higher incidence in monochorionic twin pregnancies than in the general population.
The clinical prognosis in monochorionic twin pregnancies with fetal central nervous system malformation is very bleak. Selective termination of the pregnancy can be dangerous in monochorionic twin pregnancies [18], [19], [20] because the vascular network between the fetoplacental units of the fetuses allows for the transportation of potassium chloride into the healthy fetus's circulation, and hemorrhagic complications may also develop. This can be avoided with occlusion of the umbilical cord by laser, making selective termination possible even in monochorionic twin pregnancies [21], [22].
Our investigations showed that the incidence rate of monoamnionicity in twin pregnancies with fetal central nervous system malformation was 11.7%. As regards as the general population, monoamnionicity is detected in approximately 1% of cases [12]. This information suggests that, similarly to monochorionicity, monoamnionicity is also characterized by a higher incidence of craniospinal malformations.
Our investigations verified that the incidence of neural tube defects is higher in monozygotic twins or dizygotic twin pregnancies with fetuses of the same sex. Studies by Garabedian and Fraser [23] and Iffy and Kaminetzky [24] have confirmed that finding. Observations by Rivas et al. [25] can also be mentioned at this point: he reported that the upper thoracic segments of the spinal column, neural tube defects involving the cranium, and monozygotic twin pregnancies had often been found together, running in the family. These findings were confirmed by Garabedian and Fraser [23] who drew the “anatomical borderline” at the level of the 11th thoracic vertebra.
The malformations are usually recognized before the 24th gestational week, which, at the current level of ultrasonographic diagnostics, is taken for granted. Our investigations found the median value of the date of diagnosis at approximately the 19th gestational week. According to the results of Ben-Ami et al. [28], in twin pregnancies discordant for anencephaly, diagnoses can be expected at the 15–16th gestational weeks on average. As explanation we should not forget, however, that some of the cases in the study were diagnosed many years ago, at a less developed stage of ultrasonographic diagnostics. In certain instances, pregnancies affected by hydrocephalus may be considered as exceptions because, for etiological reasons, the malformation occasionally develops at a later gestational age.
Among the associated non-central nervous system malformations, polyhydramnios was diagnosed in 23 cases (54.8%). This malformation was also commonly found in studies by Gul et al. [5] and Lipitz et al. [9]. Polyhydramnios is not only significant as a sonographically diagnosed disorder, associated with malformations of the central nervous system and affecting systems other than the central nervous system, but it is also of obstetric importance, since it may increase the risk of premature birth, thus decreasing the healthy fetus's chances of survival.
During prenatal care or decision-making about the outcome of a twin pregnancy discordant for a specific malformation, it is important to know which fetus is affected [4]. This is especially crucial in a dichorionic pregnancy, in which selective abortion can be considered. An important rule is that selective abortion involves the fetus situated farther away from the uterine orifice [26], since an intervention performed on fetus A would significantly increase the risk of a miscarriage/premature delivery. In the 2 pregnancies managed by selective termination (with DDD placentation), both B fetuses suffered from expressed hydrocephalus. In the remaining 12 cases of an affected fetus “B”, the placentation (monochorionic) did not allow selective termination or the patient simply did not accept the proposed intervention. In contrast to our cases, the aim is to perform selective abortion before the 16th gestational week if possible, as, with time passing, the intervention carries an increased risk of miscarriage [18], [19], [27]. At the same time certain studies [28] report that selective termination can be performed also at a later stage of pregnancy (28–33 weeks), though it may lead to conflict between the medical staff and the parents. Not all obstetricians personally support pregnancy termination beyond fetal viability.
When a decision is made about the outcome of a twin pregnancy discordant for a specific malformation of the central nervous system, several questions are considered. Chorionicity, amnionicity, gestational age and the position of the affected fetus in relation to the uterine orifice are basic pieces of information, as are the prognosis of the specific malformation, possible therapies or information about obstetric complications associated with the specific malformation [19].
In summary of our study, it can be concluded that malformations of the central nervous system occur at a higher rate in monochorionic twin pregnancies than in the general population. Among them, neural tube defects are more commonly found in monozygotic fetuses or dizygotic fetuses of the same sex. In a twin pregnancy discordant for a specific malformation affecting the central nervous system, the decision about the outcome of the pregnancy is based on which fetus is affected. To reveal which fetus is involved is especially important in dichorionic twin pregnancies, in which selective abortion may be an option, though also in monochorionic pregnancies laser occlusion of the umbilical cord can make the intervention possible. Polyhydramnios, often associated with malformations of the central nervous system, is also of great obstetric importance, as it can significantly increase the risk of premature births and other obstetric complications.
Acknowledgements
We would like to acknowledge the significant contribution of the colleagues at the Ultrasound Laboratory and the Genetic Counselling Unit of the 1st Department of Obstetrics and Gynecology, Semmelweis University in making the study. We would also like to thank the colleagues at the 2nd Department of Obstetrics and Gynecology, Semmelweis University for their participation.
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PII: S0301-2115(10)00407-0
doi:10.1016/j.ejogrb.2010.07.045
© 2010 Elsevier Ireland Ltd. All rights reserved.
Volume 154, Issue 1 , Pages 27-30, January 2011
