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Natural history of fetal trisomy 18 after prenatal diagnosis
  1. Annette L Burke,
  2. Katie Field,
  3. John J Morrison
  1. Galway University Hospital, National University of Ireland, Galway, Galway, Ireland
  1. Correspondence to John J Morrison, Galway University Hospital, National University of Ireland Galway, Newcastle Road, Galway, Ireland; john.morrison{at}nuigalway.ie

Abstract

Objective To evaluate the natural fetal and neonatal outcome for pregnancies with an established prenatal diagnosis of fetal trisomy 18, and a parental decision for continuation of the pregnancy.

Methods The obstetric and neonatal outcome data for 23 such pregnancies, diagnosed at a single referral Fetal Medicine Centre, were retrospectively obtained.

Results The overall intrauterine fetal death rate was 61%, with a progressive decline in live fetuses up to 39 weeks gestation. For fetuses diagnosed before 20 weeks gestation, there was a trend towards a higher intrauterine fetal death rate (88%), in comparison to those diagnosed after this period (44%) (p=0.06). For live births, the preterm delivery rate was 44%. All infants born alive died within 48 h of birth.

Conclusion These data provide reliable information for parental counselling pertaining to risk of intrauterine death when trisomy 18 is diagnosed prenatally. These findings suggest that long-term survival implications for trisomy 18 are different when it is diagnosed prenatally.

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Introduction

Trisomy 18 is the most common autosomal trisomy after Down's syndrome, and is associated with high perinatal and infant death rates. Recent advances in prenatal screening tests, and detailed ultrasound scanning, combined with greater availability of such investigations, have resulted in an increase in prenatal diagnosis of trisomy 18 in recent years.1 ,2 In addition, an apparent increase in the live born prevalence of trisomy 18 has also been reported, while infant survival has remained unchanged.1 For the vast majority of pregnant women for whom the diagnosis of trisomy 18 is made prenatally, the option of termination of pregnancy is embarked upon, because of the lethal nature of the condition. For the small minority of parents who elect to continue with the pregnancy, there is a paucity of information available to facilitate accurate counselling in relation to the possible outcomes for the fetus or neonate. While there are reliable data describing the natural history of trisomy 18 after a live birth, from studies that have included infants that were diagnosed postnatally or predominantly so,3 ,4 there are few reports pertaining to the pregnancy outcome and natural history of this condition, in a cohort of patients where the diagnosis was established prenatally. One recent report, from Austria, included 15 cases of trisomy 18 where the pregnancy was managed naturally, and reported that intrauterine fetal death occurred at a mean gestation of 22 weeks,5 but did not provide specific data about overall fetal or neonatal loss rates specific for this condition. A Japanese study, which included cases of trisomy 18 diagnosed either prenatally or postnatally, reported a total intrauterine fetal death rate of 45%, between 28 and 41 weeks gestation, and hence a live birth rate of 55%, for those diagnosed prenatally.6 There is a clear need for more studies analysing natural outcome after prenatal diagnosis of trisomy 18 in utero.5 The aim of this study was to evaluate the fetal and neonatal outcome for all pregnancies for which there was a prenatal diagnosis of trisomy 18, and a parental decision for continuation of the pregnancy.

Materials and methods

This is a retrospective study and all cases included were referred to the Fetal Medicine Unit (FMU) at Galway University Hospital, Ireland, between 2000-2009, because of a suspicion of fetal abnormality on a screening (routine) ultrasound assessment, performed as part of obstetric care with the referring clinician. After assessment, and confirmation of fetal structural abnormality, the parents were counselled in relation to invasive diagnostic testing, and offered chorionic villous sampling, or amniocentesis, depending on the timing of gestation, the placental localisation and the amniotic fluid volume. Once the diagnosis of fetal trisomy 18 was established, the parents were counselled about this result, and referred back to the original clinician for further care. For parents who opted for continuation of the pregnancy with a known diagnosis of fetal trisomy 18, the referring clinician was provided with correspondence requesting the follow-up clinical details pertaining to the fetal and neonatal outcome. This was further pursued with repeat correspondence, and telephone communication, until the details of all such pregnancies were complete. For statistical analysis, a Fisher's exact test was used for comparison of proportions between groups.

Results

There were 23 pregnancies during this time period for which the prenatal diagnosis of trisomy 18 was established, and continuation of the pregnancy took place. The clinical data are summarised in table 1, which outlines the ultrasound findings leading to FMU referral, the gestation at which karyotyping took place, and the ultimate fetal or neonatal outcome. The overall rate of intrauterine fetal death was 61% (14/23), and the live birth rate was 39% (9/23). Figure 1 demonstrates the progressive decline in live fetuses, and the reciprocal increase in fetal death, that occurred until 39 weeks gestation, in the overall group. All infants born alive died within 48 h of birth, that is, 100% perinatal mortality. For live births, the preterm delivery rate (<37 weeks) was 44% (4/9), with 56% (5/9) delivering at term.

Figure 1

Demonstrates the number of live fetuses present for each 2-week period of gestation, from 16 to 40 weeks, after prenatal diagnosis with trisomy 18.

Table 1

Antenatal sonographic abnormality, gestation at karyotyping and time of perinatal death of fetus with trisomy 18

For fetuses diagnosed before 20 weeks gestation (n=8), there was a trend towards a higher intrauterine fetal death rate, which was 88% (7/8), in comparison to that observed when the diagnosis was established after 20 weeks gestation, which was 47% (7/15) (p=0.06), but this was not statistically significant. For the subgroup that was diagnosed before 20 weeks gestation, fetal demise occurred between 16 and 33 weeks gestation. One case diagnosed before 20 weeks gestation was delivered prematurely at 33 weeks, and died at 1 h of age postnatally. The live birth rate for fetuses diagnosed after 20 weeks gestation was 53% (8/15).

Discussion

Trisomy 18 is relatively uncommon and pregnancy continuation after prenatal diagnosis of this condition is rare. Consequently, reliable data to assist in counselling prospective parents who wish to pursue this option after prenatal diagnosis, are lacking. It has also recently become clear that the outcome for fetuses diagnosed prenatally with trisomy 18 is rather different to that observed after a live birth, when the diagnosis is made postnatally.3,,5 The findings from this study are based on the natural outcome for trisomy 18 from 23 pregnancies in which the diagnosis was made prenatally, and clearly provide useful figures for management of such patients in a fetal medicine service. The overall intrauterine fetal death rate in this study was 61%, which is higher than the 45% observed in the Japanese study,6 yet lower than the 87% observed in the 15 such cases included in the Austrian study.5 In our series, all live born infants died within 48 h of birth. In the Japanese study, there were similarly no long survivors among the prenatally diagnosed fetuses with trisomy 18.6 When prospective parents are presented with the prenatal diagnosis of trisomy 18, one of the most frequently encountered queries relates to the possibility of long-term survival. It is known, from observation of the natural history of this condition when it is diagnosed postnatally in live born infants,3 that a small proportion can survive for long periods of time. The findings from this study support the view that long-term survival for fetuses with prenatally diagnosed trisomy 18 appears to be much lower than when the condition is diagnosed postnatally, and is probably close to zero.

The issue of whether the baby will die in utero, or be live born, is also central to the concerns of prospective parents in this situation. The findings from this study provide some help in counselling around this issue. First, there is a marked increase in intrauterine fetal death rates when the prenatal diagnosis is established before 20 weeks gestation (88%), in comparison to that observed when the diagnosis is made after this time (47%). This may well reflect the fact that earlier diagnosis is linked to more severe structural abnormalities, and particularly cardiac disease and hydrops. Second, while it has long been presumed that there was a natural demise of chromosomally abnormal fetuses over the course of a pregnancy, the data demonstrating this are lacking without having natural outcome information following prenatal diagnosis. In the case of trisomy 18, the natural history of this case series clearly demonstrates a progressive fetal death rate over the course of the second and third trimesters, up to 39 weeks gestation.

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Footnotes

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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