Natural outcome of trisomy 13, trisomy 18, and triploidy after prenatal diagnosis†
How to Cite this Article: Lakovschek IC, Streubel B, Ulm B. 2011. Natural outcome of trisomy 13, trisomy 18, and triploidy after prenatal diagnosis. Am J Med Genet Part A 155: 2626–2633.
Abstract
Trisomy 13, trisomy 18, and triploidy belong to the chromosomal abnormalities which are compatible with life, but which are also associated with a high rate of spontaneous abortion, intrauterine death, and a short life span. This study was conducted to analyze natural outcome after prenatal diagnosis of these disorders. Between January 1, 1999 and December 31, 2009, we investigated all amniocenteses and chorionic villus biopsies carried out at our department. All cases with fetal diagnosis of triploidy, trisomy 13, and 18 were analyzed, with a focus on cases with natural outcome. Overall, 83 (78%) cases of pregnancy termination and 24 (22%) patients with natural outcome (NO) were identified. The NO group included 15 cases of trisomy 18, six cases of triploidy, and three cases of trisomy 13. No case of triploidy was born alive. The live birth rate was 13% for trisomy 18 and 33% for trisomy 13. The three live-born infants with trisomy 13 and 18 died early after a maximum of 87 hr postpartum. Our data are consistent with the literature concerning outcome of triploidy, with none or only a few live births. Analyzes of trisomy 13 and 18 indicate a very short postnatal life span. Different study designs and diverse treatment strategies greatly affect the fetal and neonatal outcome of fetuses with triploidy, trisomy 13, and 18. More studies analyzing natural outcome after prenatal diagnosis of these chromosomal abnormalities are needed. Non-termination of these pregnancies remains an option, and specialists advising parents need accurate data for counseling. © 2011 Wiley Periodicals, Inc.
INTRODUCTION
Trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome) are, along with trisomy 21 (Down syndrome), the most common autosomal aneuploidies in the newborn, with a prevalence at birth of between one in 3,000 and one in 15,000 [Smith, 1964; Carter et al., 1985; Baty et al., 1994; Hasslod and Hunt, 2001].
Triploidy belongs to the polyploid types, and is estimated to occur in 1–2% of recognized human conceptuses. Most pregnancies with triploidy, however, are aborted spontaneously in early gestation so that the prevalence at birth of triploidy is rare: approximately one in 50,000 newborns [Doshi et al., 1983; McFadden and Kalousek, 1991].
All these chromosomal abnormalities belong to disorders which are compatible with life, but which are also associated with a high rate of spontaneous abortion, intrauterine death, and a short life span. [O'Connor, 2008].
Over the last 30 years, prenatal diagnosis of these disorders has improved due to the increasing use of fetal ultrasound screening methods in the first and second trimesters, and invasive diagnostic methods such as amniocenteses. In Austria, as in many other countries, parents are given the opportunity to terminate a pregnancy (artificially induced abortion) if a severe fetal disorder has been diagnosed. Only a few parents, therefore, decide to continue with a pregnancy after a prenatal diagnosis of trisomy 13, trisomy 18, or triploidy.
During the parent's decision process concerning continuation or termination of pregnancy, questions regarding natural outcome and potential survival of the newborn are always focus of conversation. Although there is plenty of literature regarding trisomy 13, trisomy 18, and triploidy, information on natural outcome in these infants is lacking, in part, due to a small patient population, biased due to focusing on single cases with a relatively long time of survival, differences in management of these cases and mingling of pre- and postnatal diagnosis [Sherard et al., 1986; Niemann-Seyde et al., 1993; Baty et al., 1994; Root and Carey, 1994; Chitty et al., 1996; Goc et al., 2006; Lin et al., 2006; McGraw and Perlman, 2008; Berger and Hofer, 2009].
At our department, in those cases where parents wish to continue with a pregnancy, invasive procedures are avoided and expectant management of the pregnancy and comfort care for the newborn is the standard of treatment.
The aim of this study was to analyze the outcome of continued pregnancies after prenatal chromosomal diagnosis of trisomy 13, trisomy 18, or triploidy. These new data are aimed at improving the consulting process for parents who are confronted with prenatal diagnoses of these chromosomal abnormalities.
MATERIALS AND METHODS
The Division of Obstetrics and Feto-Maternal medicine at the Department of Gynecology of the Medical University of Vienna is the biggest tertiary medical centre in Vienna and northeastern Austria, with approximately 300 amniocenteses and chorionic villus biopsies now performed each year.
After approval from the local ethics committee, we analyzed all the results of amniocenteses and chorionic villus biopsies carried out at our department between January 1, 1999 and December 31, 2009. Cases with a fetal diagnosis of trisomy 13, trisomy 18, and triploidy, and also mosaic forms of these disorders with a minimum of 60% aberrant karyotype were included regardless of the parents' decision to continue or terminate the pregnancy. We then identified those cases in which the parents continued pregnancy and selected those for further analysis. The medical records and PIA® records (an electronic database for patient administration) of all patients with a prenatal fetal diagnosis of trisomy 13, trisomy 18, and triploidy were analyzed.
We investigated the mean intrauterine survival time of the fetus and, if applicable, of the newborn after birth. Furthermore, we collected the following data: age of mother, sex of the fetus, single or multiple pregnancies, delivery mode, and gestational age at diagnosis. Signs of malformation on ultrasound examination and the corresponding gestational age of the fetus were also noted.
Malformations were classified in regard to the affected organ systems and sonographic indicators of chromosomal abnormalities such as a reduced amniotic fluid. Growth retardation and thickness of nuchal fold were also taken into account, creating a score of abnormal ultrasound findings. Every registered abnormality equaled one point, producing a score ranging from one to seven for each fetus.
Data were computerized using Excel®. Statistical analysis and calculations were performed using PASW 18®. For comparison between groups, we used the Chi-square test, Student's t-test, and the Wilcoxon test. Significance was defined as P < 0.05.
RESULTS
From January 1, 1999 and December 31, 2009, a total of 6,836 amniocenteses and chorionic villus biopsies were performed at our department. These included 133 cases (total population of the study) with a diagnosis of trisomy 13, trisomy 18, or triploidy. One of these cases was excluded because the amniocentesis was performed shortly before birth and the final diagnosis was made after the child was born. Pregnancy outcome could not be definitely determined in 25 cases because patient care was continued at different hospitals. These cases were also excluded. Details of group determination are displayed in Figure 1.
Group determination. AC, amniocenteses; CVS, chorionic villus biopsies; TP, termination of pregnancy; NO, natural outcome; n, number.
Overall, 83 (78%) cases of pregnancy termination (PT) and 24 (22%) patients with natural outcome (NO) were identified. The mean maternal age was 33 (range 19–47) in the PT group and 35 (range 23–43) in the NO group. In the NO group, gestational age at sonographic detection of initial aberrations and subsequent karyotyping, was slightly higher, though not significantly, than in the PT group. Nevertheless, the total number of sonographically recognized malformations and abnormalities were equal between groups. There were more female fetuses than males observed in both groups. Proportionally more multiple pregnancies were observed in the NO group. The most frequently diagnosed disorder was trisomy 18 (∼60%), followed by triploidy (∼25%), and trisomy 13 (∼15%). There was no difference in the number of sonographically detected abnormalities for each fetus between the two groups. Basic data comparing groups are shown in Table I.
| PT (n = 83) | NO (n = 24) | P-value | |
|---|---|---|---|
| Maternal age (y) | 32.7 ± 6.13 | 34.8 ± 7.06 | 0.15 |
| Time of first sonographic abnormalities (GA) | 16.8 ± 5.18 | 18.8 ± 7.94 | 0.15 |
| Diagnosis after AC/CVS (GA) | 17.6 ± 5.14 | 19.8 ± 8.4 | 0.11 |
| Fetal sex (m/f) | 34/49 | 8/16 | 0.50 |
| Trisomy 18 (%) | 51 (61) | 15 (63) | 0.92 |
| Trisomy 13 (%) | 13 (16) | 3 (12) | 0.70 |
| Triploidy (%) | 19 (23) | 6 (25) | 0.83 |
| Multiple pregnancy | 1 | 4 | — |
| Number of sonographic abnormalities per fetus (range) | 2.8 (1–7) | 2.8 (1–6) | 0.81 |
- PT, pregnancy termination group; NO, natural outcome group; y, years; GA, gestational age (weeks); AC, amniocenteses; CVS, chorionic villus biopsy; m, male; f, female; n, number.
- If not specified: data as mean ± SD.
The NO group included 15 cases of trisomy 18, six cases of triploidy, and three cases of trisomy 13. Data for the three diagnostic groups are shown in Table II. Triploidy was detected earlier than trisomy 13 and 18 (14 vs. 21, respectively, 20 weeks of gestation). Diagnosis of trisomy 13 was made latest in pregnancy (at approximately 22 weeks of gestation) and fetuses with this disorder showed the largest number of abnormalities on sonogram.
| T18 (n = 15) | T13 (n = 3) | Tripl (n = 6) | |
|---|---|---|---|
| Maternal age (y) | 37.1 ± 5.9 | 39.0 ± 6.1 | 27.0 ± 4.0 |
| First sonographic signs (GA) | 20.0 ± 8.9 | 21.1 ± 9.2 | 14.4 ± 1.8 |
| Diagnosis after AC/CVS (GA) | 21.2 ± 9.3 | 22.5 ± 10.5 | 15.1 ± 1.5 |
| Fetus sex (m/f) | 5/10 | 0/3 | 3/3 |
| Multiple pregnancy | 3 | 1 | 0 |
| Number of sonographic abnormalities per fetus (range) | 3 (1–6) | 3 (1–5) | 2 (1–3) |
| IUFD (%) | 10 (67) | 2 (66) | 6 (100) |
| Stillbirths (%) | 3 (20) | 0 | 0 |
| Live births (%) | 2 (13) | 1 (33) | 0 |
- T18, trisomy 18 subgroup; T13, trisomy 13 subgroup; Tripl, triploidy subgroup; y, years; GA, gestational age (weeks); AC, amniocenteses; CVS, chorionic villus biopsies; m, male; f, female; IUFD, intrauterine fetal death; n, number.
- If not specified: data as mean ± SD.
Intrauterine fetal death (IUFD) occurred in the majority of continued pregnancies (18 of 24 cases). In cases of trisomy 18, IUFD was diagnosed at a mean of 22 weeks of gestation (range 13–40). The two cases of trisomy 13 died in utero at the 13th and 28th weeks of gestation, respectively.
In our population, only two triploid karyotypes occurred: three cases of 69,XXX (including one mosaic with > 70% 69,XXX) and three cases of 69,XXY (including one mosaic 69,XXY/70,XXYY). Diagnosis of triploidy and, thus of karyotypes 69,XXX and 69,XXY was made at a mean of 15 weeks of gestation (range 13–17) after abnormalities were found on sonogram at a mean of 14 weeks of gestation. All pregnancies with a diagnosis of triploidy resulted in an IUFD in the early second trimester between 14 and 18 weeks of gestational age.
Three fetuses were stillborn and only three infants, two with trisomy 18, and one with trisomy 13, were born alive. The longest survival time (87 hr) was for a newborn with trisomy 18 under comfort care conditions. Background and outcome data for the newborn cases are summarized in Table III.
| Patient | Maternal age (y) | Case history | Sonographic abnormalities (GA) | Diagnosis (Typ/GA) | Diagnosis | Birth (GA) | Pregnancy outcome |
|---|---|---|---|---|---|---|---|
| 1 | 38 | DC/DA-Twins. St. p. ICSI. St. p. CS | 21 + 2 | AC/35 + 2 | T18 | 37 + 4 | Late AC because of healthy twin. CS because of contractions and St. p. CS. Death of the newborn 87 hr postpartum. |
| 2 | 30 | None | 34 + 1 | AC/34 + 2 | T18 | 39 + 6 | Vaginal birth. Death of newborn 6 hr postpartum. |
| 3 | 42 | Hypertonia | 30 + 5 | AC/33 + 5 | T13 | 36 + 3 | Induction of labor because of severe pre-eclampsia. Death of newborn 6 hr postpartum. |
- y, years; ICSI, intracytoplasmic sperm injection; CS, caesarean section; DC/DA, dichorionic–diamniotic; GA, gestational age (weeks + days); AC, amniocenteses.
- ses were included.
DISCUSSION
In Austria, the general implementation of prenatal diagnosis and sonographic screening methods in the first and second trimester of a pregnancy has led to a high antenatal detection rate of trisomy 13, trisomy 18, and triploidy. In these cases, parents have two opportunities concerning a pregnancy: termination or continuation.
Our results indicate that in approximately 22% of all prenatally diagnosed cases of trisomy 13, trisomy 18, and triploidy, parents will decide to continue the pregnancy. Even if in the literature this rate ranges from 0% to 60%, our percentage is higher than we expected for the population of a western country. But similar observations have been made by Hassed et al. [1993]. The process of making a decision to continue or terminate a pregnancy appears to be increasingly difficult, and parents always hope for the best until a clear diagnosis is made. The best counselling and information concerning a prenatal diagnosis can never perfectly prepare parents for such a complex situation and decision process. We observed cases in which parents did not come to the appointment where a decision was scheduled to be made, but they did come weeks later with an IUFD. It seems that for some parents the guilt which appears to be an integral part of the decision to abort a highly desired pregnancy is too big to face, and so they choose to “allow nature to take its course” [Hassed et al., 1993; Pryde et al., 1993; Drake et al., 1996; Evans et al., 1996; Leung et al., 2004; Goc et al., 2006; Hewison et al., 2007; Souka et al., 2010].
Observed Differences Between the PT and NO Groups
The reasons for terminating or continuing a pregnancy are many and varied. In our analysis, we observed a non-statistical trend of older women in the NO group. Even if Holmes-Siedle et al. [1987] found similar results, Shaffer et al. [2006] published a retrospective trial in which variation in the decision to terminate a pregnancy with fetal aneuploidy was determined in 833 cases, including trisomy 18, trisomy 13, and triploidy. In this study, women aged 35 and older were significantly more likely to end a pregnancy in cases where a fetal chromosomal disorder had been diagnosed. However, when the authors controlled for ethnicity, gestational age, and mode of diagnostic procedure, these differences disappeared [Holmes-Siedle et al., 1987; Shaffer et al., 2006].
We also observed a tendency in the NO group for sonographic detection of abnormalities and diagnosis at a later gestational age. Study groups such as Drugan et al. [1990] who analyzed this issue previously found no correlation between gestational age at diagnosis (mostly by comparison between the first and second trimester) and the decision taken by the parents [Drugan et al., 1990; Hassed et al., 1993; Evans et al., 1996; Leung et al., 2004].
Our results were secondary observations and we are aware of the small study population. There are, however, many factors contributing to the decision to continue or terminate a pregnancy and their influence can only be sufficiently addressed in a prospective study.
Natural Outcome: Triploidy
Triploidy has been estimated to occur in 1–2% of all clinically recognized conceptions with a high spontaneous abortion rate. The real incidence of trisomy 13, trisomy 18, and triploidy in pregnancy is difficult to evaluate because of early spontaneous abortions. Even if it seems that trisomy 13 should more often occur than triploidy in pregnancy, data of prenatal diagnoses in former studies indicate nearly the same rate of trisomy 13 and triploidy during the first trimester [Jacobs et al., 1978; De Vigan et al., 2001; Brancati et al., 2003].
Previous literature indicates that 69,XYY triploidy is very rare. In our analyses, this karyotype was not observed. A case series focusing on the phenotypic features of triploid fetuses reported 43 cases and found only one case of 69,XYY. Other publications were also concordant with these results and show no cases of 69,XYY in advanced gestation age. Several authors have suggested that survival in triploid fetuses may be influenced by the sex chromosomes, with only a few 69,XYY conceptions surviving beyond the embryonic period of development [Jacobs et al., 1982; Jauniaux et al., 1996; Baumer et al., 2000; Philipp et al., 2004; Huang et al., 2005; McWeeney et al., 2009].
All the triploid fetuses in our study died in utero early in the second trimester, between the 14th and 18th weeks of gestational age. Our data are confirmed by previous literature, in which long fetal survival until the third trimester is uncommon and only a few cases of live births have been reported. None of the live birth cases in the literature survived for more than 1 year and long-term survival has been associated with the mosaic form [Sherard et al., 1986; Tantravahi et al., 1986; Graham et al., 1989; Warburton et al., 1994; Hasegawa et al., 1999; Brancati et al., 2003; Forrester and Merz, 2003b; McWeeney et al., 2009].
Because of the high lethality of this disorder, leading in the majority of cases to IUFD, continuing a pregnancy and “letting nature take its course” can be an option after a triploidy prenatal diagnosis, particularly for ambivalent parents. Parents who wish to continue with the pregnancy, however, should be informed and should obtain proper counseling. We are aware of higher rates of maternal complications including pre-eclampsia, an abnormally large placenta that can result in postpartum hemorrhaging, and unnecessary obstetric intervention. If complications occur the mother should receive priority treatment and termination of the pregnancy should be evaluated [McWeeney et al., 2009].
Natural Outcome: Trisomy 13 and Trisomy 18
In previous literature, data regarding live births and survival rates varied from study to study. Live birth rates differed from 20% to 90% for trisomy 18, and 40% to 70% for trisomy 13. Survival also differed substantially, with 1-year survival rates for trisomy 18 and 13 ranging from 0% to 10%. We posit that this large spectrum of outcome data is the result of different study designs: (I) the collecting of postnatal diagnoses of live births or postnatal death rates, (II) mixed data of prenatal and postnatal diagnoses, and (III) data of spontaneous abortion rates after prenatal diagnoses without analyzing the survival rates of newborns. The outcome data of the most important papers sorted by the mentioned criteria are shown in Table IV [Weber, 1967; Carter et al., 1985; Goldstein and Nielsen, 1988; Hook et al., 1989; Baty et al., 1994; Root and Carey, 1994; Embleton et al., 1996; Huether et al., 1996; Grandjean et al., 1998; Forrester and Merz, 1999; Nembhard et al., 2001; Brewer et al., 2002; Moran et al., 2002; Rasmussen et al., 2003; Forrester and Merz, 2003a; Won et al., 2005; Yamanaka et al., 2006; Morris and Savva, 2008].
| Study | Trisomy | TC (n) | Pre (n) | Post (n) | IUFD (n) | SB (n) | LB of TC | >1 surv. of LB | MS (d) | Remarks | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| n (%) | n (%) | ||||||||||
| I | Weber 1967 | 18 | 192 | — | 192 | — | 192 | 42 (22) | ∼70 | Trisomy 17–18 cases | |
| Young et al. 1986 | 18 | 21 | — | 21 | — | 21 | 0 | 22 | Max. surviving time: 126 d | ||
| Root and Carey 1994 | 18 | 64 | — | — | 64 | 3 (5) | 4 | ||||
| Naguib et al. 1999 | 18 | 118 | — | 118 | — | 118 | 0 | ∼7 | Max. surviving time: 210 d | ||
| Nembhard et al. 2001 | 13 | 27 | — | 27 | — | 27 | 2 (7) | ∼7 | |||
| 18 | 68 | — | 68 | — | 68 | 7 (10) | ∼7 | ||||
| Brewer et al. 2002 | 13 | 32 | — | 32 | — | 32 | ∼3 (11) | 8.5 | |||
| 18 | 84 | — | 84 | — | 84 | ∼7 (10) | 6 | ||||
| Forrester and Merz 2003a | 13 | 22 | — | 22 | — | 22 | 4 (18) | — | No data of median survival | ||
| 18 | 38 | — | 38 | — | 38 | 10 (26) | — | ||||
| Rasmussen et al. 2003 | 13 | 70 | — | 70 | — | 70 | 6 (9) | ∼7 | |||
| 18 | 114 | — | 114 | — | 114 | 10 (9) | 14.5 | ||||
| Vendola et al. 2010 | 13 | 200 | — | 200 | — | 200 | 6 (3) | 4.5 | Extracting only clear data on live births | ||
| 18 | 140 | — | 140 | — | 140 | 4 (3) | 7 | ||||
| II | Carter et al. 1985 | 18 | 48 | 5 | 43 | 3 | 36 | 1 (3) | 5 | Focusing on LB | |
| Goldstein and Nielsen 1988 | 13 | 19 | 19 | 0 | 0 | 19 | 0 | 2.5 | |||
| 18 | 82 | 46 | 36 | 6 | 76 | 0 | 6 | ||||
| Embleton et al. 1996 a | 18 | 43 | 5 | 38 | 6 | 3 | 34 | 0 | 3 | Two live births were diagnosed antenatally | |
| Grandjean et al. 1998 a | 13 | 20 | 8 | 12 | 15 | 5 | 0 | 6 | Max. surviving time: 6 d | ||
| 18 | 53 | 37 | 16 | 48 | 5 | 0 | 6 | ||||
| Forrester and Merz 1999 a | 13 | 29 | 5 | 24 | 10 | 19 | 2 (7) | No data of median survival | |||
| 18 | 60 | 10 | 50 | 25 | 35 | 9 (13) | — | ||||
| Moran et al. 2002 | 13 | 6 | 2 | 4 | 0 | 3 | 3 | 0 | ∼14 | ||
| 18 | 16 | 4 | 12 | 0 | 3 | 13 | 1 (8) | ∼14 | |||
| Goc et al. 2006 | 18 | 20 | 8 | 12 | 0 | 20 | No data | 20 | Focusing on LB. Aggressive treatment | ||
| Parker et al. 2003 | 13 | 14 | 8 | 6 | 3 | 3 | 0 | 2.5 | Max. surviving time: 42 days | ||
| 18 | 22 | 14 | 8 | 6 | 6 | 0 | 5 | Max. surviving time: 254 days | |||
| Yamanaka et al. 2006 | 18 | 83 | 59 | 4 | 16 | 10 | 32 | 1 (3) | ∼7 | ||
| Lin et al. 2006 | 18 | 39 | 1 | 38 | 0 | 39 | 1 (2) | 6 | Focusing on LB | ||
| Niedrist et al. 2006 | 18 | 352 | 200 | 152 | 191 | 161 | 10 (3) | 4 | Data including termination of pregnancy. | ||
| Hsiao et al. 2009 | 18 | 31 | 3 | 28 | 0 | 31 | 2 (6) | 12 | Focusing on LB | ||
| Irving et al. 2010 a | 13 | 32 | 7 | 25 | 2 | 30 | 1 (3) | ∼7 | Authors excluding miscarriage before 24 weeks of gestation | ||
| 18 | 99 | 32 | 67 | 32 | 67 | 4 (6) | ∼7 | ||||
| III | Hook et al. 1989 | 13 | 7 | 7 | — | 3 | 4 (57) | — | — | No data of surviving of LB | |
| 18 | 36 | 36 | — | 24 | 12 (33) | — | — | ||||
| Morris and Savva 2008 a | 13 | 19 | 19 | — | 9 | 10 (52) | — | — | No data of surviving of LB | ||
| 18 | 80 | 80 | — | 56 | 24 (19) | — | — | ||||
| Won et al. 2005 | 18 | 106 | 106 | — | 34 | 72 (68) | — | — | No data of surviving of LB | ||
| IV | Current study | 13 | 3 | 3 | — | 2 | 0 | 1 (33) | 0 | 6 hr | Max. surviving time: 6 hr |
| 18 | 15 | 15 | — | 10 | 3 | 2 (13) | 0 | 46 hr | Max. surviving time: 87 hr | ||
- (I) Collecting of postnatal diagnosis of live-born children or postnatal death rates, (II) mixed data of prenatal and postnatal diagnosis, (III) data of spontaneous abortion rate after prenatal diagnosis without analyzing survival rates of newborns, IV) our results.
- TC, total cases; Pre, prenatal diagnosis; Post, postpartum diagnosis; SB, stillbirths; LB, live births; >1 surv., over 1-year survival; MS, mean survival time.
- a If artificial pregnancy termination after prenatal diagnosis is mentioned, cases were excluded and only natural outcome cases were included.
Most previous studies have only concentrated on live births. In a population-based study, Rasmussen et al. [2003] analyzed outcome and survival for trisomy 13 and 18. The data from this study indicate a 1-year survival of 5–10%. The authors also mentioned that this study is biased by two different factors: firstly, unreported cases of early deaths after birth without accurate diagnosis and; secondly, by a lack of information on the types of medical interventions provided to the newborns. Today, a policy of limiting medical interventions in trisomy 18 and 13 is commonly accepted. The outcome for newborns, therefore, would be more in line with the outcome data of Naguib et al. [1999].
Currently, parents receiving an early prenatal diagnosis of fetal trisomy 13 or 18, demand to receive more information regarding the anticipated outcome of the pregnancy from that point on, and not just a prediction of a live birth. For parents, the expected rates of miscarriage and stillbirths are as important as live births and survival rates.
To estimate the rate of miscarriage or stillbirths Morris and Savva [2008] conducted a study published in 2008. The aim of this analysis was to determine the risk of fetal loss following a prenatal diagnosis of trisomy 13 or 18. Results indicated a rate of live births of approximately 50% in cases of trisomy 13 and 30% in cases of trisomy 18. These results were dependent on gestational age at diagnosis and the sex of the fetus. A later diagnosis and female sex were associated with a higher rate of live births. In spite of excellent analyses, no outcome data for newborns or the treatment or management of pregnancies were elucidated. A similar analysis regarding the timing of the demise in fetuses with trisomy 18 conducted by Won et al. [2005] indicated a much higher live birth rate of about 70% for trisomy 18, but data on postnatal outcome and treatment procedures were also absent. The authors pointed out a very interesting result in the analyses, that after 24 weeks of gestation there was no specific time for fetal miscarriage in fetuses affected by trisomy 18 [Won et al., 2005; Morris and Savva, 2008].
The only study which is similar to ours is an analysis by Yamanaka et al. [2006]. This was a retrospective study of trisomy 18 in Japan. Basic data were primary mixed, as in previous publications, but outcomes specific to a prenatal diagnosis were also determined. In total, there were 58 cases of prenatally diagnosed trisomy 18 with a live birth rate of 55% (32 cases). Most of these infants died within 1 week (20 cases; 62% of all newborns). One child survived more than 8 years, but this was one of the cases diagnosed postpartum. This study provided good data regarding natural outcome after prenatal diagnosis in cases of trisomy 18 but information concerning postpartum treatment of newborns was not reported [Yamanaka et al., 2006].
Overall, it is difficult to compare our study with previous data because we determined the natural outcome in cases of the prenatal diagnosis of these disorders before and after birth under special conditions: expectant management and postpartum comfort care. Our analysis showed a live birth rate of about 13% for trisomy 18 and 33% for trisomy 13. These data are consistent with the lower range in the literature. The mean survival time of the newborns was 6 hr for trisomy 13 and 46 hr trisomy 18, with a maximum survival time of 87 hr. These data are much lower than in the literature. These results can be biased by the small population, but can also be explained by comfort care treatment immediately after birth for the newborn. Comfort care can be defined as supportive care and symptom management, in effect maintaining a patient in warmth and a feeling of security, and free of pain, hunger and thirst [Romsberg, 2007; Al-Alaiyan and Al-Hazzani, 2009].
The different study designs and treatment strategies greatly affect the data of patient outcome. Today, diagnosis is made early in a pregnancy and accurate knowledge based on studies which analyze these specific cases from the time of diagnosis onwards, is necessary. We are aware of our small study population and perhaps our study is too small to draw a major conclusion, but it does demonstrate that larger prospective studies should continue researching the same topic. We suspect that only studies which analyze outcome after prenatal diagnosis will be relevant in the future because early detection in pregnancy of these disorders will be the standard.
CONCLUSIONS
The world wide increase in prenatal screening for Down syndrome and other disorders in the first and second trimester of pregnancy is leading to an increase in the numbers of women referred for counseling after prenatal diagnoses. In turn, this leads to a rise in the diagnosis of triploidy because of its higher detection prevalence in the early stages of gestation, which may result in miscarriage. Combined with increasing maternal age, prenatal diagnosis will lead to a higher number of trisomy 13 and 18 cases. It is important that parents who are confronted with these fetal disorders are given reliable prognoses for the outcome of the pregnancy and the newborn, something which is also determined by the management and postpartum care of live births.
The reasons for parents deciding to continue with a pregnancy despite the definite diagnosis of a lethal fetal chromosomal abnormality are manifold. One motive is sometimes the wish to share time with their unborn infant for as long as possible. In these cases, continuing a pregnancy often means more time available for preparing to “say goodbye” and for coping with this special situation. For these parents, accurate current information is essential to develop a realistic view and understanding of prospects, advice and conversation. It is clear that “natural outcome” can never be anticipated and so parents should be prepared for every possible pregnancy outcome: IUFD, stillbirth and live birth, as well as survival condition and maternal risks. And, of course, the conversation should be multidisciplinary including obstetricians, psychologists, midwives, and neonatologists.
