Survival in trisomy 18

This is the detailed version - read the Keeping it Simple summary here.

So here you are: your fetus or newborn has a diagnosis of trisomy 18 and you ask, "How long will she live?" Your doctor tells you that it's "rare to make it to birth, but if she does, a few days; some live a few weeks"; your googling tells you that 8% live until a year; and your new online friend from the Facebook trisomy group tells you, "Don't give up hope! My daughter's 14!" (or 18 or 25), and you have no idea what on earth to say when your friends ask, "How serious is it?"

What do we actually know about survival for children with trisomy 18?

First of all, the research on survival on trisomy 18 is limited. There are three types of research:

1. The population-based study, looking at all children diagnosed with trisomy 18 in a particular country/region etc.
2. The intervention-based study, looking at all children with T18 who received a particular intervention, eg. intensive care, sometimes comparing them with a group of children with T18 who didn't receive the intervention.
3. The selected population-based study, which looks at a group of children whom the authors recruited, and uses this group to draw wider conclusions.

All of these study types have provided data on survival in trisomy 18, but unfortunately they all suffer from limitations.

Population-based studies

provide us with a particularly good source of data: there is no selection bias, as all children within the population are studied. They are useful for baseline survival data. Studies I have looked at in this group include:

• Wu et al (2013) - England and Wales
• Houlihan and Donoghue (2013) - One region in Ireland
• Niedrist et al (2006) - Switzerland

However, in all three of these areas, the standard management for a baby prenatally diagnosed with trisomy 18 is to offer comfort care only. For children who are postnatally diagnosed, some treatments are likely to be withdrawn or withheld once the diagnosis is confirmed. This, therefore, provides a biased set of statistics. If we relied on these for our understanding of how long children with trisomy 18 live, it would be like using survival data for premature infants from before the days of neonatal intensive care.

Intervention-based studies

look at the efficacy of a given intervention (or set of interventions) for children with trisomy 18. As trisomy 18 is relatively rare in the liveborn population, many such studies consist of small numbers of children. This obviously makes the data less reliable. Many studies self-select the children who receive the intervention, or such children may be selected by their parents to receive the intervention.

Sometimes the authors have biases toward or against treatment. I use two studies to look at survival. In these studies, full intensive care was offered to the infants (although, in the second study, some intensive care was withheld once diagnosis was confirmed):

• Kosho et al (2006) - small Japanese study of 26 infants with trisomy 18
• Goc et al (2006) - Polish study of 20 infants, predominantly postnatally diagnosed (8 prenatal diagnoses)

Selected population based studies

look at self-selected populations.

The only study I look at in this category is Janvier et al (2012). This study looks at 272 children with trisomies 13 and 18. The families volunteered to be in the study after being recruited via social networks, so the study suffers significantly from selection bias. This makes the survival data unreliable.

In this study, the children had significantly better survival than in any other study. This is likely because families of longer-term survivors are more likely to access social networks, and hence be included in the study. However, this is a useful study for survival data because it compares children managed 'actively' and those managed 'palliatively'. While the raw survival data is of little use, the comparison between the two groups allows some tentative conclusions to be drawn on whether children managed actively survive for longer, and if so, for how much longer.

So how long do children with trisomy 18 live?

Population-based studies

In population based studies where we can assume children are predominantly managed palliatively, survival, as you would expect, is poor.

Niedrist et al (2006)

(NE Switzerland)
Median survival: 4 days. 33% of infants died in their first day. 40% survived for a week, 22% survived for a month and 6% survived for a year. 1% were still alive at age 10.

Houlihan & Donoghue (2013)

(Region of Ireland)
Median survival: 1.5 days. Longest survival: 16 weeks.

Wu et al (2013)

(England and Wales)
Median survival: 14 days. 60% survived a week, 39% survived a month, 20% survived three months, 8% survived a year.

It is unclear why Wu et al had such good survival statistics: it was one of the largest population studies and probably had one of the most complete populations, so the data should be reliable.

Houlihan & Donoghue is a relatively small study in population terms. Their very poor survival for T18 may be due to the exceptionally high rate of preterm delivery in the study group. Interestingly, this study is the only one I can find that suggests infants with T13 survive for longer; however, gestational age in their T13 group was significantly higher than in their T18 group. With other studies showing consistent improvement in survival for increasing gestational age, this high rate of prematurity renders their survival statistics questionable.

So overall, survival with palliative care is poor. Most infants die within the first two weeks. Survival until one year is under 10%.

Intervention-based studies

Kosho et al (2006)

This is a study of 23 infants with T18 managed intensively. Median survival: 152.5 days. 25% were alive at 12 months.

Goc et al (2006)

20 infants with T18 managed intensively (though some treatments were withheld from children with confirmed diagnoses). Median survival for infants who died: 20 days, but 30% of infants were discharged from the NICU and their survival time is not mentioned.

These two intervention-based studies are difficult to interpret. Both may suffer from author bias. Goc et al is overtly anti treatment for infants with T18, whereas Kosho et al appears to be pro active treatment.

The Goc survival stats are very much skewed by the failure to include the survival length of children who were discharged. We can say that survival is longer than the average for palliative care by 1-2 weeks at least. It is likely that if the infants who were discharged were added back in, median survival time would be considerably higher. The only conclusion one can draw from this study is that intervention improves survival, but by how much is unclear.

The Kosho survival stats are also not the most reliable. They are very impressive, with consistently high survival in a group managed intensively without prejudice, although 75% of infants died before 12 months. The authors did note that prematurity (some infants were as early as 31 weeks gestation) and some abnormalities - notably diaphragmatic hernias - negatively impacted survival. So survival may in fact be higher in carefully selected children. Unlike the Goc study, no treatment that was clinically appropriate was withheld from these children.

Selected population-based studies

Janvier et al (2012) studied 273 children. 25% were managed 'as per any other child'. 75% were given comfort care only, either by the choice of their parents or because it was the only option offered. Survival to hospital discharge was the same for both groups, however survival for children managed intensively was better, with 68% alive at 3 months, 53% at 12 months and 24% at 5 years. For children managed palliatively, the survival rates were 48% at 3 months, 30% at 12 months and 16% at 5 years.

These high survival statistics are certainly down to selection bias; however, the notable increase in survival for children managed actively is well worth taking note of.

What is interesting is that there is no increase in rate of survival to hospital discharge managed actively. There are two possible explanations for this:

1. Early intensive treatment makes no difference to survival outcomes. However, children who manage to survive the neonatal period do benefit from having subsequent complications managed.
2. 'Hospital discharge' is timed differently in the two groups. Those managed palliatively are discharged quickly in order for them to spend some time at home or in the hospice with their families before they die. Where families opt for full treatment, however, infants are kept in the NICU and their complications are managed as they present. Some will never achieve the stability to get home and die in hospital.

If the second is true, then survival data would be more appropriately grouped by age than by survival to hospital discharge.

So, overall conclusions:

• If you opt for palliative care, your baby is most likely to live for between 1 and 14 days. You have around a 6-8% chance of your baby celebrating their first birthday.
• If you opt for intensive management, survival chances are increased by around 20%. Your baby has around a 25% chance of celebrating their first birthday.

Is there anything else that improves survival rates?

Yes. All the studies are fairly clear that the following improves survival for a baby:

• Being female
• Being born later

Some studies suggested that having a diaphragmatic hernia decreased survival. It also makes sense that any complex medical issues will decrease survival chances.

So if you have a girl born at 42 weeks with no diaphragmatic hernia, no significant medical problems, managed intensively, what are the chances she'll get to celebrate her first birthday? Well, likely better than 25%, and that has to be good news!

Diaphragmatic hernia and 39 weeks...
...so Rumer didn't get to her first birthday.