Outcomes of preterm birth Stefan Johansson Department of Neonatology, Karolinska university hospital Department of Medical Epidemiology and Biostatistics,

Outcomes of preterm birth

Stefan Johansson

Department of Neonatology, Karolinska university hospital

Department of Medical Epidemiology and Biostatistics, Karolinska institutet

Stockholm, Sweden

25 October 2006Stefan Johansson 2



Studies of outcomes of preterm birth- subjected to errors!

systematic errors

random errors

What are systematic and random errors?


Studies of outcomes - random errors

Measurement errors may be random few meaurements - the average value could be wrong

Outcome differences may be a random finding uneven sampling of study subjects may result in spurious results

Differences in outcomes are not detected study sample to small


BIG IS BEAUTIFUL


Studies of outcomes - systematic errors

Selection bias

Information bias

Confounding


Studies of outcomes - selection bias

The optimal study would be to include the world’s entire population, but every study have to select their subjects.

What happens if the selected study subjects are not similar to the general population?

RISK OF SELECTION BIAS!!


Studies of outcomes - selection bias

”Cardiovascular risk and running - new insight” marathon runners.

”Low mortality among preterm infants” infants in a specialized center


Studies of outcomes - information bias

The collection of information is not properly done; misclassification: a preterm infant has several infections but only one is recorded.

Misclassification can be… non-differential: the error is the same for all study subjects differential: the error is not the same for different study groups

Recall bias is a common type of differential information bias: Cancer patients report more stress than healthy control, but both

groups are similarly stressed according to objective stress tests.


Studies of outcomes - confounding

Confounding means…something (measured or unmeasured) is important for the associations between you measurements.

Neonatal nurse Pregnancy


Studies of outcomes - confounding

The association is confounded by age of neonatal nurses.

Neonatal nurse Pregnancy

Young female


Good design pays off


Parental characteristics Hospital setting Gestational age Apgar scores Blood testing X-rays Lung diseases Blood pressure Nutrition Infections Drugs Neurological symtoms Noise

Death Motor skills Vision Hearing Blood pressure Blood glucose Allergies Cognitive functions Academic performace Life span

Exposures and outcomes of preterm infants


In addition… cohort effects…

Neonatal intensive care is a ”new” speciality. 1970’s mechanical ventilation 1980’s new treatment of premature lung disease

maternal steriod treatment for threatening labour 1990’s high frequency ventilation

gentle nursing strategiestreatment of painnutrition

Preterms born in the 60’s, 70’s, 80’s and 90’s do not represent the same group of people.


What do we know from the literature!?


Preterm birth and mortality - world-wide

One million infants born preterm die during the first four weeks (26% of neonatal mortality).

Asphyxia

Preterm birth Sepsis

Congenital

Tetanus

DiarrheaOther

Lawn et al, Lancet 2005;365:891-900


Contribution of preterm birth to infant mortality

Relative risk [95% CI]* Etiologic fraction %

< 28 weeks 126,7 [124,0-129,5] 35,7

28-31 weeks 16,2 [15,4-17,0] 7,3

32-33 weeks 6,6 [6,1-7,0] 3,2

34-36 weeks 2,9 [2,8-3,0] 6,3

Infant mortality in live born infants < 37 weeks, Canada 1992-1994

*adjusted for age, parity, race, and education Reference group: infants born at term

Kramer et al, JAMA 2000;284:843


Contribution of preterm birth to infant mortality

34% of infants deaths attributed to preterm birth (USA 2002)

Of deaths attributed to preterm birth 95% of occured in infants > 32 weeks and <1500 grams two thirds occured during the first 24 hours

Callaghan et al, Pediatrics 2006;118:1566


Gestational age and mortality - Sweden

0

10

20

30

40

50

60

-27 wks 28-30 31-33 34-36 37-39 40-42 43-45

Perinatal mortality (%) in Sweden 2003,by gestational age.


Trend in mortality of infants < 1500 grams

Horbar et al, Pediatrics 2002;110:143


Infant mortality related to preeclampsia

Basso et al, JAMA 2006;296:1357


The impact of level-of-care on mortality

Liveborn infants

Mortality Odds ratio 95% CI

Unadjusted- university hospital- county hospital

9241320

14.2 %10.3 %

1.000.70 0.54 - 0.90

Adjusted- university hospital- county hospital

9241320

14.2 %10.3 %

1.001.33 0.98 - 1.81

Johansson et al, Pediatrics 2004;113:1230


The impact of level-of-care on mortality

Liveborn infants

Mortality Odds ratio 95% CI

24 - 26 weeks- university hospital- county hospital

262125

29.0 %43.2 %

1.001.84 1.11 - 3.04

27 - 31 weeks- university hospital- county hospital

6621195

8.3 %6.9 %

1.001.09 0.74 - 1.61

Johansson et al, Pediatrics 2004;113:1230


What kind of picture emerges…

Many preterm infants die. Mortality risk is inversely associated with gestation/birth weight. Preterm birth contribute greatly to infant mortality rates.

Mortality among the most immature infants has decreased. Preeclampsia related mortality has decreased. Centralizing care of the most immature infants may improve

survival rates.


What about outcome in surviving preterm infants?


Outcome in adults born preterm

166 adults BW <1000 g vs 145 adults with normal BW,born 1977-1982 in Canada.

Mean gestational age 27 weeks.

Neurosensory impairment/-s identified in 40 adults (27%) Cerebral palsy n=20 Autism n=2 Blindness n=11 Cognitive impairment n=14

Saigal et al, JAMA 2006;295:667



Educational attainments was similar in both groups(”highest achievement” excluded those with neurosensory impairment)

<1000 g Normal BW p-value

Total years ofcompleted eduaction

13.9 14.5 .02

Highest achievement .06

< high school 17% 12%

high school 54% 56%

college 24% 18%

university 5% 14%



Current employment(”Job classification” excluded those with neurosensory impairment)


Full time work 83% 84% .85

Job classification .25

un-/semi-skilled 52% 40%

skilled, technical 35% 41%

management professional

13% 20%



Independent living, marital status and parenthood


Independent living 42% 53% .19

Marital status .33

single 77% 75%

married 10% 7%

cohabitating 13% 18%

Parenthood 11% 14% .36


Outcome in 6 year old children <26 weeks

Infants <26 weeks, born in the UK in 1995.

Severe disability defined as Cerebral palsy IQ less than -3 SD Profound hearing loss Blindness

Mild disability defined as Neurologic signs, minimal

functional impairment IQ between -1 and -2 SD Mild hearing impairment Squint or refractive error

Marlow et al, NEJM 2005;352:9


What kind of picture emerges…

Studies of adults born preterm – good outcomes? Studies of children born preterm – poor outcomes?

Why contradicting results… different populations with different different health care systems? a reversed ”healthy worker” effect -

children born < 26w represent a new group of survivors?


Conclusions

Outcome of preterm birth… consider methods! High mortality, although decreasing rates/risks.

Conflicting results on long term outcome.

More knowledgeneeded, to predictand promote goodoutcomes.

Documents

Outcomes of preterm birth Stefan Johansson Department of Neonatology, Karolinska university hospital Department of Medical Epidemiology and Biostatistics,