Outcomes of preterm birth

1
Outcomes of preterm birth

• Stefan Johansson
• Department of Neonatology, Karolinska university
  hospital
• Department of Medical Epidemiology and
  Biostatistics, Karolinska institutet
• Stockholm, Sweden

2
(No Transcript)
3
(No Transcript)
4
Studies of outcomes of preterm birth- subjected
to errors!
systematic errors
random errors
What are systematic and random errors?
5
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

6
BIG IS BEAUTIFUL
7
Studies of outcomes - systematic errors

• Selection bias
• Information bias
• Confounding

8
Studies of outcomes - selection bias

• The optimal study would be to include the worlds
  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!!

9
Studies of outcomes - selection bias

• Cardiovascular risk and running - new insight
• marathon runners.
• Low mortality among preterm infants
• infants in a specialized center

10
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.

11
Studies of outcomes - confounding

• Confounding meanssomething (measured or
  unmeasured) is important for the associations
  between you measurements.

Neonatal nurse
Pregnancy
12
Studies of outcomes - confounding

• The association is confounded by age of neonatal
  nurses.

Neonatal nurse
Pregnancy
13
Good design pays off
14
Exposures and outcomes of preterm infants

• 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

15
In addition cohort effects

• Neonatal intensive care is a new speciality.
• 1970s mechanical ventilation
• 1980s new treatment of premature lung
  disease maternal steriod treatment for
  threatening labour
• 1990s high frequency ventilation gentle
  nursing strategies treatment of
  pain nutrition
• Preterms born in the 60s, 70s, 80s and 90s do
  not represent the same group of people.

16
(No Transcript)
17
What do we know from the literature!?
18
Preterm birth and mortality - world-wide

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

Lawn et al, Lancet 2005365891-900
19
Contribution of preterm birth to infant mortality
Infant mortality in live born infants lt 37 weeks,
Canada 1992-1994
Relative risk 95 CI Etiologic fraction
lt 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
adjusted for age, parity, race, and education
Reference group infants born at term
Kramer et al, JAMA 2000284843
20
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 gt 32 weeks and lt1500
  grams
• two thirds occured during the first 24 hours

Callaghan et al, Pediatrics 20061181566
21
Gestational age and mortality - Sweden
Perinatal mortality () in Sweden 2003, by
gestational age.
22
Trend in mortality of infants lt 1500 grams
Horbar et al, Pediatrics 2002110143
23
Infant mortality related to preeclampsia
Basso et al, JAMA 20062961357
24
The impact of level-of-care on mortality
Liveborn infants Mortality Odds ratio 95 CI
Unadjusted university hospital county hospital 924 1320 14.2 10.3 1.00 0.70 0.54 - 0.90
Adjusted university hospital county hospital 924 1320 14.2 10.3 1.00 1.33 0.98 - 1.81
Johansson et al, Pediatrics 20041131230
25
The impact of level-of-care on mortality
Liveborn infants Mortality Odds ratio 95 CI
24 - 26 weeks university hospital county hospital 262 125 29.0 43.2 1.00 1.84 1.11 - 3.04
27 - 31 weeks university hospital county hospital 662 1195 8.3 6.9 1.00 1.09 0.74 - 1.61
Johansson et al, Pediatrics 20041131230
26
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.

27
What about outcome in surviving preterm infants?
28
Outcome in adults born preterm

• 166 adults BW lt1000 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 n20
• Autism n2
• Blindness n11
• Cognitive impairment n14

Saigal et al, JAMA 2006295667
29
Outcome in adults born preterm

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

lt1000 g Normal BW p-value
Total years ofcompleted eduaction 13.9 14.5 .02
Highest achievement .06
lt high school 17 12
high school 54 56
college 24 18
university 5 14
30
Outcome in adults born preterm

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

lt1000 g Normal BW p-value
Full time work 83 84 .85
Job classification .25
un-/semi-skilled 52 40
skilled, technical 35 41
management professional 13 20
31
Outcome in adults born preterm

• Independent living, marital status and parenthood

lt1000 g Normal BW p-value
Independent living 42 53 .19
Marital status .33
single 77 75
married 10 7
cohabitating 13 18
Parenthood 11 14 .36
32
Outcome in 6 year old children lt26 weeks

• Infants lt26 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, minimalfunctional impairment
• IQ between -1 and -2 SD
• Mild hearing impairment
• Squint or refractive error

Marlow et al, NEJM 20053529
33
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 lt 26w represent a new group of survivors?

34
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.