Mortality of Twins and Singletons

1
Mortality of Twins and Singletons

• Yin Bun Cheung, Ph.D.
• Paul Yip, Ph.D.
• Johan Karlberg, M.D., Ph.D.
• Readings

2
Objectives mortality patterns

• Understand the patterns of gestational
  age-specific neonatal mortality in twins and
  singletons.
• Appreciate the (non-) comparability between twins
  and singletons.

3
Objectives statistical models

• Learn a flexible way to handle interaction /
  effect-modification.
• Interpretation of a (logistic) regression model
  in different ways.

4
Mortality by gestational age

• Does the mortality difference between twins
  singletons depend on gestational age?
• Do twins and singletons have the same gestational
  age pattern of mortality?

5
Difficulties in research

• Sample size
• Referral bias
• Statistical adjustment / matching

6
A study based on Swedish Medical Birth Registry

• All births born in Sweden in 1982-1995.
• Includes 32,942 twins and 1.5 million singletons.
• Details in Reading 1.

7
Cumulative distribution of GA
8
Odds ratios of short GA in twins and singletons
P 9
Varying-coefficient model

• Mortality impact of twin pregnancy as a function
  of GA
• Log oddsa1b1?GAb2?GA2 (a2c1?GAc2?GA2)?Twin
  ...

10
Varying-coefficient model

• As a model of separate curves
• Log odds in singletons
• a1b1?GAb2?GA2
• Log odds in twins
• (a1a2)(b1c1)?GA(b2c2)?GA2

11
Birth weight SDS by GA
12
Size at birth in twins

• Growth restriction in twins concentrates in late
  pregnancy.
• Physical constraints in utero?
• Limited placental function?
• Selection bias?

13
Neonatal deaths per 1000
14
A varying-coefficient logistic regression model

• The impact of twin pregnancy as a quadratic
  function of GA.
• Adjusted for confounders, e.g. prior still-birth,
  smoking.
• With without adjustment for size at birth.

15
Log OR, fully adjusted
16
Log odds, fully adjusted
17
Is twin birth hazardous? Why?

• Twins had lower odds of death prior to 36 weeks
  of GA higher odds thereafter.
• Longer GA was related to lower mortality. But the
  decline was sharper in singletons than in twins.

18
Log OR, not adjusted for size at birth
19
Log odds, not adjusted for size at birth
20
The role of fetal growth and size at birth?

• Without adjustment for size at birth the log OR
  climbed up faster after around 34 weeks.
• Twins mortality reached its lowest point at 38
  weeks it turned upward after that.

21
Clinical interpretations

• Twins have an earlier development
• In utero environment in late pregnancy not good
  for twins
• Residual confounding

22
Optimal GA for twins

• The optimal gestational age for twins appeared to
  be 37-39 weeks in terms of neonatal mortality.
• This is earlier than singletons.

23
Readings

• Cheung YB, Yip P, Karlberg J. Mortality of twins
  and singletons by gestational age. Am J Epidemiol
  20001521107-16.
• Lie RT. Intersecting perinatal mortality curves
  by gestational age -- are appearances deceiving?
  Am J Epidemiol 20001521117-19.
• Cheung YB, Yip P, Karlberg J. Respond to Are
  appearances deceiving. Am J Epidemiol
  20001521120.