Mortality of Twins and Singletons Yin Bun Cheung, Ph.D. Paul Yip, Ph.D. Johan Karlberg, M.D., Ph.D. Readings

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

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

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?

Difficulties in research Sample size Referral bias Statistical adjustment / matching

A study based on Swedish Medical Birth Registry All births born in Sweden in Includes 32,942 twins and 1.5 million singletons. Details in Reading 1.Reading 1

Cumulative distribution of GA

Odds ratios of short GA in twins and singletons * P<0.05

Varying-coefficient model Mortality impact of twin pregnancy as a function of GA: Log odds=a1+b1  GA+b2  GA 2 + (a2+c1  GA+c2  GA 2 )  Twin+...

Varying-coefficient model As a model of separate curves: Log odds in singletons: a1+b1  GA+b2  GA 2 Log odds in twins: (a1+a2)+(b1+c1)  GA+(b2+c2)  GA 2

Birth weight SDS by GA

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

Neonatal deaths per 1000

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.

Log OR, fully adjusted

Log odds, fully adjusted

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.

Log OR, not adjusted for size at birth

Log odds, not adjusted for size at birth

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 it’s lowest point at 38 weeks; it turned upward after that.

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

Optimal GA for twins The optimal gestational age for twins appeared to be weeks in terms of neonatal mortality. This is earlier than singletons’.

Readings 1Cheung YB, Yip P, Karlberg J. Mortality of twins and singletons by gestational age. Am J Epidemiol 2000;152: Am J Epidemiol 2000;152 2Lie RT. Intersecting perinatal mortality curves by gestational age -- are appearances deceiving? Am J Epidemiol 2000;152: Am J Epidemiol 2000;152 3Cheung YB, Yip P, Karlberg J. Respond to “Are appearances deceiving”. Am J Epidemiol 2000;152:1120.Am J Epidemiol 2000;152