1 Clinical Trials Centre, Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China.
2 Department of Paediatrics, University of Hong Kong, Pokfulam, Hong Kong, China.
3 Department of Statistics and Actuarial Sciences, University of Hong Kong, Pokfulam, Hong Kong, China.
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INTRODUCTION |
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As mentioned in the invited commentary, different perspectives continue to foster different interpretations of the crossover in mortality curves. A more in-depth biologic discussion is welcome, but it is not the focus of our paper and this reply. We attempted to make a comparison of the gestational age-specific mortality of twins and singletons by statistical adjustment for risk factors for short gestational duration. Professor Lie questioned this approach because gestational duration may be partly determined by unknown frailty factors that could escape from statistical adjustment. This worry is certainly justified. Although there is no commonly accepted way for measuring goodness-of-fit or residual variation in the context of logistic regression, our analysis based on the Hosmer-Lemeshow test suggested that the known factors fit the gestational duration data sufficiently (2, table 1). We proceeded to further analysis only after seeing this support of no important residual confounding. As Professor Lie agreed, our findings that adjustment for known risk factors did not remove the crossover in mortality curves are illuminating. Had we used the method of "relative gestational age," we would be still in the dark about whether the crossover was attributable to these known risk factors of short gestational duration. Of course, the interpretation of a goodness-of-fit test is again debatable, and a continued search for factors of prematurity is needed.
Professor Lie reviewed and demonstrated the method of "relative gestational age." The method is attractive and the results seem to make sense. However, the rationale of this method is elusive. It gave us an impression that the x-axis of the figures was modified to provide sensible results. We wonder if the method is partly justified by the results instead of the other way around. Furthermore, whether twin and singleton fetuses have different pathways of development has not been discussed. For instance, twins on average have a gestational duration of about 3 weeks less than singletons (2, figure 1). Is this reduction in gestational period not a developmental disadvantage? Is it then biologically justified to compare twins and singletons with different (absolute) gestational ages?
To paraphrase Professor Lie, the problems of analyzing and interpreting intersecting mortality curves have only begun to be addressed. We are delighted to see the commentary and we look forward to more research and discussion in this area.
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NOTES |
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REFERENCES |
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