Abstract

In the statistical literature, the class of survival analysis models known as cure models has received much attention in recent years. Cure models seem not, however, to be part of the statistical toolbox of perinatal epidemiologists. In this paper, we demonstrate that in perinatal epidemiological studies where one investigates the relation between a gestational exposure and a condition that can only be ascertained after several years, cure models may provide the correct statistical framework. The reason for this is that the hypotheses being tested often concern an unobservable outcome that, in view of the hypothesis, should be thought of as occurring at birth, even though it is only detectable much later in life. The outcome of interest can therefore be viewed as a censored binary variable. We illustrate our argument with a simple cure model analysis of the possible relation between gestational exposure to paracetamol and attention-deficit hyperactivity disorder, using data from the Norwegian Mother, Father and Child Cohort Study conducted by the Norwegian Institute of Public Health, and information about the attention-deficit hyperactivity disorder diagnoses obtained from the Norwegian Patient Registry.

Highlights

  • Perinatal epidemiological studies investigating the possible effects of some gestational exposure on a postnatal condition can roughly be split into two categories

  • The association between prenatal marijuana exposure on neuropsychological conditions[1] and the association between prenatal exposure to pharmaceuticals and neurodevelopmental disorders belong to the second category

  • The present study was motivated by the hypothesis linking gestational exposure to paracetamol and an increased risk of neurodevelopmental disorders, attentiondeficit hyperactivity disorder (ADHD) in particular,[2,3,4,5] hypotheses that are pertinent examples of the latter category

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Summary

Introduction

Perinatal epidemiological studies investigating the possible effects of some gestational exposure on a postnatal condition can roughly be split into two categories. A consequence of opting for a survival analysis model is that the outcome is defined as the time to diagnosis, a convenient choice due to the availability of efficient survival analysis software, but that, we argue, can in many cases be an imprecise operationalisation of the outcome in view of the hypothesis being tested The reason for this is that in perinatal studies belonging to our second group, the hypotheses often concern an exposure that is only present during pregnancy, and the outcome of interest should be thought of as occurring when the effect of the exposure ceases to have an effect, that is, at birth. The aim of this application is to investigate whether our reading of the paracetamol–ADHD hypothesis finds empirical backing, and illustrate the fact that all three classes of models are likely to lead to rather similar conclusions about the paracetamol–ADHD hypothesis

The cure model and ADHD
The paracetamol–ADHD hypothesis
The standard cure model
Fitting logistic and Cox models to cure data
Data analysis
Discussion and concluding remarks
Remark 1
Remark 2
Findings
Remark 3
Full Text
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