Assignment: For a specific exposure-outcome combination of interest to you, specify which lifecourse model is likely most appropriate and why you think this is the case. Describe the regression models you could use to test your hypothesis. Are there any possible data sets in which this test could be conducted, and if so, what concerns would you have about interpreting your proposed test of the lifecourse model?
Exposure: malaria in pregnancy
Outcome: adverse birth outcome, including premature birth, low birthweight, and neonatal mortality (i.e. neonatal death within the first 28 days).
Hypothesis: I think relatively little is known of the risk of malaria in pregnancy in the first trimester and how that can lead to increased risks of adverse birth outcomes. Additionally, it is not known known if there is a cumulative effect of the exposures (which I am guessing there is) and if being protected in your third trimester would completely reduce the risk of adverse birth outcomes? My hypothesis is that although there may be critical windows where infection may induce the greatest harm, protection during the 1st trimester vs. 2nd trimester vs. 3rd trimester may have different effects.
Proposed model: To study my hypothesis, I believe that the social mobility model would be an appropriate model to use to study this outcome including interaction terms for each of the trimesters. However, since little is known about this topic, I wonder if I can’t test for the different hypotheses using data?
Cohort: We would need to use a large cohort study of women at reproductive age and include all women who have conceived during follow-up and closely monitor their pregnancy until delivery and 28 days after to assess neonatal death. I think these cohorts are far and few, and I can only think of cohorts (i.e. randomized control trials) that have enrolled women usually late in their first trimester (~12 weeks). If anyone knows of an ideal cohort, let me know!
Potential concerns:
- Misclassification bias of the exposure. Current diagnostic methods are highly sensitive to diagnosing malaria, however most tests are done using peripheral blood. Pregnant women can clear malaria parasitemia in the blood (given they have a functional immune system), but parasites accumulative in the placental, where it can go undetected until delivery. By testing for placental malaria, you can diagnose whether a woman has an active or past infection, but timing of the past infection cannot be determined.
- Large sample size of variable women to accommodate testing of effect modification. Say we are studying the exposure at 3 time periods—first, second, and third trimester, where we denote the outcome of a woman who was infected in her first trimester, but not in her second would be Y100. We would a sufficient N of women for all 8 different combinations of exposure.