Assessing the effect of vaccine on spontaneous abortion using time-dependent covariates Cox models.
OBJECTIVE
In studying the safety of vaccine for influenza A (H1N1) given during pregnancy, spontaneous abortion (SAB) is one of the important points to consider. Because women may receive the vaccine any time during their pregnancy, evaluation of the effect of the vaccine on SAB should only take place after vaccination and in the risk window for SAB, that is, the first 20 weeks of gestation. In addition, when such studies are conducted through pregnancy registries where recruitment occurs after pregnancy recognition, the accrued subjects are left truncated in the sense that they are not followed from the start of pregnancy.


METHODS
As previously reported, left truncation needs to be properly handled using survival analysis methods to avoid bias. In the context of time-dependent vaccine exposure, a time-dependent covariate Cox model can be used to simultaneously take into account the left truncation and the vaccine exposure timing.


RESULTS
In this communication, we illustrate the approach using the Vaccine and Medication in Pregnancy Surveillance System data. We explain in details how the model is fitted using different software.


CONCLUSIONS
We recommend survival analysis methods together with collection of necessary data to study the effects of vaccine on SAB.
Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA, USA. rxu@ucsd.edu
Ronghui
R
Xu
Yunjun
Y
Luo
Christina
C
Chambers
D000022:Abortion, Spontaneous / Q000453:epidemiology*; D005260:Female; D005865:Gestational Age; D006306:Health Surveys; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D011247:Pregnancy; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors
D007252:Influenza Vaccines