6th CEN Conference

mRNA COVID-19 vaccination in pregnancy and risk of pregnancy loss: a progressive multistate model to account for time-dependent exposure

19 May 2026, 13:45

18m

Room 13 B

oral presentation Censored data 2

Speaker

Lukas Lohse (Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Clinical Pharmacology and Toxicology, Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy)

Description

The recently conducted observational Embryotox cohort study on mRNA COVID-19 vaccination aimed to assess the safety of mRNA COVID-19 vaccines in pregnancy. Here, we focus on the methodological approach used to assess the effect of the vaccination on adverse pregnancy outcomes such as spontaneous abortion and stillbirth. The data featured delayed study entry and cohort crossover as well as associated immortal time which had a substantial impact on the results if not appropriately modeled.
From contact date January 1st 2021 and including pregnancies with an estimated date of birth before October 2022 a final cohort of 8,146 prospectively ascertained pregnant women were vaccinated with an mRNA vaccine in pregnancy or up to 30 days before last menstrual period. Among them 1,478 were vaccinated only after study entry. The unvaccinated prospective comparison cohort consisted of 1,955 pregnant women. In the vaccinated cohort, 102 spontaneous abortions had been observed and 211 in the unvaccinated cohort.
To model time-dependent vaccination status and different pregnancy outcomes we used a progressive multistate model with unvaccinated/vaccinated as transient states and competing absorbing states for pregnancy outcomes split by previous transient state. Probability estimation based on the data via Aalen-Johansen was used to arrive at relative risk estimates. However, relative risks are more difficult to interpret as a consequence of the complex timing of events, where, e.g. spontaneous abortion may precede vaccination. To aid interpretation, we contrasted results with an overly simplified two-group comparison subject to immortal time bias and to a hypothetical probability estimation where vaccination does not impact hazards. We found that vaccination was associated with a smaller probability of spontaneous abortion. This observed protective association was substantially smaller than in the immortal time biased analysis and nicely illustrated in the comparison with the hypothetical scenario.
This work was funded by the German Federal Ministry of Health and the Paul-Ehrlich-Institute (PEI).

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