Increasing use of newer antiseizure medication during pregnancy: An observational study with special focus on lacosamide

Hoeltzenbein, Maria; Slimi, Sofia; Fietz, Anne‐Katrin; Stegherr, Regina; Onken, Marlies; Beyersmann, Jan; Dathe, Katarina; Schaefer, Christof

doi:10.1016/j.seizure.2023.02.015

Cited by 15 publications

(16 citation statements)

References 46 publications

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“…These crude event proportions are no valid probability estimates, as they neglect the left truncation 2 . Compared with Hoeltzenbein et al, 1 we excluded one stillbirth for technical purposes. Furthermore, we considered a twin pregnancy resulting in two livebirths as one event.…”

Section: Resultsmentioning

confidence: 99%

“…Consequently, in the published analysis of the lacosamide data, 1 we decided to report the postpone approach. In general, the choice between the ignore early approach and the postpone approach depends on the application and the focus of estimation.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, a probability of 22.64% obtained with the standard Aalen–Johansen estimator resulted from one event while the risk set was still small. Consequently, in the published analysis of the lacosamide data, 1 we decided to report the postpone approach. In general, the choice between the ignore early approach and the postpone approach depends on the application and the focus of estimation.…”

Section: Discussionmentioning

confidence: 99%

“…Lacosamide is one of the most often used newer antiseizure medications, but information about its use in pregnancy is limited. A recent study by the Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy (TIS Berlin) focused on the safety of lacosamide exposure during pregnancy 1 . Until larger prospective studies are available, analysis of small cohorts could provide at least some preliminary data for counseling inadvertently exposed women and might identify signals of possible teratogenicity.…”

Section: Introductionmentioning

confidence: 99%

“…A recent study by the Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy (TIS Berlin) focused on the safety of lacosamide exposure during pregnancy. 1 Until larger prospective studies are available, analysis of small cohorts could provide at least some preliminary data for counseling inadvertently exposed women and might identify signals of possible teratogenicity. However, with small sample sizes, choosing the correct statistical analysis method is especially important to avoid wrong conclusions about drug safety.…”

Section: Introductionmentioning

confidence: 99%

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How to account for early overly small risk sets in the analysis of pregnancy outcome data?—Comparison of different methods for stabilizing the Aalen‐Johansen estimator

Stegherr,

Fietz,

Hoeltzenbein

et al. 2023

Pharmacoepidemiology and Drug

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PurposeIn analyzing pregnancy data concerning drug exposure in the first trimester, the risk of spontaneous abortions is of primary interest. For estimating the cumulative incidence function, the Aalen–Johansen estimator is typically used, and competing risks such as induced abortion and livebirth are considered. However, the delayed study entry can lead to overly small risk sets for the first events. This results in large jumps in the estimated cumulative incidence function of spontaneous abortions or induced abortions using the Aalen–Johansen estimator, and consequently in an overestimation of the probability.MethodsSeveral approaches account for early overly small risk sets. The first approach is conditioning on the event time being greater than the event time causing the large jump. Second, the events can be ignored by censoring them. Third, the events can be postponed until a large enough number is at risk. These three approaches are compared.ResultsAll approaches are applied using data of 54 lacosamide‐exposed pregnancies. The Aalen–Johansen estimate of the probability of spontaneous abortion is 22.64%, which is relatively large for only three spontaneous abortions in the dataset. The conditional approach and the ignore approach have an estimated probability of 7.17%. In contrast, the estimate of the postpone approach is 16.45%. In this small sample, bootstrapped confidence intervals seem more accurate.ConclusionsIn the analyses of pregnancy data with rare events, the postpone approach is favorable as no events are excluded. However, the approach that ignores early events has the narrowest confidence interval.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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