Association of Topical Prostaglandin Analogue Use With Risk of Spontaneous Abortion

Abstract

rostaglandin analogues (PGAs) are one of the major pharmacological classes of glaucoma drugs used for the management of glaucoma in female individuals of reproductive age. Topical PGAs have been reported to have systemic effects from absorption, and pharmacologic data indicate PGAs can lead to uterus contraction. 1 A recent case-series analysis of the US Food and Drug Administration Adverse Event Reporting System database and the Japanese Adverse Drug Event Report database showed elevated reports of miscarriages with PGA use (reporting odds ratio, 4.35; 95% CI, 1.98-9.54; and reporting odds ratio, 12.84; 95% CI, 3.06-53.86, respectively). 2 The limitation of adverse reaction databases in general is reporting bias; lack of a proper control group means the true risk of any given adverse event is over-estimated. However, although these databases are limited in demonstrating a causal link, the hypothesis generated from this study, given the prescription patterns of these drugs in pregnant individuals with glaucoma, warrants serious attention. Thus, we undertook study with the hypothesis that use of topical PGAs is not associated with an increased risk of spontaneous abortion.

Clinical Dilemma—Topical Prostaglandin Use in Glaucoma During Pregnancy

“…However, this underreporting would likely be similar in both groups. Notably, the pregnancy rate in the work by Etminan and colleagues was lower in patients with prostaglandin prescriptions (6.7% vs 20.6%). The statistical significance of this difference was not discussed.…”

“…Glaucoma management during pregnancy presents a unique clinical challenge because of potential risks to the fetus and the lack of large-scale safety and efficacy data on glaucoma treatment in this population. 1 A 2007 survey conducted in the United Kingdom indicates uncertainty among ophthalmologists regarding glaucoma management during pregnancy. 2 Approximately onethird of the responding ophthalmologists reported having experiences treating patients with glaucoma during pregnancy.…”

“…In response to a recent report from Japan on pregnancy loss with topical prostaglandins and the FDA Adverse Event Reporting System database, Etminan and colleagues found a creative way to examine this risk in a large data set. The authors argued that although the spontaneous reporting system is a vital pharmacovigilance tool, it tends to overestimate the risk of an adverse effect because of the lack of an appropriate control group.…”

“…The study by Etminan and colleagues represents the first large-scale analysis that includes a control cohort with a similar risk profile. Despite this strength, the authors acknowledged the study’s limitations, including the lack of information on gestational age, race and ethnicity, and socioeconomic risk factors.…”

Pregnancy outcomes in the medical management of glaucoma: An international multicenter descriptive survey

“…5 Clinical safety regarding glaucoma medications has historically relied on data from small case series studies or animal models. 3 Recent studies examining safety databases, [6][7][8] analyzing a claims database, 9 and utilizing phone interviews through a teratology monitoring system 10 have provided additional human safety information, but there remains a need for further human data to better characterize the fetal safety profile of these medications. The present study aims to characterize potential fetal risk of glaucoma medications using a descriptive survey to obtain patient-reported pregnancy outcomes and complications.…”