Association between Obstetric Complications and Intravitreal Anti-Vascular Endothelial Growth Factor Agents or Intravitreal Corticosteroids

Abstract

This nationwide population-based cohort study aimed to describe the use of intravitreal injections (IVTs) of anti-vascular endothelial growth factor (anti-VEGF) agents and corticosteroids in pregnant women in France and to report on the incidence of obstetric and neonatal complications. All pregnant women in France who received any anti-VEGF or corticosteroid IVT during pregnancy or in the month preceding pregnancy from 1 January 2009 to 31 December 2018 were identified in the national medico-administrative databases. Between 2009 and 2018, there were 5,672,921 IVTs performed in France. Among these IVTs, 228 anti-VEGF or corticosteroid IVTs were administered to 139 women during their pregnancy or in the month preceding their pregnancy. Spontaneous abortion or the medical termination of pregnancy occurred in 10 women (16.1%) who received anti-VEGF agents and in one (3.1%) of the women who received corticosteroids (p = 0.09). This is the first national cohort study of pregnant women treated with anti-VEGF or corticosteroid IVTs. We found a high incidence of obstetric complications in pregnant women treated with anti-VEGF or corticosteroid IVTs but could not demonstrate a statistically significant association between the intravitreal agents and these complications. These agents should continue to be used with great caution in pregnant women.

Idiopathic Choroidal Neovascularization in Pregnancy: A Case Report

“…Fetal lesions or fetal distress was reported in 11 (17.7%) cases receiving anti-VEGF agents vs. four (12.5%) receiving CS. Multivariant analysis showed that anti-VEGF agents were not associated with a higher risk of obstetric and neonatal complications when compared with CS [ 9 ].…”

“…Contradictory to this proposed association is the prevalence of an already high miscarriage rate (30-40%) among otherwise healthy females. Others have reported uneventful pregnancies with no developmental defects after IVT anti-VEGF administration in pregnancy, though long-term follow-up data is currently not available [ 4 , 9 ]. Administration of IVT anti-VEGF during the embryogenic phase in an otherwise undiagnosed pregnancy has also shown variable results [ 14 , 15 ].…”

Idiopathische choroidale Neovaskularisation in der Schwangerschaft: ein Fallbericht

“…Eine Studie von Ben Ghezala et al [9] ist die größte Zusammenfassung solcher Fallberichte aus Frankreich. Die Arbeit berichtet von 228 intravitrealen Anti-VEGF- oder KS-Injektionen bei 139 Patientinnen entweder während der Schwangerschaft oder im Monat vor der Schwangerschaft: 93 Frauen erhielten nur den Anti-VEGF-Wirkstoff, 39 erhielten nur das KS und 7 erhielten beides.…”

“…Fötale Läsionen oder fötaler Stress wurden bei 11 der Frauen (17,7%), die eine Anti-VEGF-Injektion erhielten, berichtet, während dies bei 4 Frauen (12,5%) der Fall war, die eine KS-Injektion erhielten. Die multivariate Analyse zeigte, dass die Anti-VEGF-Wirkstoffe im Vergleich zu KS nicht mit einem höheren Risiko für obstetrische oder neonatale Komplikationen in Zusammenhang stehen [9].…”

“…Im Widerspruch zu dieser Assoziation steht die Prävalenz einer an sich hohen Fehlgeburtsrate (30–40%) bei ansonsten gesunden Frauen. Andere berichteten von ereignislosen Schwangerschaften ohne Entwicklungsstörungen nach einer in­travitrealen Anti-VEGF-Gabe während der Schwangerschaft, wobei derzeit keine langfristigen Nachbeobachtungsdaten verfügbar sind [4, 9]. Die Gabe von intravitrealem Anti-VEGF während der embyrogenen Phase in einer ansonsten unauffälligen Schwangerschaft zeigte ebenfalls unterschiedliche Ergebnisse [14, 15].…”