Ranibizumab safety in pregnancy
Reviewed by Sofia Rokerya

Vascular endothelial growth factor (VEGF) plays a pivotal role during pregnancy, and systemic anti-VEGF administration during this period should thus be avoided. VEGF is expressed in multiple embryonic and foetal tissues during development, with the highest levels found in the lung, kidney and heart. The increasing expression of this protein in placental tissues and foetal membranes throughout gestation suggests that it may play a role in embryofoetal and placental development and in the maintenance of placental vascular function during pregnancy. VEGF may also be involved in the regulation of amniotic fluid volume and composition. In animal studies, a low incidence of skeletal abnormalities and shortened supernumerary ribs was observed in monkey foetuses after the pregnant mothers were treated with 1mg/eye of ranibizumab. The 1mg/eye dose resulted in serum levels of ranibizumab up to 13 times higher than the Cmax levels predicted for single eye treatment in humans. Intravenous bevacizumab has also been shown to be embryotoxic and teratogenic when administered to rabbits, causing decreases in maternal and foetal body weights, and an increased incidence of foetal skeletal malformations. The authors report a case series of three pregnant women treated with ranibizumab. One of them had idiopathic choroidal neovascularisation (CNV) and an intravitreal ranibizumab injection was administered at 10 weeks post last menstrual period (LMP). A second injection was administered at 21 weeks post LMP. The second patient had myopic CNV and received an injection at 17 weeks post LMP. The third patient had CNV secondary to a punctuate inner choroiditis. An intravitreal injection of ranibizumab was performed at eight weeks post LMP. Cholestasis of pregnancy occurred at 35 weeks after LMP+6 days leading to an induced labour two weeks later. All three patients gave birth to healthy children at full term by post-vaginal delivery. No malformations or neonatal diseases were observed. Babies were of normal foetal size and weight. However, this does not qualify the treatment as safe. It has been advised to be used with great caution and should only be applied if visual function and / or anatomical exudation have worsened during follow-up. The benefit versus risk need to be highlighted with the patient and obtaining an informed, written consent from the patient is mandatory.

Safety of intravitreal injection of ranibizumab in early pregnancy.
Fossum P, Couret C, Briend B, et al.
EYE
2018;32:830-2.