Systemic use of corticosteroids has been reported to cause several abnormalities in the offspring. An increased risk of stillbirth has been reported with the use of systemic prednisolone during pregnancy. Intrauterine growth retardation and adrenal insufficiency have been reported in newborns of mothers who have been treated with intensive systemic corticosteroid therapy during pregnancy.
The fetal effect of topically administered corticosteroids to the pregnant woman is unknown. Animal studies have noted developmental and teratogenic effects with topical corticosteroids. Ballard et al studied the effect of three topically applied corticosteroids (dexamethasone, hydrocortisone, and prednisolone) in pregnant mice and found an association between cleft lip and palate and the use of corticosteroids. The results indicated a higher incidence of both cleft palates and sex organ abnormalities in fetuses of pregnant mice treated with these topical corticosteroids. In addition, there appeared to be a dose-related response in the width of the cleft palate among fetuses in the dexamethasone and prednisolone treated groups. Kasirsky et al reported significant fetal anomalies with the topical use of hydrocortisone, dexamethasone, and cortisone in rabbits.
Ophthalmic corticosteroids, such as prednisolone acetate and prednisolone sodium phosphate, have a Pregnancy Category C rating. No studies have been performed regarding the effects of topically applied corticosteroids on the nursing infant. It is unknown whether the topical ocular administration of corticosteroids could result in detectable levels in breast milk. However, corticosteroids administered systemically are present in breast milk in small quantities and could suppress growth or interfere with endogenous production. Given the potential for serious adverse reactions in nursing infants, corticosteroids likely should be avoided during nursing.
No known congenital defects have been reported with the use of erythromycin and polymyxin B. A study evaluating the intravenous use of parenteral gentamicin, streptomycin, tobramycin, and oral neomycin in pregnant women reported no association of teratogenic abnormalities with aminoglycoside use. Animal studies have shown a higher risk of hearing loss and nephrotoxicity after systemic aminoglycoside administration, but the relevance of these findings to the use of clinical doses in human pregnancy is unknown.
An increased incidence of cleft palate and other bony abnormalities have been seen in pregnant mice and rats that have received oral sulfonamides in doses 7 to 25 times the usual human dose. Systemic sulfonamides administered during the third trimester of pregnancy may cause hyperbilirubinemia in infants.
Systemic tetracycline can cause the discoloration of primary teeth in the offspring of mothers who receive the antibiotic after the third month of pregnancy.
No teratogenic effects have been noted in animal studies with the use of ophthalmic fluoroquinolones, including ciprofloxacin (Ciloxan), ofloxacin (Ocuflox), levofloxacin (Quixin), moxifloxacin (Vigamox), and gatifloxacin (Zymar). Decreased fetal body weights and delayed skeletal development were noted in animal studies with several of the fluoroquinolones, but this was seen with doses significantly higher than the recommended human ophthalmic dose.
The topical ophthalmic aminoglycosides (gentamicin, neomycin), polymyxin B, sulfonamide ophthalmic preparations, and fluoroquinolones are Pregnancy Category C. Erythromycin is Pregnancy Category B. Tetracycline is Pregnancy Category D. Systemic erythromycin and tetracycline are known to be excreted into breast milk. Ciprofloxacin and gatifloxacin have been measured in the breast milk of rats. Ciprofloxacin has also been reported in human breast milk after oral administration. The American Academy of Pediatrics has classified erythromycin, gentamicin, tetracycline, and ciprofloxacin as “maternal medications usually compatible with breast-feeding.”
Therapy for Choroidal Neovascularization
Fortunately, choroidal neovascularization is infrequently encountered in women of child-bearing age. The following describes information regarding the pharmacotherapy of choroidal neovascularization during pregnancy.
There are no published human studies of pregnancy outcomes after exposure to verteporfin. Studies in rat dams demonstrated an increased incidence of anophthalmia or microphthalmia in the rat fetuses with doses greater than or equal to 10 mg/kg/day. One human case report describes the inadvertent exposure to verteporfin therapy in the third week of pregnancy without any adverse effects on the pregnancy and neonatal outcome. Verteporfin has a Pregnancy Category C rating.
No human studies of pregnancy outcomes after exposure to pegaptanib have been published. Studies in mice revealed no maternal or fetal anomalies with intravenous administration of 7000 times the recommended human ophthalmic dose. Pegaptanib has a Pregnancy Category B rating.
No human studies have been conducted with the use of bevacizumab in pregnancy. The product information for Avastin notes that it may disrupt angiogenesis during fetal development resulting in adverse effects on pregnancy. Studies in rabbits given twice the recommended human dose resulted in teratogenic effects. Bevacizumab has a Pregnancy Category C rating.
Neither animal nor human studies have been performed with ranibizumab. Ranibizumab has a Pregnancy Category C rating.