Topical chloramphenicol not associated with birth defects

By Laird Harrison

The babies of women who use topical chloramphenicol during pregnancy do not appear to run an increased risk of congenital malformations, researchers say.

An analysis of births to Danish mothers picking up topical prescriptions for the antibiotic during pregnancy found a major malformation rate of 3.50% compared to 3.49% for unexposed Danish mothers, according to Vilde Thomseth, MD, of the Ophthalmology Department at Golstrub Hospital in Glostrup, Denmark and colleagues at three other Danish centres.

The researchers published their findings in Acta Ophthalmologica.  

Previous studies have shown an association between large doses of systemic chloramphenicol and grey baby syndrome.

In rats, chloramphenicol exposure in early pregnancy is associated with increased rates of omphalocele and umbilical hernia. In chick embryos exposed to the drug, splanchnopleura and neural tube defects have been reported.

And some fatal cases of aplastic anaemia have been associated with long-term use of chloramphenicol eye drops.

But Dr. Thomseth and her colleagues could not find any record of a study determining the risk of using the antibiotic as a topical treatment for eye infections during human pregnancies.

So they used the Danish Medical Birth Registry to identify 977 706 births from 1997 to 2011. They excluded records with coding errors and 4119 stillbirths. That left 966 372 births with adequate information.

Using Danish personal identification codes, they linked these births to information on drug redemptions from the Danish National Prescription Registry and congenital malformations from the Danish National Hospital Register.

In this way, the researchers identified 6024 women who redeemed at least one prescription for chloramphenicol eye drops or eye ointment during the first trimester of pregnancy.

On average, women who redeemed these prescriptions were older, more educated, wealthier, more likely to be married, and had records of more pregnancies compared to women who did not redeem such prescriptions. But the researchers found no differences in smoking or pre-pregnancy body mass index.

Fewer women picked up these prescriptions during pregnancy than in the three months prior to or following their pregnancies. In fact, 30% fewer women redeemed topical chloramphenicol prescriptions in the first trimester of their pregnancies compared to the previous three months.

This could suggest that physicians are reluctant to prescribe the drug, or that women are reluctant to take it, during pregnancies, Dr. Thomseth and her colleagues write.

Among the babies of the women who picked up topical chloramphenicol prescriptions during the first trimesters of their pregnancies, 211 (3.50%) had a diagnosis of a major congenital malformation. Among the babies of the other women, 33476 (3.49%) had such diagnoses, suggesting no association between the drug use and the malformations.

When the researchers looked at specific types of malformation, they likewise couldn’t find any associations.

The findings are similar to a previous small case-controlled study that found no increased risk of congenital malformations associated with oral chloramphenicol use during pregnancy, the researchers write.

Dr. Thomseth and her colleagues acknowledge a couple of limitation of the current study. First, a lack of information on the duration and dosage of use of the chloramphenicol the women picked up. In fact, they don’t know if the women used the prescriptions at all.

Second, despite its size, the study might not have sufficient power to compare rates of rare malformations.

Still the study at least partially fills a gap in knowledge about the risk of chloramphenicol during pregnancy, the researchers say. And judging from the drop in redemptions of prescriptions during the first trimester, that knowledge may have some importance to physicians and their patients, they write.