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dcyphr | Chloroquine and hydroxychloroquine during pregnancy: what do we know?

Abstract

This paper discusses information from several previously conducted studies on the potentially negative effects of chloroquine and hydroxychloroquine on pregnant women. It discusses the potential risks which arise from the medications’ long half lives and prolonged exposure to them. Risks coming from eye, ear, and adrenal accumulation are mentioned. Overall findings are reassuring, suggesting that the risk for developmental issues, premature birth, or low birth weight do not increase from either drug. 


Introduction

Hydroxychloroquine and chloroquine’s half lives can reach up to two months, meaning patient exposure to either drug can continue long after stopping its intake. Considering these half lives and recent widespread discussion about the two medications’ use as a COVID therapeutic, this study draws attention to potential risks they may pose for pregnant women. Negative side effects, such as ocular damage (sometimes irreversible), have been reported in the past. The question is whether such problems can arise in utero.     


Methods

The first experiment which is referenced addresses potential ocular, aural, and adrenal problems caused by chloroquine. Tests were conducted on mice, rats, and monkeys, administering very high doses (greater than 250mg/kg). 

Next, three studies on groups of 169, 130, and 774 women were referenced. These groups were exposed to chloroquine during their first trimester of pregnancy. The 169 patient group involved 300mg of chloroquine being administered once a week as a malaria chemo suppressant. The other two studies involved a 25mg/kg dose over the course of three days followed by 300mg of chloroquine given weekly. This section also mentions studies from 2015 and 2018 about teratogenicity (developmental abornmalities) and premature birth in relation to hydroxychloroquine. 

Lastly several studies analyzing potential retinal degeneration due to in utero exposure to chloroquine are cited. A 2011 case involved a child prenatally exposed to methotrexate and chloroquine. Other cases looked at ocular damage occurring in groups of 588 and 246 children, with data being gathered about drug dose and duration of use. 


Results

The experiments conducted on the animals mentioned above present several potential side effects of chloroquine. High dosage (greater than 250mg/kg) was associated with microphthalmia and anophthalmia (infant born with one or two abnormally small eyes or with one or both eyes being missing). Additionally, other in vitro and in vivo tests linked chloroquine to genetic mutations and chromosomal damage. 

The human studies on first trimester pregnant women did not connect chloroquine to a heightened risk of congenital abnormalities, utero death, or low birth weight. The studies about hydroxychloroquine did not suggest that it causes a larger risk of teratogenicity, pregnancy termination, or premature birth. Additionally, no significant risk of child eye abnormalities due to either drug was found.

Discussion

The clinical data for both drugs suggests that they do not pose serious risk for pregnant women and their children. With this being said, many of the studies referenced discuss the need for further follow up and the need for larger sampling groups. The long half life of the drugs is significant, as side effects may develop well after their intake is terminated. The paper urges that the medications be administered only when their benefit is clear and that frequent screening and precautions be taken.