Do some antibiotics really double the risk of miscarriage?

Some common types of antibiotic may double the risk of miscarriage in early pregnancy, according to research at the University of Montreal in Quebec. (But see our analysis below.)

The researchers found that the drugs (including antibiotics in the quinolones, macrolides and tetracyclines classes) appeared to raise the chance of miscarriage by between 60 and 100 per cent. However, neither nitrofurantoin nor erythromycin (common medications for a urinary tract infection) was linked to any increased risk.

The study, published in the Canadian Medical Association Journal, looked at data from 8,702 miscarriage cases and compared this with information about the medication the women were taking during their pregnancy.

Dr Anick Bérard, the study’s lead author, said: ‘Infections are prevalent during pregnancy. Although antibiotic use to treat infections has been linked to a decreased risk of prematurity and low birth weight in other studies, our investigation shows that certain types of antibiotics are increasing the risk of spontaneous abortion, with a 60 per cent to twofold increased risk.

‘The increased risk was not seen for all antibiotics, which is reassuring for users, prescribers and policymakers.’

Instant analysis
This was a case-control study assessing correlation between first trimester miscarriage and the use of antibiotics in early pregnancy. The study design is not sufficient to establish direct causality.

About 182,000 pregnancies met the study criteria; patients who had experienced miscarriage were matched with those who had not experienced miscarriage.

Almost 9,000 miscarriages occurred in this study. Antibiotic use was then analysed among the group of women and compared to those who had not experienced a miscarriage.

A doubling of risk for miscarriage was seen in macrolides (eg, azithromycin, clarithromycin), quinolones (eg, ciprofloxacin, levofloxacin), sulphonamides and metronidazole. A tripling of risk was seen with tetracyclines, which by definition are not supposed to be used in pregnancy.

At first sight this data is concerning, as is any data suggesting an increased risk of miscarriage, an event that is not merely the physical loss of a pregnancy but can also be a profound and devastating emotional experience for any expectant parents.

It must, however, be placed in perspective. The data suggests a link between miscarriage and antibiotic use and does not suggest that one is caused by the other. Antibiotic use preceding or at the beginning of pregnancy will usually have a serious reason.

For example, seven per cent of women will experience ‘asymptomatic bacteriuria’, which is a urinary tract infection without symptoms. Left untreated, up to 30 per cent of these women will go on to develop pyelonephritis, an infection of the bladder and kidney that can cause preterm labour (the number one cause of perinatal mortality or death of the baby) and can send a mother to intensive care with severe sepsis in certain cases.

The correlation in this paper should not be allowed to dictate management in this specific regard. Pregnant women can sometimes develop severe upper respiratory illness that can often require hospitalisation and without antibiotic treatment in some cases can pose a threat to the life of the mother.

Most doctors will not prescribe antibiotics for the sake of them, particularly to women in the reproductive age group.

There are other directly attributable causes of miscarriage; as a woman gets older her risk of miscarriage increases. Previous miscarriage by definition will increase the background risk of subsequent miscarriage. Pre-existing untreated diabetes, hyperthyroidism and other inflammatory conditions can also play a part. The additional magnitude of risk suggested by this study in isolation may look concerning, but must be viewed as part of the whole picture.

Take-home message: judicious use of antibiotics when indicated should not be avoided as the health of the mother is more important than a correlated risk of miscarriage.
Research score: 3/5
TSA