Macrolide Antibiotics in Early Pregnancy Linked to Birth Defects, Study Finds

Pregnant women who take certain types of antibiotics have a greater risk of having a child with birth defects, a study has found. Using data on over 100,000 children, researchers found that women given macrolide antibiotics had a slightly higher risk of having a baby with a major malformation—but they stressed leaving an infection untreated was still a bigger risk to the fetus.

The team, from the U.K.'s Great Ormond Street Institute of Child Health, University College London, examined data on 104,605 children born between 1990 to 2016, whose mothers were given either penicillin or an antibiotic known as a macrolide at some point from the fourth gestational week until she gave birth.

They also used two control groups, with one including 53,735 children who were the siblings of those in the study group, and a further 82,314 whose mothers were prescribed the drugs before they conceived. Researchers followed up with the children after an average of 5.8 years after they were born. Findings are published in the BMJ.

Macrolides are among the antibiotics most commonly prescribed to pregnant women in Western countries, according to research cited by the authors. Advice on whether they should be used on such women varies. Doctors often give them to patients who are allergic to penicillin, which has long been thought safe for pregnant women, the authors said.

Major birth defects were recorded in 21.55 per 1,000 children of whose mothers were prescribed macrolides, and 17.36 per 1,000 children whose mothers were prescribed penicillins during pregnancy.

Of those who took macrolides in the first trimester, 27.7 per 1,000 births had birth defects, compared with 19.5 per 1,000 who took them in the second to third. There was no significant difference in malformation rates between trimesters in women who took penicillin.

Using macrolides at any time during pregnancy was linked with an increased risk of children being born with malformed genitals. Taking macrolide drug erythromycin in the first trimester specifically was associated with a higher risk of a defect of any kind.

No significant link was found between the drugs and neurodevelopmental disorders such as cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder.

The authors concluded: "These findings show that macrolides should be used with caution during pregnancy and if feasible alternative antibiotics should be prescribed until further research is available."

The research follows a recent study where existing evidence on macrolides was reviewed. In it, scientists tied the drugs to an increased risk of miscarriage, but found less consistent evidence linking them to birth defects, cerebral palsy, and epilepysy.

However, the methods the researchers used meant they could not prove these drugs were the cause of the birth defects.

In a statement, Heng Fan, lead author of the BMJ paper, said that if a causal link could be shown, then "these findings suggest that an additional four children would be born with cardiovascular malformations for every 1,000 children exposed to macrolides instead of penicillins in the first trimester of pregnancy."

Co-author Ruth Gilbert added: "Our findings suggest it would be better to avoid macrolides during pregnancy if alternative antibiotics can be used." However she stressed: "Women should not stop taking antibiotics when needed, as untreated infections are a greater risk to the unborn baby."

Experts in the field who did not work on the paper also urged pregnant women not to be overly worried by the findings.

Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, U.K., said in a statement that the study was well-conducted and the results well-analyzed. "The message of the paper should be directed at prescribers rather than at patients. It is already well-known that prescribing of drugs, including antibiotics, should be done with caution in pregnancy," he said.

"Antibiotics are vital in protecting individuals against serious consequences of infection, but their over-use has led to resistance. It is not simple to reduce their use but being careful in the choice in pregnancy is entirely sensible."

Sarah Stock, senior clinical lecturer in maternal and fetal Medicine at the University of Edinburgh Usher Institute, U.K., said the study was "robust" but that this type of research cannot prove that the drug caused the birth defects.

"Using an alternative antibiotic wherever possible in early pregnancy seems sensible," she said in a statement. "However, if macrolides are the only treatment option, women can be reassured that the absolute risk of a problem is low. The highest risk was seen with early pregnancy prescriptions, where the additional risk of a heart defect associated with macrolide use was less than half a percent."

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