The baseline risk for major birth defects in the general population during pregnancy ranges from 3% to 5%, even without taking any medication. A teratogen is simply a substance that increases this risk during a specific stage of pregnancy. “The first 4 weeks operate under an all-or-nothing principle,” explained Matitiahu Berkovich, pediatrician, clinical pharmacologist, and president of the European Network of Teratology Information Services (ENTIS), during a webinar on antibiotics in pregnancy and lactation, organized by the World Organization of Family Doctors, which represents more than 90,000 family physicians.

During his presentation, he provided an overview based on current scientific evidence and focused on debunking the most common fears surrounding this issue, while shedding light on the restrictive approach taken by pharmaceutical companies and certain AI tools such as OpenEvidence.

Pharmacokinetic Factors

The pediatrician noted that during pregnancy, renal filtration increases, total body water rises, and protein binding decreases. As a result, the clearance of amoxicillin is much faster, and many obstetricians opt to prescribe higher doses: 1 g every 8 hours instead of 500 mg.

He then focused on reviewing the guidelines for the various antibiotics used during pregnancy and breastfeeding.

In the case of Escherichia coli pyelonephritis, amoxicillin/clavulanic acid and cefuroxime can be administered because they are completely safe and do not increase the risk beyond 3%-5%.

Cotrimoxazole (trimethoprim/sulfamethoxazole) is a folate antagonist. It is not the first-line treatment during the first trimester of pregnancy, but if there is no alternative, it may be used in combination with high doses of folic acid (5 mg).

The specialist also went on to discuss gentamicin (an aminoglycoside), which does not cause malformations or hearing loss in the fetus, unless there is a family history of genetic deafness. In such cases, parenteral administration is recommended.

Common Myths

Regarding quinolones (ciprofloxacin/levofloxacin), he noted that they were historically contraindicated due to cartilage damage observed in studies on young animals; however, ENTIS-endorsed studies in humans have shown that they are safe and do not cause joint problems in children. Nevertheless, they may be used if indicated by antibiotic susceptibility testing.

Nitrofurantoin is safe during the first and second trimesters and should be avoided late in pregnancy due to the risk for neonatal jaundice, whereas fosfomycin is safe and convenient because it is administered as a single dose.

The specialist noted that there is a common misconception that doxycycline (a tetracycline) is prohibited throughout pregnancy, but it can be used in the first trimester, before 14 weeks. Tooth discoloration in the baby only occurs if doxycycline is taken after week 14, which is when calcification begins.

Macrolides (azithromycin and clarithromycin), metronidazole, and clindamycin are safe during all trimesters of pregnancy.

Antibiotics During Breastfeeding

Berkovich noted that many doctors discontinue breastfeeding out of excessive caution. During breastfeeding, unlike during pregnancy, pharmacokinetic data are needed to validate safety.

Thus, among the safety criteria, he highlighted that when the relative infant dose (RID) is less than 10%, the drug is considered safe. In fact, drugs with high protein binding or high molecular weight barely pass into breast milk.

He then went on to review antibiotics during breastfeeding. Amoxicillin/clavulanate, clindamycin, and cephalosporins are compatible and have a very low RID. Gentamicin is not absorbed through the gastrointestinal tract, making it safe for the infant, while quinolones are compatible with breastfeeding due to their low RID.

Doxycycline is also compatible when used for a short term, over a period of 3-4 weeks. When treatment is chronic, alternatives should be sought.

Another group that is compatible is the macrolides: azithromycin and clarithromycin. Caution is advised with cotrimoxazole and nitrofurantoin, which are compatible. They should be avoided in premature infants, infants with jaundice, or those with glucose-6-phosphate dehydrogenase deficiency because they can affect bilirubin levels and cause hemolysis or hyperbilirubinemia.

The webinar participants declared having no relevant financial relationship. 

This story was translated from El Médico Interactivo. part of the Medscape Professional Network.