The Outcomes of Pregnancy in Women Exposed to the New Macrolides in the First Trimester

Bar‐Oz, Benjamin; Weber-Schoendorfer, Corinna; Berlin, Maya; Clementi, Maurizio; Gianantonio, Elena Di; Vries, Loes de; Santis, Marco De; Merlob, Paul; Stahl, Bracha; Eleftheriou, Giorgio; Maňáková, Eva; Hubickova-Heringova, Lucie; Youngster, Ilan; Berkovitch, Matitiahu

doi:10.2165/11630920-000000000-00000

Cited by 28 publications

(24 citation statements)

References 15 publications

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“…Four studies using data from teratology information services did not find an association between the use of macrolides and spontaneous abortion. [1][2][3][4] In contrast, a Danish study based on data from a prescription database found an increased risk of spontaneous abortion associated with the use of clarithromycin. 5 Three studies using data from teratology information services failed to show a link between the use of quinolones and the risk of spontaneous abortion, [6][7][8] and an early Medicaid study showed an association with the use of metronidazole.…”

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confidence: 94%

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Use of antibiotics during pregnancy and risk of spontaneous abortion

Muanda

Sheehy

Bérard

2017

CMAJ

117

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BACKGROUND: Although antibiotics are widely used during pregnancy, evidence regarding their fetal safety remains limited. Our aim was to quantify the association between antibiotic exposure during pregnancy and risk of spontaneous abortion. METHODS:We conducted a nested case-control study within the Quebec Pregnancy Cohort (1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009). We excluded planned abortions and pregnancies exposed to fetotoxic drugs. Spontaneous abortion was defined as having a diagnosis or procedure related to spontaneous abortion before the 20th week of pregnancy. The index date was defined as the calendar date of the spontaneous abortion. Ten controls per case were randomly selected and matched by gestational age and year of pregnancy. Use of antibiotics was defined by filled prescriptions between the first day of gestation and the index date and was compared with (a) non-exposure and (b) exposure to penicillins or cephalosporins. We studied type of antibiotics separately using the same comparator groups. RESULTS:After adjustment for potential confounders, use of azithromycin (adjusted odds ratio [OR] 1.65, 95% confidence interval [CI] 1.34-2.02; 110 exposed cases), clarithromycin (adjusted OR 2.35, 95% CI 1.90-2.91; 111 exposed cases), metronidazole (adjusted OR 1.70, 95% CI 1.27-2.26; 53 exposed cases), sulfonamides (adjusted OR 2.01, 95% CI 1.36-2.97; 30 exposed cases), tetracyclines (adjusted OR 2.59, 95% CI 1.97-3.41; 67 exposed cases) and quinolones (adjusted OR 2.72, 95% CI 2.27-3.27; 160 exposed cases) was associated with an increased risk of spontaneous abortion. Similar results were found when we used penicillins or cephalosporins as the comparator group. INTERPRETATION:After adjustment for potential confounders, use of macrolides (excluding erythromycin), quinolones, tetracyclines, sulfonamides and metronidazole during early pregnancy was associated with an increased risk of spontaneous abortion. Our findings may be of use to policy-makers to update guidelines for the treatment of infections during pregnancy.

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confidence: 94%

“…9 However, the studies were all limited by either small samples, or recall or indication bias. [1][2][3][4][5][6][7][8][9] Studies of the risk of spontaneous abortion associated with tetracyclines and nitrofurantoin are lacking.…”

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confidence: 99%

Use of antibiotics during pregnancy and risk of spontaneous abortion

Muanda

Sheehy

Bérard

2017

CMAJ

117

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“…In contrast, a widely publicized Swedish study reported increased risk of cardiovascular malformations, leading several Scandinavian countries to avoid prescribing the drug to pregnant women (14). Data concerning the fetal safety of clarithromycin, azithromycin, and roxithromycin have been limited but failed to show increased fetal risks (15)(16)(17)(18)(19)(20).…”

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confidence: 99%

Fetal Safety of Macrolides

Dinur

Koren

Matok

et al. 2013

Antimicrob Agents Chemother

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Macrolide antibiotics are largely used in pregnancy for different bacterial infections. Their fetal safety has been studied by several groups, yielding opposing results. In particular, there have been studies claiming an association between macrolides and cardiovascular malformations. Exposure in early infancy has been associated with pyloric stenosis and intussusception. This has led to an avoidance in prescribing macrolides to pregnant women in several Scandinavian countries. The Objectives of the present study was to investigate the fetal safety of this class of drug by linking a large administrative database of drug dispensing and pregnancy outcome in Southern Israel. A computerized database of medications dispensed from 1999 to 2009 to all women registered in the Clalit health maintenance organization in southern Israel was linked with two computerized databases containing maternal and infant hospitalization records. Also, medical pregnancy termination data were analyzed. The following confounders were controlled for: maternal age, ethnicity, maternal pregestational diabetes, parity, and the year the mother gave birth or went through medical pregnancy termination. First-and third-trimester exposures to macrolide antibiotics as a group and to individual drugs were analyzed. During the study period there were 105,492 pregnancies among Clalit women that met the inclusion criteria. Of these, 104,380 ended in live births or dead fetuses and 1,112 in abortion due to medical reasons. In the first trimester of pregnancy, 1,033 women were exposed to macrolides. There was no association between macrolides and either major malformations [odds ratio (OR), 1.08; 95% confidence interval (CI), 0.84 to 1.38)] or specific malformations, after accounting for maternal age, parity, ethnicity, prepregnancy diabetes, and year of exposure. During the third trimester of pregnancy, 959 women were exposed to macrolides. There was no association between such exposure and perinatal mortality, low birth weight, low Apgar score, or preterm delivery. Similarly, no associations were demonstrated with pyloric stenosis or intussusception. Use of macrolides in the first trimester of pregnancy is not associated with an increased risk of major malformations. Exposure in the third trimester is not likely to increase neonatal risks for pyloric stenosis or intussusception in a clinically meaningful manner.

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“…Risiko for spontanabort etter antibiotikabruk ble undersøkt i syv av studiene (9,14,15,17,21,29). I de tre danske der man fant signifikant økt risiko for spontanabort, var det ikke kontrollert for infeksjon etter bruk av en rekke antibiotika (klaritromycin, pivmecillinam, sulfametizol, trimetoprim).…”

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“…Gravide har noen ganger en urealistisk oppfatning av hvor farlig legemidler er for fosteret, det gjelder også trygge antibiotika som penicilliner (41). Enkelte velger å ta abort på grunn av frykt for å få et barn med misdannelser (14,15 …”

Section: Trinnunclassified