Not Dark Yet: Associations between macrolide antibiotics prescribing during pregnancy and congenital malformations.
Dear Editor
I read this paper with great interest. It appears to be a well-designed, conducted and reported study that adds information to a subject of some controversy.
However, I am surprised and disappointed by the superficial and inadequate discussion of their findings as related to other recent publications on the very subject of macrolides in pregnancy and risk of major congenital malformations. Specifically (and yes, I hold an academic conflict of interest here) I would appreciate a justification for not including the results from our 2019 paper in the discussion and perspectives of the authors' findings. We report null-results (major and cardiovascular congenital malformations) for erythromycin, azithromycin and roxythromycin in a population-wide registry study comprising more than 13.000 first-trimester exposed live-born children (1).
For comparison, the authors findings and conclusions - as pertaining to congenital malformations - are based on 2170 first trimester exposed live-born children. I am confident that the authors have been meticulous throughout and the data-set analysed produces the results presented for the population studied. But I am really at a loss as to why - among 45 references - they could not fit in the largest amount of data reported and discuss our null-results against their findings.
Signals of potential harm are picked up and promoted by media, academia, patients and all parties with interest in health-care exponentially more so than null-results. And twice that within the sensitive and often fairly controversial field on the use of drugs during pregnancy, where it is nigh on impossible to put the lid back on, regardless of the quantity and quality of data to the contrary.
The authors call for caution and warnings in drug safety leaflets based on their results. To suggest this with no real discussion of other results - which do not suggest such risk - is not justifiable. The way the results from this study are being framed and disseminated will likely (my word) result in substantial and insufficiently substantiated doubt and uncertainties among pregnant women receiving these drugs.
Pregnant women deserve better.
Per Damkier
Professor, MD PhD
1) Damkier P, Brønniche LMS, Korch-Frandsen JFB, Broe A. In utero exposure to antibiotics and risk of congenital malformations: a population-based study. Am J
Obstet Gynecol. 2019 Dec;221(6):648.e1-648.e15. doi: 10.1016/j.ajog.2019.06.050. Epub 2019 Jun 28.
Competing interests:
First author of a paper ( PMID: 31260651; DOI: 10.1016/j.ajog.2019.06.050) in which the results are not compatible with those reported here.
21 February 2020
Per Damkier
Professor, MD PhD
Departments of a) Clinical Biochemistry and Pharmacology, Odense University Hospital, Denmark & 2) Clinical Research, University of Southern Denmark, Denmark
Department of Clinical Research; University of Southern Denmark. J.B.Winsloewvej 19.2; DK-5000 Denmark
Rapid Response:
Not Dark Yet: Associations between macrolide antibiotics prescribing during pregnancy and congenital malformations.
Dear Editor
I read this paper with great interest. It appears to be a well-designed, conducted and reported study that adds information to a subject of some controversy.
However, I am surprised and disappointed by the superficial and inadequate discussion of their findings as related to other recent publications on the very subject of macrolides in pregnancy and risk of major congenital malformations. Specifically (and yes, I hold an academic conflict of interest here) I would appreciate a justification for not including the results from our 2019 paper in the discussion and perspectives of the authors' findings. We report null-results (major and cardiovascular congenital malformations) for erythromycin, azithromycin and roxythromycin in a population-wide registry study comprising more than 13.000 first-trimester exposed live-born children (1).
For comparison, the authors findings and conclusions - as pertaining to congenital malformations - are based on 2170 first trimester exposed live-born children. I am confident that the authors have been meticulous throughout and the data-set analysed produces the results presented for the population studied. But I am really at a loss as to why - among 45 references - they could not fit in the largest amount of data reported and discuss our null-results against their findings.
Signals of potential harm are picked up and promoted by media, academia, patients and all parties with interest in health-care exponentially more so than null-results. And twice that within the sensitive and often fairly controversial field on the use of drugs during pregnancy, where it is nigh on impossible to put the lid back on, regardless of the quantity and quality of data to the contrary.
The authors call for caution and warnings in drug safety leaflets based on their results. To suggest this with no real discussion of other results - which do not suggest such risk - is not justifiable. The way the results from this study are being framed and disseminated will likely (my word) result in substantial and insufficiently substantiated doubt and uncertainties among pregnant women receiving these drugs.
Pregnant women deserve better.
Per Damkier
Professor, MD PhD
1) Damkier P, Brønniche LMS, Korch-Frandsen JFB, Broe A. In utero exposure to antibiotics and risk of congenital malformations: a population-based study. Am J
Obstet Gynecol. 2019 Dec;221(6):648.e1-648.e15. doi: 10.1016/j.ajog.2019.06.050. Epub 2019 Jun 28.
Competing interests: First author of a paper ( PMID: 31260651; DOI: 10.1016/j.ajog.2019.06.050) in which the results are not compatible with those reported here.