Maternal antibiotic exposure during pregnancy and hospitalization with infection in offspring: authors’ reply

Maternal antibiotic exposure during pregnancy and hospitalization with infection in offspring:... Downloaded from https://academic.oup.com/ije/article-abstract/47/5/1724/5025719 by Ed 'DeepDyve' Gillespie user on 07 November 2018 1724 International Journal of Epidemiology, 2018, Vol. 47, No. 5 International Journal of Epidemiology, 2018, 1724 Maternal antibiotic exposure doi: 10.1093/ije/dyy097 Advance Access Publication Date: 30 May 2018 during pregnancy and hospitalization with infection in offspring: authors’ reply 1 2 3 4 5 Jessica E Miller, Chunsen Wu, Lars Henning Pedersen, Nicholas de Klerk, Jørn Olsen and David Burgner * 1 2 Murdoch Children’s Research Institute, Melbourne, VIC, Australia, Research Unit on Gynaecology and Obstetrics, Insti- tute of Clinical Research, University of Southern Denmark, Odense, Denmark, Institute for Clinical Medicine, Aarhus Uni- versity, Aarhus, Denmark, Telethon Kids Institute, University of Western Australia, Perth, WA, Australia and Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark *Corresponding author. E-mail: david.burgner@mcri.edu.au We thank Chandrakumar et al. for their interest in our unlikely to show a time-dependent effect; therefore, the work. We acknowledge some issues raised in the original risk before pregnancy would not increase once antibiotic manuscript and will address other points in detail that the exposure in pregnancy was also considered. manuscript word limit precluded. The cumulative risk from pre-pregnancy plus pregnancy In addition to the established effects on the maternal antibiotic exposure may reflect both an underlying suscept- microbiome, antibiotics before and during pregnancy may ibility and antibiotic-related dysbiosis. In infants delivered also be indicative of increased underlying susceptibility to by caesarean section, who do not receive the maternal infection. This susceptibility may further increase the risk enteric microbiome but a microbiome predominantly from of offspring infection beyond that from antibiotic-induced maternal skin and the hospital environment, an effect of dysbiosis. Data on infections in pregnancy not treated with pregnancy antibiotics on postnatal offspring infection antibiotics would be informative in disentangling the rela- would not be expected, as these infants do not receive a tive contributions, but these data are not available. dysbiotic maternal enteric microbiome. The contribution, As pre-pregnancy infection may be more indicative of if any, from potentially antibiotic-affected skin flora on an underlying susceptibility to infection in the mother infection risk is unknown, but is likely to be less. (pregnancy itself increases the risk of infection per se ), we We acknowledge the importance of breastfeeding in therefore adjusted for pre-pregnancy antibiotic use in the analysis of the risk associated with antibiotics in preg- infection susceptibility; unfortunately, these data are nancy. The association between pregnancy antibiotics and unavailable. offspring infection attenuated somewhat, suggesting that Postnatal antibiotic exposure in the mother may be infor- an underlying susceptibility to infection, manifesting by mative about her underlying susceptibility to infection, but increased antibiotic use, contributes modestly but does not interpretation of these analyses is likely to be complicated fully explain the association between pregnancy antibiotics by the likelihood that young children infect other family and offspring infection. members and vice versa. We cannot fully concur with the other interpretations suggested. We did not compare the risk associated with References pre-pregnancy and pregnancy antibiotic exposures, as the 1. Miller JE, Wu C, Pedersen LH, de Klerk N, Olsen J, Burgner DP. more meaningful comparison group is mothers unexposed Maternal antibiotic exposure during pregnancy and hospitalization to antibiotics during these periods. The observation that with infection in offspring: a population-based cohort study. Int J the overall risks were similar for offspring of mothers who Epidemiol 2018;47:561–71. had antibiotics only before pregnancy or only during preg- 2. Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the nancy is not informative about possible underlying mecha- gut microbiota on human health: an integrative view. Cell nisms. The risk doubled if the mothers were exposed 2012;148:1258–70. during both periods, implying that there are additive 3. Jamieson DJ, Theiler RN, Rasmussen SA. Emerging infections effects. An underlying susceptibility to infection would be and pregnancy. Emerg Infect Dis 2006;12:1638–43. V The Author 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Journal of Epidemiology Oxford University Press

Maternal antibiotic exposure during pregnancy and hospitalization with infection in offspring: authors’ reply

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Oxford University Press
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© The Author(s) 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association
ISSN
0300-5771
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1464-3685
D.O.I.
10.1093/ije/dyy097
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Abstract

Downloaded from https://academic.oup.com/ije/article-abstract/47/5/1724/5025719 by Ed 'DeepDyve' Gillespie user on 07 November 2018 1724 International Journal of Epidemiology, 2018, Vol. 47, No. 5 International Journal of Epidemiology, 2018, 1724 Maternal antibiotic exposure doi: 10.1093/ije/dyy097 Advance Access Publication Date: 30 May 2018 during pregnancy and hospitalization with infection in offspring: authors’ reply 1 2 3 4 5 Jessica E Miller, Chunsen Wu, Lars Henning Pedersen, Nicholas de Klerk, Jørn Olsen and David Burgner * 1 2 Murdoch Children’s Research Institute, Melbourne, VIC, Australia, Research Unit on Gynaecology and Obstetrics, Insti- tute of Clinical Research, University of Southern Denmark, Odense, Denmark, Institute for Clinical Medicine, Aarhus Uni- versity, Aarhus, Denmark, Telethon Kids Institute, University of Western Australia, Perth, WA, Australia and Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark *Corresponding author. E-mail: david.burgner@mcri.edu.au We thank Chandrakumar et al. for their interest in our unlikely to show a time-dependent effect; therefore, the work. We acknowledge some issues raised in the original risk before pregnancy would not increase once antibiotic manuscript and will address other points in detail that the exposure in pregnancy was also considered. manuscript word limit precluded. The cumulative risk from pre-pregnancy plus pregnancy In addition to the established effects on the maternal antibiotic exposure may reflect both an underlying suscept- microbiome, antibiotics before and during pregnancy may ibility and antibiotic-related dysbiosis. In infants delivered also be indicative of increased underlying susceptibility to by caesarean section, who do not receive the maternal infection. This susceptibility may further increase the risk enteric microbiome but a microbiome predominantly from of offspring infection beyond that from antibiotic-induced maternal skin and the hospital environment, an effect of dysbiosis. Data on infections in pregnancy not treated with pregnancy antibiotics on postnatal offspring infection antibiotics would be informative in disentangling the rela- would not be expected, as these infants do not receive a tive contributions, but these data are not available. dysbiotic maternal enteric microbiome. The contribution, As pre-pregnancy infection may be more indicative of if any, from potentially antibiotic-affected skin flora on an underlying susceptibility to infection in the mother infection risk is unknown, but is likely to be less. (pregnancy itself increases the risk of infection per se ), we We acknowledge the importance of breastfeeding in therefore adjusted for pre-pregnancy antibiotic use in the analysis of the risk associated with antibiotics in preg- infection susceptibility; unfortunately, these data are nancy. The association between pregnancy antibiotics and unavailable. offspring infection attenuated somewhat, suggesting that Postnatal antibiotic exposure in the mother may be infor- an underlying susceptibility to infection, manifesting by mative about her underlying susceptibility to infection, but increased antibiotic use, contributes modestly but does not interpretation of these analyses is likely to be complicated fully explain the association between pregnancy antibiotics by the likelihood that young children infect other family and offspring infection. members and vice versa. We cannot fully concur with the other interpretations suggested. We did not compare the risk associated with References pre-pregnancy and pregnancy antibiotic exposures, as the 1. Miller JE, Wu C, Pedersen LH, de Klerk N, Olsen J, Burgner DP. more meaningful comparison group is mothers unexposed Maternal antibiotic exposure during pregnancy and hospitalization to antibiotics during these periods. The observation that with infection in offspring: a population-based cohort study. Int J the overall risks were similar for offspring of mothers who Epidemiol 2018;47:561–71. had antibiotics only before pregnancy or only during preg- 2. Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the nancy is not informative about possible underlying mecha- gut microbiota on human health: an integrative view. Cell nisms. The risk doubled if the mothers were exposed 2012;148:1258–70. during both periods, implying that there are additive 3. Jamieson DJ, Theiler RN, Rasmussen SA. Emerging infections effects. An underlying susceptibility to infection would be and pregnancy. Emerg Infect Dis 2006;12:1638–43. V The Author 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Journal

International Journal of EpidemiologyOxford University Press

Published: Oct 1, 2018

References

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