Maternal antibiotic exposure during pregnancy and hospitalization with infection in offspring: a population-based cohort study

Miller, Jessica E.; Wu, Chunsen; Pedersen, Lars Henning; Klerk, Nicholas de; Olsen, Jørn; Burgner, David

doi:10.1093/ije/dyx272

Cited by 58 publications

(54 citation statements)

References 26 publications

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“…A recent study has shown that antibiotic exposures had a dose-response effect, with multiple antibiotic prescriptions having an increased association with early childhood infection-related hospitalizations, consistent with the disordered microbiome effect theory. 24 However, this may not apply to ear infection if antibiotic use affects the ear structure during a narrow window in early foetal development. Fifth, we lack information on potentially confounding crossgenerational variables, both behavioural (tendencies for mothers to seek antibiotics for themselves and their child, and for prescribers to provide) and genetic/environmental predisposition to infection.…”

Section: Discussionmentioning

confidence: 99%

Association of in Utero Antibiotic Exposure With Childhood Ear Infection Trajectories: A National Birth Cohort Study

Wang

Harwell

et al. 2020

Preprint

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BackgroundMost prescribed medicines during pregnancy are antibiotics, with unknown effects on a foetus and on the infant’s acquired microbiome. This study investigates associations between in utero antibiotic exposure and ear infection trajectories over the first decade of life, hypothesising effects on early or persistent, rather than later-developing, ear infections.MethodsDesign & Participants: The Longitudinal Study of Australian Children (LSAC) birth cohort recruited a nationally-representative sample of 5107 infants in 2004. Measures: Mothers reported antibiotic use in pregnancy when a child was 3-21 months old (wave 1), and ongoing problems with ear infection every 2 years spanning ages 0-1 to 10-11 years (waves 1 to 6). Analysis: Latent class models identified ear infection trajectories, and univariable and multivariable multinomial logistic regression determined odds of adverse trajectories by antibiotic exposure. Results4500 (88.1% of original sample) children contributed (mean baseline age 0.7 years; 51.3% boys); 10.4% of mothers reported antibiotic use in pregnancy. Four probability trajectories for ear infection emerged: “consistently low” (86.2%), “moderate to low” (5.6%), “low to moderate” (6.7%) and “consistently high” (1.4%). Antibiotic use in pregnancy was associated with children following “consistently high” (aOR 2.06, 95% CI 1.09 to 3.91, p=0.03) and “moderate to low” (aOR 1.78, 95% CI 1.25 to 2.53, p=0.001) trajectories.ConclusionsAntibiotic use in pregnancy is associated with an increased risk of persistent and early childhood ear infections. This highlights the wisdom of cautious antibiotic use during pregnancy, and the need for study of potential mechanisms underlying these associations.

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Section: Discussionmentioning

confidence: 99%

Association of in Utero Antibiotic Exposure With Childhood Ear Infection Trajectories: A National Birth Cohort Study

Wang

Harwell

et al. 2020

Preprint

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“…Other factors investigated were the follow-up times. Miller et al 49 found that shorter follow-up times (<5 years) were significant, whereas longer follow-up times up to 10 years and above 10 years had positive effects, but were insignificant.…”

Section: Main Findingsmentioning

confidence: 98%

“…The four systematic reviews varied in their overall conclusions (see Table 2). One concluded there was substantial evidence for infant antibiotic exposure increasing the risk of childhood overweight/obesity, 33 two concluded there was a small association between infant antibiotic exposure and childhood overweight/ obesity 49,34 and one concluded that there was no conclusive evidence of associations between infant antibiotic exposure and childhood overweight/obesity. 35 Reported pooled effect sizes found by the meta-analyses conducted in three of the systematic reviews were RR: 1.21 (1.09-1.33) for overweight and RR: 1.18 (1.12-1.25) for obesity (based on any exposure <24 months and any age of outcome from 2 to 12 years), 33 odds ratio (OR): 1.11 (1.02-1.20) [based on any exposure (0-2 years) and any age of outcome from >2 to 12 years] 34 and OR: 1.05 (1.00-1.11) [based on earliest age of exposure (<24 months), latest age of outcome (2-18 years) and lowest number of prescriptions in each publication].…”

Section: Main Findingsmentioning

confidence: 99%

“…35 Reported pooled effect sizes found by the meta-analyses conducted in three of the systematic reviews were RR: 1.21 (1.09-1.33) for overweight and RR: 1.18 (1.12-1.25) for obesity (based on any exposure <24 months and any age of outcome from 2 to 12 years), 33 odds ratio (OR): 1.11 (1.02-1.20) [based on any exposure (0-2 years) and any age of outcome from >2 to 12 years] 34 and OR: 1.05 (1.00-1.11) [based on earliest age of exposure (<24 months), latest age of outcome (2-18 years) and lowest number of prescriptions in each publication]. 49 Notable influential factors with greater effects, as reported by these reviews, were multiple doses of antibiotics (a few studies within the reviews also reporting dose-response relationships), broad-spectrum antibiotics (macrolides being most consistently reported 49 ) and male gender.…”

Section: Main Findingsmentioning

confidence: 99%

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The relationship of prenatal and infant antibiotic exposure with childhood overweight and obesity: a systematic review

Baron

Taye

Vaart

et al. 2019

J Dev Orig Health Dis

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AbstractThis study aimed to assess the evidence regarding the relationship between early-life antibiotic exposure and childhood overweight/obesity by reviewing observational studies on prenatal antibiotic exposure and systematic reviews on infant antibiotic exposure. A search in Pubmed, Embase and Google Scholar covering the period 1st January till 1st December 2018 led to the identification of five studies on prenatal antibiotic exposure and four systematic reviews on infant antibiotic exposure. Positive trends between prenatal antibiotic exposure and overweight/obesity were reported in all studies; two studies reported a significant overall relationship and the other three reported significant relationships under certain conditions. Effect sizes ranged from odds ratio (OR): 1.04 (0.62–1.74) to relative risk (RR): 1.77 (1.25–2.51). Regarding infant antibiotics, one review concluded there was substantial evidence that infant antibiotic exposure increased the risk of childhood overweight/obesity [pooled effect sizes: RR: 1.21 (1.09–1.33) for overweight and RR: 1.18 (1.12–1.25) for obesity]. Two reviews concluded there was some evidence for a relationship [pooled effect sizes: OR: 1.05 (1.00–1.11) and OR: 1.11 (1.02–1.20)]. The fourth review concluded the studies were too heterogeneous for meta-analyses and the evidence regarding the relationship between infant antibiotic exposure and childhood overweight/obesity was inconclusive. More well-designed studies are needed that include data on intra-partum antibiotics and address important potential confounders (including maternal and childhood infections). This review points to some evidence of a relationship between early-life antibiotic exposure and childhood overweight/obesity; this is especially evident in certain children (i.e. exposed to multiple and broad-spectrum antibiotics, earlier postnatal exposure and male gender) and merits further research.

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“…Notably, antibiotics are frequently prescribed for symptoms (asthma, respiratory, and gastrointestinal infections) that are more likely among cesarean delivered infants [33]. Exposure to antibiotics during the first year of life is associated with subsequent antibiotic exposure throughout the life span [34]. Population-based investigation of antibiotics frequently report the effect size of the exposure as antibiotic episodes (1-4+) associated with a change in a given health outcome [35].…”

Section: Introductionmentioning

confidence: 99%

Postnatal pediatric systemic antibiotic episodes during the first three years of life are not associated with mode of delivery

et al. 2020

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BackgroundDelivery by cesarean section (C-section) is associated with adverse short-term and longterm infant outcomes. Given that antibiotics during early life are prescribed for infant outcomes that are more likely among c-section deliveries, we hypothesized that postnatal antibiotic exposure will be greater among c-section infants compared to vaginally delivered infants. ObjectiveThe aim of this paper was to evaluate if mode of infant delivery was associated with patterns of systemic antibiotic exposure in children during their first three years. MethodsPediatric electronic health records from UFHealth, 2011 to 2017 were reviewed. We included singleton, term infants (37-42 weeks gestation) with a birth weight � 2500 grams, with documented mode of delivery and well visits on record. Infants with a neonatal intensive care unit stay were excluded. Both oral and intravenous antibiotics for a 10-day duration were classified as a single episode. The primary outcome was antibiotic episodes in the first three years of life, and a sub-analysis was performed to compare broad-spectrum versus narrow-spectrum antibiotic exposures. ResultsThe mean number of antibiotic episodes in 4,024 full-term infants was 0.34 (SD = 0.79) and 24.1% of infants had at least one antibiotic episode. Penicillins were the most prescribed antibiotic in children 0-1 years (66.9%) and cephalosporins were the most common PLOS ONE PLOS ONE | https://doi.org/10.1371/journal.pone.0229861 March 4, 2020 1 / 12 OPEN ACCESS Citation: Lemas DJ, Mack JA, Schoch JJ, Cacho N, Plasencia E, Rhoton-Vlasak AS, et al. (2020) Postnatal pediatric systemic antibiotic episodes during the first three years of life are not associated with mode of delivery. PLoS ONE 15(3): e0229861.

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Maternal antibiotic exposure during pregnancy and hospitalization with infection in offspring: a population-based cohort study

Abstract: Antibiotic exposure before or during pregnancy was associated with increased risk of childhood hospitalized infections. Alteration of the maternally derived microbiome and shared heritable and environmental determinants are possible contributory mechanisms.

Cited by 58 publications

References 26 publications

Association of in Utero Antibiotic Exposure With Childhood Ear Infection Trajectories: A National Birth Cohort Study

Association of in Utero Antibiotic Exposure With Childhood Ear Infection Trajectories: A National Birth Cohort Study

The relationship of prenatal and infant antibiotic exposure with childhood overweight and obesity: a systematic review

Postnatal pediatric systemic antibiotic episodes during the first three years of life are not associated with mode of delivery

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