Association of prenatal antibiotics with measures of infant adiposity and the gut microbiome

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2022/07/15

study design

prospective cohort

Citation

PMID PubMed identifier for scientific articles.

31226994

DOI Digital object identifier for electronic documents.

10.1186/s12941-019-0318-9

URI

Authors

Zhang M, Differding MK, Benjamin-Neelon SE, Østbye T, Hoyo C, Mueller NT

Journal

Annals of clinical microbiology and antimicrobials

Year

2019

Keywords:

Antibiotic, Child health, Gut microbiome, Pediatric obesity, Pregnancy, Prenatal exposure

BACKGROUND: Prenatal antibiotic exposure has been associated with an altered infant gut microbiome composition and higher risk of childhood obesity, but no studies have examined if prenatal antibiotics simultaneously alter the gut microbiome and adiposity in infants. METHOD: In this prospective study (Nurture: recruitment 2013-2015 in North Carolina, United States), we examined in 454 infants the association of prenatal antibiotic exposure (by any prenatal antibiotic exposure; by trimester of pregnancy; by number of courses; by type of antibiotics) with infant age- and sex-specific weight-for-length z score (WFL-z) and skinfold thicknesses (subscapular, triceps, abdominal) at 12 months of age. In a subsample, we also examined whether prenatal antibiotic exposure was associated with alterations in the infant gut microbiome at ages 3 and 12 months. RESULTS: Compared to infants not exposed to prenatal antibiotics, infants who were exposed to any prenatal antibiotics had 0.21 (95% confidence interval [CI] 0.02, 0.41) higher WFL-z at 12 months, and 0.28 (95% CI 0.02, 0.55) higher WFL-z if they were exposed to antibiotics in the second trimester, after adjustment for potential confounders, birth weight, and gestational age. We also observed a dose-dependent association (P-value for trend = 0.006) with infants exposed to ≥ 3 courses having 0.41 (95% CI 0.13, 0.68) higher WFL-z at 12 months. After further adjustment for delivery method, only second-trimester antibiotic exposure remained associated with higher infant WFL-z (0.27, 95% CI 0.003, 0.54) and subscapular skinfold thickness (0.49 mm, 95% CI 0.11, 0.88) at 12 months. Infants exposed to second-trimester antibiotics versus not had differential abundance of 13 bacterial amplicon sequence variants (ASVs) at age 3 months and 17 ASVs at 12 months (false discovery rate adjusted P-value < 0.05). CONCLUSIONS: Prenatal antibiotic exposure in the second trimester was associated with an altered infant gut microbiome composition at 3 and 12 months and with higher infant WFL-z and subscapular skinfold thickness at 12 months.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/07/15

Curated date: 2021/01/10

Curator: WikiWorks

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Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Antimicrobial agent antibiotic,antibiotics,Antibiotika,Antibiotikum,antibiotique,antimicrobial,antimicrobial agents,microbicide,microbicides,Antimicrobial agent,antimicrobial agent

Group 0 name Corresponds to the control (unexposed) group for case-control studies: 3-month old infants not exposed to antibiotics during the second trimester

Group 1 name Corresponds to the case (exposed) group for case-control studies: 3-month-old infants exposed to antibiotics in the second trimester

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: infants born after 28 weeks gestation with no congenital abnormalities who were exposed to antibiotics during the second trimester

Group 0 sample size Number of subjects in the control (unexposed) group: 56

Group 1 sample size Number of subjects in the case (exposed) group: 12

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Statistical test: Beta Binomial Regression

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: body mass index, household income, smoking behavior, education level, marital status, maternal age, race

Signature 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/07/15

Curated date: 2021/01/10

Curator: Mst Afroza Parvin

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Source: Figure 1, Table S2

Description: Differential microbial abundance between infants who were and were not exposed to antibiotics in the second trimester

Abundance in Group 1: increased abundance in 3-month-old infants exposed to antibiotics in the second trimester

NCBI	Quality Control	Links
Fusicatenibacter
Enterococcus

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Signature 2

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Source: Figure 1, Table S2

Description: Differential microbial abundance between infants who were and were not exposed to antibiotics in the second trimester

Abundance in Group 1: decreased abundance in 3-month-old infants exposed to antibiotics in the second trimester

NCBI	Quality Control	Links
Akkermansia muciniphila
Bacteroides
Clostridium neonatale
Enterobacteriaceae
Limosilactobacillus antri
Pasteurellaceae
Schaalia odontolytica
Staphylococcus
Streptococcus
Veillonella

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Experiment 3

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: 12-month-old infants not exposed to antibiotics during the second trimester

Group 1 name Corresponds to the case (exposed) group for case-control studies: 12-month-old infants exposed to antibiotics during the second trimester