Antibiotics are commonly prescribed for infants. In addition to increasing concern about antibiotic resistance, there is a concern about the potential negative impact of antibiotics on the gut microbiota and health and development outcomes.
The aim of this study was to investigate the association between early life antibiotic exposure and later neurocognitive outcomes.
Participants were infants born to mothers enrolled in the probiotics study. The initial study was designed to evaluate the effect of two different probiotics on allergy outcomes in childhood. Antibiotic exposure was based on parent report and categorised according to the following timing of the first exposure: 0–6 months, 6–12 months, 12–24 months or not at all. At 11 years of age, children’s neurocognitive outcomes were assessed using psychologist-administered, parent-report and self-report measures. The relationship between the timing of antibiotic exposure and neurocognitive outcomes was examined using regression models.
Of the 474 participants initially enrolled, 342 (72%) children had a neurocognitive assessment at 11 years of age. After adjustment for mode of delivery, probiotic treatment group assignment, income and breastfeeding, children who had received antibiotics in the first 6 months of life had significantly lower overall cognitive and verbal comprehension abilities, increased risk of problems with metacognition, executive function, impulsivity, hyperactivity, attention-deficit hyperactivity disorder, anxiety and emotional problems.
These results provide further evidence that early exposure to antibiotics may be associated with detrimental neurodevelopmental outcomes.
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Angeli E, Korpa T, Johnson EO, Apostolakou F, Papassotiriou I, Chrousos GP, Pervanidou P (2018) Salivary cortisol and alpha-amylase diurnal profiles and stress reactivity in children with attention deficit hyperactivity disorder. Psychoneuroendocrinology 90:174–181. https://doi.org/10.1016/j.psyneuen.2018.02.026
Bennet R, Eriksson M, Nord CE (2002) The fecal microflora of 1–3-month-old infants during treatment with eight oral antibiotics. Infection 30:158–160. https://doi.org/10.1007/s15010-002-2140-z
Borre YE, O’Keeffe GW, Clarke G, Stanton C, Dinan TG, Cryan JF (2014) Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med 20:509–518. https://doi.org/10.1016/j.molmed.2014.05.002
Carlson AL, Xia K, Azcarate-Peril MA, Goldman BD, Ahn M, Styner MA, Thompson AL, Geng X, Gilmore JH, Knickmeyer RC (2018) Infant gut microbiome associated with cognitive development. Biol Psychiatry 83:148–159. https://doi.org/10.1016/j.biopsych.2017.06.021
Chai G, Governale L, McMahon AW, Trinidad JP, Murphy JD (2012) Trends of outpatient prescription drug utilization in US children, 2002-2010. Pediatrics 130:23–31. https://doi.org/10.1542/peds.2011-2879.
Clarke G, Grenham S, Scully P, Fitzgerald P, Moloney RD, Shanahan F, Dinan TG, Cryan JF (2013) The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry 18:666–673. https://doi.org/10.1038/mp.2012.77
Collado MC, Cernada M, Baüerl C, Vento M, Pérez-Martínez G (2012) Microbial ecology and host-microbiota interactions during early life stages. Gut Microbes 3:352–365. https://doi.org/10.4161/gmic.21215
Dinan TG, Cryan JF, Stanton C (2018) Gut microbes and brain development have black box connectivity. Biol Psychiatry 83:97–99. https://doi.org/10.1016/j.biopsych.2017.11.005
Fröhlich EE, Farzi A, Mayerhofer R, Reichmann F, Jačan A, Wagner B, Zinser E, Bordag N, Magnes C, Fröhlich E, Kashofer K, Gorkiewicz G, Holzer P (2016) Cognitive impairment by antibiotic-induced gut dysbiosis: analysis of gut microbiota-brain communication. Brain Behav Immun 56:140–155. https://doi.org/10.1016/j.bbi.2016.02.020.
Leclercq S, Mian FM, Stanisz AM, Bindels LB, Cambier E, Ben-amram H, Koren O, Forsythe P, Bienenstock J (2017) Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior. Nat Commun 8:15062. https://doi.org/10.1038/ncomms15062
Lu C, Ni Y (2015) Gut microbiota and the development of pediatric diseases. J Gastroenterol 50:720–726. https://doi.org/10.1007/s00535-015-1082-z
Ma L, Chen Y, Chen H, Liu Y, Wang Y (2010) The function of hypothalamus–pituitary–adrenal axis in children with ADHD. Brain Res 1368:159–162. https://doi.org/10.1016/j.brainres.2010.10.045
Neufeld KM, Kang N, Bienenstock J, Foster JA (2011) Effects of intestinal microbiota on anxiety-like behavior. Commun Integr Biol 4:492–494. https://doi.org/10.4161/cib.15702
Pärtty A, Kalliomäki M, Wacklin P, Salminen S, Isolauri E (2015) A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood: a randomized trial. Pediatr Res 77:823–828. https://doi.org/10.1038/pr.2015.51
Rogawski ET, Platts-Mills JA, Seidman JC, John S, Mahfuz M, Ulak M, Shrestha SK, Soofi SB, Yori PP, Mduma E, Svensen E, Ahmed T, Lima AA, Bhutta ZA, Kosek MN, Lang DR, Gottlieb M, Zaidi AK, Kang G, Bessong PO, Houpt ER, Guerrant RL (2017) Use of antibiotics in children younger than two years in eight countries: a prospective cohort study. Bull World Health Organ 95:49–61. https://doi.org/10.2471/BLT.16.176123
Slykerman RF, Thompson J, Waldie KE, Murphy R, Wall C, Mitchell EA (2017) Antibiotics in the first year of life and subsequent neurocognitive outcomes. Acta Paediatr 106:87–94. https://doi.org/10.1111/apa.13613
Slykerman RF, Kang J, Van Zyl N, Barthow C, Wickens K, Stanley T, Coomarasamy C, Purdie G, Murphy R, Crane J, Mitchell EA (2018) Effect of early probiotic supplementation on childhood cognition, behaviour and mood a randomised, placebo‐controlled trial. Acta Paediatr 107:2172–2178. https://doi.org/10.1111/apa.14590
Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu XN, Kubo C, Koga Y (2004) Postnatal microbial colonization programs the hypothalamic-adrenal-pituitary system for stress response in mice. J Physiol 558:263–275. https://doi.org/10.1113/jphysiol.2004.063388
Vangay P, Ward T, Gerber J, Knights D (2015) Antibiotics, pediatric dysbiosis, and disease. Cell Host Microbe 17:553–564. https://doi.org/10.1016/j.chom.2015.04.006
Wickens K, Black P, Stanley T, Mitchell E, Fitzharris P, Crane J (2007) A differential effect of two probiotics in the prevention of eczema and atopy. World Allergy Organ J :S316. DOI: https://doi.org/10.1097/01.WOX.0000301532.49363.c1.
Funding for measuring the cognitive outcomes was provided by Fonterra Cooperative Group, New Zealand and Cure Kids New Zealand. Funding for the original probiotics study and follow-up was provided by the Health Research Council of New Zealand. EA Mitchell is supported by Cure Kids New Zealand. The funders had no role in the study design, data collection and analysis, the decision to publish or preparation of the manuscript.
The study was approved by the Central Health and Disability Ethics Committee (15/CEN/75/AM02). The parent or guardian and the child gave written consent.
The authors declare that they have no conflict of interest.
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This article belongs to a Special Issue on Microbiome in Psychiatry & Psychopharmacology.
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Slykerman, R.F., Coomarasamy, C., Wickens, K. et al. Exposure to antibiotics in the first 24 months of life and neurocognitive outcomes at 11 years of age. Psychopharmacology 236, 1573–1582 (2019). https://doi.org/10.1007/s00213-019-05216-0
- Attention-deficit hyperactivity disorder