The Causes of Autism

Who are the stupendous authors, what is the title of the study, and what year was it published?

Authors: Marie K Hickey, Neely C Miller, Jacob Haapala, Ellen W Demerath, Kathleen M Pfister, Michael K Georgieff, Cheryl A Gale

Title: Infants exposed to antibiotics after birth have altered recognition memory responses at one month of age. Pediatr Res. 2021 May; 89(6): 1500–1507.

Year: 2021

What is the study about?

This study is to explore the potential link between antibiotic exposure in newborn infants and altered recognition memory responses at one month old. The study focuses on brain function and compares event-related potentials (ERPs) in response to an auditory stimulus between infants who were exposed to antibiotics and those who were not. The hypothesis is that antibiotic exposure can lead to changes in recognition memory responses in infants at one month of age.

What previous research is there on this topic?

The paper cites previous research indicating that antibiotic exposure during childhood is linked to an increased risk of chronic diseases such as obesity, asthma, and inflammatory bowel disease (IBD). Studies on animals also showed that neonatal exposure to antibiotics results in abnormal learning and memory and changes in gut microbes. Animal model evidence further suggests that gut microbes play a role in modulating brain function, including cognition and behavior. However, evidence of this relationship in humans, especially during the rapid brain development period in infancy, was previously lacking. The study aims to address this gap and examine the association between antibiotic exposure in newborns and altered recognition memory responses at one month of age.

What methods were used?

Participants

In this research, the authors analyzed the data of 72 infants to compare the effects of antibiotics on recognition memory at one month of age. Out of these, 15 infants were in the antibiotic-exposed group, and 57 infants were in the unexposed group. The study group infants received antibiotics such as ampicillin and gentamicin due to suspected early onset sepsis (EOS), which they were diagnosed with due to maternal risk factors and clinical examination after birth. The infants underwent auditory recognition memory assessments by recording event-related potentials (ERPs) in response to mother’s and stranger’s voice. All infants in both groups received maternal breast milk for at least a portion of their feedings.

Auditory Memory Assessment

Both the treatment and control groups of infants underwent a hearing test to see how well they remembered different sounds. This was done using a special method called event-related potentials (ERPs), which records brain activity through electrodes on the scalp. The test involved playing the sound of the mother’s voice (a familiar sound) and a stranger’s voice (a new sound) to the infants. The sounds were played 50 times each, and there was a 2.5-second pause between each sound. The sound was the word “baby,” and it was played through speakers located 36 inches from the baby’s head. After measuring the infant’s head size, the ERPs were recorded using a special system with 64 electrodes on the scalp. The recordings were checked for accuracy, and any errors were removed.

Treatment and Control Groups

The study compared a treatment group of infants exposed to antibiotics after delivery due to suspected early onset sepsis (EOS) to a control group of infants who were not exposed to antibiotics pre or postnatally and were born at ≥37 weeks. All infants in both groups were enrolled after obtaining informed parental consent. The treatment group received intravenous antibiotics (Ampicillin 100 mg/kg every 12 hours and Gentamicin 3.5 mg/kg every 24 hours) for the treatment of EOS. The control group infants were delivered at various hospitals within the Twin Cities metro area and were recruited prenatally from Health Partners Clinics and Research Institute, Minneapolis, MN.

What were the findings?

What is PT2?

P2 amplitude refers to a type of electrical brain activity measured through Event-Related Potentials (ERPs) in response to auditory stimuli. The P2 component is a positive voltage peak that occurs in the brain’s electrical activity within a certain time frame after the presentation of an auditory stimulus. P2 amplitude refers to the size or strength of this positive voltage peak, which can be used as an indicator of the brain’s response to the auditory stimuli.

Feature Comparisons

The study found that both groups of infants had similar waveforms with a P2 response to both mother’s and stranger’s voices, indicating the presence of intact neuronal circuitry. However, analysis of the overall mean P2 amplitude by group revealed a main effect of group, with lower overall mean P2 amplitude in the antibiotic-exposed group. Furthermore, infants exposed to antibiotics had significantly smaller P2 amplitude in response to both the mother’s voice and stranger’s voice in several scalp regions, which persisted with adjustments for sex, gestational age, and delivery mode. Infants in the antibiotic-treated group also demonstrated a reversal of the typical response exhibited by unexposed infants. The study did not find any significant differences in NSW areas in response to mother’s versus stranger’s voice in either antibiotic-exposed or unexposed groups or between groups

Inflammatory Markers

The researchers wanted to see if inflammation caused by infection affected the results of the study. They measured the levels of pro-inflammatory proteins in the blood of the infants in the antibiotic group. The researchers looked at how the levels of these proteins related to the changes in P2 amplitude associated with antibiotic exposure. They found that high levels of TNF-α were associated with lower P2 amplitudes in response to the mother’s voice in the left frontal lead. TNF-α (tumor necrosis factor-alpha) is a cytokine that is involved in inflammation, apoptosis, and the regulation of the immune system.

However, no other inflammatory markers were negatively associated with P2 amplitudes in relevant leads, and IL-6 was actually positively associated with P2 amplitudes. IL-6 (interleukin-6) is a cytokine that plays a role in the regulation of the immune response and inflammation.

The researchers concluded that inflammation does not appear to be a factor in the results of the study in the antibiotic group.

What are the implications of this study for future research?

This research study found that taking antibiotics during infancy can cause a disruption in the normal gut microbial communities, which may lead to changes in brain development. The study discovered that infants exposed to antibiotics demonstrated altered attentional perceptual discrimination responses at one month of age. Although the study detected ERP changes in underlying circuitry, the small sample size and scope of this pilot study precluded multivariate analysis of all potential covariables.

However, the study provides support for the existence of a Microbiome-Gut-Brain Axis in infants, and raises the possibility that disruption of this axis affects brain development. Larger, prospective studies are needed to determine the role of gut microbes and the potential long-term clinical significance of early-life antibiotic exposure.

One implication of this study’s findings is that infants discharged following a negative sepsis evaluation after birth may have unrealized risk factors for altered brain development, including the clinical factors that increase suspicion for infection, and the factors that result from antibiotic treatment and hospitalization.

What other research within the library is this study related to?

The study by Volkova et al. (2021) found that early life penicillin exposure resulted in changes in gene expression in the amygdala and prefrontal cortex, as well as the gut microbiome.

Combined, these this study and the one by Volkova et al. indicate possible changes in amygdala, prefrontal cortex, microbiome, and memory responses due to early antibiotic exposure.

Can I read the full study somewhere?

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