Interaction between Maternal Immune Activation and Antibiotic Use during Pregnancy and Child Risk of Autism Spectrum Disorder

Holingue, Calliope; Brucato, Martha; Ladd‐Acosta, Christine; Hong, Xiumei; Volk, Heather E.; Mueller, Noel T.; Wang, Xiaobin; Fallin, M. Daniele

doi:10.1002/aur.2411

Cited by 31 publications

(20 citation statements)

References 62 publications

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“…Notably, in contrast to all the other results in this study, systemic antifungal medications were associated with an increased risk of ASD. While this association may be due to the severity of the infection rather than to the iatrogenic effects of the prescribed antimicrobials (49,50), this finding should be regarded with caution since only 15 women (0.6%) in our sample were prescribed this medication.…”

Section: Discussionmentioning

confidence: 74%

Association Between Antenatal Antimicrobial Therapy and Autism Spectrum Disorder—A Nested Case-Control Study

Abelson

Meiri

Solomon³

et al. 2021

Front. Psychiatry

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Background: Multiple prenatal factors have been associated with autism spectrum disorder (ASD) risk. However, current data about the association between antimicrobial use during pregnancy and ASD is limited.Methods: A nested matched case-control study of children with ASD (cases), and children without ASD or other psychiatric or genetic disorders (controls). We compared the use of antimicrobial therapy during the 3 months before conception or during pregnancy between mothers of cases and controls and used multivariate conditional logistic regression models to assess the independent association between maternal use of antimicrobials during pregnancy and the risk of ASD in their offspring.Results: More than half of the mothers in the study (54.1%) used antimicrobial drugs during the 3 months before conception or during pregnancy. Rates of antimicrobial use were lower for mothers of children with ASD compared to mothers of controls (49.0 vs. 55.1%, respectively; p = 0.02), especially during the third trimester of pregnancy (18.8 vs. 22.9%, respectively; p = 0.03), and for the use of penicillins (15.7 vs. 19.7%, respectively; p = 0.06). These case–control differences suggest that antimicrobial administration during pregnancy was associated with a reduced risk of ASD in the offspring (aOR = 0.75, 95% CI = 0.61–0.92). Interestingly, this association was seen only among Jewish but not for the Bedouin mothers (aOR = 0.62, 95% CI = 0.48–0.79 and aOR = 1.21, 95% CI = 0.82–1.79).Conclusions: The reduced risk of ASD associated with prenatal antimicrobials use only in the Jewish population suggest the involvement of other ethnic differences in healthcare services utilization in this association.

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Section: Discussionmentioning

confidence: 74%

Association Between Antenatal Antimicrobial Therapy and Autism Spectrum Disorder—A Nested Case-Control Study

Abelson

Meiri

Solomon³

et al. 2021

Front. Psychiatry

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“…The analysis showed an interaction between the effect of flu and antibiotic use during pregnancy on the risk of ASD in the child. In women with antibiotic use during pregnancy, flu in trimester two was not associated with ASD, while in those without antibiotic use, flu in second trimester was significantly associated with increased risk of ASD [89]. The pathophysiological mechanisms underlying this positive association remains elusive but is likely to be two-fold [88].…”

Section: Maternal Cytokines In Asdmentioning

confidence: 98%

“…However, a meta-analysis by Jiang et al, systematically examining 15 studies and 40,000 cases of ASD, concluded that maternal infections during pregnancy, particularly those requiring hospitalisation, do indeed increase the risk of ASD in new-borns [88]. A recent prospective birth cohort study with 116 ASD cases and 860 typically developing (TD) children looked at the effect of antibiotic use on the relationship between immune activation and the ASD risk [89]. The analysis showed an interaction between the effect of flu and antibiotic use during pregnancy on the risk of ASD in the child.…”

Section: Maternal Cytokines In Asdmentioning

confidence: 99%

Critical Role of the Maternal Immune System in the Pathogenesis of Autism Spectrum Disorder

Ravaccia

Ghafourian

2020

Biomedicines

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Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterised by impairments in communication, social interaction, and the presence of restrictive and repetitive behaviours. Over the past decade, most of the research in ASD has focused on the contribution of genetics, with the identification of a variety of different genes and mutations. However, the vast heterogeneity in clinical presentations associated with this disorder suggests that environmental factors may be involved, acting as a “second hit” in already genetically susceptible individuals. To this regard, emerging evidence points towards a role for maternal immune system dysfunctions. This literature review considered evidence from epidemiological studies and aimed to discuss the pathological relevance of the maternal immune system in ASD by looking at the proposed mechanisms by which it alters the prenatal environment. In particular, this review focuses on the effects of maternal immune activation (MIA) by looking at foetal brain-reactive antibodies, cytokines and the microbiome. Despite the arguments presented here that strongly implicate MIA in the pathophysiology of ASD, further research is needed to fully understand the precise mechanisms by which they alter brain structure and behaviour. Overall, this review has not only shown the importance of the maternal immune system as a risk factor for ASD, but more importantly, has highlighted new promising pathways to target for the discovery of novel therapeutic interventions for the treatment of such a life-changing disorder.

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“…Reports have documented that maternal diet during lactation modulates the composition of breast milk, glucose tolerance, and weight of the infant (7). Also, it had been confirmed that negative physiological conditions such as obesity, overweight, or overnutrition with energy-dense diets are associated with a pro-inflammatory profile and immune activation in the plasma of the infants after birth (114)(115)(116)(117)(118). In humans, 25% of calorie intake in obese people comes from snacks and junk food (119), which could have a negative contribution on breastfeeding composition and health in the newborns from obese mothers.…”

Section: Maternal Diet Modulates Breast Milk-gut Microbiome Interplay and Immunity In The Newbornmentioning

confidence: 97%

Breastfeeding Contributes to Physiological Immune Programming in the Newborn

et al. 2021

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The first 1,000 days in the life of a human being are a vulnerable stage where early stimuli may program adverse health outcomes in future life. Proper maternal nutrition before and during pregnancy modulates the development of the fetus, a physiological process known as fetal programming. Defective programming promotes non-communicable chronic diseases in the newborn which might be prevented by postnatal interventions such as breastfeeding. Breast milk provides distinct bioactive molecules that contribute to immune maturation, organ development, and healthy microbial gut colonization, and also secures a proper immunological response that protects against infection and inflammation in the newborn. The gut microbiome provides the most critical immune microbial stimulation in the newborn in early life, allowing a well-trained immune system and efficient metabolic settings in healthy subjects. Conversely, negative fetal programming by exposing mothers to diets rich in fat and sugar has profound effects on breast milk composition and alters the immune profiles in the newborn. At this new stage, newborns become vulnerable to immune compromise, favoring susceptibility to defective microbial gut colonization and immune response. This review will focus on the importance of breastfeeding and its immunological biocomponents that allow physiological immune programming in the newborn. We will highlight the importance of immunological settings by breastfeeding, allowing proper microbial gut colonization in the newborn as a window of opportunity to secure effective immunological response.

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Interaction between Maternal Immune Activation and Antibiotic Use during Pregnancy and Child Risk of Autism Spectrum Disorder

Cited by 31 publications

References 62 publications

Association Between Antenatal Antimicrobial Therapy and Autism Spectrum Disorder—A Nested Case-Control Study

Association Between Antenatal Antimicrobial Therapy and Autism Spectrum Disorder—A Nested Case-Control Study

Critical Role of the Maternal Immune System in the Pathogenesis of Autism Spectrum Disorder

Breastfeeding Contributes to Physiological Immune Programming in the Newborn

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