Prenatal caffeine consumption and neurobehavioral disorders - A systematic review.

Studies have suggested associations between gestational exposure to caffeine and adverse outcomes, however the evidence is still limited. Therefore, a systematic review was conducted to investigate the association between prenatal caffeine exposure and neurobehavioral disorders. The MEDLINE (PubMed), EMBASE, Scopus, Web of Science, and LILACS databases were searched. Observational studies involving women with documented caffeine consumption during pregnancy were eligible for inclusion. The outcomes evaluated were behavioral and intellectual development, Attention Deficit Hyperactivity Disorder, and related behaviors. The data were analyzed by qualitative synthesis. The ROBINS-I tool was employed to assess the risk of bias, and the certainty of evidence was evaluated using GRADE (PROSPERO: CRD42023421164). The search yielded fourteen studies that met the inclusion/exclusion criteria. The sample size among pregnant women ranged from 173 to 64,189, and among children ranged from 88 to 49,190. Maternal caffeine consumption during pregnancy ranged from 0 to 1000 mg/day, with the highest levels observed during mid-pregnancy. Seven studies indicated a potential association between prenatal caffeine exposure and neurobehavioral/neurodevelopment deficits, one study showed that prenatal caffeine exposure improved peer problems, and six studies did not show a significant effect of prenatal caffeine consumption on neurobehavioral disorders. The included studies were classified as moderate for the risk of bias and with very low certainty of evidence. Thus, the evidence is insufficient to confirm with certainty that the prenatal caffeine exposure leads to neurobehavioral disorders. Studies heterogenicity, as well as their variable quality and the presence of several confounding factors, generate uncertainty.

Gestational lead exposure and its effects on fetal/infant development - A systematic review.

Studies suggest that gestational exposure to lead (Pb) is related to spontaneous abortions, preterm birth, lower infant birth weight and length, and neurological dysfunctions. However, the evidence about its effects during pregnancy exposure on fetal and child development is still poor. Thus, the aim of this systematic review was to verify the association between prenatal exposure to Pb and the occurrence of neurobehavioral deficits, miscarriages, and child mortality. Observational studies with pregnant women exposed to Pb during pregnancy were included, without gender or ethnicity restrictions. The MEDLINE, Cochrane Library, EMBASE, Scopus, Web of Science, and LILACS databases were searched. The reading of titles and abstracts was conducted, followed by reading in full format and data extraction, that were performed independently by two reviewers. The included studies were evaluated by Downs and Black tool and qualitatively synthesized. Certainty of evidence was assessed by Grading of Recommendations Assessment, Development, and Evaluations (GRADE). The study protocol was registered with the Prospective Registry of Systematic Reviews (PROSPERO; CRD42022296750). Among twenty-one studies included, sixteen were classified as prospective cohort, two case-control, one nested case-control, one cohort, and one longitudinal study. No study that evaluated child mortality associated with gestational Pb exposure was found. There is a very low certainty of evidence in the association of gestational Pb exposure and neurobehavioral deficits or miscarriages. This systematic review reflects the poor evidence and the challenges of human toxicology studies, since it was not possible to associate gestational Pb exposure to neurobehavioral deficits, miscarriages, and child mortality.

Murine response to the opportunistic bacterium Pseudomonas aeruginosa infection in gut dysbiosis caused by 5-fluorouracil chemotherapy-induced mucositis.

AIMS: This manuscript aims to explain the relationship between mucositis caused by 5-FU over gut bacterial species and susceptibility to opportunistic infection caused by P. aeruginosa. MAIN METHODS: BALB/c mice were intraperitoneally treated with PBS or 5-FU. Bodyweight and faecal consistency were checked daily. Mice faecal DNA was extracted, and bacterial phylogenetic groups were analysed using qPCR or high-throughput sequencing. Immunofluorescence was used to evaluate BMDM activation by mice-treated faecal content. Mice were challenged intratracheally with virulent P. aeruginosa, and the CFU and histology were analysed. Faecal microbiota were transplanted to evaluate the gut microbiota and resistance to pulmonary P. aeruginosa recovery. KEY FINDINGS: The animals treated with 5-FU presented mucositis with great weight loss, altered faecal consistency, bacterial gut dysbiosis and histological changes in the intestinal mucosa. Mice under 5-FU treatment were more susceptible to lung infection by the bacteria P. aeruginosa and had more extensive tissue damage during their lung infection with greater pro-inflammatory gene expression. It was observed that the mucositis remained in the groups with 5-FU even with the FMT. The results caused by mucositis in animals that received allogeneic FMT were reversed, however, with a decrease in P. aeruginosa susceptibility in animals treated with 5-FU and allogeneic FMT compared to animals treated with 5-FU and autologous FMT. SIGNIFICANCE: Treatment with 5-FU in a murine model makes it more susceptible to pulmonary infection by the bacterium P. aeruginosa, FMT offers an opportunity to protect against this susceptibility to infection.