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OBJECTIVE: To assess whether labour variables (i.e. individuals characteristics, labour characteristics and medical interventions) impact maternal and newborn microbiomes. DESIGN: Prospective monocentric study. SETTING: Saint-Joseph Hospital tertiary maternity unit, in Paris, France. POPULATION: All consecutive primiparous women with a physiological pregnancy and term labour from 15 April to 1 June 2017. METHODS: 16S ribosomal RNA gene sequencing of the maternal vaginal, newborn skin and newborn oral microbiomes from 58 mother-baby dyads. MAIN OUTCOME MEASURES: Analysis of the effects of 19 labour variables on the composition and diversity of these microbiomes. RESULTS: The 19 labour variables explained a significant part of the variability in the vaginal, newborn oral and skin microbiomes (44%-67%). Strikingly, duration of rupture of membranes was the single factor that explained the greatest variability (adjusted R2 : 7.7%-8.4%, p ≤ 0.002) and conditioned, by itself, the compositions of the three microbiomes under study. Long duration of rupture of membranes was specifically associated with a lower relative abundance of the Lactobacillus genus (1.7-fold to 68-fold reduction, p < 0.0001) as well as an increase in microbiome diversity, including genera implicated in nosocomial infections. The effects of duration of rupture of membranes were also present in newborns delivered by non-elective caesarean section. CONCLUSIONS: Maternal and newborn microbiomes were greatly affected by labour variables. Duration of rupture of membranes, even in non-elective caesarean sections, should be considered in epidemiological and microbiological studies, as well as in vaginal seeding practices.
RESUMO
Aim: We previously conducted exome-wide association study in acute lymphoblastic leukemia patients and identified association of five SNPs with asparaginase-related thrombosis. Here we aimed to replicate these findings in an independent patient cohort and through analyses in vitro. Patients & methods: SNPs located in IL16, MYBBP1A, PKD2L1, RIN3 and MPEG1 genes were analyzed in patients receiving Dana-Farber Cancer Institute acute lymphoblastic leukemia treatment protocols 05-001 and 11-001. Thrombophilia-related variations were also analysed. Results: IL16 rs11556218 conferred higher risk of thrombosis and higher in vitro sensitivity to asparaginase. The association was modulated by the treatment protocol, risk group and immunophenotype. A crosstalk between factor V Leiden, non-O blood groups and higher risk of thrombosis was also seen. Conclusion: IL16 and factor V Leiden variations are implicated in asparaginase-related thrombosis.
This study looked at how certain genetic variations are related to a higher risk of blood clots in children with a type of cancer called acute lymphoblastic leukemia who are receiving a certain treatment (asparaginase). The study found that one specific genetic variation (IL16 rs11556218) was linked to a higher risk of blood clots (thrombosis), and that this risk was influenced by disease and treatment features. The study also found that a certain genetic variation (factor V Leiden), which makes blood more likely to clot, and blood type (non-O) were linked to a higher risk of thrombosis. The conclusion of this study is that genetic variations may play a role in blood clots in children with acute lymphoblastic leukemia receiving asparaginase, and if further confirmed, these variations can serve to advance personalized treatment strategies.
