BMC Pregnancy and Childbirth最新文献

Background: This retrospective before-after study aimed to evaluate whether tuberculosis preventive treatment (TPT) for tuberculosis infection (TBI, previously referred to as "latent TB infection" or LTBI) is associated with improved pregnancy outcomes in infertile women undergoing in vitro fertilization and embryo transfer (IVF-ET), and whether outcomes differ by the TPT duration and embryo origin.

Methods: All participants initiated the WHO-recommended 3HP regimen (once-weekly isoniazid plus rifapentine; 12 doses over 3 months) after active TB was excluded. In this retrospective real-world cohort, the total documented duration of combination therapy varied in the medical record (3-18 months). Using a within-patient design, we compared pregnancy outcomes between embryo transfer cycles conducted before and after TPT. Post-TPT cycles were further stratified by TPT duration (3 months, 6 months, 12 months, 18 months) and embryo origin (embryos were cryopreserved from a cycle prior to TPT or derived after TPT ) to compare pregnancy outcomes within each stratum.

Results: After TPT, biochemical pregnancy, clinical pregnancy, and live birth rates increased significantly, while early miscarriage rates decreased. Live birth rates did not differ significantly across the TPT duration subgroups (range: 32.69-39.29%). Among women with recurrent implantation failure, the live birth rate increased to 34.38% after TPT. Pregnancy outcomes did not differ by embryo origin.

Conclusions: In infertile women with TBI undergoing IVF-ET, initiation of TPT with the guideline-recommended 3-month 3HP regimen was associated with improved pregnancy outcomes. In exploratory analyses, longer documented durations beyond 3 months were not associated with higher live-birth rates, supporting consideration of the standard course while acknowledging residual confounding inherent to this retrospective design.

Background: Meconium serves as a valuable biological matrix for characterizing fetal metabolic signatures throughout gestation. Selective fetal growth restriction (sFGR) is associated with adverse neurological outcomes, potentially mediated by underlying metabolic perturbations. However, the specific relationship between dysregulated meconium metabolome and brain injury in sFGR remains poorly understood.

Methods: Untargeted metabolomics analysis was performed on meconium samples from sFGR (n = 20) and monochorionic diamniotic twins with birth weight concordance (MCDA-C, n = 13) to quantify metabolic alterations. Neonatal brain injury was assessed via cranial ultrasonography, and long-term neurodevelopmental outcomes were evaluated at 2-3 years of age using the Ages and Stages Questionnaire-third edition subscale. Univariate analysis, partial least-squares discrimination analysis (PLSDA) and pathway analysis were employed to compare the metabolic profiles across different brain injury categories. Machine learning algorithms and receiver operating characteristic (ROC) curve were utilized to identify potential biomarkers associated with neonatal brain injury. Spearman's-based correlation analysis was employed to correlate metabolites levels with physical development and long-term neurodevelopmental outcomes.

Results: In our study, PLSDA revealed distinct clustering of meconium metabolites profiles in neonates with severe brain injury compared to those with mild brain injury or normal findings. In all sFGR neonates, logistic regression identified two fatty acid metabolism products, 13, 16-docosadienoic acid and nonadecanoic acid, as notably associated with neonatal severe brain injury. Divergent meconium metabolic signatures associated with severe brain injury were observed between the smaller fetus (sFGR-S) and larger fetus (sFGR-L) in sFGR twins. In particular, nicotinamide, hippuric acid, citramalic acid and succinic acid were closely associated with severe brain injury in sFGR-S. Pathway analysis implicated significant dysregulation of the citrate cycle in this subgroup. For sFGR-L, histidine and trans-4-hydroxyproline emerged as best predictive markers for severe brain injury and showed significant correlations with long-term neurodevelopmental outcomes including gross motor and fine motor.

Conclusions: Dysregulated fatty acid metabolites in the meconium of sFGR neonates are associated with severe brain injury. Divergent metabolomic profiles between sFGR-S and sFGR-L revealed distinct pathological mechanisms underlying brain injury. These findings provide novel insights into metabolic mechanisms of brain injury in sFGR and offer potential predictive biomarkers for adverse neurological outcomes.