The early life microbiome plays an important role in developmental and long-term health outcomes. However, it is unknown whether adverse pregnancy complications affect the offspring's gut... Show moreThe early life microbiome plays an important role in developmental and long-term health outcomes. However, it is unknown whether adverse pregnancy complications affect the offspring's gut microbiome post-natally and in early years. In a longitudinal cohort with a five-year follow-up of mother-child pairs affected by preeclampsia (PE) or spontaneous preterm birth (sPTB), we evaluated offspring gut alpha and beta diversity as well as taxa abundances considering factors like breastfeeding and mode of delivery. Our study highlights a trend where microbiome diversity exhibits comparable development across adverse and normal pregnancies. However, specific taxa at genus level emerge with distinctive abundances, showing enrichment and/or depletion over time in relation to PE or sPTB. These findings underscore the potential for certain adverse pregnancy complications to induce alterations in the offspring's microbiome over the course of early life. The implications of these findings on the immediate and long-term health of offspring should be investigated in future studies. Show less
Background: Prenatal vitamin D deficiency is associated with asthma or recurrent wheezing in offspring. However, evidence from randomized trials on the efficacy of vitamin D supplementation is... Show moreBackground: Prenatal vitamin D deficiency is associated with asthma or recurrent wheezing in offspring. However, evidence from randomized trials on the efficacy of vitamin D supplementation is inconclusive. Objectives: We aimed to examine the differential efficacy of prenatal vitamin D supplementation based on the maternal baseline vitamin D status and the starting time of supplementation to prevent early life asthma or recurrent wheezing. Methods: We conducted a secondary analysis of the Vitamin D Antenatal Asthma Reduction Trial (VDAART), a randomized double-blind trial of prenatal vitamin D supplementation initiated at 10-18 weeks (wks) of gestation (4400 IU of intervention/day compared with 400 IU of placebo/day) to prevent offspring asthma or recurrent wheezing by the age of 6 years. We assessed the effect of modification of supplementation by maternal baseline vitamin D status at enrollment and the timing of initiation of supplementation. Results: An inverse relationship was observed between maternal 25-hydroxyvitamin D (25(OH)D) levels at trial entry and 25(OH)D levels during late pregnancy (32-38 wks of gestation) in both supplementation arms (P < 0.001). Overall, supplementation efficacy was not dependent on the maternal baseline 25(OH)D status. However, a trend toward the reduction of asthma or recurrent wheezing was observed across the baseline groups in the intervention arm (P = 0.01), with the greatest reduction observed in the most severely vitamin D-deficient women (25(OH)D < 12 ng/mL; adjusted odds ratio [aOR] = 0.48; confidence interval [CI]: 0.17, 1.34). Gestational age at trial enrollment modified supplementation efficacy, showing a greater reduction of offspring asthma or recurrent wheezing with earlier intervention during pregnancy (aOR = 0.85; CI = 0.76, 0.95), particularly in women who were 9-12 wk pregnant (aOR = 0.45; CI = 0.24, 0.82). Conclusions: Pregnant women with severe vitamin D deficiency show the greatest 25(OH)D improvement because of supplementation. In these women, a vitamin D dose of 4400 IU might have a preventive role in the development of early life offspring asthma or recurrent wheezing. Gestational age is suggested to modify the efficacy of prenatal vitamin D supplementation, showing the highest beneficial effect if supplementation is started during the first trimester of pregnancy. This study is an ancillary analysis from the VDAART, which is registered in ClinicalTrials.gov as NCT00902621. Show less
Objective To facilitate patient disease subset and risk factor identification by constructing a pipeline which is generalizable, provides easily interpretable results, and allows replication by... Show moreObjective To facilitate patient disease subset and risk factor identification by constructing a pipeline which is generalizable, provides easily interpretable results, and allows replication by overcoming electronic health records (EHRs) batch effects. Material and Methods We used 1872 billing codes in EHRs of 102 880 patients from 12 healthcare systems. Using tools borrowed from single-cell omics, we mitigated center-specific batch effects and performed clustering to identify patients with highly similar medical history patterns across the various centers. Our visualization method (PheSpec) depicts the phenotypic profile of clusters, applies a novel filtering of noninformative codes (Ranked Scope Pervasion), and indicates the most distinguishing features. Results We observed 114 clinically meaningful profiles, for example, linking prostate hyperplasia with cancer and diabetes with cardiovascular problems and grouping pediatric developmental disorders. Our framework identified disease subsets, exemplified by 6 "other headache" clusters, where phenotypic profiles suggested different underlying mechanisms: migraine, convulsion, injury, eye problems, joint pain, and pituitary gland disorders. Phenotypic patterns replicated well, with high correlations of >= 0.75 to an average of 6 (2-8) of the 12 different cohorts, demonstrating the consistency with which our method discovers disease history profiles. Discussion Costly clinical research ventures should be based on solid hypotheses. We repurpose methods from single-cell omics to build these hypotheses from observational EHR data, distilling useful information from complex data. Conclusion We establish a generalizable pipeline for the identification and replication of clinically meaningful (sub)phenotypes from widely available high-dimensional billing codes. This approach overcomes datatype problems and produces comprehensive visualizations of validation-ready phenotypes. Show less
