ABSTRACT
ObjectiveTo design a prospective nested case-control study based on a city-wide birth cohort of Shanghai， so as to understand their health status and explore the influencing factors of birth defects. MethodsBased on the birth registration covering the entire city of Shanghai， the nested case-control study of children with severe birth defects was designed. Children born with severe birth defects were selected as the case group， and healthy children were matched as the control group. Basic information， health status， maternal pregnancy history， and survival outcome of children both in the case group and the control group were collected through medical history review and home visits. The logistic regression model was used for multivariate analysis. ResultsA total of 18 875 infants born between January 1， 2011， and December 31， 2021， were included， among which 11 500 （60.93%） were children with severe birth defects and 7 375 （39.07%） were healthy children. The logistic regression model analysis showed that being male （OR=1.20， 95%CI：1.13‒1.29）， non-Shanghai residency （OR=1.16， 95%CI： 1.06‒1.25）， multiple births （OR=8.41， 95%CI：6.25‒11.30）， artificial insemination （OR=2.31， 95%CI：1.34‒3.99）， in vitro fertilization （IVF） （OR=1.85， 95%CI：1.44‒2.38）， maternal exposure to radiation （OR=1.83， 95%CI：1.07‒3.14）， maternal illness during pregnancy （OR=1.61， 95%CI：1.49‒1.74）， experiencing a traumatic event during pregnancy （OR=2.34， 95%CI：1.88‒2.92）， paternal chemical exposure （OR=1.88， 95%CI：1.32‒2.69）， paternal radiation exposure （OR=1.65， 95%CI： 1.18‒2.33）， family history of birth defects （OR=8.18， 95%CI： 3.96‒16.89）， being overweight before pregnancy （OR=1.16， 95%CI： 1.07‒1.27）， being obese before pregnancy （OR=1.15， 95%CI：1.03‒1.30）， and being excessively obese before pregnancy （OR=1.52， 95%CI：1.26‒1.83） were risk factors for the occurrence of birth defects. Analysis by type of birth defect found that prematurity was a risk factor for cardiac malformations and cheilopalatoschisis （OR=27.87， 95%CI： 20.84‒37.27）， especially ranking first in cardiac malformations. ConclusionAfter controlling for influencing factors， maternal overweight， obesity， and excessive obesity before pregnancy， artificial insemination， and IVF are independent risk factors for the occurrence of birth defects. Choosing a healthy lifestyle， improving physical and mental health during pregnancy， and controlling BMI during pregnancy are beneficial in reducing the risk of birth defects.
ABSTRACT
Objective:To explore the molecular mechanism of pathological changes in osteoarthritis (OA) through applying bioinformatics to analyze the miRNA-mRNA regulatory network.Methods:MiRNA expression data from human serum samples were downloaded from the Gene Expression Omnibus database. Differentially-expressed miRNA was identified using the linear modelling package of the Bioconductor software suite. The target differentially-expressed mRNA was predicted using version 2.0 of the miRWalk database. Version 3.7.1 of the Cytoscape software was used to construct the miRNA-mRNA regulatory network for OA. The target genes were analyzed by using gene ontology and the Kyoto Encyclopedia of Genes and Genomes. The protein-protein interaction network was constructed and the core genes in osteoarthritis pathology were screened out.Results:A total of 7 differentially-expressed miRNAs (all down-regulated) and 900 mRNAs were identified, mostly involved in the negative regulation of protein binding, DNA binding, or transcription in the cell cycle. Ten core genes were screened out: MAPK1, TP53, MAPK14, CCND1, EP300, POLR2E, POLR2F, ABL1, RAC1 and SKIV2L2.Conclusions:Multiple miRNAs, target genes and signaling pathways are involved in the development of OA. The miRNA-mRNA regulatory network identified provides new ideas for exploring the molecular mechanism of OA′s pathology and its clinical diagnosis and treatment.