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Published on: November 20, 2015
Identification and prediction model of placenta-brain axis genes associated with neurodevelopmental delay in moderate
Yumin Zhu1,2, Yimin Zhang3, Yunfan Jin4
1Medical School, Nanjing University, Nanjing, Jiangsu, China. zhuyumin2011@163.com.
Insights
Moderate and late preterm birth increases neurodevelopmental delay risk in children, particularly boys. Placental genes APOE and CST3 may serve as biomarkers for early detection and intervention in these infants.
Area of Science:
- Neuroscience
- Genetics
- Public Health
Background:
- Moderate and late preterm (MLPT) birth is a significant global health concern.
- Understanding the link between MLPT birth and neurodevelopmental delays, including biological mechanisms, is crucial.
- The placenta-brain axis (PBA) offers a novel framework for investigating gene regulation and predicting neurodevelopmental outcomes in MLPT infants.
Purpose of the Study:
- To investigate the association between MLPT birth and neurodevelopmental outcomes in children.
- To identify biological mechanisms, specifically placental gene regulation via the PBA, underlying these delays.
- To develop a predictive model for neurodevelopmental delay in MLPT children.
Main Methods:
- Utilized multivariate logistic regression with data from 129 MLPT infants and 3136 full-term controls.
- Employed bioinformatics analysis of RNA-seq data and RT-qPCR to identify dysregulated PBA genes in MLPT placentas.
- Developed prediction models for neurodevelopmental delay using machine learning algorithms.
Main Results:
- MLPT birth was associated with an increased risk of neurodevelopmental delay at 6, 18, and 48 months, with a higher incidence in boys.
- The genes APOE and CST3 were significantly correlated with motor and social development in 6-month-old male MLPT infants.
- A sex-specific association between MLPT and neurodevelopmental delays was observed.
Conclusions:
- MLPT birth exhibits a sex-specific association with neurodevelopmental delays.
- APOE and CST3 are identified as potential placental biomarkers for neurodevelopmental delay.
- Findings support improved etiological investigation, risk prediction, and early intervention strategies for MLPT children.
Background:
Moderate and late preterm (MLPT) birth accounts for the vast majority of preterm births, which is a global public health problem. The association between MLPT and neurobehavioral developmental delays in children and the underlying biological mechanisms need to be further revealed. The "placenta-brain axis" (PBA) provides a new perspective for gene regulation and risk prediction of neurodevelopmental delays in MLPT children.
Methods:
The authors performed multivariate logistic regression models between MLPT and children's neurodevelopmental outcomes, using data from 129 MLPT infants and 3136 full-term controls from the Ma'anshan Birth Cohort (MABC). Furthermore, the authors identified the abnormally regulated PBA-related genes in MLPT placenta by bioinformatics analysis of RNA-seq data and RT-qPCR verification on independent samples. Finally, the authors established the prediction model of neurodevelopmental delay in children with MLPT using multiple machine learning models.
Results:
The authors found an increased risk of neurodevelopmental delay in children with MLPT at 6 months, 18 months, and 48 months, especially in boys. Further verification showed that APOE and CST3 genes were significantly correlated with the developmental levels of gross-motor domain, fine-motor domain, and personal social domain in 6-month-old male MLPT children.
Conclusions:
These findings suggested that there was a sex-specific association between MLPT and neurodevelopmental delays. Moreover, APOE and CST3 were identified as placental biomarkers. The results provided guidance for the etiology investigation, risk prediction, and early intervention of neurodevelopmental delays in children with MLPT.
