Autologous cord blood mononuclear cell infusion for the prevention of bronchopulmonary dysplasia in very preterm monozygotic twins: A study protocol for a randomized, placebo-controlled, double-blinded multicenter trial.

Background: Preterm-associated complications remain the main cause of neonatal death. Survivors face the challenges of short- and long-term complications. Among all complications, bronchopulmonary dysplasia (BPD) remains the first important cause of neonatal mortality and morbidity. Current treatment does not address this main preterm complication. Cord blood is regarded as a convenient source of stem cells. The paracrine bioactive factors of stem cells contribute to tissue repair and immune modulation. Our clinical studies and those of others have shown that cord blood cell infusion is both safe and possibly effective in the prevention and treatment of BPD. The therapeutic use of cord blood has emerged as a promising therapy. However, the genetic heterogeneity between control and intervention groups may reduce the comparability especially among small sample trials. The purpose of this study protocol is to investigate the effects of autologous cord blood mononuclear cell (ACBMNC) infusion on the prevention of BPD in very preterm monozygotic twins of less than 32 gestation weeks. Methods: In this prospective, randomized, placebo-controlled, double-blinded multicenter clinical trial, 60 pairs of monozygotic twin preterm neonates of less than 32 weeks admitted to the Neonatal Intensive Care Unit are randomly assigned to receive intravenous ACBMNC infusion (targeted at 5 × 107 cells/kg) or placebo (normal saline) within 24 h after birth in a 1:1 ratio. The primary outcome will be survival without BPD at 36 weeks of postmenstrual age. The secondary outcomes will include the mortality rate, BPD severity, other common preterm complication rates, respiratory support duration, length and cost of hospitalization, and long-term respiratory and neurodevelopmental outcomes during a 2-year follow-up. Furthermore, we will perform single-cell RNA sequencing for cord blood cells and blood cells 3-10 days after intervention and detect whether reactive oxygen species and inflammatory cytokines are present. Conclusion: This will be the first randomized, placebo-controlled, double-blinded trial to evaluate the efficacy of ACBMNC infusion to prevent BPD in monozygotic twin premature infants and investigate the underlying protective mechanisms. The results of this trial will provide valuable clinical evidence for translational application of cord blood cell therapy in very preterm infants.Trial registration: ClinicalTrials.gov, NCT05087498, registered 10/09/2021, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BAD7&selectaction=Edit&uid=U0002PLA&ts=2&cx=qvyylv.

Relationship between maternal adverse childhood experiences and preschool children s emotional and behavioral problems / 中国学校卫生

Objective@#To explore the relationship and gender difference between maternal adverse childhood experiences (ACEs) with emotional and behavioral problems (EBPs) in preschool children, and to provide a reference to promote emotional and behavioral problems among preschool children.@*Methods@#Using the method of stratified cluster sampling, 9 647 children from kindergartens in three cities of Anhui Province were selected in June 2021. Maternal adverse childhood experiences were investigated with the WHO Adverse Childhood Experiences International Questionnaire(ACEs-IQ), preschool children s emotional and behavioral problems were investigated with Strengths and Difficulties Questionnaire.@*Results@#The detection rate of abnormal emotional behavior was 17.4%, emotional symptoms 16.3%, conduct problems 18.3%, hyperactivity 22.7%, peer problems 34.2%, prosocial behaviors 18.5%. Multivariate Logistic regression analysis showed that maternal adverse childhood experiences were positively associated with the risk of emotional and behavioral problems ( OR =1.51-2.97, P <0.01). Maternal cumulative adverse childhood experiences were also positively associated with the risk of emotional and behavioral problems( OR =3.13-9.61, P <0.01). The association of maternal emotional abuse, physical abuse and community violence with peer problems were stronger in boys than that of girls ( ROR =1.25, 1.26, 1.41, P <0.05).@*Conclusion@#The findings suggest maternal adverse childhood experiences were associated with emotional behavior problems among preschool children. Focusing on the maternal adverse childhood experiences is crucial for the prevention and control of childhood emotional and behavioral problems.