Placental programming of infant neurodevelopment in the context of maternal care

孕产妇护理背景下婴儿神经发育的胎盘编程

• 批准号: 1942116
• 金额: --
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1942116
• 关键词: Placental; programming; infant; neurodevelopment; context

Providing a biological explanation for the relationship between the mother's mental health and her child's neurodevelopmental outcomes represents one of the greatest challenges of perinatal medicine. Maternal stress, anxiety and depression have all been shown to increase the risk of psychopathology in children while poor maternal care has similarly adverse outcomes. In an experimental model, we have shown that placental endocrine dysfunction programs both poor maternal care and adverse offspring behaviour. These observations lead us to the novel hypothesis that placental endocrine dysfunction underlies the co-occurrence of maternal mood disorders, impaired maternal care and adverse infant neurodevelopmental outcomes frequently reported in human pregnancies. Our recently published research (Psychological Medicine 2016) supports the relationship between placental endocrine dysfunction and prenatal depression. We now have a unique and timely opportunity to further test our hypothesis captilising on a current MRC funded human study cohort called Grown in Wales, to examine the role of placental endocrine dysfunction in the programming of maternal care and abnormal infant behaviour. Analysing infant neurodevelopment and parenting behaviour in this cohort will build on our current MRC study adding value and significantly enriching our understanding of the consequence of placental endocrine dysfunction. Importantly, the inclusion of similar measurements of parenting behaviour and infant outcomes in the ALSPAC-G2 study will substantially increase the wider impact of the proposed work. Added value: Existing data on maternal mood, maternal biological characteristics and lifestyles, maternal blood and saliva, cord blood, placenta, RNAseq of placenta from mothers with highest and lowest scores, follow-on maternal data at 2 and 12 months, infant assessment data at 12 months and access to data from the ALSPAC-G2 study. Aim 1. To assess infant cognitive, emotional and behavioural development alongside maternal care in a cohort of mother-infant pairs with well characterised pre and postnatal maternal mood data. Aim 2. To establish whether placental endocrine dysfunction and aberrant imprinting correlate with a) quality of maternal care and/or b) infant neurodevelopmental outcomes Aim 3. To determine the wider relevance of these findings within ALSPAC-G2. Aim 4. Where exposure-characterstic-outcome is established, apply a causal analysis framework to strengthen causal inference. Research training: Next generation sequencing, bioinformatics, theoretical, methodological and advanced data analytic skills (recognised as an area of significant skills deficiency in UK social science), multivariate statistics and analysis of longitudinal data (through formal courses and supervision by the applicants), user engagement and dissemination. Multidisciplinary: developmental epigenetics, infant neurodevelopment, epidemiology and social science.Supporting Documentation.

为母亲的心理健康与孩子的神经发育结果之间的关系提供生物学解释是围产期医学面临的最大挑战之一。母亲的压力、焦虑和抑郁都被证明会增加儿童患精神病理学的风险，而不良的母亲护理也会产生类似的不良后果。在实验模型中，我们发现胎盘内分泌功能障碍会导致不良的孕产妇护理和不良的后代行为。这些观察结果使我们得出一个新的假设，即胎盘内分泌功能障碍是人类妊娠中经常报告的母亲情绪障碍、母亲护理受损和婴儿神经发育不良结果同时发生的基础。我们最近发表的研究（Psychological Medicine 2016）支持胎盘内分泌功能障碍与产前抑郁症之间的关系。现在，我们有一个独特而及时的机会来进一步检验我们的假设，利用目前 MRC 资助的名为“Grown in Wales”的人类研究队列，以检查胎盘内分泌功能障碍在孕产妇护理和婴儿异常行为规划中的作用。分析该队列中的婴儿神经发育和养育行为将以我们目前的 MRC 研究为基础，增加价值并显着丰富我们对胎盘内分泌功能障碍后果的理解。重要的是，ALSPAC-G2 研究中纳入类似的育儿行为和婴儿结局测量将大大增加拟议工作的更广泛影响。附加价值：母亲情绪、母亲生物学特征和生活方式、母体血液和唾液、脐带血、胎盘、最高和最低分数母亲的胎盘RNAseq的现有数据、2个月和12个月的后续母亲数据、婴儿评估数据12 个月时并可访问 ASPAC-G2 研究的数据。目标 1. 通过具有明确特征的产前和产后母亲情绪数据，在母婴对队列中评估婴儿认知、情感和行为发展以及母亲护理。目标 2. 确定胎盘内分泌功能障碍和异常印记是否与 a) 孕产妇护理质量和/或 b) 婴儿神经发育结果相关 目标 3. 确定这些发现在 ASPAC-G2 中更广泛的相关性。目标 4. 在建立暴露特征结果后，应用因果分析框架来加强因果推断。研究培训：下一代测序、生物信息学、理论、方法和高级数据分析技能（被认为是英国社会科学中严重技能缺乏的领域）、多元统计和纵向数据分析（通过正规课程和申请人的监督），用户参与和传播。多学科：发育表观遗传学、婴儿神经发育、流行病学和社会科学。支持文档。

项目成果

The placenta protects the fetal circulation from anxiety-driven elevations in maternal serum levels of brain-derived neurotrophic factor.

• DOI: 10.1038/s41398-020-01176-8
• 发表时间: 2021-01-18
• 期刊: Translational psychiatry
• 影响因子: 6.8
• 作者: Dingsdale H;Nan X;Garay SM;Mueller A;Sumption LA;Chacón-Fernández P;Martinez-Garay I;Ghevaert C;Barde YA;John RM
• 通讯作者: John RM

Risk factors for excessive gestational weight gain in a UK population: a biopsychosocial model approach.

• DOI: 10.1186/s12884-020-03519-1
• 发表时间: 2021-01-10
• 期刊: BMC pregnancy and childbirth
• 影响因子: 3.1
• 作者: Garay SM;Sumption LA;Pearson RM;John RM
• 通讯作者: John RM

Persistence of anxiety symptoms after elective caesarean delivery.

• DOI: 10.1192/bjo.2018.48
• 发表时间: 2018-09
• 期刊: BJPsych open
• 影响因子: 5.4
• 作者: Janssen AB;Savory KA;Garay SM;Sumption L;Watkins W;Garcia-Martin I;Savory NA;Ridgway A;Isles AR;Penketh R;Jones IR;John RM
• 通讯作者: John RM