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了生物学解释，这是围产医学最大的挑战之一。孕产妇的压力，焦虑和抑郁症都被证明会增加儿童心理病理学的风险，而较差的孕产妇护理也会产生类似的不良后果。在实验模型中，我们已经表明，胎盘内分泌功能障碍计划既不良产妇护理和不良后代行为。这些观察结果使我们提出了这样一种新的假设，即胎盘内分泌功能障碍是孕产妇情绪障碍同时发生的基础，孕产妇护理和不良婴儿神经发育结果经常在人类妊娠中经常报道。我们最近发表的研究（心理医学，2016年）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，可以进一步检验我们对当前MRC资助的人类研究队列中的假设，以研究胎盘内分泌功能障碍在孕产妇护理和异常婴儿行为编程中的作用。分析该队列中的婴儿神经发育和育儿行为将建立在我们当前的MRC研究的基础上，从而增加了价值，并显着丰富了我们对胎盘内分泌功能障碍后果的理解。重要的是，在ALSPAC-G2研究中纳入了育儿行为和婴儿结果的类似测量，将大大增加所提出的工作的更广泛影响。附加价值：现有有关母体情绪，母体生物学特征和生活方式，孕妇血液和唾液，脐带血，胎盘，胎盘，胎盘的RNASEQ，来自分数最高和最低的母亲，2个月和12个月的孕产妇数据，婴儿评估数据在12个月时以及来自ALSPAC-G2研究的数据。目的1。在一系列母亲的孕产前和产后母体情绪数据中评估婴儿的认知，情感和行为发展以及孕产妇护理。目的2。确定胎盘内分泌功能障碍和异常烙印与a）孕产妇护理和/或b）婴儿神经发育结果的质量是否目标3。确定这些发现在Alspac-G2中的更广泛相关性。 AIM 4。在建立暴露 - 特征的结果时，请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，方法论和先进的数据分析技能（被公认为是英国社会科学中重要技能缺乏的领域），多元统计以及对纵向数据的分析（通过申请人的正式课程和监督），用户参与和散布。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