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.

为母亲的心理健康和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疾病的风险，而糟糕的母亲护理也有类似的不良后果。在一个实验模型中，我们已经表明胎盘内分泌功能障碍程序既差的产妇护理和不良的后代行为。这些观察结果使我们提出了一种新的假设，即胎盘内分泌功能障碍是孕妇情绪障碍、产妇护理受损和婴儿神经发育不良的共同发生的基础，这些在人类妊娠中经常报道。我们最近发表的研究（心理医学2016）支持胎盘内分泌功能障碍与产前抑郁之间的关系。我们现在有一个独特而及时的机会来进一步验证我们的假设，利用MRC资助的一项名为“威尔士生长”的人类研究队列，研究胎盘内分泌功能障碍在产妇护理和婴儿异常行为中的作用。在这个队列中分析婴儿神经发育和父母行为将建立在我们目前的MRC研究的基础上，增加价值，并显著丰富我们对胎盘内分泌功能障碍后果的理解。重要的是，在alspaco - g2研究中纳入类似的父母行为和婴儿结果测量将大大增加拟议工作的更广泛影响。附加价值：评分最高和最低母亲的现有产妇情绪、产妇生物学特征和生活方式、产妇血液和唾液、脐带血、胎盘、胎盘RNAseq数据、2个月和12个月产妇随访数据、12个月婴儿评估数据以及alspaco - g2研究数据。目的1。评估婴儿的认知，情感和行为发展与产妇护理的母婴对队列具有良好的特征产前和产后产妇情绪数据。目标2。确定胎盘内分泌功能障碍和异常印记是否与a)产妇护理质量和/或b)婴儿神经发育结局相关。确定这些发现在alspaco - g2中更广泛的相关性。目标4。在建立了暴露特征-结果的情况下，应用因果分析框架来加强因果推理。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重大技能不足的领域），多元统计和纵向数据分析（通过正式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.

剖腹产后，焦虑症状的持久性。

• 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