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Project

The effect of perinatal stress on the development of preterm infants

Worldwide, more than 10% of all babies are born preterm (< 37 weeks of gestation). In the global burden of disease, preterm birth complications account for 3.1% of all Disability Adjusted Life Years (i.e. the amount of years of healthy life lost due to death and non-fatal impairment or illness) which is in the same order of magnitude such as HIV/AIDS (Murray et al.; 2013). Advances in neonatal care, such as the use of antenatal corticosteroids, surfactant administration and assisted ventilation have improved survival rates in high-income countries. However, very preterm infants remain at risk for adverse health outcome and neurodevelopmental disability. Cerebral palsy, serious motor delays, cognitive impairments, learning deficits, and an increase in behavioural (ADHD, autism) and emotional problems have been observed in very preterm infants (Aarnoudse-Moens et al., 2009; Reijneveld et al., 2006). As  these maladaptive outcomes have a severe effect on these children’s quality of life and a huge economic impact on society, the current proposal study aims to improve our understanding about a factor that has been proposed as crucial: exposure to perinatal distress.

The period during which preterm infants are admitted to the Neonatal Intensive Care Unit (NICU) is distressing for both infant and parents. Researchers are increasingly concerned about the impact of stress during this vulnerable period of rapid brain growth on the infant’s development and on bonding and attachment processes between parents and infants. Early life stress predisposes individuals to a number of psychiatric syndromes, particularly mood and anxiety disorders (Heim at al., 2010), and causes profound and lasting changes in biological stress response systems such as the HPA axis (Carpenter et al., 2007). Evidence from animal research shows that stress in early life has adverse effects on later emotional and cognitive functioning (Mirescu et al., 2004; Pechtel et al. 2011). In normal development, the detrimental effect of distress is attenuated by mother’s sensitive support and the associated development of children’s secure attachment bonds with their mother. However, parents of very preterm children perceive the period of hospitalization of their child as a period of great distress and posttraumatic stress symptoms are described in mothers of preterm children. As distress disrupts the parent’s ability to provide sensitive support, preterm infants could be more vulnerable to develop insecure attachment bonds (Singer et al., 2010), and consequently for the effects of perinatal distress. The mediational role of parent personality profiles, their resilience and competence, in the long term development of the child’s personality and behaviour has been well studied in typically developing children but not in preterm infants. Finally, recent studies have shown that early life stress affects gene expression profiles trough epigenetic modification, such as methylation changes at the promotor site of the glucocorticoid receptor (GR) gene NR3C1 (Glover et al., 2010).

Project goals and their impact on societal challenges

Objective 1: The first goal of the project is to identify objective stress markers that can be obtained easily and non-invasively in preterm infants during NICU hospitalization. This will include the development of novel techniques to measure stress related heart rate variability (HRV) and EEG maturation, as well as sleep stage markers. On a societal and economical level, reliable measures of the degree of distress in a hospitalized preterm infant will enable the evaluation of the direct effects of stress-reducing interventions such as NICU architecture changes and early intervention programs in cost benefit analyses. (Work package 1)

Objective 2: Second, we aim to study the emotional and bonding processes in parents of preterm infants. Parental distress in terms of depressive symptoms, anxiety, perceived stress and parent-infant bonding will be measured at multiple time points. This will lead to the validation of psychometric instruments in the specific population of parents of preterm infants. Also, we will investigate the effect and predictive value of the course of parental depression, anxiety and stress on children’s developmental outcome and on parent-infant bonding and attachment. Knowledge about the short and long term risks of parental emotional distress are important to implement sufficient and tailored support to parents. (Work package 2)

Objective 3: Third, studies on epigenetic changes due to prenatal stress are still scarce in humans. The research group of Prof. dr. Stephan Claes, who supports the current project, recently found preliminary evidence that prenatal stress affects the methylation state of the NR3C1promotor regions (Hompes et al., 2013). More recent research of his group, done by Van Geel et al. (2015), revealed an association between prenatal maternal stress and  the DNA methylation in the imprinted genes IGF2 and GNASXL, two genes involved in specific gene networks that control fetal growth (Varrault et al. 2006). In our study, we will include a cohort of mothers experiencing profound prenatal stress due to preterm labor, which will complement the earlier work that has been carried out in a low-risk population. We expect more profound changes in methylation state of the previously studied NR3C1 and IGF2 genes in our cohort of mothers exposed to important prenatal stress. The methylation of oxytocin receptor genes will also be studied in relation to attachment and bonding. On a societal level, knowledge about the impact of adverse maternal psychological well-being during pregnancy on the epigenome is important, for example to justify prevention campaigns. (Work package 3)

Overall objective: An important overall goal of the project is to develop a Perinatal Stress Calculator that combines the values of the different neonatal, endocrinological, psychological and physiological stress-related parameters to predict differences in psychomotor, cognitive, behavioural, and emotional development. (Work package 5) Our prospective longitudinal study design will enable us to use the perinatal stress calculator to study the relation between the perinatal stress parameters and later developmental disabilities such as motor impairment, cognitive deficits, and language delay but also social and behavioural problems such as attentional deficits and emotional self-regulation dysfunction. (Work package 4) We will not only be able to weigh perinatal infant characteristics in the model, but also parental characteristics such as distress, resilience and personality as well as bonding and attachment measures. On a societal and economic level, the results of the project will be important for health policy decision-making. Improved prediction of the developmental trajectory of preterm infants could lead to earlier and targeted interventions to decrease maladaptive outcomes.

 

 

Date:1 Oct 2015 →  30 Sep 2018
Keywords:Preterm infants, Attachment, Perinatal stress
Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences
Project type:PhD project