Maternal distress in late pregnancy alters obstetric outcomes and the expression of genes important for placental glucocorticoid signalling
Introduction
There is now an extensive body of evidence showing that the in utero experience is a critical determinant of fetal outcome (Langley-Evans, 2006). One factor that has been extensively studied in this regard is the adverse effect of maternal prenatal distress on birth outcomes (Bussières et al., 2015). This is important, as understanding the relationship between prenatal distress and unfavourable births outcomes may allow for targeted maternal or fetal surveillance in high-risk pregnancies, or timely intervention to decrease the risk of an adverse outcome. The term ‘prenatal distress’ is often used to collectively refer to negative psychological wellbeing, and encompasses stress, anxiety and depression. The prevalence of prenatal distress is estimated to be 31%, 28% and 12% for stress, anxiety and depression respectively (McDonald et al., 2013). Thus, a significant proportion of women experience clinically significant levels of maternal distress during pregnancy, highlighting the need to study its impact on birth outcomes.
A number of epidemiological studies have shown that fetal exposure to maternal prenatal distress can alter fetal development and increase short and long term disease risk. Prenatal stress and anxiety increases the risk of preterm birth (PTB) and low birth weight (LBW) (Bussières et al., 2015, Ding et al., 2014, Khashan et al., 2009, Khashan et al., 2008). Prenatal depression has been found to increase the risk of operative deliveries (Hu et al., 2015), PTB and LBW (Grote et al., 2010). However, in a more recent meta-analysis, Accortt and colleagues reported significant variability in existing studies (Accortt et al., 2015), highlighting the need for further studies examining the association between prenatal distress and birth outcomes.
While the clinical outcomes have been the subject of intensive investigation, the molecular and biological parallels of these changes in human populations is not well known. Given the well-known effect of stress on glucocorticoid signalling, one proposed hypothesis is that alterations in placental glucocorticoid signalling, leads to overexposure of the fetus to maternal cortisol (Cottrell et al., 2013). This has been proposed as a key biological mechanism underpinning the programming effect of prenatal distress on poor outcomes (Cottrell et al., 2013). In particular, prenatal distress has been shown to alter the expression of three important genes in the placenta; 11-beta hydroxysteroid dehydrogenase type 2 (HSD11B2) (Jensen Pena et al., 2012, O'Donnell et al., 2012, Seth et al., 2015), the glucocorticoid receptor (NR3C1) (Palma-Gudiel et al., 2015) and FK506 binding protein (FKBP5) (Monk et al., 2016). Expression of these genes have been shown to correlate with infant birthweight (Green et al., 2015, Mulligan et al., 2012) and growth restriction (Zhao et al., 2014), suggesting that altered placental glucocorticoid signalling may play a role in determining newborn outcome. Further alterations in the epigenetic status and expression of HSD11B2 (Appleton et al., 2015), NR3C1 (Sheinkopf et al., 2016), and FKBP5 (Paquette et al., 2014) have been shown to be predictive of neurobehavioral problems in infancy.
The primary objective of this study was to evaluate the link between prenatal stress, depression and/or anxiety in late pregnancy on neonatal and obstetric outcomes in pregnant women receiving antenatal care at Cork University Maternity Hospital. The secondary goal was to examine whether prenatal stress, depression and/or anxiety in late pregnancy led to any changes in key genes involved in placental glucocorticoid signalling that have previously been linked to unfavourable birth outcomes and poorer neurodevelopment in infancy.
Section snippets
Participant recruitment
This study was carried out with full ethical approval from the Research Ethics Committee of Cork Teaching Hospital. Women receiving antenatal care at Cork University Maternity Hospital (CUMH), Cork, Ireland between July 2015 and September 2016 were invited to participate in this study. The inclusion criteria were; 1. 18 years of age or older, 2. English speaking, 3. having a current singleton pregnancy and 4. plans to give birth in the maternity hospital. The participants were recruited when
Descriptive statistics
159 pregnant women were initially recruited into the study and completed the questionnaires. Participants were removed from the study if they were less than 28 weeks’ gestation when they completed the questionnaires (16.9%), had incomplete survey information (1.8%) or if medical records were unavailable (5.0%) (Fig. 1). The final analysis included 121 participants. The mean age of the participants was 31.75 years (SD=4.54, range 17–41). The average BMI was 26.33 (SD=4.60, range 18.6–38.8). The
Discussion
The present study adds to the existing literature highlighting a negative role for prenatal distress in mediating adverse pregnancy and birth outcomes. Prenatal distress is commonly reported during pregnancy and varies in its definition. Psychological wellbeing encompasses a broad area of health that expands beyond diagnosable mental health disorders such as depression, anxiety and posttraumatic stress disorder. There are a wide range of screening tools used to identify women who may be at risk
Conflict of interest
The authors declare no conflict of interest.
Funding source
This work was supported by Research Centres grant (Grant#: INFANT-12/RC/2272) (L.K.), a Research Frontiers Program grant (Grant#: 10/RFP/NES2786) (G.O.’K.), from Science Foundation Ireland, and a Translational Research Access Program (TRAP) award from the School of Medicine UCC (GOKL/LK).
Acknowledgments
The authors would like to acknowledge the contribution of the staff in the delivery ward at Cork University Maternity Hospital who assisted in the collection of placental samples.
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