2.3 Prenatal stress
Stress is a normal and necessary part of life – something every individual experiences. Have you considered:
- What the short- and long-term outcomes might be for the fetus if the stress experienced by a pregnant person is prolonged or excessive?
- How the placenta usually acts in a protective role towards the fetus in response to gestational parent stress?
- How drug use during pregnancy such as alcohol or medically indicated synthetic forms of glucocorticoid could affect offspring stress physiology?
Maternal stress
Cortisol, as discussed in the module overview, is a stress hormone that gets released into the bloodstream to help the body cope with more acute stressors. The hypothesis that stress experienced during pregnancy can influence fetal development and longer term health and developmental outcomes is an area of active study in both animal and human research. Listen as Dr. Chris Kuzawa talks about the work of one of his former PhD students and what her research findings revealed about the association of reported prenatal stress, maternal cortisol levels, and infant stress responses after birth.
The body of scientific evidence supporting the hypothesis presented by Kuzawa continues to grow. A synthesis of scientific findings regarding prenatal stress is outlined in the next reading on the Encyclopedia on Early Childhood Development website.
According to a review about fetal outcomes from glucocorticoid programming by Moisiadis & Matthews (2014a), developmental outcomes may be influenced by factors such as the type, severity, and duration of stress experienced during pregnancy, the timing during development, as well as the level of glucocorticoid and mineralocorticoid receptors that are in specific areas of the developing brain (p.398). The earlier link on this page to a synthesis of research findings noted small associations in a few studies between prenatal stress and birth outcomes of prematurity and low birth weight. It also mentioned mild amounts of prenatal stress may be associated with some potentially positive child development outcomes. Listen as Dr. Stephen Matthews, professor of Physiology, Obstetrics and Gynaecology and Medicine at the University of Toronto, discusses some intriguing findings regarding child development outcomes in cases where individuals experienced adversity as high levels of anxiety or in some instances, depression during their pregnancies.
Read more about what is being discovered about child behaviour and cognitive outcomes linked to prenatal stress in the next reading by Dr. Vivette Glover (2019) on the Encyclopedia on Early Childhood Development website.
The normal course of fetal brain maturation and development may be altered not only in situations where there is chronic anxiety or an acute stress response in a pregnant person (e.g., in situations where there is a death of a loved one), but also when a neuropsychiatric disorder such as depression exists (Ross & Desai, 2012, p. 91). According to the Public Health Agency of Canada’s fact sheet Pregnancy and Women’s Mental Health in Canada: Results from the Canadian Maternity Experiences Survey (2014c), 15.5% of Canadian women surveyed reported having had a depression diagnosis or treatment with anti-depressants prior to becoming pregnant. They also reveal that 12.5% of women reported they found most days stressful in the year prior to giving birth (Summary section).
Watch the next video as Monica, beginning her 3rd trimester, discusses her social supports and the strategies she uses for managing stress.
What do you see as some of Monica’s positive coping strategies?
In what situations or circumstances might managing stress effectively during the prenatal period become significantly more challenging?
From Kuzawa’s example presented earlier on this page, we see how prenatal stress can be studied through subjectively reported experiences of stress during pregnancy combined with physiologic stress responses measured objectively through cortisol levels. Objective measures of stress can also be studied through levels of hardship experienced when unfortunate naturally occurring disasters arise during pregnancy.
An ice storm that hit Quebec, Canada in the winter of 1998 provided an opportunity to study objective prenatal stress and associated child development outcomes. Listen as Dr. Kolb, professor at the Canadian Centre for Behavioural Neuroscience, University of Lethbridge, explains what is being revealed about child development outcomes from this work.
Read Zeindler (2013) as they describe more intriguing findings from some ice storm studies on the Douglas Mental Health University Institute website, an affiliate of McGill University.
Another area being examined through scientific research is whether prenatal factors such as gestational parent diet, drug exposure, or obstetrical conditions like preeclampsia down regulate the placental enzyme, 11β –HSD2 that converts the hormone cortisol to cortisone (Dy et al. as cited in Ross & Desai, 2012, p. 91). Ross and Desai (2012) point out that fetal brain development and maturation could potentially be altered if enzyme down regulation occurs in these instances, as more cortisol could then be allowed to pass through to the fetus. Recall from Dr. Lye’s earlier video clip in the overview of the module that poor placental function is one factor whereby a fetus may alter its physiology in response to an oxygen supply that is less than adequate for meeting its needs. In an earlier reading on this page by Dr. Glover it was also pointed out that altered placental function may be one of the ways more cortisol passes through to the fetus. Listen (by clicking on the audio icon that appears at the bottom of the next animation) as Dr. Daniel Hardy explains some of his earlier work in the lab where he studied the placental enzyme 11β-HSD2 and how it responds to lower oxygen levels in cell cultures.
Prenatal alcohol and the HPA axis
In the next video, Dr. Joanne Weinberg discusses her research about the effects of prenatal alcohol exposure on the developing stress (HPA) system in animal models. She adds an interesting layer to this work by including what we are now learning about the stress system in prenatal alcohol exposed children.
Listen as Weinberg expands our knowledge of gene by environment interactions through the next two video clips by discussing her research findings about prenatal alcohol exposure and changes in gene expression, particularly for genes related to stress, depression and immune function.
Synthetic glucocorticoids and the HPA axis
Another example of a drug that can affect the developing HPA axis may be medically indicated in cases of preterm labour. To prevent a condition in the newborn known as respiratory distress, a synthetic form of glucocorticoid may be administered to a gestational parent at risk for delivering preterm to try to mature the fetal lungs. In the next two videos, Matthews explains what normally occurs with fetal glucocorticoid levels during prenatal development. He goes on to explain the history of the medical practice of prescribing synthetic glucocorticoids when these more complex obstetric situations of preterm labour are encountered.
Listen as Matthews details what we are learning about outcomes related to prenatal synthetic glucocorticoid exposure from his work on animal models in the laboratory.
Next Matthews describes what we are learning from his lab work on animal models in terms of the impact of glucocorticoids on the epigenome. He explains how increased risk for cardiometabolic disease and neurological disorder may develop if cortisol regulation is altered throughout life as a result of fetal programming.
The next two animated diagrams are based on information from the review article “Glucocorticoids and Fetal Programming Part 2: Mechanisms” by Moisiadis and Matthews (2014b). This review notes that the placental enzyme 11β-HSD2, which works quite effectively in the placenta at reducing amounts of cortisol passing through to the fetus, does not work very well as a barrier in decreasing the synthetic version of a glucocorticoid (sGC) from passing into the circulation of the fetus. They state, however, that P- glycoprotein, a protein known as a “drug efflux transporter”, may function in trophoblast cells in the placenta to pump some of the sGC back into the gestational parent circulation, thereby lowering amounts that pass through to the fetus (Sun et al.; Iqbal et al. & Matthews; and Yates et al. as cited in Moisiadis & Matthews, 2014b). Look at the next diagram to visualize how P-glycoprotein may be at work in the placenta.
Moisiadis and Matthews (2014b) also explain that from work in animal models, there is a developing fetal blood brain barrier in which P-glycoprotein (P-gp) may work in endothelial cells to decrease the amount of sGC that is able to pass into the fetal brain. By pumping some of this drug back into the fetal circulation along the blood brain barrier, less sGC (that passed into fetal circulation through the placenta) will enter into the sensitive fetal brain (Iqbal, et al. as cited in Moisiadis & Matthews, 2014b). Look at the next diagram to visualize how P-glycoprotein may be at work to efflux synthetic versions of glucocorticoid that reach the developing blood brain barrier.
Additionally, Moisiadis and Matthews (2014b) point out timing of exposure to synthetic glucocorticoids might be a factor linked with the amount of synthetic glucocorticoid that passes through the placenta to the fetus, given that both P-gp and 11β-HSD2 levels in the placenta appear to vary over the course of gestation. More specifically, an increase has been noted in levels of P-gp within endothelial cells of the developing mammalian fetal blood brain barrier which correlates with a decrease in the levels that have been found towards term within the placenta (Sun et al.; & Iqbal et al. as cited in Moisiadis & Matthews, 2014b).
