Prenatal stress

Prenatal stress (or prenatal maternal stress) is exposure of an expectant mother to psychosocial or physical stress, which can be caused by daily life events or by environmental hardships. Around 10-20% of women suffer from mental health concerns during the perinatal period due to their vulnerability and emotion.Liu C., Erdei C., Mittal L. (2021) “Risk factors for depression, anxiety and PTSD symptoms in perinatal women during the COVID-19 Pandemic.” ''Psychiatry Research''. 295, 113552. https://doi.org/10.1016/j.psychres.2020.113552

This psychosocial or physical stress that the expectant mother is going through then impacts the fetus. According to the Developmental Origins of Health and Disease (DOHaD), a wide range of environmental factors a woman may experience during the perinatal period can contribute to biological impacts and changes in the fetus that then causes health risks later in the child's life.McKenna B., Hendrix C., Brennan P., Smith A., Stowe Z., Newport D., Knight A. (2020). “Maternal prenatal depression and epigenetic age deceleration: testing potentially confounding effects of prenatal stress and SSRI use.” Epigenetics. https://doi.org/10.1080/15592294.2020.1795604  

Health risks include impaired cognitive development, low birth weight and risk of mental disorders in the offspring.

Conducting Research

Studies have been conducted longitudinally in order to explore the way that prenatal stress impacts the fetus and its development. These studies took place over the course of the pregnancy and months after in order to collect the data necessary. The stress of the mothers was assessed using self-questionnaires like the Perceived Stress Scale (PSS)Saboory E., Rabiepoor S., Abedi M. (2020). “Prenatal stress and infants’ development: association with cortisol and leptin levels in cord blood and saliva.” Physiology and Pharmacology. 24, 54-62. http://ppj.phypha.ir/article-1-1512-en.pdfJahnke J., Teran E., Murgueitio F., Cabrera H., Thompson A. (2021). “Maternal stress, placental 11β-hydroxysteroid dehydrogenase type 2, and infant HPA axis development in humans: Psychosocial and physiological pathways.” Placenta. 104, 179-187. https://doi.org/10.1016/j.placenta.2020.12.008   and the Patient Health Questionnaire-8 (PHQ8).

While focusing on the stress of the mothers during the pregnancy, researchers also focused on the hypothalamic-pituitary adrenal axis (HPA axis) which is a set of glucocorticoid feedback interactions through the mother to the placenta and then to the fetus. Focusing on the HPA axis allowes researchers to see in what way prenatal stress impacts the fetus development.

Some research includes studies like McKenna et al. suggesting that the idea of pregnancy can cause an increased risk of psychopathology and these exposures during gestation impacts epigenetics. The mother's usage of selective serotonin reuptake inhibitors (SSRIs) was observed while the epegentic age of the child was calculated through fetal umbilical cord blood.

Saboory et al. found that prenatal psychosocial stress can cause delays in child growth and development through assessing the child's weight, height and head circumference every two months after they were born. They also assessed the child's cognitive development through the use of the Ages and Stages Questionnaite (ASQ).

Another study, Brannigan et al. focused on how prenatal stress contributes to personality disorders by looking at children decades later born from mothers who spent time in a mental health clinic in Finland.

This research all found negative correlations between prenatal stress and the child's development.

Timing of prenatal stress and impact on development

A study by Sandman and Davis shows that the timing of prenatal stress is crucial to understanding how prenatal stress affects prenatal and postnatal development. Cortisol is often used to measure stress as it is a hormone that is released during stressful events. If an expectant mother is experiencing a stressful event such as income insecurity or being a teenage mother, cortisol is secreted as a result. However, as demonstrated by Sandman and Davis, the timing of cortisol release can sometimes have a harmful effect on development and sometimes not depending on when in pregnancy stress is experienced.

Sandman and Davis studied "125 full- term infants at 3, 6, and 12 months of age" to determine the effects of maternal cortisol timing differences on development. They found that "exposure to elevated concentrations of cortisol early in gestation was associated with a slower rate of development over the 1st year and lower mental development scores at 12 months" and "elevated levels of maternal cortisol late in gestation were associated with accelerated cognitive development and higher scores at 12 months". Overall, cortisol's effects on infant cognitive development are dependent upon the timing of cortisol release.

Prenatal stress and gender differences in hormones

Pups that underwent prenatal stress showed lower plasma testosterone when compared to the control pups. This is caused by the disruption of prenatal development which did not allow the complete masculinization of the prenatally stressed pups’ central nervous system.

Particularly in the striatum of the prenatally stressed male pups showed an increase in vanilmandelic acid, dopamine, serotonin, 5-hydroxyindoleacetic acid which all can affect sexual behavior. The prenatally stressed male pups showed a significant latency in mounting behavior when compared to controls.

When doing the radial arm maze task prenatally stressed male rats showed a greater increase in dopamine than the prenatally stressed females, which is suggested to facilitate the impairment for the males doing the maze task, but improved the female's performance. There was also an effect on the corticosterone secretion for prenatally stressed females.

Being prenatally stressed increased the anxiety response of the female rats. Yet, it had no effect on the males.

Sexually dimorphic brain regions

Prenatal stress inhibits the masculinization of the male brain by inhibiting the growth of the sexually dimorphic nucleus of the preoptic area. Prenatal stress does have an effect on brain sexual differentiation after measuring the volume of the sexually dimorphic nucleus of the preoptic area of both female and males in the control and stressed groups.

Previous studies found that a decrease in testosterone is seen in pups of prenatally stressed mothers. Authors suggest this may cause the reduced in the sexually dimorphic nucleus of the preoptic area and says it is similar to the effects of neonatal castration. Also, stressed males had larger sexually dimorphic nucleus of the preoptic area at birth, but then at 20 and 60 days are found to only have 50% of the volume of the control males. Whereas control males are two times larger than control females on days 20 and 60, but the stressed males show no statistical difference to control females on respective days. These findings show support that the male brain is not showing the expected sexual dimorphism when prenatally stressed.

Another study led by Kerchner et al. investigated the volume of the medial amygdala and the two compartments posterodorsal and the posteroventral in mice that also were prenatally stressed. Posterodorsal is thought to show organizational and activational effects from gonadal steroids. The medial amygdala for the control and stressed males was 85% larger than females with the males (stressed and control) resembling each other.

To look for specific regions within the medial amygdala that may have been affected, data showed that both the posterodorsal and posteroventral, all male groups were larger in volume than the females, but male groups did not significantly differ from each other. This study confirmed that the medial amygdala is sexually dimorphic; the males are larger than the females.

The posterodorsal and posteroventral were shown to be sexually dimorphic too. The writer suggested that these areas may act similarly to sexually dimorphic nucleus of the preoptic area in response to testosterone, but prenatal stress did not show an effect on the medial amygdala as it does on the sexually dimorphic nucleus of the preoptic area. Also, the posteroventral was 40% larger in control males than females. These results were thought to be caused by the sensitive period of the medial amygdala which is in the first days after birth. The medial amygdala, posterodorsal and posteroventral all show to be resistant against demasculinization from prenatal stress.

Prenatal stress and gender roles

A longitudinal study done on prenatal stress and gender roles showed that prenatal stress only plays a small part in the gender roles the offspring takes on and mentions it has more to do with older siblings, maternal use of alcohol and/or tobacco, maternal education, and the observance or teaching of “traditional sex roles” from the parents.

Prenatal stress and mindfulness-based interventions

Prenatal stress and negative mood during pregnancy has been shown to increase the risk for poor childbirth outcomes and postnatal maternal mood problems. Prenatal distress can interfere with the mother-infant attachment and child development outcomes. Despite the clear association between prenatal stress and child outcomes, women do not receive screening, prevention, or treatment for mood or stress concerns.

It is essential to examine interventions that aim to reduce anxiety, depression, and stress during pregnancy. Mindfulness-based stress reduction has been demonstrated to reduce anxiety and depression for people with stress-related and chronic medical conditions.

One pilot study shows promise for the potential of a mindfulness-based intervention to reduce negative affect and anxiety of women during pregnancy. Based out of the California Pacific Medical Center Research Institute, investigators Dr. Cassandra Vieten and Dr. John Astin conducted a wait-list control pilot study that tested a group-based mindfulness intervention. There were 31 women enrolled in the study: 13 women were assigned to the intervention and 18 women were assigned to the control group.

Measures of anxiety, negative affect, positive affect, depression, mindfulness, perceived stress, and affect regulation were taken before intervention or control was assigned and after the intervention or control was completed. Measures were repeated at a follow-up visit 3 months after the intervention or control was completed. The investigators found a significant decrease in anxiety (p<.05) and negative affect (p <.04) in women who completed the mindfulness based intervention, but not a significant decrease in depression, positive affect, mindfulness, affect regulation, and perceived stress.

These results suggest that mindfulness intervention during pregnancy reduce anxiety and negative affect of mothers. This study is a promising start to the potential impact that mindfulness based interventions could have on reducing prenatal stress, and thereby improving child outcomes.

References

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Obstetrics
Stress (biological and psychological)
Midwifery