Maternal fetal stress transfer
Maternal fetal stress transfer is a physiological phenomenon in which psychosocial stress experienced by a mother during her pregnancy can be transferred to the fetus. Psychosocial stress describes the brain's physiological response to perceived social threat. Because of a link in blood supply between a mother and fetus, it has been found that stress can leave lasting effects on a developing fetus, even before a child is born. According to recent studies, these effects are mainly the result of two particular stress biomarkers circulating in the maternal blood supply: cortisol and catecholamines.
Mechanism of action
[edit]Cortisol is type of hormone called a glucocorticoid, which glucose usage in the body and tends to be activated during a fight-or-flight response. Cortisol is produced in the adrenal gland, whose activity is mediated by the hypothalamus and pituitary glands of the brain. Together, the collective signaling of the hypothalamus, pituitary gland, and adrenal gland is known as the hypothalamo-pituitary-adrenal (HPA) axis. During a period of psychosocial stress, cortisol is released, leading to physiological manifestations of stress such as increased maternal blood pressure (MBP) and maternal heart rate (MHR).[1]
In the case of a pregnant woman, the release of cortisol from the adrenal glands also has an effect on the fetus being carried in the womb. Cortisol is a steroid hormone, and, like all steroid hormones, the receptors for cortisol are located intracellularly. In other words, cortisol does not need an extracellular receptor in order to enter the nucleus of cells and affect their gene expression. Because of this feature of steroid hormones, cortisol diffuses directly across the placenta, the barrier that separates the fetus from the mother. Luckily, the fetus has a protective mechanism against the inundation of cortisol from a stressed mother. There is an enzyme in the placenta called 11beta-hydroxysteroid dehydrogenase type 2 that is capable of inactivating the vast majority of the cortisol passing through the placental barrier to the fetus.[2]
In cases of very high levels of maternal cortisol, this placental enzyme's expression and activity are greatly reduced, thus buffering the fetus less from the mother's high cortisol levels. There are detrimental effects to this loss of placental enzymatic activity. One such effect is a change in the set point for the HPA axis.[1] Myriad studies in animal models indicate that, if fetal cortisol levels are high, then the HPA axis will be more active postnatally.[3]
High levels of fetal cortisol induce higher CRH expression in the paraventricular nucleus of the hypothalamus (PVN) and the central nucleus of the amygdala.[3] In other words, excessive cortisol crossing the placental barrier causes the hypothalamus and amygdala to increase transcription of CRH, which in turn stimulates HPA axis activity early in postnatal life. With such an overactive HPA axis, glucocorticoid receptor expression in the brain increases,[3] making it so that the release of minimal levels of cortisol elicit a substantial response at developing synapses. It is speculated that the HPA axis will more rapidly develop its neural circuitry as a result.
Etiology
[edit]Susceptibility of Foetus’ to Exogenous Influences
[edit]During the pregnancy, a foetus’ brain is extremely malleable as it is in its prime developmental phase. The parts of the brain which are most susceptible to extraneous influences are those responsible for the stress response: the hypothalamus and the pituitary gland. This is due to the fact that the stress response in humans forms very early in our foetal stage, therefore is vulnerable to the mother's mental, physical and emotional state during the gestational period.[4]
If the mother herself experiences unusually high levels of stress, her body would respond by increasing cortisol levels to an abnormal standing. These hormones would then be passed from the mother's bloodstream into the foetus’.[5] The reason that this phenomenon only occurs when the mother is experiencing an excessive amount of stress, and does not occur from the usual, everyday stress that many individuals experience, is due to one protective mechanism that takes place in the placenta.[6]
This mechanism can be understood by first comparing cortisol concentrations in mother and foetus.
Cortisol concentrations in the mother are five to ten times higher than the concentration in the foetus. This ratio of maternal : foetus cortisol concentration is maintained by an enzyme in the placenta which alters the cortisol molecule into an inactive metabolite (11-keto products), called Placental 11 β-hydroxysteroid-dehydrogenase. The problem lies in the multiplying factor arising from this ratio, i.e., if maternal cortisol levels rise by 10-20% it could cause foetal cortisol levels to double, which is what occurs when the mother experiences psychological distress.[6] Additionally, persistent antenatal stress experienced toward the end of the gestation period is shown to inflict severe and permanent damage on the foetus’ physiological development, potentially leading to early growth retardation, aka intrauterine growth restriction, preterm labour and delayed motor development in infancy.[7][8]
Studying the foetal stress response in vivo is not commonly done due to various ethical considerations, but the few studies which have managed to conduct research into this phenomenon during a human pregnancy have reached similar conclusions. This is that maternal-foetal stress transfer occurs through the mechanism of cortisol moving from mother to baby through the placenta.[5] This means that a mother's stress levels become her child's stress levels as she passes down her own over-sensitive stress response, through non-genetic means.
Alcohol
[edit]This biological phenomena is problematic due to the impact that an increased level of cortisol has on the foetal HPA axis. The major source of a cortisol increase are stimuli which provoke consistently high levels of psychosocial stress, but another source of high cortisol concentrations that is often overlooked is the ingestion of alcohol. It is already well known that women who drink alcohol during pregnancy are more likely to give birth to children with physical or neurological defects, but this occurs with large amounts of alcohol intake. Smaller but still significant portions of alcohol intake can trigger a rise in cortisol levels in the mother's bloodstream, hence causing the cortisol levels to rise in the foetus as well, resulting in the same consequences as maternal-foetal stress transfer.[9]
Obesity
[edit]Obesity later in life is linked to the changes in the HPA-axis activity in the fetus. As mothers experience increased stress, they may begin to participare in risky health behaviors such as poor dietary habits. This increases the chance of obesity in the mother and the fetus. The fetus has an increased chance of obesity as high stress is used to predict the potential environment the fetus lives in. Two specific types of glucocorticoids, dexamethasone and betamethasone, are transferred to the fetus. CRH as well, also influences the fetus' health and disease.This exposure, in addition to a higher energy diet, increase the likelihood of obesity later on in life. This is due to glucocorticoids not only regulating stress in the fetus, but also appetite, obesity and metabolism in animals and humans.[10]
Consequences and Long-Term Effects
[edit]A mother's antenatal stress is correlated with detrimental neurobehavioural outcomes in the child.[11] There are a myriad of consequences on a child after birth, such as psychiatric disorders, behavioural abnormalities, dysfunctional emotional regulation and delays in motor production.[7]
Exposure during important neurodevelopment periods increase risk of metabolic disorders including obesity, Type 2 diabetes , and a poor lipid profile. This risk is most present at a later stage of pregnancy and can be seen as early as six months of age.[12] The likelihood further increases when children experience high levels of stress.[13]
The most commonly occurring psychiatric disorders which develop are attention-deficit / hyperactivity disorder,[14] minor depressive and neurotic symptoms, schizophrenia, a tendency toward alcoholism/drug-addiction and criminal behaviour.[8] These psychiatric disorders can, in turn, either lead to or exacerbate behavioural irregularities such as hyperactivity, an unusually low threshold for irritation or frustration, antisocial and inconsiderate behaviour, as well as profuse clinging or crying (especially at a younger age). Furthermore, the feminisation of male behaviour and an increase in timidity has also been observed in children born out of a stressful antenatal environment.[15]
Biologically speaking, this phenomenon can also cause the hippocampus, a very important component of the stress response, to be defective and not function as it should. The reason being that the hippocampus is one of the parts of the brain which is seen to be most vulnerable to maternal stress hormones. Some may believe that this physiological consequence of maternal-foetal stress transfer can be said to be the cause of the psychiatric disorders and behavioural abnormalities outlined above, alongside other factors.[15]
Moreover, an overexposure to cortisol during infancy can lead to the extreme response of desensitisation to cortisol in the child. Desensitisation or the blocking of cortisol receptors can occur because of irregularities in the HPA axis, which form in utero due to the passing of cortisol through the placenta from mother to baby.[16] The conversion from extremely high to low cortisol levels can be said to be a defence mechanism of sorts, as one (unconsciously) experiences withdrawal, avoidance and denial in an effort to disengage with any challenging or discomforting stimuli, sometimes manifesting in alexithymia. People are often left feeling empty and isolated due to their state of emotional numbness and dissociation.[17]
The continuity of maternal stress from during, to after, pregnancy is a progression of maternal-foetal stress transfer which is significant in impacting the infant's overall wellbeing. Postnatal maternal stress, such as postpartum depression, has an enormous impact on the emotion, mental and behavioural growth of a child, hence can aggravate and intensify the impacts of maternal-foetal stress transfer. Roughly 13% of women experience at least one depressive episode during or directly after pregnancy, thus encouraging the increased interest in identifying the effects of antenatal maternal stress on the development of an individual during the foetal and infancy stages of life.[4]
Reversal of Consequences
[edit]As stated by epigenetics and one of the conclusions of the nature vs. nurture debate, most behavioural and psychological problems arise due to a combination of biological and environmental/sociocultural factors. Therefore, environmental factors such as parental care and nutritional availability, alongside help given to the child such as psychotherapy can aid in the reversal of the impacts of maternal-foetal stress transfer.[7]
See also
[edit]References
[edit]- ^ a b Rakers, Florian; Bischoff, Sabine; Schiffner, Rene; Haase, Michelle; Rupprecht, Sven; Kiehntopf, Michael; Kühn-Velten, W. Nikolaus; Schubert, Harald; Witte, Otto W.; Nijland, Mark J.; Nathanielsz, Peter W.; Schwab, Matthias (November 2015). "Role of catecholamines in maternal-fetal stress transfer in sheep". American Journal of Obstetrics and Gynecology. 213 (5): 684.e1–684.e9. doi:10.1016/j.ajog.2015.07.020. PMID 26212181.
- ^ Duthie, Leanne; Reynolds, Rebecca M. (2013). "Changes in the Maternal Hypothalamic-Pituitary-Adrenal Axis in Pregnancy and Postpartum: Influences on Maternal and Fetal Outcomes". Neuroendocrinology. 98 (2): 106–115. doi:10.1159/000354702. PMID 23969897.
- ^ a b c Li, Yong; Gonzalez, Pablo; Zhang, Lubo (August 2012). "Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: Mechanisms and possible interventions". Progress in Neurobiology. 98 (2): 145–165. doi:10.1016/j.pneurobio.2012.05.010. PMC 3404248. PMID 22627492.
- ^ a b Kinsella, Michael T.; Monk, Catherine (2009-09-01). "Impact of Maternal Stress, Depression and Anxiety on Fetal Neurobehavioral Development". Clinical Obstetrics & Gynecology. 52 (3): 425–440. doi:10.1097/GRF.0b013e3181b52df1. ISSN 0009-9201. PMC 3710585. PMID 19661759.
- ^ a b Gitau, Rachel; Fisk, Nicholas M.; Teixeira, Jeronima M. A.; Cameron, Alan; Glover, Vivette (2001-01-01). "Fetal Hypothalamic-Pituitary-Adrenal Stress Responses to Invasive Procedures Are Independent of Maternal Responses 1". The Journal of Clinical Endocrinology & Metabolism. 86 (1): 104–109. doi:10.1210/jcem.86.1.7090. ISSN 0021-972X. PMID 11231985. S2CID 23177322.
- ^ a b Murphy, Vanessa E.; Smith, Roger; Giles, Warwick B.; Clifton, Vicki L. (2006-04-01). "Endocrine Regulation of Human Fetal Growth: The Role of the Mother, Placenta, and Fetus". Endocrine Reviews. 27 (2): 141–169. doi:10.1210/er.2005-0011. hdl:1959.13/26989. ISSN 0163-769X. PMID 16434511. S2CID 2958458.
- ^ a b c Edwards, Heather E; Burnham, W McIntyre (2001-10-01). "The Impact of Corticosteroids on the Developing Animal". Pediatric Research. 50 (4): 433–440. doi:10.1203/00006450-200110000-00003. ISSN 0031-3998. PMID 11568284. S2CID 19168971.
- ^ a b Huttunen, Matti O. (1978-04-01). "Prenatal Loss of Father and Psychiatric Disorders". Archives of General Psychiatry. 35 (4): 429–431. doi:10.1001/archpsyc.1978.01770280039004. ISSN 0003-990X. PMID 727894.
- ^ Washburn, Shannon E.; Tress, Ursula; Lunde, Emilie R.; Chen, Wei-Jung A.; Cudd, Timothy A. (2013-02-01). "The role of cortisol in chronic binge alcohol-induced cerebellar injury: Ovine model". Alcohol. 47 (1): 53–61. doi:10.1016/j.alcohol.2012.10.004. PMC 3544992. PMID 23218665.
- ^ Lamichhane, Nishan; Olsen, Nanna Julie; Mortensen, Erik Lykke; Obel, Carsten; Heitmann, Berit Lilienthal; Händel, Mina Nicole (2019-10-23). "Associations between maternal stress during pregnancy and offspring obesity risk later in life—A systematic literature review". Obesity Reviews. 21 (2): e12951. doi:10.1111/obr.12951. ISSN 1467-7881. PMID 31642601. S2CID 204848924.
- ^ Talge, Nicole M.; Neal, Charles; Glover, Vivette; the Early Stress, Translational Research and Prevention Science Network: Fetal and Neonatal Experience on Child and Adolescent Mental Health (2007-03-01). "Antenatal maternal stress and long-term effects on child neurodevelopment: how and why?". Journal of Child Psychology and Psychiatry. 48 (3–4): 245–261. doi:10.1111/j.1469-7610.2006.01714.x. ISSN 0021-9630. PMC 11016282. PMID 17355398.
- ^ Cattane, Nadia; Räikkönen, Katri; Anniverno, Roberta; Mencacci, Claudio; Riva, Marco A.; Pariante, Carmine M.; Cattaneo, Annamaria (2020-07-06). "Depression, obesity and their comorbidity during pregnancy: effects on the offspring's mental and physical health". Molecular Psychiatry. 26 (2): 462–481. doi:10.1038/s41380-020-0813-6. ISSN 1359-4184. PMC 7850968. PMID 32632208.
- ^ Burgueño, Adriana L.; Juarez, Yamila R.; Genaro, Ana M.; Tellechea, Mariana L. (January 2020). "Systematic review and meta-analysis on the relationship between prenatal stress and metabolic syndrome intermediate phenotypes". International Journal of Obesity. 44 (1): 1–12. doi:10.1038/s41366-019-0423-z. ISSN 1476-5497. PMID 31332277. S2CID 198138218.
- ^ Lesesne, Catherine A.; Visser, Susanna N.; White, Carla P. (2003-05-01). "Attention-deficit/hyperactivity disorder in school-aged children: association with maternal mental health and use of health care resources". Pediatrics. 111 (5 Pt 2): 1232–1237. doi:10.1542/peds.111.S1.1232. ISSN 1098-4275. PMID 12728144. S2CID 12062341.
- ^ a b Weinstock, Marta (1997-01-01). "Does Prenatal Stress Impair Coping and Regulation of Hypothalamic-Pituitary-Adrenal Axis?". Neuroscience & Biobehavioral Reviews. 21 (1): 1–10. doi:10.1016/S0149-7634(96)00014-0. PMID 8994205. S2CID 46090011.
- ^ Oquendo, M A; Echavarria, G; Galfalvy, H C; Grunebaum, M F; Burke, A; Barrera, A; Cooper, T B; Malone, K M; John Mann, J (2003-03-01). "Lower Cortisol Levels in Depressed Patients with Comorbid Post-Traumatic Stress Disorder". Neuropsychopharmacology. 28 (3): 591–598. doi:10.1038/sj.npp.1300050. ISSN 0893-133X. PMID 12629542. S2CID 5768753.
- ^ Lumley, Mark A.; Neely, Lynn C.; Burger, Amanda J. (2007-11-14). "The Assessment of Alexithymia in Medical Settings: Implications for Understanding and Treating Health Problems". Journal of Personality Assessment. 89 (3): 230–246. doi:10.1080/00223890701629698. ISSN 0022-3891. PMC 2931418. PMID 18001224.