Maternal stress in pregnancy, maternal mental health disorders and fetal neurodevelopment: an in-depth scientific review based on Massimo Fagioli’s Human Birth Theory.


The relationship between a pregnant woman and the fetus is the object of countless studies aimed at investigating the link between maternal ‘stress’ in pregnancy and a healthy fetal neurodevelopment.  With his Human Birth theory, psychiatrist Massimo Fagioli highlighted how what is psychic develops after birth, when there starts a relationship between the Self and the other, which includes a separation. More recent neurophysiology studies seem to support the idea based on which the brain only becomes active at birth following the cerebral matter’s reaction to photons.

An article published in The Lancet examines the numerous data available in the national and international scientific literature supporting the assumption of an altered fetal neurodevelopment resulting from ante-partum maternal mental disorders. This article concludes that the connection between perinatal mental disorders and an increased risk of psychic adverse events in newborns is not inevitable, being the association mild or moderate. On the other hand, this same article underlines how other factors, i.e. socioeconomic conditions, the lack of social care, or support from the partner, and the persistence of a mental disorder in the parent, can lead to an increased risk of psychic side-effects in infants.

We will also dwell on the relevance of one the main stress-related hormones, i.e. cortisol. Some studies highlight how increased maternal stress may lead to the activation of the hypothalamic-pituitary-adrenal (HPA) axis in the fetus too, with many relevant neuropsychologic implications. On the other hand, many other studies have shown how cortisol does not freely cross the placenta as it is inactivated by 11-β-hydroxysteroid dehydrogenase-type 2 (11β-HSD2). This enzyme is expressed in placental syncytiotrofoblast, which represents the first barrier between maternal and fetal circulation, preventing cortisol from reaching the latter.  The fetus is thus protected against adverse events caused by excessive maternal glucocorticoids, this being true from early pregnancy. For instance, ontogeny studies show how inactivating 11β-HSD2 is expressed soon after conception, increasing with gestational age and decreasing around term. Human chorionic gonadotropin (hCG) is assumed to be responsible for increased expression of the enzyme during placental trophoblast syncytialization. Most interestingly, these studies underline how promoter methylation, thus, regulation of the gene encoding 11β-HSD2 is already set-up in blastocysts, which proves how maternal stress does not impact on the outcome of conception. Indeed, pathological conditions impairing the placental glucocorticoid barrier, via inactivation or diminished expression of the inactivating enzyme, can cause fetal issues including intrauterine growth restriction (IUGR).

By expounding the two points above and examining in detail the many studies available in the international scientific literature, we aim at defining a possible dialogue between psychiatry and neurobiology, which can lead us to highlight how neuro-fetal development is not affected by the mother’s mental health. Relevant data are increasingly confirming the tenets of Human Birth Theory based on which, human brain starts functioning at birth, which implies that physic and psychic life begins at that very instant, making the existence of the fetus a pure biological phenomenon.


  • Fagioli, M. (2017). Istinto di morte e conoscenza. Roma: L’Asino d’oro edizioni;
  • Gatti, M.G., Becucci, E., Fargnoli, F., Fagioli, M., Aden, U. & Buonocore, G. (2012). Functional maturation of neocortex: a base of viability. Journal of Maternal-Fetal and Neonatal Medicine, 25(1), 101-3;
  • Stein, A., Pearson, R.M., Goodman, S.H., Rapa, E., Rahman, A., McCallum, M., Howard, L.M., Pariante, C.M. (2014). Effects of perinatal mental disorders on the fetus and child. Lancet, 384, 1800-19;
  • Stirrat, L.I., Sengers, B.G., Norman, J.E., Homer, N.Z.M., Andrew, R., Lewis, R.M., Reynolds, R.M. (2018). Transfer and Metabolism of Cortisol by the Isolated Perfused Human Placenta. The Journal of Clinical  Endocrinology and Metabolism, 103(2), 640-64.