Endocrinol. (1992). The thermoregulatory theory of yawning: what we know from over 5 years of research. J. Obstet. 125, 28. doi: 10.1016/j.autneu.2007.04.008, de Vries, J. I. P., Visser, G. H. A., and Prechtl, H. F. R. (1982). Brain. Am J Physiol Heart Circ Physiol. 2009 Aug 12;302(6):660-8. From 7 to 8 WGA gray and white matter differentiate and, by the end of the 1st trimester, after the embryo has become a fetus, it is possible to recognize all the main brain structures, including the choroid plexus, thalamus, hypothalamus, amygdala, basal ganglia, corpus callosum, brainstem nuclei, cerebellum, and the neural plate of the insula (Moore et al., 2016; Hill, 2021b). Psychol. 27, 8994. For example, the maternal pain and anxiety due to uterine contractions induce an activation of the sympathetic division (Jones and Greiss, 1982), whereas the release of the hormone oxytocin instead activates the parasympathetic division (Gamer and Bchel, 2012). Moreover, prophylactic antibiotic use during vaginal or cesarean delivery may indirectly lead to epigenetic changes in the fetus, with possible implications in the immune system and stress response (Tribe et al., 2018), consequently involving vagus nerve development and suggesting, therefore, the utility to consider potential alternative approaches (Ledger and Blaser, 2013). According to a recent systematic analysis, FMs can affect the ANS as revealed through modifications in the time-domain and frequency-domain fHRV metrics. J. Matern. Nevertheless, the placental microbiome could be an interesting factor to be taken into account by the clinicians as a potential regulator of vagus nerve development. (2021). A second component of the chemoreflex response to hypoxemia is parasympathetic, mediated via the vagus nerve, resulting in a fall in heart rate. They may show altered pain reactivity and parasympathetic cardiac modulation during recovery after an acute noxious event (De las Cuevas and Sanz, 2006), which lasts up to two months, and also altered HPA stress response patterns and hippocampal plasticity (Morrison et al., 2005; Oberlander et al., 2009; Gemmel et al., 2019). 25, 535537. Sex differences in neurodevelopmental and neurodegenerative disorders: focus on microglial function and neuroinflammation during development. Cell. doi: 10.1371/journal.pone.0074431, Hoyer, D., Zebrowski, J., Cysarz, D., Gonalves, H., Pytlik, A., Amorim-Costa, C., et al. Comp. 85, 120126. Postnatal outcomes in lambs exposed antenatally and acutely postnatally to fluoxetine. 78, 12621282. J. Obstet. Factors that modulate fetal anaerobic reserve are myocardial glycogen stores, placental exchange capacity and chronic hypoxia. Doussard-Roosevelt, J. (2006). 300, R330R339. 10:413. doi: 10.3389/fcimb.2020.00413, Oliveira, V., von Rosenberg, W., Montaldo, P., Adjei, T., Mendoza, J., Shivamurthappa, V., et al. Perinatal hypoxia contributes significantly to the possibility of perinatal brain injury (Gotsch et al., 2007). Am. 80, 8291. doi: 10.1055/s-0036-1597135, Caez, M. S., Reed, K. L., and Shenker, L. (1987). Heart rate variability analysis allows early asphyxia detection in ovine fetus. 30, 20552064. J. Med. doi: 10.1016/s0022-2828(05)82386-7, Morrison, J. L., Berry, M. J., Botting, K. J., Darby, J. R. T., Frasch, M. G., Gatford, K. L., et al. 18, 359379. Intensiva 31, 296302. Nurs. The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis. doi: 10.1016/j.smrv.2018.03.004, Weber, A., and Harrison, T. M. (2019). Statistically, severe fetal acidemia (pH < 7.00) has been shown to occur in between 0.5 and 10% of human births. This detects changes in the normal FHR pattern at the time of labor, reassuring your obstetrician if its safe to proceed. One of such responses, able to perform homeokinetic adjustments, is the cholinergic anti-inflammatory pathway (CAP). Pathol. Regul. ANS, autonomic nervous system; CAN, central autonomic network; fHRV, fetal heart rate variability; FM, fetal movement; GM, general movement; PNS, parasympathetic nervous system; WGA, weeks gestational age. Am. which intrinsic homeostatic response is the fetus demonstrating . While late decelerations sometimes point to an abnormally low concentration of fetal blood oxygen (i.e., fetal hypoxemia), various other factors could be at play. The spleen begins to develop at 5 WGA as a lobulated organ, appears clearly around 8 WGA, and initially functions as a hematopoietic center; then, during fetal development, it gradually loses both this role and its lobules (Moore et al., 2016; Hill, 2021a). Nutrients 7, 20012014. Methods Mol. Neurosci. doi: 10.1097/EDE.0b013e318187cc5d, Hantoushzadeh, S., Anvari Aliabad, R., and Norooznezhad, A. H. (2020). In mice, neonatal CD8 T cells originate from distinct hematopoietic stem cell sources than adult CD8 T cells and exhibit rapid and short-lived responses as compared to adults ( 92, 93 ), exhibiting a layering of immune function similar to that of human fetal CD4 T cells ( 51 ). Is intrapartum asphyxia preventable? Crit. doi: 10.1016/0002-9378(78)90280-6, Fritze, D., Zhang, W., Li, J.-Y., Chai, B., and Mulholland, M. (2014). 128:1443. doi: 10.1111/1471-0528.16674, Gold, N., Herry, C. L., Wang, X., and Frasch, M. G. (2021). Bone Jt. 61, 242251. Circulating catecholamines increase heart rate variability.18, Animal experiments have shown that blockage of the parasympathetic system with atropine results in a reduction in short-term variability. The fetuses, moreover, appear to have an increased risk of preterm birth (Morrison et al., 2005; Suri et al., 2007; Oyebode et al., 2012) and poor neonatal adaptation syndrome (Lattimore et al., 2005; Sivojelezova et al., 2005). 2016 Mar 1;594(5):1265-77. 10:188. doi: 10.3389/fcimb.2020.00188, Heazell, A. E. P., Budd, J., Li, M., Cronin, R., Bradford, B., McCowan, L. M. E., et al. doi: 10.1093/pch/pxy028, Liu, H. L., Garzoni, L., Herry, C., Durosier, L. D., Cao, M., Burns, P., et al. Autonomic development in preterm infants is associated with morbidity of prematurity. The body of literature, that disputes the statement that moderate variability reliably excludes the presence of metabolic acidemia, continues to grow. Mercury exposure and heart rate variability: a systematic review. doi: 10.1016/j.psyneuen.2017.10.004, Uvns-Moberg, K., Ekstrm-Bergstrm, A., Berg, M., Buckley, S., Pajalic, Z., Hadjigeorgiou, E., et al. Notably, this effect is limited to inhibitory-onto-excitatory neuron . These results do not vary in co-administration with opioids (Caez et al., 1987), whereas the association with sGC should deserve greater attention by the clinicians (Verdurmen et al., 2017). doi: 10.1002/ajim.4700210312, Zhang, X., Sliwowska, J. H., and Weinberg, J. Diagn. Am. A qualitative exploration of the views and experiences of women with pregnancy related pelvic girdle pain. Alcohol. Vagal blockade eliminated these decelerations in the non-acidemic sheep. The heart itself contributes to variability. In addition, the vagus nerve has been recognized as the primary afferent pathway capable of transmitting information to the brain from every organ of the body. Pediatr. 1994 Jan;73(1):39-44. (1998). (2019). Dev. doi: 10.1177/1073858406296401, Micheli, K., Komninos, I., Bagkeris, E., Roumeliotaki, T., Koutis, A., Kogevinas, M., et al. Hence, measuring HRV during different sleep states can help better assess ANS development (Yiallourou et al., 2012; Dereymaeker et al., 2017). Oxytocin promotes functional coupling between paraventricular nucleus and both sympathetic and parasympathetic cardioregulatory nuclei. (Paris). Am. (2014). which intrinsic homeostatic response is the fetus demonstrating Sci. The influence of corticosteroids on fetal heart rate variability: a systematic review of the literature. doi: 10.1038/jes.2013.19, Dogra, Y., Suri, V., Aggarwal, N., and Dogra, R. K. (2019). Molecular control of the neural crest and peripheral nervous system development. Drugs including theophylline, caffeine, and methylxanthine, used to support respiratory functions have the potential of altering sleep quality and induce drowsiness. Maternal micronutrient deficiency, fetal development, and the risk of chronic disease. 62, 6877. BJOG. (2006). Am J Obstet Gynecol. 39:100703. doi: 10.1016/j.dcn.2019.100703, Martens, D. S., Capozzoli, M., Cox, B., and Nawrot, T. S. (2019). (2019). ArXiv200808625 Q-Bio. Early Hum. Sci. 7:1031. doi: 10.3389/fmicb.2016.01031, Oberlander, T. F., Gingrich, J. Maternal psychopathology influences infant heart rate variability: generation R study. Women Birth 32, 12. The effects of epidural anesthesia on electronic fetal heart rate monitoring. (1998). Can we learn to assess this individual experience? Fetal development assessed by heart rate patternstime scales of complex autonomic control. ArXiv190905198 Q-Bio. Classic teaching on the mechanisms of variable decelerations is outlined in Figure 2. Autonomic responses to sighs in healthy infants and in victims of sudden infant death. The effect of magnesium sulfate tocolysis on the fetal biophysical profile. As the 3rd trimester advances, specific nociceptive event-related potentials in the brain increasingly develop until 3537 WGA (Verriotis et al., 2016). doi: 10.1016/j.preghy.2020.03.003, Moreira Neto, R., and Porovic, S. (2018). Montreal, QC: Acta Medica Publ. Migration and diversification of the vagal neural crest. Rev. doi: 10.1080/14767058.2018.1509067, Brown, A., and Johnston, R. (2013). (2004). Comput. 1996;8(3):471-82. J. Physiol. Vagal NC cells then give rise to the parasympathetic, sympathetic, and sensory ganglia (Hutchins et al., 2018; Simkin et al., 2019; Fedele and Brand, 2020). which intrinsic homeostatic response is the fetus demonstrating Preterm newborns have an immature ANS, which has great repercussions on cardiac and respiratory functions (Mulkey and du Plessis, 2018). At 56 WGA, the 12 cranial nerves appear (Moore et al., 2016). Regarding the PNS, the vagus nerve has been recognized as a fundamental afferent pathway for sensing the milieu interior in peripheral tissues, thus allowing the organism to respond by activating complex networks involving the whole ANS, endocrine, metabolic, innate, and adaptive immune systems (Frasch et al., 2018b; Bonaz et al., 2021). Thanaboonyawat, I., Wataganara, T., Boriboonhiransarn, D., Viboonchart, S., and Tontisirin, P. (2006). Auditory brain development in premature infants: the importance of early experience: McMahon et al. Med. Biol. Rep. 38:BSR20171234. J. Obstet. doi: 10.1016/j.ijgo.2007.08.012, Sahota, P. K., Jain, S. S., and Dhand, R. (2003). Neurosci. doi: 10.1196/annals.1314.006, Sehmbi, H., D'Souza, R., and Bhatia, A. J. Clin. 9:147. doi: 10.3389/fnhum.2015.00147, Brar, B., Jackson, D., Nat, M., Patil, P., Iriye, B., and Planinic, P. (2020). Although CS delivery is far faster than a vaginal birth modality, the fetus is still subjected to significant stress that can create changes in the development of some systems, including the ANS (Tribe et al., 2018). Dev. Long-term neurodevelopmental outcome of children born to prospectively followed pregnancies of women with systemic lupus erythematosus and/or antiphospholipid syndrome. doi: 10.1016/j.clp.2012.12.012, Shea, C. A., Rolfe, R. A., and Murphy, P. (2015).