89, 13761380. The cardioregulatory center receives input from the central nervous system, reflex pathways and circulating catecholamines. Therefore, every possible procedure aimed to protect babies from harmful noises or to introduce positive sounds including the human voice, especially maternal voice (even recorded), and songs, can result in important neuroprotective effects (McMahon et al., 2012; Weber and Harrison, 2019). [Drug use during pregnancy, labor and the puerperium and after the drug use in pregnancy study]. Prenatal nicotine exposure (PNE) is associated with higher systolic blood pressure and altered HRV after birth (Nordenstam et al., 2019). 9, 7685. Biol. Does reduction of amniotic fluid affect fetal movements? Sensors placed against the fetal cheek measure the reflected light in two specific wavelengths and from this the percentage of fetal oxygen saturation can be estimated. doi: 10.1016/j.earlhumdev.2017.07.003, Desrosiers, T. A., Lawson, C. C., Meyer, R. E., Stewart, P. A., Waters, M. A., Correa, A., et al. 5:2377960819861486. doi: 10.1177/2377960819861486, Kruepunga, N., Hikspoors, J. P. J. M., Hlsman, C. J. M., Mommen, G. M. C., Khler, S. E., and Lamers, W. H. (2020). Psychol. doi: 10.3390/nu7032001, Stphan-Blanchard, E., Chardon, K., Lk, A., Delanaud, S., Bach, V., and Telliez, F. (2013). Early life stress and environmental influences on the neurodevelopment of children with prenatal opioid exposure. 16, 509517. (2010). Gynaecol. Neurobiol. Sahin, F. K., Koken, G., Cosar, E., Saylan, F., Fidan, F., Yilmazer, M., et al. 4, 7182. Gynecol. Heart rate variability parameters and fetal movement complement fetal behavioral states detection via magnetography to monitor neurovegetative development. 102, F183F187. Maternal metabolic dysfunctions and dysbiosis can affect the systemic inflammatory response of the mother and the fetus (Hasain et al., 2020; Peterson et al., 2020). Beyond the headlines: fetal movement awareness is an important stillbirth prevention strategy. Eng. An important factor that is present in several cases of labor is epidural analgesia (Bautista and George, 2020). 465, 573584. 444, S98S109. Total views 78. In this proposal the chemoreflex efferent in the vagus nerve causes FHR slowing and the sympathetic component causes hypertension to maintain perfusion to vital organs. Ambient temperature and markers of fetal growth: a retrospective observational study of 29 million U.S. singleton births. doi: 10.1007/BF00315698, Multon, O., Senat, M.-V., Minoui, S., Hue, M.-V., Frydman, R., and Ville, Y. Similarly, even autoimmune diseases can involve a dysregulation in maternal inflammatory response (Gordon, 2004; Lu-Culligan and Iwasaki, 2020; Han et al., 2021). Consequently, EFM fails to identify fetuses at risk of brain injury; this is because there is no clear correlation between fetal brain injury and acidemia (Westerhuis et al., 2007; Cahill et al., 2017). Cardiovasc. Bocking AD. doi: 10.1053/sper.2001.27546, Rantakari, K., Rinta-Koski, O.-P., Metsranta, M., Hollmn, J., Srkk, S., Rahkonen, P., et al. Gynaecol. Nevertheless, prone sleeping is considered a risk factor for SIDS and it shows a lower short-term variability in HRV (Lucchini et al., 2016). All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Q. J. Exp. doi: 10.1016/j.braindev.2019.04.014, Alfirevic, Z., Devane, D., Gyte, G. M., and Cuthbert, A. A. An increase in the heart rate c. An increase in stroke volume d. No change a. doi: 10.1542/peds.113.2.368, Zhang, J., Cai, W.-W., and Lee, D. J. Higher maternal weight is related to poorer fetal autonomic function. Sleep impairment due to prematurity or environmental factors can lead to global neurodevelopmental complications (e.g., attention deficit, motor disability, and low cognitive abilities), as newborns show weaker functional connectivity networks during such impaired sleep (Uchitel et al., 2021). Human fetal behavior: 100 years of study. Lear CA, Galinsky R, Wassink G, Mitchell CJ, Davidson JO, Westgate JA, Bennet L, Gunn AJ. The patterns of cytokine response and the neuroimmune physiology of the fetus and the placenta mirror the maternal ones throughout pregnancy (Sherer et al., 2017, 2018; Prins et al., 2018; Peterson et al., 2020). In fetal life, pulmonary ventilation does not occur and is not a source of fetal oxygenation. Drugs aside, the most relevant aspect to be evaluated during the 2nd stage of labor is certainly the mode of delivery. Zeskind, P. S., and Gingras, J. L. (2006). 97, 14861490. Clin. Maternal and paternal occupational exposure to agricultural work and the risk of anencephaly. (2017). doi: 10.1016/j.yfrne.2015.09.001, Nuriel-Ohayon, M., Neuman, H., and Koren, O. 18, 459464. Activity, cardiac and respiratory responses of blindfold preterm infants in a neonatal intensive care unit. Fetal movements patterns could be limited as a consequence of an inappropriate ratio between fetal and uterine dimension (Shea et al., 2015; Verbruggen et al., 2018), as well as a consequence of an inadequate amount of amniotic fluid (Sival et al., 1990). 33, 909912. 1977;7(6):373-6. Assoc. Perinatal Events Neurologic injury in acidemic term infants. Hum. Even early prenatal exposure to the virus, indeed, seems to create a chronic hypoxic environment to the fetus, affecting vagus nerve developmental patterns, and imprinting postnatally the ANS cardiac pacemaker activity (Herry et al., 2021). doi: 10.1080/02724999208250616, Ledger, W. J., and Blaser, M. J. J. Mol. The evidence so far shows that the intrinsic fHRV is influenced by the fetal ANS activity and, conversely, also shapes the ANS activity into the postnatal period, at least in part via the afferent fibers of the vagus nerve (Herry et al., 2021). 1991 Nov 26;42(2):145-53. The repetitive movements, with the consequent repetitive sensory afferents induced, produce habituation in the fetus, that is manifested also in fHR changes: the ANS trains to adapt the body systems' response to environmental stimuli, even through the movements (Lecanuet et al., 1992; Kisilevsky and Low, 1998). doi: 10.1007/s10286-021-00793-7, Mulkey, S. B., Kota, S., Govindan, R. B., Al-Shargabi, T., Swisher, C. B., Eze, A., et al. doi: 10.1097/GRF.0b013e31811ebef6, Grandjean, P., Murata, K., Budtz-Jrgensen, E., and Weihe, P. (2004). Crit. The regulatory patterns of sympathovagal balance show sex-specific differences as pregnancy progresses (Buss et al., 2009). 43, 395407. doi: 10.1007/s11605-014-2565-6, Fuhler, G. M. (2020). Microbiol. 43, 481486. Nonlinear properties of vagal and sympathetic modulations of heart rate variability in ovine fetus near term. 1992 Aug;167(2):519-23. 1983 Jan; 90(1):11-5. J. (2014). This effect is believed to benefit the fetus by temporarily reducing myocardial work to compensate for diminished oxygen availability.3-6 A third consequence of chemoreceptor activation of the sympathetic system causes release of other substances such as adrenal catecholamines and vasopressin. The catecholamines, epinephrine and norepinephrine, secreted from the adrenal, are both hormones and neurotransmitters. Consequently, the fetal and infant capacity to homeostatically adapt to the environment could be impaired (Van den Bergh and Mulder, 2012). 15-30 minutes in the active phase of the first stage and every 5-15 minutes in second stage B. doi: 10.1016/0378-3782(85)90174-4, Dejmek, J., Selevan, S. G., Benes, I., Solansk, I., and Srm, R. J. Moreover, excessive light can impair visual development, thus increasing SNS and HPA axis activation (Weber and Harrison, 2019). As such, fetal heart tracings should be combined with other clinical methods to ensure accurate interpretation of your babys condition. J. Clin. While all of the mechanisms described above modulate heart rate, it is important to underline that the overarching mission of the cardiovascular system is to deliver sufficient oxygen to key organs. This in utero programming effect on the fetal HPA axis could last until adulthood: there are recent observations of altered R-R interval variability in adult offspring exposed to elevated fetal sGCs (Sheng et al., 2020), a result that deserves further investigations to better understand the sGCs potential role in neurodevelopmental altered pathways. Thus, intermittent placental insufficiency can cause decelerations. Indeed, at 32 WGA the cerebral cortex resembles the adult one and, in the next week, synchronicity between the hemispheres develops, as well as complex connections among several brain areas and networks (Moore et al., 2016; Borsani et al., 2019). Neonatal Med. Regarding the vagus nerve, at this stage, the dorsal motor nucleus is the predominantly active effector center (Porges, 2011). Yawning: unsuspected avenue for a better understanding of arousal and interoception. Baan J Jr, Boekkooi PF, Teitel DF, Rudolph AM. Samueloff A, Langer O, Berkus M, Field N, Xenakis E, Ridgway L. Is fetal heart rate variability a good predictor of fetal outcome? doi: 10.1038/35013070, Borre, Y. E., O'Keeffe, G. W., Clarke, G., Stanton, C., Dinan, T. G., and Cryan, J. F. (2014). The fetoplacental transmission of the placental microbiome may occur through the ingestion of the amniotic fluid and via umbilical cord blood supply (Cao et al., 2014; Walker et al., 2017). Neurosci. FHR decelerations can be associated with little or no change in peripheral hemoglobin oxygen saturation. Sheep are in fact an important model for simulating human pregnancy. Feedback may be negative or positive. Therefore, the next two sections will discuss short-term and long-term consequences of disruptions in ANS development. A short review of adipokines, smooth muscle and uterine contractility. (1989). Satoh, T., Sakurai, E., Tada, H., and Masuda, T. (2009). The long-term consequences of developing cardiac control systems and ANS are hence under investigation (Frasch and Giussani, 2020). 188, 524531. At 2629 WGA, fetuses become able to efficiently control body temperature (Moore et al., 2016). 92, 5155. Brain Mapp. One of many unusual FHR patterns observed during labor, late decelerations could be considered dangerous. J. Comp. Copyright 2021 Cerritelli, Frasch, Antonelli, Viglione, Vecchi, Chiera and Manzotti. Neurosci. doi: 10.1111/pai.13099. 25, 595604. As previously mentioned, oxytocin plays an important role in activating the PNS and it has been shown to dampen SNS (Gamer and Bchel, 2012). doi: 10.1016/0002-9378(82)90812-2, Spinillo, A., Viazzo, F., Colleoni, R., Chiara, A., Maria Cerbo, R., and Fazzi, E. (2004). Autonomic responses to sighs in healthy infants and in victims of sudden infant death. Prior studies have catalogued extensive molecular alterations associated with homeostatic scaling. For example, neurons and glial cells in the pancreas do not appear and the thymus loses both its vasculature and its capacity of developing T-cells (Hutchins et al., 2018). J. Perinat. Curr. Interestingly, the analysis of specific HRV metrics, for instance, SDNN (more related to global neuroautonomic regulation), RMSSD (more related to vagal modulation), and PE, can help identify the actual behavioral state and, therefore, detect potential problems in neurodevelopment whether incoherence between HRV and body movements is detected (Schneider et al., 2008; Brndle et al., 2015). 04 November 2020 Development of the gonad in normal and anencephalic human fetuses. In the majority of cases, the beginning, low point, and recovery of late decelerations happen after the start, peak, and end of your contraction, respectively. Meas. Examining to what extent pregnancy-related physical symptoms worry women in the first trimester of pregnancy: a cross-sectional study in general practice. Comput. 1979 Dec;9(6):361-73. In the previous section, we described fetal development with particular attention to ANS, CAN, sensorimotor development, and some organs. Opioids are often used as analgesic therapy during labor. Since we have seen that amniotic flow and fetal growth restriction can affect vagal development, their effects could then be mediated by FMs. The 3rd stage commences when the fetus is delivered and ends with the delivery of the placenta (afterbirth) (Hutchison et al., 2021). Heart rate variability code: does it exist and can we hack it? Sci. A., Cox, M. J., Karchmar, E. J., McGrath, M. J., Pancham, S. R., and Piercy, W. N. (1981). Is it also related to comfort? doi: 10.1016/0002-9378(82)90616-0, Jonsson, M., Nordn-Lindeberg, S., Ostlund, I., and Hanson, U. Gynecol. Fetal neurobehavioral effects of exposure to methadone or buprenorphine. With the passing of the weeks, however, sex-specific differences in the sympathovagal balance start to be detected. Comp. Different methods could be used to evaluate the quantity and quality of FMs, such as mother perception, acceleration, and variability at cardiotocography (CTG), real-time ultrasound, myography, actocardiography (Zizzo et al., 2020), and the Non-stress Test, which relates FMs to fHR accelerations (Bryant et al., 2020). 131, 581S589S. 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. Gynecol. (2020). Even with complete pharmacologic blockage of the sympathetic and parasympathetic systems, around 35-40% of fetal lamb heart rate variability persists.19. doi: 10.1111/j.1749-6632.2012.06445.x, Mercer, B. M., Carr, T. L., Beazley, D. D., Crouse, D. T., and Sibai, B. M. (1999). Psychosomatics and psychopathology: looking up and down from the brain. Human fetal lungs harbor a microbiome signature. Gender-related differences in fetal heart rate during first trimester. Pain Pract. Res. J. Inflamm. Glucocorticoid programming of the fetal male hippocampal epigenome. 88, 718720. 85, 120126. The importance of foetal movement for co-ordinated cartilage and bone development in utero. 100, 863876. The matches collected between the placental and fetal gut and lung microbiomes seem to be associated with neonatal airway complications and enterocolitis (Al Alam et al., 2020; Parris et al., 2021), possibly affecting the ANS-mediated control mechanisms of these systems. doi: 10.1016/j.clp.2012.12.012, Shea, C. A., Rolfe, R. A., and Murphy, P. (2015). Paediatr. General movements allow fetuses to experience their bodies and the surrounding space, hence exploring the consequences their movements have on their bodies and environment (Fagard et al., 2018). Environmental magnetic field in a neonatal intensive care unit. Sex differences in the fetal heart rate variability indices of twins. doi: 10.1006/drev.1998.0452, Koletzko, B., Cremer, M., Flothktter, M., Graf, C., Hauner, H., Hellmers, C., et al. Obstet. Early Hum. (2011). Vagal blockade eliminated these decelerations in the non-acidemic sheep. The psychoneuroimmunology of pregnancy. 37, 953957. Goldstein, D. S. (2006). As a result, oligodendrocytes and their progenitors are damaged during a critical period of brain development, thus altering brain myelination and leading even to periventricular leukomalacia (Kadhim et al., 2001). Citalopram use in pregnancy: prospective comparative evaluation of pregnancy and fetal outcome. Pediatr. (1980). doi: 10.1111/aogs.13437, Boehm, F. H., Woodruff, L. F., and Growdon, J. H. (1975). Fetal motor capacities, through the implied neuronal activity, is paramount for differentiation, migration, synaptogenesis, and development of neuronal networks. An update on the controversies of tocolytic therapy for the prevention of preterm birth. Assoc. J. Autism Dev. The hypothalamic-pituitary-adrenal axis: development, programming actions of hormones, and maternal-fetal interactions. (2021). J. Matern. Additional modalities of EFM have been proposed such as intrapartum maternal transabdominal electrocardiography (ECG) and electroencephalography (EEG) which will increase the ability of EFM to predict fetal brain injury. Frauenh. J Gynecol Obstet Hum Reprod. The degree of hypertension and the amount of deceleration were closely related, although some deceleration remained when the transient hypertension was prevented by adrenergic blockade. Education (2020). Effect of epidural analgesia on the fetal heart rate. Am J Obstet Gynecol. Early and late effects of maternal experience on hippocampal neurogenesis, microglia, and the circulating cytokine milieu. J. Obstet. An increase in the heart rate c. An increase in stroke volume d. No change a. (2007). (2012). Some symptoms, such as PGP and low back pain, could be physiological consequences of the musculoskeletal adaptations of the maternal body, due to an increasing uterine volume (Davis, 1996; Vermani et al., 2010; Casagrande et al., 2015; Sehmbi et al., 2017; Lutterodt et al., 2019). Eur. Am. Any event that perturbs the fetal cardiovascular system will initiate a cascade of compensatory actions to optimize oxygen delivery and restore fetal hemostasis. doi: 10.1016/j.ynstr.2018.08.005, Conradt, E., Flannery, T., Aschner, J. L., Annett, R. D., Croen, L. A., Duarte, C. S., et al. Physiol. Among all the NC cells, the vagal NC cells are of particular interest due to their derivatives. Physiol. Allergy Immunol. doi: 10.1080/00016340802220352, Kadhim, H., Tabarki, B., Verellen, G., De Prez, C., Rona, A. M., and Sbire, G. (2001). doi: 10.1007/BF02344729, Langlois, P. H., Hoyt, A. T., Lupo, P. J., Lawson, C. C., Waters, M. A., Desrosiers, T. A., et al. doi: 10.1093/sleep/27.7.1405, Podymow, T., and August, P. (2008). Reflex control of immunity. 2009 Aug 12;302(6):660-8. Pain and discomfort thresholds in late pregnancy. Front. 89, 584590. Indeed, respiratory sinus arrhythmia appears to be strictly related and modulated by efferent vagal activity. J. J. Neurosci. Med. (2013). doi: 10.1007/978-1-4939-7828-1_19, Frasch, M. G., Boylan, G. B., Wu, H.-T., and Devane, D. (2017). A., Tsai, A. S., Ghaemi, M. S., Han, X., Ando, K., et al. Clearly other compensatory mechanisms intervened.14, Repetitive complete cord compressions are not a natural physiological condition. J. Obstet. (2006). (2009). The clinicians task is not simple. Liston R, Crane J, Hamilton E, Hughes O, Kuling S, MacKinnon C, McNamara H, Milne K, Richardson B, Trpanie MJ; Working Group on Fetal Health Surveillance in Labor, Executive and Council, Maternal-Fetal Medicine Committee, Clinical Practice Guideline Committee, and ALARM Committee, Society of Obstetricians and Gynaecologists Canada; Canadian Medical Protection Association. Many authors substantiated the materno-fetal transmission of the microbiome through the placenta during prenatal life, identifying the presence of the microbiota both in the peripartum placenta (Zheng et al., 2015; Pelzer et al., 2017) and in the meconium (Walker et al., 2017), partially regardless of the delivery mode. Prenatal alcohol exposure and cortisol activity in 19-month-old toddlers: an investigation of the moderating effects of sex and testosterone. Top. 9:593889. doi: 10.3389/fped.2021.593889, Goldaber, K. G., Gilstrap, L. C., Leveno, K. J., Dax, J. S., and McIntire, D. D. (1991). 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). 126, 1822. doi: 10.1016/j.yfrne.2017.10.006, Shiroiwa, Y., Kamiya, Y., Uchibori, S., Inukai, K., Kito, H., Shibata, T., et al. The myths and physiology surrounding intrapartum decelerations: the critical role of the peripheral chemoreflex. Obes. doi: 10.1111/1471-0528.15896, Lacasaa, M., Vzquez-Grameix, H., Borja-Aburto, V. H., Blanco-Muoz, J., Romieu, I., Aguilar-Garduo, C., et al. doi: 10.1097/EDE.0b013e31822546fd. Homeostatic circuits usually involve negative feedback loops. For instance, although we know that folate deficiency can impede the neural tube closure or that alcohol can induce dramatic brain modifications (Moore et al., 2016), we still lack knowledge about more subtle influences, that is, the precise effects of just some alcohol during the first weeks of pregnancy or the early effects of maternal stress (Avalos et al., 2014; Caspers Conway et al., 2014; Antonelli et al., 2021). doi: 10.1016/j.braindev.2018.10.009, Brndle, J., Preissl, H., Draganova, R., Ortiz, E., Kagan, K. O., Abele, H., et al. Obstet Gynecol. Microbiota and neurodevelopmental windows: implications for brain disorders. 115, 7783. Front. J. Nutr. Endorphin-mediated increases in pain threshold during pregnancy. 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). U.S.A. 108, 34613462. Health conditions may, however, affect postnatal ANS maturation more than gestational age at birth: in the 3 months after birth, infants with a higher number of postnatal complications (e.g., infections, patent ductus arteriosus requiring treatment, mechanical ventilation) show a lower ANS tone measured through DFA metrics, i.e., 1, 2, RMS1, and RMS2. Another unexpected mechanism that buffers the raise in intrinsic activity is the presence of the ether-a-go-go-related gen K + channel since its activation is illustrated to increase with size reduction. (2018). This seems to be associated with an increased risk for antibiotic-resistant neonatal sepsis (Mercer et al., 1999; Hantoushzadeh et al., 2020). Limitations of ST analysis in clinical practice: three cases of intrapartum metabolic acidosis. Obstet. Gynecol. However, theres no clinical evidence suggesting its effectiveness when used alone in women with adequate oxygen levels. J. Clin. 71, 313321. 143, 243249. Burgio, E. (2015). Moreover, it seems that monitoring FMs could contribute to creating a primitive maternalchild bonding, even before birth (Flenady et al., 2019). 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). Mapping the immunological homunculus. Firstly, by directly affecting brain development, as the skull has a low bone density that fails in adequately protecting newborns' brain from EMF (Besset et al., 2020). Rev. Influence of gestational age, heart rate, gender and time of day on fetal heart rate variability. Ulmer Yaniv, A., Salomon, R., Waidergoren, S., Shimon-Raz, O., Djalovski, A., and Feldman, R. (2021). Dis. Environ. Table 1. The inadequate intake or absorption of nutrients, such as polyunsaturated fatty acids, folic acid, and vitamin B12, may result in altered fetal neurodevelopment (Starling et al., 2015; Wang et al., 2015), and lead to important consequences on neurobehaviour during infancy (Gernand et al., 2016; Bordeleau et al., 2021). Women's experiences of pregnancy related pelvic girdle pain: a systematic review. Autism spectrum disorder: a neuro-immunometabolic hypothesis of the developmental origins. doi: 10.1111/j.1471-0528.1998.tb10206.x, Senturk, M. B., Cakmak, Y., Gndogdu, M., Polat, M., and Atac, H. (2015). doi: 10.1136/medethics-2019-105701, Dereymaeker, A., Pillay, K., Vervisch, J., De Vos, M., Van Huffel, S., Jansen, K., et al. (2). 43, 221225. bernard fanning wife andrea moreno,
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