The cardioacceleratory center increases heart rate directly via sympathetic cardiac nerves which interact with the sinoatrial node to increase the heart rate. Cahill AG, Tuuli MG, Stout MJ, Lpez JD, Macones GA. A prospective cohort study of fetal heart rate monitoring: deceleration area is predictive of fetal acidemia. Environ. J. Psychiatry 164, 12061213. Early Hum. The chances of fetal hypoxia remain low if repeated decelerations arent present and fetal heart tracing is otherwise normal. Pediatr. On the other hand, we are learning that certain factors (e.g., choline supplementation) may protect the fetus from excessive HPA axis activation and have long-lasting (into adulthood) effects on cognition through neural and epigenetic modifications (Korsmo et al., 2019). J. Obstet. (2020). Hence, further research is needed about these drugs' impact on fetal vagus nerve development. 22, 158168. doi: 10.1038/s41398-021-01198-w, Hanamsagar, R., and Bilbo, S. D. (2016). doi: 10.1038/s41390-019-0309-8, Noben, L., Verdurmen, K. M. J., Warmerdam, G. J. J., Vullings, R., Oei, S. G., and van Laar, J. O. E. H. (2019). Frasch, M. G. (2020). doi: 10.1016/j.preghy.2020.03.003, Moreira Neto, R., and Porovic, S. (2018). Primary benefits associated with the use of standardized. (2016). doi: 10.1016/0020-7292(84)90018-3, Schneebaum Sender, N., Govindan, R. B., Whitehead, M. T., Massaro, A. N., Metzler, M., Wang, J., et al. 92, 691693. doi: 10.1016/j.biopsycho.2012.01.003, van Geijn, H. P., Jongsma, H. W., Doesburg, W. H., Lemmens, W. A. J. G., de Haan, J., and Eskes, T. K. A. Better instrumentation has improved the measurement of physiological responses in animal experiments and electronic databases have increased our capacity to test hypothesis on tracings collected from human births. (2019). (2017). Neurosci. Gynecol. Quantitative aspects. 2004 Jan;190(1):118-23. Immun. Multiomic immune clockworks of pregnancy. the parasympathetic nervous system maintains beat to beat variability the ductus venosus allows well oxygenated blood to enter the fetal heart directly by bypassing the liver true or false metabolic acidosis is more easily reversible and potentially less detrimental to the fetus when compared to respiratory acidosis false catabolism Monit. Moreover, through the production of corticotropin-releasing hormone (CRH), the placenta stimulates adrenocorticotropic hormone release in the anterior pituitary of the fetus, affecting both fetal HPA axis and amygdala development (Seckl and Meaney, 2004). Autonomic nervous system activity in premature and full-term infants from theoretical term to 7 years. doi: 10.1002/bdrc.21129, Cardosi, R. J., and Chez, R. A. J. Perinat. 113, 87103. PLoS ONE 8:e68211. Semin Perinatol. Obstet. (2017). University of Erlangen Nuremberg, Germany. Diminished perception of this motor activity, could therefore be worrisome for the mother, leading to an increased amount of stress, which in turn may have an impact on fetal neurodevelopment (Bryant et al., 2020). 85, 10321040. Thrombin mediates vagal apoptosis and dysfunction in inflammatory bowel disease. Microbiol. 1984 Mar 1; 148(5):490-8. All authors reviewed, edited and approved the final version of the paper. doi: 10.1002/ca.22280, Wang, M., Wang, Z.-P., Gao, L.-J., Yang, H., and Zhao, Z.-T. (2015). doi: 10.1016/j.ajog.2003.12.023, Stallworth, J. C., Yeh, S.-Y., and Petrie, R. H. (1981). Howland, M. A., Sandman, C. A., Davis, E. P., and Glynn, L. M. (2020). 15, 209218. Res. Psychol. 2009 Sep;36(3):655-72. doi: 10.1016/j.clp.2009.06.009. (2017). 80, 8291. It is instead well known that methylmercury from seafood impairs the higher centers of cardiac autonomic function (Karita et al., 2018), leading to severe ANS abnormalities (Srensen et al., 1999; Grandjean et al., 2004; Murata et al., 2006; Gribble et al., 2015). During this period (48 WGA), from the NCs several derivatives arise: the dorsal root ganglia, the sympathetic ganglia, the renal, celiac, and intestinal ganglia and plexus, the afferent ganglia of cranial nerves, and the suprarenal medulla (Newbern, 2015; Moore et al., 2016). Fetal heart rate and variability: stability and prediction to developmental outcomes in early childhood. 78, 17881798. 16, 479494. Nutrients 11:1823. doi: 10.3390/nu11081823, Kozar, M., Tonhajzerova, I., Mestanik, M., Matasova, K., Zibolen, M., Calkovska, A., et al. In fetal life, pulmonary ventilation does not occur and is not a source of fetal oxygenation. Moreover, the heartbeat can be heard through ultrasound as early as the 6th WGA, the HR accelerates constantly during the first 8 WGA (Rodgers et al., 2015) and it was recently discovered that an intrinsic fHRV (i.e., due to sino-atrial node rhythms) existsit can affect the global fHRV and be influenced by pregnancy events (e.g., hypoxia) (Frasch et al., 2020a) and it shows a specific signature, that is, specific HRV metrics (Herry et al., 2019). doi: 10.1016/j.clp.2012.12.012, Shea, C. A., Rolfe, R. A., and Murphy, P. (2015). Obstet Gynecol. 35, 19431959. doi: 10.1053/smrv.2002.0243, Montagna, A., and Nosarti, C. (2016). Pediatrics 113, 368375. Exposure to opioids prenatally could result in programming effects on stress response systems, leading also to long-term consequences (Conradt et al., 2018, 2019). As a consequence, by relying on appropriate animal models, several authors have defined potential critical windows related to human brain development (see, for instance, Figure 1 in Morrison et al., 2018). Standards of measurement, physiological interpretation, and clinical use. 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). PLoS ONE 12:e0180167. 10:922. doi: 10.3389/fphys.2019.00922, Ouellet-Morin, I., Dionne, G., Lupien, S. J., Muckle, G., Ct, S., Prusse, D., et al. Clin. Environ. doi: 10.1016/j.jcrc.2010.11.008, Mulder, E. J. H., Derks, J. The timing of the onset, nadir and end of the deceleration was delayed with respect to the occlusion and mirrored the timeline of the hypertensive response. A. Baroreceptor B. Catecholamine C. Sympathetic correct answerA. Does performing cesarean section after onset of labor has positive effect on neonatal respiratory disorders? The cardioinhibitory center slows the heart rate via the parasympathetic vagus nerve which can slow heart rate by modulation at various levels, including the sino-atrial node. doi: 10.1016/j.neuropharm.2006.03.001, Kamendi, H. W., Cheng, Q., Dergacheva, O., Gorini, C., Jameson, H. S., Wang, X., et al. Physiological changes in pregnancy. 12, 354356. (2013). J. Obstet. (2020). Early Hum. Hypertension developed in response to compression of the umbilical arteries. 7:1031. doi: 10.3389/fmicb.2016.01031, Oberlander, T. F., Gingrich, J. 55, 1721. Ann. Gold et al. Prenatal influences on temperament development: the role of environmental epigenetics. During this stage, various components come into play that create an alternate activity between SNS and PNS (Norman et al., 2011; Musa et al., 2017). The fetal electrocardiogram to detect the effects of betamethasone on fetal heart rate variability. Front. Homeostatic circuits usually involve negative feedback loops. Dev. Obes. Fetal Heart Rate Monitoring. In the previous section, we described fetal development with particular attention to ANS, CAN, sensorimotor development, and some organs. (14), Shallow gradual deceleration that are late in timing and accompanied by a normal baseline and moderate baseline variability are inconsistent markers of low Apgar scores or metabolic acidosis. The autonomic nervous system (ANS) is one of the main biological systems that regulates the body's physiology. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Front. Low back pain in pregnancy: investigations, management, and role of neuraxial analgesia and anaesthesia: a systematic review. Can we learn to assess this individual experience? 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. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. doi: 10.4103/jdmimsu.jdmimsu_194_20, Sheng, J. One of many unusual FHR patterns observed during labor, late decelerations could be considered dangerous. That is, the machine (computer) learns from the actual data. It is noteworthy that all the adaptations required to pass from intrauterine to extrauterine life seem to rely on cortisol, whose release is markedly reduced in case of preterm birth or lack of labor (Hillman et al., 2012; Morton and Brodsky, 2016). doi: 10.1111/j.1552-6909.1996.tb02516.x, De Jonckheere, J., and Storme, L. (2019). Neurosci. Sleep in late pregnancy predicts length of labor and type of delivery. This situation puts newborns at risk of cardiovascular and metabolic dysfunctions, which can then negatively affect the developing brain by inducing inflammation or glucose deficiency (Hillman et al., 2012; Morton and Brodsky, 2016; Mulkey and du Plessis, 2018). Proc. Am. Around 20 WGA and for the rest of the 2nd trimester, myelination occurs (Borsani et al., 2019). 22, 337358. 2000 Apr; 107(4):461-6. (2020b). Placental vascular calcification and cardiovascular health: it is time to determine how much of maternal and offspring health is written in stone. Meas. Fetal development of complex autonomic control evaluated from multiscale heart rate patterns. (2010). J. Med. (2014). 1975 Feb;45(2):142-6. Parer JT, Ikeda T. A framework for standardized management of intrapartum fetal heart rate patterns.Am J Obstet Gynecol. Fetal heart rate is a vital indicator of your baby's health. which intrinsic homeostatic response is the fetus demonstrating . Rivolta, M. W., Stampalija, T., Casati, D., Richardson, B. S., Ross, M. G., Frasch, M. G., et al. J. Obstet. Pediatr. Uchitel, J., Vanhatalo, S., and Austin, T. (2021). (1991). Using fetal oximetry probes many centers reported images of deep decelerations with little or no change in fetal oxygen saturation. Meas. 36, 23692378. II. Delayed cord clamping in healthy term infants: more harm or good? Stimulating the vagus nerve typically produces: a. doi: 10.1523/JNEUROSCI.3846-13.2013, Khedun, S. M., Maharaj, B., and Moodley, J. Indeed, fetuses with intrauterine growth restriction (IUGR) frequently present an oxygenation impairment, with a decrease of breathing movements and GMs, and an increasing number of HR decelerations (Bekedam et al., 1991). Orthop. Early life stress and environmental influences on the neurodevelopment of children with prenatal opioid exposure. 193, 20042009. The fetal heart rate pattern we observe is the combined results of many physiological actions. J Appl Physiol (1985). A variety of different ANS and vagus nerve pattern activities are now well-established between different sexes, which can be well-represented by HRV tracking even during fetal life. doi: 10.1007/s00424-013-1258-4, Cibils, L. A., and Votta, R. (1993). (2020). These changes were suggested to result from the effects of chronic hypoxiawhich ZIKV infection is known to causeon the interactions between the ANS and the cardiac pacemaker cell development which generates intrinsic HRV (Frasch et al., 2020a; Herry et al., 2021). doi: 10.1038/nrendo.2016.37, Gintzler, A. R. (1980). Persistent low variability is concerning, especially when present on admission or associated with decelerations and tachycardia.16 Low variability must not be ignored, but it appears that moderate variability does not guarantee the absence of acidemia. Maternal positioning affects fetal heart rate changes after epidural analgesia for labour. Psychoneuroendocrinology 87, 2734. Sex differences in neurodevelopmental and neurodegenerative disorders: focus on microglial function and neuroinflammation during development. doi: 10.1088/0967-3334/37/9/1436, Lu-Culligan, A., and Iwasaki, A. It is noteworthy that earmuffs show ambiguous results, that is, they can both help oxygenation and sleep and provoke stress (Zahr and de Traversay, 1995; Aita et al., 2013; Almadhoob and Ohlsson, 2020). ArXiv210207768 Phys. 85, 633638. doi: 10.1136/thorax.57.6.555, Eid, R. S., Chaiton, J. 130, 403407. 2009 Jul; 114(1):192-202. Rev. (2003). These methods are not held to a specific clinical hypothesis. Fetal motor capacities, through the implied neuronal activity, is paramount for differentiation, migration, synaptogenesis, and development of neuronal networks. The autonomic nervous system (ANS) is one of the main biological systems that regulates the body's physiology: in particular, the interaction between its two branchesthe sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS)allows the organism to efficiently cope with endogenous and exogenous stressors (Goldstein, 2006; Bonaz et al., 2021). Our current clinical management of fetal and maternal health is not individualized and intermittent, suffering from a pattern of catching up with clinical symptoms instead of using biometric data to predict and steer developmental trajectories and health outcomes for the pregnant mother and her fetus during the delivery and after to their fullest potential. Front. doi: 10.2165/00128072-200002060-00002, Kisilevsky, B. S., and Low, J. 12, 170177. Maternal nutrition is a substantial part of the developmental or metabolic programming of newborns (Koletzko et al., 2018, 2019), with short- and long-term consequences on health and a relevant impact on fetoplacental growth patterns (Morrison and Regnault, 2016). American College of Obstetricians and Gynecologists. Women's experiences of pregnancy related pelvic girdle pain: a systematic review. 28, 16641668. 7:80. doi: 10.3389/fpsyg.2016.00080. Assessment of fetal development using cardiac valve intervals. [Low back pain during pregnancy. Pain 27, 6368. Adverse health outcomes associated with fetal alcohol exposure: a systematic review focused on immune-related outcomes. Pediatr. Maternal and paternal occupational exposure to agricultural work and the risk of anencephaly. Hull J, Dodd KL. Pediatrics 139, S38S49. The emergence of fetal behaviour. Psychol. Infant stress reactivity and prenatal alcohol exposure. At 1819 WGA, nociceptive neurons and the typical hormonal response to pain appear (Borsani et al., 2019; Chen et al., 2021), thus hinting that primitive pain perception might begin at this stage. IX: prolonged pregnancy. Physiol. Sci. Castel, A., Burns, P. M., Benito, J., Liu, H. L., Kuthiala, S., Durosier, L. D., et al. The effect of labor on maternal and fetal circulating catecholamines. J. In the next weeks, the nervous system rapidly grows: the five secondary brain vesicles, along with the four ventricles and the meninges form, while the glioblasts (the glial cells precursors) start to differentiate and migrate throughout the developing nervous system. Med. (2001). Psychopathol. Contributions of the maternal oral and gut microbiome to placental microbial colonization in overweight and obese pregnant women. PeriGens EFM Scholarship Program, Basics of Electronic Fetal Monitoring ( EFM ). In response to sudden auditory stimulation, the central nervous system activates the cardioacceleratory center. (2010). doi: 10.1159/000488106, Morton, S. U., and Brodsky, D. (2016). Gynecol. (2021). Rezk, A. Y., Abdulqawi, K., Mustafa, R. M., El-Azm, T. M. A., and Al-Inany, H. (2008). Sameshima H, Ikenoue T, Ikeda T, Kamitomo M, Ibara S. Unselected low-risk pregnancies and the effect of continuous intrapartum fetal heart rate monitoring on umbilical blood gases and cerebral palsy. How yawning switches the default-mode network to the attentional network by activating the cerebrospinal fluid flow: how yawning switches the DMN to the attentional network. Although the ANS and vagus nerve activity appear to have an endogenous circadian rhythm (Hilton et al., 2000; Kentish et al., 2013), with a pacemaker system that regulates its behavior regardless of sleep-awake states (Malpas and Purdie, 1990; Hilton et al., 2000), a circadian variation pattern of vagal activity can be recorded via HR variations. Can. Am J Obstet Gynecol. doi: 10.1136/jclinpath-2020-206536, Passi, R., Doheny, K. K., Gordin, Y., Hinssen, H., and Palmer, C. (2017). Drugs to Support Fetal Growth Synthetic glucocorticoids (sGCs) are the therapy of choice to support fetal maturation for the risk of preterm delivery. Burgio, E. (2015). [Epub ahead of print]. At 56 WGA, the 12 cranial nerves appear (Moore et al., 2016). (2015). 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. These patterns are altered by pain and could hence not only be pre-emptive for negative outcomes for labor and birth (Goldenberg et al., 2008), but also suggest their influence on the neurodevelopment of the fetal vagal system itself (Borovikova et al., 2000; Tracey, 2009; Frasch et al., 2016). Gender differences in neurodevelopment and epigenetics. Gynecol. 1:CD010333. 7:57. doi: 10.3389/fnint.2013.00057, Gemmel, M., De Lacalle, S., Mort, S. C., Hill, L. A., Charlier, T. D., and Pawluski, J. L. (2019). Sahin, F. K., Koken, G., Cosar, E., Saylan, F., Fidan, F., Yilmazer, M., et al. 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). doi: 10.1002/bdrc.21139, Facco, F. L., Kramer, J., Ho, K. H., Zee, P. C., and Grobman, W. A. (2017). Newborns can also be subject to EMFs, from the incubator or the care unit environment. Fetal cardiovascular decompensation during labor predicted from the individual heart rate tracing: a machine learning approach in near-term fetal sheep model. periodic accelerations can indicate all of the following except: A. Stimulation of fetal chemoreceptors B. Tracing is maternal C. Umbilical vein compression A. Stimulation of fetal chemoreceptors All of the following are likely causes of prolonged decelerations except: A. A study with autonomic blocking agents in fetal lambs. (2009). Neuropharmacology 144, 7081. Sleep Med. A second component of the chemoreflex response to hypoxemia is parasympathetic, mediated via the vagus nerve, resulting in a fall in heart rate. doi: 10.1007/978-1-4939-7828-1_18, Frasch, M. G., and Giussani, D. A. 37, 668672. doi: 10.1007/s00404-019-05390-8, Low, J. Pediatr. Even if further research is needed, maternal vitamin D intake deficit correlates with altered metabolic and contractile development of the heart and the control mechanisms of blood pressure in fetuses (Morris et al., 1995; Gale et al., 2008). Prenatal opioid exposure: neurodevelopmental consequences and future research priorities. Am. Med. The hallmark of a negative feedback loop is that it counteracts a change, bringing the value of a parametersuch as temperature or blood sugarback towards it set point. Once born, newborns have to deal with the extrauterine environment that, especially for preterm babies, is constituted by the incubator. doi: 10.1016/0002-9378(81)90208-8, Starling, P., Charlton, K., McMahon, A. T., and Lucas, C. (2015). 14, 107114. (2019). doi: 10.1067/mob.2003.136, Sun, S., Spangler, K. R., Weinberger, K. R., Yanosky, J. D., Braun, J. M., and Wellenius, G. A. This phenomenon has the potential of altering ANS in three ways, especially in preterm or vulnerable infants. 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). Opioids are often used as analgesic therapy during labor. Occup. 9, 7685. 2002 Mar;24(3):250-76. doi: 10.1088/1361-6579/aa5fca, Hutchins, E. J., Kunttas, E., Piacentino, M. L., Howard, A. G. A., Bronner, M. E., and Uribe, R. A. When they suspect fetal hypoxia, they must determine the delivery timing to prevent serious consequences for your newborn. A relevant verification. However, more recently, several papers brought to light the importance of the ANS highlighting the fact that the early developmental disruption of the connections between the ANS and the limbic system might restrict the capacity of the ANS to respond to the environment and can be later implicated in neuropsychiatric disorders of the infant (Montagna and Nosarti, 2016; Frasch et al., 2018a, 2020b). Statistically, severe fetal acidemia (pH < 7.00) has been shown to occur in between 0.5 and 10% of human births. J. Environ. Core temperature variation is associated with heart rate variability independent of cardiac index: a study of 278 trauma patients. 27, 8994. Obstet. Heart rate variability in hypertensive pregnancy disorders: a systematic review. doi: 10.1503/cmaj.191372, Beauchaine, T. P., Gatzke-Kopp, L., and Mead, H. K. (2007). J. Pediatr. Biol. 524, 12591269. 54, 3437. Gynaecol. Psychopharmacology (Berl.) Similarly, even autoimmune diseases can involve a dysregulation in maternal inflammatory response (Gordon, 2004; Lu-Culligan and Iwasaki, 2020; Han et al., 2021). 18, 129. Yawning: unsuspected avenue for a better understanding of arousal and interoception. doi: 10.1038/sj.jp.7211352, Lauder, A. P., Roche, A. M., Sherrill-Mix, S., Bailey, A., Laughlin, A. L., Bittinger, K., et al. J. Obstet. 7, 54. doi: 10.3390/jcdd7040054, Fischer, L. A., Demerath, E., Bittner-Eddy, P., and Costalonga, M. (2019). Vagal regulation of heart rate in the prediction of developmental outcome for very low birth weight preterm infants. 41, 197219. (2017). (2017). The influence of corticosteroids on fetal heart rate variability: a systematic review of the literature. Fetal Neonatal Ed. doi: 10.1016/j.ajog.2005.05.012, Sklerov, M., Dayan, E., and Browner, N. (2019). (2012). 89, 380387. Eur. The emergence of fetal behaviour. 37, 95110. Rev. doi: 10.1016/j.ajog.2016.10.003, McEwen, B. S., Nasca, C., and Gray, J. D. (2016). Physiol. They suggested that late decelerations tend to occur in a fetus with limited reserves that is exposed to modest reductions in uterine blood flow that would not cause bradycardia in a healthy fetus. J. Nurs. (2006). Correlation between human nervous system development and acquisition of fetal skills: an overview. Front. Occasionally these mechanisms are overwhelmed and fetal death or injury occurs. Validation of functional fetal autonomic brain age score fABAS in 5 min short recordings. Maternal obesity, in particular, both before conception and during pregnancy, is associated with impaired fHRV and poorer ANS development (Christifano et al., 2020). Intrapartum management of category II fetal heart rate tracings: towards standardization of care. Some authors have challenged the role of the baroreceptor response as the sole or major cause of fetal heart rate decelerations.6, 13-15 Clinicians who use fetal heart rate recording are strongly encouraged to read in detail excellent summaries of their studies on the mechanisms of fetal heart rate decelerations.6, 13-15, In one set of sheep experiments, blood pressure and fetal cerebral oxygenated hemoglobin were measured during complete cord compression. PLoS ONE 9:e104193. (2019). Preterm newborns have an immature ANS, which has great repercussions on cardiac and respiratory functions (Mulkey and du Plessis, 2018). doi: 10.1016/j.bbi.2013.02.001, Hasain, Z., Mokhtar, N. M., Kamaruddin, N. A., Mohamed Ismail, N. A., Razalli, N. H., Gnanou, J. V., et al. 15-30 minutes in the active phase of the first stage and . C Embryo Today Rev. In this paragraph, we will consider the studies that simulate the 1st stage of labor. Perinatal fluoxetine has enduring sexually differentiated effects on neurobehavioral outcomes related to social behaviors. The chemoreceptor mediated ventillatory response is inhibited in fetal life and other components of the chemoreflex responses are more apparent.8. Scand. Biol. Cord compression and uterine contractions can induce decelerations. (2009). Impact of fetal alcohol exposure on body systems: a systematic review. (2). J Physiol. As the vagus nerve affects the body metabolism in a pleiotropic manner, such a review could help better understand the networks underlying this effect and how to harness them for improving fetal and neonatal health (Castel et al., 2020). 61, 242251. Lastly, early pain reactivity measured through HRV in alcohol-exposed newborns seems to be blunted, suggesting different responsiveness to environmental stimuli even after birth (Oberlander et al., 2010). 92, 5155. Maternal perception of FMs, in conclusion, is one of the factors that could influence in a relevant way the emotional state of the mother. Res. Rev. doi: 10.1007/978-1-4939-7828-1_19, Frasch, M. G., Boylan, G. B., Wu, H.-T., and Devane, D. (2017). However, the literature shows that the ANS can be assessed through fHRV from 15 to 20 WGA (Hoyer et al., 2012, 2013b, 2015, 2019; Shuffrey et al., 2019). Many viral infections, such as cytomegalovirus and other TORCH organisms or ZIKV infection, can lead to preterm birth and induce severe neurodevelopmental alterations in the fetus (Silasi et al., 2015; Vohr et al., 2017). Transl. doi: 10.1016/j.biopsycho.2010.11.006, Nugent, B. M., and Bale, T. L. (2015). Effect of epidural analgesia on the fetal heart rate. doi: 10.1038/35013070, Borre, Y. E., O'Keeffe, G. W., Clarke, G., Stanton, C., Dinan, T. G., and Cryan, J. F. (2014). As the 3rd trimester advances, specific nociceptive event-related potentials in the brain increasingly develop until 3537 WGA (Verriotis et al., 2016). Furthermore, ANS alterations in newborns can lead to neurological dysfunctions including cerebral palsy at 2 years of age (Dimitrijevi et al., 2016). doi: 10.1016/j.neuropharm.2018.10.009, Gernand, A. D., Schulze, K. J., Stewart, C. P., West, K. P., and Christian, P. (2016). 2017 Feb;216(2):163.e1-163.e6. This seems to be associated with an increased risk for antibiotic-resistant neonatal sepsis (Mercer et al., 1999; Hantoushzadeh et al., 2020). Br J Obstet Gynaecol. In addition, this paper will focus on which factorsi.e., fetal characteristics and behaviors, maternal lifestyle and pathologies, placental health and dysfunction, labor, incubator conditions, and drug exposuremay have an impact on the development of the vagus during the above-mentioned critical window and how. Sci. Oxytocin specifically enhances valence-dependent parasympathetic responses. Lastly, maternal mood disorders and depression seem to strongly impact the fetal neuroendocrine systems, in particular the amygdala (McEwen et al., 2016) and the hippocampus (Nemoda et al., 2015), strongly involved in the CAN (Harrison et al., 2013; Thome et al., 2017). We show that deletion of insulin-like growth factor-1 receptor (IGF-1R) limits firing rate homeostasis in response . doi: 10.1016/j.earlhumdev.2016.05.014, DiPietro, J. In particular, by 6 WGA, the first parasympathetic ganglia can be detected (Mller and O'Rahilly, 1989) and, by 10 WGA, the sympathetic trunks have appeared throughout the vertebral column (Kruepunga et al., 2021) and, apart from the colonic loop, the extrinsic innervation of the enteric nervous system (ENS) is complete (Kruepunga et al., 2020). This could suggest a different developmental pattern of the vagus nerve, both sex- and time-specific. doi: 10.1037/0012-1649.40.3.445, DiPietro, J. doi: 10.3945/jn.109.116327, Christifano, D. N., Taylor, M. K., Carlson, S. E., Colombo, J., and Gustafson, K. M. (2020). J. Matern. 66, 201209. 1981 Dec 1; 141(7):797-806. Endocrinol. Immunol. 12:20160545. doi: 10.1098/rsbl.2016.0545, Gallup, A. C., and Eldakar, O. T. (2013). doi: 10.1007/s10803-020-04467-7. Health Rep. 2, 304314. VIII. (2017). One of such responses, able to perform homeokinetic adjustments, is the cholinergic anti-inflammatory pathway (CAP). Front.

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