Curr. The fetal autonomic nervous system, the fetal heart rate and the beat-to-beat irregularity. doi: 10.1016/j.braindev.2019.04.014, Alfirevic, Z., Devane, D., Gyte, G. M., and Cuthbert, A. (2006). Psychol. 201, 10021006. Biol. Biobehav. Psychiatry 5:e545. (2007). (2000). (2016). Cahill AG, Roehl KA, Odibo AO, Macones GA. Association and prediction of neonatal acidemia. The omniscient placenta: metabolic and epigenetic regulation of fetal programming. doi: 10.3390/nu7053067, Wang, X., Durosier, L. D., Ross, M. G., Richardson, B. S., and Frasch, M. G. (2014). 86, 174180. doi: 10.1016/j.physio.2018.05.001, Cogan, R., and Spinnato, J. Effect of dexamethasone and betamethasone on fetal heart rate variability in preterm labour: a randomised study. Since the development of ANS and the vagus influence have been shown to be reflected in cardiac variability, this paper will rely in particular on studies using fetal heart rate variability (fHRV) to monitor the continued growth and health of both animal and human fetuses. Heart J. This seems to confirm the PAE effects on HPA axis stress reactivity, possibly via changes in central serotonin levels and/or HPA axis functions, and on the vagus nerve development itself (Haley et al., 2006). doi: 10.1016/j.jpeds.2003.10.058, Graven, S. N., and Browne, J. V. (2008). doi: 10.1530/jrf.0.0600193, Bale, T. L. (2016). doi: 10.1016/j.psyneuen.2011.05.007, Gartstein, M. A., and Skinner, M. K. (2018). doi: 10.1016/j.wombi.2018.12.001, Fox, G. P. P., and Matthews, T. G. (1989). Med. Many postnatal pathologiese.g., hyperbilirubinemia, congenital heart disease, respiratory distress syndrome, respiratory syncytial virus, NEC, and sepsiscan lead to ANS impairment, probably due to inflammatory cytokines and toxins that can bypass the brain-blood barrier and induce neural death in areas paramount to ANS control (Fritze et al., 2014; Al-Shargabi et al., 2017; Bonaz et al., 2021). In particular, we will study what events can interfere with the correct development of these two systems by analyzing the evidence from preclinical and clinical studies in this regard, with the aim of preventing potential complications with long-term consequences. A. Baroreceptor B. Catecholamine C. Sympathetic correct answerA. Biobehav. Eng. Comput. To simulate decreased uteroplacental oxygen delivery, they applied repeated occlusions to the maternal hypogastric artery12. doi: 10.1002/14651858.CD006066.pub3, Allen, L. H. (2001). 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). The Developing Human: Clinically Oriented Embryology, 10th Edn. The dysregulation of placental functions can induce an insufficient intake of nutrients for the fetus, thus, especially during mid and late gestation, impairing the development of various brain areas, including the hypothalamus that seems to be particularly sensitive to the nutrient deficiency (Nugent and Bale, 2015). Am. Child. Argent. In this model hypertension followed by baroreceptor response were proposed as the key steps stimulating the cardioinhibitory center and causing slowing of the heart rate mediated via the vagus. Electronic fetal heart rate monitoring: research guidelines for interpretation. Scand. doi: 10.1016/j.berh.2004.02.012, Gotsch, F., Romero, R., Kusanovic, J. P., Mazaki-Tovi, S., Pineles, B. L., Erez, O., et al. Physiology and immunology of the cholinergic antiinflammatory pathway. (2012). Struggling with daily life and enduring pain: a qualitative study of the experiences of pregnant women living with pelvic girdle pain. Since ANS development is coupled with FMs development, ANS alterations can heavily affect CNS and neurobehavioral growth: on the one hand, FMs are usually considered the base for the fight-or-flight response, thus influencing the stress response (Schmidt et al., 2014); on the other hand, ANS immaturity correlates with altered cerebral and psychomotor development (Hoyer et al., 2014; Schmidt et al., 2014; Schneider et al., 2018), and even with altered cognitive, language, playing, and social skills (Doussard-Roosevelt et al., 1997, 2001; Bornstein et al., 2002; DiPietro et al., 2007; Siddiqui et al., 2017). Raczyska, A., and Gulczyska, E. (2019). Arch. Gynecol. Online detection of fetal acidemia during labour by testing synchronization of EEG and heart rate: a prospective study in fetal sheep. The isolation of fetal homeostasis or of that of any other group of animals inhabiting a highly specialized environment, for example, desert-swellers, divers, or hibernators from homeostasis in general implies that there is something particular about the circumstances in which it is operating. doi: 10.1016/S0029-7844(98)00212-9, Carvajal de la Osa, J., Santana Gonzlez, J., Herrera Galn, M., Snchez Grau, A., and Prez Almirall, I. But these cells also contribute to the formation of organs such as the heart (especially, the intrinsic cardiac nervous system), thyroid and parathyroids, thymus, lung, and pancreas ganglia. Fetal movement, in StatPearls (Treasure Island, FL: StatPearls Publishing). 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. 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). (Paris). 33, 847850. Labor is usually induced through the administration of synthetic oxytocin (sOT). This association is important because all contemporary EFM classification methods place high reliance upon baseline fetal heart rate variability to exclude the presence of metabolic acidosis.23-30 The 2008 NICHD Update publication in which the Category I, II, III classification method was first described includes a statement that moderate variability reliably predicts the absence of metabolic acidemia at the time that it is observed.24 This concept was softened in the 2009 ACOG Practice Bulletin 106 with the statement The data relating FHR variability to clinical outcomes, however, are sparse.25 This practice bulletin endorsed the 3-level categorization of tracings where the third level required absent baseline variability. 108, 174180. Fetal heart rate and motor activity associations with maternal organochlorine levels: results of an exploratory study. Then, as gestation progresses, the amount of movement, both spontaneous and in response to vibroacoustic stimuli, gradually increases: indeed, mothers begin to feel their babies' movements (Moore et al., 2016; Borsani et al., 2019). J. Obstet. J. Obstet. doi: 10.1016/0378-3782(90)90011-7, Preston, R., Crosby, E. T., Kotarba, D., Dudas, H., and Elliott, R. D. (1993). Umbilical cord compression has been created in research environments by actually compressing the fetal cord with implanted mechanical devices that could be manipulated to compress the cord to different degrees and durations. Korean J. Pediatr. (2018). PLoS ONE 6:e22100. Dev. The prenatal gut microbiome: are we colonized with bacteria in utero? Contributions of the maternal oral and gut microbiome to placental microbial colonization in overweight and obese pregnant women. Res. Porges, S. W., and Furman, S. A. (2018). In adult cardiology, ECG changes are very helpful to diagnose myocardial infarction because there is a direct relationship, precisely defined by anatomy and electromagnetic physics, linking the presence of Q waves in the 12-lead ECG to the location of injured myocardium. Parer JT, Ikeda T. A framework for standardized management of intrapartum fetal heart rate patterns.Am J Obstet Gynecol. 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. J Physiol. Regarding the vagus nerve, at this stage, the dorsal motor nucleus is the predominantly active effector center (Porges, 2011). doi: 10.1111/ijpo.12217, Wallingford, M. C., C, B., Nw, C., Mt, C., and Mg, F. (2018). Fetal heart rate, heart rate variability, and heart rate/movement coupling in the safe passage study. Other work by Bennet et al has also challenged common teaching about the relationship between hypertension and decelerations. Nevertheless, neonatal intensive care units have improved so much in the years that babies born as early as 2022 weeks can survive if properly treated (Moore et al., 2016). Gynaecol. Category II Application doi: 10.5546/aap.2020.eng.e246, Casagrande, D., Gugala, Z., Clark, S. M., and Lindsey, R. W. (2015). 9, Freeman RK, Garite TJ, Nageotte MP, Miller LA. doi: 10.1089/bfm.2008.0002, Jones, C. M., and Greiss, F. C. (1982). J. Obstet. J. Calif. Perinat. Eur. 48, 829842. Otherwise, especially in case of a difficult delivery or CS without labor, the fetus may experience hypoxia and have difficulties in secreting pulmonary surfactant, thus developing respiratory pathologies that can backfire, in particular, on ANS brainstem centers through oxygen deprivation and hinder autonomic regulation (Hillman et al., 2012; Morton and Brodsky, 2016; Mulkey and du Plessis, 2018). Media Coverage Clin. doi: 10.1097/EDE.0b013e31822546fd. 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. (2016). doi: 10.1093/jpepsy/jsj031, Zeskind, P. S., and Stephens, L. E. (2004). The nadir of the deceleration was very close to the end of the compression period in both groups. Psychobiol. The relationship of the fetal head size to the pelvis is important. Comput. By 10 WGA, fetal circulation passively exchanges gas mainly with the placenta and breathing begins. Sleep Med. 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). Front. Physiol. J. Perinatol. For this reason, before birth neuroendocrine signaling (e.g., catecholamines, cortisol, thyroid hormones, and renin-angiotensin) surges, and SNS outflow from CAN (e.g., hypothalamus, cortical, and brainstem centers) greatly increases. 90, 131139. Around the transition between the 1st and 2nd trimester, even the circumventricular organs, in particular, the area postrema, appear: they are organs devoid of the brain-blood barrier that, hence, allow the brain to be directed informed about the biochemical status of the internal milieu (Gokozan et al., 2016). doi: 10.1542/peds.2015-4271, Conradt, E., Crowell, S. E., and Lester, B. M. (2018). (2007). Dev. An examination of changes in maternal neuroimmune function during pregnancy and the postpartum period. In-house obstetrical coverage, drills to increase the rapidity of emergency cesarean, safer oxytocin management protocols also contribute to better outcomes. Occasionally these mechanisms are overwhelmed and fetal death or injury occurs. The effects of epidural anesthesia on electronic fetal heart rate monitoring. doi: 10.1016/j.semnephrol.2010.10.007. Acta Obstet. which intrinsic homeostatic response is the fetus demonstratingjavascript open new tab but stay on current page . An increase in the heart rate c. An increase in stroke volume d. No change a. It is widely known that comorbidities such as NEC or hypoxic-ischemic encephalopathy (HIE) can negatively affect ANS (Schlatterer et al., 2021). 4, 167170. 23, 233246. Neonates affected by in utero exposure to SSRIs display fewer HRV rhythms and changes in behavioral states, based on the time drugs were administered (Zeskind and Stephens, 2004). Cardiovasc. doi: 10.4103/jdmimsu.jdmimsu_194_20, Sheng, J. 17, 641650. Even if the effects on the vagus nerve are still to be defined, the hazards exposure may affect the fetal motor activity (DiPietro et al., 2014) and be related to delayed neurobehavioural development in neonates (Handal et al., 2008). Obstet Gynecol. doi: 10.1016/j.autneu.2007.04.008, de Vries, J. I. P., Visser, G. H. A., and Prechtl, H. F. R. (1982). 181:108894. doi: 10.1016/j.envres.2019.108894, Bhide, A., and Acharya, G. (2018). doi: 10.1097/PCC.0000000000000643, Lobmaier, S. M., Mller, A., Zelgert, C., Shen, C., Su, P. C., Schmidt, G., et al. Clinicians shoulder a major and challenging responsibility while caring for mother and baby in labor. Nonetheless, the importance of ANS and vagus nerve regulation in fetal and neonatal development is still underrepresented (Sadler, 2012; Moore et al., 2016). Am J Obstet Gynecol. Am. Glucocorticoid programming. J. Obstet. Ther. Placenta Microbiome Diversity Is Associated with Maternal Pre-Pregnancy Obesity and Placenta Biogeography. A Clin. In conclusion, many diseases can impact the placental function, which in turn seems to have a role in regulating the neurodevelopment of the main actors that interact with the fetal vagus nerve, and the monitoring of placenta secretome could be a useful biomarker of diseases and potential developmental disruptions of the ANS in the fetus (Aplin et al., 2020). 118, e246e251. Natl. Neurosci. The placenta can be defined as a neuro-immune-endocrine secretive organ, with the essential role of conveying nutrients and developing modulatory signals to fetuses, limiting their exposure to any factors that could alter their physiologic developmental patterns. (2020). Arch. doi: 10.1136/archdischild-2015-310045. Therefore, dysregulation of sympathetic control . Gynaecol. doi: 10.1016/j.compbiomed.2011.05.003, Hoyer, D., Nowack, S., Bauer, S., Tetschke, F., Rudolph, A., Wallwitz, U., et al. We . Med. Bone Jt. Development of the sympathetic trunks in human embryos. Sahin, F. K., Koken, G., Cosar, E., Saylan, F., Fidan, F., Yilmazer, M., et al. (2018). During pregnancy, the maturation pattern of fetal gonads must be taken into account. Med. doi: 10.1016/0002-9378(78)90280-6, Fritze, D., Zhang, W., Li, J.-Y., Chai, B., and Mulholland, M. (2014). 1997 Dec; 177(6): 1385-90. Lastly, yawning amount and duration seem to correlate with neuronal development in mammals (Gallup et al., 2016). doi: 10.1016/j.psyneuen.2005.04.014, Thome, J., Densmore, M., Frewen, P. A., McKinnon, M. C., Thberge, J., Nicholson, A. doi: 10.1038/s41390-021-01497-4. 63, 281287. The association between variability and metabolic acidosis is less clear. PLOS ONE 13:e0200799. Auditory brain development in premature infants: the importance of early experience: McMahon et al. 193, 20042009. Gynecol. The consequences on the long-term capacity of CAP inflammatory response are worthy of further investigations. Am. Afferent and efferent components of the cardiovascular reflex responses to acute hypoxia in term fetal sheep. 35, 12911301. Reprod. The autonomic nervous system (ANS) is one of the main biological systems that regulates the body's physiology. Intrinsic Influences on the Fetal Heart Rate . Moore, K. L., Persaud, T. V. N., and Torchia, M. G. (2016). The farther away newborns stay from the incubator power, the less the ANS is affected (Bellieni et al., 2008; Passi et al., 2017). This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). doi: 10.1007/s00404-019-05390-8, Low, J. The Heart's rhythm n blues: sex differences in circadian variation patterns of vagal activity vary by depressive symptoms in predominantly healthy employees. Comparison of placenta samples with contamination controls does not provide evidence for a distinct placenta microbiota. J. Reprod. Med. During the 2nd trimester, the body becomes covered with lanugo, a fine downy hair that plays a paramount role in neurodevelopment. doi: 10.1006/drev.1998.0452, Koletzko, B., Cremer, M., Flothktter, M., Graf, C., Hauner, H., Hellmers, C., et al. Increases baseline b. Decreases baseline b. Moreover, maternal psychopathology influences HRV tracking also after birth, showing a higher mean HR and lower vagal modulation and confirming the impact of this prenatal disorder on vagal neurodevelopment (Dierckx et al., 2009). 2013 Aug; 209(2):89-97. Dev. 14, 259265. A., Drogtrop, A. P., Gyselaers, W. J. Am. Midwifery 29, 13461351. Interface 15:20170593. doi: 10.1098/rsif.2017.0593, Verdurmen, K. M. J., Hulsenboom, A. D. J., Laar, J. O. E. H., and van Oei, S. G. (2017). Am J Obstet Gynecol. 2009 Aug 12;302(6):660-8. Semin. Obstet Gynecol. J. Pediatr. When a doctor suspects fetal hypoxia, they must determine the delivery timing to prevent serious consequences for your newborn.

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