Med. Nutrients 7, 30673077. 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. (1980). Maturation of heart rate and blood pressure variability during sleep in term-born infants. doi: 10.1016/0378-3782(82)90033-0, de Vries, J. I. P., Visser, G. H. A., and Prechtl, H. F. R. (1985). Fetal heart rate patterns, together with GMs and REM recording, are the main factors to define the passage through fetal sleep states (Van den Bergh and Mulder, 2012), pointing out the direct relationship between vagal activity and circadian rhythm. Rev. Scand. doi: 10.1016/j.wombi.2018.12.001, Fox, G. P. P., and Matthews, T. G. (1989). J. Physiol. Ther. (2015). The resulting hypertension induces the barorflex, stimulating the cardioinhibitory center and its vagal efferent to slow the heart rate. Effect of antenatal betamethasone and dexamethasone administration on fetal heart rate variability in growth-retarded fetuses. Hull J, Dodd KL. Nutr. Dev. Dev. An increase in arterial blood pressure produces vessel distension and causes arterial baroreceptors to send neuronal messages to the cardioinhibitory center, which in turn causes rapid slowing of the fetal heart rate via the parasympathetic vagus nerve. Even with complete pharmacologic blockage of the sympathetic and parasympathetic systems, around 35-40% of fetal lamb heart rate variability persists.19. A., Zimmerman, A., Hamadia, S., Ziv, O., Gurevich, V., Fichtman, B., et al. doi: 10.1159/000501906. PLoS ONE 9:e104193. doi: 10.1126/science.7414330, Glover, V. (2015). Am. Adverse health outcomes associated with fetal alcohol exposure: a systematic review focused on immune-related outcomes. Environmental magnetic field in a neonatal intensive care unit. Maternal and transabdominal ECG recorded in the early third trimester carry information about the chronic exposure of the motherfetus dyad to stress detectable by deep learning, a form of artificial intelligence techniques (Sarkar et al., 2021). Exposure to opioids prenatally could result in programming effects on stress response systems, leading also to long-term consequences (Conradt et al., 2018, 2019). Eur. 22, 337358. Abnormal heart rate characteristics before clinical diagnosis of necrotizing enterocolitis. Cerebral modulation of the autonomic nervous system in term infants. Nutr. Available online at: http://www.ncbi.nlm.nih.gov/books/NBK513398/ (accessed April 23, 2021). 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. The fetal heart rate results from the combined effect of several fluctuating influences mediated through extrinsic cardiac control mechanisms (sympathetic and parasympathetic nerves and circulating catecholamines), as well as intrinsic cardiac factors (myocardium and its conducting system). Hill, M. A. 237, 655671. Am. Pathologic fetal acidemia. 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). BJGP Open 3:bjgpopen19X101674. Electronic evaluation of the fetal heart rate. B. Received: 07 June 2021; Accepted: 19 August 2021; Published: 20 September 2021. Caton Alissa, R., Bell Erin, M., Druschel Charlotte, M., Werler Martha, M., Lin Angela, E., Browne Marilyn, L., et al. 216, 226231. 28, 16641668. Philadelphia, PA: Llippincott Williams and Wilkins. North Am. Diseases 6:23. doi: 10.3390/diseases6020023, Vohr, B. R., Davis, E. P., Wanke, C. A., and Krebs, N. F. (2017). This detects changes in the normal FHR pattern at the time of labor, reassuring your obstetrician if its safe to proceed. Am. 12:20160545. doi: 10.1098/rsbl.2016.0545, Gallup, A. C., and Eldakar, O. T. (2013). Frauenh. ArXiv201102000 Eess Q-Bio. Front. Clin. 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. Aging 78, 117. 42:ac010e. Core temperature variation is associated with heart rate variability independent of cardiac index: a study of 278 trauma patients. Biological examples of positive feedback are much less common. J. Obstet. Analg. 196: Communication of Fetal Heart Monitoring Information . Med. Since, according to the Polyvagal theory (Beauchaine et al., 2007), the social/emotional development is related to the vagal system, any insult such as maternal distress suffered during the autonomic trajectory development will interfere with the maturation of the cerebral cortices structures and of the ANS disrupting the development of the Social Engagement System of the child (Porges and Furman, 2011). Psychopathol. The effect of magnesium sulfate tocolysis on the fetal biophysical profile. Recently, placenta calcifications samples collected at delivery have been speculated to act as a memory of prenatal maternal stress and diseases exposure, hence highlighting the potential role of placenta in regulating the offspring's future cardiovascular and metabolic health, even through the in utero modulation of the developing ANS (Wallingford et al., 2018). (2009). Thanaboonyawat, I., Wataganara, T., Boriboonhiransarn, D., Viboonchart, S., and Tontisirin, P. (2006). Recording and manipulation of vagus nerve electrical activity in chronically instrumented unanesthetized near term fetal sheep. Occupational exposure to chemicals and fetal growth: the generation R study. 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). A preliminary report. doi: 10.1016/j.ajog.2016.10.003, McEwen, B. S., Nasca, C., and Gray, J. D. (2016). J. Gynecol. Off. (2016). 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). Here, we show that hyperactivity-induced REST/NRSF activation, triggers a homeostatic rearrangement of GABAergic inhibition, with increased frequency of miniature inhibitory postsynaptic currents (IPSCs) and amplitude of evoked IPSCs in mouse cultured hippocampal neurons. 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). Norepinephrine binds to beta receptors in the heart causing an increase in heart rate, contractility and stroke volume. J. which intrinsic homeostatic response is the fetus demonstrating . (2017). Safety of selective serotonin reuptake inhibitors in pregnancy. Is less noise, light and parental/caregiver stress in the neonatal intensive care unit better for neonates? (2020). Catecholamine mediated effects are relatively slow reflecting their half-life of 2 to 3 minutes. Ann. Autonomic cardiorespiratory physiology and arousal of the fetus and infant, in SIDS Sudden Infant and Early Childhood Death: The Past, the Present and the Future, eds J. R. Duncan and R. W. Byard (Adelaide, AU: University of Adelaide Press). doi: 10.1071/RD05030, Morsi, A., DeFranco, D., and Witchel, S. F. (2018). Increases baseline b. Decreases baseline b. Briefly, through the vagus nerve, the brain receives information about the body's inflammatory milieu and, thus, activates neuroimmune responses to dampen the detected inflammation (Garzoni et al., 2013; Frasch, 2020; Bonaz et al., 2021). Gynaecol. Int. The discrepancy between these studies may be partly due to the different experimental variables. The emergence of fetal behaviour. Inserted sensors measured blood pressure, heart rate and acid base status duringthe experiments. Lie down in the left lateral, knee-chest, or right lateral position to relieve compression of the large vein (or vena cava) by your pregnant uterus. Sampling rate of heart rate variability impacts the ability to detect acidemia in ovine fetuses near-term. Dev. Eur. General movements quality, as well as their variability and modulation in intensity and velocity, could be valid indicators of fetal neurodevelopment, in particular concerning supra-spinal control on motor activity (Moreira Neto and Porovic, 2018). These processes can be implemented through cell autonomous or intercellular signaling. Dev. (2000). Am. 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. The hypothalamic-pituitary-adrenal axis and the fetus. A., Drogtrop, A. P., Gyselaers, W. J. Frasch, M. G. (2020). Pediatrics 139, S38S49. doi: 10.1016/j.mehy.2008.09.033, Cahill, A. G., Mathur, A. M., Smyser, C. D., Mckinstry, R. C., Roehl, K. A., Lpez, J. D., et al. At 2629 WGA, fetuses become able to efficiently control body temperature (Moore et al., 2016). doi: 10.2165/00128072-200002060-00002, Kisilevsky, B. S., and Low, J. Physiology of transition from intrauterine to extrauterine life. As discussed throughout this article the relationship between heart rate and the underlying fetal condition is complex. doi: 10.1097/OGX.0000000000000007, Verdurmen, K. M. J., Warmerdam, G. J. J., Lempersz, C., Hulsenboom, A. D. J., Renckens, J., Dieleman, J. P., et al. (2019). The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors. FC, MC, SV, CV, MA, and MF wrote the first draft. Integr. Rivolta, M. W., Stampalija, T., Casati, D., Richardson, B. S., Ross, M. G., Frasch, M. G., et al. 31, 189196. The homeostatic response that preserves the . Allergy Immunol. Field DR, Parer JT, Auslender R, Baker BW, Ross BK, Leicht CH. 36, 23692378. doi: 10.1016/0002-9378(81)90015-6, Lucchini, M., Fifer, W. P., Sahni, R., and Signorini, M. G. (2016). Ontogeny of reticular framework of white pulp and marginal zone in human spleen: immunohistochemical studies of fetal spleens from the 17th to 40th week of gestation. Embryol. J. Obstet. Orthop. Studies on developmental neurology in the human fetus. Bennet L, Westgate JA, Liu YC, Wassink G, Gunn AJ. Placenta dysbiosis can be related to antepartum infections (Aagaard et al., 2014; Doyle et al., 2017; Pelzer et al., 2017), maternal nutrition (Aagaard et al., 2014), maternal weight gain (Antony et al., 2015; Zheng et al., 2015; Benny et al., 2019), gestational diabetes mellitus (Bassols et al., 2016; Pelzer et al., 2017), use of probiotics/antibiotics (Pelzer et al., 2017), and periodontal pathogens (Fischer et al., 2019), and can lead to several adverse outcomes, such as preeclampsia and chorioamnionitis (Amarasekara et al., 2015; Doyle et al., 2017; Fischer et al., 2019; Olaniyi et al., 2020). Nutrients 7, 69246937. (2010). Acta Obstet Gynecol Scand. 27, 223232. A second component of the chemoreflex response to hypoxemia is parasympathetic, mediated via the vagus nerve, resulting in a fall in heart rate. Your doctor might administer oxygen in response to late decelerations. Impact of chronic fetal hypoxia and inflammation on cardiac pacemaker cell development. VIII. Med. Among antihypertensive drugs, methyldopa does not seem to particularly affect fetal well-being. Ultimately, any influence on heart rate is mediated by one or more of these structures. J. Exp. doi: 10.5665/sleep.1616, Yurdakk, K. (2012). It has been shown that a pattern of hyperactive uterine contractions (often caused by the administration of sOT), during the last 2 h of labor, is strongly associated with acidemia and hypoxia at birth and with fHR and fHRV alterations (Freidman and Sachtleben, 1978; Woodson et al., 1979; Cibils and Votta, 1993; Ladfors et al., 2002; Jonsson et al., 2008; Verspyck and Sentilhes, 2008; Aye et al., 2014). In fetal life, pulmonary ventilation does not occur and is not a source of fetal oxygenation. A qualitative exploration of the views and experiences of women with pregnancy related pelvic girdle pain. doi: 10.1111/jog.12619. 105, 13121314. J. Pediatr. As such, fetal heart tracings should be combined with other clinical methods to ensure accurate interpretation of your babys condition. In the first weeks, these glands are undifferentiated between male and female fetuses and complete the cellular differentiation process around the 44th post-conceptional day (Baker and Scrimgeour, 1980). Prenatal alcohol exposure, therefore, induces a dysregulated fetal immune response, increasing the risk for infections, chorioamnionitis, and/or placental abruption, which can favor premature delivery (Reid et al., 2019). doi: 10.3390/nu7053067, Wang, X., Durosier, L. D., Ross, M. G., Richardson, B. S., and Frasch, M. G. (2014). 57:101. doi: 10.3345/kjp.2014.57.3.101. doi: 10.1109/CIC.2000.898490, Ho, J. J., Subramaniam, P., and Davis, P. G. (2020). 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. 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. Stimulating the vagus nerve typically produces: a. Occupational exposure to pesticides during pregnancy and neurobehavioral development of infants and toddlers. Standard monitoring provides only the heart rate, not the ECG. Exposure to SSRIs during the 3rd trimester is associated with blunted FMs and reactivity to VAS, as well as with reduced fHRV at 36 WGA (Oberlander et al., 2009; Nguyen et al., 2019). In summary, the FMs make it possible to start developing a primitive body map. doi: 10.1164/rccm.201911-2127LE, Aldrete-Cortez, V., Poblano, A., Tafoya, S. A., Ramrez-Garca, L. A., and Casasola, C. (2019). In the absence of improvement, immediate delivery is a strong possibility. (2016). doi: 10.1159/000307075, Walusinski, O. When the timing of deceleration is delayed, it means that the lowest point is occurring past the peak of your uterine contraction. doi: 10.1016/j.spen.2018.05.004, Mulkey, S. B., and du Plessis, A. J. Biol. Can we learn to assess this individual experience? (2015). Whereas, 1 differs already at birth, the other metrics show different trajectories after 3040 days, hinting at different ANS development due to the experienced postnatal comorbidities (Schlatterer et al., 2021). doi: 10.1016/j.sleep.2014.12.006, Mirmiran, M., Maas, Y. G. H., and Ariagno, R. L. (2003). doi: 10.1371/journal.pone.0022100, Frasch, M. G., Lobmaier, S. M., Stampalija, T., Desplats, P., Pallars, M. E., Pastor, V., et al. Fetal Neonatal Med. General movements analysis can differentiate specific movement patterns, concerning a specific part of the fetal body, from non-specific movement patterns, involving more than one body segment (de Vries et al., 1982, 1985). Drugs Used to Manage the Timing of Delivery. Parer JT, Ikeda T. A framework for standardized management of intrapartum fetal heart rate patterns.Am J Obstet Gynecol. Sleep deprivation during pregnancy and maternal and fetal outcomes: is there a relationship? 31, 514. Fetal Diagn. (13) and Bennet et al. doi: 10.1055/a-0713-1058, Koletzko, B., Godfrey, K. M., Poston, L., Szajewska, H., van Goudoever, J. doi: 10.1016/0002-9378(82)90616-0, Jonsson, M., Nordn-Lindeberg, S., Ostlund, I., and Hanson, U. The 1st stage of labor does not always occur naturally and without complications: consequently, there may be an artificial intervention that causes the induction of labor to increase uterine contractions. doi: 10.1111/j.1742-7924.2010.00142.x, Parris, K. M., Amabebe, E., Cohen, M. C., and Anumba, D. O. (2019). doi: 10.7326/0003-4819-134-5-200103060-00012. Physiol. While intracellular Ca 2+ has long been hypothesized to be a feedback control signal, the molecular machinery enabling a network-wide homeostatic response remains largely unknown. B 44, 279303. Front. doi: 10.1159/000471764, Selander, J., Rylander, L., Albin, M., Rosenhall, U., Lewn, M., and Gustavsson, P. (2019). Proc. Gut microbiota: the conductor in the orchestra of immuneneuroendocrine communication. Such a failure in maintaining cardiac output during labor could facilitate brain injury in newborns and can be detected on the individual basis using fHRV analysis from EFM (Gold et al., 2021; Roux et al., 2021). As excessive maternal cortisol, sGCs override the placenta mediator system (Sheng et al., 2020) and induce transient HRV modification toward sympathetic suppression (Multon et al., 1997; Senat et al., 1998; Subtil et al., 2003; Mulder et al., 2004; Schneider et al., 2010). The development of the nociceptive brain. Frasch, M. G., Szynkaruk, M., Prout, A. P., Nygard, K., Cao, M., Veldhuizen, R., et al. (2001). 37, 668672. Med. 2:38. doi: 10.3389/fped.2014.00038, Edlow, A. G. (2017). Factors that modulate fetal anaerobic reserve are myocardial glycogen stores, placental exchange capacity and chronic hypoxia. Front. The frequency and size of deceleration are important indicators as well as the nature of the FHR between contractions and trends over time. Catecholamine C. Sympathetic - CORRECT ANSWERS A. Baroreceptor Surv. Of the neonates in this series, 20% will have neurological consequences including cerebral palsy and HIE (Goldaber et al., 1991; DuPont et al., 2013). These opinions on late decelerations are consistent with human observations by Sameshima et al who reported that that acidemia was present at birth in only 20% of babies with recurrent late decelerations and loss of variability. . doi: 10.1016/0028-2243(80)90060-X, Venkata, C., and Venkateshiah, S. B. (2018). Lastly, instrumental malfunctioning can induce life-threatening conditions (Carvajal de la Osa et al., 2020). Physiol. Congenital heart defects of fetus after maternal exposure to organic and inorganic environmental factors: a cohort study. Transient loss of variability usually is associated with benign conditions like fetal sleep or maternal medications. (2017). doi: 10.1111/j.1552-6909.1996.tb02516.x, De Jonckheere, J., and Storme, L. (2019). 15:721605. doi: 10.3389/fnins.2021.721605. When they suspect fetal hypoxia, they must determine the delivery timing to prevent serious consequences for your newborn. 40, 445456. Pediatr. A., Porges, S. W., Scanlon, J. W., Alemi, B., and Scanlon, K. B. 16, 213218. Fletcher AJ, Gardner DS, Edwards CM, Fowden AL, Giussani DA. Moore, K. L., Persaud, T. V. N., and Torchia, M. G. (2016). The soft tissues of the birth canal (the cervix and pelvic floor musculature) provide resistance during labor. Paediatr. Homeostatic plasticity is thought to be crucial for preventing synaptic saturation, thus allowing for new memory formation, and may be disrupted in several neurological disorders, including Alzheimer's disease (14) and ASD (15-18). (2020). This experiment also demonstrated that adequate time between cord compressions reperfusion time was essential to maintain normal acid base status. Heres how to tell if youre experiencing them. The musculature of the pelvic floor facilitates rotation and flexion for the fetal head. doi: 10.1038/npp.2015.171, McKenna, D. S., Ventolini, G., Neiger, R., and Downing, C. (2006). (2018). Low back pain and pelvic girdle pain in pregnancy. Placental microbialmetabolite profiles and inflammatory mechanisms associated with preterm birth. According to a recent systematic analysis, FMs can affect the ANS as revealed through modifications in the time-domain and frequency-domain fHRV metrics. Med. The chances of fetal hypoxia remain low if repeated decelerations arent present and fetal heart tracing is otherwise normal. Sleep disturbances in pregnancy. Biol. Scand. Cochrane Database Syst. Dev. J. Nutr. Brain Dev. 1252, 1724. doi: 10.1093/jn/131.2.581S, Almadhoob, A., and Ohlsson, A. 123, 1116. Since yawning has been related to thermoregulatory behaviors and the ability of switching between arousal and rest states, both of which are strictly dependent on ANS functionality, the detection of yawning at this early age could represent a useful indicator of ANS development or, as suggested, brainstem functionality (Walusinski, 2006, 2010, 2014; Gallup and Eldakar, 2013). What could and should we do to disrupt this status quo and enable individualized insights into the various developmental effects the vagus nerve maturation and pleiotropic physiology provide? The Heart's rhythm n blues: sex differences in circadian variation patterns of vagal activity vary by depressive symptoms in predominantly healthy employees. 3-15 Chemoreceptors are found in peripheral locations such as in the aortic arch and carotid arteries where they are sensitive to low oxygen levels. doi: 10.1097/EDE.0b013e31822546fd. Eur. (2021). 9:1044. doi: 10.3389/fphys.2018.01044, Walusinski, O. Obstet. Therefore, the present paper aims to review the fetal and perinatal development by focusing on the development of the ANS and, in particular, of the vagus nerve to identify possible critical windows that could impact their maturation. Front. Obstructive sleep apnea in pregnancy and fetal outcome. Drug Saf. Reproduction 60, 193199. The importance of foetal movement for co-ordinated cartilage and bone development in utero. J. Ind. Chronic pain during pregnancy: a review of the literature. 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. doi: 10.1093/jpepsy/jsj031, Zeskind, P. S., and Stephens, L. E. (2004). Child Health 23, 285291. The autonomic nervous system (ANS) is one of the main biological systems that regulates the body's physiology. (2007). Microbiome of the placenta in pre-eclampsia supports the role of bacteria in the multifactorial cause of pre-eclampsia. Neurorobotics 12:23. doi: 10.3389/fnbot.2018.00023, Fairchild, K. D., Srinivasan, V., Randall Moorman, J., Gaykema, R. P. A., and Goehler, L. E. (2010). They may detect several clusters or subgroups that are associated with the adverse outcome and provide an estimated probability of that occurrence. However, when late decels occur in more than 50 percent of the contractions of your uterus, then fetal hypoxia is a plausible explanation. (2019). Schmidt, A., Schneider, U., Witte, O. W., Schleuner, E., and Hoyer, D. (2014). Heart J. Assessment of fetal development using cardiac valve intervals.