J. Obstet. The use of nifedipine concurrently with magnesium sulfate (MgSO4) seems associated with severe hypotension, neuromuscular blockade, and cardiac depression in the fetus (Khedun et al., 2000). 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). 579, 893907. Indeed, it is known to increase with worsening acidemia (Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996; Frasch et al., 2007, 2009a,b; Durosier et al., 2014). The placenta harbors a unique microbiome. doi: 10.1152/ajpregu.00487.2010, Fedele, L., and Brand, T. (2020). Regulation of firing rate homeostasis constitutes a fundamental property of central neural circuits. Dis. Rev. For a concise review of the historical experimental work elucidating the mechanisms of fetal heart rate decelerations and response to hypoxemia, the reader is referred to excellent descriptions by Freeman et al and 2012 and Martin et al 2008 2,9. Sleep Med. doi: 10.1177/1054773812469223, Al Alam, D., Danopoulos, S., Grubbs, B., Ali, N. A. Rev. 2004 Jan;190(1):118-23. Impact of chronic fetal hypoxia and inflammation on cardiac pacemaker cell development. In the same way, improper light and noise can disrupt newborns' sleep duration, especially in preterm and very preterm ones (Gogou et al., 2019). 4445:101671. doi: 10.1016/j.bpg.2020.101671, Gale, C. R., Robinson, S. M., Harvey, N. C., Javaid, M. K., Jiang, B., Martyn, C. N., et al. (1986). 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). doi: 10.1016/S0301-2115(01)00363-3, Caputo, C., Wood, E., and Jabbour, L. (2016). Sadler, T. W. (2012). Stages of labor, in StatPearls (Treasure Island, FL: StatPearls Publishing). A preliminary report. In addition, even mild inflammatory states in the mother might affect the placental conversion of maternal tryptophan to serotonin upstream of the fetal brain (Goeden et al., 2016). At 2629 WGA, fetuses become able to efficiently control body temperature (Moore et al., 2016). Factors that contribute to progressive oxygen debt are strength, duration and frequency of decelerations. Additionally, your doctor should check for the absence/presence of decelerations, degree of variability, and immediately address the root cause of late decelerations. Front. (2013). It could also affect the role of placenta as the immune pacemaker of pregnancy, increasing the risk of preterm birth (Allen, 2001; Peterson et al., 2020) and thus impairing vagal development during the last weeks of gestation. Therefore, temperature that constantly deviates from newborns' one can lead to excessive ANS activation. Fetal monitors are better at separating maternal and fetal heart rate. In particular, centers that are paramount to neurotransmitters (e.g. BMC Pregnancy Childbirth 18:264. doi: 10.1186/s12884-018-1900-4, Krueger, C., and Garvan, C. (2019). The effect of unilateral stroke on autonomic function in the term newborn. (2019). Neurosci. Psychiatry Res. Moreover, it has been observed a correlation between placenta dysbiosis and preterm birth (Aagaard et al., 2014; Antony et al., 2015; Bassols et al., 2016; Prince et al., 2016; Pelzer et al., 2017; Fischer et al., 2019). 2017 Feb;216(2):163.e1-163.e6. (2018). Health Perspect. By 29 WGA, all the major corticospinal, spinothalamic, and spinocortical tracts as well their myelination are completed, whereas from 24 WGA functional connectivity patterns in the fetal brain are recognizable. Total views 78. Front. Crit. (2013). Biological mechanisms that might underlie iron's effects on fetal growth and preterm birth. Cells 9:733. doi: 10.3390/cells9030733, Frasch, M. G., Herry, C. L., Niu, Y., and Giussani, D. A. Mercury exposure and heart rate variability: a systematic review. In conclusion, apart from unrelenting bradycardia, there is no signal FHR marker that consistently indicates serious fetal compromise. 90, 131139. 78, 17881798. 87, 745750. 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. Clin. The fetal autonomic nervous system, the fetal heart rate and the beat-to-beat irregularity. The emergence of fetal behaviour. (2007). First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy. However, when late decels occur in more than 50 percent of the contractions of your uterus, then fetal hypoxia is a plausible explanation. Wakatsuki A, Murata Y, Ninomiya Y, Masaoka N, Tyner JG, Kutty KK. In this sense, dysregulations in mother circadian rhythm, due to disturbed sleep-awake patterns, could interfere with the development of circadian control systems of the fetus and, consequently, with the circadian profile of the vagus nerve, impacting the physiologic vagal neurodevelopment itself. Biol. 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). Evidence of a non-vagal (intrinsic myocardial) source of deceleration was demonstrated in experiments with complete vagotomy. Burgio, E. (2015). The Physiology and Pathology of Exposure to Stress, 1st Edn. Development of extrinsic innervation in the abdominal intestines of human embryos. Obstet. 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. Ann. Eur. 596, 55035504. https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1016/j.ijgo.2015.06.020 Behav. *Correspondence: Marco Chiera, marco.chiera.90@gmail.com, New Insights into the Role of the Vagus Nerve in Health and Disease: Basic and Clinical Studies, View all
doi: 10.3390/nu7085315, Zhou, L., and Xiao, X. Other work by Bennet et al has also challenged common teaching about the relationship between hypertension and decelerations. Anesth. doi: 10.1016/j.compbiomed.2011.05.003, Hoyer, D., Nowack, S., Bauer, S., Tetschke, F., Rudolph, A., Wallwitz, U., et al. A., et al. 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. 1993;19:105-11. This hypothesis could be reinforced by the evidence that yawning seems to rely on interoception, the inner sense that constantly monitors the internal milieu and for which the vagus nerve plays a central role, and to be processed by the CAN (in particular, insula, hypothalamus, locus coeruleus, and reticular activating system) (Walusinski, 2006). Early Hum. doi: 10.1111/j.1742-7924.2010.00142.x, Parris, K. M., Amabebe, E., Cohen, M. C., and Anumba, D. O. As several vital systems are forming around the end of the 2nd trimester (e.g., alveolar ductal development and surfactant secretion begin at 24 WGA), babies born prematurely before 26 WGA have a higher chance of dying or developing neurodevelopmental disability (Moore et al., 2016; Morton and Brodsky, 2016; Hill, 2021c). Short-term outcomes of newborns with perinatal acidemia who are not eligible for systemic hypothermia therapy. 8:313. doi: 10.3389/fphys.2017.00313, Massaro, A. N., Campbell, H. E., Metzler, M., Al-Shargabi, T., Wang, Y., du Plessis, A., et al. Epub 2007 Sep 17. doi: 10.1016/j.ejogrb.2014.02.032, Baker, T. G., and Scrimgeour, J. 56, 3539. Clin. 444, S98S109. Heres how to tell if youre experiencing them. An idea of neuroimmunological homunculus has been proposed and requires further research (Conway et al., 2006; Tracey, 2007; Diamond and Tracey, 2011; Frasch et al., 2018a; Castel et al., 2020). 27, 197200. Moreover, some studies have highlighted that the same factors can differently affect development based on the exposure period (i.e., early vs. late gestation) (Schulz, 2010; Gartstein and Skinner, 2018; Kasahara et al., 2020, 2021). Fetal cardiovascular decompensation during labor predicted from the individual heart rate tracing: a machine learning approach in near-term fetal sheep model. doi: 10.1523/JNEUROSCI.3846-13.2013, Khedun, S. M., Maharaj, B., and Moodley, J. Drugs 2, 419436. 41, 928939. 144, 169176. The role of gut microbiota in the effects of maternal obesity during pregnancy on offspring metabolism. 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). J. Obstet. Microbiol. This event shows how the fetal ANS quickly reacts in the face of a stressor. doi: 10.1371/journal.pone.0074431, Hoyer, D., Zebrowski, J., Cysarz, D., Gonalves, H., Pytlik, A., Amorim-Costa, C., et al. J. Perinatol. (1992). doi: 10.1002/9780470987483.ch7, Besset, D., Selmaoui, B., Tourneux, P., Leke, A., Delanaud, S., de Seze, R., et al. Continuous positive airway pressure (CPAP) for respiratory distress in preterm infants. Gender differences in neurodevelopment and epigenetics. The fear of missing fetal injury during labor has led to soaring CS rates and the failure of the EFM has resulted in the misguided dissent over its utility in general throwing the proverbial baby with the bathwater. Nutrients 7, 30673077. ABP, arterial blood pressure; ANS, autonomic nervous system; ASD, autism spectrum disorders; CAM, cardiac autonomic modulation; CAN, central autonomic network; CAP, cholinergic anti-inflammatory pathway; CNS, central nervous system; CRH, corticotropin-releasing hormone; CS, cesarean section; CTG, cardiotocography; ECG, electrocardiography; EEG, electroencephalography; EFM, electronic fetal monitoring; EMF, electromagnetic field; ENS, enteric nervous system; FASD, fetal alcohol spectrum disorders; fHR, fetal heart rate; fHRV, fetal heart rate variability; FM, fetal movement; GM, general movement; HIE, hypoxic-ischemic encephalopathy; HPA, hypothalamic-pituitary-adrenal; HR, heart rate; HRV, heart rate variability; NAS, neonatal abstinence syndrome; NC, neural crest; NEC, necrotizing enterocolitis; NOWS, neonatal opioid withdrawal syndrome; PAE, prenatal alcohol exposure; PGP, pelvic girdle pain; PNE, prenatal nicotine exposure; PNS, parasympathetic nervous system; REM, rapid eye movements; SDB, sleep-disordered breathing; sGC, synthetic glucocorticoid; SIDS, sudden infant death syndrome; SNS, sympathetic nervous system; sOT, synthetic oxytocin; SSRI, selective serotonin reuptake inhibitor; VAS, vibroacoustic stimulation; WGA, week gestational age; ZIKV, Zika virus. The mechanisms of homeostatic intrinsic plasticity depend on the abundance and spatial distribution of voltage-gated ion channels (Na+,K+ and Ca2+ channels) at the plasma membrane, and on their biophysical characteristics. J. Obstet. During the 1st trimester, there are significant negative correlations between the amount of maternal cigarette smoking and fHRV metrics, highlighting the disrupted temporal organization of autonomic regulation before birth (Zeskind and Gingras, 2006; Kapaya et al., 2015). doi: 10.1159/000475744, Patural, H., Pichot, V., Flori, S., Giraud, A., Franco, P., Pladys, P., et al. 6:237ra65. Clark SL, Nageotte MP, Garite TJ, Freeman RK, Miller DA, Simpson KR, Belfort MA, Dildy GA, Parer JT, Berkowitz RL, DAlton M, Rouse DJ, Gilstrap LC, Vintzileos AM, van Dorsten JP, Boehm FH, Miller LA, Hankins GD. Its influence on the development of the ANS and the vagus nerve can be understood through a careful examination of fHRV changes. 38, 5666. In fact, fHRV is a non-invasive marker whose changes have been associated with ANS development, vagal modulation, systemic and neurological inflammatory reactions, and even fetal distress during labor. Nat. Catecholamine mediated effects are relatively slow reflecting their half-life of 2 to 3 minutes. Epidemiology 10, 370375. Identified Q&As 100+ Solutions available. 41-49 One can speculate on some reasons. The size, shape and timing of decelerations induced by cord compression or uterine artery compression tend to converge in the presence of marked fetal acidemia. N. Y. Acad. As aids for the readers, Table 1 contains the meaning of the several HRV metrics cited in the following sections, whereas Figure 1 and Table 2 summarize the main findings of the current review. Effect of tocolytic drugs on fetal heart rate variability: a systematic review. The effects of maternal hyperoxia on fetal breathing movements, body movements and heart rate variation in growth retarded fetuses. Scand. 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. 2008 Aug;32(4):239-42. It reaches a stable set point only when its control functions meet the conditions on convexity and relative goals described in the text. Viral infections during pregnancy. 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. Res. 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). The first stage of dilatation begins with the initiation of true labor contractions and ends when the cervix is fully dilated. 27, 8994. 63, 649656. The pathway on the left was thought to be initiated during umbilical cord compression that was not accompanied by hypoxemia or pH changes. Gender-specific evolution of fetal heart rate variability throughout gestation: a study of 8823 cases. Fetal Neonatal Med. These modifications seem to last at worst 4 days after the first dose (Mulder et al., 2004; Verdurmen et al., 2013) and the influence on ANS modulation seems minor (Verdurmen et al., 2018; Noben et al., 2019). (2017). Am. doi: 10.1172/JCI30555, Tracey, K. J. Res. (2007). Electromagnetic field coming from the incubator power influences the ANS as revealed by HRV analysis as LF/HF increases, whereas HF decreases (Bellieni et al., 2008). The effects of prenatal alcohol exposure (PAE) on fetuses are collectively known as fetal alcohol spectrum disorders (FASD). Effects of antihypertensive drugs on the unborn child. Keep in mind this doesnt mean youll need an instrumental vaginal or cesarean delivery right away. 31, 415424. This stimulation reaches the brainstem, in particular the nucleus of the solitary tractthe main afferent nucleus of the vagus nervebut also other nuclei including the parabrachial ones, and then more cortical structures such as the hypothalamic paraventricular nucleus and the posterior insular cortex. Moreover, the prolonged administration of MgSO4 seems to be associated with a change in fetal breathing movements (Peaceman et al., 1989) and to affect fHRV dose-dependently (Cardosi and Chez, 1998; Kamitomo et al., 2000). Media Coverage 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). Cell. doi: 10.1016/j.yfrne.2015.09.001, Nuriel-Ohayon, M., Neuman, H., and Koren, O. More recent work provides a simpler proposal namely that the chemoreflex with both parasympathetic and sympathetic components is the major initiator of fetal heart rate decelerations. Gender-related differences in fetal heart rate during first trimester. Its dominance results in what effect to the FHR baseline? J Physiol. 55, 1721. Argent. Autonomic nervous system impairment may have consequences on the global development that persist during infancy, adolescence, and adult life. (2021d). Even painful procedures during hospitalization seem to induce alteration in stress regulation and brain development in newborns (Holsti et al., 2006). NeoReviews 15, e537e545. Stress 9, 4854. Vagal blockade eliminated these decelerations in the non-acidemic sheep. Gynecol. Regarding the ANS, brainstem, and hypothalamic centers form several connections with the other CAN structures, that is, insula, anterior cingulate gyrus, hippocampus, hypothalamus, and amygdala (Mulkey and du Plessis, 2018; Schlatterer et al., 2021). (2017). doi: 10.1111/aogs.13437, Boehm, F. H., Woodruff, L. F., and Growdon, J. H. (1975). 28, 377382. doi: 10.1038/pr.2016.155, Bautista, L., and George, R. B. 89, 584590. Pediatrics 113, 368375. 17, 641650. Sci. 40, 2751. Gynecol. Doussard-Roosevelt, J. 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. Nature 405, 458462. Prenatal influences on temperament development: the role of environmental epigenetics. 1991 Nov 26;42(2):145-53. J. Perinatol. Dalton KJ, Dawes GS, Patrick JE. Even if the light-dark cycle does not seem to significantly affect the fetal circadian rhythm, there are age-dependent fHRV patterns after transabdominal fetal stimulation with halogen light, similarly to the VAS (Peleg and Goldman, 1980), which seem increasingly definite in the later stages of pregnancy, when the fetal optic pathways and ANS control on the cardiac activity reach maturity (Thanaboonyawat et al., 2006). J. Obstet. Gynaecol. J. Obstet. The fetal inflammatory response syndrome. Psychol. A relevant verification. doi: 10.31887/DCNS.2016.18.4/tbale, Barlow-Anacker, A. J., Fu, M., Erickson, C. S., Bertocchini, F., and Gosain, A. doi: 10.1016/j.neubiorev.2011.02.003, Korsmo, H. W., Jiang, X., and Caudill, M. A. doi: 10.1038/s41390-021-01460-3, Ray-Griffith, S. L., Wendel, M. P., Stowe, Z. N., and Magann, E. F. (2018). Front. A., Velez, M., Elko, A., Williams, E., Milio, L., et al. 15-30 minutes in the active phase of the first stage and every 5-15 minutes in second stage B. 14:887. doi: 10.3389/fnins.2020.00887, Chang, J. J., Pien, G. W., Duntley, S. P., and Macones, G. A. The implications of these infection-associated immunological events on fetal neurodevelopment seem to be time-dependent, thus supporting the clinical relevance of carefully evaluating the interfering factors throughout the entire pregnancy (Meyer et al., 2007). 9, 477483. The persistent exposure to photic stimuli or high noise during pregnancy, for instance, due to the mother's occupation, seems to correlate with reduced fetal growth (Selander et al., 2019), increased incidence of congenital heart diseases (Gong et al., 2017), impaired development of cortical areas (Zhang et al., 1992; Wilson et al., 2008), and potential disruption of the vagus nerve maturation. Nevertheless, the presence of many confounding factors and the small sample sizes make unclear the mechanism of action of glucocorticoids on fHRV and consequently the impact on ANS development (Verdurmen et al., 2013). Decreased uteroplacental oxygen delivery was generally simulated by compressing the arteries supplying blood to the uterus or controlling the levels inspired of oxygen. Eur. Arch. On the other hand, the ANS activity, as measured through heart rate variability (HRV)a non-invasive biomarker evaluating the variability of the time intervals between successive heartbeatsis affected by the developmental and health conditions of both fetus and infant. 105, 13121314. 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. Am. Am. Trends Mol. The high immunoreactivity of the premature infants' gut could also lead to neurodevelopmental disorders (Cao et al., 2014). (2018). In the same way, side position during feeding seems to have stabilizing effects on both ANS, as revealed by HR, and oxygenation in preterm newborns (Thoyre et al., 2012), although results are conflicting (Raczyska and Gulczyska, 2019). Pattern of brain injury and depressed heart rate variability in newborns with hypoxic ischemic encephalopathy. doi: 10.1109/CIC.2000.898490, Ho, J. J., Subramaniam, P., and Davis, P. G. (2020). J. Neurosci. Child Dev. The association between variability and metabolic acidosis is less clear. doi: 10.1126/science.7414330, Glover, V. (2015). The neural tube also begins to thin to form the central canal of the spinal cord (Moore et al., 2016). Effect of epidural labor analgesia on fetal heart rate and neonatal outcome. (2019). Pain and discomfort thresholds in late pregnancy. Paraphrased from a personal communication with Dr. Barry Schifrin. Scand. Regul. Off. 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. Immunol. Freeman RK, Garite TJ, Nageotte MP. 85, 830834. Furthermore, ANS alterations in newborns can lead to neurological dysfunctions including cerebral palsy at 2 years of age (Dimitrijevi et al., 2016).
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