Sci. Research is increasingly pointing toward the existence of an HRV code, that is, specific HRV spatio-temporal alterations related to specific organic alterations (e.g., hypoxia, cerebral, cardiac, or gut pathologies) (Herry et al., 2019; Frasch, 2020), to the impact of external factors (e.g., smoking, physical activity, diabetes), and to the fetal brain and nervous development (Hoyer et al., 2012, 2013a, 2015, 2017, 2019). Am. Mucus plug: What is it and how do you know you've lost it during pregnancy? 90, 131139. J. Obstet. Pregnancy Hypertens. 2022 PeriGen, Inc. 100 Regency Forest Drive, Suite 200 Cary, NC 27518 | PeriGen is a registered trademark of PeriGen, Inc. |, Clinical Decision Support and Early Warning System, Expert Review by PeriGen Highlights Need for Advanced Labor Curve Models in Clinical Practice, http://www.nice.org.uk/nicemedia/live/11837/36273/36273.pdf accessed February 28, Artificial Intelligence: A Primer for Perinatal Clinicians, How L&D Units are Tackling Ongoing Education, Alana McGolrick joins PeriGen as Clinical Outcomes Executive, First of many EFM Scholarships awarded @ AWHONN2017, Free Continuing Education Reception @ AWHONN, Coming soon! In fetal life, pulmonary ventilation does not occur and is not a source of fetal oxygenation. Infant stress reactivity and prenatal alcohol exposure. (2013). The placental microbiota seems to display an evolutionary pattern during pregnancy and appears to be diversified in the various areas of the placenta (Aagaard et al., 2014; Cao et al., 2014; Pelzer et al., 2017). Psychopharmacology (Berl.) The maternal pain perception, moreover, can undermine her emotional state, contributing to increased stress and worries (Persson et al., 2013; Clarkson and Adams, 2018; Mackenzie et al., 2018; Lutterodt et al., 2019), and this could additionally interfere with the vagus nerve development of the fetus. Midwifery 56, 102111. Indeed, respiratory sinus arrhythmia appears to be strictly related and modulated by efferent vagal activity. It is also in common use during the peripartum period to administer the mother antibiotic prophylaxis. Aging 78, 117. J. Obstet. Fetal Neonatal Med. doi: 10.1080/00016340802220352, Kadhim, H., Tabarki, B., Verellen, G., De Prez, C., Rona, A. M., and Sbire, G. (2001). Drugs 5, 615627. J. Obstet. Am J Obstet Gynecol. Social interactions, including skin-to-skin contact between mother and newborns, help increase ANS maturation as well as stress responsivity and circadian rhythms, in particular in preterm infants (Ulmer Yaniv et al., 2021). Heart rate variability in neonates of type 1 diabetic pregnancy. Its dominance results in what effect to the FHR baseline? A., Costigan, K. A., and Voegtline, K. M. (2015). 1981 Dec 1; 141(7):797-806. 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. Fertil. 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). 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. 10, 187201. J. Perinatol. Identified Q&As 100+ Solutions available. 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. Gynaecol. Systemic lupus erythematosus and antiphospholipid antibody syndrome, for instance, entail the presence of IgG antiphospholipid antibodies, which can cross the placenta, interfering with the brain development and impacting the cardiovascular system of the fetus (Buyon, 1998; Nalli et al., 2017). Reconsidering fetal pain. Psychoneuroendocrinology 87, 2734. This hypothesis is highly clinically relevant because, in the case of repetitive umbilical cord occlusions with worsening acidemia, fetuses may easily develop cardiovascular decompensation, a phenomenon that occurs through ABP responses to HR decelerations. doi: 10.1093/sleep/27.7.1405, Podymow, T., and August, P. (2008). In conclusion, apart from unrelenting bradycardia, there is no signal FHR marker that consistently indicates serious fetal compromise. Am J Physiol Heart Circ Physiol. 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. Am J Obstet Gynecol. 33, 909912. Reprod. Med. 10. Pathol. doi: 10.1177/1073858406296401, Micheli, K., Komninos, I., Bagkeris, E., Roumeliotaki, T., Koutis, A., Kogevinas, M., et al. 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). 2010 Nov;116(5):1232-40. A. 27, 201209. 16, 483488. (2017). Reprod. doi: 10.1007/BF02344729, Langlois, P. H., Hoyt, A. T., Lupo, P. J., Lawson, C. C., Waters, M. A., Desrosiers, T. A., et al. Regul. doi: 10.1016/0378-3782(86)90187-8, Shuffrey, L. C., Myers, M. M., Odendaal, H. J., Elliott, A. J., du Plessis, C., Groenewald, C., et al. Microbiol. https://www.acog.org/~/media/For%20Patients/faq015.pdf Horne, R. S. (2018). A., Parisi, V. M., and Creasy, R. K. (1989). Nat. J. Obstet. Med. Nevertheless, from 30 WGA, cortisol, thyroxine, and catecholamines levels rise to prepare the fetus for birth. doi: 10.2147/JIR.S248382, Haraldsdottir, K., Watson, A. M., Goss, K. N., Beshish, A. G., Pegelow, D. F., Palta, M., et al. 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). 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. Babies' position is another factor that could impact ANS. doi: 10.1089/bfm.2008.0002, Jones, C. M., and Greiss, F. C. (1982). Similar hints can also be gained by monitoring organ development due to the research regarding the CAP and the systemic interactions of the vagus nerve (Bonaz et al., 2021). Indeed, dysfunctional CAP can fail in regulating inflammation, thus letting the immune system go unchecked and free to induce tissue damage, shock, and even death, whereas, on the other hand, a functional CAP can prevent microglia activation, thus showing a neuroprotective effect (Garzoni et al., 2013; Frasch et al., 2016). 14, 107114. Increases baseline b. Decreases baseline b. J. Med. Lastly, yawning amount and duration seem to correlate with neuronal development in mammals (Gallup et al., 2016). An antenatal marker of neurodevelopmental outcomes in infants with congenital heart disease. Biol. Giussani DA, Spencer JA, Moore PJ, Bennet L, Hanson MA. doi: 10.1042/BSR20171234, Zizzo, A. R., Kirkegaard, I., Hansen, J., Uldbjerg, N., and Mlgaard, H. (2020). Higher maternal weight is related to poorer fetal autonomic function. doi: 10.1016/0002-9378(82)90616-0, Jonsson, M., Nordn-Lindeberg, S., Ostlund, I., and Hanson, U. The influence of betamethasone on fetal heart rate variability, obtained by non-invasive fetal electrocardiogram recordings. (2012). 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. Assoc. The occlusions resulted in fetal hypertension and vagally mediated decelerations. Your doctor checks the status during labor and delivery by monitoring and measuring their heart rate using special equipment. Since we have seen that amniotic flow and fetal growth restriction can affect vagal development, their effects could then be mediated by FMs. (2018). 57:101. doi: 10.3345/kjp.2014.57.3.101. Neural crest cells also contribute to spleen development (Barlow-Anacker et al., 2017). 85, 633638. Hypotheses 67, 614. Available online at: http://www.ncbi.nlm.nih.gov/books/NBK470566/ (accessed February 22, 2021). Psychosom. doi: 10.2165/00128072-200002060-00002, Kisilevsky, B. S., and Low, J. 336, 287297. J. Matern. Despite the fact that there are contrasting results about the sensitivity of fetal activity reported by the mother (Sorokin et al., 1982; Schmidt et al., 1984), it appears that there is an association between the increase of force and frequency of perceived movements and a reduced risk of stillbirth and negative outcomes (Heazell et al., 2018). Moreover, except the third trimester (Mulkey and du Plessis, 2018, 2019), literature usually lacks an analysis of potential critical windows in the perinatal period that may give information about ANS development. In particular, metabolic and cardiovascular pathologies, like obesity, diabetes, hypertension, and preeclampsia, can disrupt vagus nerve development (Brown et al., 2008; Russell et al., 2016; Moors et al., 2020). Sleep deprivation during pregnancy and maternal and fetal outcomes: is there a relationship? 596, 57095722. At about 1820 WGA, rapid eye movements (REM) can be detected (Borsani et al., 2019) as well as quiet and active sleeping states (Dereymaeker et al., 2017), although fetal behavioral states do not show particular coherence with ANS tone (Brndle et al., 2015). (2018). Catecholamine mediated effects are relatively slow reflecting their half-life of 2 to 3 minutes. Reprod. Available online at: http://www.ncbi.nlm.nih.gov/books/NBK513398/ (accessed April 23, 2021). 176, 112118. Front. *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 Health Rep. 2, 304314. BMJ Open 8:e020031. 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). At 4 WGA, neurulation occurs: the neural folds arise from the neural plate and begin to fuse in both cranial and caudal direction, thus forming the neural tube, that is, the future central nervous system (CNS). Most of the medication administered to the mother during pregnancy can cross the placental barrier and reach the fetus. Med. Pediatr. Cardiac orienting to auditory stimulation in the fetus. The cervix undergoes biochemical changes that increase its elasticity. 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. (2017). A., Caulfield, L. E., Costigan, K. A., Merialdi, M., Nguyen, R. H. N., Zavaleta, N., et al. ArXiv190905198 Q-Bio. doi: 10.1159/000488106, Morton, S. U., and Brodsky, D. (2016). (2019). doi: 10.1055/a-0713-1058, Koletzko, B., Godfrey, K. M., Poston, L., Szajewska, H., van Goudoever, J. 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. About Moreover, a recent pilot study described that in utero ZIKV-affected babies display HRV metrics abnormalities. Microbial changes during pregnancy, birth, and infancy. All authors reviewed, edited and approved the final version of the paper. 12:20160545. doi: 10.1098/rsbl.2016.0545, Gallup, A. C., and Eldakar, O. T. (2013). 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). Psychol. doi: 10.1371/journal.pone.0022100, Frasch, M. G., Lobmaier, S. M., Stampalija, T., Desplats, P., Pallars, M. E., Pastor, V., et al. Gold et al. Surv. doi: 10.1038/jp.2013.63, Subtil, D., Tiberghien, P., Devos, P., Therby, D., Leclerc, G., Vaast, P., et al. Fetal autonomic brain age scores, segmented heart rate variability analysis, and traditional short term variability. Delivery without labor or preterm birth is associated with lower cortisol, angiotensin, and catecholamines levels compared to labored or full-term delivery. 33, 747748. 42, 335341. 40:064002. doi: 10.1088/1361-6579/ab205f, Hoyer, D., Schneider, U., Kowalski, E.-M., Schmidt, A., Witte, O. W., Schleuner, E., et al. This could lead to profound epigenetic changes in the fetal nervous system development and specifically in the vagal functionality, with possible long-term consequences (Crudo et al., 2013; Chang, 2014). That is, the machine (computer) learns from the actual data. Fetal sleep organization: a biological precursor of self-regulation in childhood and adolescence? Pediatr. Gynecol. Monitoring fetal electrocortical activity during labour for predicting worsening acidemia: a prospective study in the ovine fetus near term. In animal studies, Martin demonstrated that in sheep the initial fetal heart rate response to sudden hypoxemia was a slowing of the heart rate with increased variability.12 Others observed similar changes in sheep and in monkeys.31-33 Field et al found initial decreases in heart rate variability with iliac occlusion in sheep, but variability returned to normal by 36 minutes despite worsening metabolic acidosis.34 These observations of normal variability in the face of acidemia led researchers to postulate that some aspect of variability control could be different in animals compared to humans.