Anat., joa. doi: 10.1002/jlb.63.3.281, Bystrova, K. (2009). Fetal neurobehavioral development: a tale of two cities. This could suggest a different developmental pattern of the vagus nerve, both sex- and time-specific. Usually, it is administered between 24 and 34 WGA, mainly to ensure optimal fetal pulmonary development (Mulder et al., 2004; Committee on Fetus and Newborn and Section on Anesthesiology and Pain Medicine, 2016). Fetal yawning, in Frontiers of Neurology and Neuroscience, ed. It is interesting that fetal ANS impairment can also have consequences on infant temperament at both 3 and 6 months (Howland et al., 2020). doi: 10.1016/j.ecl.2019.08.011, Crudo, A., Suderman, M., Moisiadis, V. G., Petropoulos, S., Kostaki, A., Hallett, M., et al. Early Hum. 82, 417436. 40:064002. doi: 10.1088/1361-6579/ab205f, Hoyer, D., Schneider, U., Kowalski, E.-M., Schmidt, A., Witte, O. W., Schleuner, E., et al. doi: 10.1542/peds.2015-4271, Conradt, E., Crowell, S. E., and Lester, B. M. (2018). Lear CA, Galinsky R, Wassink G, Mitchell CJ, Davidson JO, Westgate JA, Bennet L, Gunn AJ. J. Obstet. Reducing low back and posterior pelvic pain during and after pregnancy using OMT. Obstet. Bone Jt. Available online at: https://embryology.med.unsw.edu.au/embryology/index.php/Neural_System_Development (accessed April 23, 2021). A., Thorp, J. Gynecol. The prenatal gut microbiome: are we colonized with bacteria in utero? 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). The Dutch Hunger Winter and the developmental origins of health and disease. Heart rate fall during acute hypoxemia: a measure of chemoreceptor response in fetal sheep. Autonomic nervous system impairment may have consequences on the global development that persist during infancy, adolescence, and adult life. 118, e246e251. Fetal motor capacities, through the implied neuronal activity, is paramount for differentiation, migration, synaptogenesis, and development of neuronal networks. 179, 551569. 12, 317. (2019). I. Qualitative aspects. (2014). Breastfeed. Moreover, excessive light can impair visual development, thus increasing SNS and HPA axis activation (Weber and Harrison, 2019). (2020). These therapies can affect fetal neurodevelopment: the increase prescriptions for opioids during pregnancy, for example, correlates to an increased incidence of neonatal abstinence syndrome (NAS), resulting in sleeping and feeding difficulties, as well as a dysregulation in newborns' CNS (Pryor et al., 2017; Ray-Griffith et al., 2018). Although the induction of the hormone oxytocin has no cardiac repercussions, it can still influence the development of the vagus nerve and the ANS in the last hours of labor. 54, 3437. doi: 10.1038/jp.2017.59, Silasi, M., Cardenas, I., Kwon, J.-Y., Racicot, K., Aldo, P., and Mor, G. (2015). Nat. (2019). Front. 28, 16641668. (2009). Around 89 WGA, it is possible to clearly record GMs (Prechtl, 1990). Res. Moreover, a recent pilot study described that in utero ZIKV-affected babies display HRV metrics abnormalities. Specific kinds of brain injuries seem also to specifically affect ANS: for instance, DFA revealed that white matter injury, watershed stroke, basal ganglia injury, or global injury can show characteristic HRV signatures (Metzler et al., 2017). doi: 10.1016/j.outlook.2018.11.002, Westerhuis, M. E. M. H., Kwee, A., van Ginkel, A. Dev. C Embryo Today Rev. doi: 10.1002/pd.4932, Edwards, N., Middleton, P. G., Blyton, D. M., and Sullivan, C. E. (2002). 130, 403407. Eng. (2006). doi: 10.1159/000089065, McMahon, E., Wintermark, P., and Lahav, A. Secondly, by suppressing melatonin secretion, thus altering the immune system and, potentially, the CAP, with all the negative consequences already mentioned. doi: 10.1093/sleep/27.7.1405, Podymow, T., and August, P. (2008). Gynecol. 16, 509517. Biol. Dynamic touch reduces physiological arousal in preterm infants: a role for c-tactile afferents? Res. Continuous cardiotocography (CTG) as a form of electronic fetal monitoring (EFM) for fetal assessment during labour. Stress revisited: a critical evaluation of the stress concept. J. Obstet. 524, 12591269. doi: 10.1016/j.molmed.2014.05.002, Borsani, E., Della Vedova, A. M., Rezzani, R., Rodella, L. F., and Cristini, C. (2019). Ther. The cardioregulatory center receives input from the central nervous system, reflex pathways and circulating catecholamines. Drugs including theophylline, caffeine, and methylxanthine, used to support respiratory functions have the potential of altering sleep quality and induce drowsiness. Indeed, ANS responsiveness seems to remain quite low even when preterm infants reach term-equivalent ages compared to full-term newborns (Mulkey et al., 2018; Patural et al., 2019; Schlatterer et al., 2021). Multiomic immune clockworks of pregnancy. Early biological aging and fetal exposure to high and low ambient temperature: a birth cohort study. Microbiol. Diet and lifestyle before and during pregnancy practical recommendations of the germany-wide healthy start young family network. 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). Physiologists continue to elucidate the important role of fetal chemoreceptors and their effect on fetal heart rate. What is amiss is the understanding and acting upon the fact that each fetus and newborn are not truly new, but, rather, come with weeks and months of experience in utero. (2021d). Environmental stimuli, per se, induce motor reactions, as the sensory system maturation proceeds. Viral infections during pregnancy. 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). doi: 10.1038/jp.2013.63, Subtil, D., Tiberghien, P., Devos, P., Therby, D., Leclerc, G., Vaast, P., et al. Clin. 15, 448455. 27, 910920. Baltimore, MD: Johns Hopkins University Press. 3, 127139. doi: 10.1016/j.ajog.2005.05.012, Sklerov, M., Dayan, E., and Browner, N. (2019). B 44, 279303. Prenatal exposure to sGC may interfere both with the fetal endogenous cortisol sensitivity, which involves the hippocampus, amygdala, and HPA axis and with the fetal cardiovascular and metabolic regulatory systems (Seckl and Meaney, 2004). Although CS delivery is far faster than a vaginal birth modality, the fetus is still subjected to significant stress that can create changes in the development of some systems, including the ANS (Tribe et al., 2018). Reprod. 2007 Nov;114(11):1442-4. Antihypertensive medication use during pregnancy and the risk of cardiovascular malformations. Westgate JA, Wibbens B, Bennet L, Wassink G, Parer JT, Gunn AJ. Expert Help. During labor, the recommended fetal heart rate assessment interval for auscultation is every A. The regulatory patterns of sympathovagal balance show sex-specific differences as pregnancy progresses (Buss et al., 2009). 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? In particular, the subplate (a central hub for cortical connectivity) becomes visible and begins to receive connection from the thalamus, basal forebrain, and brainstem. 89, 584590. Gynecol. Indeed, the first findings relating HRV alterations to fetal death, thus hinting to a potential predictive role of HRV, date back to the early sixties of the twentieth century (Hon and Lee, 1963). 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: 10.7556/jaoa.2018.108, Snijder, C. A., Roeleveld, N., te Velde, E., Steegers, E. A. P., Raat, H., Hofman, A., et al. Magnesium sulfate, maternal hypothermia, and fetal bradycardia with loss of heart rate variability. 36, 10551064. Update on the use of antihypertensive drugs in pregnancy. doi: 10.31887/DCNS.2016.18.4/tbale, Barlow-Anacker, A. J., Fu, M., Erickson, C. S., Bertocchini, F., and Gosain, A. Neural crest cells contribute an astrocyte-like glial population to the spleen. doi: 10.1089/ther.2018.0019. Women Birth 32, 12. Med. Some authors but not all have shown that a reduction in long-term variability occurs after sympathetic blockade.19-22 Fetal heart rate variability is more than the simple push-pull interactions between the inhibitory and acceleratory limbs of the autonomic nervous system. 14, 259265. As revealed by HRV analysis, the ANS constantly develops. The sympathetic component induces peripheral vasoconstriction and hypertension to maintain perfusion and adequate oxygen delivery to vital organs. Am. (2011). 8:503. doi: 10.3389/fped.2020.00503. 1781, 341352. (2015). (2017). Tendais, I., Figueiredo, B., Gonalves, H., Bernardes, J., Ayres-de-Campos, D., and Montenegro, N. (2015). doi: 10.1080/07420528.2018.1439499, Jarrell, J. Diseases 6:23. doi: 10.3390/diseases6020023, Vohr, B. R., Davis, E. P., Wanke, C. A., and Krebs, N. F. (2017). 88, 718720. Anat. Am J Obstet Gynecol. 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). As the nervous system of the fetus develops, around 3639 WGA a different fHRV pattern is detectable according to different acoustic stimuli, as for example human speech (Lecanuet et al., 1992; Krueger and Garvan, 2019). The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors. Research on the ovine species, reproducing the conditions of human labor, is indeed leading to the discovery and evidence of different algorithms to prevent pathological complications (Frasch et al., 2011; Wang et al., 2014). Indeed, through lanugo, the flow of amniotic fluid and FMs stimulate the low-threshold unmyelinated C afferent fibers (Bystrova, 2009), which have been found to be essential for both nociception and interoception. Dev. 17, 354381. (2019). The fetus is exposed to the lower intervillous oxygen levels only when the uterine contraction forces are sufficient to impede intramyometrial perfusion. The production of testosterone in male fetuses begins during the 2nd month of pregnancy and reaches the maximum in the 2nd trimester (Chung and Auger, 2013), just before when vagal tone starts to rise (Mulkey and du Plessis, 2019). Prenatal maternal psychological distress and fetal developmental trajectories: associations with infant temperament. Fetal cardiovascular function during prolonged magnesium sulfate tocolysis. 34, 668675. Am. First Foods and Gut Microbes. Chiera, M., Cerritelli, F., Casini, A., Barsotti, N., Boschiero, D., Cavigioli, F., et al. Environmental magnetic field in a neonatal intensive care unit. Antihypertensive drugs in pregnancy. It is worth remembering that the two ANS branches are anything but antagonists: in fact, the regulation of many organic functions (Goldstein, 2006), including the immune and inflammatory responses (Bonaz et al., 2021), strictly depends on the synergy between the two branches. 30, N1N10. doi: 10.1530/jrf.0.0600193, Bale, T. L. (2016). Fetal chemoreception: a developing story. These situations increase the risk of impairment of fetal brain development resulting in emotional, behavioral, and/or cognitive problems in later life (Glover, 2015; Antonelli et al., 2021). Reprod. Kleinhout J, Stolte LA, Janssens J, Knoop AA. (2014). doi: 10.1084/jem.20180794, PubMed Abstract | CrossRef Full Text | Google Scholar, Abrams, R. M., and Gerhardt, K. J. 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). Available online at: http://arxiv.org/abs/2011.02000 (accessed May 13, 2021). Dis. Gynaecol. J. Calif. Perinat. Electrical grounding improves vagal tone in preterm infants. (2015). Development of extrinsic innervation in the abdominal intestines of human embryos. Front. Off. Child Dev. Res. ArXiv190905198 Q-Bio. Normal and abnormal US findings in early first-trimester pregnancy: review of the society of radiologists in ultrasound 2012 consensus panel recommendations. Med. Environmental radiofrequency electromagnetic field levels in a department of pediatrics. In another, set of experiments with sheep in labor, uterine contractions were associated with decelerations. As thermoregulation is one of the most important ANS functions, the temperature can easily affect ANS development. In this proposal the chemoreflex efferent in the vagus nerve causes FHR slowing and the sympathetic component causes hypertension to maintain perfusion to vital organs. Safety of selective serotonin reuptake inhibitors in pregnancy. The resulting hypertension induces the barorflex, stimulating the cardioinhibitory center and its vagal efferent to slow the heart rate. doi: 10.1016/j.earlhumdev.2015.11.003, Sabir, H., Stannigel, H., Schwarz, A., and Hoehn, T. (2010). J. Perinat. In fact, epidural analgesia itself does not show precise or significant changes in fHRV (Lavin, 1982), but it can interact with other aspects already existing in the mother. Autonomic nervous system regulation of baseline heart rate in the fetal lamb. Semergen 42, e59e64. Intern. Maternal micronutrient deficiency, fetal development, and the risk of chronic disease. The hypothalamic-pituitary-adrenal axis and the fetus. doi: 10.1038/nri2566, Tribe, R. M., Taylor, P. D., Kelly, N. M., Rees, D., Sandall, J., and Kennedy, H. P. (2018). 1977 Feb 15; 127(4): 414-24. Am. Clin. Occup. A decrease in the heart rate The vagus nerve begins maturation 26 to 28 weeks. India 15, 382386. Off. Pharmacol. 57:101. doi: 10.3345/kjp.2014.57.3.101. (1998). 1981 Dec 1; 141(7):797-806. Dev. Fetal heart rate variability is suppressed by factors that depress fetal brain function. Continued pain and discomfort throughout the pregnancy can induce both a sensitization of the maternal nervous system, with a lower pain threshold (Gintzler, 1980; Cogan and Spinnato, 1986; Eid et al., 2019), and a dysregulation in the inflammatory response, mediated by the CAP via the vagus nerve (Garzoni et al., 2013). Despite knowing that the CAN coordinates autonomic function and that left and right hemispheres modulate PNS and SNS tone, respectively (Mulkey et al., 2021), we have conflicting results on how the brain precisely controls ANS in newborns. Supine position with manual restraint for flexion seems to have positive effects on ANS as measured through HRV (Gomes et al., 2019). J. Anaesth. Available online at: https://embryology.med.unsw.edu.au/embryology/index.php/Neural_System_Development (Accessed April 23, 2021). Gynaecol. Fetal audition. Gynecol. 465, 573584. Maternal inflammation disrupts fetal neurodevelopment via increased placental output of serotonin to the fetal brain. 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. Gynecol. Moreover, considering the role of the vagus nerve in the CAP, which involves immune cells such as macrophages (Borovikova et al., 2000; Tracey, 2007; Fairchild et al., 2010; Frasch et al., 2016), and the sex-related neurodevelopment impact of microglial functions (Hanamsagar and Bilbo, 2016), the different characteristics of the developmental pattern of vagus nerve between male and female fetuses could predispose for sex-specific susceptibility and outcomes in many neurodevelopmental disorders (Berntson and Cacioppo, 2004). 1993 Feb;461:431-49. Rates of and factors associated with delivery-related perinatal death among term infants in Scotland. Similarly, calcium, zinc, and iron assumption during pregnancy seems to affect fetal cardiovascular development and autonomic regulatory function (Christian and Stewart, 2010). Furthermore, chronic dysfunction of your placenta is sometimes brought on by maternal diseases, like diabetes, collagen-vascular disorders, or hypertension. (2017). Total Environ. Newborn Infant Nurs. Regarding vagal activity in fetuses, not all the authors agree in observing significative sex-related differences (Oguch and Steer, 1998; DiPietro et al., 2004; Lange et al., 2005; Bhide and Acharya, 2018), even when the same methodologies were used. doi: 10.1016/j.earlhumdev.2010.05.018, Schneider, U., Frank, B., Fiedler, A., Kaehler, C., Hoyer, D., Liehr, M., et al. doi: 10.1080/14767058.2018.1509067, Brown, A., and Johnston, R. (2013). The patterns of cytokine response and the neuroimmune physiology of the fetus and the placenta mirror the maternal ones throughout pregnancy (Sherer et al., 2017, 2018; Prins et al., 2018; Peterson et al., 2020). Sex differences in fetal heart rate and variability assessed by antenatal computerized cardiotocography. 2009 Aug 12;302(6):660-8. Your doctor checks the status during labor and delivery by monitoring and measuring their heart rate using special equipment. Maternal consumption of non-staple food in the first trimester and risk of neural tube defects in offspring. Sleep disorders during pregnancy. Sleep and sleep disorders in pregnancy. Meas. Cogn. Available online at: http://www.ncbi.nlm.nih.gov/books/NBK470566/ (accessed February 22, 2021). With complete vagal and and adrenergic blockade, the decelerations persisted. (2003). doi: 10.1111/j.1552-6909.1996.tb02516.x, De Jonckheere, J., and Storme, L. (2019). (2010). Newborns can also be subject to EMFs, from the incubator or the care unit environment. Premature infant responses to noise reduction by earmuffs: effects on behavioral and physiologic measures. Alcohol. Front. We . Both sexes demonstrate an evolutionary pattern with increased entropy indexes until 34 WGA, with a slight decrease after 37 WGA. Bennet L, Westgate JA, Liu YC, Wassink G, Gunn AJ. Obstet. doi: 10.1053/sper.2001.27546, Rantakari, K., Rinta-Koski, O.-P., Metsranta, M., Hollmn, J., Srkk, S., Rahkonen, P., et al. Psychopathol. Use Misuse 49, 14371445. Rev. Diurnal, respiratory, and other rhythms of fetal heart rate in lambs. Frasch, M. G., Baier, C. J., Antonelli, M. C., and Metz, G. A. S. (2018a). Your doctor checks the status during labor and delivery by monitoring and measuring their heart rate using special equipment. J. Physiol. Gynecol. Thanaboonyawat, I., Wataganara, T., Boriboonhiransarn, D., Viboonchart, S., and Tontisirin, P. (2006). Behav. Any event that perturbs the fetal cardiovascular system will initiate a cascade of compensatory actions to optimize oxygen delivery and restore fetal hemostasis. Around 20 WGA and for the rest of the 2nd trimester, myelination occurs (Borsani et al., 2019). Antony, K. M., Ma, J., Mitchell, K. B., Racusin, D. A., Versalovic, J., and Aagaard, K. (2015). Coregulated approach to feeding preterm infants with lung disease: effects during feeding. Placenta 54, 3037. J. Nutr. 17, 641650. J. Obstet. The onset of fetal breathing movements, in particular, induces a variation in the main vagal nerve activity parameters: RMSSD and HF power increase, while LH/HF power decreases. Arch. doi: 10.1097/NNR.0b013e31824b02ad, Tong, L., and Kalish, B. T. (2020). Front. 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. (2014). Outlook 67, 169189. Neurosci. Environ. Williams KP, Galerneau F. Intrapartum fetal heart rate patterns in the prediction of neonatal acidemia. Prior studies have catalogued extensive molecular alterations associated with homeostatic scaling. 43, 395407. Maternal and paternal occupational exposure to agricultural work and the risk of anencephaly. Epidemiol. Although incubator EMF seems to be under the normative value, EMFs could become dangerous when the incubator, and thus the newborn, is surrounded by other instruments or staff's devices that, through their own EMF, can give rise to electromagnetic interference (Besset et al., 2020). They do not make assumptions about linear relationships or require independent effects and they can consider trends over time. Front. fHRV undergoes fewer changes with the use of the full lateral position, compared with the use of wedged supine position (Preston et al., 1993). Indeed, fHRV can be affected by both neural factors (i.e., ANS) and non-neural factors, e.g., metabolic and organic functions (DiPietro et al., 2015). 85, 10321040. The newborn is not new, and neither is the fetus. Dev. Dev. doi: 10.1016/S1389-9457(03)00107-2, Frasch, M. G. (2018). Sleep 35, 177186. (Berl.) Biol. doi: 10.1289/ehp.99107475, Derbyshire, S. W., and Bockmann, J. C. (2020). 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). Med. doi: 10.1093/humrep/der437, Soma-Pillay, P., Nelson-Piercy, C., Tolppanen, H., and Mebazaa, A. Pediatr. The chances of fetal hypoxia remain low if repeated decelerations arent present and fetal heart tracing is otherwise normal. Frasch, M. G. (2020). A., Gierczak, M., Pattillo, C., Glynn, L. M., et al. Classic teaching on the mechanisms of Late decelerations is outlined in Figure 3. Mapping the immunological homunculus. A., Velez, M., Elko, A., Williams, E., Milio, L., et al. Neuropharmacology 144, 7081. 62, 6877. 23, 539549. Neurosci. Prevention and management of procedural pain in the neonate: an update. Is it also related to comfort? The circadian dynamics of fHR is synchronized with the maternal rhythm of the activity at rest, HR, cortisol, melatonin, and body temperature. doi: 10.1016/0002-9378(82)90812-2, Spinillo, A., Viazzo, F., Colleoni, R., Chiara, A., Maria Cerbo, R., and Fazzi, E. (2004). BJOG Int. A clinical perspective of necrotizing enterocolitis: past, present, and future. Metab. Health conditions may, however, affect postnatal ANS maturation more than gestational age at birth: in the 3 months after birth, infants with a higher number of postnatal complications (e.g., infections, patent ductus arteriosus requiring treatment, mechanical ventilation) show a lower ANS tone measured through DFA metrics, i.e., 1, 2, RMS1, and RMS2. Neurosci. Effect of magnesium sulphate on fetal heart rate parameters: a systematic review. Circadian variation of heart rate variability. doi: 10.1016/j.ynstr.2018.08.005, Conradt, E., Flannery, T., Aschner, J. L., Annett, R. D., Croen, L. A., Duarte, C. S., et al. Psychoneuroendocrinology 37, 8793. Fetal heart rate and variability: stability and prediction to developmental outcomes in early childhood. Pediatrics 144::e20190128. (2020). Antenatal interventions based upon fetal surveillance of the daily opioid-exposed fetus: a descriptive analysis. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. BMJ Open 8:e020031. Sculpting the sculptors: methods for studying the fetal cholinergic signaling on systems and cellular scales. Early development of sleep and brain functional connectivity in term-born and preterm infants. doi: 10.1038/clpt.2009.201, Oberlander, T. F., Jacobson, S. W., Weinberg, J., Grunau, R. E., Molteno, C. D., and Jacobson, J. L. (2010). Dev. doi: 10.1053/smrv.2002.0243, Montagna, A., and Nosarti, C. (2016). The consequences can be quite severe: from apnea to hypoxemia, from sleep disruption to decreased growth, from immunity impairment to neuroendocrine alterations (Almadhoob and Ohlsson, 2020). N. Y. Acad. Assessed occupational exposure to chlorinated, aromatic and Stoddard solvents during pregnancy and risk of fetal growth restriction. doi: 10.1097/PCC.0000000000001094, Mattingly, J. E., D'Alessio, J., and Ramanathan, J. Gynaecol. Sleep and prematurity: sleep outcomes in preterm children and influencing factors. 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). A possible critical event during the first stage of labor is certainly the risk of cardiac events. doi: 10.1080/j.1600-0412.2003.820101.x, Jansson, L. M., DiPietro, J. 86: . J. Obstet. (1995). Engl. 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. The occupational and environmental exposure to pollution may be another important disrupting factor for fetal ANS development. Furthermore, without uterus protection, newborns can be particularly sensitive to sounds, which usually overcome the 45 dB limit recommended by the American Academy of Pediatrics (Almadhoob and Ohlsson, 2020), thus resulting in toxic stress (Weber and Harrison, 2019). Birt. Ingemarsson, I., and Lamont, R. F. (2003). 1:CD010333. In practice, clinicians must integrate clinical data with electronic fetal monitoring patternsin order to project what is likely to happen and how quickly it might occur. During the 3rd trimester of pregnancy, emerging fetal sleep states are detectable, with the onset of the functional organization of the sleep cycle around 2830 WGA, and these patterns gradually consolidate around 36 WGA (Van den Bergh and Mulder, 2012). doi: 10.1159/000480620, Vitetta, L., Vitetta, G., and Hall, S. (2018). Hill, M. A. doi: 10.1016/j.psyneuen.2011.05.007, Gartstein, M. A., and Skinner, M. K. (2018). A thermal imaging study. Pediatr. An antenatal marker of neurodevelopmental outcomes in infants with congenital heart disease. 31, 7085. Perinatol. doi: 10.3390/nu7053067, Wang, X., Durosier, L. D., Ross, M. G., Richardson, B. S., and Frasch, M. G. (2014). doi: 10.1016/j.yfrne.2015.09.001, Nuriel-Ohayon, M., Neuman, H., and Koren, O. Homeo-static intrinsic plasticity is outside the scope of this review, but has been reviewed in detail [e.g. Front. Heres how to tell if youre experiencing them. Hillman, N. H., Kallapur, S. G., and Jobe, A. H. (2012). Even in the sheep experiments using precisely controlled conditions, consistent fetal heart rate decelerations could not be produced equally in all animals despite 2 hours of repetitive maternal vascular occlusions.12 The late decelerations induced by constricting the sheep uterine arteries with and without acidemia are redrawn to scale on the grid used by fetal monitoring paper in Figure 4. 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. 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. Interestingly, the analysis of specific HRV metrics, for instance, SDNN (more related to global neuroautonomic regulation), RMSSD (more related to vagal modulation), and PE, can help identify the actual behavioral state and, therefore, detect potential problems in neurodevelopment whether incoherence between HRV and body movements is detected (Schneider et al., 2008; Brndle et al., 2015). An examination of changes in maternal neuroimmune function during pregnancy and the postpartum period. Standards of measurement, physiological interpretation, and clinical use. (2016). 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