188, 524531. New York, NY: W. W. Norton. First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy. doi: 10.1038/jp.2017.59, Silasi, M., Cardenas, I., Kwon, J.-Y., Racicot, K., Aldo, P., and Mor, G. (2015). Oxytocin specifically enhances valence-dependent parasympathetic responses. The effect of diazepam administration during pregnancy or labor on the heart rate variability of the newborn infant. J Physiol. J. Neurosci. Environ. Hypotension and uterine hypertonia, for instance, can create significant imbalances in the fHRV during epidural analgesia in labor (Lavin, 1982). 71, 679683. Neurosci. doi: 10.1111/aogs.12681, Haley, D. W., Handmaker, N. S., and Lowe, J. Alcohol. Validation of functional fetal autonomic brain age score fABAS in 5 min short recordings. This detects changes in the normal FHR pattern at the time of labor, reassuring your obstetrician if its safe to proceed. Fetal audition. The cardioregulatory center receives input from the central nervous system, reflex pathways and circulating catecholamines. Clinical study of fetal neurobehavior by the KANET test. 116: Management of intrapartum fetal heart rate tracings. Physiology, pain, in StatPearls (Treasure Island, FL: StatPearls Publishing). Am J Obstet Gynecol. U.S.A. 107, 1675716758. Rev. Am. Cardiovascular System - Spleen Development - Embryology. Citalopram use in pregnancy: prospective comparative evaluation of pregnancy and fetal outcome. Clin. 1977 Feb 15; 127(4): 414-24. Maturation of the human fetal startle response: evidence for sex-specific maturation of the human fetus. doi: 10.2139/ssrn.3441806, Bernardes, J., Gonalves, H., Ayres-de-Campos, D., and Rocha, A. P. (2008). Invest. Electronic storage of vast amounts of clinical data and tracings makes it feasible to study rare outcomes like severe metabolic acidemia or hypoxic ischemic encephalopathy. doi: 10.1038/pr.2017.94, Meyer, U., Yee, B. K., and Feldon, J. doi: 10.1111/aogs.13437, Boehm, F. H., Woodruff, L. F., and Growdon, J. H. (1975). The inadequate intake or absorption of nutrients, such as polyunsaturated fatty acids, folic acid, and vitamin B12, may result in altered fetal neurodevelopment (Starling et al., 2015; Wang et al., 2015), and lead to important consequences on neurobehaviour during infancy (Gernand et al., 2016; Bordeleau et al., 2021). doi: 10.1016/S1701-2163(15)30382-0, Newbern, J. M. (2015). 26:101221. doi: 10.1016/j.siny.2021.101221. Front. Regul. doi: 10.1080/j.1600-0412.2003.820101.x, Jansson, L. M., DiPietro, J. Beyond the headlines: fetal movement awareness is an important stillbirth prevention strategy. Epidemiology and causes of preterm birth. 89, 13761380. (2017). 21, 144147. (2019). Physiol. Int. Despite the evidence of positive effects of non-surgical and non-pharmacological treatments, such as physiotherapeutic interventions, acupuncture, or osteopathic manipulations (Gutke et al., 2015; Gallo-Padilla et al., 2016; Ray-Griffith et al., 2018; Smith et al., 2018; Cerritelli et al., 2020), the use of drugs for pain relief (e.g., low-dose aspirin, acetaminophen, non-steroidal anti-inflammatory drugs, and opioids) during pregnancy is still very common (Ray-Griffith et al., 2018). As a consequence, by relying on appropriate animal models, several authors have defined potential critical windows related to human brain development (see, for instance, Figure 1 in Morrison et al., 2018). doi: 10.1126/scitranslmed.3008599, Abdel-Haq, R., Schlachetzki, J. C. M., Glass, C. K., and Mazmanian, S. K. (2018). 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). J. Gynaecol. 1977;7(6):373-6. J. The endotoxemia, through lipopolysaccharide molecules, seems to interfere with the cardiac pacemaker synchronization system, altering the fHRV pattern (Frasch and Giussani, 2020). (2018). doi: 10.1016/j.lfs.2015.02.001, Al-Shargabi, T., Govindan, R. B., Dave, R., Metzler, M., Wang, Y., du Plessis, A., et al. Hypoxia can induce heart failure which is revealed by accelerations and decelerations in fHRV (Rivolta et al., 2014). Factors that modulate fetal anaerobic reserve are myocardial glycogen stores, placental exchange capacity and chronic hypoxia. Autonomic nervous system regulation of baseline heart rate in the fetal lamb. 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. Mol. 11:578898. doi: 10.3389/fphys.2020.578898, Keywords: fetal development, autonomic nervous system, vagus nerve, cholinergic anti-inflammatory pathway, heart rate variability, critical window, maternal health, Citation: Cerritelli F, Frasch MG, Antonelli MC, Viglione C, Vecchi S, Chiera M and Manzotti A (2021) A Review on the Vagus Nerve and Autonomic Nervous System During Fetal Development: Searching for Critical Windows. Med. Commentary: Computerised interpretation of fetal heart rate during labour (INFANT): a randomised controlled trial. Fetal heart rate and motor activity associations with maternal organochlorine levels: results of an exploratory study. J Physiol. Heart rate variability in hypertensive pregnancy disorders: a systematic review. 14:612705. doi: 10.3389/fncel.2020.612705, Bornstein, M. H., DiPietro, J. Pulm. Semin. Here low pH and hypoxemia trigger the chemoreceptor response causing peripheral vasoconstriction. Am. Lancet Lond. After 2 minutes of complete cord compression, the FHR in the deceleration began to recover despite continuing fall in cerebral oxygenation and rising hypertension. Induction of labor with oxytocin in pregnancy with low-risk heart disease: a randomized controlled trial. Psychoneuroendocrinology 87, 2734. The impact of positioning on bottle-feeding in preterm infants ( 34 GA). Gynecol. Dev. Am J Physiol Heart Circ Physiol. 40, 11361141. Sci. Am. Lack of detection of a human placenta microbiome in samples from preterm and term deliveries. J. Obstet. Environ. 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). The high immunoreactivity of the premature infants' gut could also lead to neurodevelopmental disorders (Cao et al., 2014). 10, 134144. Nurs. 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. Reprod. 48, 829842. Continuous positive airway pressure (CPAP) for respiratory distress in preterm infants. Front. Fetal mediators of the relationships between increased pregnancy and labour blood pressure and newborn irritability. doi: 10.1007/s11605-014-2565-6, Fuhler, G. M. (2020). Physiol. Sheep are in fact an important model for simulating human pregnancy. doi: 10.1159/000480620, Vitetta, L., Vitetta, G., and Hall, S. (2018). Fetal heart rate acceleration in response to light Stimulation s a clinical measure of fetal well-being. In this context, further research is needed to better clarify the relationship between maternal neuroendocrine dysregulation, due to chronobiological impairments, and the impact on fetal neurodevelopment, particularly on the CAP. Analg. 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).

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