which intrinsic homeostatic response is the fetus demonstrating
Gynecol. Dev. 18, 349354. Alcohol. doi: 10.1515/jpme.1993.21.2.107, Clarkson, C. E., and Adams, N. (2018). Maternal consumption of non-staple food in the first trimester and risk of neural tube defects in offspring. Fetal cardiovascular decompensation during labor predicted from the individual heart rate tracing: a machine learning approach in near-term fetal sheep model. Perinatal psychoneuroimmunology: protocols for the study of prenatal stress and its effects on fetal and postnatal brain development, in Psychoneuroimmunology Methods in Molecular Biology, ed Q. Yan (New York, NY: Springer New York), 353376. Decreased neuroinflammation correlates to higher vagus nerve activity fluctuations in near-term ovine fetuses: a case for the afferent cholinergic anti-inflammatory pathway? doi: 10.1016/j.braindev.2018.10.009, Brndle, J., Preissl, H., Draganova, R., Ortiz, E., Kagan, K. O., Abele, H., et al. Gynaecol. Physiol. Perinatol. 42, 335341. Maternal perception, tocodynamometric findings and real-time ultrasound assessment of total fetal activity. doi: 10.1007/978-1-4939-1372-5_13, Goeden, N., Velasquez, J., Arnold, K. A., Chan, Y., Lund, B. T., Anderson, G. M., et al. With complete vagal and and adrenergic blockade, the decelerations persisted. B., de Waard, M., et al. A., Velez, M., Elko, A., Williams, E., Milio, L., et al. Med. The major critical events that can affect vagus nerve and ANS development occur in premature births and delivery by CS at term (Hillman et al., 2012; Tribe et al., 2018; Mulkey et al., 2019). 135, 7177. 80, vii94. Fetal heart rate, heart rate variability, and heart rate/movement coupling in the safe passage study. Front. (2018). 102, F183F187. Regarding sensorimotor development, around 15 WGA a complex set of movements (e.g., breathing movements, general body movements, isolated limb, head, and neck movements, startle and twitch movements, and swallowing) are available, whereas, by 18 WGA, stable handedness can be detected. Several animal studies in vertebrates and mammals show that vagal NC cells ablation heavily impairs the development and function of the aforementioned tissues. (2007). Since ANS development is coupled with FMs development, ANS alterations can heavily affect CNS and neurobehavioral growth: on the one hand, FMs are usually considered the base for the fight-or-flight response, thus influencing the stress response (Schmidt et al., 2014); on the other hand, ANS immaturity correlates with altered cerebral and psychomotor development (Hoyer et al., 2014; Schmidt et al., 2014; Schneider et al., 2018), and even with altered cognitive, language, playing, and social skills (Doussard-Roosevelt et al., 1997, 2001; Bornstein et al., 2002; DiPietro et al., 2007; Siddiqui et al., 2017). Synchronous caregiving from birth to adulthood tunes humans' social brain. (2007). doi: 10.1016/j.ajog.2019.04.029, Flenady, V., Ellwood, D., Bradford, B., Coory, M., Middleton, P., Gardener, G., et al. The clinicians task is not simple. The role of immune factors in shaping fetal neurodevelopment. In particular, a steep rise in PNS tone can be detected around 3738 WGA and basal fetal cardiovascular function becomes more influenced by the PNS. Fetal Neonatal Ed. Timeline Human Development - Embryology. Med. Rev. The evidence so far shows that the intrinsic fHRV is influenced by the fetal ANS activity and, conversely, also shapes the ANS activity into the postnatal period, at least in part via the afferent fibers of the vagus nerve (Herry et al., 2021). The ANS regulatory capacity begins before birth as the sympathetic and parasympathetic activity contributes significantly to the fetus' development (Hoyer et al., 2017; Mulkey and du Plessis, 2018; Zizzo et al., 2020). Abnormal heart rate characteristics before clinical diagnosis of necrotizing enterocolitis. Cardiac autonomic activity in methylmercury neurotoxicity: 14-year follow-up of a Faroese birth cohort. doi: 10.14814/phy2.13620, Harrison, N. A., Cooper, E., Voon, V., Miles, K., and Critchley, H. D. (2013). doi: 10.1016/j.smrv.2018.03.004, Weber, A., and Harrison, T. M. (2019). J Appl Physiol (1985). Commentary: Computerised interpretation of fetal heart rate during labour (INFANT): a randomised controlled trial. Short-term outcomes of newborns with perinatal acidemia who are not eligible for systemic hypothermia therapy. (2018). At this developmental stage, the fetus shows alternating behavioral states, passing through non-REM sleep and REM sleep, which lasts about 7090 min (Visser et al., 1992), with usually a wake state duration under 10%. Whereas, in the previous section we described the fetal development in relation to ANS maturation, showing potential short-term and long-term alteration in case something should negatively affect pregnancy or labor, this section will now detail what factors can alter ANS development and in which ways. Oncotarget 8, 100717100723. (2018). The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis. Available online at: http://arxiv.org/abs/2001.08264 (accessed April 23, 2021). (2011). Obstet. doi: 10.1016/j.spen.2018.05.004, Mulkey, S. B., and du Plessis, A. J. Integr. These patterns are altered by pain and could hence not only be pre-emptive for negative outcomes for labor and birth (Goldenberg et al., 2008), but also suggest their influence on the neurodevelopment of the fetal vagal system itself (Borovikova et al., 2000; Tracey, 2009; Frasch et al., 2016). Vagal NC cells emerge adjacent to the somites 17, rostral to the head NCs and caudal to the trunk and sacral ones, and are the ENS precursors (Hutchins et al., 2018; Simkin et al., 2019). (2018). Proc. (1998). 188, 524531. Am. 36, 441468. Moreover, maternal psychopathology influences HRV tracking also after birth, showing a higher mean HR and lower vagal modulation and confirming the impact of this prenatal disorder on vagal neurodevelopment (Dierckx et al., 2009). Hence, further research is needed about these drugs' impact on fetal vagus nerve development. Transl. In this physiological model, the first pathway also involves hypertension. (2020). doi: 10.1080/00016340802220352, Kadhim, H., Tabarki, B., Verellen, G., De Prez, C., Rona, A. M., and Sbire, G. (2001). Of the various organ systems affected by FASD, the brain is the most severely impacted: even if the hippocampus seems to be spared, other CAN structures show an impaired development, including the thalamus, hypothalamus, and prefrontal cortex, and also the spinal cord (Caputo et al., 2016). J. Obstet. Bistoletti P, Lagercrantz H, Lunell NO. doi: 10.1126/science.7414330, Glover, V. (2015). Nonetheless, the importance of ANS and vagus nerve regulation in fetal and neonatal development is still underrepresented (Sadler, 2012; Moore et al., 2016). 37, 953957. The last column shows an additional mechanism thought to be present with marked fetal acidemia where the heart rate slows due to direct myocardial effects. 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). doi: 10.1172/JCI30555, Tracey, K. J. 1032, 6384. Obstet Gynecol. 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). Field DR, Parer JT, Auslender R, Baker BW, Ross BK, Leicht CH. Mayo Clin. Catecholamine mediated effects are relatively slow reflecting their half-life of 2 to 3 minutes. FC, MC, SV, CV, and AM conceptualized the paper. Reprod. Fetal heart rate deceleration, albeit somewhat delayed, still occurred in response to cord compression. Paraphrased from a personal communication with Dr. Barry Schifrin. Neural System Development - Embryology. doi: 10.2147/IJWH.S151845, Reich, D. A., Govindan, R. B., Whitehead, M. T., Wang, J., Chang, T., Kota, S., et al. Hypothermia Temp. doi: 10.1016/0028-2243(80)90060-X, Venkata, C., and Venkateshiah, S. B. 4, 167170. Epidemiology 10, 370375. doi: 10.1073/pnas.1100329108, Dierckx, B., Tulen, J. H. M., van den Berg, M. P., Tharner, A., Jaddoe, V. W., Moll, H. A., et al. Indeed, warm incubators tend to increase SNS tone and reduce PNS activity, whereas the opposite is true for incubators 2C colder than newborns' temperature (Franco et al., 2003; Stphan-Blanchard et al., 2013). Res. 2:38. doi: 10.3389/fped.2014.00038, Edlow, A. G. (2017). Maternal nutrition is a substantial part of the developmental or metabolic programming of newborns (Koletzko et al., 2018, 2019), with short- and long-term consequences on health and a relevant impact on fetoplacental growth patterns (Morrison and Regnault, 2016). Manag. (2007). Rev. Supine position with manual restraint for flexion seems to have positive effects on ANS as measured through HRV (Gomes et al., 2019). J. Matern. 89, 584590. Bras. Cochrane Database Syst. Ter. Fetal heart rate variability responsiveness to maternal stress, non-invasively detected from maternal transabdominal ECG. Yawn duration predicts brain weight and cortical neuron number in mammals. Hum. 2012 Sep; 207(3):206. e1-8. 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). (2004). Yawning: unsuspected avenue for a better understanding of arousal and interoception. 29, 218223. 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). The prenatal gut microbiome: are we colonized with bacteria in utero? Horm. Perinatol. Several reports based on observations in human births do not support the reliability of moderate baseline variability to excluded acidemia. Dev. 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. 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). J. Obstet. 89, 380387. We have become accustomed the term a Perfect Storm when a collection of adverse conditions converge to produce calamity. 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. J. Gynecol. (2019). 1, 3342. doi: 10.1016/j.autneu.2007.04.008, de Vries, J. I. P., Visser, G. H. A., and Prechtl, H. F. R. (1982). The most frequently observed symptoms are: low back pain, headache, pelvic girdle pain (PGP), leg cramps, breast tenderness, abdominal pain, and ligament pain (Davis, 1996; Jarrell, 2017; Lutterodt et al., 2019). 105, 13121314. Diseases 6:23. doi: 10.3390/diseases6020023, Vohr, B. R., Davis, E. P., Wanke, C. A., and Krebs, N. F. (2017). Doussard-Roosevelt, 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). Ultimately, any influence on heart rate is mediated by one or more of these structures. J. Obstet. Neurosci. Turk. doi: 10.1016/j.ejogrb.2014.02.032, Baker, T. G., and Scrimgeour, J. Giussani DA, Spencer JA, Moore PJ, Bennet L, Hanson MA. The 1st stage begins when significant and regular contractions start and ends when there is a full cervical dilation of 10 cm. Macones GA, Hankins GD, Spong CY, Hauth J, Moore T. The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring: update on definitions, interpretation, and research guidelines. Clin. 68, 9881001. Impaired autonomic function in adolescents born preterm. (2011). Sex differences in the fetal heart rate variability indices of twins. Sleep patterns in late pregnancy and risk of preterm birth and fetal growth restriction. 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). Scand. J. R. Soc. Secondly, by suppressing melatonin secretion, thus altering the immune system and, potentially, the CAP, with all the negative consequences already mentioned. Period Med. 63, 281287. doi: 10.1038/s41574-020-0372-6, Avalos, L. A., Roberts, S. C., Kaskutas, L. A., Block, G., and Li, D.-K. (2014). doi: 10.2139/ssrn.3441806, Bernardes, J., Gonalves, H., Ayres-de-Campos, D., and Rocha, A. P. (2008). (2019). (Berl.) Changing heart rate is an important component of this mission but not the only one. Am J Obstet Gynecol. doi: 10.1055/a-0713-1058, Koletzko, B., Godfrey, K. M., Poston, L., Szajewska, H., van Goudoever, J. Autonomic development in preterm infants is associated with morbidity of prematurity. Primary benefits associated with the use of standardized. (2009). A study with autonomic blocking agents in fetal lambs. J. Perinat. Sadler, T. W. (2012). 42, 397412. Inflammatory cytokines in the pathogenesis of periventricular leukomalacia. 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. Novel mechanism of human fetal growth regulation: a potential role of lanugo, vernix caseosa and a second tactile system of unmyelinated low-threshold C-afferents. Montreal, QC: Acta Medica Publ. Human fetal lungs harbor a microbiome signature. 3, 127139. 1985 Jul 1;152(5):524-39. doi: 10.1002/14651858.CD010333.pub3, AlSaif, S., Mumtaz, S., and Wray, S. (2015). 17, 354381. Very little is known, however, about the central representation, the information processing network, of the vagus nerve. BJOG. Perinatol. Prenatal alcohol exposure also impacts the limbic-HPA axis development and functioning, leading to disrupted cortisol response (Ouellet-Morin et al., 2011). [Epub ahead of print]. Freeman RK, Garite TJ, Nageotte MP. Front. An aspect that should not be underestimated in the administration of epidural analgesia is the position of the mother. Dev. Then, as gestation progresses, the amount of movement, both spontaneous and in response to vibroacoustic stimuli, gradually increases: indeed, mothers begin to feel their babies' movements (Moore et al., 2016; Borsani et al., 2019). (2009). doi: 10.1515/jpm-2014-0031. Clin. Rev. J. Perinatol. The pathologies that induce chronic hypoxemia in the mother, including SBD (Pien and Schwab, 2004) and anemia, may induce dysregulations in the vagal control systems. 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). Epidural analgesia in labour. Your doctor checks the status during labor and delivery by monitoring and measuring their heart rate using special equipment. doi: 10.1016/j.braindev.2019.04.014, Alfirevic, Z., Devane, D., Gyte, G. M., and Cuthbert, A. 43, 395407. 9:593889. doi: 10.3389/fped.2021.593889, Goldaber, K. G., Gilstrap, L. C., Leveno, K. J., Dax, J. S., and McIntire, D. D. (1991). Heart Assoc. doi: 10.1038/s41390-019-0320-0, Reid, N., Moritz, K. M., and Akison, L. K. (2019). The consequences on the long-term capacity of CAP inflammatory response are worthy of further investigations. N. Y. Acad. Am. Maternal sleep during pregnancy and poor fetal outcomes: a scoping review of the literature with meta-analysis. Predictive value of electronic fetal monitoring for intrapartum fetal asphyxia with metabolic acidosis. Front. Am. Clin. 90, 131139. Microbiol. which intrinsic homeostatic response is the fetus demonstrating Obstet. (2011). Res. Med. J. Matern. 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. BJGP Open 3:bjgpopen19X101674. Heart rate variability in neonates of type 1 diabetic pregnancy. In order to prevent severe brain injury from a lack of oxygen, your doctor must revive the fetus and quickly address the source of late decels. (2015). Effect of tocolytic drugs on fetal heart rate variability: a systematic review. 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).