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Results: Fetuses are awake about 10% of the total time in the last gestational weeks, and they can be aroused by external stimuli. We retrieved the papers that fulfilled the research criteria, with particular attention to the second half of pregnancy, the period when most fetal surgery is performed. Methods: We performed a careful literature review (1990–2016) on fetal arousability, and on the possibility that ENIn at the average fetal blood levels induce actual anesthesia. Aim: To retrieve evidences about fetal pain, fetal arousability and about the level of sedation induced by the ENIn, in order to assess the necessity of direct fetal anesthesia during prenatal fetal surgery. We also recommend more effort to find out analgesic treatments tailored to the specific exigencies of PMIįetal pain and fetal anesthesia are still matter of debate: some authors hypothesize that several intrauterine endocrine neuroinhibitors (ENIn) anesthetize the fetus, keeping it in a constant state of sleep, and making pharmacological fetal anesthesia useless for fetal surgery, while others argue fetal pain is possible and shoud be prevented with fetal anesthesy. These data raise concern about the actual guarantees for persons lacking judgmental ability enrolled in potentially painful trials.
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PMI and NI enrolled in clinical trials as controls rarely receive analgesia and few studies exist to find out analgesic treatments shaped on PMI’s exigencies. All these studies were not performed to evaluate a possible analgesic strategy but to assess PMI’s pain responsiveness and no analgesia was used. We retrieved only one article where PMP was performed in PMI for clinical reasons (venipuncture) in 13 more studies, pain was experimentally provoked by noxious stimuli such as heat, electricity, or arm mobilization. We retrieved 46 studies that exposed NI to PMP only in 14.2% of the studies, a validated analgesic treatment was administered to the control group. We performed a Medline search to retrieve the studies published in 20, in which NI and PMI underwent PMP. We examined those trials in which patients undergo painful minor procedures (PMP) because these procedures are frequent and severely stressful for NI and PMI. We performed the present study to assess whether this also happens in clinical trials that should statutorily guarantee basic patients’ rights. People lacking judgmental ability (newborn infants and persons with mental impairment ) are reported to receive less analgesic treatments than people who can give adequate informed consent. This evidence becomes weaker before this date, though we cannot exclude its increasing presence since the beginning of the second half of the gestation.Īim. CONCLUSIONS: Most studies disclose the possibility of fetal pain in the third trimester of gestation. Against this possibility, some authors report the immaturity of the cortex with the consequent lack of awareness, and the almost continuous state of sleep of the fetus. In favor of a 2nd trimester perception of pain is the early development of spino-thalamic pathways (approximately from the 20th week), and the connections of the thalamus with the subplate (approximately from the 23rd week).
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But the presence of fetal pain in the 2nd trimester is less evident. Most endocrinological, behavioral and electrophysiological studies of fetal pain are performed in the third trimester, and they seem to agree that the fetus in the 3rd trimester can experience pain. RESULTS: We retrieved 217 papers of which 157 were highly informative some reported similar data or were only case-reports, and were not quoted. We focused on: (a) fetal development of nociceptive pathways (b) fetal electrophysiological, endocrinological and behavioral reactions to stimuli and pain. MATERIAL AND METHODS: We performed a Medline research from 1995, matching the following key words: "pain" and "fetus", with the following: "subplate", "thalamocortical", "myelination", "analgesia", "anesthesia", "brain", "behavioral states", "substance p". Due to the progress in fetal surgery, it is important to acquire data about fetal pain.