Analgesia for fetal pain during prenatal surgery: 10 years of progress.

Some doubts on the necessity and safety of providing analgesia to the fetus during prenatal surgery were raised 10 years ago. They were related to four matters: fetal sleep due to neuroinhibitors in fetal blood, the immaturity of the cerebral cortex, safety, and the need for fetal direct analgesia. These objections now seem obsolete. This review shows that neuroinhibitors give fetuses at most some transient sedation, but not a complete analgesia, that the cerebral cortex is not indispensable to feel pain, when subcortical structures for pain perception are present, and that maternal anesthesia seems not sufficient to anesthetize the fetus. Current drugs used for maternal analgesia pass through the placenta only partially so that they cannot guarantee a sufficient analgesia to the fetus. Extraction indices, that is, how much each analgesic drug crosses the placenta, are provided here. We here report safety guidelines for fetal direct analgesia. In conclusion, the human fetus can feel pain when it undergoes surgical interventions and direct analgesia must be provided to it. IMPACT: Fetal pain is evident in the second half of pregnancy. Progress in the physiology of fetal pain, which is reviewed in this report, supports the notion that the fetus reacts to painful interventions during fetal surgery. Evidence here reported shows that it is an error to believe that the fetus is in a continuous and unchanging state of sedation and analgesia. Data are given that disclose that drugs used for maternal analgesia cross the placenta only partially, so that they cannot guarantee a sufficient analgesia to the fetus. Safety guidelines are given for fetal direct analgesia.

The Congress "Yes to Life": A Hand Offered in Dialogue.

The Congress "Yes to Life," devoted to the ethical problems in perinatology, has been an important carrefour for the intercultural dialogue on these themes. This paper describes the aim of the Congress and why it was proposed.

Analgesia, nil or placebo to babies, in trials that test new analgesic treatments for procedural pain.

UNLABELLED: This review assessed how often neonates in control groups experienced unnecessary pain during clinical trials involving procedural pain. We retrieved 45 studies in the 30 months up to June 2015 and found that in 29 (64%) the control babies received either placebos or no treatment. Placebos were used in 15/25 (60%) studies involving heel pricks and in 6/8 (75%) involving venepuncture. CONCLUSION: Despite international guidelines, neonates included in control groups during painful procedures do not receive analgesia in the majority of cases. Several historical reasons can explain this, but in the light of present knowledge, this should not continue. Ethical committees are thereof invited since now to not permit clinical trials that do not explicitly rule out pain during treatments and journals are invited to not publish them.

Blue Light and Ultraviolet Radiation Exposure from Infant Phototherapy Equipment.

Phototherapy is the use of light for reducing the concentration of bilirubin in the body of infants. Although it has become a mainstay since its introduction in 1958, a better understanding of the efficacy and safety of phototherapy applications seems to be necessary for improved clinical practices and outcomes. This study was initiated to evaluate workers' exposure to Optical Radiation from different types of phototherapy devices in clinical use in Italy. During infant phototherapy the staff monitors babies periodically for around 10 min every hour, and fixation of the phototherapy beam light frequently occurs: almost all operators work within 30 cm of the phototherapy source during monitoring procedures, with most of them commonly working at ≤25 cm from the direct or reflected radiation beam. The results of this study suggest that there is a great variability in the spectral emission of equipments investigated, depending on the types of lamps used and some phototherapy equipment exposes operators to blue light photochemical retinal hazard. Some of the equipment investigated presents relevant spectral emission also in the UVA region. Taking into account that the exposure to UV in childhood has been established as an important contributing factor for melanoma risk in adults and considering the high susceptibility to UV-induced skin damage of the newborn, related to his pigmentary traits, the UV exposure of the infant during phototherapy should be "as low as reasonably achievable," considering that it is unnecessary to the therapy. It is recommended that special safety training be provided for the affected employees: in particular, protective eyewear can be necessary during newborn assistance activities carried out in proximity of some sources. The engineering design of phototherapy equipment can be optimized. Specific requirements for photobiological safety of lamps used in the phototherapy equipment should be defined in the safety product standard for such equipment.

Ankyloglossia in newborns: incidence and breastfeeding follow-up at 1 and 6 months.

BACKGROUND: Ankyloglossia is an anatomical variation of the lingual frenulum that negatively interferes with the functionality of the tongue. This condition can affect breastfeeding negatively. The aim of this study is to assess the prevalence of ankyloglossia among healthy babies born in Siena Hospital and the correlation between ankyloglossia and breastfeeding difficulties. METHODS: We performed an observational prospective study conducted on healthy and breastfed newborns born in Siena Hospital in the period between January and June 2022. The evaluation of lingual frenulum in the first few days of life was performed by Martinelli's Lingual Frenulum Protocol with scores for Infants (MLFPI), while the clinical assessment of breastfeeding initiation was performed by the Breastfeeding Observation and Evaluation Form according to WHO-UNICEF guidelines. We also compared the reliability in predicting breastfeeding of a tool that measured the features of the tongue frenulum: the Bristol Tongue Assessment Tool (BTT). Breastfeeding at one and six months of babies' age was assessed by telephone interview, and information among children's nutrition, weight growth and difficulties found in breastfeeding was also collected. This study was approved by the Pediatric Ethics Committee for Clinical Trials of the Tuscany Region. RESULTS: One hundred and ninety infants were included in the study; 21 (11.05%) had a MLFPI score ≥13. Data at one month of age showed a statistically higher MLFPI score (P value <0.001) in babies with breastfeeding difficulties (median score 13.0, IQR 5.5-14), than in those without (median score 5.0, IQR 2.0-7.5). Data at 6 months of age showed a similar difference in babies with and without breastfeeding difficulties (median 12.0, IQR 4.0-14.0 vs. 5.0, IQR 2.0-8.0 respectively). A MLFPI score ≥13 is positively associated with breastfeeding difficulties at 1 and 6 months. Also, the BTT was positively a risk factor for problems in breastfeeding at 1 and 6 months. CONCLUSIONS: A high MLFPI score is a risk factor of breastfeeding difficulties. In these cases, a referral to experienced personnel is advisable: they can provide the emotional and professional support to the mother-child dyad, and/or refer for surgical evaluation and frenotomy. In our cohort, the usefulness of either MLFPI score or BTT was evident in predicting breastfeeding difficulties; the rate of surgical removal of the frenulum was nonetheless low.

Abortion and subsequent mental health: Review of the literature.

The risk that abortion may be correlated with subsequent mental disorders needs a careful assessment, in order to offer women full information when facing a difficult pregnancy. All research papers published between 1995 and 2011, were examined, to retrieve those assessing any correlation between abortion and subsequent mental problems. A total of 36 studies were retrieved, and six of them were excluded for methodological bias. Depression, anxiety disorders (e.g. post-traumatic stress disorder) and substance abuse disorders were the most studied outcome. Abortion versus childbirth: 13 studies showed a clear risk for at least one of the reported mental problems in the abortion group versus childbirth, five papers showed no difference, in particular if women do not consider their experience of fetal loss to be difficult, or if after a fetal reduction the desired fetus survives. Only one paper reported a worse mental outcome for childbearing. Abortion versus unplanned pregnancies ending with childbirth: four studies found a higher risk in the abortion groups and three, no difference. Abortion versus miscarriage: three studies showed a greater risk of mental disorders due to abortion, four found no difference and two found that short-term anxiety and depression were higher in the miscarriage group, while long-term anxiety and depression were present only in the abortion group. In conclusion, fetal loss seems to expose women to a higher risk for mental disorders than childbirth; some studies show that abortion can be considered a more relevant risk factor than miscarriage; more research is needed in this field.

Neonatal Infant Pain Scale in assessing pain and pain relief for newborn male circumcision.

Circumcision-partial or total removal of the penile prepuce-requires cutting nerve-laden, sensitive genital tissue and is therefore liable to be painful. The aim of this review is to evaluate the evidence concerning pain felt by newborns during circumcision and to determine whether current analgesic methods can eliminate such pain. I performed a search in medical databases, selecting the trials published in the last 20 years that assessed pain in neonatal circumcision. Twenty-three trials have been retrieved. To get reliable findings, those trials that used validated pain scales were selected; then it was investigated which trials had comparable data for using the same pain scale. The only pain scale that was used in more than two trials was the modified Neonatal Infant Pain Scale (mNIPS) that ranges 0-6. The results of these trials show that none of the analgesic strategies used obtained the absence of pain. Some differences between circumcision techniques can be noticed, but most assessments exceed the score of 3, chosen as the clinically significant pain.

Normal values of creatine kinase and of MB-creatine kinase at birth in healthy babies.

BACKGROUND: Today, few studies have been accomplished in order to determine serum creatine kinase (CK) activity in newborns by considering small groups of babies and without taking into account gestational age (GA) differences. Some authors have demonstrated that neonatal CK activity value at birth is higher than the normal range of CK activity considering for adults or older children. The objective of this study is to assess normal values of CK and MB-CK in neonatal blood, according to babies' GA. METHODS: We retrieved the clinical files of 140 babies admitted into Siena Hospital NICU in a 2-years period, when CK was assessed routinely to all babies at birth. We selected files from 114 newborns and we divided the cohort into group A (non-stressed; N.=41) and group B (stressed; N.=73) on the basis of Apgar Score and signs of neurological lesions. We compared CK and MB-CK values in the two groups according to GA. RESULTS: Mean CK value of the 41 non-stressed babies' samples: 413 IU/L (232 SD). CK significantly increases with GA. No differences are present in total CK activity between stressed vs. non-stressed babies; but a significant difference appears in these two groups for MB-CK (mean values: 456 vs. 175 IU/L). CONCLUSIONS: This is the first study that compares CK and MB-CK values at birth according to the GA of the babies. CK values increase with GA, and stressed babies have higher MB-CK values than the non-stressed babies. These reference values are important for clinical practice.

Consents or waivers of responsibility? Parents' information in NICU.

BACKGROUND: Informing the patient is a base of modern medicine; nonetheless, a great discrepancy exists between hospitals on the way this information should be administered. This is particularly important when the patient are babies: the information should be given to their parents who should approve or disapprove the treatment. Aim of this study is to assess the adequacy of the information administered to the parents of babies admitted into the Neonatal Intensive Care Units. METHODS: We analyzed the consent forms of center-north Italy NICUs. To this aim, we assessed if the forms had acceptable length and other features; we then asked some volunteers to simulate an information process and to score the forms for their easiness, comprehensibility and explicability to others. RESULTS: Twenty-one NICUs accepted to participate. Only 7 out of 21 had an adequate information form; the other 14 could be described as "waiver of responsibility" (WOR), because they were too prolix and contained too many hypothetical procedures. The overall level of easiness, comprehensibility and explicability to others was suboptimal, being lower in those forms we defined WOR. CONCLUSIONS: The results are far to be optimal. More care should be devoted to the process of informing parents at the admission into the NICU: an information overload should be avoided and information should be tailored on the baby's state. Further analysis should be devoted to whether the use of WOR is routine in other countries.

Values of PCT in neonates.

BACKGROUND: Procalciton (PCT) is a precursor polypeptide of the hormone calcitonin, produced in C cells of the thyroid. It has been demonstrated that microbial toxins and proinflammatory mediators can cause the release of PCT from tissues and cells in the body. PCT thus has become an important marker in the diagnosis of infection. METHODS: In this retrospective study we analyzed blood samples performed for clinical purposes from the newborns present in our hospital in the year 2019. We developed a database of 1356 PCT values obtained from 224 infants at risk for neonatal infection; we selected those PCT values obtained within 24 hours from a blood sampling for blood culture. RESULTS: Babies with positive blood culture had PCT values more elevated than those with negative blood culture (17.061 ng/mL [C.I. 10.8-23.2] vs. 4.6 ng/mL [C.I. 2.6-6.6]). No statistically significant difference was found between babies with negative blood culture born before or after 37 weeks of gestation. CONCLUSIONS: This paper gives useful data of PCT values in non-infective babies. It is worth to show that the normality values should not be confused with those of older children or adults. Moreover, it shows the reliability of PCT as an infection index.

The ethics of pain clinical trials on persons lacking judgment ability: much to improve.

AIM: People lacking judgmental ability (newborn infants [NIs] and persons with mental impairment [PMI]) are reported to receive less analgesic treatments than people who can give adequate informed consent. We performed the present study to assess whether this also happens in clinical trials that should statutorily guarantee basic patients' rights. We examined those trials in which patients undergo painful minor procedures (PMP) because these procedures are frequent and severely stressful for NI and PMI. MATERIALS AND METHODS: We performed a Medline search to retrieve the studies published in 2009 and 2010, in which NI and PMI underwent PMP. RESULTS: 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 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. All these studies were not performed to evaluate a possible analgesic strategy but to assess PMI's pain responsiveness and no analgesia was used. CONCLUSION: 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. These data raise concern about the actual guarantees for persons lacking judgmental ability enrolled in potentially painful trials. We also recommend more effort to find out analgesic treatments tailored to the specific exigencies of PMI.

Distracting effect of TV watching on children's reactivity.

The experiment, aimed to evaluate the distracting effect of television, was carried out on 122 children, divided into three groups. All groups performed the auditory vigilance test (AVT) to assess reaction time (RT) to an auditory stimulus and the number of errors in responding to the stimulus. Children in group 1 performed the AVT while in front of a blank TV set and listening to the soundtrack of a movie (SO test), then watching a black and white cartoon (BW test). Children in group 2 performed the AVT while in front of a blank TV set and listening to the soundtrack of a movie (SO test), then watching a color cartoon (CC test). Group 3 performed SO, BW, and CC tests consecutively. RT and the number and type of errors were measured. In each group, 30 days separated one session from the following. A significant increase of median RTs (more than 10%) and errors (twice and more) was observed both in the case of BW and CC tests with respect to SO test. RT increased throughout all tests. During SO test, errors are mainly "false reactions", but in BW and CC tests, errors are more numerous, and they are mainly "omissions". TV movies have a significant distracting and attention-capturing effect, which increases throughout the vision of the show. No advantage in decreasing this effect is offered by removing color from the movie.

Nurses and Doctors Heroes? A Risky Myth of the COVID19 Era.

Recent newspapers reports have named health professionals as "heroes". This is surprising, because in the last few decades, doctors and nurses have been taken into account by mass media only to describe cases of misconduct or of violence. This change was due to the coronavirus pandemic scenario that has produced fear in the population and the need for an alleged "savior". This need for health professionals seen as heroes is also disclosed by the fact that even politicians have abdicated to their role in favor of the healthcare "experts" to whom important decisions on social life during this pandemic have been delegated, even those decisions that fall outside of the specific health field. This commentary is a claim to framing the job of caregivers in its correct role, neither angel nor devil, but allied to the suffering person, that the image of "heroes" risks to overshadow.

Flaws in the assessment of the best interests of the newborn.

UNLABELLED: We examined the literature on ethical decisions regarding neonates, to assess whether personal beliefs and prejudices influence end-of-life decisions taken by caregivers. Studies show that religion and familiarity with disability influence caregivers' decisions, whereas the influx of already being a parent, age, sex and professional experience is controverse. Caregivers' attitudes towards end-of-life decisions are also affected by personal concerns about litigation, prejudices and their view of disability. The concept of 'poor quality of life' is widely used as a reference in end-of-life decisions, but this can be interpreted differently, leaving room for a wide range of personal viewpoints. In most cases, parents' opinions are considered important and are sometimes the main determinant in decision making. However, it is unclear whether parents' decisions are based on their own wishes or on the best interests of the newborn. CONCLUSION: In neonatal end-of-life decisions, patients may not receive cures based only on their best interests.

New insights into fetal pain.

Fetal pain is difficult to assess, because the main feature needed to spot pain, is the subject's capability of declaring it. Nonetheless, much can be affirmed about this issue. In this review we first report the epochs of the development of human nociceptive pathways; then we review since when they are functioning. We also review the latest data about the new topic of analgesia and prenatal surgery and about the scarce effect on fetal pain sentience of the natural sedatives fetuses produce. It appears that pain is a neuroadaptive phenomenon that emerges in the middle of pregnancy, at about 20-22 weeks of gestation, and becomes more and more evident for bystanders and significant for the fetus, throughout the rest of the pregnancy.

Is fetal analgesia necessary during prenatal surgery?

Fetal 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. 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. 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. 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. RESULTS: Fetuses are awake about 10% of the total time in the last gestational weeks, and they can be aroused by external stimuli. ENIn have not an anesthetic effect at normal fetal values, but only when they areartificialy injected at high doses; their blood levels in the last trimester of average pregnancies are not dissimilar either in the fetus or in the mother. CONCLUSIONS: During the second half of the pregnancy, external stimuli can awake the fetuses, although they spend most of the time in sleeping state; the presence of ENIn is absolutely not enough to guarantee an effective anesthesia during surgery. Thus, direct fetal analgesia/anesthesia is mandatory, though further studies on its possible drawbacks are necessary.