Mathias Nelle

The efficacy of non-pharmacological interventions in the management of procedural pain in preterm and term neonates: A systematic literature review

Background: Neonates in a neonatal intensive care unit are exposed to a high number of painful procedures. Since repeated and sustained pain can have consequences for the neurological and behaviour‐oriented development of the newborn, the greatest attention needs to be paid to systematic pain management in neonatology. Non‐pharmacological treatment methods are being increasingly discussed with regard to pain prevention and relief either alone or in combination with pharmacological treatment.

Toxic epidermal necrolysis and Stevens-Johnson syndrome: A review*

Objectives: The aims of this review are to summarize the definitions, causes, and clinical course as well as the current understanding of the genetic background, mechanism of disease, and therapy of toxic epidermal necrolysis and Stevens-Johnson syndrome. Data Sources: PubMed was searched using the terms toxic epidermal necrolysis, Stevens-Johnson syndrome, drug toxicity, drug interaction, and skin diseases. Data Synthesis: Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute inflammatory skin reactions. The onset is usually triggered by infections of the upper respiratory tract or by preceding medication, among which nonsteroidal anti-inflammatory agents, antibiotics, and anticonvulsants are the most common triggers. Initially the diseases present with unspecific symptoms, followed by more or less extensive blistering and shedding of the skin. Complete death of the epidermis leads to sloughing similar to that seen in large burns. Toxic epidermal necrolysis is the most severe form of drug-induced skin reaction and includes denudation of >30% of total body surface area. Stevens-Johnson syndrome affects <10%, whereas involvement of 10%–30% of body surface area is called Stevens-Johnson syndrome/toxic epidermal necrolysis overlap. Besides the skin, mucous membranes such as oral, genital, anal, nasal, and conjunctival mucosa are frequently involved in toxic epidermal necrolysis and Stevens-Johnson syndrome. Toxic epidermal necrolysis is associated with a significant mortality of 30%–50% and long-term sequelae. Treatment includes early admission to a burn unit, where treatment with precise fluid, electrolyte, protein, and energy supplementation, moderate mechanical ventilation, and expert wound care can be provided. Specific treatment with immunosuppressive drugs or immunoglobulins did not show an improved outcome in most studies and remains controversial. The mechanism of disease is not completely understood, but immunologic mechanisms, cytotoxic reactions, and delayed hypersensitivity seem to be involved. Conclusion: Profound knowledge of exfoliative skin diseases is needed to improve therapy and outcome of these life-threatening illnesses.

Salt Sensitivity of Children With Low Birth Weight

Compromised intrauterine fetal growth leading to low birth weight (<2500 g) is associated with adulthood renal and cardiovascular disease. The aim of this study was to assess the effect of salt intake on blood pressure (salt sensitivity) in children with low birth weight. White children (n=50; mean age: 11.3±2.1 years) born with low (n=35) or normal (n=15) birth weight and being either small or appropriate for gestational age (n=25 in each group) were investigated. The glomerular filtration rate was calculated using the Schwartz formula, and renal size was measured by ultrasound. Salt sensitivity was assigned if mean 24-hour blood pressure increased by ≥3 mm Hg on a high-salt diet as compared with a controlled-salt diet. Baseline office blood pressure was higher and glomerular filtration rate lower in children born with low birth weight as compared with children born at term with appropriate weight (P<0.05). Salt sensitivity was present in 37% and 47% of all of the low birth weight and small for gestational age children, respectively, higher even than healthy young adults from the same region. Kidney length and volume (both P<0.0001) were reduced in low birth weight children. Salt sensitivity inversely correlated with kidney length (r2=0.31; P=0.005) but not with glomerular filtration rate. We conclude that a reduced renal mass in growth-restricted children poses a risk for a lower renal function and for increased salt sensitivity. Whether the changes in renal growth are causative or are the consequence of the same abnormal “fetal programming” awaits clarification.

The adsorption of biomolecules to multi-walled carbon nanotubes is influenced by both pulmonary surfactant lipids and surface chemistry

BackgroundDuring production and processing of multi-walled carbon nanotubes (MWCNTs), they may be inhaled and may enter the pulmonary circulation. It is essential that interactions with involved body fluids like the pulmonary surfactant, the blood and others are investigated, particularly as these interactions could lead to coating of the tubes and may affect their chemical and physical characteristics. The aim of this study was to characterize the possible coatings of different functionalized MWCNTs in a cell free environment.ResultsTo simulate the first contact in the lung, the tubes were coated with pulmonary surfactant and subsequently bound lipids were characterized. The further coating in the blood circulation was simulated by incubating the tubes in blood plasma. MWCNTs were amino (NH2)- and carboxyl (-COOH)-modified, in order to investigate the influence on the bound lipid and protein patterns. It was shown that surfactant lipids bind unspecifically to different functionalized MWCNTs, in contrast to the blood plasma proteins which showed characteristic binding patterns. Patterns of bound surfactant lipids were altered after a subsequent incubation in blood plasma. In addition, it was found that bound plasma protein patterns were altered when MWCNTs were previously coated with pulmonary surfactant.ConclusionsA pulmonary surfactant coating and the functionalization of MWCNTs have both the potential to alter the MWCNTs blood plasma protein coating and to determine their properties and behaviour in biological systems.

Oral Sucrose and “Facilitated Tucking” for Repeated Pain Relief in Preterms: A Randomized Controlled Trial

OBJECTIVES: To test the comparative effectiveness of 2 nonpharmacologic pain-relieving interventions administered alone or in combination across time for repeated heel sticks in preterm infants. METHODS: A multicenter randomized controlled trial in 3 NICUs in Switzerland compared the effectiveness of oral sucrose, facilitated tucking (FT), and a combination of both interventions in preterm infants between 24 and 32 weeks of gestation. Data were collected during the first 14 days of their NICU stay. Three phases (baseline, heel stick, recovery) of 5 heel stick procedures were videotaped for each infant. Four independent experienced nurses blinded to the heel stick phase rated 1055 video sequences presented in random order by using the Bernese Pain Scale for Neonates, a validated pain tool. RESULTS: Seventy-one infants were included in the study. Interrater reliability was high for the total Bernese Pain Scale for Neonates score (Cronbach’s α: 0.90–0.95). FT alone was significantly less effective in relieving repeated procedural pain (P < .002) than sucrose (0.2 mL/kg). FT in combination with sucrose seemed to have added value in the recovery phase with lower pain scores (P = .003) compared with both the single-treatment groups. There were no significant differences in pain responses across gestational ages. CONCLUSIONS: Sucrose with and without FT had pain-relieving effects even in preterm infants of <32 weeks of gestation having repeated pain exposures. These interventions remained effective during repeated heel sticks across time. FT was not as effective and cannot be recommended as a nonpharmacologic pain relief intervention for repeated pain exposure.

Carotenoid supply in breast-fed and formula-fed neonates

Abstract Carotenoids have various biological functions including their role as antioxidants. For humans fruits and vegetables are the only source of carotenoids. In the first months breast milk and/or formula preparations are the only nutrition for infants. To study the influence of nutrition on the plasma carotenoid profile in newborns, breast milk, different formula preparations, and the plasma of breast-fed (BF) and formula-fed (FF) newborns were analyzed by high-performance liquid chromatography. The method used allowed β-carotene, α-carotene, lycopene, and β-cryptoxanthine to be detected and all four were found in breast milk. In colostrum carotenoids were up to five times higher than in mature breast milk (P < 0.05). In contrast, not all carotenoids could be found in formula preparations. β-Carotene was detected in four out of eight, and β-cryptoxanthine in three out of eight formula preparations. Lycopene and α-carotene were not detectable in any of the formula preparations. Four formula preparations did not contain any carotenoids. FF infants had different plasma carotenoid profiles compared to BF infants. β-Carotene was significantly lower in FF infants [14 (0–32) μg/l, median and interquartile ranges] than in infants after birth [24 (19–310) μg/l, P < 0.05], and BF infants [32 (22–63) μg/l, P < 0.05]. While newborns after birth had measurable plasma concentrations of lycopene (16 [14–18] μg/l) and of α-carotene [5 (0–8) μg/l), these carotenoids were no longer detectable in FF infants after day 14. Conclusion FF and BF infants show significant biochemical differences in plasma carotenoid concentrations.

The effect of Leboyer delivery on blood viscosity and other hemorheologic parameters in term neonates

OBJECTIVE This study was done to compare postnatal alterations in blood viscosity, hematocrit value, plasma viscosity, red blood cell aggregation, and red blood cell deformability in term neonates undergoing both early umbilical cord clamping and delivery according to the Leboyer method. STUDY DESIGN The umbilical cords of 15 healthy, term infants were clamped within 10 seconds of birth (early cord clamping), and 15 infants delivered according to the Leboyer method were placed on the mothers abdomen, and the umbilical cords were clamped 3 minutes after birth. Hemorheologic parameters were studied in umbilical cord blood at 2 hours, 24 hours, and 5 days from the time of delivery. RESULTS The residual fetal placental blood volume decreased from 45 +/- 8 ml/kg (x +/- SD) after early cord clamping to 25 +/- 5 ml/kg after delivery by the Leboyer method. After Leboyer-method delivery, the hematocrit value rose from 48% +/- 5% at birth to 58% +/- 6% 2 hours after delivery, 56% +/- 7% at 24 hours, and 54% +/- 8% after 5 days. Blood viscosity in the Leboyer-method group increased by 32% within the first 2 hours but did not change significantly during the following 5 days. Plasma viscosity, red blood cell aggregation, and red blood cell deformability were not affected by the mode of cord clamping. CONCLUSIONS Delivery by the Leboyer method leads to a significant increase in blood viscosity as a result of increasing hematocrit value, whereas other hemorheologic parameters are similar to those of infants with early cord clamping.

Perinatal care at the limit of viability between 22 and 26 completed weeks of gestation in Switzerland 2011 Revision of the Swiss recommendations

Perinatal care of pregnant women at high risk for preterm delivery and of preterm infants born at the limit of viability (22-26 completed weeks of gestation) requires a multidisciplinary approach by an experienced perinatal team. Limited precision in the determination of both gestational age and foetal weight, as well as biological variability may significantly affect the course of action chosen in individual cases. The decisions that must be taken with the pregnant women and on behalf of the preterm infant in this context are complex and have far-reaching consequences. When counselling pregnant women and their partners, neonatologists and obstetricians should provide them with comprehensive information in a sensitive and supportive way to build a basis of trust. The decisions are developed in a continuing dialogue between all parties involved (physicians, midwives, nursing staff and parents) with the principal aim to find solutions that are in the infants and pregnant womans best interest. Knowledge of current gestational age-specific mortality and morbidity rates and how they are modified by prenatally known prognostic factors (estimated foetal weight, sex, exposure or nonexposure to antenatal corticosteroids, single or multiple births) as well as the application of accepted ethical principles form the basis for responsible decision-making. Communication between all parties involved plays a central role. The members of the interdisciplinary working group suggest that the care of preterm infants with a gestational age between 22 0/7 and 23 6/7 weeks should generally be limited to palliative care. Obstetric interventions for foetal indications such as Caesarean section delivery are usually not indicated. In selected cases, for example, after 23 weeks of pregnancy have been completed and several of the above mentioned prenatally known prognostic factors are favourable or well informed parents insist on the initiation of life-sustaining therapies, active obstetric interventions for foetal indications and provisional intensive care of the neonate may be reasonable. In preterm infants with a gestational age between 24 0/7 and 24 6/7 weeks, it can be difficult to determine whether the burden of obstetric interventions and neonatal intensive care is justified given the limited chances of success of such a therapy. In such cases, the individual constellation of prenatally known factors which impact on prognosis can be helpful in the decision making process with the parents. In preterm infants with a gestational age between 25 0/7 and 25 6/7 weeks, foetal surveillance, obstetric interventions for foetal indications and neonatal intensive care measures are generally indicated. However, if several prenatally known prognostic factors are unfavourable and the parents agree, primary non-intervention and neonatal palliative care can be considered. All pregnant women with threatening preterm delivery or premature rupture of membranes at the limit of viability must be transferred to a perinatal centre with a level III neonatal intensive care unit no later than 23 0/7 weeks of gestation, unless emergency delivery is indicated. An experienced neonatology team should be involved in all deliveries that take place after 23 0/7 weeks of gestation to help to decide together with the parents if the initiation of intensive care measures appears to be appropriate or if preference should be given to palliative care (i.e., primary non-intervention). In doubtful situations, it can be reasonable to initiate intensive care and to admit the preterm infant to a neonatal intensive care unit (i.e., provisional intensive care). The infants clinical evolution and additional discussions with the parents will help to clarify whether the life-sustaining therapies should be continued or withdrawn. Life support is continued as long as there is reasonable hope for survival and the infants burden of intensive care is acceptable. If, on the other hand, the health care team and the parents have to recognise that in the light of a very poor prognosis the burden of the currently used therapies has become disproportionate, intensive care measures are no longer justified and other aspects of care (e.g., relief of pain and suffering) are the new priorities (i.e., redirection of care). If a decision is made to withhold or withdraw life-sustaining therapies, the health care team should focus on comfort care for the dying infant and support for the parents.

Diffusion-weighted MR Imaging of the Placenta in Fetuses with Placental Insufficiency

PURPOSE To evaluate diffusion-weighted magnetic resonance (MR) imaging of the human placenta in fetuses with and fetuses without intrauterine growth restriction (IUGR) who were suspected of having placental insufficiency. MATERIALS AND METHODS The study was approved by the local ethics committee, and written informed consent was obtained. The authors retrospectively evaluated 1.5-T fetal MR images from 102 singleton pregnancies (mean gestation ± standard deviation, 29 weeks ± 5; range, 21-41 weeks). Morphologic and diffusion-weighted MR imaging were performed. A region of interest analysis of the apparent diffusion coefficient (ADC) of the placenta was independently performed by two observers who were blinded to clinical data and outcome. Placental insufficiency was diagnosed if flattening of the growth curve was detected at obstetric ultrasonography (US), if the birth weight was in the 10th percentile or less, or if fetal weight estimated with US was below the 10th percentile. Abnormal findings at Doppler US of the umbilical artery and histopathologic examination of specimens from the placenta were recorded. The ADCs in fetuses with placental insufficiency were compared with those in fetuses of the same gestational age without placental insufficiency and tested for normal distribution. The t tests and Pearson correlation coefficients were used to compare these results at 5% levels of significance. RESULTS Thirty-three of the 102 pregnancies were ultimately categorized as having an insufficient placenta. MR imaging depicted morphologic changes (eg, infarction or bleeding) in 27 fetuses. Placental dysfunction was suspected in 33 fetuses at diffusion-weighted imaging (mean ADC, 146.4 sec/mm(2) ± 10.63 for fetuses with placental insufficiency vs 177.1 sec/mm(2) ± 18.90 for fetuses without placental insufficiency; P < .01, with one false-positive case). The use of diffusion-weighted imaging in addition to US increased sensitivity for the detection of placental insufficiency from 73% to 100%, increased accuracy from 91% to 99%, and preserved specificity at 99%. CONCLUSION Placental dysfunction associated with growth restriction is associated with restricted diffusion and reduced ADC. A decreased ADC used as an early marker of placental damage might be indicative of pregnancy complications such as IUGR. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10092283/-/DC1.

Differential Role of the Lectin Pathway of Complement Activation in Susceptibility to Neonatal Sepsis

BACKGROUND. The incidence of bacterial sepsis during the neonatal period is high. Mannan-binding lectin (MBL), L-ficolin, and H-ficolin recognize microorganisms and activate the complement system via MBL-associated serine proteases (MASPs). This study investigated whether cord blood concentrations of the lectin pathway proteins are associated with neonatal sepsis. METHODS. This was a case-control study including 47 infants with culture-proven sepsis during the first month of life and 94 matched controls. MBL, L-ficolin, H-ficolin, MASP-2, and MASP-3 levels were measured in cord blood with use of enzyme-linked immunosorbent assay and time-resolved immunofluorometric assay. Multivariate logistic regression was performed. RESULTS. Infants with gram-positive sepsis had significantly lower H-ficolin cord blood concentrations than controls (multivariate odds ratio [OR], 4.00; 95% confidence interval [CI], 1.51-10.56; P = .005), whereas infants with gram-negative sepsis had lower MBL cord blood concentrations (OR, 2.99; 95% CI, 0.86-10.33; P = .084). When excluding patients with postoperative sepsis, multivariate analysis confirmed that low H-ficolin was associated with a significantly higher risk of gram-positive sepsis (OR, 3.71; 95% CI, 1.26-10.92; P = .017) and late-onset sepsis (OR, 3.14; 95% CI, 1.07-9.21; P = .037). In contrast, low MBL was associated with a significantly higher risk of gram-negative sepsis (OR, 4.39; 95% CI, 1.10-17.45; P = .036) and early-onset sepsis (OR, 3.87; 95% CI, 1.05-14.29; P = .042). The concentrations of all the lectin pathway proteins increased with gestational age (P < .01). CONCLUSIONS. These preliminary results indicate that low MBL concentrations are a susceptibility factor for gram-negative sepsis, and low H-ficolin concentrations indicate susceptibility to gram-positive sepsis. The decreased expression of lectin pathway proteins in neonates must be considered to be an additional form of neonatal immunodeficiency.