Johan Ågren

Transepidermal water loss in infants born at 24 and 25 weeks of gestation

The rate of evaporation of water from the skin of 13 infants born at 24 (n= 3) and 25 (n= 10) weeks of gestation was measured on the first day after birth and at postnatal ages of 1,3,7 and 28 d, using the gradient method. Transepidermal water loss was estimated from this rate and corrected to an ambient relative humidity (RH) of 50%. Transepidermal water loss, corrected to 50% RH, was high on the first day after birth (58.4 ± 14.8gm 2 h?1) and remained at the same level during the second day (59.3 ± 17.6gm?2h?1). It then decreased significantly to 43.8 ± 9.5 at a postnatal age of 3 d, 36.1 ± 12.6 at 7 d and 24.2 ± 7.7gm?2h?1 at 28 d (p < 0.001). Within the group investigated, there was no significant correlation between transepidermal water loss and body or skin temperature, birth weight, gender, mode of delivery or gestational age. Transepidermal water loss on the first day after birth was somewhat lower than the highest losses previously found in infants born at 25 weeks of gestation, and of the same magnitude as previously reported for infants born at 25‐27 weeks. Transepidermal water loss at postnatal ages of 1,3,7 and 28 d in the present study was higher than that previously found in the group of infants born at 25‐27 weeks. In conclusion, in infants born at 24‐25 completed weeks of gestation transepidermal water loss was high immediately after birth and decreased with increasing postnatal age, but at a slower rate than previously reported for slightly more mature infants.

Transepidermal Water Loss in Developing Rats: Role of Aquaporins in the Immature Skin

In the extremely preterm infant, high transepidermal water loss (TEWL) can result in severe dehydration. TEWL has been attributed to the structural properties of the epidermis but might also be influenced by mechanisms that facilitate water transport. To investigate whether aquaporins (AQP) may be involved in the extreme losses of water through immature skin, we examined the presence and cellular distributions of AQP-1 and AQP-3 in embryonic and adult rat skin by immunohistochemistry. The expression of AQP mRNA in skin was analyzed with the use of semiquantitative reverse transcription-PCR. In rat pups of different embryonic (E) and postnatal (P) ages (days), TEWL and skin hydration were measured. AQP-1 was detected in dermal capillaries, and AQP-3 was abundant in basal epidermal layers. Both AQP displayed several times higher expression in embryonic than in adult skin. TEWL was highest at embryonic day 18 (E18) (133 ± 18 g/m2h) and lower at E20 (25 ± 1 g/m2h) and P4 (9 ± 2 g/m2h). Skin hydration measured as skin electrical capacitance paralleled TEWL, being highest in fetal skin (794 ± 15 pF at E18) and decreasing to 109 ± 11 pF at E20 and to 0 ± 0 pF at P4. We conclude that, as in infants, water loss through the skin of rats decreases markedly with maturation during the perinatal period. The expression and cellular localization of the AQP are such that they might influence skin hydration and water transport and contribute to the high losses of water through the immature skin.

Systematic review of neonatal seizure management strategies provides guidance on anti-epileptic treatment.

There is a lack of scientific evidence to support the best management of neonatal seizures. Current strategies for neonatal seizure management were investigated by analysis of all surveys published during the time period 2000–2012. Methods for seizure diagnosis and availability of electroencephalogram (EEG), including monitoring, varied. Phenobarbital was the drug of first choice, and the use of off‐label drugs and treatment times varied. Conclusion: We conclude that there is an urgent need for more evidence‐based studies to guide neonatal seizure management.

Efficacy and safety of lidocaine for treatment of neonatal seizures.

Treatment of neonatal seizures still relies primarily on phenobarbital, despite an estimated efficacy of less than 50% and concern over neurodegenerative side effects. The objective of this study was to evaluate the efficacy and safety of lidocaine as second‐line treatment of neonatal seizures in infants following benzodiazepine treatment but without previous treatment with phenobarbital.

Skin conductance measurements as pain assessment in newborn infants born at 22-27 weeks gestational age at different postnatal age

BACKGROUND To assess pain or stress in newborn infants submitted to intensive care is important but difficult, as different observational pain scales are not always reliable in premature infants. As an indicator of pain, skin conductance (SC) measurements have detected increased sweating in newborn infants >28 gestational age (GA) submitted to heel lancing. OBJECTIVE To measure SC during heel lancing and routine care in newborn infants, born at 22 to 27 GA, with special relation to postnatal age (PNA). METHODS In six infants <28+0 GA and 4 infants ≥28+0 GA spontaneous SC activity and behavioural state (Neonatal Pain Agitation and Sedation Scale (N-PASS)) was measured before, during and after each intervention. Measurements were repeated in each patient at different PNA. RESULTS Baseline SC prior to intervention took longer time to stabilise and was higher in <28 than in ≥28+0 PNA. The combination of heel lancing and squeezing gave an increased SC in <28 PNA, whereas heel lancing alone gave the same SC response in ≥28+0 PNA. A possibly continued immature response in SC measurements was not observed. Oral glucose admission prior to heel lancing increased SC. Routine care did not give any changes in SC. Except during orogastric tube placement no signs of discomfort or pain could be detected by the neonatal pain, agitation and sedation scale (N-PASS) in <28 PNA. CONCLUSION Changes in SC could be detected in infants at <28+0 PNA and related to the combination of heel lancing and squeezing. A maturational development of the SC was observed in infants born <28 GA. SC seems to be able to differentiate between pain and discomfort.

Suboptimal care and metabolic acidemia is associated with neonatal encephalopathy but not with neonatal seizures alone: a population‐based clinical audit

To determine the incidence of moderate to severe neonatal encephalopathy (NE) and neonatal seizures without encephalopathy, and the association with metabolic acidemia. Secondly, to investigate the occurrence of suboptimal intrapartum care and its impact on neonatal outcome.

Water and heat--the priority for the newborn infant.

Maintaining fluid and heat balance is of vital importance to the newborn infant. At birth, the infant is exposed to a cold and dry environment, and preterm neonates in particular, are then at risk of dehydration and hypothermia. These conditions may have serious consequences and significantly influence mortality and morbidity. Preterm neonates have a high rate of water and heat loss mainly as a consequence of their immature skin. The care environment influences the magnitude of water and heat exchange and needs to be individually tailored on the basis of the infants clinical status, maturity at birth and postnatal age. This paper reviews data obtained from series of studies on neonatal water and heat exchange using non-invasive measurements of insensible water loss and calculations of different modes of heat exchange. These studies have influenced the way in which newborn infants are being nursed today.

Antenatal Corticosteroids and Postnatal Fluid Restriction Produce Differential Effects on AQP3 Expression, Water Handling, and Barrier Function in Perinatal Rat Epidermis

Loss of water through the immature skin can lead to hypothermia and dehydration in preterm infants. The water and glycerol channel aquaglyceroporin-3 (AQP3) is abundant in fetal epidermis and might influence epidermal water handling and transepidermal water flux around birth. To investigate the role of AQP3 in immature skin, we measured in vivo transepidermal water transport and AQP3 expression in rat pups exposed to clinically relevant fluid homeostasis perturbations. Preterm (E18) rat pups were studied after antenatal corticosteroid exposure (ANS), and neonatal (P1) rat pups after an 18 h fast. Transepidermal water loss (TEWL) and skin hydration were determined, AQP3 mRNA was quantified by RT-PCR, and in-situ hybridization and immunocytochemistry were applied to map AQP3 expression. ANS resulted in an improved skin barrier (lower TEWL and skin hydration), while AQP3 mRNA and protein increased. Fasting led to loss of barrier integrity along with an increase in skin hydration. These alterations were not paralleled by any changes in AQP3. To conclude, antenatal corticosteroids and early postnatal fluid restriction produce differential effects on skin barrier function and epidermal AQP3 expression in the rat. In perinatal rats, AQP3 does not directly determine net water transport through the skin.

Transcutaneous Pco(2) Monitoring in. Newborn Infants During General Anesthesia Is Technically Feasible

BACKGROUND:Transcutaneous (TC) measurement of PCO2 (TC PCO2) is a well-established method to monitor assisted ventilation in neonatal intensive care, but its use in the operating room is limited, and the data regarding its performance during general anesthesia of the newborn are lacking. The aim of this study is to evaluate the performance of continuous TC PCO2 monitoring during general anesthesia in newborn infants. METHODS:Infants (n = 25) with a gestational age of 23 to 41 weeks and a birth weight of 548 to 4114 g were prospectively enrolled. During general anesthesia and surgery, TC PCO2 was measured continuously and recorded at 1-minute intervals. Five-minute mean values were compared with simultaneously obtained blood gas (BG) analyses of PCO2. Only the first paired TC and BG samples were used in this analysis. We defined precision as 2.1 times the standard deviation of the difference of the 2 samples. P < .01 was considered statistically significant. RESULTS:We obtained samples from 25 infants. The difference between TC and BG was 0.3 ± 0.7 kPa (mean ± standard deviation) giving a precision of 1.47 kPa. Nineteen of twenty-five (76%) sample pairs displayed a difference of <1 kPa (99% confidence interval, 48%–92%, P = .016). The difference in paired samples was similar for different gestational and postnatal ages and did not appear to be affected by electrocautery. CONCLUSIONS:In this small study, we did not demonstrate that TC CO2 monitoring was accurate at P < .01. This partly reflects the small size of the study, resulting in wide 99% confidence bounds.

Adverse effects following lidocaine treatment are limited with current dosing regimens

Sir, We read with great interest the article by Lundqvist et al. (1), which evaluated the efficacy and safety of lidocaine for treating neonatal seizures in infants (gestational age ≥37 week, age ≤28 days) following benzodiazepines, but not preceding phenobarbital treatment. The authors reported that the treatment stopped seizures in 16 of the 30 infants studied. Suspected adverse effects were only seen in one patient, who developed a transient bradycardia. Indeed, several studies indicate that lidocaine is an effective agent for intractable neonatal seizures that do not respond to firstgeneration antiepileptic drugs (AEDs). However, data on the use of lidocaine are limited and it is used off-label in neonates with refractory seizures (2). Phenobarbital, a firstgeneration AED, is still widely used for the treatment of neonatal seizures. It is still preferable because of its efficacy and tolerability. In addition, it is a cost-effective pharmacologic treatment for lowand middle-income countries. There are some disadvantages of lidocaine in clinical practice. For example, the distribution volume and unbound fraction of lidocaine is greater in neonates than in adults who have a low concentration of plasma proteins. In addition, lower glomerular filtration rates reduce renal clearance of lidocaine and its active metabolites, thereby increasing the risk of toxicity in neonates when used for prolonged periods. There is no consensus regarding the dose of lidocaine infusion. Its higher plasma concentrations may cause seizure activity (‘proconvulsant’ effect), and one study highlighted the risk of developing cardiac arrhythmias (bradycardia, tachycardia, prolonged QRS complex and/or irregular heart) (3). For this reason, continuous cardiac and serum monitoring of neonates is indicated. Furthermore, neurotoxic effects of lidocaine in newborns are also reported. Therefore, we think that lidocaine should only be used as an alternative treatment in infants who are not responding to first-generation AEDs. There is an urgent need for prospective, randomised, controlled trials to assess the pharmacokinetic, efficacy and safety of lidocaine in neonates.