Cecilia Janér

Expression of the Epithelial Sodium Channel in Airway Epithelium of Newborn Infants Depends on Gestational Age

OBJECTIVE. In the newborn infant, removal of fetal lung liquid from the airways depends on ion transport through the airway epithelium. The epithelial sodium channel is considered rate limiting for the postnatal clearance of lung liquid, but it is unknown whether during the early postnatal period the expression of epithelial sodium channel is associated with maturity. Our objective was to study the relationship between gestational age and epithelial sodium channel expression in airway epithelium. METHODS. In 90 newborn infants (preterm [gestational age < 37]: n = 29; term [gestational age ≥ 37]: n = 61), we measured the expression of epithelial sodium channel (reported as attomoles of subunit expression normalized to femtomoles of expression of cytokeratin 18) in nasal epithelium at 1 to 5 and 22 to 28 hours after birth. RESULTS. At 1 to 5 hours postnatally, airway expression of α-, β-, and γ-subunits of epithelial sodium channel was lower in preterm than in term infants. At this time point, significant correlations existed between gestational age and airway expression of α- and β-epithelial sodium channel. By 22 to 28 hours after birth, only the expression of β-epithelial sodium channel had decreased significantly in the preterm infants, whereas the expression of all epithelial sodium channel subunits had decreased significantly in the term infants. At this time point, no difference in expression of any of the subunits was found between preterm and term infants. CONCLUSIONS. Airway expression of epithelial sodium channel at 1 to 5 hours of age is significantly lower in preterm than in term infants. Low postnatal expression of α-, β-, and γ-epithelial sodium channel subunits in the airway epithelium may contribute to the development of respiratory distress in the preterm infant.

Cooling for Newborns with Hypoxic Ischemic Encephalopathy

adverse effects of cooling and ‘early’ indicators of neurodevelopmental outcome. Data Collection and Analysis: Four review authors independently selected, assessed the quality of and extracted data from the included studies. Study authors were contacted for further information. Meta-analyses were performed using risk ratios (RR) and risk differences (RD) for dichotomous data, and weighted mean difference for continuous data with 95% confidence intervals (CI). Main Results: We included 11 randomized controlled trials in this updated review, comprising 1,505 term and late preterm infants with moderate/severe encephalopathy and evidence of intrapartum asphyxia. Therapeutic hypothermia resulted in a statistically significant and clinically important reduction in the combined outcome of mortality or major neurodevelopmental disability to 18 months of age (typical RR 0.75 (95% CI 0.68–0.83); typical RD –0.15, 95% CI –0.20 to –0.10); number needed to treat for an additional beneficial outcome (NNTB) 7 (95% CI 5–10) (8 studies, 1,344 infants). Cooling also resulted in statistically significant reductions in mortality (typical RR 0.75 (95% CI 0.64–0.88), typical RD –0.09 (95% CI –0.13 to –0.04); NNTB 11 (95% CI 8–25) (11 studies, 1,468 infants) and in neurodevelopmental disability in survivors (typical RR 0.77 (95% CI 0.63–0.94), typical RD –0.13 (95% CI –0.19 to –0.07); NNTB 8 (95% CI 5–14) (8 studies, 917 infants). Some adverse effects of hypothermia included an increase sinus bradycardia and a significant increase in thrombocytopenia. Cochrane Abstract

Delayed Lung Liquid Absorption after Cesarean Section at Term

Background: Delayed postnatal removal of lung liquid may result in respiratory distress, which is more common in infants born by cesarean section. Vertical artefacts (B-lines) arising from the lung surface in lung ultrasound have been shown to correlate with the liquid content of the lungs. Objectives: We studied whether lung ultrasound could be used for the assessment of postnatal lung liquid in healthy term infants born vaginally and by cesarean section. Methods: Lung ultrasound was performed 1, 3 and 24 h after birth to 22 vaginally born infants and 20 infants born by elective cesarean section. The abundance of B-lines was scored for each infant and time point by two independent observers blinded to the mode of delivery and time point on the examination on a five-step scale. Results: In both groups, a significant decrease in abundance of B-lines, indicative of lung liquid absorption, was observed during the first 24 h. 3 h after birth cesarean section was associated with significantly higher lung liquid content than vaginal delivery. Conclusion: The noninvasive bedside ultrasound method for estimation of lung liquid is a promising tool for the early identification of infants at risk for pulmonary maladaptation.

Airway Expression of the Epithelial Sodium Channel α-Subunit Correlates With Cortisol in Term Newborns

BACKGROUND: Glucocorticoids have profound effects on lung maturation and function. In in vitro and animal models, they induce epithelial sodium channels (ENaCs) in the airway epithelium, a process that is important to perinatal lung fluid clearance. OBJECTIVE: The objective of this study was to determine whether, in newborn infants, airway ENaC expression is associated with cortisol concentrations. METHODS: Cord blood, saliva, and cells from nasal epithelium were obtained from 69 infants delivered at term. Epithelial and saliva sampling was repeated 3 times: <3, 22 to 29, and 40 to 54 hours postnatally. Cortisol, thyrotropin, and free triiodothyronine concentrations were measured with immunoassays, and expression of α-ENaC and β-ENaC was quantified with real-time reverse-transcriptase polymerase chain reaction. RESULTS: Expression of α-ENaC <30 minutes postnatally correlated with cord plasma cortisol in infants delivered by elective cesarean delivery. In addition, in the total study population <2 hours postnatally, α-ENaC expression correlated with salivary cortisol concentrations. β-ENaC expression, in contrast, showed no association with cortisol concentrations. A significant decrease in β-ENaC expression during the first postnatal day was revealed, whereas timing of the peak in α-ENaC expression seemed to depend on mode of delivery. CONCLUSIONS: These results support a role in humans for endogenous glucocorticoids in the regulation of airway ion transport. This finding may be a physiologic mechanism mediating pulmonary adaptation in the newborn infant.

Low monocyte HLA-DR expression as an indicator of immunodepression in very low birth weight infants

Background:As a protective response to an inflammatory stimulus, the antigen-presenting molecules (human leukocyte antigen-DR (HLA-DR)) on monocytes are downregulated. If severe, the response may lead to immunodepression or immunoparalysis, associated with an increased rate of morbidity and mortality in adults. In very low birth weight (VLBW) infants, birth and intensive care present major immunological challenges.Methods:We measured monocyte HLA-DR expression by flow cytometry and determined 13 plasma cytokines in 56 VLBW infants (gestational age (GA): 23.7–31.8 wk) and 25 controls (GA: 34.1–41.4 wk).Results:HLA-DR expression decreased postnatally both in VLBW and in control infants. In VLBW infants, GA and respiratory distress syndrome (RDS) both showed associations with HLA-DR nadir on day 3, when 45% of them met the criteria of immunodepression. HLA-DR expression was lower in those infants subsequently developing infection (74 vs. 49% (day 3) and 85 vs. 68% (day 7); both P = 0.002). Interleukin (IL)-6 on day 1 was a predictor of the HLA-DR nadir.Conclusion:VLBW infants are in a state of immunodepression postnatally. This immunodepression correlated with GA and was a predisposing factor for late infections. The downregulation of HLA-DR during RDS probably indicates an RDS-induced antigen load on the immune system.

Antenatal Betamethasone Associates with Transient Immunodepression in Very Low Birth Weight Infants

Background: Antenatal betamethasone (BM) treatment for mothers at risk for premature delivery is effective in reducing neonatal morbidity. Immunodepression, defined as monocyte human leukocyte antigen (HLA)-DR expression <60%, is common in patients in intensive care. In very low birth weight (VLBW) infants, immunodepression correlates with gestational age and may predispose to infections. Objectives: To evaluate whether timing of antenatal BM associates with immunodepression in VLBW infants. Methods: We determined monocyte HLA-DR expression by flow cytometry and measured 13 cytokines, cortisol, and BM in plasma from 56 VLBW infants. We calculated total glucocorticoid index as the sum of BM and cortisol at the ratio 33.3:1. Results: HLA-DR expression both in cord (R2 = 0.175, p = 0.033, n = 26) and on day 1 (R2 = 0.125, p = 0.011, n = 51) showed an association with timing of BM. A short interval from BM to birth induced more pronounced and prolonged immunodepression, with lower HLA-DR% on postnatal day 7. On day 3, 25 infants (45%) met the criteria of immunodepression. HLA-DR expression correlated negatively with total glucocorticoid index (cord: R2 = -0.573, p = 0.003, n = 13; day 1: R2 = -0.213, p = 0.008, n = 32). Elapsed time from maternal BM correlated positively with concentrations of cytokines IL-6 and IL-10 on day 1. Conclusions: In VLBW infants, antenatal BM associated with transient immunodepression in a time-dependent manner. Suppression of both anti- and proinflammatory cytokines occurred. These effects may lead to an increased risk for later infections.

Duration of Gestation and Mode of Delivery Affect the Genes of Transepithelial Sodium Transport in Pulmonary Adaptation

Background: Respiratory distress due to inadequate lung liquid clearance is a significant problem in infants delivered late preterm or early term, especially by elective cesarean delivery (CD). Lung liquid clearance depends on epithelial ion transport and in animals is induced by glucocorticoids. Objectives: In newborn late preterm and term infants to study airway epithelial gene expressions of epithelial sodium channel (ENaC), and the serum and glucocorticoid-inducible kinase 1 (SGK1), and their association with cortisol, mode of delivery, and gestational age (GA). Methods: Infants were delivered at 350/7-416/7 weeks. Cortisol in umbilical cord plasma was analyzed with liquid chromatography-tandem mass spectrometry. ENaC and SGK1 mRNAs in airway epithelial cells obtained within 3 h and at 1 day postnatally were quantified with real-time PCR. Results: ENaC and SGK1 mRNAs were significantly lower in late preterm and early term infants than in those ≥390/7 weeks. Significant correlations existed between both ENaC and SGK1 and cord cortisol and GA. In term infants, SGK1 mRNA at 1.5 h was higher after vaginal delivery than elective CD. Conclusions: In late preterm and early term infants, low expression of ENaC and SGK1 may parallel insufficient lung liquid clearance predisposing to respiratory distress. Lower SGK1 expression after term CD could translate into insufficient sodium and lung liquid absorption. The findings demonstrate a central role for cortisol in regulation of ENaC and potentially perinatal sodium and lung liquid clearance.

Lung Ultrasound and Static Lung Compliance during Postnatal Adaptation in Healthy Term Infants

Background: B-lines in lung ultrasound can be used to estimate lung liquid. B-lines are ring-down artifacts that arise from alterations to subpleural lung parenchyma. Lung ultrasound has been used to differentiate between diseases causing respiratory symptoms in neonates. B-lines are also seen in healthy infants during postnatal adaptation. Static lung compliance is a measure of the elasticity of the lungs. Objectives: Our aim was to document lung ultrasound findings, static lung compliance and their relationship during postnatal adaptation in healthy term infants. Methods: Lung ultrasound and measurement of static lung compliance were performed in 34 infants at ages of 0-4 and 24 h. B-lines in lung ultrasound were scored using a 5-step scale. Separate ultrasound scores for the upper and lower fields were also calculated. Results: A significant decrease in the abundance of B-lines and a concomitant significant improvement in static lung compliance was observed from <4 to 24 h of age. At <4 h the B-lines were significantly more abundant in the lower fields. No significant correlation existed between lung ultrasound and static lung compliance. Conclusion: The concomitant decrease in the B-lines in ultrasound and the increase in lung compliance during the first 24 h are likely to reflect clearance of lung liquid.

High tissue factor in lungs and plasma associates with respiratory morbidity in preterm infants

Aim:  In preterm infants, inflammation and intra‐alveolar fibrin formation characterize respiratory distress syndrome (RDS). Tissue factor (TF) is a link between inflammation and coagulation pathways. We investigated the relationship between TF and cytokines in preterm infants to gain information of the role of TF in the inflammatory response.

Contents Vol. 108, 2015

K. Allegaert, Leuven S. Andersson, Helsinki E. Bancalari, Miami, Fla. D. Bassler, Zurich J. Bhatia, Augusta, Ga. C. Bührer, Berlin W. Carlo, Birmingham, Ala. R. Christensen, Salt Lake City, Utah T. Curstedt, Stockholm C. Dani, Florence B. Darlow, Christchurch M. Hallman, Oulu W.W. Hay, Jr., Aurora, Colo. S.E. Juul, Seattle, Wash. M. Kaplan, Jerusalem B. Kramer, Maastricht R.J. Martin, Cleveland, Ohio C.J. Morley, Cambridge J. Neu, Gainesville, Fla. P.C. Ng, Hong Kong M.W. Obladen, Berlin W.S. Park, Seoul A.G.S. Philip, Sebastopol, Calif. M. Roth-Kleiner, Lausanne E. Saliba, Tours O.D. Saugstad, Oslo M.S. Schimmel, Jerusalem M.P. Sherman, Columbia, Mo. E.S. Shinwell, Tsfat K. Simmer, Perth, W.A. J. Smith, Tygerberg R.F. Soll, Burlington, Vt. (Cochrane Review Updates) B. Sun, Shanghai N. Takahashi, Tokyo N. Vain, Buenos Aires F. van Bel, Utrecht J.N. van den Anker, Washington, D.C. M. Vento Torres, Valencia F.J. Walther, Leiden M. Weindling, Liverpool J.A. Widness, Iowa City, Iowa T.F. Yeh, Taipei Fetal and Neonatal Research