Katrin Mehler

Outcome of extremely low gestational age newborns after introduction of a revised protocol to assist preterm infants in their transition to extrauterine life

Aim:  To evaluate the outcome of a cohort of extremely low gestational age newborn infants (ELGAN) below 26‐week gestation who were treated following a revised, gentle delivery room protocol to assist them in the transition and adaptation to extrauterine life.

Serum concentrations of vascular endothelial growth factor in an infant treated with ranibizumab for retinopathy of prematurity.

ganglion cells were first discovered 10 years ago, and many important aspects of their function remains unknown, not least the important question of how much or how little light is needed to maintain stable photoentrainment. Melanopsin-driven photoentrainment of circadian rhythms and pupillary response to short wavelength light are coupled, and looking at the pupillary light response to blue light is a clinically useful indirect measurement of the function of the melanopsin containing retinal ganglion cells. Melanopsin is a bi-stable molecule (Mure et al. 2009) that is reflected in the enhanced pupillary constriction to blue light after prior exposure to blue light (Hansen et al. 2011). Pupillary blue light response depends on pupil size and is greater after pupillary dilation (Nissen et al. 2011). Yet surprisingly, melanopsinmediated pupillary blue light response is enhanced with age in spite of age-related miosis and reduced lens transmission (Herbst et al. 2012). Speculatively, the system may adapt to decreased blue light levels with age by increasing the sensitivity. These observations demonstrate the complexity of the system and difficulties encountered when extrapolating from the filtering effects of the lens or IOLs to the photoentrainment potential of the aged or even pseudophakic eye. We felt there were too many unknown factors to compute a photoentrainment potential for the aged eye and hence restricted our computations to the effect of the lens. One aspect of the debate is whether blue-blocking IOLs are detrimental to photoentrainment of circadian rhythms or not. Equally important is the question of whether to use blue-blocking IOLs or not. The main rationale for using blueblocking IOLs is the theory that blue light is involved in the pathogenesis of age-related macular degeneration (AMD). As we write in our paper, the theory has not been scientifically proven and concluding that we argue that the ‘chromophores they consider to be optically insignificant to adversely affect circadian photoentrainment might somehow reduce the risk of AMD’ is a twisting of our argumentation. What we do write is that if someone were to conduct a study proving a protective effect of blue-blocking IOLs on AMD, the study would need to have a considerable time perspective. We do not yet have the scientific proof to say whether blue-blocking IOLS do or do not reduce the risk of AMD. Sleep disturbances increase with age, and a correlation with lens yellowing has been found (Kessel et al. 2011). Cataract surgery (with UV-blocking IOLs) leads to better sleep and well-being (Asplund & Lindblad 2004) indicating that short wavelength filtering by the lens is important for the photoentrainment of circadian rhythms in vivo. Our results showed that the difference of yellow-tinted and UV-only blocking IOLs is exceeded by several folds by the natural discoloration of the human lens. How this may affect photoentrainment is – of course – speculation and as Dr. Mainster and Dr. Turner states prospective, randomized clinical trials are needed to determine the clinical significance.

Respiratory and general outcome in neonates with renal oligohydramnios—a single-centre experience

BACKGROUND Renal oligohydramnion (ROH) is predominantly caused by congenital abnormalities of the kidney and urogenital tract (CAKUT). Although the number of neonates born with chronic renal failure is small, they provide many challenges, and among the most problematic are respiratory management and long-term treatment of chronic renal failure. We studied the value of prenatal and perinatal variables to predict survival and the general long-term outcome of our ROH population. Method. A single-centre retrospective chart review was conducted in 36 neonates with ROH treated between 1996 and 2007. Respiratory data sets including minimum inspiratory oxygen concentration (FiO(2), 1d), best oxygenation index (BOI, 1d) and minimum arterial partial carbon dioxide (pCO(2), 1d) at the first day of life were available in 23 children requiring intubation. RESULTS ROH causes were obstructive uropathy (n = 19), polycystic kidney disease [autosomal recessive polycystic kidney disease (ARPKD) n = 5 and autosomal dominant polycystic kidney disease n = 1], renal agenesis/dysplasia (n = 10) and bilateral renal vein thrombosis (n = 1). Survival until discharge was 64% (23/36), and overall survival was 58% (21/36). Seven patients died within 48 h from respiratory failure. Non-survivors had a higher minimum FiO(2) and pCO(2) (1d) compared to survivors (P < 0.001). Mean BOI (1d) was 6.2 in survivors versus 43.9 in the non-surviving group (P < 0.001). Logistic regression showed that BOI (28 gestational weeks) retained significance in predicting survival until discharge. CONCLUSIONS The attitude toward initiating dialysis in neonates is changing and long-term outcome in the absence of severe comorbidity is promising. Prenatal prediction concerning respiratory and renal outcome in fetuses with ROH is difficult. Our data suggest that BOI (1d) and onset of ROH may be reliable predictors of respiratory prognosis in children born with ROH.

High Rate of Symptomatic Cytomegalovirus Infection in Extremely Low Gestational Age Preterm Infants of 22-24 Weeks' Gestation after Transmission via Breast Milk

Background: Very immature preterm infants are at risk of developing symptomatic or severe infection if cytomegalovirus is transmitted via breast milk. It is still a matter of debate whether human cytomegalovirus (HCMV) infection may lead to long-term sequelae. Objectives: We hypothesized that symptomatic and severe HCMV infection transmitted via breast milk affects extremely immature infants at a very high rate. Methods: In 2012, untreated breast milk was fed to extremely low birth weight infants after parental informed consent was obtained. We retrospectively analyzed data on HCMV infection of infants born in 2012 between 22 and 24 weeks of gestation. Results: 17 infants were born to HCMV IgG-seropositive mothers. 11 (65%) of these were diagnosed with symptomatic infection. In all cases, thrombocytopenia was the reason to analyze the infants urine. HCMV infection was diagnosed at a median time of 12 weeks after birth. In 5 (45%) infants, thrombocytopenia was the only symptom and resolved without antiviral therapy or platelet transfusion. 6 (55%) infants developed sepsis-like disease with mildly elevated CRP values and showed signs of respiratory failure. 3 (27%) were able to be stabilized on CPAP, 3 (27%) had to be intubated and mechanically ventilated. 4 children were treated with ganciclovir and/or valganciclovir. 55% failed otoacoustic emissions and/or automated auditory brainstem response testing at discharge. Conclusions: In very immature infants born at the border of viability and suffering from multiple preexisting problems, HCMV infection may trigger a severe deterioration of the clinical course.

Observations on the effects of inhaled isoflurane in long-term sedation of critically Ill children using a modified AnaConDa©-system.

Long-term intravenous sedation may present problems due to dependence and side effects. Medical records of children who were administered isoflurane were reviewed. 15 patients (9 boys, 6 girls) with a mean age of 11.8 month (+2.4) were analysed.Analgesia and sedation was given in mean 9.7+1.1 days before commencing inhalation using a modified application device (AnaConDa©). Administration was given over a period of 7.2+1.4 days. Depth of sedation was monitored by using Comfort- and Hartwig-scores. Observations included continuous monitoring of heart-rate, pulse oxymetry, blood pressure and cerebral tissue oxygenation.Within 4 h post administration of isoflurane a satisfactory increase in the depth of sedation was seen and kept till extubation. 6/15 patients received tracheostomies during the observation period. None of the patients observed suffered life-critical events of the modified application of isoflurane proceeded without complications. Ketamine and clonidine infusion rates were significantly reduced (p<0.005) as well as the use and overall infusion rate of midazolam, γ-hydroxy butyrate, fentanyl and morphine (p<0.05).Isoflurane inhalation may provide an additional option for long-term sedation in a specific group of critically ill infants but neurodegenerative toxic effects will have to be taken into account when using volatile anesthetics at any time during infancy.

Disorders of fatty acid oxidation and autosomal recessive polycystic kidney disease—different clinical entities and comparable perinatal renal abnormalities

BackgroundDifferential diagnosis of prenatally detected hyperechogenic and enlarged kidneys can be challenging as there is a broad phenotypic overlap between several rare genetic and non-genetic disorders. Metabolic diseases are among the rarest underlying disorders, but they demand particular attention as their prognosis and postnatal management differ from those of other diseases.MethodsWe report two cases of cystic, hyperechogenic and enlarged kidneys detected on prenatal ultrasound images, resulting in the suspected diagnosis of autosomal recessive polycystic kidney disease (ARPKD). Postnatal clinical course and work-up, however, revealed early, neonatal forms of disorders of fatty acid oxidation (DFAO) in both cases, namely, glutaric acidemia type II, based on identification of the novel, homozygous splice-site mutation c.1117-2A > G in the ETFDH gene, in one case and carnitine palmitoyltransferase II deficiency in the other case.ResultsReview of pre- and postnatal sonographic findings resulted in the identification of some important differences that might help to differentiate DFAO from ARPKD. In DFAO, kidneys are enlarged to a milder degree than in ARPKD, and the cysts are located ubiquitously, including also in the cortex and the subcapsular area. Interestingly, recent studies have pointed to a switch in metabolic homeostasis, referred to as the Warburg effect (aerobic glycolysis), as one of the underlying mechanisms of cell proliferation and cyst formation in cystic kidney disease. DFAO are characterized by the inhibition of oxidative phosphorylation, resulting in aerobic glycolysis, and thus they do resemble the Warburg effect. We therefore speculate that this inhibition might be one of the pathomechanisms of renal hyperproliferation and cyst formation in DFAO analogous to the reported findings in ARPKD.ConclusionsNeonatal forms of DFAO can be differentially diagnosed in neonates with cystic or hyperechogenic kidneys and necessitate immediate biochemical work-up to provide early metabolic management.

An Echocardiographic Screening Program Helps to Identify Pulmonary Hypertension in Extremely Low Birthweight Infants with and without Bronchopulmonary Dysplasia: A Single-Center Experience

Background: Pulmonary hypertension (PH) affects 1 in 6 infants with a birthweight <1,000 g (extremely low birthweight; ELBW) and is frequently associated with bronchopulmonary dysplasia (BPD). If untreated, the mortality rates of the disease are high. Objectives: The aim of this study was to characterize risk factors for PH in ELBW infants and to describe the timing of onset of the disease by setting up a screening program. Methods: ELBW infants treated at the Department of Neonatology (level III neonatal intensive care unit at the University of Cologne Medical Centre, Germany) between January 2010 and March 2015 were included. Echocardiography screening for PH was performed either before discharge or if BPD was diagnosed. Additionally, infants had at least 1 echocardiographic scan after discharge. Survival with PH, age at diagnosis of PH, and risk factors associated with PH were assessed. Results: In total, 34/188 (18%) infants had PH. Of these, 14 (41%) were identified after discharge. Another 11 (32%) were diagnosed with PH without suffering from moderate or severe BPD. The risk factors for diagnosis of PH were moderate (odds ratio, OR 4 [2-8]) or severe BPD (OR 13 [2-71]), prolonged rupture of membranes >7 days (OR 5 [1-19]), and birthweight below the 3rd percentile (OR 3 [1-9]). All infants with PH before discharge and 50% diagnosed after discharge were treated with sildenafil (2.0 mg/kg/day). PH resolved and sildenafil was discontinued in all patients after a median duration of 13 months (IQR 8-20). Conclusions: An echocardiographic screening program may help to identify infants with PH. Examinations should include all ELBW infants irrespective of the presence of BPD and be continued after discharge.

Less invasive surfactant administration and complications of preterm birth

In a large cohort study of the German Neonatal Network (GNN) we aimed to evaluate whether less invasive surfactant administration (LISA) strategy is associated with complications of preterm birth. Within the observational period n = 7533 very-low-birth-weight infants (VLBWI) with gestational age 22 0/7 to 28 6/7 weeks were enrolled in GNN; n = 1214 VLBWI never received surfactant, n = 2624 VLBWI were treated according to LISA procedure, n = 3695 VLBWI had surfactant via endotracheal tube (ETT). LISA was associated with a reduced risk for adverse outcome measures including mortality [odds ratio (OR) 0.66 (95% CI: 0.51–0.84), p < 0.001] bronchopulmonary dysplasia [BPD; OR 0.55 (95% CI: 0.49–0.62), p < 0.001], intracerebral hemorrhage (ICH) grade II-IV [OR 0.55 (95% CI: 0.48–0.64), p < 0.001] and retinopathy of prematurity [ROP; OR 0.62 (95% CI: 0.45–0.85), p < 0.001]. Notably, LISA was associated with an increased risk for focal intestinal perforation [FIP; OR 1.49 (95% CI: 1.14–1.95), p = 0.002]. The differences in FIP rates were primarily observed in VLBWI born <26 weeks (LISA: 10.0 vs. ETT: 7.4%, p = 0.029). Our observational data confirm that LISA is associated with improved outcome. In infants <26 weeks we noted an increased risk for FIP. Future randomized controlled trials including LISA need to integrate safety analyses for this particular subgroup.

Blood sampling via a peripheral artery catheter decreases cerebral oxygenation index in very low‐birthweight infants

This study evaluated the impact of blood sampling via peripheral arterial catheters on cerebral oxygenation and blood volume as a function of blood sampling velocity.

Schmerzen bei Früh- und Neugeborenen

Schmerzen treten bei intensivmedizinisch betreuten Neugeborenen und Frühgeborenen einerseits im Rahmen ihrer jeweiligen Grunderkrankung oder einer entstandenen Komplikation (z.B. nekrotisierende Enterokolitis) auf, andererseits bei einer Vielfalt medizinischer Prozeduren. Schmerzen müssen erkannt und möglichst vermieden werden.