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Background Medical simulation training requires realistic simulators with high fidelity. This prospective multi-center study investigated anatomic precision, physiologic characteristics, and fidelity of four commercially available very low birth weight infant simulators. Methods We measured airway angles and distances in the simulators Premature AirwayPaul (SIMCharacters), Premature Anne (Laerdal Medical), Premie HAL S2209 (Gaumard), and Preterm Baby (Lifecast Body Simulation) using computer tomography and compared these to human cadavers of premature stillbirths. The simulators’ physiologic characteristics were tested, and highly experienced experts rated their physical and functional fidelity. Results The airway angles corresponded to those of the reference cadavers in three simulators. The nasal inlet to glottis distance and the mouth aperture to glottis distance were only accurate in one simulator. All simulators had airway resistances up to 20 times higher and compliances up to 19 times lower than published reference values. Fifty-six highly experienced experts gave three simulators (Premature AirwayPaul: 5.1 ± 1.0, Premature Anne 4.9 ± 1.1, Preterm Baby 5.0 ± 1.0) good overall ratings and one simulator (Premie HAL S2209: 2.8 ± 1.0) an unfavorable rating. Conclusion The simulator physiology deviated significantly from preterm infants’ reference values concerning resistance and compliance, potentially promoting a wrong ventilation technique. Impact Very low birth weight infant simulators showed physiological properties far deviating from corresponding patient reference values. Only ventilation with very high peak pressure achieved tidal volumes in the simulators, as aimed at in very low birth weight infants, potentially promoting a wrong ventilation technique. Compared to very low birth weight infant cadavers, most tested simulators accurately reproduced the anatomic angular relationships, but their airway dimensions were relatively too large for the represented body. The more professional experience the experts had, the lower they rated the very low birth weight infant simulators.

PurposeSeveral clinical phenotypes including fetal hydrops, central conducting lymphatic anomaly or capillary malformations with arteriovenous malformations 2 (CM-AVM2) have been associated with EPHB4 (Ephrin type B receptor 4) variants, demanding new approaches for deciphering pathogenesis of novel variants of uncertain significance (VUS) identified in EPHB4, and for the identification of differentiated disease mechanisms at the molecular level.MethodsTen index cases with various phenotypes, either fetal hydrops, CM-AVM2, or peripheral lower limb lymphedema, whose distinct clinical phenotypes are described in detail in this study, presented with a variant in EPHB4. In vitro functional studies were performed to confirm pathogenicity.ResultsPathogenicity was demonstrated for six of the seven novel EPHB4 VUS investigated. A heterogeneity of molecular disease mechanisms was identified, from loss of protein production or aberrant subcellular localization to total reduction of the phosphorylation capability of the receptor. There was some phenotype–genotype correlation; however, previously unreported intrafamilial overlapping phenotypes such as lymphatic-related fetal hydrops (LRFH) and CM-AVM2 in the same family were observed.ConclusionThis study highlights the usefulness of protein expression and subcellular localization studies to predict EPHB4 variant pathogenesis. Our accurate clinical phenotyping expands our interpretation of the Janus-faced spectrum of EPHB4-related disorders, introducing the discovery of cases with overlapping phenotypes.

Less invasive surfactant administration (LISA) is a method to deliver surfactant to spontaneously breathing premature infants via a thin catheter. Here we report the two-year outcome from the AMV (avoid mechanical ventilation) study, the first randomized controlled trial on this mode of surfactant delivery. No statistically significant differences in weight, length or neurodevelopmental outcome (Bayley II scores) were found between the LISA intervention group (n = 95) and the control group (n = 84) that received standard treatment.Conclusion: No differences in outcome were observed at 2 years. LISA seems safe in that aspect. What is Known:• LISA is a method that is in increasing use for surfactant delivery to spontaneously breathing infants. LISA reduces the need for mechanical ventilation. What is New:• Outcome data at 2 years from the first randomized study with LISA raise no safety concerns in comparison to a group of infants that received standard treatment.

ObjectiveTo determine if survival rates of preterm infants receiving active perinatal care improve over time.DesignThe German Neonatal Network is a cohort study of preterm infants with birth weight Setting43 German level III neonatal intensive care units (NICUs).Patients8222 preterm infants with a gestational age between 22/0 and 28/6 weeks who received active perinatal care.InterventionsParticipating NICUs were grouped according to their specific survival rate from 2011 to 2013 to high (percentile >P75), intermediate (P25–P75) and low (Main outcome measuresDeath by any cause before discharge.ResultsTotal survival increased from 85.8% in 2011–2013 to 87.4% in 2014–2016. This increase was due to reduced mortality of NICUs with low survival rates in 2011–2013. Survival increased in these centres from 53% to 64% in the 22–24 weeks strata and from 73% to 84% in the 25–26 weeks strata.ConclusionsOur data support previous reports that active perinatal care of very immature infants improves outcomes at the border of viability and survival rates at higher gestational ages. The high total number of surviving infants below 24 weeks of gestation challenges national recommendations exclusively referring to gestational age as the single criterion for providing active care. However, more data are needed before recommendations for parental counselling should be reconsidered.Trial registrationApproval by the local institutional review board for research in human subjects of the University of Lübeck (file number 08–022) and by the local ethic committees of all participating centres has been given.

The aims of this study were to compare the skin conductance (SC) of newborns with opiate-induced neonatal abstinence syndrome (NAS) to that of unexposed newborns and to evaluate the potential of SC readings to detect distress in the context of NAS objectively. The SC of 12 newborns with NAS and 12 unexposed newborns was measured at nine specific times during their first 6 weeks of life. The number of SC fluctuations per second (NSCF/s), the amplitude of SC fluctuation, and the mean level of SC were recorded and analyzed. The SC of newborns treated for symptoms of NAS differed significantly from the SC of unexposed newborns with regard to the NSCF/s (p = 0.04). With the mean level of SC, we observed an interaction between groups over time (p value for interaction = 0.02). With increasing postnatal age, we observed higher values in all three SC parameters.The NSCF/s and the mean level of SC appear to be suitable to reflect the distress of newborns suffering from NAS. As it is known that the sensitivity of SC increases with the level of stress experienced, its potential to indicate elevated stress levels in infants with NAS should be investigated in future studies evaluating different therapy regimens.• Skin conductance is a result of the filling of palmar and plantar sweat glands innervated by the sympathetic nervous system • Skin conductance can be used as a measure of stress and pain in newborns What is New: • Skin conductance of newborns with neonatal abstinence syndrome (NAS) differs significantly from the SC of non-substance-exposed newborns during the first 6 weeks of life • Skin conductance appears to reflect the increased distress of infants with NAS.

Preterm birth and survival rates of very low birth-weight (VLBW:1.500g) infants have increased. Although new parents are frequently affected by depressive symptoms, little is known about prevalence, risk, and predictors of parental postpartum depression (PPD) following VLBW birth. Furthermore, most studies assessing PPD in parents of preterm children relied on self-report only.As part of the HaFEn cohort-study, data from the index groups of parents with VLBW infants and the control group of parents with term infants were cross-sectionally analysed. Families were recruited at the three largest centres of perinatal medical care in Hamburg, Germany. PPD was evaluated one month postpartum using standardized questionnaires and clinical interviews. Socioeconomic status, social support, risks during pregnancy, and psychiatric lifetime diagnoses were also assessed. A multiple random coefficient model was used to examine predictors of PPD in both parents simultaneously.230 mothers and 173 fathers were included. Depending on the measure, the risk of being postnatally depressed was 4 to 18 times higher in mothers and 3 to 9 times higher in fathers from the index group. The most relevant risk factor for PPD was the birth of a VLBW infant, followed by female sex, lifetime psychiatric disorder, and low social support.Results presented here, are based on cross sectional data. Therefore no temporal relationships can be established.Our findings highlight the importance of early screening for PPD in both parents of VLBW infants. Factors contributing to developing depression should also be considered in neonatal care.

Aim Providing less invasive surfactant administration (LISA) to spontaneously breathing preterm infants has been reported to reduce mechanical ventilation and bronchopulmonary dysplasia (BPD) in randomised controlled trials. This large cohort study compared these outcome measures between LISA-treated infants and controls. Methods Infants receiving LISA, who were born before 32 gestational weeks and enrolled in the German Neonatal Network, were matched to control infants by gestational age, umbilical cord pH, Apgar-score at 5 min, small for gestational age status, antenatal treatment with steroids, gender and highest supplemental oxygen during the first 12 h of life. Outcome data were compared with chi-square and Mann–Whitney U-tests and adjusted for multiple comparisons. Results Between 2009 and 2012, 1103 infants were treated with LISA at 37 centres. LISA infants had lower rates of mechanical ventilation (41% versus 62%, p

Preterm births rates of infants with very low birth weight (VLBW 1500 g) are increasing. Prematurity poses several risks for emotional child development, e.g., internalizing symptoms. Our understanding of this condition in young children is limited, for at preschool age, symptoms have mostly been assessed from the mother's perspective only.As part of the longitudinal HaFEn cohort-study in Hamburg, Germany, we measured the level of internalizing symptoms in VLBW and term preschoolers as well as predictors from four informants' perspectives: mother, father, teacher, and child. A multilevel model was constructed to examine predictors of internalizing symptoms. n = 104 VLBW and n = 79 term children were included.From both their parents' perspective, children with VLBW had a significantly higher level of internalizing symptoms. From the teacher's and child's own perspectives, there were no significant mean group differences. In the multilevel analyses, the results were different regarding the four perspectives. VLBW did not predict internalizing symptoms. From mother's perspective, her own postpartum psychological distress, and from father's perspective, his postpartum and current psychological distress predicted a higher level of internalizing symptoms in their offspring. From teacher's perspective, socio-economic status predicted internalizing symptoms.The sample size was relatively small. Exclusion criteria and drop out of families could have created some selection bias.Our findings point to the importance of early identification of parental postpartum psychological distress given the potential for later internalizing symptoms in their children or the perception of their offspring as vulnerable and symptomatic, which may also impact the child's development.

Object Patients with spina bifida are particularly vulnerable to developing immunoglobulin E (IgE)–mediated latex sensitization. Even though many risk factors leading to latex allergy in these patients have been described, it is still unclear whether the increased prevalence of latex sensitization is disease associated or due to the procedures used to treat spina bifida. The aim of this study was to assess prenatal latex sensitization in patients with spina bifida by examining IgE levels in umbilical cord blood. Methods Patients with spina bifida and matched healthy infants were recruited from the University Medical Center Hamburg-Eppendorf and Children's Hospital Altona. Latex-specific and total IgE were assessed in umbilical cord blood using ImmunoCAP testing to evaluate the degree of prenatal latex sensitization. Results Twenty-two subjects, 10 with spina bifida and 12 healthy individuals, were included. Subjects were selected after matching for sex, gestational age, weight, parental allergy profile, number of prenatal examinations, and utilization of latex tools during pregnancy (propensity score estimates, p = 0.36). In patients with spina bifida, latex-specific and total IgE levels were significantly higher than those in healthy individuals (p = 0.001). After normalization to total IgE, latex-specific IgE levels were higher, yet not significantly increased (p = 0.085). Conclusions Perinatally, there is a significant augmentation of total and latex-specific IgE in patients with spina bifida. After correcting for total IgE, latex-specific IgE was increased, yet not significantly higher than in matched, healthy controls. This pilot study gives novel insights in the immunological reactions related to spina bifida. The increased latex-specific IgE levels could possibly be associated with the occurrence of a latex allergy in the future.

Very premature delivery is a major cause of infant morbidity and mortality. Obesity, diabetes and pregnancy hypertension are known risk factors for pregnancy complications. The study aimed to scrutinize differences of pregnancy complications in a cohort of very premature deliveries compared to a national group. In a multicenter study performed between January 2009 and December 2010 including 1,577 very low birth weight (VLBW) infants, we compared parental reported pregnancy problems of VLBW infants with a national cohort (KIGGS). We compared reported pregnancy complications to reasons for premature delivery and neonatal outcome within the group of VLBW infants. While parents of the national cohort reported pregnancy-induced hypertension in 8 %, parents of VLBW infants reported this complication more frequently (27 %). Mothers of the national cohort were significantly younger (1 year), suffered less from obesity, anaemia, diabetes. Regression analysis showed that hypertension (OR = 5.11) and advanced maternal age (OR = 1.03) increased the risk for premature birth. Women with hypertension were likely to experience a clinically indicated premature delivery, had more VLBW infants with a moderate growth restriction, but less multiples and their infants had less intraventricular haemorrhages grade 3 or 4. Otherwise, neonatal outcome was correlated with gestational age but not with the pregnancy complications diabetes, hypertension or obesity. Premature birth seems to be correlated to gestational hypertension and associated problems in about ¼ of VLBW infants. Further studies should focus on preventing and treating gestational hypertension to avoid premature delivery and associated neonatal morbidity.

Objective To assess whether breastmilk feeding is associated with a reduced risk of bronchopulmonary dysplasia (BPD). Secondary outcome measures analyzed were retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC). Study design In an ongoing multicenter cohort study, the data of 1433 very low birth weight infants born before 32 weeks of gestation and discharged in 2013 were analyzed. We compared growth and neonatal complications of infants who received breastmilk exclusively (N = 223) with those who received formula feedings exclusively (N = 239). Logistic regression models were estimated for BPD, ROP, and NEC using nutrition as an independent variable. The Firth logistic regression model and Lasso were used for sensitivity analyses. Results Exclusively breastmilk-fed infants gained less weight compared with formula-fed infants. SDS for weight decreased between birth and discharge (median (Q1-Q3): formula −0.9 (−1.4 to [−0.5]) vs breastmilk −1.1 (−1.7 to [−0.6])). Exclusive formula feeding of very low birth weight infants was associated with increased risks of BPD (OR 2.6) as well as NEC (OR 12.6) and ROP (OR 1.80) after controlling for known risk factors. Conclusions Exclusive breastmilk feeding was associated with lower growth rates and a reduced risk of BPD as well as NEC and ROP.

Aim: ATP-binding cassette member A 3 (ABCA3) plays a critical role for the transport of surfactant phospholipids into the lamellar bodies of type II alveolar epithelial cells. Term infants carrying the E292V missense mutation of the gene encoding ABCA3 are likely to develop respiratory distress syndrome, and the mutation has also been linked to interstitial lung disease in paediatric patients. The aim of this study was to investigate the association of the E292V genotype with pulmonary morbidity in a large cohort of very-low-birth-weight (VLBW) infants. Methods: We performed a genetic association study with a prospective, population-based multi-centre cohort of 3177 VLBW infants born in 16 German study centres between 2003 and 2009 (German Neonatal Network). The ABCA3 genotype was determined by restriction fragment length polymorphism–PCR in genomic DNA samples derived from buccal swabs. Results: In a large cohort of 3177 VLBW infants, 11 individuals were found to be heterozygote for the E292V mutation (0.34%). After stratification according to ABCA3 genotype, no differences were noted for clinical characteristics, necessary treatments and neonatal pulmonary outcomes. Conclusions: Within the size limits of our study cohort, the ABCA3 missense mutation E292V had no remarkable effect on pulmonary outcome in VLBW infants. Present results do not rule out the possibility that E292V phenotype is associated with minor difference in the morbidity.

Infants of mothers addicted to drugs are recognised to have a special risk for SID. The paper elucidates indications and clinical symptoms of different substitution therapies based on a literature review and clarified by case reports. For many infants the therapy has to be carried out during the whole first year of life or even longer. The case reports are focused on a family with drug addiction and affected by SID twice raising the question for respiratory depression due to high drug levels. Regarding this problem the records of a cardiac-respiration-monitor used for the infant who died second are introduced. The records had been made shortly before death and support our interpretation of morphological and toxicological findings.

Surfactant is usually given to mechanically ventilated preterm infants via an endotracheal tube to treat respiratory distress syndrome. We tested a new method of surfactant application to spontaneously breathing preterm infants to avoid mechanical ventilation.In a parallel-group, randomised controlled trial, 220 preterm infants with a gestational age between 26 and 28 weeks and a birthweight less than 1·5 kg were enrolled in 12 German neonatal intensive care units. Infants were independently randomised in a 1:1 ratio with variable block sizes, to standard treatment or intervention, and randomisation was stratified according to centre and multiple birth status. Masking was not possible. Infants were stabilised with continuous positive airway pressure and received rescue intubation if necessary. In the intervention group, infants received surfactant treatment during spontaneous breathing via a thin catheter inserted into the trachea by laryngoscopy if they needed a fraction of inspired oxygen more than 0·30. The primary endpoint was need for any mechanical ventilation, or being not ventilated but having a partial pressure of carbon dioxide more than 65 mm Hg (8·6 kPa) or a fraction of inspired oxygen more than 0·60, or both, for more than 2 h between 25 h and 72 h of age. Analysis was by intention to treat. This study is registered, number ISRCTN05025922.108 infants were assigned to the intervention group and 112 infants to the standard treatment group. All infants were analysed. On day 2 or 3 after birth, 30 (28%) infants in the intervention group were mechanically ventilated versus 51 (46%) in the standard treatment group (number needed to treat 6, 95% CI 3-20, absolute risk reduction 0·18, 95% CI 0·30-0·05, p=0·008). 36 (33%) infants in the intervention group were mechanically ventilated during their stay in the hospital compared with 82 (73%) in the standard treatment group (number needed to treat: 3, 95% CI 2-4, p0·0001). The intervention group had significantly fewer median days on mechanical ventilation, (0 days. IQR 0-3 vs 2 days, 0-5) and a lower need for oxygen therapy at 28 days (30 infants [30%] vs 49 infants [45%], p=0·032) compared with the standard treatment group. We recorded no differences between groups for mortality (seven deaths in the intervention group vs five in the standard treatment group) and serious adverse events (21 vs 28).The application of surfactant via a thin catheter to spontaneously breathing preterm infants receiving continuous positive airway pressure reduces the need for mechanical ventilation.German Ministry of Research and Technology, University of Lübeck, and Chiesi Pharmaceuticals.

OBJECTIVES:: To determine whether the tumor necrosis factor-alpha -308 G/A polymorphism is associated with blood culture-proven sepsis in two large cohorts of very-low-birth-weight infants. DESIGN:: Genetic association studies. SETTING:: Prospective, population-based, multicentered cohort of 1944 very-low-birth-weight infants born in 14 German study centers between 2003 and 2008 and 976 mothers, and a second prospective cohort of 926 very-low-birth-weight infants born in 2009 (German Neonatal Network). MEASUREMENTS AND MAIN RESULTS:: In cohort I, 344 of 1944 (18.2) very-low-birth-weight infants had at least one episode of blood culture-proven sepsis develop. The sepsis incidence stratified to genotype was 19.3 for G/G, 15.8 for G/A, 10.0 for A/A genotype (Cochrane-Armitage trend test: G/G vs. G/A: odds ratio, 1.32; 95 confidence interval, 1.03-1.71; G/G vs. A/A: odds ratio, 1.74; 95 confidence interval, 1.06-2.91; p = .03). There was a trend for association of tumor necrosis factor-alpha -308 A/G genotype with late-onset sepsis episodes (incidence: 17.2 for G/G, 12.5 for G/A, 10.0 for A/A genotype; Cochrane-Armitage trend test: G/G vs. G/A: odds ratio, 1.43; 95 confidence interval, 1.09-1.9; G/G vs. A/A: odds ratio, 2.05; 95 confidence interval, 1.19-3.56; p = .009). However, after adjustment for multiple testing, no significant associations were found. Furthermore, the genotype of the investigated 976 mothers had no impact on sepsis risk for their very-low-birth-weight infants. We additionally studied a second prospective cohort of 926 very-low-birth-weight infants and found no associations with sepsis risk. CONCLUSIONS:: No association was found between the tumor necrosis factor-alpha -308 G/A polymorphism blood culture-proven sepsis in two large cohorts of very-low-birth-weight infants. A recent meta-analysis demonstrated that the tumor necrosis factor-alpha -308 A allele is associated with higher sepsis risk in adult cohorts. Thus, potential differences between adults and infants need to be incorporated in future study designs evaluating risk profiles for sepsis.

Controversy exists regarding the optimal enteral feeding regimen of very low birth weight infants (VLBW). Rapid advancement of enteral feeding has been associated with an increased rate of necrotizing enterocolitis. In contrast, delaying enteral feeding may have unfavorable effects on nutrition, growth, and neurodevelopment. The aim is to compare the short-term outcomes of VLBW infants in tertiary care centers according to their enteral feeding advancement.We prospectively studied the influence of center-specific enteral feeding advancement in 1430 VLBW infants recruited from 13 tertiary neonatal intensive care units in Germany on short-term outcome parameters. The centers were post hoc stratified to "rapid advancement to full enteral feeds" (median duration of advancement to full enteral feedsor =12.5 days; 6 centers), that is, rapid advancement (RA), or "slow advancement to full enteral feeds" (median duration of advancement to full enteral feeds12.5 days; 7 centers), that is, slow advancement (SA).VLBW infants born in centers with SA (n = 713) had a significantly higher rate of sepsis compared with VLBW infants born in centers with RA (n = 717), which was particularly evident for late-onset sepsis (14.0% vs 20.4%; P = 0.002). Furthermore, more central venous lines (48.6% vs 31.1%, P0.001) and antibiotics (92.4% vs 77.7%, P0.001) were used in centers with SA.Center differences in enteral feeding advancement occur and may have a significant impact on short-term outcomes such as nosocomial sepsis. Large, multicenter, prospective trials are required to further elucidate the optimal feeding strategy for VLBW infants.

We observed two unrelated consanguineous families with malformation syndromes sharing anophthalmia and distinct eyebrows as common signs, but differing for alveolar capillary dysplasia or complex congenital heart defect in one and diaphragmatic hernia in the other family. Homozygosity mapping revealed linkage to a common locus on chromosome 15, and pathogenic homozygous mutations were identified in STRA6, a member of a large group of "stimulated by retinoic acid" genes encoding novel transmembrane proteins, transcription factors, and secreted signaling molecules or proteins of largely unknown function. Subsequently, homozygous STRA6 mutations were also demonstrated in 3 of 13 patients chosen on the basis of significant phenotypic overlap to the original cases. While a homozygous deletion generating a premature stop codon (p.G50AfsX22) led to absence of the immunoreactive protein in patient's fibroblast culture, structural analysis of three missense mutations (P90L, P293L, and T321P) suggested significant effects on the geometry of the loops connecting the transmembrane helices of STRA6. Two further variations in the C-terminus (T644M and R655C) alter specific functional sites, an SH2-binding motif and a phosphorylation site, respectively. STRA6 mutations thus define a pleiotropic malformation syndrome representing the first human phenotype associated with mutations in a gene from the "STRA" group.

Both preterm delivery and survival rates of very low birth weight (VLBW:1500 g) infants are increasing. To date, the focus on studies about postpartum mental health after preterm birth has been on depression and on women. There is a paucity of research regarding prevalence, risks, and predictors of postpartum anxiety in parents after VLBW birth.Parents with VLBW infants and parents with term infants were recruited into the longitudinal HaFEn-study at the three largest centers of perinatal care in Hamburg, Germany. State anxiety was assessed with the State-Trait-Anxiety Inventory and anxiety and adjustment disorders with a clinical interview one month postpartum. Psychiatric lifetime diagnoses, social support, trait anxiety, stress during birth, socioeconomic status, risks during pregnancy, and mode of delivery were also evaluated. To examine predictors of postpartum state anxiety in both parents simultaneously a multiple random coefficient model was used.230 mothers and 173 fathers were included. The risk for minor/major anxiety symptoms and adjustment disorders was higher in parents with VLBW infants compared to the term group. The risk for anxiety disorders was not higher in parents with VLBW infants. The most important predictors for postpartum state anxiety were high trait anxiety, the birth of a VLBW infant, high stress during birth, and low social support.Data reported here are cross-sectional. Thus, temporal relationships cannot be established.Our results emphasize the importance of early screening for postpartum anxiety in both parents with VLBW infants.

Patients with spina bifida are particularly vulnerable to developing immunoglobulin E (IgE)-mediated latex sensitization. Even though many risk factors leading to latex allergy in these patients have been described, it is still unclear whether the increased prevalence of latex sensitization is disease associated or due to the procedures used to treat spina bifida. The aim of this study was to assess prenatal latex sensitization in patients with spina bifida by examining IgE levels in umbilical cord blood.Patients with spina bifida and matched healthy infants were recruited from the University Medical Center Hamburg-Eppendorf and Children's Hospital Altona. Latex-specific and total IgE were assessed in umbilical cord blood using ImmunoCAP testing to evaluate the degree of prenatal latex sensitization.Twenty-two subjects, 10 with spina bifida and 12 healthy individuals, were included. Subjects were selected after matching for sex, gestational age, weight, parental allergy profile, number of prenatal examinations, and utilization of latex tools during pregnancy (propensity score estimates, p = 0.36). In patients with spina bifida, latex-specific and total IgE levels were significantly higher than those in healthy individuals (p = 0.001). After normalization to total IgE, latex-specific IgE levels were higher, yet not significantly increased (p = 0.085).Perinatally, there is a significant augmentation of total and latex-specific IgE in patients with spina bifida. After correcting for total IgE, latex-specific IgE was increased, yet not significantly higher than in matched, healthy controls. This pilot study gives novel insights in the immunological reactions related to spina bifida. The increased latex-specific IgE levels could possibly be associated with the occurrence of a latex allergy in the future.

Introduction: We evaluated blood culture-proven sepsis episodes occurring in microclusters in very-low-birth-weight infants born in the German Neonatal Network (GNN) during 2009-2010. Methods: Thirty-seven centers participated in GNN; 23 centers enrolled ≥50 VLBW infants in the study period. Data quality was approved by on-site monitoring. Microclusters of sepsis were defined as occurrence of at least two blood-culture proven sepsis events in different patients of one center within 3 months with the same bacterial species. For microcluster analysis, we selected sepsis episodes with typically cross-transmitted bacteria of high clinical significance including gram-negative rods and Enterococcus spp. Results: In our cohort, 12/2110 (0.6%) infants were documented with an early-onset sepsis and 235 late-onset sepsis episodes (≥72 h of age) occurred in 203/2110 (9.6%) VLBW infants. In 182/235 (77.4%) late-onset sepsis episodes gram-positive bacteria were documented, while coagulase negative staphylococci were found to be the most predominant pathogens (48.5%, 95%CI: 42.01-55.01). Candida spp. and gram-negative bacilli caused 10/235 (4.3%, 95%CI: 1.68% -6.83%) and 43/235 (18.5%) late-onset sepsis episodes, respectively. Eleven microclusters of blood-culture proven sepsis were detected in 7 hospitals involving a total 26 infants. 16/26 cluster patients suffered from Klebsiella spp. sepsis. The median time interval between the first patient's Klebsiella spp. sepsis and cluster cases was 14.1 days (interquartile range: 1-27 days). First patients in the cluster, their linked cases and sporadic sepsis events did not show significant differences in short term outcome parameters. Discussion: Microclusters of infection are an important phenomenon for late-onset sepsis. Most gram-negative cluster infections occur within 30 days after the first patient was diagnosed and Klebsiella spp. play a major role. It is essential to monitor epidemic microclusters of sepsis in surveillance networks to adapt clinical practice, inform policy and further improve quality of care. © 2012 Härtel et al. OA gold

ATP-binding cassette member A 3 (ABCA3) plays a critical role for the transport of surfactant phospholipids into the lamellar bodies of type II alveolar epithelial cells. Term infants carrying the E292V missense mutation of the gene encoding ABCA3 are likely to develop respiratory distress syndrome, and the mutation has also been linked to interstitial lung disease in paediatric patients. The aim of this study was to investigate the association of the E292V genotype with pulmonary morbidity in a large cohort of very-low-birth-weight (VLBW) infants.We performed a genetic association study with a prospective, population-based multi-centre cohort of 3177 VLBW infants born in 16 German study centres between 2003 and 2009 (German Neonatal Network). The ABCA3 genotype was determined by restriction fragment length polymorphism-PCR in genomic DNA samples derived from buccal swabs.In a large cohort of 3177 VLBW infants, 11 individuals were found to be heterozygote for the E292V mutation (0.34%). After stratification according to ABCA3 genotype, no differences were noted for clinical characteristics, necessary treatments and neonatal pulmonary outcomes.Within the size limits of our study cohort, the ABCA3 missense mutation E292V had no remarkable effect on pulmonary outcome in VLBW infants. Present results do not rule out the possibility that E292V phenotype is associated with minor difference in the morbidity.

BACKGROUND: Recently in a report of a single center a method has been described to apply surfactant via a thin endotracheal catheter to very low birth weight infants spontaneously breathing with nasal continuous positive airway pressure. We now analyzed available multicenter data. PATIENTS AND METHODS: In a multicenter study investigating genetic risk factors, clinical and outcome data and data of antenatal and postnatal treatment of infants with a birth weight below 1 500 g were prospectively recorded. The measures of infants treated with the new method of surfactant application were compared to those of infants who received standard care. The analysis was restricted to infants with a gestational age below 31 weeks (n=1 541). RESULTS: 319 infants were treated with the new method and 1 222 with standard care. The need for mechanical ventilation during the first 72 h (29% vs. 53%, p

Background: Surfactant, a standard treatment for respiratory distress syndrome in preterm infants, is usually administered to mechanically ventilated infants via the endotracheal tube. In this randomized controlled trial, we evaluated a new method of surfactant application to spontaneously breathing preterm infants in order to avoid mechanical ventilation. Methods: 220 preterm infants with a gestational age between 26+0 and 28+6 weeks and a birth weight below 1500 grams were enrolled in the trial. In the intervention group, surfactant was given to spontaneously breathing infants who needed more than 30% oxygen via a thin catheter which was placed in the trachea. Results: On day two or three of life 30 (27.8%) of 108 infants in the spontaneously breathing group but 51 (45.5%) of 112 infants in the standard treatment group were mechanically ventilated (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.3-0.8, p=0.008). At 28 days, there was a lower need for oxygen therapy in the spontaneously breathing group. If any mechanical ventilation during the stay in the hospital was analyzed, 36 (33%) infants in the spontaneously breathing group but 82 (73%) infants in the standard treatment group needed intubation and mechanical ventilation (OR 0.18, 95%CI 0.1-0.3, p= 0.0000000038). The spontaneously breathing group had considerable fewer days of mechanical ventilation. No differences were observed for overall mortality and serious adverse events. Conclusions: The application of surfactant to spontaneously breathing preterm infants with a thin catheter reduces the need for mechanical ventilation.