Epidemiology and One-Year Follow-Up of Neonates with CDH-Data from Health Insurance Claims in Germany.

Congenital diaphragmatic hernia (CDH) is a major congenital malformation with high mortality. Outcome data on larger unselected patient groups in Germany are unavailable as there is no registry for CDH. Therefore, routine data from the largest German health insurance fund were analyzed for the years 2009-2013. Main outcome measures were incidence, survival and length of hospital stay. Follow-up was 12 months. 285 patients were included. The incidence of CDH was 2.73 per 10,000 live births. Overall mortality was 30.2%. A total of 72.1% of the fatalities occurred before surgery. Highest mortality (64%) was noted in patients who were admitted to specialized care later as the first day of life. Patients receiving surgical repair had a better prognosis (mortality: 10.8%). A total of 67 patients (23.5%) were treated with ECMO with a mortality of 41.8%. The median cumulative hospital stay among one-year survivors was 40 days and differed between ECMO- and non-ECMO-treated patients (91 vs. 32.5 days, p < 0.001). This is the largest German cohort study of CDH patients with a one-year follow-up. The ECMO subgroup showed a higher mortality. Another important finding is that delayed treatment in specialized care increases mortality. Prospective clinical registries are needed to elucidate the treatment outcomes in detail.

Different Effects of Two Protocols for Pre-Procedural Analgosedation on Vital Signs in Neonates during and after Endotracheal Intubation.

BACKGROUND: Analgosedation is often used for endotracheal intubation in neonates, but no consensus exists on the optimal pre-procedural medication. AIMS: To compare the time to intubation and vital signs during and after intubation in 2 NICUs using different premedication protocols. METHODS: Prospective observational study in 2 tertiary NICUs, comparing fentanyl and optional vecuronium for elective neonatal endotracheal intubation (NICU-1) with atropine, morphine, midazolam and optional pancuronium (NICU-2). Primary endpoints were: time to intubate and number of intubation attempts; secondary endpoints were: deviations of heart rate, oxygen saturation and blood pressure from baseline until 20 min post intubation. RESULTS: 45 and 30 intubations were analyzed in NICU-1 and NICU-2. Time to intubation was longer in NICU-1 (7 min) than in NICU-2 (4 min; p=0.029), but the mean number of intubation attempts did not differ significantly. Bradycardias (34 vs. 1, p<0.001) and hypoxemias (136 vs. 48, p<0.001) were more frequent in NICU-1, and tachycardias (59 vs. 72, p<0.001) more frequent in NICU-2. Mean arterial blood pressure (MAP) increased in NICU-1 (+6.18 mmHg) and decreased in NICU-2 (-5.83 mmHg), whereas mean heart rates (HR) decreased in NICU-1 (-19.29 bpm) and increased in NICU-2 (+15.93 bpm). MAP and HR returned to baseline 6-10 min after intubation in NICU-1 and after 11-15 min and 16-20 min in NICU-2, respectively. CONCLUSIONS: The two protocols yielded significant differences in the time to intubation and in the extent and duration of physiologic changes during and post-intubation. Short acting drugs should be preferred and vital signs should be closely monitored at least 20 min post intubation. More studies are required to identify analgosedation protocols that minimize potentially harmful events during endotracheal intubation.

Application of two different nasal CPAP levels for the treatment of respiratory distress syndrome in preterm infants-"The OPTTIMMAL-Trial"-Optimizing PEEP To The IMMAture Lungs: study protocol of a randomized controlled trial.

BACKGROUND: Nasal continuous positive airway pressure (CPAP) applies positive end-expiratory pressure (PEEP) and has been shown to reduce the need for intubation and invasive mechanical ventilation in very low birth weight infants with respiratory distress syndrome. However, CPAP failure rates of 50% are reported in large randomized controlled trials. A possible explanation for these failure rates is the application of insufficient low levels of PEEP during nasal CPAP treatment to maintain adequate functional residual capacity shortly after birth. The optimum PEEP level to treat symptoms of respiratory distress in very low birth weight infants has not been assessed in clinical studies. The aim of the study is to compare two different PEEP levels during nasal CPAP treatment in preterm infants. METHODS: In this randomized multicenter trial, 216 preterm infants born at 26 + 0-29 + 6 gestational weeks will be allocated to receive a higher (6-8 cmH2O) or a lower (3-5 cmH2O) PEEP during neonatal resuscitation and the first 120 h of life. The PEEP level within each group will be titrated throughout the intervention based on the FiO2 (fraction of inspired oxygen concentration) requirements to keep oxygenation within the target range. The primary outcome is defined as the need for intubation and mechanical ventilation for > 1 h or being not ventilated but reaching one of the two pre-defined CPAP failure criteria (FiO2 > 0.5 for > 1 h or pCO2 ≥ 70 mmHg in two consecutive blood gas analyses at least 2 h apart). DISCUSSION: Based on available data from the literature, the optimum level of PEEP that most effectively treats respiratory distress syndrome in preterm infants is unknown, since the majority of large clinical trials applied a wide range of PEEP levels (4-8 cmH2O). The rationale for our study hypothesis is that the early application of a higher PEEP level will more effectively counteract the collapsing properties of the immature and surfactant-deficient lungs and that the level of inspired oxygen may serve as a surrogate marker to guide PEEP titration. Finding the optimum noninvasive continuous distending pressure during early nasal CPAP is required to improve CPAP efficacy and as a consequence to reduce the exposure to ventilator-induced lung injury and the incidence of chronic lung disease in this vulnerable population of very preterm infants. TRIAL REGISTRATION: drks.de DRKS00019940 . Registered on March 13, 2020.

Decentralized surgery of abdominal wall defects in Germany.

PURPOSE: Neonatal surgery for abdominal wall defects is not performed in a centralized manner in Germany. The aim of this study was to investigate whether treatment for abdominal wall defects in Germany is equally effective compared to international results despite the decentralized care. METHODS: All newborn patients who were clients of the major statutory health insurance company in Germany between 2009 and 2013 and who had a diagnosis of gastroschisis or omphalocele were included. Mortality during the first year of life was analysed. RESULTS: The 316 patients with gastroschisis were classified as simple (82%) or complex (18%) cases. The main associated anomalies in the 197 patients with omphalocele were trisomy 18/21 (8%), cardiac anomalies (32%) and anomalies of the urinary tract (10%). Overall mortality was 4% for gastroschisis and 16% for omphalocele. Significant factors for non-survival were birth weight below 1500 g for both groups, complex gastroschisis, volvulus and anomalies of the blood supply to the intestine in gastroschisis, and female gender, trisomy 18/21 and lung hypoplasia in omphalocele. CONCLUSIONS: Despite the fact that paediatric surgical care is organized in a decentralized manner in Germany, the mortality rates for gastroschisis and omphalocele are equal to those reported in international data.

Epidemiology and Outcome of Major Congenital Malformations in a Large German County.

INTRODUCTION: Congenital malformations are associated with substantial neonatal morbidity and mortality. Furthermore, only sparse data are available on the modalities of care provided to and the associated clinical outcomes in affected neonates. In this study, we focused on five malformations that require surgery during the neonatal period: duodenal stenosis and atresia (DA), gastroschisis (GA), omphalocele (OM), congenital diaphragmatic herniation (CDH), and esophageal atresia (EA). MATERIALS AND METHODS: We reviewed the Hessian neonatal registry (2010-2015) to identify records including the ICD-10 (International Classification of Diseases, Tenth Edition) codes for the aforementioned diagnoses and identified 283 patients who were affected by at least one of these conditions. Multiple regression analyses were performed to further identify risk factors for mortality and extended length of hospital stay. RESULTS: The incidence rates per 10,000 live births and inhospital mortality rates were as follows: DA: 1.79 and 3.6%; GA: 1.79 and 1.8%; OM: 1.60 and 24%; CDH: 1.32 and 27.5%; and EA: 2.67 and 11.1%, respectively. Thirty-three percent of the patients had not been born in a perinatal center in which corrective surgeries were performed. The following risk factors were significantly associated with early mortality: trisomy 13 and 18, congenital heart defects, prematurity, and high-risk malformations (OM and CDH). The predictors of length of stay were as follows: gestational age, number of additional malformations, and treatment in the center with the highest patient volume. CONCLUSION: Epidemiology and outcome of major congenital malformations in Hesse, Germany, are comparable to previously published data. In addition, our data revealed a volume-outcome association with regard to the length of hospital stay.

Necrotizing enterocolitis as a prognostic factor for the neurodevelopmental outcome of preterm infants - match control study after 2years.

PURPOSE: Necrotizing enterocolitis (NEC) in very low birth weight infants is a risk factor for developmental delay. To our knowledge, there are no studies published investigating the neurodevelopmental outcome of patients with NEC comparing surgically treated and conservatively treated patients versus match paired controls. The aim of this retrospective case control study was to measure the neurodevelopmental outcome of patients with NEC who were treated surgically or conservatively METHODS: All patients were identified, who have been diagnosed with NEC (ICD-10 code, P77) born between 2006 and 2013. Patients with NEC received antibiotic therapy, nasogastric decompression and fasting. Surgical treatment was indicated for patients with Bell stages IIIb. We excluded patients suffering from other relevant diseases with a possible impact on their neurodevelopmental outcome (e.g., intraventricular hemorrhage, associated malformations, asphyxia, focal intestinal perforation, short bowel syndrome). Patients were tested at the corrected gestational age of 24months according to the Bayley Scales of Infant Development II. Each participant was compared to a child of the same sex, gestational age at birth (+/-two days), birth weight (+/-10%), and age at neurodevelopmental testing (IRB approval, No. 14/2014). The outcome measures were the psychomotor index (PDI) and the mental developmental index (MDI). RESULTS: We included 13 conservatively and 24 surgically treated patients. The patients in group A (without surgery) achieved a mean PDI of 106, and those in group B (with surgery) a mean PDI of 90. These values were significantly higher in the conservative group A. The mean MDIs were 99 in the patient group A and 85 in patient group B. This difference was also significant. CONCLUSION: We found significantly lower MDIs and PDIs in children with surgical treatment of NEC. Further systematic prospective research on the prevention of NEC and systematic follow-ups at later stages in the patients' development are necessary in order to implement early intervention. TYPE OF STUDY: case control study. LEVEL OF EVIDENCE: III.

Immune cell subsets at birth may help to predict risk of late-onset sepsis and necrotizing enterocolitis in preterm infants.

BACKGROUND: Parameters predicting late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants would be valuable. Ten-color flow-cytometry enables the estimation of cellular immune status requiring only small sample volumes. AIMS: Identifying predictive parameters for LOS and NEC in the cellular immune status of preterm infants. STUDY DESIGN AND SUBJECTS: In this prospective study in 40 preterm infants (week 26+0 to 30+6) and 10 healthy full-term newborn infants (control group, week 37+0 to 40+6), flow cytometric analyses of lymphocyte subpopulations were performed between the 2nd and the 6th day of life, with a follow-up until the preterm infant reached the calculated gestational age of week 40. Patients' episodes of infections and NEC were analyzed according to the NEO-KISS criteria of the German National Reference Center. RESULTS: Ten preterm infants showed events within the first week of life and were excluded from the analysis. Of the other 30, five developed NEC, twelve LOS. In patients with LOS, the proportion of double-negative (DN) T cells was significantly elevated compared to patients without LOS, while immune-regulatory CD56bright and CD56negCD16+ NK cells were significantly decreased (p<0.05). Patients with NEC showed a reduction in the NK cell proportion (<3.7%) and significantly decreased naïve cytotoxic CD45RA+CD62L+ T cells (p<0.05). CONCLUSION: NK cells and DN-T cell counts within the first week of life may be predictors for NEC and LOS in preterm infants. In order to identify patients at risk early, further analysis of these populations might be of interest.

Primary laparotomy is effective and safe in the treatment of necrotizing enterocolitis.

INTRODUCTION: There is ongoing controversy regarding the surgical treatment of necrotizing enterocolitis (NEC) in infants with extremely low birth weight (ELBW). We hypothesize that primary laparotomy is a safe and effective treatment for all infants with surgical NEC. METHODS: We retrospectively compared a group of ELBW infants (<1,000 g, group A, n = 39) with preterm infants (≥1,000 g, group B, n = 18) with surgical NEC during a 4-year period (10/2008-09/2012). Indications for emergency operation were Bell stages IIIa or IIIb. The main outcome measure was survival. Data were analyzed using Chi squared test and Spearman's rank correlation coefficient. RESULTS: Fifty-seven patients were included with a gestational age from 24 to 30 weeks in group A and 27-38 weeks in group B. There were no significant differences in Bell stage (IIIa; IIIb) and NEC type (focal; segmental; pannecrosis). The operative techniques were not significantly different between the groups and included resection and stoma formation in 44 of 57 (77 %) patients; resection and anastomosis in 6 of 57 (11 %); and inspection only, followed by withdrawal of care, in 7 of 57 (12 %). Overall mortality was 10 of 57 (17 %) with no significant difference between the groups. The only significant correlation was observed between the length of necrotic bowel and mortality. In total, 7 of 57 infants required repeated surgery after initial treatment. We observed stoma complications in 36 % of the patients in group A and 21 % in group B without the need of stoma revision. All stomas were successfully closed at the time of the study. One of 44 patients with stoma closure required a relaparotomy due to bowel obstruction. CONCLUSIONS: Early primary laparotomy is safe and effective for the management of surgical NEC in ELBW infants. Outcome of affected infants is not influenced by age or weight at surgery but by the length of necrotic bowel.

Purpura fulminans after therapeutic hypothermia in an asphyxiated neonate with streptococcemia.

OBJECTIVE: Therapeutic hypothermia is an established therapeutic regimen in severely asphyxiated term neonates. The amount of cerebral injury is reduced resulting in an improved neurologic outcome. Therapeutic hypothermia-induced side effects mostly affect the circulatory system, kidney, and liver. However, asphyxia and hypothermia in itself reduce the hemostatic capacity of each individual organism. STUDY DESIGN: A case of a neonate with severe asphyxia and purpura fulminans after hypothermia is described. RESULTS AND CONCLUSION: Although purpura fulminans cannot be attributed to hypothermia solely, the influence of hypothermia on hemostasis may have promoted severe coagulopathy with a fatal outcome. Further studies are necessary to reveal therapeutic hypothermia as a trigger for severe coagulopathies in asphyxiated neonates, especially in those with sepsis and overt coagulopathy prior to therapeutic hypothermia.

Feeding of very low birth weight infants born to HCMV-seropositive mothers in Germany, Austria and Switzerland.

AIM: To evaluate the enteral feeding practice of preterm infants <32 weeks (W) gestational age (GA) or <1500 g birth weight (BW) from human cytomegalovirus (HCMV)-seropositive mothers in Germany, Austria and Switzerland. METHODS: This prospective cross-sectional study included all neonatal units (NU) admitting preterm infants <32W or <1500g BW in Germany, Austria and Switzerland. In June and July 2009, an anonymized questionnaire was sent via e-mail, asking whether mothers of the above patients were screened for HCMV, and about the enteral feeding protocol for preterm infants <32W GA or <1500g BW from HCMV-seropositive mothers. RESULTS: During the study period, 58.6% of the questionnaires (123/210) from Germany, 50% (13/26) from Austria and 50% (6/12) from Switzerland were returned, yielding a total of 6232 preterm infants for analysis. Formula was given to the mentioned preterm infants in 28.5% (35/123) of the German NUs but not in Austria or Switzerland. Untreated breast milk was given in 66.6% (4/6) of the Swiss, 14.6% (18/123) of the German and no Austrian NU. Long-term pasteurized breast milk was given in 32.5% (40/123) of the German and 38.5% (5/13) of the Austrian NUs, but not in Switzerland. Short-term pasteurized breast milk was given only in 5.7% (7/123) of German NUs. Freeze-thawed breast milk was given in Germany (4.9%; 6/123), Austria (61.5%; 8/13) and Switzerland (16.7%; 1/6). CONCLUSION: Preterm infants <32W GA or <1500g BW born to HCMV-seropositive mothers are fed according to different regimes in German-speaking countries. About 28.5% of the German VLBW-infants receive formula, which is not recommended.

Intracerebral mass bleeding in a term neonate: manifestation of hereditary protein S deficiency with a new mutation in the PROS1 gene.

BACKGROUND: Vitamin K deficiency is the major cause of coagulopathy-induced intracranial bleeding in term neonates and is considered first in any term neonate with severe hemorrhage. The most common manifestation of hereditary prothrombotic disorders during the neonatal period is thrombosis of the A. cerebri media or sinus thrombosis. CASE REPORT: A 4-day-old newborn was admitted with seizures and hemorrhagic shock. Ultrasound revealed a left-sided intraparenchymatous bleeding. MRI findings supported a subarachnoidal and intracerebral mass bleeding. Vitamin K deficiency-related bleeding or hemophiliac diseases were excluded; however, homozygous protein S deficiency with a new mutation in the protein S (PROS1) gene (c.701A>G, p.Tyr234Cys) was found. The patient experienced an additional thrombosis of the A. abdominalis and expired. CONCLUSION: Congenital prothrombotic disorders have to be considered in the differential diagnosis of neonatal intracranial hemorrhage. This newly described mutation in the PROS1 gene (c.701A>G, p.Tyr234Cys) appears to be of clinical relevance.

Incidence and clinical outcome of cytomegalovirus transmission via breast milk in preterm infants

AIM: To evaluate incidence, timing and clinical relevance of acquired human cytomegalovirus (HCMV) infection in preterm infants. METHODS: The prospective longitudinal study included preterm infants

Recombinant activated Factor VII as a hemostatic agent in very low birth weight preterms with gastrointestinal hemorrhage and disseminated intravascular coagulation.

OBJECTIVE: Acute hemorrhage in preterm infants leads immediately to a life-threatening event because of the small circulating blood volume. The beneficial use of recombinant activated Factor VII (rFVIIa; NovoSeven, NovoNordisk, Gentofte, Denmark) as hemostatic treatment in neonates with hemorrhagic shock has been described. Necrotizing enterocolitis is a challenge in neonatology as the disease represents one of the leading causes of mortality in preterm infants. We report on the use of rFVIIa in very low birth weight (<1500 g), preterms with intestinal hemorrhage, and disseminated intravascular coagulation (DIC). DESIGN: Retrospective analysis of 5 cases. PATIENTS: Five preterm infants

Outcome of preterm and term neonates of mothers with malignant diseases diagnosed during pregnancy.

OBJECTIVE: To investigate the outcome of preterm and term neonates born to mothers with malignant diseases diagnosed during pregnancy. METHODS: A retrospective analysis with a matched-paired control group in a third level obstetric department and third level neonatal department of the University Hospital Frankfurt. Patients were preterm and term neonates from mothers with oncologic diseases diagnosed during pregnancy and matched-paired preterm and term neonates from healthy mothers. MEASUREMENTS AND RESULTS: Nineteen preterm and three term (1 x twins) neonates from 21 mothers with oncologic diseases and matched-paired neonates from 21 healthy mothers were included. With the exception of one case, pregnancy was terminated because of the necessity for maternal oncological treatment. Children from mothers with malignant diseases had a significantly lower birth weight and a tendency towards a higher incidence of high-grade respiratory distress syndrome. No significant differences concerning Apgar scores, red blood cell (RBC), white blood cell (WBC), and platelet (PLT) counts postpartum, and duration of hospital days between the two groups of neonates were observed. CONCLUSION: Direct perinatal outcome of preterm or term neonates from mothers with malignant diseases diagnosed during ongoing intact pregnancy does not differ from the outcome of a comparable group of neonates from healthy mothers. This might be in contrast to the long-term outcome of this special patient group. In our study we could find no elevated mortality in neonates where pregnancy was terminated because of the need for maternal chemotherapeutic therapy.

Linezolid treatment of glycopeptide-resistant Enterococcus faecium in very low birth weight premature neonates.

Glycopeptide-resistant Enterococcus faecium has emerged as an important nosocomial pathogen with limited therapeutic options. Here we report the successful treatment of glycopeptide-resistant E. faecium infection in two very low birth weight premature infants with the new oxazolidinone linezolid. Treatment with linezolid at a dosage of 10 mg/kg every 8 h intravenously for a duration of 16 days and 14 days, respectively, was well tolerated and led to complete clinical recovery and clearance of the organism from all body sites. The two cases support the clinical efficacy and safety of linezolid in very low birth weight premature neonates with glycopeptide-resistant E. faecium infections.

Fatal transplacental infection with non-typhoidal Salmonella.

We report a case of transplacentally acquired neonatal sepsis with non-typhoid Salmonella. The infant's mother, a 36-y-old woman, presented with fever and malaise in the 25th week of gestation. Because of a pathological cardiotocogram, Caesarean section was performed a few h following admission. The premature infant had clinical signs of sepsis with multiorgan failure and died 4 d later despite intensive medical care. Maternal blood cultures and swab cultures taken from within the uterine cavity and from cutaneous and mucosal surfaces of the infant grew Salmonella virchow. This case and the few sporadic reports in the literature indicate that septicaemia due to non-typhoidal Salmonella spp. during pregnancy is highly lethal to the foetus or newborn, whereas prognosis for the mother apparently is excellent.