Christian Wieg

Publications (8)61.36 Total impact

• Article: Causes of delivery and outcomes of very preterm twins stratified to zygosity.

  Juliane Spiegler, Christoph Härtel, Lena Schulz, Nicole von Wurmb-Schwark, Thomas Hoehn, Angela Kribs, Helmut Küster, Jens Siegel, Christian Wieg, Jan Weichert, Egbert Herting, Wolfgang Göpel
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  ABSTRACT: The increasing rates of preterm birth among twins implicate that solid data on associated risks and outcomes are required. Assessment of zygosity is often based on clinical criteria (evaluation of placenta; same gender, birth weight discordance as surrogate criteria for monochorionic/monozygotic twins). The aim of this study was to compare clinical versus genetic assessment of zygosity and to compare causes of preterm delivery as well as outcome data of very-low-birth-weight (VLBW; birth weight <1,500 g) twins stratified to zygosity. In a multicenter study, we selected n=176 sets of same gender twins and determined zygosity genetically. In a subgroup of 123 sets of twins, the attending physicians at the study centers were asked to document the parameter 'zygosity' (monozygotic/dizygotic) on the basis of their clinical judgment. Concordance between genetic and clinical assessment was 62.7% for monozygotic twins and 88.9% for dizygotic twins, respectively. Outcome parameters (death, BPD, ROP, NEC, IVH) were comparable in both groups. Genetically dizygotic twins were significantly more often born due to intrauterine infection (33% vs. 20% in monozygotic twins, p<.01) and antenatal antibiotics were more frequently given to mothers of dizygotic twins (62% vs. 47% in monozygotic twins, p<.01). Obstetric complications such as twin-twin-transfusion-syndrome were only seen in monozygotic twins as expected. The unexpected increase of antenatal antibiotic treatment and birth due to intrauterine infection in dizygotic twins should be confirmed in additional VLBW twin-cohorts.
  Twin Research and Human Genetics 08/2012; 15(4):532-6. · 1.70 Impact Factor
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  Available from: PubMed Central

  Article: Epidemic microclusters of blood-culture proven sepsis in very-low-birth weight infants: experience of the German Neonatal Network.

  Christoph Härtel, Kirstin Faust, Stefan Avenarius, Bettina Bohnhorst, Michael Emeis, Corinna Gebauer, Peter Groneck, Friedhelm Heitmann, Thomas Hoehn, Mechthild Hubert, [......], Anja Stein, Matthias Vochem, Ursula Weller, Axel von der Wense, Christian Wieg, Jürgen Wintgens, Claudia Hemmelmann, Arne Simon, Egbert Herting, Wolfgang Göpel
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  ABSTRACT: 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. 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. 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. 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.
  PLoS ONE 01/2012; 7(6):e38304. · 4.09 Impact Factor
• Article: ATP-binding cassette member A3 (E292V) gene mutation and pulmonary morbidity in very-low-birth-weight infants.

  Christoph Härtel, Ursula Felderhoff-Müser, Corinna Gebauer, Thomas Hoehn, Angela Kribs, Reinhard Laux, Jens Möller, Hugo Segerer, Norbert Teig, Axel von der Wense, Christian Wieg, Guido Stichtenoth, Egbert Herting, Wolfgang Göpel
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  ABSTRACT: 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.
  Acta Paediatrica 12/2011; 101(4):380-3. · 2.07 Impact Factor
• Article: Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial.

  Wolfgang Göpel, Angela Kribs, Andreas Ziegler, Reinhard Laux, Thomas Hoehn, Christian Wieg, Jens Siegel, Stefan Avenarius, Axel von der Wense, Matthias Vochem, Peter Groneck, Ursula Weller, Jens Möller, Christoph Härtel, Sebastian Haller, Bernhard Roth, Egbert Herting
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  ABSTRACT: 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, p<0·0001). 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.
  The Lancet 09/2011; 378(9803):1627-34. · 38.28 Impact Factor
• Article: Tumor necrosis factor-α promoter -308 G/A polymorphism and susceptibility to sepsis in very-low-birth-weight infants.

  Christoph Härtel, Claudia Hemmelmann, Kirstin Faust, Corinna Gebauer, Thomas Hoehn, Angela Kribs, Reinhard Laux, Werner Nikischin, Hugo Segerer, Norbert Teig, Axel von der Wense, Christian Wieg, Egbert Herting, Wolfgang Göpel
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  ABSTRACT: To determine whether the tumor necrosis factor-α -308 G/A polymorphism is associated with blood culture-proven sepsis in two large cohorts of very-low-birth-weight infants. Genetic association studies. 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). 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-α -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. No association was found between the tumor necrosis factor-α -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-α -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.
  Critical care medicine 05/2011; 39(5):1190-5. · 6.37 Impact Factor
• Article: Does the enteral feeding advancement affect short-term outcomes in very low birth weight infants?

  Christoph Härtel, Berit Haase, Kathryn Browning-Carmo, Corinna Gebauer, Evelyn Kattner, Angela Kribs, Hugo Segerer, Norbert Teig, Axel von der Wense, Christian Wieg, Egbert Herting, Wolfgang Göpel
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  ABSTRACT: 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 feeds < or =12.5 days; 6 centers), that is, rapid advancement (RA), or "slow advancement to full enteral feeds" (median duration of advancement to full enteral feeds >12.5 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%, P < 0.001) and antibiotics (92.4% vs 77.7%, P < 0.001) 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.
  Journal of pediatric gastroenterology and nutrition 05/2009; 48(4):464-70. · 2.18 Impact Factor
• Article: Very low birth weight infants as a model to study genetic influences on neonatal weight gain.

  Juliane Spiegler, Evelyn Kattner, Matthias Vochem, Helmuth Küster, Jens Möller, Dirk Müller, Angela Kribs, Hugo Segerer, Christian Wieg, Werner Nikischin, Axel von der Wense, Corinna Gebauer, Egbert Herting, Wolfgang Göpel
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  ABSTRACT: In a cohort of 829 preterm infants (birth weight below 1500 g) we identified 13 monozygotic, 10 same-sex dizygotic, and 12 same-sex matched singleton pairs. The difference in daily weight gain within pairs was significantly lower in monozygotic twins compared with dizygotic twins or matched singleton pairs. Our data support a strong genetic influence on postnatal growth in preterm infants. Therefore, weight gain of preterm infants may be an interesting model to study polymorphic variants of genes regulating neonatal resorption, metabolism, or energy expenditure, and their influence on weight gain in preterm infants.
  Journal of pediatric gastroenterology and nutrition 02/2008; 46(1):113-6. · 2.18 Impact Factor
• Article: Genetic polymorphisms of hemostasis genes and primary outcome of very low birth weight infants.

  Christoph Härtel, Inke König, Stefan Köster, Evelyn Kattner, Eckhardt Kuhls, Helmut Küster, Jens Möller, Dirk Müller, Angela Kribs, Hugo Segerer, Christian Wieg, Egbert Herting, Wolfgang Göpel
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  ABSTRACT: Recent investigations have reported an influence of thrombophilic mutations and antithrombotic risk factors with development of intraventricular hemorrhage. It was our objective for this study to investigate the impact of genetic polymorphisms of hemostasis genes on the primary outcome measures of sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, and periventricular leukomalacia in a large cohort of very low birth weight infants. There were 586 very low birth weight infants enrolled prospectively in a multicenter trial between September 2003 and July 2005, and an additional 595 very low birth weight infants, who had been recruited in a previous prospective trial, were studied. DNA samples were taken by buccal swab, and genotypes of factor V Leiden mutation, prothrombin G20210A mutation, the factor VII-323 del/ins polymorphism, and the factor XIII-Val34Leu polymorphisms were determined by polymerase chain reaction and restriction enzyme digestion. In contrast to data published previously, the frequency of intraventricular hemorrhage or periventricular leukomalacia was not significantly influenced by any of the genetic variants tested. Carriers of the factor XIII-Val34Leu polymorphism, however, had a higher sepsis rate and a longer period of hospital care compared with noncarriers. The factor VII-323 del/ins polymorphism was found to be a potential protective factor against bronchopulmonary dysplasia. We could not confirm previously reported associations of hemostasis gene variants and development of intraventricular hemorrhage in very low birth weight infants. To better understand gene-disease associations in very low birth weight infants, the prospective development of large-scale cohorts with well-defined phenotypes and corresponding DNA samples is essential.
  PEDIATRICS 09/2006; 118(2):683-9. · 4.47 Impact Factor