Summary Background 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. Method 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. Findings 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). Interpretation The application of surfactant via a thin catheter to spontaneously breathing preterm infants receiving continuous positive airway pressure reduces the need for mechanical ventilation. Funding German Ministry of Research and Technology, University of Lübeck, and Chiesi Pharmaceuticals.
Gastrointestinal complications during the neonatal period, i.e. necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP), are associated with adverse short-term outcome in ...very-low-birthweight infants (VLBWI, <1500 g birth weight). However, little is known about the neurological outcome of survivors at school age. We analysed data of 2241 infants followed-up at the age of 6 years. To determine the effect of NEC and SIP on cognitive outcome in consideration of other important confounding factors, we used multivariable logistic regression models. In addition, infants with surgical diagnosis of NEC (n = 43) or SIP (n = 41) were compared to NEC (n = 43) or SIP (n = 41) negative controls using Mahalanobis distance matching. Infants with a history for NEC had a three times increased risk (RR 3.0 1.8-4.2, p < 0.001) to develop IQ scores <85 while history of surgical SIP did not increase the relative risk for lower IQs at school age (RR 1.0 0.4-2.1, p = 1.000). In a matched-cohort analysis, we confirmed that infants with surgical NEC had lower mean IQ results than unaffected controls (±SD) (85±17 vs. 94±14, p = 0.023) while no differences were found for history of SIP. Our results reflect that the different aetiology and inflammatory extent of NEC and SIP may lead to disparate neurodevelopment trajectories. Hence, our data suggest a potential role of early gut-brain axis distortion in infants with NEC which needs to be further explored.
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.
•Internalizing symptoms in preterm and term preschoolers were assessed from four perspectives.•From the parents’ perspective, higher levels of internalizing symptoms were found in preterm ...children.•From the teacher's and the child's own perspective, the group differences were not significant.•Parental postpartum psychological distress predicted higher levels of children´s internalizing symptoms.•Prematurity did not predict internalizing symptoms from any of the four perspectives.
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.
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 < 0.001), postnatal dexamethasone treatment (2.5% versus 7%, p < 0.001), BPD (12% versus 18%, p = 0.001) and BPD or death (14% versus 21%, p < 0.001) than the controls.
Conclusion
Surfactant treatment of spontaneously breathing infants was associated with lower rates of mechanical ventilation and BPD. Additional large‐scale randomised controlled trials are needed to assess the possible long‐term benefits of LISA.
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.
Objective To evaluate outcome data in an observational cohort of very low birth weight infants of the German Neonatal Network stratified to prophylactic use of Lactobacillus acidophilus / ...Bifidobacterium infantis probiotics. Study design Within the observational period (September 1, 2010, until December 31, 2012, n = 5351 infants) study centers were categorized into 3 groups based on their choice of Lactobacillus acidophilus / Bifidobacterium infantis use: (1) no prophylactic use (12 centers); (2 a/b) change of strategy nonuser to user during observational period (13 centers); and (3) use before start of observation (21 centers). Primary outcome data of all eligible infants were determined according to center-specific strategy. Results The use of probiotics was associated with a reduced risk for necrotizing enterocolitis surgery (group 1 vs group 3: 4.2 vs 2.6%, P = .028; change of strategy: 6.2 vs 4.0%, P < .001), any abdominal surgery, and hospital mortality. Infants treated with probiotics had improved weight gain/day, and probiotics had no effect on the risk of blood-culture confirmed sepsis. In a multivariable logistic regression analysis, probiotics were protective for necrotizing enterocolitis surgery (OR 0.58, 95% CI 0.37-0.91; P = .017), any abdominal surgery (OR 0.7, 95% CI 0.51-0.95; P = .02), and the combined outcome abdominal surgery and/or death (OR 0.43; 95% CI 0.33-0.56; P < .001). Conclusions Our observational data support the use of Lactobacillus acidophilus / Bifidobacterium infantis probiotics to reduce the risk for gastrointestinal morbidity but not sepsis in very low birth weight infants.
Several 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.
Ten 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.
Pathogenicity 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.
This 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.
Abstract Background Preterm birth and survival rates of very low birth-weight (VLBW: <1.500 g) 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. Methods 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. Results 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. Limitations Results presented here, are based on cross sectional data. Therefore no temporal relationships can be established. Conclusions 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.
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