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DELAYED MATURATION OF THE STRUCTURAL WHOLE BRAIN CONNECTOME IN NEONATES WITH CONGENITAL HEART DISEASE
Abstract
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Background
Brain development can be delayed in congenital heart disease infants (CHD), whose perioperative structural whole brain connectome remains unknown. We aimed to characterize pre- and postoperative structural connectomes in CHD neonates and assess risk factors for disturbed network development.
Methods
In this prospective cohort study, 114 term neonates with CHD underwent cardiopulmonary bypass surgery at the University Children’s Hospital Zurich. Pre- and postoperative structural connectomes were derived from mean FA values of fiber pathways traced using diffusion tractography. Forty-six healthy term newborns were included as controls. Graph theory parameters calculated across iterative proportional cost thresholds were compared between groups by multi-threshold permutation correction (MTPC) adjusted for confounders. Network based statistics (NBS) was calculated for edgewise network comparison. White matter injury (WMI) volume was quantified on 3D T1-weighted images. Random coefficient mixed models with interaction terms for CHD subtype and WMI volume with scanning age respectively were built to assess effects on network development.
Results
At the global and nodal level, global/nodal efficiency was higher in controls compared to CHD with the opposite between group difference for local efficiency and transitivity (all p<0.05) (Figure). At the edge-level, multiple subnetwork differences were identified pre- and postoperatively. No difference in slopes among CHD subtypes was found for network development. WMI volume was negatively associated with global efficiency and strength (p=0.0097; p=0.0026).
Conclusions
The maturation of the structural connectome is delayed in CHD infants. WMI predicts a perturbated neonatal connectome. Aberrant structural network development in CHD may represent neural correlates of neurodevelopmental sequelae.
THE EFFECT OF INITIAL HIGH VS. LOW FIO2 ON DIAPHRAGM ACTIVITY IN PRETERM INFANTS AT BIRTH
Abstract
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Background and Aim
The initial FiO2 to stabilize preterm infants at birth is still a matter of debate. Our recent randomized trial suggested that, in preterm infants, an initial high FiO2 (100% O2-group) resulted in a higher minute volume (MV) in the first 5 minutes compared to an initial low FiO2 (30% O2-group). In a subgroup of the infants included in this trial, diaphragm activity was measured with transcutaneous electromyography of the diaphragm (dEMG). We aimed to investigate whether diaphragm activity differed between high and low FiO2, thereby, partly, explaining the observed difference in MV.
Methods
Infants <30 weeks of gestation were included and randomized to an initial high or low FiO2, followed by saturation-based oxygen titration. To monitor diaphragm activity with dEMG, two skin electrodes were placed on the frontal diaphragm and one reference on the sternum. Primary outcome measures were peak and tonic diaphragm activity in the first fifteen minutes.
Results
Twenty-nine infants were included in the dEMG analysis (gestational age 27.6 ± 1.7 weeks, birth weight 1026 ± 283 g) of whom 14 were randomized to the 30% O2-group and 15 to the 100% O2-group. Average peak activity (12.2 (IQR 7.7 – 14.4) µV vs. 8.8 (6.6 – 12.8) µV, p=0.32, Figure 1) and tonic diaphragmatic activity (4.0 (3.5-6.5) µV vs. 3.6 (2.5 – 4.2) µV, p= 0.13) were not significantly different between both groups.
Conclusion
Our study comparing preterm infants receiving initial high or low FiO2 during stabilization at birth, diaphragm activity was not statistically different.
A DOUBLE-BLIND, RANDOMIZED, THREE-ARM, PARALLEL-GROUP, PLACEBO CONTROLLED STUDY TO ASSESS THE EFFECT OF INSULIN DERIVED ENTERALLY ON THE INFANT INTESTINAL MICROBIOME
Abstract
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Objectives/Study:Human milk insulin might be associated with changes in infant gastrointestinal microbiome.Insulin retains biological activity in the gastrointestinal tract and may be an additional factor that contributes to the colonization of the infant intestinal microbiome.The objective of this randomized controlled trial was to assess the efficacy of 2 doses of enteral insulin administration compared to placebo with respect to early differences in microbiota.
Methods:A total of 17 preterm patients were recruited at the NICU.Subjects received 2000µIU of Insulin/ml(n=6),400µIU of Insulin/ml(n=6) or placebo(n=5) for 28 days administered once per day.Extracted DNA from fecal samples collected at the beginning and end of treatment were analyzed.The 16S rRNA V4 region was amplified and sequenced in a Miseq(Illumina®)sequencer using 2x250 bp paired-end.Resulting reads were filtered and analyzed using Qiime2 software.Outcome measure was different in infant gastrointestinal microbiome composition before and after intervention.Data is expressed as mean±SD or Median(min-max).
Results:We found that patients that received the highest doses of insulin presented less microbial diversity than placebo(p=0.0192).We found an effect of treatment on Clostridiaceae,positive difference in percentage between end and start of treatment in both groups treated with insulin vs 0.1 in placebo(Table).Dosis of 2000µIU of Insulin/ml did not modifiy microbiota compared to placebo.Dosis of 400µIU of Insulin/ml increased Firmicutes and decrease Proteobacteria(Table).
Conclusion:In very preterm infants,enteral insulin administration results in an increase in Clostridiaceae.Our results indicate that insulin at 400µIU/ml may accelerate maturation of gut microbiota.
| Phylum Firmicutes | Phylum Proteobacteria | FamilyClostridiaceae | |
| 2000µIU Insulin/ml | 0.5(-30.43-71.72) | 2.9(-71.92-30.70) | 5.9 (-18.6-52.2) |
| 400µIU Insulin/ml | 28.4(-68.09-54.49) | -26.1(-54.50-70.07) | 21.3(-24.4-34) |
| Placebo | 1.4(-15.14-54.49) | 0.2(-54,49-22.62) | 0.1(0.0-0.7) |
EFFICACY AND SAFETY OF ENTERAL RECOMBINANT HUMAN INSULIN IN PRETERM INFANTS: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
Abstract
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Background and aims: Enteral insulin may promote intestinal maturation in preterm infants. Insulin is absent in formula and the natural insulin concentration in human milk declines rapidly postpartum. The objective of this double-blind RCT was to assess the effect of two different doses recombinant human (rh) insulin as additive to formula or human milk on time to reach full enteral feeding for three consecutive days.
Methods: Preterm infants (gestational age (GA) 26-32 weeks and birth weight (BW) ≥500 grams) were randomly assigned to receive either investigational drug containing low dose (LD) rh-insulin (400 µU/mL), high dose (HD) rh-insulin (2000 µU/mL), or placebo for 28 days.
Results: 262 infants were included in the intention-to-treat analysis. Median (IQR) GA was 28.9 (27.7-30.6) weeks and BW was 1200 (987-1430) grams. Time to full enteral feeding was 10.0 (7.0-22.0) days in the LD group (n=95), 10.0 (6.0-15.8) days in the HD group (n=82), and 14.0 (8.0-28.0) days in the placebo group (n=85) and, compared to placebo, significantly shorter in the LD group (p=0.033) and HD (p=0.005) group. Weight gain rates during intervention were not different between the groups (LD: 17.2 (14.1-19.9 g/kg/day), HD: 16.6 (14.4-18.9) g/kg/day, placebo: 17.6 (14.8-19.4) g/kg/day). Severe necrotizing enterocolitis (LD: 4.2%, HD: 4.9%, placebo: 9.4%) and mortality (LD: 4.2%, HD: 1.2%, placebo: 4.7%) rates were not higher in the intervention groups.
Conclusion: Enteral administration of two different doses rh-insulin, compared to placebo, significantly reduces time to full enteral feeding in preterm infants with a GA 26-32 weeks.
NEUROLOGICAL ONTOGENESIS IMPAIRMENT IN CHILDREN WITH AUTISM SPECTRUM DISORDERS: PROSPECTIVE STUDY
Abstract
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Background and aims.
Autism Spectrum Disorders are not singly related to a field of psychiatry. Often changes of motor development and neurological condition occur that worsen socialization of these patients and subsequently their quality of life. Frequently patients do not communicate with peers because they cannot fulfil tasks that typically developing children are capable of.
Methods.
219 patients with ASD (F84.0) were examined using Autism Comorbidity Interview, parent’s questionnaires, neurological examination, dynamometry, Box and Blocks test, and the 9-hole peg test. Patients aged 5 to 15, mean age - 7years2months.
Results.
26.9% of children with ASD had no comorbid neurological pathology. 34.8% had uni/bilateral pyramidal tract insufficiency, 21.9% had perinatal lesion of the Central Nervous System (F82), 10.0% had Cerebral Palsy (G80), and 11.8% had epilepsy (G40). 25.7% of patients had an increase of muscle tone in distal parts of lower/upperlimbs, 18.8% had a decreased range of passive motions in the joints of the lower limbs. Fine hand function was impaired in 46.7% of patients, both manipulative and grasping abilities were worse in comparison to average scores in non-impaired peer groups.
Conclusions.
Changes in neurological state of patients with ASD are common. There is an acute necessity to identify and code them accordingly. This will benefit complex treatment approach for these patients. Indicates the necessity for the rehabilitation of ASD patients to be multidirectional.