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Outcomes of neonatal encephalopathy (NE) have improved since the widespread implementation of therapeutic hypothermia (TH) in high-resource settings. While TH for NE in term and near-term infants has proven beneficial, 30-50% of infants with moderate-to-severe NE treated with TH still suffer death or significant impairments. There is therefore a critical need to find additional pharmacological and non-pharmacological interventions that improve the outcomes for these children. There are many potential candidates; however, it is unclear whether these interventions have additional benefits when used with TH. Although primary and delayed (secondary) brain injury starting in the latent phase after HI are major contributors to neurodisability, the very late evolving effects of tertiary brain injury likely require different interventions targeting neurorestoration. Clinical trials of seizure management and neuroprotection bundles are needed, in addition to current trials combining erythropoietin, stem cells, and melatonin with TH. IMPACT: The widespread use of therapeutic hypothermia (TH) in the treatment of neonatal encephalopathy (NE) has reduced the associated morbidity and mortality. However, 30-50% of infants with moderate-to-severe NE treated with TH still suffer death or significant impairments. This review details the pathophysiology of NE along with the evidence for the use of TH and other beneficial neuroprotective strategies used in term infants. We also discuss treatment strategies undergoing evaluation at present as potential adjuvant treatments to TH in NE.

Additional file 3. Table S2. LPS induced cytokine responses in children with mTBI versus controls.

Additional file 1. Table S1. Detailed demographics of children with TBI.

To assess the association between placental morphology and neonatal and infant anthropometry, including analysis by sex. Data from the ROLO Kids [Randomized COntrol Trial of LOw Glycaemic Index in Pregnancy] study were analyzed including placental weight and morphology. Placental, anthropometric and skinfold measurements were recorded as markers of adiposity in 196 neonates and 215 infants at 6 months of age. Ratios including subscapular-to-triceps skinfold ratio and waist-to-height ratio were used as markers of central adiposity, while the sum of all skinfolds and subscapular plus triceps skinfolds were used as markers of general adiposity. Analysis was performed for total groups and by sex. On simple linear regression placental weight was associated with neonatal and infant anthropometric measurements. On multiple regression, the placental weight was associated with birth weight. In the neonatal period placental weight was associated with general adiposity in males only (sum of skinfolds (B 0.007, p < .001) and subscapular + triceps skinfolds a marker of general adiposity (B 0.004 p < .001)). At 6 months of age placental length was positively associated with central adiposity in the total group (B 0.006, p .036) and maximum cord diameter was inversely associated with infant central adiposity (B − 0.309 p .043) in males only. The placental phenotype is associated with anthropometry at birth and this association persists to early infancy with a stronger relationship noted in this cohort amongst males. This suggests sexual dimorphism may play a role in the impact of the placenta on infant anthropometry.

Additional file 1. : SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents.

Additional file 1: Appendix A. COHESION Consent form – Delphi survey. Appendix B. COHESION Participant Information Leaflet – Delphi Survey. Appendix C. Spirit 2013 Checklist.

The coronavirus disease 2019 (COVID-19) pandemic has predominantly affected adults of higher age groups, and the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on infants and neonates appears to be small. While we are gathering emerging evidence on the exact SARS-CoV-2 disease process, intrauterine or perinatal transmission of SARS-CoV-2 remains ambiguous and vertical transmission has yet to be proven although viral RNA by reverse transcription polymerase chain reaction has been found in placental membranes and breast milk. [...]

Background: The COVID-19 pandemic threatens global newborn health. We describe the current state of national and local protocols for managing neonates born to SARS-CoV-2-positive mothers. Methods: Care providers from neonatal intensive care units on six continents exchanged and compared protocols on the management of neonates born to SARS-CoV-2-positive mothers. Data collection was between March 14 and 21, 2020. We focused on central protocol components, including triaging, hygiene precautions, management at delivery, feeding protocols, and visiting policies. Results: Data from 20 countries were available. Disease burden varied between countries at the time of analysis. In most countries, asymptomatic infants were allowed to stay with the mother and breastfeed with hygiene precautions. We detected discrepancies between national guidance in particular regarding triaging, use of personal protection equipment, viral testing, and visitor policies. Local protocols deviated from national guidance. Conclusions: At the start of the pandemic, lack of evidence-based guidance on the management of neonates born to SARS-CoV-2-positive mothers has led to ad hoc creation of national and local guidance. Compliance between collaborators to share and discuss protocols was excellent and may lead to more consensus on management, but future guidance should be built on high-level evidence, rather than expert consensus. Impact: At the rapid onset of the COVID19 pandemic, all countries presented protocols in place for managing infants at risk of COVID19, with a certain degree of variations among regions.A detailed review of ad hoc guidelines is presented, similarities and differences are highlighted.We provide a broad overview of currently applied recommendations highlighting the need for international context-relevant coordination.

Background: To determine the association of maternal and fetal inflammatory factors with gender-specific infant adiposity, independent of leptin. Methods: Analysis of anthropometry from 265 mother–infant pairs at birth and 280 pairs at 6 months from the randomised control trial of low glycaemic index diet in pregnancy (ROLO) study (Randomised control trial of low glycaemic index diet) and their association with Maternal TNF-alpha, interleukin 6 and leptin as measured in early and late pregnancy and fetal levels in cord blood. Results: No associations were noted in the male cohort. On multiple regression amongst the female neonatal cohort late pregnancy IL-6 was inversely associated with sum of skinfolds (p ≤ .001); at 6 months infant sum of skinfolds were positively associated with early pregnancy IL-6 (p = .046) and central adiposity positively associated with early pregnancy TNF alpha (p = .018) independent of leptin. Conclusion: Although maternal inflammatory cytokines were not associated with neonatal adiposity independent of leptin (as this association is known), both IL-6 and TNF-α were associated with female infant anthropometry at 6 months of age independent of leptin. These results suggest inflammatory cytokines may exert an in-utero influence on later infant adiposity with a tendency to influence female adiposity more than male. Further research is required to ascertain whether these cytokines may be used as reliable early predictors of infant adiposity.

Neonates display a marked gender disparity in morbidity and mortality. A higher percentage of premature male than female infants require invasive respiratory support and preterm males have a higher incidence of lung disease e.g. bronchopulmonary dysplasia (BPD).The TLR4 pathway is an essential component of innate immunity and results in NFκB activation. Many TLR4 signalling genes are encoded on the X chromosome, including IKBKG/NEMO, IRAK-1, and BTK. Genes which escape X chromosome inactivation (XCI) may contribute to the immune advantage observed in female neonates. The aim of this study was to quantify expression of X-linked TLR4 signalling intermediates in umbilical cord blood from term female versus male neonates. Cord blood samples were collected from neonates (≥37w+0) delivered by elective Caesarean section (M:F, 10:10, n=20). RNA was isolated from the buffy coat, cDNA was synthesised and used in qRT-PCR reactions with IKBKG/NEMO (Xq28), IRAK-1 (Xq28), and BTK (Xq21) gene-specific primers. IRAK-1 protein expression was quantifed by Western blot and subcellular localisation was characterised in PBMCs by confocal microscopy. At the mRNA level, there was no significant difference in relative expression of IKBKG/NEMO or BTK. IRAK-1 gene and protein expression was significantly higher in females versus males (p

Baseline anthropometric measurements among the total sample and by intervention group of the original ROLO study (DOC 39Â kb)

Correlation of fetal C-peptide and leptin from cord blood with neonatal anthropometric measures (DOC 53Â kb)

Correlation of fetal C-peptide and leptin from cord blood with neonatal anthropometric measures (DOC 53Â kb)

The original version of this Article contained an error in the spelling of the author Marina Degtyareva, which was incorrectly given as Marina Degtyaeva. This has now been corrected in both the PDF and HTML versions of the Article.