Congenital sodium diarrhoea (CSD) refers to a form of secretory diarrhoea with intrauterine onset and high faecal losses of sodium without congenital malformations. The molecular basis for CSD remains unknown. We clinically characterised a cohort of infants with CSD and set out to identify disease-causing mutations by genome-wide genetic testing.

Harlequin ichthyosis (HI) is a severe autosomal recessive developmental disorder of the skin that is frequently but not always fatal in the first few days of life. In HI, mutations in both ABCA12 gene alleles must have a severe impact on protein function and most mutations are truncating. The presence of at least one nontruncating mutation (predicting a residual protein function) usually causes a less severe congenital ichthyosis (lamellar ichthyosis or congenital ichthyosiform erythroderma). Here we report on a girl with severe HI diagnosed by prenatal ultrasound at 33 5/7 week gestation. Ultrasound findings included ectropion, eclabium, deformed nose, hands and feet, joint contractures, hyperechogenic amniotic fluid and polyhydramnion. After birth, palliative treatment was provided and she died on her first day of life. Sequence analysis of the ABCA12 gene identified two novel mutations, c.1857delA (predicting p.Lys619) in exon 15 and c.5653-5655delTAT (predicting p.1885delTyr) in exon 37, each in heterozygous state. The c.5653-5655delTAT mutation is not truncating, but the deleted tyrosine at position 1885 is perfectly conserved among vertebrates and molecular studies evaluated the mutation as probably disease causing and damaging.

One of the numerous challenges preterm birth poses for parents and physicians is prognostic disclosure. Prognoses are based on scientific evidence and medical experience. They are subject to individual assessment and will generally remain uncertain with regard to the individual. This can result in differences in prognostic framing and thus affect the recipients' perception. In neonatology, data on the effects of prognostic framing are scarce. In particular, it is unclear whether parents prefer a more optimistic or a more pessimistic prognostic framing.

The conserved oligomeric Golgi (COG) complex consists of eight subunits and plays a crucial role in Golgi trafficking and positioning of glycosylation enzymes. Mutations in all COG subunits, except subunit 3, have been detected in patients with congenital disorders of glycosylation (CDG) of variable severity. So far, 3 families with a total of 10 individuals with biallelic COG6 mutations have been described, showing a broad clinical spectrum. Here we present 7 additional patients with 4 novel COG6 mutations. In spite of clinical variability, we delineate the core features of COG6-CDG i.e. liver involvement (9/10), microcephaly (8/10), developmental disability (8/10), recurrent infections (7/10), early lethality (6/10), and hypohidrosis predisposing for hyperthermia (6/10) and hyperkeratosis (4/10) as ectodermal signs. Regarding all COG6-related disorders a genotype-phenotype correlation can be discerned ranging from deep intronic mutations found in Shaheen syndrome as the mildest form to loss-of-function mutations leading to early lethal CDG phenotypes. A comparison with other COG deficiencies suggests ectodermal changes to be a hallmark of COG6-related disorders. Our findings aid clinical differentiation of this complex group of disorders and imply subtle functional differences between the COG complex subunits.

Background: Intubation of neonates is difficult and hazardous. Factors associated with procedure-related adverse events and unsuccessful intubation attempts are insufficiently evaluated, especially during neonatal nasotracheal intubations. Objective: Aim of this study was to determine the frequency of tracheal intubation-associated events (TIAEs) during neonatal nasotracheal intubations and to identify factors associated with TIAEs and unsuccessful intubation attempts in our neonatal unit. Methods: This was a prospective, single-site, observational study from May 2017 to November 2019, performed at a tertiary care neonatal intensive care unit in a German academic teaching hospital. All endotracheal intubation encounters performed by the neonatal team were recorded. Results: Two hundred and fifty-eight consecutive intubation encounters in 197 patients were analyzed. One hundred and forty-eight (57.4%) intubation encounters were associated with at least one TIAE. Intubation inexperience (<10 intubation encounters) (OR = 2.15; 95% CI, 1.257-3.685) and equipment problems (OR = 3.43; 95% CI, 1.12-10.52) were predictive of TIAEs. Intubation at first attempt (OR = 0.10; 95% CI, 0.06-0.19) and videolaryngoscopy (OR = 0.47; 96% CI, 0.25-0.860) were predictive of intubation encounters without TIAEs. The first intubation attempt was commonly done by pediatric residents (67.8%). A median of two attempts were performed until successful intubation. Restricted laryngoscopic view (OR = 3.07; 95% CI, 2.08-4.53; Cormack-Lehane grade 2 vs. grade 1), intubation by pediatric residents when compared to neonatologists (OR = 1.74; 95% CI, 1.265-2.41) and support by less experienced neonatal nurses (OR = 1.60; 95% CI, 1.04-2.46) were associated with unsuccessful intubation attempts. Conclusions: In our unit, TIAEs and unsuccessful intubation attempts occurred frequently during neonatal nasotracheal intubations. To improve success rates, quality improvement und further research should target interprofessional education and training, equipment problems and videolaryngoscopy.