Providing facilities for parents to stay in the neonatal unit from admission to discharge may reduce the total length of stay for infants born prematurely. The reduced risk of moderate-to-severe bronchopulmonary dysplasia needs additional investigation.

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BackgroundHeterozygous loss-of-function mutations in the X-linked CASK gene cause progressive microcephaly with pontine and cerebellar hypoplasia (MICPCH) and severe intellectual disability (ID) in females. Different CASK mutations have also been reported in males. The associated phenotypes range from nonsyndromic ID to Ohtahara syndrome with cerebellar hypoplasia. However, the phenotypic spectrum in males has not been systematically evaluated to date.MethodsWe identified a CASK alteration in 8 novel unrelated male patients by targeted Sanger sequencing, copy number analysis (MLPA and/or FISH) and array CGH. CASK transcripts were investigated by RT-PCR followed by sequencing. Immunoblotting was used to detect CASK protein in patient-derived cells. The clinical phenotype and natural history of the 8 patients and 28 CASK-mutation positive males reported previously were reviewed and correlated with available molecular data.ResultsCASK alterations include one nonsense mutation, one 5-bp deletion, one mutation of the start codon, and five partial gene deletions and duplications; seven were de novo, including three somatic mosaicisms, and one was familial. In three subjects, specific mRNA junction fragments indicated in tandem duplication of CASK exons disrupting the integrity of the gene. The 5-bp deletion resulted in multiple aberrant CASK mRNAs. In fibroblasts from patients with a CASK loss-of-function mutation, no CASK protein could be detected. Individuals who are mosaic for a severe CASK mutation or carry a hypomorphic mutation still showed detectable amount of protein.ConclusionsBased on eight novel patients and all CASK-mutation positive males reported previously three phenotypic groups can be distinguished that represent a clinical continuum: (i) MICPCH with severe epileptic encephalopathy caused by hemizygous loss-of-function mutations, (ii) MICPCH associated with inactivating alterations in the mosaic state or a partly penetrant mutation, and (iii) syndromic/nonsyndromic mild to severe ID with or without nystagmus caused by CASK missense and splice mutations that leave the CASK protein intact but likely alter its function or reduce the amount of normal protein. Our findings facilitate focused testing of the CASK gene and interpreting sequence variants identified by next-generation sequencing in cases with a phenotype resembling either of the three groups.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-015-0256-3) contains supplementary material, which is available to authorized users.

Leukocyte adhesion deficiency II has been described in only 2 patients; herein we report extensive investigation of another patient. The physical stigmata were detected during prenatal ultrasonographic investigation. Sialyl-Lewis X (sLex) was absent from the surface of polymorphonuclear neutrophils, and cell binding to E- and P-selectin was severely impaired, causing an immunodeficiency. The elevation of peripheral neutrophil counts occurred within several days after birth. A severe hypofucosylation of glycoconjugates bearing fucose in different glycosidic links was present in all cell types investigated, demonstrating that leukocyte adhesion deficiency II is not only a disorder of leukocytes but a generalized inherited metabolic disease affecting the metabolism of fucose.

Elevated dietary fructose intake, altered intestinal motility, and barrier function may be involved in the development of nonalcoholic fatty liver disease (NAFLD). Because intestinal motility and permeability are also regulated through the bioavailability of serotonin (5-HT), we assessed markers of hepatic injury in serotonin reuptake transporter knockout (SERT(-/-)) and wild-type mice chronically exposed to different monosaccharide solutions (30% glucose or fructose solution) or water for 8 wk. The significant increase in hepatic triglyceride, TNF-alpha, and 4-hydroxynonenal adduct as well as portal endotoxin levels found in fructose-fed mice was associated with a significant decrease of SERT and the tight-junction occludin in the duodenum. Similar effects were not found in mice fed glucose. In contrast, in SERT(-/-) mice fed glucose, portal endotoxin levels, concentration of occludin, and indices of hepatic damage were similar to those found in wild-type and SERT(-/-) mice fed fructose. In fructose-fed mice treated with a 5-HT3 receptor antagonist, hepatic steatosis was significantly attenuated. Our data suggest that a loss of intestinal SERT is a critical factor in fructose-induced impairment of intestinal barrier function and subsequently the development of steatosis.

ObjectivesKangaroo Mother Care (KMC), prolonged skin-to-skin care of the low birth weight baby with the mother plus exclusive breastfeeding reduces neonatal mortality. Global KMC coverage is low. This study was conducted to develop and evaluate context-adapted implementation models to achieve improved coverage.DesignThis study used mixed-methods applying implementation science to develop an adaptable strategy to improve implementation. Formative research informed the initial model which was refined in three iterative cycles. The models included three components: (1) maximising access to KMC-implementing facilities, (2) ensuring KMC initiation and maintenance in facilities and (3) supporting continuation at home postdischarge.Participants3804 infants of birth weight under 2000 g who survived the first 3 days, were available in the study area and whose mother resided in the study area.Main outcome measuresThe primary outcomes were coverage of KMC during the 24 hours prior to discharge and at 7 days postdischarge.ResultsKey barriers and solutions were identified for scaling up KMC. The resulting implementation model achieved high population-based coverage. KMC initiation reached 68%–86% of infants in Ethiopian sites and 87% in Indian sites. At discharge, KMC was provided to 68% of infants in Ethiopia and 55% in India. At 7 days postdischarge, KMC was provided to 53%–65% of infants in all sites, except Oromia (38%) and Karnataka (36%).ConclusionsThis study shows how high coverage of KMC can be achieved using context-adapted models based on implementation science. They were supported by government leadership, health workers’ conviction that KMC is the standard of care, women’s and families’ acceptance of KMC, and changes in infrastructure, policy, skills and practice.Trial registration numbersISRCTN12286667; CTRI/2017/07/008988; NCT03098069; NCT03419416; NCT03506698.

Almost 65% of all premature neonates with a birth weight <1,500 g receive at least one erythrocyte transfusion during their first weeks of life. In the present study, we examined the feasibility of autologous transfusions in neonates, using placental blood. Placental blood was obtained from 131 of 141 preterm and term infants using a special placental blood collecting system. Approximately 20 ml of placental blood per kilogram body weight could be harvested, irrespective of birth weight. One placental blood sample was contaminated with maternal erythrocytes; aerobe or anaerobe contamination was observed in any of the stored placental blood products (n = 119) after 35 days of storage. 19 of the 141 newborns needed allogeneic erythrocyte transfusions during the first 12 weeks of life. In 5 of these 19 patients, the amount of placental blood collected would have been enough to dispense with further allogeneic blood transfusions. After completion of the preclinical study, we transfused a total of 22 children, using autologous placental blood. 8 of the 10 infants with a birth weight between 1,000 and 2,000 g and 3 of 5 infants requiring surgical intervention directly after birth needed no further allogeneic blood transfusions. We, therefore, conclude that the collection and preparation of placental blood is feasible for clinical use. The target groups of neonates who are most likely to benefit are infants with a birth weight between 1,000 and 2,000 g and neonates requiring surgical intervention directly after birth.