Breastfeeding was not associated with any crude IQ advantage or difference in neurological soft signs in children at 9 years. The greater IQ score associated with breastfeeding is accounted for by confounding, with maternal and socio-economic characteristics particularly important.

BackgroundArthrogryposis, renal dysfunction and cholestasis (ARC) syndrome is a multisystem autosomal-recessive disorder caused by defects in the VPS33B and VIPAR genes, involved in localization of apical membrane proteins. Affected children usually die by 1 year of age, often secondary to infective complications. The classic renal manifestation previously described in ARC syndrome is proximal–tubular dysfunction. The aim of this study is to gain further insight into the renal manifestations of this syndrome.MethodsClinical review of three cases of ARC syndrome presenting to a tertiary centre. Together with measurement of VPS33B and VIPAR protein expression in the human glomerulus.ResultsThe cases demonstrated severe failure to thrive and in addition to commonly described features profound proteinuria and albuminuria, together with hypoalbuminaemia, suggesting glomerular involvement of this syndrome. Western blotting of conditionally immortalized human glomerular cells and ex vivo immunofluorescent analysis of the human glomerulus revealed that VPS33B and VIPAR were highly expressed in glomerular endothelium, and podocytes, but not in the mesangium.ConclusionsARC syndrome affects the glomerulus as well as the proximal tubule in the kidney. Our molecular studies suggest that both cell types that constitute the glomerular filtration barrier are affected in this condition, providing an explanation for the albuminuria that we have observed in our cases.

ObjectivesTo investigate whether infants with weight faltering have impaired psychosocial and educational outcomes in later childhood.DesignFollow-up of infants with weight faltering in a large UK cohort study.SettingThe Avon Longitudinal Study of Parents and Children (ALSPAC).Participants11 534 term infants from ALSPAC with complete weight records. Weight gain (conditional on initial weight) was calculated for three periods: from birth to 8 weeks, 8 weeks to 9 months, and birth to 9 months. Cases of weight faltering were defined as those infants with a conditional weight gain below the 5th centile, and these were compared with the rest of the cohort as the control group.OutcomesBetween 6 and 11 years, social, emotional and behavioural development was measured by direct assessment of the children and parental and teacher report. Educational outcomes included Standardised Assessment Test results at 7 and 11 years and Special Educational Needs status at age 11.ResultsDifferences seen on univariate analysis in attention, non-verbal accuracy, educational attainment and special educational needs became non-significant after adjustment for confounding. Children with weight faltering in infancy did not differ from controls on any measures of self-esteem, peer relationships, experience of bullying, social cognition, antisocial activities, anxiety, depression or behavioural problems.ConclusionsWeight faltering in early infancy was associated with poorer educational outcomes in later childhood, but these associations were explained by confounding. The subsequent psychosocial development of infants with slow weight gain was not different from that of their peers.

Aims Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome is an autosomal recessive disorder caused by defects in two proteins (VPS33B and VIPAR), involved in regulation of intracellular protein trafficking. ARC patients usually die by 2 years of age, often secondary to infective complications. It was previously thought that the defect affects the proximal tubule in the kidney, as well as the liver and the musculoskeletal system. We have recently managed three cases with varying clinical presentations and found that in addition to commonly described features, they all demonstrated marked albuminuria suggesting the glomerulus is also involved in this syndrome. Methods Case-note review of the three cases of ARC syndrome and glomerular mapping of the VPS33B expression using western blotting in conditionally immortalised cells of the glomerulus (Podocytes, Glomerular Endothelial cells and Mesangial cells). Results All cases had severe failure to thrive, arthrogryposis, renal tubular acidosis, nephrotic range albuminuria, conjugated hyperbilirubinaemia with normal γ GT, gastro-oesophageal reflux with difficulty establishing well tolerated feed regimens, metabolic bone disease with fractures and recurrent septic episodes. The primary case had a confirmed VPS33B mutation and died of overwhelming sepsis at the age of 4 months. The subsequent two cases have a clinical diagnosis of ARC, but negative initial VPS33B mutation analysis. These children are still alive at five and 6 months of age respectively. We are currently analysing the expression of VPS33B in the cells of the glomerulus to identify the mechanism of action of this mutation in this site. The initial experiments showed that VPS33B was highly expressed in human glomerular endothelium but much less in podocyte and mesangial cell lines. Review of the literature suggests ARC syndrome has an expanding clinical spectrum and may be more common than previously thought. Nephrotic range albuminuria as a feature of ARC syndrome has only been previously described in a small number of cases. Conclusion The cases demonstrate severe failure to thrive and nephrotic range albuminuria as common features of ARC syndrome. Nephrotic range albuminuria may contribute to the infective complications of this condition.